WO2014144414A1 - Diketopiperazine containing copolymers and preparation methods - Google Patents

Diketopiperazine containing copolymers and preparation methods Download PDF

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Publication number
WO2014144414A1
WO2014144414A1 PCT/US2014/028816 US2014028816W WO2014144414A1 WO 2014144414 A1 WO2014144414 A1 WO 2014144414A1 US 2014028816 W US2014028816 W US 2014028816W WO 2014144414 A1 WO2014144414 A1 WO 2014144414A1
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WIPO (PCT)
Prior art keywords
polymer
formula
unit
diketopiperazine
units
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PCT/US2014/028816
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French (fr)
Inventor
Jay Kouba
David James
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Glyce, Inc.
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Publication of WO2014144414A1 publication Critical patent/WO2014144414A1/en

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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
    • C08G73/06—Polycondensates having nitrogen-containing heterocyclic rings in the main chain of the macromolecule
    • C08G73/0622—Polycondensates containing six-membered rings, not condensed with other rings, with nitrogen atoms as the only ring hetero atoms
    • C08G73/0633—Polycondensates containing six-membered rings, not condensed with other rings, with nitrogen atoms as the only ring hetero atoms with only two nitrogen atoms in the ring
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
    • C08G63/68—Polyesters containing atoms other than carbon, hydrogen and oxygen
    • C08G63/685—Polyesters containing atoms other than carbon, hydrogen and oxygen containing nitrogen
    • C08G63/6854—Polyesters containing atoms other than carbon, hydrogen and oxygen containing nitrogen derived from polycarboxylic acids and polyhydroxy compounds
    • C08G63/6856—Dicarboxylic acids and dihydroxy compounds
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
    • C08G63/78—Preparation processes

Definitions

  • High performance plastics that are strong and durable are useful in a number of applications including automobiles, agricultural, medical and food packaging, and biomedical devices and packaging.
  • Aromatic polyesters have aromatic rings in their polymeric backbone and possess excellent thermal and mechanical properties. In addition, they are relatively easy to process. As a result, aromatic polyesters have excellent commercial applicability in molded parts, fibers, films, and sheeting.
  • PET polyethylene terephthalate
  • PET is a commercially important polyester, which is formed from the reaction of terephthalic acid and ethylene glycol.
  • Polymer modifiers e.g., alternative monomer units, can be added to the backbone of polymers to enhance the performance of the polymers.
  • the polymer modifiers can build on the strengths of the base polymers and enhance the performance of these polymers.
  • co-polyesters containing 2,2,4,4-tetramethyl-l,3-cyclobutanediol (TMCD) exhibit a good combination of impact strength, hardness, and heat resistance.
  • Copolymers of polyesters with naphthalene based monomers which introduce a double ring structure into the polymeric backbone, have improved thermal, chemical, mechanical, and barrier performance.
  • the invention provides a polymer comprising at least two monomer units of a dicarboxylate unit and at least two monomer units of a dialkoxy unit except that (a) some of the dicarboxylate units are replaced by a diketopiperazine unit of aspartic acid and/or a diketopiperazine unit of glutamic acid and/or (b) some of the dialkoxy units are replaced by a diketopiperazine unit of serine, diketopiperazine unit of homoserine, and/or a
  • the polymer can be of the formula -[-R ⁇ -O-R ⁇ O-]- (I) comprising at least two monomer units of R 1 , which can be the same or different, and at least two monomer units of
  • R 2 which can be the same or different.
  • Each R 1 is of formula (II), (III), (IV), (V), or (VI):
  • R 3 is a Ci - C 36 straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group.
  • R 2 is a C 2 - Cs straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group.
  • R 5 is -CH 2 -, -CH 2 CH 2 -, or -CH(CH 3 )-.
  • the invention also provides a method of preparing a polymer of the invention, which method comprises reacting dicarboxylic acids and/or dicarboxylic esters with aliphatic glycols, along with one or more diketopiperazme units of aspartic acid, glutamic acid, serine, homoserine, and/or threonine in the presence of a suitable catalyst.
  • the method can comprise combining, in a reaction vessel, (a) one or more compounds of formula R 1 (OH) 2 and R 1 (OR 6 ) 2 wherein R 6 is a lower alkyl group, (b) one or more aliphatic glycols of formula R 2 (OH) 2 , (c) one or more diketopiperazme units of aspartic acid and/or glutamic acid, wherein the mole ratio of the diketopiperazme units of aspartic acid and glutamic acid to the compounds of formula R 1 (OH) 2 or R x (OR 6 ) 2 is about 0.01 to about 0.8, and/or one or more diketopiperazme units of serine, homoserine, and/or threonine, wherein the mole ratio of the diketopiperazme units of serine, homoserine, and threonine to the aliphatic glycols R 2 (OH) 2 is about 0.01 to about 0.8, and (d) a suitable catalyst
  • the reaction vessel is purged with an inert gas and heated to a first suitable temperature and a suitable pressure.
  • the temperature of the reaction vessel is then raised to a second suitable temperature, while reducing the pressure in the reaction vessel to suitable pressure, thereby synthesizing the polymer.
  • about 0.01 to 0.8 mole fraction of R 1 is replaced by one or more diketopiperazine units of aspartic acid and/or glutamic acid, and/or about 0.01 to 0.8 mole fraction of R 2 is replaced by one or more diketopiperazine units of serine, homoserine, and/or threonine.
  • the invention also provides a method of improving the thermal properties and/or biodegradability of a corresponding conventional polymer by incorporating one or more diketopiperazines therein.
  • corresponding conventional polymer has the formula -[-R 1 -0-R 2 -0-]- wherein R 1 and R 2 are not replaced by diketopiperazines.
  • Fig. 1 is a graph of storage modulus (MPa) in a logarithmic scale (Y-axis) plotted against temperature (°C) (X-axis) comparing the storage modulus of polyethylene terephthalate (PET) and a PET copolymer containing aspartate DKP- (3 mole %) by dynamic mechanical analysis (DMA).
  • MPa storage modulus
  • Y-axis logarithmic scale
  • X-axis comparing the storage modulus of polyethylene terephthalate (PET) and a PET copolymer containing aspartate DKP- (3 mole %) by dynamic mechanical analysis (DMA).
  • Fig. 2 is a graph of Tan Delta (Y-axis) plotted against temperature (°C) (X-axis).
  • the maximum in the Tan Delta is a measure of the glass transition temperature (Tg), i.e. providing the onset of the transition from the glassy state to the rubbery region.
  • Tg glass transition temperature
  • the data in Figure 2 thus provides a comparison of the glass transition temperature (Tg) of polyethylene terephthalate (PET) and a PET copolymer containing aspartate DKP-(3 mole %) by dynamic mechanical analysis (DMA).
  • PET polyethylene terephthalate
  • DMA dynamic mechanical analysis
  • Fig. 3 is a graph of storage modulus (MPa) in a logarithmic scale (Y-axis) plotted against temperature (°C) (X-axis) comparing the storage modulus of polyethylene adipate (PEA) and a PEA copolymer containing aspartate DKP-(10 mole %) by dynamic mechanical analysis (DMA).
  • MPa storage modulus
  • Y-axis logarithmic scale
  • X-axis comparing the storage modulus of polyethylene adipate (PEA) and a PEA copolymer containing aspartate DKP-(10 mole %) by dynamic mechanical analysis (DMA).
  • Fig. 4 is a graph of Tan Delta (Y-axis) plotted against temperature (°C) (X-axis) comparing the glass transition temperature (Tg) of polyethylene adipate (PEA) and a PEA copolymer containing aspartate DKP-(10 mole %) by dynamic mechanical analysis (DMA).
  • Tg glass transition temperature
  • DMA dynamic mechanical analysis
  • the invention provides a polymer comprising at least two monomer units of a dicarboxylate unit and at least two monomer units of a dialkoxy unit except that (a) some of the dicarboxylate units are replaced by diketopiperazine units of aspartic acid and/or glutamic acid, and/or (b) some of the dialkoxy units are replaced by a diketopiperazine unit of serine, homoserine, and/or threonine.
  • Homoserine is an intermediate in the biosynthesis of three essential a-amino acids, namely, methionine, threonine, and isoleucine and is an isomer of threonine.
  • the polymer can be of a formula -[-R ⁇ -O-R ⁇ O-]- (I) comprising, consisting essentially of, or consisting of at least two monomer units of R 1 , which can be the same or different, and at least two monomer units of R 2 , which can be the same or different.
  • Each monomer unit R 1 is independently of formula (II), (III), (IV), (V), or (VI):
  • R 3 is a Ci - C 36 straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group.
  • Each monomer unit R 2 is independently a C 2 - Cg straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group.
  • R 1 Some of the monomer units R 1 are replaced by diketopiperazine units of aspartic acid and/or diketopiperazine units of glutamic acid. In particular, either (a) about 0.01 to about 0.8 mole fraction of R 1 is replaced by a diketopiperazine unit of formula (VII):
  • the diketopiperazme unit of formula (VII), wherein R 4 is -CH 2 C(0)-, represents a diketopiperazme unit of aspartic acid.
  • the diketopiperazme unit of formula (VII), wherein R 4 is -CH 2 CH 2 C(0)-, represents a diketopiperazme unit of glutamic acid.
  • a polymer as described herein e.g., the polymer of the formula -[-R 1 -0-R 2 -0-]-, can have any suitable terminal, or capping, atoms or groups.
  • the capping atom or group can be a hydrogen atom, a Ci - C 6 alkyl group, or any combination thereof.
  • the polymer can be of formula, e.g., HO-[-R 1 -0-R 2 -0-]-H, H 3 CO-[-R 1 -0-R 2 -0-]-H, and the like.
  • R 1 represents a dicarboxylate unit which is a monomer unit of an aromatic dicarboxylic acid, aromatic dicarboxylic ester, aliphatic dicarboxylic acid, or aliphatic dicarboxylic ester.
  • the polymer of the invention can comprise at least two different monomer units of R 1 , e.g., 2, 3, 4, 5, 6, 7, or more different monomer units of R 1 .
  • the polymer can have at least one monomer unit R 1 of formula (II), (IV), (V), or (VI) and at least one monomer unit R 1 of a formula (III).
  • the polymer of formula (I) can comprise all of the same monomer units of R 1 , i.e., a polymer wherein all of the monomer units of R 1 are of formula (II), all of the monomer units of R 1 are of formula (III), all of the monomer units of R 1 are of formula (IV), all of the monomer units of R 1 are of formula (V), or all of the monomer units of R 1 are of formula (VI).
  • R 3 can be a Ci - C 36 straight, branched, non-aromatic cyclic, saturated, unsaturated, substituted, unsubstituted, or aliphatic group, such as a C 2 - C 24 , C 2 - C 18 , or C 2 - C 12 straight, branched, non-aromatic cyclic, saturated, unsaturated, substituted, or unsubstituted aliphatic group.
  • R 3 can be a straight chain or branched Ci - C 24 alkyl group, a straight chain or branched Ci - C 18 alkyl group, a straight chain or branched Ci - C 12 alkyl group, a straight chain or branched Ci - Cg alkyl group, a straight chain or branched Ci - C 4 alkyl group, a straight chain or branched C 2 - C 24 alkyl group, a straight chain or branched C 2 - C 18 alkyl group, a straight chain or branched C 2 - C 12 alkyl group, a straight chain or branched C 2 - C8 alkyl group, a straight chain or branched C 2 - C 4 alkyl group, a straight chain or branched C 4 - C 24 alkyl group, a straight chain or branched C 4 - C 18 alkyl group, a straight chain or branched C 4 - C 12 alkyl group, a straight chain or branched
  • R 3 can be a -CH 2 CH 2 - group, which can be derived from succinic acid or a lower (e.g., Ci - C 6 ) alkyl succinate, e.g., dimethyl succinate.
  • R 3 can be a -CH 2 CH 2 CH 2 - group, which can be derived from glutaric acid or a lower (e.g., Ci - C 6 ) alkyl glutarate, e.g., dimethyl glutarate.
  • R 3 can be -CH 2 (CH 2 ) 2 CH 2 - group, which can be derived from adipic acid or a lower (e.g., Ci - C 6 ) alkyl adipate, e.g., dimethyl adipate.
  • R 3 can be of Formula (IX), e.g.,
  • R 3 can be - CH 2 (CH 2 ) 6 CH 2 -, -CH 2 (CH 2 ) 8 CH 2 - or -CH 2 (CH 2 )i 4 CH 2 -.
  • lower alkyl means Ci - C 6 alkyl group comprising straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group.
  • each monomer unit of R 1 can be the same.
  • the polymer comprises only 1 (one) type of dicarboxylate unit as a monomer in which about 0.01 to about 0.8 mole fraction of R 1 is replaced by diketopiperazine unit of formula (VII).
  • each monomer unit of R 1 can be of formula (II).
  • each monomer unit of R 1 can be one of formula (III), (IV), (V), or (VI).
  • R 3 in formula (VI) can be any one of groups described in above paragraphs.
  • the polymer of formula (I) can comprise R 1 of any known dicarboxylate unit in addition to those of formula (II), (III), (IV), (V), and (VI).
  • R 1 can be an aromatic dicarboxylate unit with Cs to about C 2 o carbon atoms.
  • R 1 can be derived from substituted or unsubstituted aromatic dicarboxylic acids, or lower alkyl (e.g., Ci to C 6 ) esters of dicarboxylic acids.
  • R 1 can also be a biphenyl dicarboxylate unit, diphenyl ether dicarboxylate unit, diphenyl sulfide dicarboxylate unit, diphenyl sulfone dicarboxylate unit, methylene bis(benzoate), or mixture of any two or more thereof, and the like.
  • glycol, dihydric alcohol, and diol refer to a primary, secondary, or tertiary alcohol containing two hydroxyl groups. These terms can be used interchangeably.
  • dialkoxy unit refers to an aliphatic glycol described above in which the hydrogen atoms from the two hydroxyl groups have been removed.
  • the polymer of formula (I) can comprise at least two different monomer units of R 2 , e.g., 2, 3, 4, 5, 6, 7, and the like.
  • the polymer of formula (I) can have at least one monomer unit of R 2 where R 2 can be a C 2 - Cg straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group.
  • R 2 can be C 2 - Cg, C 2 - C 6 , C 2 - C 4 , C 4 - Cg, C 4 - C 6 , C 6 - Cg straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group and the like.
  • the monomer unit of R 2 can be -CH2CH2-,-CH 2 CH(CH3 ,-CH2CH 2 CH2-, -CH 2 (CH 2 )2CH 2 -,
  • each monomer unit of R 2 can be the same.
  • the polymer comprises only 1 (one) type of dialkoxy unit in which, about 0.01 to about 0.8 mole fraction of R 2 is replaced by diketopiperazine unit of formula (VIII).
  • each monomer unit of R 2 can be of formula -CH 2 CH 2 -.
  • each monomer unit of R 2 can be one of -CH 2 CH(CH 3 )-,-CH 2 CH 2 CH 2 -,
  • the polymer of formula (I) can comprise additional dialkoxy units R 2 known in the art.
  • at least one of the monomeric units of R 2 can be of the formula (X) or (XI):
  • the monomeric unit of formula (X) is derived from 1 ,4-cyclohexanedimethanol (CHDM), and the monomeric unit of formula (XI) is derived from
  • TMCD 2,2,4,4-tetramethyl-l,3-cyclobutanediol
  • the diketopiperazines are a class of cyclic organic compounds that result from peptide bonds between two amino acids. Any suitable a-amino acid can be used to prepare a diketopiperazme.
  • diketopiperazme unit is a monomeric unit of diketopiperazme in the polymer of formula (I).
  • the diketopiperazme unit of formula (VII) is
  • the diketopiperazme units of formula (VII) may be derived from aspartic acid and/or glutamic acid, and/or mixtures of the two.
  • diketopiperazme units of formula (VIII) may be derived from serine, homoserine, threonine, and/or mixtures thereof.
  • At least one monomeric unit of R 1 can be replaced by the diketopiperazme unit of formula (VII), wherein R 4 is -CH 2 C(0)-. At least one monomeric unit of R 1 can also be replaced by the diketopiperazme unit of formula (VII), wherein R 4 is -CH 2 CH 2 C(0)-. In certain embodiments, in the polymer of formula (I), when the monomeric unit of R 1 is replaced by the diketopiperazine unit of formula (VII), the monomeric unit of R 2 is not replaced by a diketopiperazine unit.
  • At least one monomeric unit of R 2 can also be replaced by the diketopiperazine unit of formula (VIII), wherein R 5 is only -CH 2 -. At least one monomeric unit of R 2 can also be replaced by the diketopiperazine unit of formula (VIII), wherein R 5 is only -CH 2 CH 2 -. At least one monomeric unit of R 2 can also be replaced by the diketopiperazine unit of formula (VIII), wherein R 5 is only -CH(CH 3 )-.
  • VIII diketopiperazine unit of formula
  • the monomeric unit of R 1 when the monomeric unit of R 2 is replaced by the diketopiperazine unit of formula (VIII), the monomeric unit of R 1 is not replaced by a diketopiperazine unit.
  • the diketopiperazine unit can be of the form: (1, 1), (1, d), (d, 1), or (d, d) or any mixture of two or more thereof.
  • the term “1” is known in the art as levorotatory and the term “d” is known in the art as dextrorotatory.
  • R 4 is -CH 2 C(0)-, which represents a diketopiperazine units of aspartic acid and/or - CH 2 CH 2 C(0)-, which represents a diketopiperazine unit of glutamic acid.
  • a diketopiperazine unit of formula (VII) e.g., greater than about 0.02, greater than about 0.03, greater than about 0.04, greater than about 0.05, greater than about 0.07, greater than about 0.09, greater than about 0.1, greater than about 0.15, greater than about 0.2, greater than about 0.3, greater than about 0.4, greater than about 0.5, greater than about 0.6, greater than about 0.7, greater than about 0.8 mole fraction of R 1 is replaced by a diketopiperazine unit of formula (VII).
  • VII diketopiperazine unit of formula
  • less than about 0.8 mole fraction of R 1 is replaced by a diketopiperazine unit of formula (VII), e.g., less than about 0.7, less than about 0.6, less than about 0.5, less than about 0.4, less than about 0.3, less than about 0.2, less than about 0.15, less than about 0.1, less than about 0.09, less than about 0.07, less than about 0.05, less than about 0.04, less than about 0.03, less than about 0.02, less than about 0.01 mole fraction of R 1 is replaced by a diketopiperazine unit of formula (VII).
  • VII diketopiperazine unit of formula
  • the mole fraction of R 1 replaced by a diketopiperazine unit of formula (VII) can be of an amount bounded by any two of the foregoing endpoints.
  • the mole fraction of R 1 is replaced by a diketopiperazine unit of formula (VII) can be, e.g., about 0.01 to about 0.8, about 0.01 to about 0.7, about 0.01 to about 0.6, about 0.01 to about 0.5, about 0.01 to about 0.4, about 0.01 to about 0.3, about 0.01 to about 0.2, about 0.01 to about 0.15, about 0.01 to about 0.1, about 0.01 to about 0.09, about 0.01 to about 0.07, about 0.01 to about 0.05, about 0.01 to about 0.04, about 0.01 to about 0.03, about 0.01 to about 0.02, about 0.02 to about 0.8, about 0.02 to about 0.7, about 0.02 to about 0.6, about 0.02 to about 0.5, about 0.02 to about 0.4, about
  • a diketopiperazine unit of formula (VIII) e.g., greater than about 0.02, greater than about 0.03, greater than about 0.04, greater than about 0.05, greater than about 0.07, greater than about 0.09, greater than about 0.1, greater than about 0.15, greater than about 0.2, greater than about 0.3, greater than about 0.4, greater than about 0.5, greater than about 0.6, greater than about 0.7, greater than about 0.8 mole fraction of R 2 is replaced by a diketopiperazine unit of formula (VIII).
  • VIII diketopiperazine unit of formula
  • less than about 0.8 mole fraction of R 2 is replaced by a diketopiperazine unit of formula (VIII), e.g., less than about 0.7, less than about 0.6, less than about 0.5, less than about 0.4, less than about 0.3, less than about 0.2, less than about 0.15, less than about 0.1, less than about 0.09, less than about 0.07, less than about 0.05, less than about 0.04, less than about 0.03, less than about 0.02, less than about 0.01 mole fraction of R 2 is replaced by a diketopiperazine unit of formula (VIII).
  • VIII diketopiperazine unit of formula
  • the mole fraction of R 2 replaced by a diketopiperazine unit of formula (VIII) can be of an amount bounded by any two of the foregoing endpoints.
  • the mole fraction of R 2 is replaced by a diketopiperazine unit of formula (VIII) can be, e.g., about 0.01 to about 0.8, about 0.01 to about 0.7, about 0.01 to about 0.6, about 0.01 to about 0.5, about 0.01 to about 0.4, about 0.01 to about 0.3, about 0.01 to about 0.2, about 0.01 to about 0.15, about 0.01 to about 0.1, about 0.01 to about 0.09, about 0.01 to about 0.07, about 0.01 to about 0.05, about 0.01 to about 0.04, about 0.01 to about 0.03, about 0.01 to about 0.02, about 0.02 to about 0.8, about 0.02 to about 0.7, about 0.02 to about 0.6, about 0.02 to about 0.5, about 0.02 to about 0.4, about
  • the polymer of formula (I) about 0.01 to about 0.8 mole fraction of one monomer unit of R 1 can be replaced by a diketopiperazine unit of formula (VII) and at the same time about 0.01 to about 0.8 mole fraction of one monomer unit of R 2 can be replaced by a diketopiperazine unit of formula (VIII).
  • the mole fractions of R 1 replaced by a diketopiperazine unit of formula (VII) or R 2 replaced by a diketopiperazine unit of formula (VIII) can be of an amount bounded by any two of the foregoing endpoints.
  • polymer of formula (I) about 0.01 to about 0.8 mole fraction of one monomer unit of R 1 can be replaced by a diketopiperazine unit of formula (VII) but no R 2 is replaced by diketopiperazine unit of formula (VIII).
  • polymer of formula (I) about 0.01 to about 0.8 mole fraction of one monomer unit of R 2 can be replaced by a diketopiperazine unit of formula (VIII), but no R 1 is replaced by diketopiperazine unit of formula (VII).
  • the polymer of formula (I) can have any suitable molecular weight.
  • the polymer of formula (I) can have a molecular weight of about 500 g/mol or more (e.g., about 1,000 g/mol or more, about 3,000 g/mol or more, about 10,000 g/mol or more, about 20,000 g/mol or more, or about 100,000 g/mol or more, or 1 million g/mol or more).
  • the molecular weight of the polymer of formula (I) typically can be about 1 million g/mol or less, e.g., about 100,000 g/mol or less, about 20,000 g/mol or less, about 10,000 g/mol or less, about 3,000 g/mol or less, about 1,000 g/mol or less, or about 500 g/mol or less).
  • the polymer of formula (I) can have a molecular weight of an amount bounded by any two of the foregoing endpoints.
  • the polymer of formula (I) can have a molecular weight of about 500 g/mol to about 1 million g/mol, about 500 g/mol to about 100,000 g/mol, about 500 g/mol to about 20,000 g/mol, about 500 g/mol to about 10,000 g/mol, about 500 g/mol to 3,000 g/mol, about 500 g/mol to about 1,000 g/mol, about 1,000 g/mol to about 1 million g/mol, about 1,000 g/mol to about 100,000 g/mol, about 1,000 g/mol to about 20,000 g/mol, about 1,000 g/mol to about 10,000 g/mol, about 1000 g/mol to 3,000 g/mol, about 3,000 g/mol to about 1 million g/mol, about 3,000 g/mol to about 100,000 g/mol, about 3,000 g/mol to about 20,000 g/mol, about 3,000 g/mol to about 10,000 g/mol, about 10,000 g/mol, about 10,000 g/mol to about 1 million
  • the polymer of formula (I) can have any suitable number of units of
  • the polymer of formula (I) can have a number of units of R 1 of 2 or more, about 3 or more, about 4 or more, about 13 or more, about 40 or more, about 85 or more, or about 400 or more, or about 4000 or more.
  • the polymer of formula (I) can have a number of units of -[-R 1 -0-R 2 -0-]- of about 4500 or less, e.g., about 450 or less, about 90 or less, about 45 or less, about 15 or less, about 6 or less, or about 4 or less.
  • the polymer of formula (I) can have a number of units of
  • the polymer of formula (I) can have a number of units of -[-R ⁇ O-R ⁇ O-]- of 2 to about 4500,
  • the polymer as described herein can be prepared by any suitable method.
  • Suitable methods include the use of conventional polyesterification procedures and solid state polymerization, except utilizing the diketopiperazines as described herein.
  • the polymer of the invention can be prepared by way of a method that comprises reacting one or more dicarboxylic acids and/or one or more dicarboxylic esters with one or more aliphatic glycols, along with one or more diketopiperazine units of aspartic acid, glutamic acid, serine, homoserine, and/or threonine in the presence of a suitable catalyst.
  • the dicarboxylic acid can be used directly or by way of a lower alkyl dicarboxylic ester or an anhydride.
  • the polymer of formula (I) of this invention is conveniently prepared by direct polymerization by heating the dicarboxylic acid and/or dicarboxylic ester and/or mono-alkyl ester of a dicarboxylic acid and/or an anhydride with the aliphatic glycol in the presence of a suitable catalyst.
  • a suitable catalyst Preferably, phthalic, succinic, maleic anhydrides, or the like, may be used.
  • the method of preparing a polymer described herein comprises combining in a reaction vessel (a) one or more compounds of formula R 1 (OH) 2 or R 1 (OR 6 ) 2 , wherein R 6 is an alkyl group, (b) one or more aliphatic glycols of formula R 2 (OH) 2 , (c) one or more diketopiperazine units of aspartic acid and/or glutamic acid, wherein the mole ratio of the diketopiperazine units of aspartic acid and glutamic acid to the compounds of formula R 1 (OH) 2 or R ⁇ OR 6 ⁇ is about 0.01 to about 0.8, and/or one or more diketopiperazine units of serine, homoserine, and/or threonine, wherein the mole ratio of the diketopiperazine units of serine, homoserine, and threonine to the aliphatic glycols R 2 (OH) 2 is about 0.01 to about 0.8, and
  • the reaction vessel is purged with an inert gas and heated to a first suitable temperature and a suitable pressure.
  • the temperature of the reaction vessel is then raised to a second suitable temperature, while reducing the pressure in the reaction vessel to suitable pressure, thereby synthesizing the polymer.
  • about 0.01 to 0.8 mole fraction of R 1 is replaced by one or more diketopiperazine units of aspartic acid and/or glutamic acid, and/or about 0.01 to 0.8 mole fraction of R 2 is replaced by one or more diketopiperazine units of serine, homoserine, and/or threonine.
  • a desired amount of the diketopiperazine units of aspartic acid and/or glutamic acid, and/or the diketopiperazine units of serine, homoserine, and/or threonine are added.
  • the diketopiperazine units of aspartic acid and glutamic acid can be used directly or as lower alkyl (e.g., Ci - C 6 ) dicarboxylic ester.
  • the diketopiperazine units of serine, homoserine, and threonine can be used directly.
  • the reactants are mixed in a suitable inert atmosphere and heated to a suitable first high temperature.
  • SSP Polymerization
  • Aromatic Dicarboxylic Acids Esters, Anhydrides, and Aromatic Mono-Alkyl Esters of Dicarboxylic Acids
  • any suitable aromatic dicarboxylic acid, lower alkyl (e.g., Ci - C 6 ) dicarboxylic ester, anhydrides, and/or lower alkyl (e.g., Ci - C 6 ) mono-alkyl ester of a dicarboxylic acid can be used.
  • the aromatic dicarboxylic acids can be aryl, heteroaryl, substituted, or unsubstituted aromatic dicarboxylic acids.
  • the aromatic dicarboxylic acids can include, e.g., Ci - C 2 o carbons.
  • the aromatic dicarboxylic acids can include C 5 - C 2 o, C 6 - C 2 o, Cg - C 2 o, Cio - C 2 o, C 12 - C 20 , and the like carbons.
  • some useful aromatic diacids can include those derived from phthalates, terephthalates, isophthalates, naphthalates, and the like.
  • aromatic dicarboxylic acid can include terephthalic acid, 1 ,4-naphthalene dicarboxylic acid, 2,6-napthalene dicarboxylic acid, 2,7- naphthalenedicarboxylic acid, 4,4'-biphenyl dicarboxylic acid, 3,4'-biphenyl dicarboxylic acid, 4,4 '-methylene bis(benzoic acid), 3,4'-diphenyl ether dicarboxylic acid, 4,4'-diphenyl ether dicarboxylic acid, 3,4'-diphenyl sulfide dicarboxylic acid, 4,4'-diphenyl sulfide dicarboxylic acid, 3,4'-diphenyl sulfone dicarboxylic acid, 4,4'-diphenyl sulfone dicarboxylic acid, 3,4'-benzophenonedicarboxylic acid, 4,4'-benzophenonedicarboxylic acid, 4,
  • the aromatic dicarboxylic acids are phthalic acid, isophthalic acid, terephthalic acid, 2,6-naphthalene dicarboxylic acid, or mixtures of two or more thereof.
  • any suitable aromatic dicarboxylic esters can also be used in place of aromatic dicarboxylic acids.
  • lower alkyl esters e.g., Ci - C 6
  • aromatic dicarboxylic esters with two lower alkoxy groups each of which is, for example, Ci - C 6
  • aromatic ring carbons for example, C 2 - C 2 o
  • the aromatic dicarboxylic esters have a total number of carbons of C 7 - C 32 , C 10 - C 32 , C 12 - C 32 , C 7 - C 24 , Cio - C 24 , and the like.
  • the aromatic dicarboxylic esters can be aryl, heteroaryl, substituted, or unsubstituted aromatic dicarboxylic esters.
  • some useful aromatic dicarboxylic esters can include those derived from phthalates, terephthalates, isophthalates, and naphthalates.
  • aromatic dicarboxylic acid components can include dimethyl isophthalate, dimethyl terephthalate, dimethyl- 1 ,4-naphthalate, dimethyl- 2,6-naphthalate, dimethyl-2,7-naphthalate, dimethyl phthalate, dimethyl-3,4'diphenyl ether dicarboxylate, dimethyl-4,4'-diphenyl ether dicarboxylate, dimethyl-3,4'-diphenyl sulfide dicarboxylate, dimethyl-4,4'-diphenyl sulfide dicarboxylate, dimethyl-3,4'-diphenyl sulfone dicarboxylate, dimethyl-4,4'-diphenyl sulfone dicarboxylate, dimethyl-3,4'- benzophenonedicarboxylate, dimethyl-4,4'-benzophenonedicarboxylate, dimethyl- 1 ,4- naphthalate, dimethyl-4, 4'-methylenebis(benzonedicar
  • any suitable aromatic mono-alkyl ester of a dicarboxylic acid can also be used in place of an aromatic dicarboxylic acid.
  • a lower alkyl e.g., Ci - C 6
  • the aromatic mono-alkyl ester of a dicarboxylic acid can be aryl, heteroaryl, substituted, or unsubstituted aromatic mono-alkyl ester of a dicarboxylic acid.
  • some useful aromatic mono-alkyl esters of dicarboxylic acids can include those derived from phthalates, terephthalates, isophthalates, and naphthalates.
  • useful mono-alkyl esters of dicarboxylic acids can include monomethyl isophthalate, monomethyl terephthalate, 1 ,4-naphthalene dicarboxylic acid monomethyl ester, 2,6-naphthalene dicarboxylic acid monomethyl ester, 2,7-naphthalene dicarboxylic acid monomethyl ester, monomethyl phthalate, and the like, and mixtures of two or more thereof.
  • any suitable aromatic anhydride may be used.
  • the anhydride can be straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated anhydride.
  • the anhydride can include, e.g., C 3 - C 36 carbons.
  • phthalic, succinic, maleic anhydrides, or the like may be used.
  • phthalic acid may be used.
  • any suitable aliphatic dicarboxylic acid, and/or lower alkyl (e.g., Ci - C 6 ) aliphatic dicarboxylic esters, or mono-alkyl ester of a dicarboxylic acid can be used.
  • the aliphatic dicarboxylic acids can be straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic dicarboxylic acids.
  • the aliphatic dicarboxylic acids can include, e.g., Ci - C 36 carbons. In other embodiments the aliphatic dicarboxylic acids can include C 3 - C 36 , C 5 - C 36 , C 3 - C 2 o, C 5
  • some useful aliphatic diacids can include those derived from succinate, glutarate, adipate, cyclohexane-1 ,4- dicarboxylate, dodecanedioate, isosanedioate, and the like.
  • Specific examples of some useful aliphatic dicarboxylic acids can include 1 , 10-decanedicarboxylic acid,
  • the aliphatic dicarboxylic acids used herein are succinic acid, glutaric acid, adipic acid, cyclohexane-l ,4-dicarboxylic acid, dodecanedioic acid, isosanedioic acid, and mixtures of two or more thereof.
  • any suitable aliphatic anhydride may be used.
  • the anhydride can be straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated anhydride.
  • the anhydride can include, e.g., C 3 - C 36 carbons.
  • succinic and maleic anhydrides, or the like may be used.
  • any suitable aliphatic dicarboxylic esters can also be used in place of aromatic dicarboxylic acids.
  • lower alkyl esters e.g., Ci - C 6
  • C 2 - C 36 aliphatic dicarboxylic esters can be used, i.e., aliphatic dicarboxylic esters with two lower alkoxy groups (each of which is, for example, Ci
  • the aliphatic dicarboxylic esters have a total number of carbons of C 5 - C 4 g, C 5 - C 36 , C 5 - C 3 o, C 5 - C 24 , and the like.
  • the aliphatic dicarboxylic esters can be straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic dicarboxylic esters.
  • some useful aliphatic dicarboxylic esters can include succinate, glutarate, adipate, cyclohexane-1,4- dicarboxylate, dodecanedioate, isosanedioate, and the like.
  • Specific examples of some useful aliphatic dicarboxylic esters can include dimethyl adipate, dimethyl azelate, dimethyl glutarate, dimethyl malonate, dimethyl succinate, dimethyl succinate, dimethyl- 1,3- yclohexanedicarboxylate, and dimethyl- 1 ,4-cyclohexanedicarboxylate, and the like, and mixtures of two or more thereof.
  • the aliphatic dicarboxylic esters used herein are dimethyl succinate, dimethyl glutarate, dimethyl adipate, dimethyl cyclohexane-1,4- dicarboxylate, dimethyl isosanedioate, or mixtures of two or more thereof.
  • any suitable aliphatic mono-alkyl ester of a dicarboxylic acid can also be used in place of an aromatic dicarboxylic acid.
  • a lower mono-alkyl ester e.g., Ci - C 6
  • a C 4 - C 42 aliphatic mono- alkyl ester of a dicarboxylic acid can be used.
  • dicarboxylic acid can be straight, branched, non-aromatic cyclic, saturated, substituted, or aliphatic mono-alkyl ester of a dicarboxylic acid.
  • some useful aliphatic mono-alkyl esters of dicarboxylic acids can include mono-alkyl esters of succinic acid, glutaric acid, adipic acid, 1 ,4-cyclohexanedicarboxylic acid, dodecanoic acid, and the like.
  • aliphatic mono-alkyl esters of dicarboxylic acids can include adipic acid-monomethyl ester, azelaic acid-monomethyl ester, glutaric acid- monomethyl ester, 1,3-cyclohexanedicarboxylic acid-monomethyl ester, 1,4- cyclohexanedicarboxylic acid-monomethyl ester and the like, and mixtures of two or more thereof.
  • any suitable aliphatic glycol can be used.
  • the aliphatic glycol can be straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic glycol.
  • the aliphatic glycol can include, e.g., C 2 - Cg linear carbons.
  • some useful aliphatic glycols can include ethylene glycol, 1,3 -propanediol, 1,3-butanediol, 1 ,4-butanediol, 1 ,6-hexanediol, neopentyl glycol, 1 ,2-propanediol, 1 ,2-butanediol, 2-methyl- 1,3 -propanediol, 1 ,6-hexanediol, poly(ethylene ether) glycols, and the like, and mixtures of two or more thereof.
  • any suitable catalyst may be used.
  • the catalysts that may be used include salts of Ca, Ge, Li, Mg, Mn, Pb, Sb, Sn, Ti, and Zn, e.g., acetate salts and oxides, including glycol adducts, and alkoxides.
  • the catalysts used herein can be any suitable catalysts that are known in the art. A person of ordinary skill in the art may select a single catalyst, a combination, or a sequence of catalysts with relative ease and without undue experimentation. The preferred catalyst can be different depending upon the conditions and the starting reactants.
  • dicarboxylic acid monomer may require a different catalyst than a dicarboxylic ester monomer.
  • choice of a different aliphatic glycol, or a different diketopiperazine may also require a different preferred suitable catalyst.
  • a method of preparing a homopolymer of dicarboxylate units and dialkoxy unit is also described in U.S. Patent No. 5,955,565.
  • a method of preparing diketopiperazines is also described in P.M. Fischer, Diketopiperazines in Peptide and Combinatorial Chemistry, 9 J.
  • the diketopiperazine unit can be of the form: (1, 1), (1, d), (d, 1), or (d, d) or any mixture of two or more thereof.
  • the term "1" is known in the art as levorotatory and the term
  • a polymer product prepared from the polymer of the invention will depend on several factors including the composition, mole fraction of R 1 and/or R 2 replaced with the diketopiperazines, the method of forming the polymer of the invention, and whether the polymer product was prepared with any specialized alignments. These factors affect many properties of the polymer product, such as chemical resistance, dielectric strength and constant, elongation at break, heat impact strength, melting point, shrinkage, tensile modulus, tensile strength, deflection temperature, and the like.
  • the properties of the polymer product may be further adjusted by adding certain additives and fillers to the polymeric composition, such as antioxidants, colorants, dyes, lubricants, antiblock agents, plasticizers, slip agents, UV and thermal stabilizers, and the like.
  • certain additives and fillers such as antioxidants, colorants, dyes, lubricants, antiblock agents, plasticizers, slip agents, UV and thermal stabilizers, and the like.
  • the polymer of the invention may be blended with one or more other polymers to improve its desired characteristics.
  • the polymers of the invention can be used in any suitable end use, including but not limited to, the same end uses of the corresponding conventional polymers, such as in molded parts for automotive, industrial and consumer products; fibers for clothing, fishing line and rope; and films for packaging. Because of their biodegradability and
  • some of the polymers of the invention can have important applications in bioengineering and biomaterials, e.g., drug delivery and medical devices.
  • the polymer of the invention can have improved dyeability as compared to the corresponding conventional polymer.
  • the dyeability of the polymer of the invention is a manifestation of a broader enhancement of surface properties.
  • the polymer of the invention can exhibit improved metallization, paint adhesion, adhesive bonding, interlayer adhesion in extrusion, and printability as compared to the corresponding convention polymer.
  • Diketopiperazines are naturally occurring dimers of a-amino acids.
  • the a-amino acids can be prepared by fermentation or enzymatic treatment of renewable feedstocks such as sugars, starches, and cellulosics.
  • renewable feedstocks such as sugars, starches, and cellulosics.
  • diketopiperazines are sustainable materials. Therefore, the products prepared from the polymer of the invention have the advantage of being formed, at least in part, from a renewable starting monomer.
  • R 1 is of formula
  • R 3 is a Ci - C 36 straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group
  • R 2 is a C 2 - C 8 straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group, except that (a) about 0.01 to about 0.8 mole fraction of R 1 is replaced by a diketopiperazine unit of formula (VII)
  • R 4 is -CH 2 C(0)- or -CH 2 CH 2 C(0)-, and/or (b) about 0.01 to about 0.8 mole fraction of R 2 is replaced by a diketopiperazine unit of formula (VIII)
  • R 5 is -CH 2 -, -CH 2 CH 2 -,or -CH(CH 3 )-.
  • embodiment (2) is presented a polymer of embodiment (1), wherein R 5 is only -CH 2 -.
  • embodiment (6) is presented a polymer of embodiment (4) or (5), wherein at least one monomer unit or R 1 us if formula (III).
  • embodiment (7) is presented a polymer of any one of embodiments (4)-(6), wherein at least one monomer unit of R 1 is of formula (IV).
  • embodiment (8) is presented a polymer of any one of embodiments (4)-(7), wherein at least one monomer unit of R 1 is of formula (V).
  • embodiment (9) is presented a polymer of any one of embodiments (4)-(8), wherein at least one monomer unit of R 1 is of formula (VI).
  • R 1 is of formula (VI), wherein R 3 is - CH 2 (CH 2 ) 2 CH 2 -.
  • embodiment (24) is presented a polymer of embodiment (16), wherein R 1 is of formula (VI), and R 3 is -CH 2 (CH 2 ) 2 CH 2 -.
  • embodiment (26) is presented a polymer of embodiment (16), wherein R 1 is of formula (VI), and R 3 is -CH 2 (CH 2 )i 4 CH 2 -.
  • embodiment (27) is presented a polymer of embodiment (16), wherein R 1 is of formula (VI), and R 3 is -CH 2 (CH 2 ) 8 CH 2 -.
  • embodiment (28) is presented a polymer of any one of embodiments (1)- (27), wherein the polymer comprises at least two different monomer units of R 2 .
  • embodiment (29) is presented a polymer of embodiment (28), wherein at least one monomer unit of R 2 is -CH 2 CH 2 -.
  • embodiment (30) is presented a polymer of embodiment (28) or (29), wherein at least one monomer unit of R 2 is -CH 2 CH(CH 3 )-.
  • embodiment (40) is presented a polymer of any one of embodiments (1)- (27), wherein each monomer unit of R 2 is the same.
  • embodiment (42) is presented a polymer of embodiment (40), wherein R 2 is -CH 2 CH(CH 3 )-.
  • IInn eemmbl odiment (46) is presented a polymer of embodiment (40), wherein R 2 is -CH 2 C(CH 3 ) 2 CH 2 -.
  • embodiment (47) is presented a polymer of embodiment (40), wherein R 2 is -CH 2 CH(CH 2 CH 3 )-.
  • embodiment (48) is presented a polymer of embodiment (40), wherein R 2 is -CH 2 (CH 2 ) 3 CH 2 -.
  • embodiment (49) is presented a polymer of embodiment (40), wherein R 2 is -CH 2 (CH 2 ) 4 CH 2 -.
  • embodiment (50) is presented a polymer of embodiment (40), wherein R 2 is -CH 2 (CH 2 ) 5 CH 2 -.
  • embodiment (51) is presented a polymer of embodiment (40), wherein R 2 is -CH 2 (CH 2 ) 6 CH 2 -.
  • embodiment (52) is presented a polymer of any one of embodiments (1)- (51), wherein at least one monomeric unit of R 1 is replaced by the diketopiperazme unit of formula (VII), wherein R 4 is -CH 2 C(0)-.
  • embodiment (53) is presented a polymer of any one of embodiments (1)- (51), wherein at least one monomeric unit of R 1 is replaced by the diketopiperazme unit of formula (VII), wherein R 4 is -CH 2 CH 2 C(0)-.
  • embodiment (54) is presented a polymer of embodiment (52) or (53), wherein the monomeric unit of R 2 is not replaced by a diketopiperazme unit.
  • embodiment (55) is presented a polymer of embodiment (52) or (53), wherein at least one monomeric unit of R 2 is replaced by the diketopiperazme unit of formula (VIII), wherein R 5 is -CH 2 -.
  • embodiment (56) is presented a polymer of any one of embodiments (52), (53), and (55), wherein at least one monomeric unit of R 2 is replaced by the diketopiperazme unit of formula (VIII), wherein R 5 is -CH(CH 3 )-.
  • embodiment (57) is presented a polymer of any one of embodiments (52), (53), (55), and (56), wherein at least one monomeric unit of R 2 is replaced by the
  • embodiment (59) is presented a polymer of any one of embodiments (1)- (51), and (58), wherein at least one monomeric unit of R 2 is replaced by the diketopiperazine unit of formula (VIII), wherein R 5 is only -CH(CH 3 )-.
  • embodiment (60) is presented a polymer of any one of embodiments in paragraphs (1)-(51), (58), and (59), wherein at least one monomeric unit of R 2 is replaced by the diketopiperazine unit of formula (VIII), wherein R 5 is only -CH 2 CH 2 -.
  • embodiment (63) is presented a polymer of any one of embodiments (1)- (61), wherein the diketopiperazine units are of form (d, d).
  • embodiment (64) is presented a polymer of any one of embodiments (1)- (61), wherein the diketopiperazine units are of form (1, d).
  • embodiment (65) is presented a polymer of any one of embodiments (1)- (61), wherein the diketopiperazine units are of form (d, 1).
  • embodiment (66) is presented a polymer of any one of embodiments (1)- (61), wherein the diketopiperazine units are of at least two different forms selected from (1, 1), (l, d), (d, l), and (d, d).
  • embodiment (67) is presented a polymer of any one of embodiments (1)- (53) and (62)-(66), wherein about 0.01 to about 0.3 mole fraction of one monomeric unit of R 1 is replaced by a diketopiperazine unit of formula (VII).
  • embodiment (68) is presented a polymer of embodiment (67), wherein about 0.01 to about 0.1 mole fraction of one monomeric unit of R 1 is replaced by a diketopiperazine unit of formula (VII).
  • (69) In embodiment (69) is presented a polymer of embodiment (68), wherein about 0.02 to about 0.07 mole fraction of one monomeric unit of R 1 is replaced by a diketopiperazine unit of formula (VII).
  • (70) In embodiment (70) is presented a polymer of any one of embodiments (1)- (53) and (55)-(69), wherein about 0.01 to about 0.3 mole fraction of R 2 is replaced by a diketopiperazine unit of formula (VIII).
  • embodiment (71) is presented a polymer of embodiment (70), wherein about 0.01 to about 0.1 mole fraction of one monomeric unit of R 2 is replaced by a diketopiperazine unit of formula (VIII).
  • embodiment (72) is presented a polymer of embodiment (71), wherein about 0.02 to about 0.07 mole fraction of one monomeric unit of R 2 is replaced by a diketopiperazine unit of formula (VIII).
  • embodiment (73) is presented a polymer of any one of embodiments (1)- (72), wherein at least one of the monomeric units of R 2 is of the formula
  • embodiment (74) is presented a polymer of embodiment (73), wherein at least one of the monomeric units of R 2 is of formula (X), and at least one of the monomeric units of R 2 is of formula (XI).
  • embodiment (75) is presented a polymer of embodiment (73), wherein at least one of the monomeric units of R 2 is of formula (X).
  • embodiment (76) is presented a polymer of embodiment (73), wherein at least one of the monomeric units of R 2 is of formula (XI).
  • embodiment (77) is presented a polymer of any one of embodiments (1)- (76), wherein the polymer has a molecular weight of about 500 g/mol to about 1 million g/mol.
  • embodiment (78) is presented a polymer of embodiment (77), wherein the polymer has a molecular weight of about 20,000 g/mol to about 1 million g/mol.
  • embodiment (79) is presented a polymer of embodiment (78), wherein the polymer has a molecular weight of about 20,000 g/mol to about 100,000 g/mol.
  • (80) In embodiment (80) is presented a polymer of embodiment (77), wherein the polymer has a molecular weight of about 500 g/mol to about 100,000 g/mol. [0164] (81) In embodiment (81) is presented a polymer of embodiment (80), wherein the polymer has a molecular weight of about 500 g/mol to about 20,000 g/mol.
  • embodiment (82) is presented a polymer of embodiment (81), wherein the polymer has a molecular weight of about 500 g/mol to about 10,000 g/mol.
  • embodiment (83) is presented a polymer of embodiment (82), wherein the polymer has a molecular weight of about 500 g/mol to about 3,000 g/mol.
  • embodiment (84) is presented a method of preparing a polymer of any one of embodiments (l)-(83) comprising: (i) combining in a reaction vessel (a) one or more compounds of formula R 1 (OH) 2 or R 1 (OR 6 ) 2 , wherein R 6 is an alkyl group, (b) one or more aliphatic glycols of formula R 2 (OH) 2 , (c) one or more diketopiperazme units of aspartic acid and/or glutamic acid, wherein the mole ratio of the diketopiperazme units of aspartic acid and glutamic acid to the compounds of formula R 1 (OH) 2 or R 1 (OR 6 ) 2 is about 0.01 to about 0.8, and/or one or more diketopiperazme units of serine and/or threonine, wherein the mole ratio of the diketopiperazme units of serine and threonine to the aliphatic glycols R 2 (OH)
  • subpart (c) only includes one or more diketopiperazme units of aspartic acid and/or glutamic acid.
  • subpart (c) is presented a method of embodiment (84), wherein subpart (c) only includes one or more diketopiperazme units of of serine, homoserine, and/or threonine.
  • embodiment (87) is presented a method of embodiment (86), wherein subpart (c) only includes one or more diketopiperazme units of serine.
  • embodiment (88) is presented a method of embodiment (86), wherein subpart (c) only includes one or more diketopiperazme units of homoserine.
  • embodiment (92) is presented a method of embodiment (90), wherein at least one monomer unit of R 1 is of formula (II).
  • embodiment (93) is presented a method of embodiment (91) or (92), wherein at least one monomer unit of R 1 is of formula (III).
  • embodiment (109) is presented a method of embodiment (103), wherein R 1 is of formula (VI), and R 3 is -CH 2 CH 2 CH 2 -.
  • embodiment (112) is presented a method of embodiment (103), wherein R 1 is of formula (VI), and R 3 is -CH 2 (CH 2 )i 4 CH 2 -.
  • embodiment (115) is presented a method of embodiment (114), wherein at least one monomer unit of R 2 is -CH 2 CH 2 -.
  • embodiment (116) is presented a method of embodiment (114) or (115), wherein at least one monomer unit of R 2 is -CH 2 CH(CH 3 )-.
  • R 2 is -CH 2 CH 2 -.
  • embodiment (130) is presented a method of embodiment (126), wherein R 2 is -CH 2 CH 2 CH 2 -.
  • embodiment (132) is presented a method of embodiment (126), wherein R 2 is -CH 2 C(CH 3 ) 2 CH 2 -.
  • embodiment (133) is presented a method of embodiment (126), wherein R 2 is -CH 2 CH(CH 2 CH 3 )-.
  • embodiment (134) is presented a method of embodiment (126), wherein R 2 is -CH 2 (CH 2 ) 3 CH 2 -.
  • embodiment (136) is presented a method of embodiment (126), wherein R 2 is -CH 2 (CH 2 ) 5 CH 2 -.
  • embodiment (137) is presented a method of embodiment (126), wherein R 2 is -CH 2 (CH 2 ) 6 CH 2 -.
  • embodiment (138) is presented a method of any one of embodiments (84)-(137), wherein the reaction vessel contains at least one diketopiperazme unit of aspartic acid.
  • embodiment (139) is presented a method of any one of embodiments (84)-(138), wherein the reaction vessel contains at least one diketopiperazme unit of glutamic acid.
  • embodiment (140) is presented a method of embodiment (138) or (139), wherein the reaction vessel does not contain any diketopiperazme unit of serine, homoserine, or threonine.
  • embodiment (141) is presented a method of embodiment (138) or (139), wherein the reaction vessel contains at least one diketopiperazme unit of serine.
  • reaction vessel contains at least one diketopiperazme unit of threonine.
  • reaction vessel contains at least one
  • embodiment (144) is presented a method of any one of embodiments (84)-(137), wherein the reaction vessel contains at least one diketopiperazme unit of serine.
  • embodiment (145) is presented a method of any one of embodiments (84)-(137) and (144), wherein the reaction vessel contains at least one diketopiperazme unit of threonine.
  • embodiment (147) is presented a method of any one of embodiments (144)-(146), wherein the reaction vessel does not contain a diketopiperazme unit of either aspartic acid or glutamic acid.
  • embodiment (148) is presented a method of any one of embodiments (138)-(146), wherein the diketopiperazme units are of form (1, 1).
  • embodiment (149) is presented a method of any one of embodiments (138)-(146), wherein the diketopiperazme units are of form (d, d).
  • embodiment (150) is presented a method of any one of embodiments (138)-(147), wherein the diketopiperazme units are of form (1, d).
  • embodiment (151) is presented a method of any one of embodiments (138)-(147), wherein the diketopiperazme units are of form (d, 1).
  • embodiment (152) is presented a method of any one of embodiments (138)-(147), wherein the diketopiperazme units are of at least two different forms selected from (1, 1), (1, d), (d, 1), and (d, d).
  • embodiment (153) is presented a method of any one of embodiments (84) and (90)-(152), wherein the mole ratio of the diketopiperazme unit of aspartic acid and glutamic acid to the compounds of formula R 1 (OH) 2 or R ⁇ OR 6 ⁇ is about 0.01 to about 0.3 and/or the mole ratio of the diketopiperazme units of serine, homoserine, and threonine to the aliphatic glycols of formula R 2 (OH) 2 is about 0.01 to about 0.3.
  • embodiment (154) is presented a method of any one of embodiments (84)- (152), wherein the mole ratio of the diketopiperazme unit of aspartic acid and glutamic acid to the compounds of formula R 1 (OH) 2 or R 1 (OR 6 ) 2 is about 0.01 to about 0.3 and/or the mole ratio of the diketopiperazine units of serine, and threonine to the aliphatic glycols of formula R 2 (OH) 2 is about 0.01 to about 0.3.
  • embodiment (155) is presented a method of embodiment (153), wherein the mole ratio of the diketopiperazine unit of aspartic acid and glutamic acid to the compounds of formula R 1 (OH) 2 or R 1 (OR 6 ) 2 is about 0.01 to about 0.1 and/or the mole ratio of the diketopiperazine units of serine, homoserine, and threonine to the aliphatic glycols of formula R 2 (OH) 2 is about 0.01 to about 0.1.
  • embodiment (156) is presented a method of embodiment (154), wherein the mole ratio of the diketopiperazine unit of aspartic acid and glutamic acid to the compounds of formula R 1 (OH) 2 or R x (OR 6 ) 2 is about 0.01 to about 0.1 and/or the mole ratio of the diketopiperazine units of serine and threonine to the aliphatic glycols of formula R 2 (OH) 2 is about 0.01 to about 0.1.
  • embodiment (157) is presented a method of embodiment (155), wherein the mole ratio of the diketopiperazine unit of aspartic acid and glutamic acid to the compounds of formula R 1 (OH) 2 or R x (OR 6 ) 2 is about 0.02 to about 0.07 and/or the mole ratio of the diketopiperazine units of serine, homoserine, and threonine to the aliphatic glycols of formula R 2 (OH) 2 is about 0.02 to about 0.07.
  • embodiment (158) is presented a method of embodiment (156), wherein the mole ratio of the diketopiperazine unit of aspartic acid and glutamic acid to the compounds of formula R 1 (OH) 2 or R x (OR 6 ) 2 is about 0.02 to about 0.07 and/or the mole ratio of the diketopiperazine units of serine and threonine to the aliphatic glycols of formula R 2 (OH) 2 is about 0.02 to about 0.07.
  • embodiment (159) is presented a method of any one of embodiments (84)-(157), further comprising adding at least one of the compounds of formulas (XII) and (XIII)
  • reaction vessel preferably prior to heating the reaction vessel.
  • R 1 is of formula
  • R is a Ci - C 19 straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group
  • R 2 is a C 2 - Cg straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group, by (a) replacing about 0.01 to about 0.8 mole fraction of R 1 by a diketopiperazine unit of formula (VII)
  • R 5 is -CH 2 -, -CH 2 CH 2 -, or -CH(CH 3 )-.
  • embodiment (161) is presented a method of embodiment (160), wherein R 5 is -CH 2 - or -CH(CH 3 )-.
  • R 1 is an aliphatic or aromatic dicarboxylate unit
  • the aliphatic dicarboxylate unit comprises a C 3 - C 36 straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group
  • the aromatic dicarboxylate unit comprises a C 5 - C 2 o aryl, heteroaryl, substituted, or unsubstituted aromatic dicarboxylate group
  • R 2 is a C 2 - Cs straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group, except that (a) about 0.01 to about 0.8 mole fraction of R 1 is replaced by a diketopiperazine unit of formula (VII)
  • R 4 is -CH 2 C(0)- or -CH 2 CH 2 C(0)-, and/or (b) about 0.01 to about 0.8 mole fraction of R 2 is replaced by a diketopiperazine unit of formula (VIII)
  • R 5 is -CH 2 -, -CH 2 CH 2 -, or -CH(CH 3 )-.
  • embodiment (163) is presented a polymer of embodiment (162), wherein R 5 is only -CH 2 -.
  • embodiment (164) is presented a polymer of embodiment (162), wherein R 5 is only -CH(CH 3 )-.
  • embodiment (165) is presented a polymer of embodiment (162), wherein R 5 is only -CH 2 CH 2 -.
  • This example demonstrates a method of preparing a homopolymer of polyethylene terephthalate (PET).
  • the reaction vessel was placed in an aluminum-housed heating mantle and, with stirring, was heated at a temperature of 190 °C for 1 hour, then at a temperature of 210 °C for 1.5 hour, and then at a temperature of 260 °C for 30 minutes. Vacuum was gradually applied over the next 30 minutes until a pressure of about 133.3 Pa (1 mm Hg) was obtained. After 10 minutes, the temperature was increased to 270 °C, and full vacuum was maintained for a total time of 1 hour. Upon completion, the pressure of the reaction vessel was brought to atmospheric pressure, and the hot contents of the flask were slowly poured into an aluminum container with ice water to form an amorphous strand of polymer. The intrinsic viscosity of the resulting homopolymer was measured in o-chlorophenol solvent as 0.576 dL/g.
  • This example demonstrates a method of preparing a copolymer from terephthalic acid, ethylene glycol, and diketopiperazine unit of serine.
  • the reaction vessel was placed in an aluminum-housed heating mantle and, with stirring, was heated at a temperature of 190 °C for 1.5 hours, then at a temperature of 210 °C for 1.5 hour, and then at a temperature of 230 °C for 1 hour and 20 minutes. Vacuum was gradually applied over the next 30 minutes until a pressure of less than about 133.3 Pa (less than 1 mm Hg) was obtained. Full vacuum was maintained for another 50 minutes. Upon completion, the pressure of the reaction vessel was brought to atmospheric pressure. The hot contents of the flask, which had solidified on the stirrer, were removed from the reactor and collected on an aluminum sheet. The intrinsic viscosity of the resulting copolymer was measured in o-chlorophenol solvent as 0.123 dL/g.
  • This example demonstrates a method of preparing higher molecular weight copolymer containing diketopiperazine using the Solid State Polymerization process.
  • This example demonstrates a method of preparing a copolymer of a terephthalate, ethylene glycol, and a diketopiperazine unit of aspartate.
  • the reaction vessel was placed in an aluminum-housed heating mantle and, with stirring, was heated at a temperature of 190 °C for 1 hour, then at a temperature of 210 °C for 1.5 hour, and then at a temperature of 250 °C for 30 minutes. Vacuum was gradually applied over the next 30 minutes until a pressure of 133.3 Pa (about 1 mm Hg) was obtained. After 10 minutes, the temperature was increased to 260 °C, and a full vacuum was maintained for a total time of 1 hour.
  • This example compares certain physical and thermal properties between a homopolymer of polyethylene terephthalate (PET) and a copolymer in which 0.03 mole fraction of the dialkoxy units were replaced with the diketopiperazine units of serine (serine- DKP (3 mol%)/PET copolymer).
  • PET prepared in accordance with Example 1 and serine-DKP (3 mol%)/PET copolymer prepared in accordance with Example 3 were each subjected to an analysis for the properties indicated in Table 1. The results are set forth in Table 1. The thermal properties were determined by differential scanning calorimetry (DSC). [0265] Table 1 : Comparison between the physical and thermal properties of polyethylene terephthalate (PET) and serine -DKP (3 mol%)/PET copolymer.
  • serine-DKP (3 mol%)/PET copolymer had a lower glass transition temperature (Tg) and a higher melting temperature (Tm).
  • serine-DKP (3 mol%)/PET copolymer had a lower temperature of crystallization on heating (Tch) from the amorphous state and a higher temperature of crystallization (Tec) on cooling from the melt.
  • the heat of crystallization on heating (Hch) was also higher for serine-DKP (3 mol%)/PET copolymer as compared to PET, thereby indicating that serine-DKP (3 mol%)/PET copolymer had greater crystallinity than PET.
  • This example compares the physical and thermal properties of a homopolymer of polyethylene terephthalate (PET), a copolymer in which 0.03 mole fraction of the terephthalate monomer units were replaced with the diketopiperazme units of aspartic acid (aspartic acid-DKP (3 mol%)/PET copolymer), and a second copolymer in which 0.1 mole fraction of the terephthalate monomer units were replaced with the diketopiperazme units of aspartic acid (aspartic acid-DKP (10 mol%)/PET copolymer).
  • PET prepared in accordance with Example 1 aspartic acid-DKP (3 mol%)/PET copolymer prepared in accordance with Example 2, and aspartic acid-DKP (10 mol%)/PET copolymer were each subjected to an analysis for the properties identified in Table 2. The results are set forth in Table 2.
  • Table 2 Comparison between the physical and thermal properties of polyethylene terephthalate (PET), aspartic acid-DKP (3 mol%)/PET copolymer, and aspartic acid-DKP (10 mol%)/PET copolymer.
  • Aspartic acid-DKP (10 mol %)/PET copolymer became insoluble in typical solvents used to measure intrinsic viscosity, e.g., trifluoroacetic acid and
  • This example compares the mechanical and thermal properties of a homopolymer of polyethylene terephthalate (PET) and a copolymer in which 0.03 mole fraction of the terephthalate monomer units were replaced with the diketopiperazine units of aspartate (aspartate-DKP (3 mol%)/PET copolymer).
  • Samples were prepared by compression molding using a press. Prior to applying the force, the material was heated to 255 °C in the press and kept at this temperature for 10 minutes. Then, the material was pressed into a sheet at a temperature of 255 °C under 2 tons of force for an additional 10 minutes. At the end of 10 minutes, the mold was removed from the press and allowed to cool at room temperature on a lab bench. The thickness of the material produced from this process was about 1.4 mm.
  • the DMA samples were prepared by filing the fragments of the pressed material into a rectangular form using fine grain sandpaper. The final dimension of the test samples were approximately 15 mm long, 9 mm wide, and 1.4 mm thick.
  • DMA Run Conditions All polymer samples were tested using the same test parameters. DMA measurements were performed in a Mettler Toledo DMA861e instrument but any suitable instrument may be used. The temperature program had a two-step profile. The temperature of the sample was held at 26 °C for three minutes and then heated from 26 °C to 150 °C at 5 °C/min. The force and displacement amplitude values were 1 Newton (N) and 2 ⁇ , respectively for both PET and aspartate-DKP (3 mol%)/PET copolymer samples.
  • Fig. 1 shows a comparison of storage modulus data for samples of polyethylene terephthalate (PET) and aspartate-DKP (3 mol%)/PET copolymer.
  • PET polyethylene terephthalate
  • aspartate-DKP 3 mol%)/PET copolymer
  • the mechanical properties of PET are altered by the incorporation of low levels of aspartate DKP.
  • the aspartate-DKP (3 mol%)/PET copolymer demonstrated a higher storage modulus, which means that the aspartate-DKP (3 mol%)/PET copolymer was stiffer than the base PET.
  • Fig. 2 shows a comparison of tan delta data for samples of PET and the aspartate- DKP (3 mol%)/PET copolymer as measured by DMA.
  • the maximum value of tan delta is a measure of the glass transition temperature (Tg), which reflects the onset of the transition of the polymer from a glassy to a rubbery state.
  • Fig. 2 shows that the glass transition
  • Tg temperature of the aspartate-DKP (3 mol%)/PET copolymer is lower than the base PET.
  • This example demonstrates a method of preparing a homopolymer of polyethylene adipate (PEA).
  • the reaction vessel was stirred at 60 rpm and placed in a hot oil bath, which was heated at a temperature of 170 °C for 1 hour, then at a temperature of 180 °C for 0.5 hour, then at a temperature of 190 °C with the stirrer speed set at 100 rpm for 0.5 hour, then at a temperature of 200 °C with the stirrer speed set at 150 rpm for 1 hour, and then at a temperature of 210 °C with the stirrer speed maintained at 150 rpm for 0.75 hour.
  • Vacuum was gradually applied over the next 40 minutes until a pressure of about 66.7 Pa (0.5 mm of Hg) was obtained. After 30 minutes, the temperature was increased to 220 °C for 1.75 hours, then to 230 °C for 1 hour, and then to 240 °C for 0.25 hour. During the period that the reaction was at full vacuum (i.e., 66.7 Pa (0.5 mm of Hg) or lower), the stirrer speed was gradually increased in 50 rpm increments until a final speed of 600 rpm was achieved. The stirrer speed of 600 rpm was maintained for the final hour of the reaction.
  • This example demonstrates a method of preparing a copolymer of an adipate, ethylene glycol and diketopiperazine of aspartate at 5 mole %.
  • the reaction vessel was stirred at 60 rpm and placed in a hot oil bath, which was heated at a temperature of 170 °C for 1 hour, then at a temperature of 180 °C for 0.5 hour, then at a temperature of 190 °C with the stirrer speed set at 100 rpm for 0.5 hour, then at a temperature of 200 °C with the stirrer speed set at 150 rpm for 1 hour, and then at a temperature of 210 °C with the stirrer speed maintained at 150 rpm for 0.75 hour.
  • Vacuum was gradually applied over the next 40 minutes until a pressure of about 66.7 Pa (0.5 mm of Hg) was obtained. After 30 minutes, the temperature was increased to 220 °C for 1 hour, then to 230 °C for 0.75 hour, and then to 240 °C for 0.25 hour. During the period that the reaction was at full vacuum (i.e., 66.7 Pa (0.5 mm of Hg) or lower), the stirrer speed was gradually increased in 50 rpm increments until a final speed of 600 rpm was achieved. The stirrer speed of 600 rpm was maintained for the final hour of the reaction.
  • This example demonstrates a method of preparing a copolymer of an adipate, ethylene glycol and diketopiperazine of aspartate at 10 mole %.
  • the reaction vessel was stirred at 60 rpm and placed in a hot oil bath, which was heated at a temperature of 170 °C for 1 hour, then at a temperature of 180 °C for 0.5 hour, then at a temperature of 190 °C with the stirrer speed set at 100 rpm for 0.5 hour, then at a temperature of 200 °C with the stirrer speed set at 150 rpm for 1 hour, and then at a temperature of 210 °C with the stirrer speed maintained at 150 rpm for 0.75 hour. To the reaction mixture was then added 0.4 g of dibutyltin diacetate (449 ppm).
  • Vacuum was gradually applied over the next 40 minutes until a pressure of about 66.7 Pa (0.5 mm of Hg) was obtained. After 30 minutes, the temperature was increased to 220 °C for 1 hour, and then to 225 °C for 0.5 hour. During the period that the reaction was at full vacuum (i.e., 66.7 Pa (0.5 mm of Hg) or lower), the stirrer speed was gradually increased in 50 rpm increments until a final speed of 400 rpm was achieved. The stirrer speed of 400 rpm was maintained for the final hour of the reaction. During the final hour of the reaction, stirrer torque gradually increased to a final value of 33-lb-in.
  • This example provides a method using proton nuclear magnetic resonance (NMR) spectroscopy to provide the relative molecular weight data for the polymers prepared in Examples 8, 9, and 10.
  • NMR proton nuclear magnetic resonance
  • the solvent of the polymer was deuterochloroform (CDCI 3 ).
  • a synthetic sample of polyethylene adipate (PEA) was obtained from Sigma- Aldrich (#181919, Lot
  • Table 3 Comparison of proton NMR data from PEA of Sigma- Aldrich (control) of 10,000 molecular weight as determined by GPC to PEA homopolymer from Example 7 and PEA containing 5 mole% aspartate (Example 8), and 10 mole% aspartate (Example 9).
  • This example demonstrates a comparison between the mechanical and thermal properties of a homopolymer of polyethylene adipate (PEA) and a copolymer in which 0.10 mole fraction of the adipate monomer units were replaced with the diketopiperazine units of aspartate (aspartate -DKP (10 mol%)/PEA copolymer).
  • PEA polyethylene adipate
  • a copolymer in which 0.10 mole fraction of the adipate monomer units were replaced with the diketopiperazine units of aspartate (aspartate -DKP (10 mol%)/PEA copolymer).
  • Samples were prepared by compression molding using a press. These materials were pressed into a sheet at a temperature of 55 °C under 4 tons of force for 10 minutes. The material was then cooled to room temperature using the water cooling system in the press. After cooling, the material was folded and subjected to a second compression molding step using the same parameters. The samples were kept at ambient conditions for a minimum time period of 24 hours before testing.
  • Rectangular DMA samples were prepared by cutting the sheet with a die cutter.
  • the die had a dog bone shape, and the gage section was cut out to form the DMA sample.
  • the nominal dimensions of the samples were 9 mm long, 3 mm wide, and 0.5 mm thick.
  • DMA Run Conditions The polyester samples were tested under the same temperature programs but at different force and displacement amplitude values to account for the differences in the mechanical properties observed while handling the samples.
  • the base PEA polymer was brittle, and the PEA copolymer containing 10 mole% aspartate was more flexible.
  • DMA measurements were performed in a Mettler Toledo DMA861e instrument but any suitable instrument may be used.
  • the temperature program had a three-step profile. First, the temperature was cooled from room temperature to -58 °C; then, it was held at -58 °C for three minutes; and finally the temperature was raised from -55 °C to 35 °C at 5 °C/min.
  • the force and displacement amplitude values used for the two samples are given in Table 4. These values were found to be within the linear viscoelastic limit for each material.
  • Fig. 3 shows a comparison of storage modulus data for samples of polyethylene adipate (PEA) and a PEA copolymer containing aspartate DKP- (10 mole %) (aspartate-DKP (10 mol%)/PEA copolymer) as measured by DMA.
  • the mechanical properties of PEA are altered by the incorporation of low levels of aspartate DKP.
  • the aspartate-DKP (10 mol%)/PEA copolymer demonstrated an increased stiffness at sub-ambient temperatures and reduced stiffness, i.e. increased flexibility, at temperatures closer to ambient conditions.
  • the aspartate-DKP (10 mol%)/PEA copolymer had a significant improvement in structural integrity compared to the base PEA.
  • the base PEA is rigid and brittle the aspartate-DKP (10 mol%)/PEA copolymer was flexible.
  • Fig. 4 shows a comparison of tan delta data for samples of PEA and the aspartate-DKP (10 mol%)/PEA copolymer as measured by DMA.
  • the data presented in Fig. 4 show that the glass transition temperature (Tg) of the aspartate-DKP (10 mol%)/PEA copolymer is higher than that for the base PEA.
  • Tg glass transition temperature
  • This example demonstrates a method of preparing a copolymer from a
  • reaction vessel is placed in an aluminum-housed heating mantle and, with stirring, is heated at a temperature of 190 °C for 1.5 hours, then at a temperature of 210 °C for 1.5 hour, and then at a temperature of 230 °C for 1 hour and 20 minutes. Vacuum is gradually applied over the next 30 minutes until a pressure of less than about 133.3 Pa (less than 1 mm Hg) is obtained. Full vacuum is maintained for another 50 minutes.
  • This example illustrates the expected properties of a copolymer prepared from terephthalic acid as the dimethyl ester, ethylene glycol, and diketopiperazine unit of threonine (threonine -DKP/PET copolymer), as compared to the corresponding conventional polymer, polyethylene terephthalate (PET).
  • threonine -DKP/PET copolymer a copolymer prepared from terephthalic acid as the dimethyl ester, ethylene glycol, and diketopiperazine unit of threonine
  • Threonine -DKP units replace the dialkoxy units in the conventional copolymer PET.
  • the threonine -DKP /PET copolymer shows a lower glass transition temperature (Tg), and a higher degree of crystallinity than the base PET.
  • Threonine - DKP/PET copolymer also shows improved biodegradability.
  • This example demonstrates a method of preparing a copolymer of an adipate, ethylene glycol and diketopiperazine of threonine.
  • the reaction vessel is placed in hot oil bath and, with stirring set at 60 rpm, is heated at a temperature of 170 °C for 1 hour, then at a temperature of 180 °C for 0.5 hour, then at a temperature of 190 °C with the stirrer speed set at 100 rpm for 0.5 hour, then at a temperature of 200 °C with the stirrer speed set at 150 rpm for 1 hour, and then at a temperature of 210 °C with the stirrer speed maintained at 150 rpm for 0.75 hour.
  • Vacuum is gradually applied over the next 40 minutes until a pressure of about 66.7 Pa (0.5 mm of Hg) is obtained. After 30 minutes, the temperature is increased to 220 °C for 1 hour, then to 230 °C for 0.75 hour, and then to 240 °C for 0.25 hour. During the period that the reaction is at full vacuum, stirrer speed is gradually increased in 50 rpm increments until a final speed of 600 rpm is achieved. A stirrer speed of 600 rpm is maintained for the final hour of the reaction.
  • This example illustrates the expected properties of a copolymer prepared from adipic acid as the dimethyl ester, ethylene glycol, and diketopiperazine unit of threonine (threonine -DKP/PEA copolymer), as compared to the corresponding conventional polymer, polyethylene adipate (PEA).
  • Threonine -DKP units replace the dialkoxy units in the conventional copolymer PEA.
  • threonine-DKP/PEA copolymer shows a higher glass transition temperature (Tg), a higher melting temperature (Tm), an improved temperature of crystallization on heating (Tch) when heated from the amorphous state, and an improved temperature of crystallization (Tec) when cooled from the melt.
  • Threonine-DKP/PEA copolymer also shows improved biodegradability.
  • This example demonstrates a method of preparing a copolymer from a
  • reaction vessel is placed in an aluminum-housed heating mantle and, with stirring, is heated at a temperature of 190 °C for 1.5 hours, then at a temperature of 210 °C for 1.5 hour, and then at a temperature of 230 °C for 1 hour and 20 minutes. Vacuum is gradually applied over the next 30 minutes until a pressure of less than about 133.3 Pa (less than 1 mm Hg) is obtained. Full vacuum is maintained for another 50 minutes.
  • This example illustrates the expected properties of a copolymer prepared from terephthalic acid as the dimethyl ester, ethylene glycol, and diketopiperazine unit of homoserine (homoserine-DKP/PET copolymer), as compared to the corresponding conventional polymer, polyethylene terephthalate (PET).
  • Homoserine-DKP units replace the dialkoxy units in the conventional copolymer PET.
  • the homoserine-DKP /PET copolymer shows a lower glass transition temperature (Tg), and a higher degree of crystallinity than the base PET.
  • Homoserine-DKP/PET copolymer also shows improved biodegradability.
  • This example demonstrates a method of preparing a copolymer of an adipate, ethylene glycol and diketopiperazine of homoserine.
  • the reaction vessel is placed in hot oil bath and, with stirring set at 60 rpm, is heated at a temperature of 170 °C for 1 hour, then at a temperature of 180 °C for 0.5 hour, then at a temperature of 190 °C with the stirrer speed set at 100 rpm for 0.5 hour, then at a temperature of 200 °C with the stirrer speed set at 150 rpm for 1 hour, and then at a temperature of 210 °C with the stirrer speed maintained at 150 rpm for 0.75 hour.
  • Vacuum is gradually applied over the next 40 minutes until a pressure of about 66.7 Pa (0.5 mm of Hg) is obtained. After 30 minutes, the temperature is increased to 220 °C for 1 hour, then to 230 °C for 0.75 hour, and then to 240 °C for 0.25 hour. During the period that the reaction is at full vacuum, stirrer speed is gradually increased in 50 rpm increments until a final speed of 600 rpm is achieved. A stirrer speed of 600 rpm is maintained for the final hour of the reaction.
  • This example illustrates the expected properties of a copolymer prepared from adipic acid as the dimethyl ester, ethylene glycol, and diketopiperazine unit of homoserine (homoserine-DKP/PEA copolymer), as compared to the corresponding conventional polymer, polyethylene adipate (PEA).
  • Homoserine-DKP units replace the dialkoxy units in the conventional copolymer PEA.
  • homoserine-DKP/PEA copolymer shows a higher glass transition temperature (Tg), a higher melting temperature (Tm), an improved temperature of
  • reaction vessel is placed in an aluminum-housed heating mantle and, with stirring, is heated at a temperature of 190 °C for 1.5 hours, then at a temperature of 210 °C for 1.5 hour, and then at a temperature of 230 °C for 1 hour and 20 minutes. Vacuum is gradually applied over the next 30 minutes until a pressure of less than about 133.3 Pa (less than 1 mm Hg) is obtained. Full vacuum is maintained for another 50 minutes.
  • This example illustrates the expected properties of a copolymer prepared from terephthalic acid as the dimethyl ester, ethylene glycol, and diketopiperazine unit of glutamic acid (glutamate -DKP/PET copolymer), as compared to the corresponding conventional polymer, polyethylene terephthalate (PET).
  • Glutamate-DKP units replace the dicarboxy units in the conventional copolymer PET.
  • the glutamate-DKP /PET copolymer shows a lower glass transition temperature (Tg), and a higher degree of crystallinity than the base PET.
  • Glutamate- DKP/PET copolymer also shows improved biodegradability.
  • This example demonstrates a method of preparing a copolymer of an adipate, ethylene glycol and diketopiperazine of glutamate.
  • a glass reaction vessel fitted with a stirrer and a Dean-Stark trap with a condenser are added 283.51 g of dimethyl adipate (1.628 mole), 35.05 g of dimethyl ester of glutamate diketopiperazine (0.122 moles), 152.07 g of ethylene glycol (2.45 moles), 0.055 g zinc acetate dihydrate (54 ppm), and 0.40 g of dibutyltin diacetate (449 ppm). The vessel is purged with nitrogen for 5 minutes.
  • the reaction vessel is placed in hot oil bath and, with stirring set at 60 rpm, is heated at a temperature of 170 °C for 1 hour, then at a temperature of 180 °C for 0.5 hour, then at a temperature of 190 °C with the stirrer speed set at 100 rpm for 0.5 hour, then at a temperature of 200 °C with the stirrer speed set at 150 rpm for 1 hour, and then at a temperature of 210 °C with the stirrer speed maintained at 150 rpm for 0.75 hour.
  • Vacuum is gradually applied over the next 40 minutes until a pressure of about 66.7 Pa (0.5 mm of Hg) is obtained. After 30 minutes, the temperature is increased to 220 °C for 1 hour, then to 230 °C for 0.75 hour, and then to 240 °C for 0.25 hour. During the period that the reaction is at full vacuum, stirrer speed is gradually increased in 50 rpm increments until a final speed of 600 rpm is achieved. A stirrer speed of 600 rpm is maintained for the final hour of the reaction.
  • This example illustrates the expected properties of a copolymer prepared from adipic acid as the dimethyl ester, ethylene glycol, and diketopiperazine unit of glutamic acid (glutamate -DKP/PEA copolymer), as compared to the corresponding conventional polymer, polyethylene adipate (PEA).
  • Glutamate-DKP units replace the dicarboxy units in the conventional copolymer PEA.
  • glutamate-DKP/PEA copolymer shows a higher glass transition temperature (Tg), a higher melting temperature (Tm), an improved temperature of crystallization on heating (Tch) when heated from the amorphous state, and an improved temperature of crystallization (Tec) when cooled from the melt.
  • Glutamate-DKP/PEA copolymer also shows improved biodegradability.

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Abstract

The invention provides a polymer containing at least two monomer units of a dicarboxylate unit and at least two monomer units of a dialkoxy unit except that (a) some of the dicarboxylate units are replaced by diketopiperazine units of aspartic acid and/or a diketopiperazine units of glutamic acid, and/or (b) some of the dialkoxy units are replaced by diketopiperazine units of serine, and/or homoserine, and/or threonine. The invention also provides a method of preparing the polymer comprising reacting a dicarboxylic acid and/or an anhydride, a dicarboxylic ester and/or a mono-alkyl ester of a dicarboxylic acid with an aliphatic glycol, along with diketopiperazine units of aspartic acid, glutamic acid, serine, homoserine, and/or threonine in the presence of a suitable catalyst.

Description

DIKETOPIPERAZINE CONTAINING COPOLYMERS AND PREPARATION METHODS
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This patent application claims the benefit of U.S. Provisional Patent Application No. 61/798,565, filed March 15, 2013, which is incorporated by reference in its entirety herein.
BACKGROUND OF THE INVENTION
[0002] High performance plastics that are strong and durable are useful in a number of applications including automobiles, agricultural, medical and food packaging, and biomedical devices and packaging.
[0003] The physical and mechanical properties of a polymer are affected by the nature of the monomer units making up the polymer and the molecular weight of the polymer.
Aromatic polyesters have aromatic rings in their polymeric backbone and possess excellent thermal and mechanical properties. In addition, they are relatively easy to process. As a result, aromatic polyesters have excellent commercial applicability in molded parts, fibers, films, and sheeting. For example, polyethylene terephthalate (PET) is a commercially important polyester, which is formed from the reaction of terephthalic acid and ethylene glycol.
[0004] High end applications often require precise combinations of physical and mechanical properties that are not possessed by generic polyesters. Furthermore, generic aromatic polyesters are not biodegradable and thus are an environmental burden. Aliphatic polyesters can be biodegradable, but do not have the thermal and mechanical properties required for high end applications.
[0005] Polymer modifiers, e.g., alternative monomer units, can be added to the backbone of polymers to enhance the performance of the polymers. The polymer modifiers can build on the strengths of the base polymers and enhance the performance of these polymers. For example, co-polyesters containing 2,2,4,4-tetramethyl-l,3-cyclobutanediol (TMCD) exhibit a good combination of impact strength, hardness, and heat resistance. Copolymers of polyesters with naphthalene based monomers, which introduce a double ring structure into the polymeric backbone, have improved thermal, chemical, mechanical, and barrier performance. Likewise, a variety of biologically active monomers, e.g., L-polylactic acid, lactide, glycolide, butyrolactone, and caprolactone can introduce biodegradability to polymers. Linear homopolyesters of (S)-2-hydroxy-4-methylpentanoic acid, (S)-2-hydroxy- 3-phenylpropionic acid, (S)-2-hydroxy-3-methylpentanoic acid, (S)-2-hydroxy-3- methylbutanoic acid, and their copolyesters also have been known to improve
biodegradability.
[0006] In an attempt to provide a biodegradable polymer, homopolymers of
diketopiperazines and with either diacid or diol (glycol) groups (about 1 : 1 ratio) have been reportedly synthesized. However, these polymers are expected to be difficult to fabricate into useful products and expensive to produce.
[0007] Therefore, there remains a need to provide polymers, especially polyesters, with enhanced physical and mechanical properties, desirably with improved biocompatibility and biodegradability features.
BRIEF SUMMARY OF THE INVENTION
[0008] The invention provides a polymer comprising at least two monomer units of a dicarboxylate unit and at least two monomer units of a dialkoxy unit except that (a) some of the dicarboxylate units are replaced by a diketopiperazine unit of aspartic acid and/or a diketopiperazine unit of glutamic acid and/or (b) some of the dialkoxy units are replaced by a diketopiperazine unit of serine, diketopiperazine unit of homoserine, and/or a
diketopiperazine unit of threonine.
[0009] The polymer can be of the formula -[-R^-O-R^O-]- (I) comprising at least two monomer units of R1, which can be the same or different, and at least two monomer units of
R2, which can be the same or different. Each R1 is of formula (II), (III), (IV), (V), or (VI):
Figure imgf000003_0001
(II) (in) (IV) (V) (VI) wherein R3 is a Ci - C36 straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group. Each R2 is a C2 - Cs straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group. In the polymer, (a) about 0.01 to about 0.8 mole fraction of R1 is replaced by a diketopiperazme unit of formula (VII):
Figure imgf000004_0001
(VII) wherein R4 is -CH2C(0)- or -CH2CH2C(0)-, and/or (b) about 0.01 to about 0.8 mole fraction of R2 is replaced by a diketopiperazme unit of formula (VIII)
Figure imgf000004_0002
(VIII)
wherein R5 is -CH2-, -CH2CH2-, or -CH(CH3)-.
[0010] The invention also provides a method of preparing a polymer of the invention, which method comprises reacting dicarboxylic acids and/or dicarboxylic esters with aliphatic glycols, along with one or more diketopiperazme units of aspartic acid, glutamic acid, serine, homoserine, and/or threonine in the presence of a suitable catalyst.
[0011] The method can comprise combining, in a reaction vessel, (a) one or more compounds of formula R1(OH)2 and R1(OR6)2 wherein R6 is a lower alkyl group, (b) one or more aliphatic glycols of formula R2(OH)2, (c) one or more diketopiperazme units of aspartic acid and/or glutamic acid, wherein the mole ratio of the diketopiperazme units of aspartic acid and glutamic acid to the compounds of formula R1(OH)2 or Rx(OR6)2 is about 0.01 to about 0.8, and/or one or more diketopiperazme units of serine, homoserine, and/or threonine, wherein the mole ratio of the diketopiperazme units of serine, homoserine, and threonine to the aliphatic glycols R2(OH)2 is about 0.01 to about 0.8, and (d) a suitable catalyst. The reaction vessel is purged with an inert gas and heated to a first suitable temperature and a suitable pressure. The temperature of the reaction vessel is then raised to a second suitable temperature, while reducing the pressure in the reaction vessel to suitable pressure, thereby synthesizing the polymer. In the resulting polymer, about 0.01 to 0.8 mole fraction of R1 is replaced by one or more diketopiperazine units of aspartic acid and/or glutamic acid, and/or about 0.01 to 0.8 mole fraction of R2 is replaced by one or more diketopiperazine units of serine, homoserine, and/or threonine.
[0012] The invention also provides a method of improving the thermal properties and/or biodegradability of a corresponding conventional polymer by incorporating one or more diketopiperazines therein.
[0013] The term "corresponding conventional polymer" as used herein has the formula -[-R1-0-R2-0-]- wherein R1 and R2 are not replaced by diketopiperazines.
BRIEF DESCRIPTION OF THE FIGURES
[0014] Fig. 1 is a graph of storage modulus (MPa) in a logarithmic scale (Y-axis) plotted against temperature (°C) (X-axis) comparing the storage modulus of polyethylene terephthalate (PET) and a PET copolymer containing aspartate DKP- (3 mole %) by dynamic mechanical analysis (DMA).
[0015] Fig. 2 is a graph of Tan Delta (Y-axis) plotted against temperature (°C) (X-axis). The maximum in the Tan Delta is a measure of the glass transition temperature (Tg), i.e. providing the onset of the transition from the glassy state to the rubbery region. The data in Figure 2 thus provides a comparison of the glass transition temperature (Tg) of polyethylene terephthalate (PET) and a PET copolymer containing aspartate DKP-(3 mole %) by dynamic mechanical analysis (DMA).
[0016] Fig. 3 is a graph of storage modulus (MPa) in a logarithmic scale (Y-axis) plotted against temperature (°C) (X-axis) comparing the storage modulus of polyethylene adipate (PEA) and a PEA copolymer containing aspartate DKP-(10 mole %) by dynamic mechanical analysis (DMA).
[0017] Fig. 4 is a graph of Tan Delta (Y-axis) plotted against temperature (°C) (X-axis) comparing the glass transition temperature (Tg) of polyethylene adipate (PEA) and a PEA copolymer containing aspartate DKP-(10 mole %) by dynamic mechanical analysis (DMA). DETAILED DESCRIPTION OF THE INVENTION
[0018] The invention provides a polymer comprising at least two monomer units of a dicarboxylate unit and at least two monomer units of a dialkoxy unit except that (a) some of the dicarboxylate units are replaced by diketopiperazine units of aspartic acid and/or glutamic acid, and/or (b) some of the dialkoxy units are replaced by a diketopiperazine unit of serine, homoserine, and/or threonine. Homoserine is an intermediate in the biosynthesis of three essential a-amino acids, namely, methionine, threonine, and isoleucine and is an isomer of threonine.
[0019] The polymer can be of a formula -[-R^-O-R^O-]- (I) comprising, consisting essentially of, or consisting of at least two monomer units of R1, which can be the same or different, and at least two monomer units of R2, which can be the same or different. Each monomer unit R1 is independently of formula (II), (III), (IV), (V), or (VI):
Figure imgf000006_0001
(II) (in) (IV) (V) (VI) wherein R3 is a Ci - C36 straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group. Each monomer unit R2 is independently a C2 - Cg straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group.
[0020] Some of the monomer units R1 are replaced by diketopiperazine units of aspartic acid and/or diketopiperazine units of glutamic acid. In particular, either (a) about 0.01 to about 0.8 mole fraction of R1 is replaced by a diketopiperazine unit of formula (VII):
Figure imgf000007_0001
(VII) wherein R4 is -CH2C(0)- or -CH2CH2C(0)-, (b) about 0.01 to about 0.8 mole fraction of R2 is replaced by a diketopiperazme unit of formula (VIII):
Figure imgf000007_0002
(VIII) wherein R5 is -CH2-, -CH2CH2-, or -CH(CH3)-, or (c) both (a) and (b).
[0021] The diketopiperazme unit of formula (VII), wherein R4 is -CH2C(0)-, represents a diketopiperazme unit of aspartic acid. The diketopiperazme unit of formula (VII), wherein R4 is -CH2CH2C(0)-, represents a diketopiperazme unit of glutamic acid. The
diketopiperazme unit of formula (VIII), wherein R5 is -CH2-, represents a diketopiperazme unit of serine. The diketopiperazme unit of formula (VIII), wherein R5 is -CH2CH2-, represents a diketopiperazme unit of homoserine. The diketopiperazme unit of formula (VIII), wherein R5 is -CH(CH3)-, represents a diketopiperazme unit of threonine.
[0022] Terminal Units
[0023] A polymer as described herein, e.g., the polymer of the formula -[-R1-0-R2-0-]-, can have any suitable terminal, or capping, atoms or groups. For example, the capping atom or group can be a hydrogen atom, a Ci - C6 alkyl group, or any combination thereof. Thus, the polymer can be of formula, e.g., HO-[-R1-0-R2-0-]-H, H3CO-[-R1-0-R2-0-]-H, and the like. [0024] RJ Units
[0025] R1 represents a dicarboxylate unit which is a monomer unit of an aromatic dicarboxylic acid, aromatic dicarboxylic ester, aliphatic dicarboxylic acid, or aliphatic dicarboxylic ester.
[0026] The polymer of the invention can comprise at least two different monomer units of R1, e.g., 2, 3, 4, 5, 6, 7, or more different monomer units of R1. For example, the polymer can have at least one monomer unit R1 of formula (II), (IV), (V), or (VI) and at least one monomer unit R1 of a formula (III). Alternatively, the polymer of formula (I) can comprise all of the same monomer units of R1, i.e., a polymer wherein all of the monomer units of R1 are of formula (II), all of the monomer units of R1 are of formula (III), all of the monomer units of R1 are of formula (IV), all of the monomer units of R1 are of formula (V), or all of the monomer units of R1 are of formula (VI).
[0027] When the polymer of formula (I) has at least one monomer unit of R1 of formula (VI), R3 can be a Ci - C36 straight, branched, non-aromatic cyclic, saturated, unsaturated, substituted, unsubstituted, or aliphatic group, such as a C2 - C24, C2 - C18, or C2 - C12 straight, branched, non-aromatic cyclic, saturated, unsaturated, substituted, or unsubstituted aliphatic group. For example, R3 can be a straight chain or branched Ci - C24 alkyl group, a straight chain or branched Ci - C18 alkyl group, a straight chain or branched Ci - C12 alkyl group, a straight chain or branched Ci - Cg alkyl group, a straight chain or branched Ci - C4 alkyl group, a straight chain or branched C2 - C24 alkyl group, a straight chain or branched C2 - C18 alkyl group, a straight chain or branched C2 - C12 alkyl group, a straight chain or branched C2 - C8 alkyl group, a straight chain or branched C2 - C4 alkyl group, a straight chain or branched C4 - C24 alkyl group, a straight chain or branched C4 - C18 alkyl group, a straight chain or branched C4 - C12 alkyl group, a straight chain or branched C4 - Cg alkyl group, a straight chain or branched Ci - C24 alkenyl group, a straight chain or branched Ci - C18 alkenyl group, a straight chain or branched Ci - C12 alkenyl group, a straight chain or branched Ci - Cg alkenyl group, a straight chain or branched Ci - C4 alkenyl group, a straight chain or branched C2 - C24 alkenyl group, a straight chain or branched C2 - C18 alkenyl group, a straight chain or branched C2 - C12 alkenyl group, a straight chain or branched C2 - Cg alkenyl group, a straight chain or branched C2 - C4 alkenyl group, a straight chain or branched C4 - C24 alkenyl group, a straight chain or branched C4 - C18 alkenyl group, a straight chain or branched C4 - C12 alkenyl group, a straight chain or branched C4 - Cg alkenyl group, an optionally substituted cyclic or heterocyclic C3 - C24 alkyl group, an optionally substituted cyclic or heterocyclic C3 - C18 alkyl group, an optionally substituted cyclic or heterocyclic C3 - C12 alkyl group, an optionally substituted cyclic or heterocyclic C3 - Cg alkyl group, an optionally substituted cyclic or heterocyclic C3 - C4 alkyl group, an optionally substituted cyclic or heterocyclic C3 - C24 alkyl group, an optionally substituted cyclic or heterocyclic C3 - Ci8 alkyl group, an optionally substituted cyclic or heterocyclic C3 - C12 alkyl group, an optionally substituted cyclic or heterocyclic C3 - Cg alkyl group, an optionally substituted cyclic or heterocyclic C3 - C4 alkyl group, an optionally substituted cyclic or heterocyclic C4 - C24 alkyl group, an optionally substituted cyclic or heterocyclic C4 - C18 alkyl group, an optionally substituted cyclic or heterocyclic C4 - C12 alkyl group, an optionally substituted cyclic or heterocyclic C4 - Cg alkyl group, an optionally substituted cyclic or heterocyclic C3 - C24 alkenyl group, an optionally substituted cyclic or heterocyclic C3 - C18 alkenyl group, an optionally substituted cyclic or heterocyclic C3 - C12 alkenyl group, an optionally substituted cyclic or heterocyclic C3 - Cg alkenyl group, an optionally substituted cyclic or heterocyclic C3 - C4 alkenyl group, an optionally substituted cyclic or heterocyclic C3 - C24 alkenyl group, an optionally substituted cyclic or heterocyclic C3 - C18 alkenyl group, an optionally substituted cyclic or heterocyclic C3 - C12 alkenyl group, an optionally substituted cyclic or heterocyclic C3 - Cg alkenyl group, an optionally substituted cyclic or heterocyclic C3 - C4 alkenyl group, an optionally substituted cyclic or heterocyclic C4 - C24 alkenyl group, an optionally substituted cyclic or heterocyclic C4 - C18 alkenyl group, an optionally substituted cyclic or heterocyclic C4 - C12 alkenyl group, an optionally substituted cyclic or heterocyclic C4 - Cg alkenyl group, an optionally substituted Ci - C24 heterocyclic, straight, or branched chain alkyl group having 1 to 3 nitrogen atom(s), oxygen atom(s), and/or sulfur atom(s).
[0028] In an embodiment, R3 can be a -CH2CH2- group, which can be derived from succinic acid or a lower (e.g., Ci - C6) alkyl succinate, e.g., dimethyl succinate. R3 can be a -CH2CH2CH2- group, which can be derived from glutaric acid or a lower (e.g., Ci - C6) alkyl glutarate, e.g., dimethyl glutarate. R3 can be -CH2(CH2)2CH2- group, which can be derived from adipic acid or a lower (e.g., Ci - C6) alkyl adipate, e.g., dimethyl adipate. R3 can be of Formula (IX), e.g.,
Figure imgf000010_0001
(ix), which can be derived from cyclohexane-l,4-dicarboxylic acid or an alkyl
cyclohexane-l,4-dicarboxylate, e.g., dimethyl cyclohexane-l,4-dicarboxylate. R3 can be - CH2(CH2)6CH2-, -CH2(CH2)8CH2- or -CH2(CH2)i4CH2-.
[0029] As used anywhere herein, the term lower alkyl means Ci - C6 alkyl group comprising straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group.
[0030] In the polymer of formula (I), each monomer unit of R1 can be the same. In such an embodiment, the polymer comprises only 1 (one) type of dicarboxylate unit as a monomer in which about 0.01 to about 0.8 mole fraction of R1 is replaced by diketopiperazine unit of formula (VII). Thus, for example, in formula (I), each monomer unit of R1 can be of formula (II). Similarly, for example, each monomer unit of R1 can be one of formula (III), (IV), (V), or (VI). When, in the polymer described herein, R1 is of formula (VI), R3 in formula (VI) can be any one of groups described in above paragraphs.
[0031] The polymer of formula (I) can comprise R1 of any known dicarboxylate unit in addition to those of formula (II), (III), (IV), (V), and (VI). For example, R1 can be an aromatic dicarboxylate unit with Cs to about C2o carbon atoms. Typically, R1 can be derived from substituted or unsubstituted aromatic dicarboxylic acids, or lower alkyl (e.g., Ci to C6) esters of dicarboxylic acids. R1 can also be a biphenyl dicarboxylate unit, diphenyl ether dicarboxylate unit, diphenyl sulfide dicarboxylate unit, diphenyl sulfone dicarboxylate unit, methylene bis(benzoate), or mixture of any two or more thereof, and the like.
[0032] R2 Units
[0033] The terms glycol, dihydric alcohol, and diol as used herein refer to a primary, secondary, or tertiary alcohol containing two hydroxyl groups. These terms can be used interchangeably. The term dialkoxy unit as used herein refers to an aliphatic glycol described above in which the hydrogen atoms from the two hydroxyl groups have been removed. [0034] The polymer of formula (I) can comprise at least two different monomer units of R2, e.g., 2, 3, 4, 5, 6, 7, and the like. The polymer of formula (I) can have at least one monomer unit of R2 where R2 can be a C2 - Cg straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group. In some embodiments, R2 can be C2 - Cg, C2 - C6, C2 - C4, C4 - Cg, C4 - C6, C6 - Cg straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group and the like. For example, the monomer unit of R2 can be -CH2CH2-,-CH2CH(CH3 ,-CH2CH2CH2-, -CH2(CH2)2CH2-,
-CH2CH(CH3)CH2-, -CH2C(CH3)2CH2-, -CH2CH(CH2CH3)-, -CH2(CH2)3CH2-,
-CH2(CH2)4CH2-, -CH2(CH2)5CH2-, CH2(CH2)6CH2-, and the like, or mixtures of any two or more thereof.
[0035] In the polymer of formula (I), each monomer unit of R2 can be the same. In such an embodiment, the polymer comprises only 1 (one) type of dialkoxy unit in which, about 0.01 to about 0.8 mole fraction of R2 is replaced by diketopiperazine unit of formula (VIII). Thus, for example, each monomer unit of R2 can be of formula -CH2CH2-. Similarly, for example, each monomer unit of R2 can be one of -CH2CH(CH3)-,-CH2CH2CH2-,
-CH2(CH2)2CH2-, -CH2CH(CH3)CH2-, -CH2C(CH3)2CH2-, -CH2CH(CH2CH3)-,
-CH2(CH2)3CH2-, -CH2(CH2)4CH2-, -CH2(CH2)5CH2-, -CF^CF^eCtV, or the like.
[0036] The polymer of formula (I) can comprise additional dialkoxy units R2 known in the art. In the polymer of formula (I), at least one of the monomeric units of R2 can be of the formula (X) or (XI):
Figure imgf000011_0001
(X) (XI).
The monomeric unit of formula (X) is derived from 1 ,4-cyclohexanedimethanol (CHDM), and the monomeric unit of formula (XI) is derived from
2,2,4,4-tetramethyl-l,3-cyclobutanediol (TMCD). In the polymer of formula (I), at least one of the monomeric units of R2 can be of formula (X), and at least one of the monomeric units of R2 can be of formula (XI). In the polymer of formula (I), at least one of the monomeric units of R2 can be of formula (X), or alternatively, in the polymer of formula (I), at least one of the monomeric units of R2 can be of formula (XI).
[0037] Diketopiperazme Units
[0038] As used herein, the diketopiperazines are a class of cyclic organic compounds that result from peptide bonds between two amino acids. Any suitable a-amino acid can be used to prepare a diketopiperazme.
[0039] As used herein, diketopiperazme unit is a monomeric unit of diketopiperazme in the polymer of formula (I). For example, the diketopiperazme unit of formula (VII) is
Figure imgf000012_0001
(VII) wherein R4 is -CH2C(0)- or -CH2CH2C(0)-, and the diketopiperazme unit of formula (VIII) is
Figure imgf000012_0002
(VIII) wherein R5 is -CH2-, -CH2CH2-, or -CH(CH3)-.
[0040] In the polymer of formula (I), the diketopiperazme units of formula (VII) may be derived from aspartic acid and/or glutamic acid, and/or mixtures of the two. The
diketopiperazme units of formula (VIII) may be derived from serine, homoserine, threonine, and/or mixtures thereof.
[0041] In the polymer of formula (I), at least one monomeric unit of R1 can be replaced by the diketopiperazme unit of formula (VII), wherein R4 is -CH2C(0)-. At least one monomeric unit of R1 can also be replaced by the diketopiperazme unit of formula (VII), wherein R4 is -CH2CH2C(0)-. In certain embodiments, in the polymer of formula (I), when the monomeric unit of R1 is replaced by the diketopiperazine unit of formula (VII), the monomeric unit of R2 is not replaced by a diketopiperazine unit.
[0042] In the polymer of formula (I), at least one monomeric unit of R2 can also be replaced by the diketopiperazine unit of formula (VIII), wherein R5 is only -CH2-. At least one monomeric unit of R2 can also be replaced by the diketopiperazine unit of formula (VIII), wherein R5 is only -CH2CH2-. At least one monomeric unit of R2 can also be replaced by the diketopiperazine unit of formula (VIII), wherein R5 is only -CH(CH3)-. In certain
embodiments, in the polymer of formula (I), when the monomeric unit of R2 is replaced by the diketopiperazine unit of formula (VIII), the monomeric unit of R1 is not replaced by a diketopiperazine unit.
[0043] The diketopiperazine unit can be of the form: (1, 1), (1, d), (d, 1), or (d, d) or any mixture of two or more thereof. The term "1" is known in the art as levorotatory and the term "d" is known in the art as dextrorotatory.
[0044] In the polymer of formula (I), about 0.01 to about 0.8 mole fraction of one monomeric unit of R1 can be replaced by a diketopiperazine unit of formula (VII):
Figure imgf000013_0001
(VII) wherein R4 is -CH2C(0)-, which represents a diketopiperazine units of aspartic acid and/or - CH2CH2C(0)-, which represents a diketopiperazine unit of glutamic acid.
[0045] The replacement of R1 by diketopiperazine (VII) is independent of whether R2 is replaced by a diketopiperazine unit of formula (VIII).
[0046] In the polymer of formula (I), greater than about 0.01 mole fraction of R1 is replaced by a diketopiperazine unit of formula (VII), e.g., greater than about 0.02, greater than about 0.03, greater than about 0.04, greater than about 0.05, greater than about 0.07, greater than about 0.09, greater than about 0.1, greater than about 0.15, greater than about 0.2, greater than about 0.3, greater than about 0.4, greater than about 0.5, greater than about 0.6, greater than about 0.7, greater than about 0.8 mole fraction of R1 is replaced by a diketopiperazine unit of formula (VII). Alternatively, or in addition, in the polymer of formula (I), less than about 0.8 mole fraction of R1 is replaced by a diketopiperazine unit of formula (VII), e.g., less than about 0.7, less than about 0.6, less than about 0.5, less than about 0.4, less than about 0.3, less than about 0.2, less than about 0.15, less than about 0.1, less than about 0.09, less than about 0.07, less than about 0.05, less than about 0.04, less than about 0.03, less than about 0.02, less than about 0.01 mole fraction of R1 is replaced by a diketopiperazine unit of formula (VII). Thus, in the polymer of formula (I), the mole fraction of R1 replaced by a diketopiperazine unit of formula (VII) can be of an amount bounded by any two of the foregoing endpoints. For example, the mole fraction of R1 is replaced by a diketopiperazine unit of formula (VII) can be, e.g., about 0.01 to about 0.8, about 0.01 to about 0.7, about 0.01 to about 0.6, about 0.01 to about 0.5, about 0.01 to about 0.4, about 0.01 to about 0.3, about 0.01 to about 0.2, about 0.01 to about 0.15, about 0.01 to about 0.1, about 0.01 to about 0.09, about 0.01 to about 0.07, about 0.01 to about 0.05, about 0.01 to about 0.04, about 0.01 to about 0.03, about 0.01 to about 0.02, about 0.02 to about 0.8, about 0.02 to about 0.7, about 0.02 to about 0.6, about 0.02 to about 0.5, about 0.02 to about 0.4, about 0.02 to about 0.3, about 0.02 to about 0.2, about 0.02 to about 0.15, about 0.02 to about 0.1, about 0.02 to about 0.09, about 0.02 to about 0.07, about 0.02 to about 0.05, about 0.02 to about 0.04, about 0.02 to about 0.03, about 0.03 to about 0.8, about 0.03 to about 0.7, about 0.03 to about 0.6, about 0.03 to about 0.5, about 0.03 to about 0.4, about 0.03 to about 0.3, about 0.03 to about 0.2, about 0.03 to about 0.15, about 0.03 to about 0.1, about 0.03 to about 0.09, about 0.03 to about 0.07, about 0.03 to about 0.05, about 0.03 to about 0.04, about 0.04 to about 0.8, about 0.04 to about 0.7, about 0.04 to about 0.6, about 0.04 to about 0.5, about 0.04 to about 0.4, about 0.04 to about 0.3, about 0.04 to about 0.2, about 0.04 to about 0.15, about 0.04 to about 0.1, about 0.04 to about 0.09, about 0.04 to about 0.07, about 0.04 to about 0.05, about 0.05 to about 0.8, about 0.05 to about 0.7, about 0.05 to about 0.6, about 0.05 to about 0.5, about 0.05 to about 0.4, about 0.05 to about 0.3, about 0.05 to about 0.2, about 0.05 to about 0.15, about 0.05 to about 0.1, about 0.05 to about 0.09, about 0.05 to about 0.07, about 0.07 to about 0.8, about 0.07 to about 0.7, about 0.07 to about 0.6, about 0.07 to about 0.5, about 0.07 to about 0.4, about 0.07 to about 0.3, about 0.07 to about 0.2, about 0.07 to about 0.15, about 0.07 to about 0.1, about 0.07 to about 0.09, about 0.09 to about 0.8, about 0.09 to about 0.7, about 0.09 to about 0.6, about 0.09 to about 0.5, about 0.09 to about 0.4, about 0.09 to about 0.3, about 0.09 to about 0.2, about 0.09 to about 0.15, about 0.09 to about 0.1, about 0.1 to about 0.8, about 0.1 to about 0.7, about 0.1 to about 0.6, about 0.1 to about 0.5, about 0.1 to about 0.4, about 0.1 to about 0.3, about 0.1 to about 0.2, about 0.1 to about 0.15, about 0.15 to about 0.8, about 0.15 to about 0.7, about 0.15 to about 0.6, about 0.15 to about 0.5, about 0.15 to about 0.4, about 0.15 to about 0.3, about 0.15 to about 0.2, about 0.2 to about 0.8, about 0.2 to about 0.7, about 0.2 to about 0.6, about 0.2 to about 0.5, about 0.2 to about 0.4, about 0.2 to about 0.3, about 0.3 to about 0.8, about 0.3 to about 0.7, about 0.3 to about 0.6, about 0.3 to about 0.5, about 0.3 to about 0.4, about 0.4 to about 0.8, about 0.4 to about 0.7, about 0.4 to about 0.6, about 0.4 to about 0.5, about 0.5 to about 0.8, about 0.5 to about 0.7, about 0.5 to about 0.6, about 0.6 to about 0.8, about 0.6 to about 0.7, about 0.7 to about 0.8 mole fraction of R1 is replaced by a diketopiperazine unit of formula (VII).
[0047] In the polymer of formula (I), about 0.01 to about 0.8 mole fraction of one monomeric unit of R2 can be replaced by a diketopiperazine unit of formula (VIII):
Figure imgf000015_0001
(VIII) wherein R5 is -CH2-, -CH2CH2-, or -CH(CH3)-. The replacement of R2 by diketopiperazine (VIII) is independent of whether R1 is replaced by a diketopiperazine unit of formula (VII).
[0048] In the polymer of formula (I), greater than about 0.01 mole fraction of R2 is replaced by a diketopiperazine unit of formula (VIII), e.g., greater than about 0.02, greater than about 0.03, greater than about 0.04, greater than about 0.05, greater than about 0.07, greater than about 0.09, greater than about 0.1, greater than about 0.15, greater than about 0.2, greater than about 0.3, greater than about 0.4, greater than about 0.5, greater than about 0.6, greater than about 0.7, greater than about 0.8 mole fraction of R2 is replaced by a diketopiperazine unit of formula (VIII). Alternatively, or in addition, in the polymer of formula (I), less than about 0.8 mole fraction of R2 is replaced by a diketopiperazine unit of formula (VIII), e.g., less than about 0.7, less than about 0.6, less than about 0.5, less than about 0.4, less than about 0.3, less than about 0.2, less than about 0.15, less than about 0.1, less than about 0.09, less than about 0.07, less than about 0.05, less than about 0.04, less than about 0.03, less than about 0.02, less than about 0.01 mole fraction of R2 is replaced by a diketopiperazine unit of formula (VIII). Thus, in the polymer of formula (I), the mole fraction of R2 replaced by a diketopiperazine unit of formula (VIII) can be of an amount bounded by any two of the foregoing endpoints. For example, the mole fraction of R2 is replaced by a diketopiperazine unit of formula (VIII) can be, e.g., about 0.01 to about 0.8, about 0.01 to about 0.7, about 0.01 to about 0.6, about 0.01 to about 0.5, about 0.01 to about 0.4, about 0.01 to about 0.3, about 0.01 to about 0.2, about 0.01 to about 0.15, about 0.01 to about 0.1, about 0.01 to about 0.09, about 0.01 to about 0.07, about 0.01 to about 0.05, about 0.01 to about 0.04, about 0.01 to about 0.03, about 0.01 to about 0.02, about 0.02 to about 0.8, about 0.02 to about 0.7, about 0.02 to about 0.6, about 0.02 to about 0.5, about 0.02 to about 0.4, about 0.02 to about 0.3, about 0.02 to about 0.2, about 0.02 to about 0.15, about 0.02 to about 0.1, about 0.02 to about 0.09, about 0.02 to about 0.07, about 0.02 to about 0.05, about 0.02 to about 0.04, about 0.02 to about 0.03, about 0.03 to about 0.8, about 0.03 to about 0.7, about 0.03 to about 0.6, about 0.03 to about 0.5, about 0.03 to about 0.4, about 0.03 to about 0.3, about 0.03 to about 0.2, about 0.03 to about 0.15, about 0.03 to about 0.1, about 0.03 to about 0.09, about 0.03 to about 0.07, about 0.03 to about 0.05, about 0.03 to about 0.04, about 0.04 to about 0.8, about 0.04 to about 0.7, about 0.04 to about 0.6, about 0.04 to about 0.5, about 0.04 to about 0.4, about 0.04 to about 0.3, about 0.04 to about 0.2, about 0.04 to about 0.15, about 0.04 to about 0.1, about 0.04 to about 0.09, about 0.04 to about 0.07, about 0.04 to about 0.05, about 0.05 to about 0.8, about 0.05 to about 0.7, about 0.05 to about 0.6, about 0.05 to about 0.5, about 0.05 to about 0.4, about 0.05 to about 0.3, about 0.05 to about 0.2, about 0.05 to about 0.15, about 0.05 to about 0.1, about 0.05 to about 0.09, about 0.05 to about 0.07, about 0.07 to about 0.8, about 0.07 to about 0.7, about 0.07 to about 0.6, about 0.07 to about 0.5, about 0.07 to about 0.4, about 0.07 to about 0.3, about 0.07 to about 0.2, about 0.07 to about 0.15, about 0.07 to about 0.1, about 0.07 to about 0.09, about 0.09 to about 0.8, about 0.09 to about 0.7, about 0.09 to about 0.6, about 0.09 to about 0.5, about 0.09 to about 0.4, about 0.09 to about 0.3, about 0.09 to about 0.2, about 0.09 to about 0.15, about 0.09 to about 0.1, about 0.1 to about 0.8, about 0.1 to about 0.7, about 0.1 to about 0.6, about 0.1 to about 0.5, about 0.1 to about 0.4, about 0.1 to about 0.3, about 0.1 to about 0.2, about 0.1 to about 0.15, about 0.15 to about 0.8, about 0.15 to about 0.7, about 0.15 to about 0.6, about 0.15 to about 0.5, about 0.15 to about 0.4, about 0.15 to about 0.3, about 0.15 to about 0.2, about 0.2 to about 0.8, about 0.2 to about 0.7, about 0.2 to about 0.6, about 0.2 to about 0.5, about 0.2 to about 0.4, about 0.2 to about 0.3, about 0.3 to about 0.8, about 0.3 to about 0.7, about 0.3 to about 0.6, about 0.3 to about 0.5, about 0.3 to about 0.4, about 0.4 to about 0.8, about 0.4 to about 0.7, about 0.4 to about 0.6, about 0.4 to about 0.5, about 0.5 to about 0.8, about 0.5 to about 0.7, about 0.5 to about 0.6, about 0.6 to about 0.8, about 0.6 to about 0.7, about 0.7 to about 0.8 mole fraction of R2 is replaced by a
diketopiperazine unit of formula (VIII).
[0049] In the polymer of formula (I), about 0.01 to about 0.8 mole fraction of one monomer unit of R1 can be replaced by a diketopiperazine unit of formula (VII) and at the same time about 0.01 to about 0.8 mole fraction of one monomer unit of R2 can be replaced by a diketopiperazine unit of formula (VIII). Thus, in the polymer of formula (I), the mole fractions of R1 replaced by a diketopiperazine unit of formula (VII) or R2 replaced by a diketopiperazine unit of formula (VIII) can be of an amount bounded by any two of the foregoing endpoints.
[0050] In the polymer of formula (I), about 0.01 to about 0.8 mole fraction of one monomer unit of R1 can be replaced by a diketopiperazine unit of formula (VII) but no R2 is replaced by diketopiperazine unit of formula (VIII). Alternatively, in the polymer of formula (I), about 0.01 to about 0.8 mole fraction of one monomer unit of R2 can be replaced by a diketopiperazine unit of formula (VIII), but no R1 is replaced by diketopiperazine unit of formula (VII).
[0051] The polymer of formula (I) can have any suitable molecular weight. Typically, the polymer of formula (I) can have a molecular weight of about 500 g/mol or more (e.g., about 1,000 g/mol or more, about 3,000 g/mol or more, about 10,000 g/mol or more, about 20,000 g/mol or more, or about 100,000 g/mol or more, or 1 million g/mol or more).
Alternatively, or in addition, the molecular weight of the polymer of formula (I) typically can be about 1 million g/mol or less, e.g., about 100,000 g/mol or less, about 20,000 g/mol or less, about 10,000 g/mol or less, about 3,000 g/mol or less, about 1,000 g/mol or less, or about 500 g/mol or less). Thus, the polymer of formula (I) can have a molecular weight of an amount bounded by any two of the foregoing endpoints. For example, the polymer of formula (I) can have a molecular weight of about 500 g/mol to about 1 million g/mol, about 500 g/mol to about 100,000 g/mol, about 500 g/mol to about 20,000 g/mol, about 500 g/mol to about 10,000 g/mol, about 500 g/mol to 3,000 g/mol, about 500 g/mol to about 1,000 g/mol, about 1,000 g/mol to about 1 million g/mol, about 1,000 g/mol to about 100,000 g/mol, about 1,000 g/mol to about 20,000 g/mol, about 1,000 g/mol to about 10,000 g/mol, about 1000 g/mol to 3,000 g/mol, about 3,000 g/mol to about 1 million g/mol, about 3,000 g/mol to about 100,000 g/mol, about 3,000 g/mol to about 20,000 g/mol, about 3,000 g/mol to about 10,000 g/mol, about 10,000 g/mol to about 1 million g/mol, about 10,000 g/mol to about 100,000 g/mol, about 10,000 g/mol to about 20,000 g/mol, about 20,000 g/mol to about 1 million g/mol, about 20,000 g/mol to about 100,000 g/mol, or about 100,000 g/mol to about
1 million g/mol.
[0052] The polymer of formula (I) can have any suitable number of units of
-[-R^-O-R^O-]-, e.g., the polymer of formula (I) can have a number of units of R1 of 2 or more, about 3 or more, about 4 or more, about 13 or more, about 40 or more, about 85 or more, or about 400 or more, or about 4000 or more. Alternatively, or in addition, the polymer of formula (I) can have a number of units of -[-R1-0-R2-0-]- of about 4500 or less, e.g., about 450 or less, about 90 or less, about 45 or less, about 15 or less, about 6 or less, or about 4 or less. Thus, the polymer of formula (I) can have a number of units of
-[-R1-0-R2-0-]- in an amount bounded by any two of the foregoing endpoints. For example, the polymer of formula (I) can have a number of units of -[-R^O-R^O-]- of 2 to about 4500,
2 to about 450, 2 to about 90, 2 to about 45, about 4 to about 4500, about 4 to about 450, about 4 to about 90, about 4 to about 45, about 4 to about 15, about 13 to about 4500, about 13 to about 450, about 13 to about 90, about 13 to about 45, about 13 to about 15, about 40 to about 4500, about 40 to about 450, about 40 to about 90, about 40 to about 45, about 85 to about 4500, about 85 to about 450, about 85 to about 90, about 400 to about 4500, or about 400 to about 450.
[0053] Method of Preparation
[0054] The polymer as described herein can be prepared by any suitable method.
Suitable methods include the use of conventional polyesterification procedures and solid state polymerization, except utilizing the diketopiperazines as described herein. For example, the polymer of the invention can be prepared by way of a method that comprises reacting one or more dicarboxylic acids and/or one or more dicarboxylic esters with one or more aliphatic glycols, along with one or more diketopiperazine units of aspartic acid, glutamic acid, serine, homoserine, and/or threonine in the presence of a suitable catalyst. The dicarboxylic acid can be used directly or by way of a lower alkyl dicarboxylic ester or an anhydride. For example, the polymer of formula (I) of this invention is conveniently prepared by direct polymerization by heating the dicarboxylic acid and/or dicarboxylic ester and/or mono-alkyl ester of a dicarboxylic acid and/or an anhydride with the aliphatic glycol in the presence of a suitable catalyst. Preferably, phthalic, succinic, maleic anhydrides, or the like, may be used.
[0055] In general, the method of preparing a polymer described herein comprises combining in a reaction vessel (a) one or more compounds of formula R1(OH)2 or R1(OR6)2, wherein R6 is an alkyl group, (b) one or more aliphatic glycols of formula R2(OH)2, (c) one or more diketopiperazine units of aspartic acid and/or glutamic acid, wherein the mole ratio of the diketopiperazine units of aspartic acid and glutamic acid to the compounds of formula R1(OH)2 or R^OR6^ is about 0.01 to about 0.8, and/or one or more diketopiperazine units of serine, homoserine, and/or threonine, wherein the mole ratio of the diketopiperazine units of serine, homoserine, and threonine to the aliphatic glycols R2(OH)2 is about 0.01 to about 0.8, and (d) a suitable catalyst. The reaction vessel is purged with an inert gas and heated to a first suitable temperature and a suitable pressure. The temperature of the reaction vessel is then raised to a second suitable temperature, while reducing the pressure in the reaction vessel to suitable pressure, thereby synthesizing the polymer. In the resulting polymer, about 0.01 to 0.8 mole fraction of R1 is replaced by one or more diketopiperazine units of aspartic acid and/or glutamic acid, and/or about 0.01 to 0.8 mole fraction of R2 is replaced by one or more diketopiperazine units of serine, homoserine, and/or threonine.
[0056] In the method of preparing a polymer of the invention, a desired amount of the diketopiperazine units of aspartic acid and/or glutamic acid, and/or the diketopiperazine units of serine, homoserine, and/or threonine are added. The diketopiperazine units of aspartic acid and glutamic acid can be used directly or as lower alkyl (e.g., Ci - C6) dicarboxylic ester. The diketopiperazine units of serine, homoserine, and threonine can be used directly. The reactants are mixed in a suitable inert atmosphere and heated to a suitable first high temperature. When the evolution of water or alcohol molecules from the esterification is substantially complete, the heating is continued to a second suitable higher temperature at a reduced pressure until a desirable polymer molecular weight is obtained. It is desirable to employ a slight excess of the aliphatic glycol reactants to compensate for physical losses during polymerization. Suitable polyesterification catalysts are known to a person of ordinary skill in the art and are normally used in an amount of less than 0.05 - 2% by weight. [0057] Solid State Polymerization (SSP)
[0058] In the method of preparing a polymer of the invention, a Solid State
Polymerization (SSP) process can be used in which the polymer chain lengths are increased at an elevated temperature in the absence of oxygen and water, by means of either vacuum or purging with an inert gas to drive off the by-products of reactions. The reaction is driven by temperature, pressure, and the diffusion of by-products from the interior of polymer particles (e.g., powder, pellets, etc.) to the surface.
[0059] Aromatic Dicarboxylic Acids, Esters, Anhydrides, and Aromatic Mono-Alkyl Esters of Dicarboxylic Acids
[0060] In the method of preparing a polymer of the invention, any suitable aromatic dicarboxylic acid, lower alkyl (e.g., Ci - C6) dicarboxylic ester, anhydrides, and/or lower alkyl (e.g., Ci - C6) mono-alkyl ester of a dicarboxylic acid can be used. The aromatic dicarboxylic acids can be aryl, heteroaryl, substituted, or unsubstituted aromatic dicarboxylic acids. The aromatic dicarboxylic acids can include, e.g., Ci - C2o carbons. In other embodiments the aromatic dicarboxylic acids can include C5 - C2o, C6 - C2o, Cg - C2o, Cio - C2o, C12 - C20, and the like carbons. By way of example, some useful aromatic diacids can include those derived from phthalates, terephthalates, isophthalates, naphthalates, and the like. Specific examples of useful aromatic dicarboxylic acid can include terephthalic acid, 1 ,4-naphthalene dicarboxylic acid, 2,6-napthalene dicarboxylic acid, 2,7- naphthalenedicarboxylic acid, 4,4'-biphenyl dicarboxylic acid, 3,4'-biphenyl dicarboxylic acid, 4,4 '-methylene bis(benzoic acid), 3,4'-diphenyl ether dicarboxylic acid, 4,4'-diphenyl ether dicarboxylic acid, 3,4'-diphenyl sulfide dicarboxylic acid, 4,4'-diphenyl sulfide dicarboxylic acid, 3,4'-diphenyl sulfone dicarboxylic acid, 4,4'-diphenyl sulfone dicarboxylic acid, 3,4'-benzophenonedicarboxylic acid, 4,4'-benzophenonedicarboxylic acid, isophthalic acid, phthalic acid, terephthalic acid, and the like, and mixtures of two or more thereof.
Preferably, the aromatic dicarboxylic acids are phthalic acid, isophthalic acid, terephthalic acid, 2,6-naphthalene dicarboxylic acid, or mixtures of two or more thereof.
[0061] In the method of preparing a polymer of the invention, any suitable aromatic dicarboxylic esters can also be used in place of aromatic dicarboxylic acids. Preferably, lower alkyl esters (e.g., Ci - C6) having C2 - C2o aromatic dicarboxylic esters can be used, i.e., aromatic dicarboxylic esters with two lower alkoxy groups (each of which is, for example, Ci - C6) having aromatic ring carbons (for example, C2 - C2o) such that the total number of carbons for the aromatic dicarboxylic esters is C4 - C32. In other embodiments the aromatic dicarboxylic esters have a total number of carbons of C7 - C32, C10 - C32, C12 - C32, C7 - C24, Cio - C24, and the like. The aromatic dicarboxylic esters can be aryl, heteroaryl, substituted, or unsubstituted aromatic dicarboxylic esters. By way of example, some useful aromatic dicarboxylic esters can include those derived from phthalates, terephthalates, isophthalates, and naphthalates. Specific examples of useful aromatic dicarboxylic acid components can include dimethyl isophthalate, dimethyl terephthalate, dimethyl- 1 ,4-naphthalate, dimethyl- 2,6-naphthalate, dimethyl-2,7-naphthalate, dimethyl phthalate, dimethyl-3,4'diphenyl ether dicarboxylate, dimethyl-4,4'-diphenyl ether dicarboxylate, dimethyl-3,4'-diphenyl sulfide dicarboxylate, dimethyl-4,4'-diphenyl sulfide dicarboxylate, dimethyl-3,4'-diphenyl sulfone dicarboxylate, dimethyl-4,4'-diphenyl sulfone dicarboxylate, dimethyl-3,4'- benzophenonedicarboxylate, dimethyl-4,4'-benzophenonedicarboxylate, dimethyl- 1 ,4- naphthalate, dimethyl-4, 4'-methylenebis(benzoate), and the like, and mixtures of two or more thereof. Preferably, the aromatic dicarboxylic esters are dimethyl isophthalate, dimethyl phthalate, dimethyl terephthalate, dimethyl naphthalate, or mixtures of two or more thereof.
[0062] In the method of preparing a polymer of the invention, any suitable aromatic mono-alkyl ester of a dicarboxylic acid can also be used in place of an aromatic dicarboxylic acid. Preferably, a lower alkyl (e.g., Ci - C6) having a C6 - C26 aromatic mono-alkyl ester of a dicarboxylic acid can be used. The aromatic mono-alkyl ester of a dicarboxylic acid can be aryl, heteroaryl, substituted, or unsubstituted aromatic mono-alkyl ester of a dicarboxylic acid. By way of example, some useful aromatic mono-alkyl esters of dicarboxylic acids can include those derived from phthalates, terephthalates, isophthalates, and naphthalates.
Specific examples of useful mono-alkyl esters of dicarboxylic acids can include monomethyl isophthalate, monomethyl terephthalate, 1 ,4-naphthalene dicarboxylic acid monomethyl ester, 2,6-naphthalene dicarboxylic acid monomethyl ester, 2,7-naphthalene dicarboxylic acid monomethyl ester, monomethyl phthalate, and the like, and mixtures of two or more thereof.
[0063] In the method of preparing a polymer of the invention, any suitable aromatic anhydride may be used. The anhydride can be straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated anhydride. The anhydride can include, e.g., C3 - C36 carbons. Preferably, phthalic, succinic, maleic anhydrides, or the like, may be used. Most preferably, phthalic acid may be used. [0064] Aliphatic Dicarboxylic Acids, Anhydride, Esters, and Aliphatic Mono-Alkyl Esters of Dicarboxylic Acids
[0065] In the method of preparing a polymer of the invention, any suitable aliphatic dicarboxylic acid, and/or lower alkyl (e.g., Ci - C6) aliphatic dicarboxylic esters, or mono-alkyl ester of a dicarboxylic acid can be used. The aliphatic dicarboxylic acids can be straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic dicarboxylic acids. The aliphatic dicarboxylic acids can include, e.g., Ci - C36 carbons. In other embodiments the aliphatic dicarboxylic acids can include C3 - C36, C5 - C36, C3 - C2o, C5
- C2o, Cg - C2o, C12 - C2o, and the like carbons. By way of example, some useful aliphatic diacids can include those derived from succinate, glutarate, adipate, cyclohexane-1 ,4- dicarboxylate, dodecanedioate, isosanedioate, and the like. Specific examples of some useful aliphatic dicarboxylic acids can include 1 , 10-decanedicarboxylic acid,
1 , 1 1-undecanedicarboxylic acid, 1 , 12-dodecanedicarboxylic acid, 1 , 1-cyclohexanediacetic acid, 1 ,3-cyclohexanedicarboxylic acid, 1 ,4-cyclohexanedicarboxylic acid,
2,2,5, 5-tetramethylhexanedioic acid, 2-methylglutaric acid, 3-methyladipic acid,
3-methylglutaric acid, adipic acid, azelaic acid, docosanedioic (22) acid, glutaric acid, hexadecanedioic acid, malonic acid, methylsuccinic acid, pimelic acid, sebacic acid, suberic acid, succinic acid, tetracosanedioic acid, undecanedioic acid, and the like, and mixtures of two or more thereof. Preferably, the aliphatic dicarboxylic acids used herein are succinic acid, glutaric acid, adipic acid, cyclohexane-l ,4-dicarboxylic acid, dodecanedioic acid, isosanedioic acid, and mixtures of two or more thereof.
[0066] In the method of preparing a polymer of the invention, any suitable aliphatic anhydride may be used. The anhydride can be straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated anhydride. The anhydride can include, e.g., C3 - C36 carbons. Preferably, succinic and maleic anhydrides, or the like, may be used.
[0067] In the method of preparing a polymer of the invention, any suitable aliphatic dicarboxylic esters can also be used in place of aromatic dicarboxylic acids. Preferably, lower alkyl esters (e.g., Ci - C6) having C2 - C36 aliphatic dicarboxylic esters can be used, i.e., aliphatic dicarboxylic esters with two lower alkoxy groups (each of which is, for example, Ci
- C6) having aliphatic bridge carbons (for example, C2 - C36) such that the total number of carbons for the aliphatic dicarboxylic esters is C4 - C48. In other embodiments the aliphatic dicarboxylic esters have a total number of carbons of C5 - C4g, C5 - C36, C5 - C3o, C5 - C24, and the like. The aliphatic dicarboxylic esters can be straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic dicarboxylic esters. By way of example, some useful aliphatic dicarboxylic esters can include succinate, glutarate, adipate, cyclohexane-1,4- dicarboxylate, dodecanedioate, isosanedioate, and the like. Specific examples of some useful aliphatic dicarboxylic esters can include dimethyl adipate, dimethyl azelate, dimethyl glutarate, dimethyl malonate, dimethyl succinate, dimethyl succinate, dimethyl- 1,3- yclohexanedicarboxylate, and dimethyl- 1 ,4-cyclohexanedicarboxylate, and the like, and mixtures of two or more thereof. Preferably, the aliphatic dicarboxylic esters used herein are dimethyl succinate, dimethyl glutarate, dimethyl adipate, dimethyl cyclohexane-1,4- dicarboxylate, dimethyl isosanedioate, or mixtures of two or more thereof.
[0068] In the method of preparing a polymer of the invention, any suitable aliphatic mono-alkyl ester of a dicarboxylic acid can also be used in place of an aromatic dicarboxylic acid. Preferably, a lower mono-alkyl ester (e.g., Ci - C6) having a C4 - C42 aliphatic mono- alkyl ester of a dicarboxylic acid can be used. The aliphatic mono-alkyl ester of a
dicarboxylic acid can be straight, branched, non-aromatic cyclic, saturated, substituted, or aliphatic mono-alkyl ester of a dicarboxylic acid. By way of example, some useful aliphatic mono-alkyl esters of dicarboxylic acids can include mono-alkyl esters of succinic acid, glutaric acid, adipic acid, 1 ,4-cyclohexanedicarboxylic acid, dodecanoic acid, and the like. Specific examples of some useful aliphatic mono-alkyl esters of dicarboxylic acids can include adipic acid-monomethyl ester, azelaic acid-monomethyl ester, glutaric acid- monomethyl ester, 1,3-cyclohexanedicarboxylic acid-monomethyl ester, 1,4- cyclohexanedicarboxylic acid-monomethyl ester and the like, and mixtures of two or more thereof.
[0069] Aliphatic Glycols
[0070] In the method of preparing a polymer of the invention, any suitable aliphatic glycol can be used. The aliphatic glycol can be straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic glycol. The aliphatic glycol can include, e.g., C2- Cg linear carbons. By way of example, some useful aliphatic glycols can include ethylene glycol, 1,3 -propanediol, 1,3-butanediol, 1 ,4-butanediol, 1 ,6-hexanediol, neopentyl glycol, 1 ,2-propanediol, 1 ,2-butanediol, 2-methyl- 1,3 -propanediol, 1 ,6-hexanediol, poly(ethylene ether) glycols, and the like, and mixtures of two or more thereof. [0071] Catalysts
[0072] In the method of preparing a polymer of the invention, any suitable catalyst may be used. The catalysts that may be used include salts of Ca, Ge, Li, Mg, Mn, Pb, Sb, Sn, Ti, and Zn, e.g., acetate salts and oxides, including glycol adducts, and alkoxides. The catalysts used herein can be any suitable catalysts that are known in the art. A person of ordinary skill in the art may select a single catalyst, a combination, or a sequence of catalysts with relative ease and without undue experimentation. The preferred catalyst can be different depending upon the conditions and the starting reactants. It is possible that the use of a dicarboxylic acid monomer may require a different catalyst than a dicarboxylic ester monomer. Similarly, the choice of a different aliphatic glycol, or a different diketopiperazine may also require a different preferred suitable catalyst.
[0073] A method of preparing a homopolymer of dicarboxylate units and dialkoxy unit is also described in U.S. Patent No. 5,955,565. A method of preparing diketopiperazines is also described in P.M. Fischer, Diketopiperazines in Peptide and Combinatorial Chemistry, 9 J.
PEPTIDE SCI. 9 (2003), which is incorporated by reference in its entirety herein.
[0074] The diketopiperazine unit can be of the form: (1, 1), (1, d), (d, 1), or (d, d) or any mixture of two or more thereof. The term "1" is known in the art as levorotatory and the term
"d" is known in the art as dextrorotatory.
[0075] Properties of the Polymer of the Invention
[0076] The properties exhibited by a polymer product prepared from the polymer of the invention will depend on several factors including the composition, mole fraction of R1 and/or R2 replaced with the diketopiperazines, the method of forming the polymer of the invention, and whether the polymer product was prepared with any specialized alignments. These factors affect many properties of the polymer product, such as chemical resistance, dielectric strength and constant, elongation at break, heat impact strength, melting point, shrinkage, tensile modulus, tensile strength, deflection temperature, and the like.
[0077] The properties of the polymer product may be further adjusted by adding certain additives and fillers to the polymeric composition, such as antioxidants, colorants, dyes, lubricants, antiblock agents, plasticizers, slip agents, UV and thermal stabilizers, and the like. Alternatively, the polymer of the invention may be blended with one or more other polymers to improve its desired characteristics. [0078] Utility of the Polymer of the Invention
[0079] The polymers of the invention can be used in any suitable end use, including but not limited to, the same end uses of the corresponding conventional polymers, such as in molded parts for automotive, industrial and consumer products; fibers for clothing, fishing line and rope; and films for packaging. Because of their biodegradability and
biocompatibility, some of the polymers of the invention can have important applications in bioengineering and biomaterials, e.g., drug delivery and medical devices.
[0080] As a result of the presence of amide functional groups, the polymer of the invention can have improved dyeability as compared to the corresponding conventional polymer. The dyeability of the polymer of the invention is a manifestation of a broader enhancement of surface properties. Thus, the polymer of the invention can exhibit improved metallization, paint adhesion, adhesive bonding, interlayer adhesion in extrusion, and printability as compared to the corresponding convention polymer.
[0081] Diketopiperazines are naturally occurring dimers of a-amino acids. The a-amino acids can be prepared by fermentation or enzymatic treatment of renewable feedstocks such as sugars, starches, and cellulosics. As such, diketopiperazines are sustainable materials. Therefore, the products prepared from the polymer of the invention have the advantage of being formed, at least in part, from a renewable starting monomer.
[0082] The following examples further illustrate the invention but, of course, should not be construed as in any way limiting its scope.
[0083] Embodiments
[0084] (1) In embodiment (1) is presented a polymer of formula
-[-R^O-R^O-]- (I)
comprising at least two monomer units of R1, which can be the same or different, and at least two monomer units of R2, which can be the same or different, wherein R1 is of formula
Figure imgf000026_0001
(II) (III) (IV) (V) (VI) wherein R3 is a Ci - C36 straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group, and R2 is a C2 - C8 straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group, except that (a) about 0.01 to about 0.8 mole fraction of R1 is replaced by a diketopiperazine unit of formula (VII)
Figure imgf000026_0002
(VII)
wherein R4 is -CH2C(0)- or -CH2CH2C(0)-, and/or (b) about 0.01 to about 0.8 mole fraction of R2 is replaced by a diketopiperazine unit of formula (VIII)
Figure imgf000026_0003
(VIII)
wherein R5 is -CH2-, -CH2CH2-,or -CH(CH3)-.
[0085] (2) In embodiment (2) is presented a polymer of embodiment (1), wherein R5 is only -CH2-.
[0086] (3) In embodiment (3) is presented a polymer of embodiment (1), wherein R5 is only -CH(CH3)-.
[0087] (4) In embodiment (4) is presented a polymer of any one of embodiments (l)-(3), wherein the polymer comprises at least two different monomer units of R1. [0088] (5) In embodiment (5) is presented a polymer of embodiment (4), wherein at least one monomer unit of R1 is of formula (II).
[0089] (6) In embodiment (6) is presented a polymer of embodiment (4) or (5), wherein at least one monomer unit or R1 us if formula (III).
[0090] (7) In embodiment (7) is presented a polymer of any one of embodiments (4)-(6), wherein at least one monomer unit of R1 is of formula (IV).
[0091] (8) In embodiment (8) is presented a polymer of any one of embodiments (4)-(7), wherein at least one monomer unit of R1 is of formula (V).
[0092] (9) In embodiment (9) is presented a polymer of any one of embodiments (4)-(8), wherein at least one monomer unit of R1 is of formula (VI).
[0093] (10) In embodiment (10) is presented a polymer of any one of embodiments (4)-
(9) wherein at least one monomer unit of R1 is of formula (VI), and R3 is -CH2CH2-.
[0094] (11) In embodiment (11) is presented a polymer of any one of embodiments (4)-
(10) , wherein at least one monomer unit of R1 is of formula (VI), wherein R3 is - CH2CH2CH2-.
[0095] (12) In embodiment (12) is presented a polymer of any one of embodiments (4)-
(11) , wherein at least one monomer unit of R1 is of formula (VI), wherein R3 is - CH2(CH2)2CH2-.
[0096] (13) In embodiment (13) is presented a polymer of any one of embodiments (4)-
(12) , wherein at least one monomer unit of R1 is of formula (VI), wherein R3 is of formula (IX)
Figure imgf000027_0001
(IX).
[0097] (14) In embodiment (14) is presented a polymer of any one of embodiments (4)-
(13) , wherein at least one monomer unit of R1 is of formula (VI), wherein R3 is -
Figure imgf000027_0002
[0098] (15) In embodiment (15) is presented a polymer of any one of embodiments (4)-
(14) , wherein at least one monomer unit of R1 is of formula (VI), wherein R3 is - CH2(CH2)8CH2-. [0099] (15) In embodiment (16) is presented a polymer of any one of embodiments (1)-
(3), wherein each monomer unit of R is the same.
[0100] (17) In embodiment (17) is presented a polymer of embodiment (16), wherein R1 is of formula (II).
[0101] (18) In embodiment (18) is presented a polymer of embodiment (16), wherein R1 is of formula (III).
[0102] (19) In embodiment (19) is presented a polymer of embodiment (16), wherein R1 is of formula (IV).
[0103] (20) In embodiment (20) is presented a polymer of embodiment (16), wherein R1 is of formula (V).
[0104] (21) In embodiment (21) is presented a polymer of embodiment (16), wherein R1 is of formula (VI).
[0105] (22) In embodiment (22) is presented a polymer of embodiment (16), wherein R1 is of formula (VI), and R3 is -CH2CH2-.
[0106] (23) In embodiment (23) is presented a polymer of embodiment (16), wherein R1 is of formula (VI), and R3 is -CH2CH2CH2-.
[0107] (24) In embodiment (24) is presented a polymer of embodiment (16), wherein R1 is of formula (VI), and R3 is -CH2(CH2)2CH2-.
[0108] (25) In embodiment (25) is presented a polymer of embodiment (16), wherein R1 is of formula (VI), and R3 is of formula (IX)
Figure imgf000028_0001
(IX).
[0109] (26) In embodiment (26) is presented a polymer of embodiment (16), wherein R1 is of formula (VI), and R3 is -CH2(CH2)i4CH2-.
[0110] (27) In embodiment (27) is presented a polymer of embodiment (16), wherein R1 is of formula (VI), and R3 is -CH2(CH2)8CH2-.
[0111] (28) In embodiment (28) is presented a polymer of any one of embodiments (1)- (27), wherein the polymer comprises at least two different monomer units of R2. [0112] (29) In embodiment (29) is presented a polymer of embodiment (28), wherein at least one monomer unit of R2 is -CH2CH2-.
[0113] (30) In embodiment (30) is presented a polymer of embodiment (28) or (29), wherein at least one monomer unit of R2 is -CH2CH(CH3)-.
[0114] (31) In embodiment (31) is presented a polymer of any one of embodiments (28)-
(30) , wherein at least one monomer unit of R2 is -CH2CH2CH2-.
[0115] (32) In embodiment (32) is presented a polymer of any one of embodiments (28)-
(31) , wherein at least one monomer unit of R2 is -CH2(CH2)2CH2-.
[0116] (33) In embodiment (33) is presented a polymer of any one of embodiments (28)-
(32) , wherein at least one monomer unit of R2 is -CH2CH(CH3)CH2-.
[0117] (34) In embodiment (34) is presented a polymer of any one of embodiments (28)-
(33) , wherein at least one monomer unit of R2 is -CH2C(CH3)2CH2-.
[0118] (35) In embodiment (35) is presented a polymer of any one of embodiments (28)-
(34) , wherein at least one monomer unit of R2 is -CH2CH(CI¾CH3)-.
[0119] (36) In embodiment (36) is presented a polymer of any one of embodiments (28)-
(35) , wherein at least one monomer unit of R2 is -CH2(CH2)3CH2-.
[0120] (37) In embodiment (37) is presented a polymer of any one of embodiments (28)-
(36) , wherein at least one monomer unit of R2 is -CH2(CI¾)4CH2-.
[0121] (38) In embodiment (38) is presented a polymer of any one of embodiments (28)-
(37) , wherein at least one monomer unit of R2 is -CH2(CI¾)5CH2-.
[0122] (39) In embodiment (39) is presented a polymer of any one of embodiments (28)-
(38) , wherein at least one monomer unit of R2 is -CH2(CI¾)6CH2-.
[0123] (40) In embodiment (40) is presented a polymer of any one of embodiments (1)- (27), wherein each monomer unit of R2 is the same.
[0124] (41) In embodiment (41) is presented a polymer of embodiment (40), wherein R2
Figure imgf000029_0001
[0125] (42) In embodiment (42) is presented a polymer of embodiment (40), wherein R2 is -CH2CH(CH3)-.
[0126] (43) In embodiment (43) is presented a polymer of embodiment (40), wherein R2
Figure imgf000029_0002
[0127] (44) In embodiment (44) is presented a polymer of embodiment (40), wherein R2 is -CH2(CH2)2CH2-. [0128] (45) In embodiment (45) is presented a polymer of embodiment (40), wherein R2 is -CH2CH(CH3)CH2-.
[[00112299]] ((4466)) IInn eemmbl odiment (46) is presented a polymer of embodiment (40), wherein R2 is -CH2C(CH3)2CH2-.
[0130] (47) In embodiment (47) is presented a polymer of embodiment (40), wherein R2 is -CH2CH(CH2CH3)-.
[0131] (48) In embodiment (48) is presented a polymer of embodiment (40), wherein R2 is -CH2(CH2)3CH2-.
[0132] (49) In embodiment (49) is presented a polymer of embodiment (40), wherein R2 is -CH2(CH2)4CH2-.
[0133] (50) In embodiment (50) is presented a polymer of embodiment (40), wherein R2 is -CH2(CH2)5CH2-.
[0134] (51) In embodiment (51) is presented a polymer of embodiment (40), wherein R2 is -CH2(CH2)6CH2-.
[0135] (52) In embodiment (52) is presented a polymer of any one of embodiments (1)- (51), wherein at least one monomeric unit of R1 is replaced by the diketopiperazme unit of formula (VII), wherein R4 is -CH2C(0)-.
[0136] (53) In embodiment (53) is presented a polymer of any one of embodiments (1)- (51), wherein at least one monomeric unit of R1 is replaced by the diketopiperazme unit of formula (VII), wherein R4 is -CH2CH2C(0)-.
[0137] (54) In embodiment (54) is presented a polymer of embodiment (52) or (53), wherein the monomeric unit of R2 is not replaced by a diketopiperazme unit.
[0138] (55) In embodiment (55) is presented a polymer of embodiment (52) or (53), wherein at least one monomeric unit of R2 is replaced by the diketopiperazme unit of formula (VIII), wherein R5 is -CH2-.
[0139] (56) In embodiment (56) is presented a polymer of any one of embodiments (52), (53), and (55), wherein at least one monomeric unit of R2 is replaced by the diketopiperazme unit of formula (VIII), wherein R5 is -CH(CH3)-.
[0140] (57) In embodiment (57) is presented a polymer of any one of embodiments (52), (53), (55), and (56), wherein at least one monomeric unit of R2 is replaced by the
diketopiperazme unit of formula (VIII), wherein R5 is -CH2CH2-. [0141] (58) In embodiment (58) is presented a polymer of any one of embodiments (1)- (51), wherein at least one monomeric unit of R2 is replaced by the diketopiperazine unit of formula (VIII), wherein R5 is only -CH2-.
[0142] (59) In embodiment (59) is presented a polymer of any one of embodiments (1)- (51), and (58), wherein at least one monomeric unit of R2 is replaced by the diketopiperazine unit of formula (VIII), wherein R5 is only -CH(CH3)-.
[0143] (60) In embodiment (60) is presented a polymer of any one of embodiments in paragraphs (1)-(51), (58), and (59), wherein at least one monomeric unit of R2 is replaced by the diketopiperazine unit of formula (VIII), wherein R5 is only -CH2CH2-.
[0144] (61) In embodiment (61) is presented a polymer of any one of embodiment (58)-
(60) , wherein the monomeric unit of R1 is not replaced by a diketopiperazine unit.
[0145] (62) In embodiment (62) is presented a polymer of any one of embodiments (1)-
(61) , wherein the diketopiperazine units are of form (1, 1).
[0146] (63) In embodiment (63) is presented a polymer of any one of embodiments (1)- (61), wherein the diketopiperazine units are of form (d, d).
[0147] (64) In embodiment (64) is presented a polymer of any one of embodiments (1)- (61), wherein the diketopiperazine units are of form (1, d).
[0148] (65) In embodiment (65) is presented a polymer of any one of embodiments (1)- (61), wherein the diketopiperazine units are of form (d, 1).
[0149] (66) In embodiment (66) is presented a polymer of any one of embodiments (1)- (61), wherein the diketopiperazine units are of at least two different forms selected from (1, 1), (l, d), (d, l), and (d, d).
[0150] (67) In embodiment (67) is presented a polymer of any one of embodiments (1)- (53) and (62)-(66), wherein about 0.01 to about 0.3 mole fraction of one monomeric unit of R1 is replaced by a diketopiperazine unit of formula (VII).
[0151] (68) In embodiment (68) is presented a polymer of embodiment (67), wherein about 0.01 to about 0.1 mole fraction of one monomeric unit of R1 is replaced by a diketopiperazine unit of formula (VII).
[0152] (69) In embodiment (69) is presented a polymer of embodiment (68), wherein about 0.02 to about 0.07 mole fraction of one monomeric unit of R1 is replaced by a diketopiperazine unit of formula (VII). [0153] (70) In embodiment (70) is presented a polymer of any one of embodiments (1)- (53) and (55)-(69), wherein about 0.01 to about 0.3 mole fraction of R2 is replaced by a diketopiperazine unit of formula (VIII).
[0154] (71) In embodiment (71) is presented a polymer of embodiment (70), wherein about 0.01 to about 0.1 mole fraction of one monomeric unit of R2 is replaced by a diketopiperazine unit of formula (VIII).
[0155] (72) In embodiment (72) is presented a polymer of embodiment (71), wherein about 0.02 to about 0.07 mole fraction of one monomeric unit of R2 is replaced by a diketopiperazine unit of formula (VIII).
[0156] (73) In embodiment (73) is presented a polymer of any one of embodiments (1)- (72), wherein at least one of the monomeric units of R2 is of the formula
Figure imgf000032_0001
(X) (XI).
[0157] (74) In embodiment (74) is presented a polymer of embodiment (73), wherein at least one of the monomeric units of R2 is of formula (X), and at least one of the monomeric units of R2 is of formula (XI).
[0158] (75) In embodiment (75) is presented a polymer of embodiment (73), wherein at least one of the monomeric units of R2 is of formula (X).
[0159] (76) In embodiment (76) is presented a polymer of embodiment (73), wherein at least one of the monomeric units of R2 is of formula (XI).
[0160] (77) In embodiment (77) is presented a polymer of any one of embodiments (1)- (76), wherein the polymer has a molecular weight of about 500 g/mol to about 1 million g/mol.
[0161] (78) In embodiment (78) is presented a polymer of embodiment (77), wherein the polymer has a molecular weight of about 20,000 g/mol to about 1 million g/mol.
[0162] (79) In embodiment (79) is presented a polymer of embodiment (78), wherein the polymer has a molecular weight of about 20,000 g/mol to about 100,000 g/mol.
[0163] (80) In embodiment (80) is presented a polymer of embodiment (77), wherein the polymer has a molecular weight of about 500 g/mol to about 100,000 g/mol. [0164] (81) In embodiment (81) is presented a polymer of embodiment (80), wherein the polymer has a molecular weight of about 500 g/mol to about 20,000 g/mol.
[0165] (82) In embodiment (82) is presented a polymer of embodiment (81), wherein the polymer has a molecular weight of about 500 g/mol to about 10,000 g/mol.
[0166] (83) In embodiment (83) is presented a polymer of embodiment (82), wherein the polymer has a molecular weight of about 500 g/mol to about 3,000 g/mol.
[0167] (84) In embodiment (84) is presented a method of preparing a polymer of any one of embodiments (l)-(83) comprising: (i) combining in a reaction vessel (a) one or more compounds of formula R1(OH)2 or R1(OR6)2, wherein R6 is an alkyl group, (b) one or more aliphatic glycols of formula R2(OH)2, (c) one or more diketopiperazme units of aspartic acid and/or glutamic acid, wherein the mole ratio of the diketopiperazme units of aspartic acid and glutamic acid to the compounds of formula R1(OH)2 or R1(OR6)2 is about 0.01 to about 0.8, and/or one or more diketopiperazme units of serine and/or threonine, wherein the mole ratio of the diketopiperazme units of serine and threonine to the aliphatic glycols R2(OH)2 is about 0.01 to about 0.8, and (d) a catalyst, (ii) purging the reaction vessel with an inert gas, (iii) heating the reaction vessel to a first temperature of about 180 to about 270 °C at a pressure of about 0.5 to about 10 atmospheres (about 50 kPa to 1010 kPa), (iv) raising the temperature of the reaction vessel to a second temperature of about 250 to about 320 °C, (v) reducing the pressure in the reaction vessel to about 0.0001 and 0.01 atmospheres (about 10 Pa to about 1010 Pa), and (vi) thereby providing the polymer of any one of embodiments (l)-(83).
[0168] (85) In embodiment (85) is presented a method of embodiment (84), wherein subpart (c) only includes one or more diketopiperazme units of aspartic acid and/or glutamic acid.
[0169] (86) In embodiment (86) is presented a method of embodiment (84), wherein subpart (c) only includes one or more diketopiperazme units of of serine, homoserine, and/or threonine.
[0170] (87) In embodiment (87) is presented a method of embodiment (86), wherein subpart (c) only includes one or more diketopiperazme units of serine.
[0171] (88) In embodiment (88) is presented a method of embodiment (86), wherein subpart (c) only includes one or more diketopiperazme units of homoserine.
[0172] (89) In embodiment (89) is presented a method of embodiment (86), wherein subpart (c) only includes one or more diketopiperazme units of threonine. [0173] (90) In embodiment (90) is presented a method of any one of embodiments (84)-
(89) , wherein the catalyst is zinc acetate dihydrate and dibutyltin diacetate.
[0174] (91) In embodiment (91) is presented a method of any one of embodiments (84)-
(90) , wherein the one or more compounds of formula R1(OH)2 or R1(OR6)2 comprises at least two different monomer units of R1.
[0175] (92) In embodiment (92) is presented a method of embodiment (90), wherein at least one monomer unit of R1 is of formula (II).
[0176] (93) In embodiment (93) is presented a method of embodiment (91) or (92), wherein at least one monomer unit of R1 is of formula (III).
[0177] (94) In embodiment (94) is presented a method of any one of embodiments (91)-
(93) , wherein at least one monomer unit of R1 is of formula (IV).
[0178] (95) In embodiment (95) is presented a method of any one of embodiments (91)-
(94) , wherein at least one monomer unit of R1 is of formula (V).
[0179] (96) In embodiment (96) is presented a method of any one of embodiments (91)-
(95) , wherein at least one monomer unit of R1 is of formula (VI).
[0180] (97) In embodiment (97) is presented a method of any one of embodiments (91)-
(96) , wherein at least one monomer unit of R1 is of formula (VI), and R3 is -CH2CH2-.
[0181] (98) In embodiment (98) is presented a method of any one of embodiments (91)-
(97) , wherein at least one monomer unit of R1 is of formula (VI), and R3 is -CH2CH2CH2-.
[0182] (99) In embodiment (99) is presented a method of any one of embodiments (91)-
(98) , wherein at least one monomer unit of R1 is of formula (VI), and R3 is -CH2(CH2)2CH2-.
[0183] (100) In embodiment (100) is presented a method of any one of embodiments
(91) -(99), wherein at least one monomer unit of R1 is of formula (VI), and R3 is of formula (IX)
Figure imgf000034_0001
(IX).
[0184] (101) In embodiment (101) is presented a method of any one of embodiments (91)-(100), wherein at least one monomer unit of R1 is of formula (VI), wherein R3 is -CH2(CH2)i4CH2-. [0185] (102) In embodiment (102) is presented a method of any one of embodiments (91)-(101), wherein at least one monomer unit of R1 is of formula (VI), wherein R3 is
-CH2(CH2)8CH2-.
[0186] (103) In embodiment (103) is presented a method any one of embodiments (84)-
(89), wherein each monomer unit of R is the same
[0187] (104) In embodiment (104) is presented a method of embodiment (103), wherein R1 is of formula (II).
[0188] (105) In embodiment (105) is presented a method of embodiment (103), wherein R1 is of formula (III).
[0189] (106) In embodiment (106) is presented a method of embodiment (103), wherein R1 is of formula (IV).
[0190] (107) In embodiment (107) is presented a method of embodiment (103), wherein R1 is of formula (V).
[0191] (108) In embodiment (108) is presented a method of embodiment (103), wherein R1 is of formula (VI).
[0192] (109) In embodiment (109) is presented a method of embodiment (103), wherein R1 is of formula (VI), and R3 is -CH2CH2CH2-.
[0193] (HO) In embodiment (110) is presented a method of embodiment (103), wherein R1 is of formula (VI), and R3 is -CH2(CH2)2CH2-.
[0194] (111) In embodiment (111) is presented a method of embodiment (103), wherein R1 is of formula (VI), and R3 is
Figure imgf000035_0001
(IX).
[0195] (112) In embodiment (112) is presented a method of embodiment (103), wherein R1 is of formula (VI), and R3 is -CH2(CH2)i4CH2-.
[0196] (113) In embodiment (113) is presented a method of embodiment (103), wherein R1 is of formula (VI), and R3 is -CH2(CH2)8CH2-. [0197] (114) In embodiment (114) is presented a method of any one of embodiments (84)-(l 13), wherein the aliphatic glycols of formula R2(OH)2 comprises at least two different monomer units of R2.
[0198] (115) In embodiment (115) is presented a method of embodiment (114), wherein at least one monomer unit of R2 is -CH2CH2-.
[0199] (116) In embodiment (116) is presented a method of embodiment (114) or (115), wherein at least one monomer unit of R2 is -CH2CH(CH3)-.
[0200] (117) In embodiment (117) is presented a method of any one of embodiments
(114)-(116), wherein at least one monomer unit of R2 is -CH2CH2CH2-.
[0201] (118) In embodiment (118) is presented a method of any one of embodiments
(114)-(117), wherein at least one monomer unit of R2 is -CH2(CH2)2CH2-.
[0202] (119) In embodiment (119) is presented a method of any one of embodiments
(114)-(118), wherein at least one monomer unit of R2 is -CH2CH(CH3)CH2-.
[0203] (120) In embodiment (120) is presented a method of any one of embodiments
(114)-(119), wherein at least one monomer unit of R2 is -CH2C(CH3)2CH2-.
[0204] (121) In embodiment (121) is presented a method of any one of embodiments
(114)-(120), wherein at least one monomer unit of R2 is -CH2CH(CH2CH3)-.
[0205] (122) In embodiment (122) is presented a method of any one of embodiments
(114)-(121), wherein at least one monomer unit of R2 is -CH2(CH2)3CH2-.
[0206] (123) In embodiment (123) is presented a method of any one of embodiments
(114)-(122), wherein at least one monomer unit of R2 is -CH2(CH2)4CH2-.
[0207] (124) In embodiment (124) is presented a method of any one of embodiments
(114)-(123), wherein at least one monomer unit of R2 is -CH2(CH2)5CH2-.
[0208] (125) In embodiment (125) is presented a method of any one of embodiments
(114)-(124), wherein at least one monomer unit of R2 is -CH2(CH2)6CH2-.
[0209] (126) In embodiment (126) is presented a method of any one of embodiments in paragraphs (84)-(l 13), wherein each monomer unit of R2 is the same.
[0210] (127) In embodiment (127) is presented a method of embodiment (126), wherein
R2 is -CH2CH2-.
[0211] (128) In embodiment (128) is presented a method of embodiment (126), wherein R2 is -CH2CH(CH3)-. [0212] (129) In embodiment (129) is presented a method of embodiment (126), wherein R2 is -CH2(CH2)2CH2-.
[0213] (130) In embodiment (130) is presented a method of embodiment (126), wherein R2 is -CH2CH2CH2-.
[0214] (131) In embodiment (131) is presented a method of embodiment (126), wherein R2 is -CH2CH(CH3)CH2-.
[0215] (132) In embodiment (132) is presented a method of embodiment (126), wherein R2 is -CH2C(CH3)2CH2-.
[0216] (133) In embodiment (133) is presented a method of embodiment (126), wherein R2 is -CH2CH(CH2CH3)-.
[0217] (134) In embodiment (134) is presented a method of embodiment (126), wherein R2 is -CH2(CH2)3CH2-.
[0218] (135) In embodiment (135) is presented a method of embodiment (126), wherein R2 is -CH2(CH2)4CH2-.
[0219] (136) In embodiment (136) is presented a method of embodiment (126), wherein R2 is -CH2(CH2)5CH2-.
[0220] (137) In embodiment (137) is presented a method of embodiment (126), wherein R2 is -CH2(CH2)6CH2-.
[0221] (138) In embodiment (138) is presented a method of any one of embodiments (84)-(137), wherein the reaction vessel contains at least one diketopiperazme unit of aspartic acid.
[0222] (139) In embodiment (139) is presented a method of any one of embodiments (84)-(138), wherein the reaction vessel contains at least one diketopiperazme unit of glutamic acid.
[0223] (140) In embodiment (140) is presented a method of embodiment (138) or (139), wherein the reaction vessel does not contain any diketopiperazme unit of serine, homoserine, or threonine.
[0224] (141) In embodiment (141) is presented a method of embodiment (138) or (139), wherein the reaction vessel contains at least one diketopiperazme unit of serine.
[0225] (142) In embodiment (142) is presented a method of any one of embodiments (138), (139), or (141), wherein the reaction vessel contains at least one diketopiperazme unit of threonine. [0226] (143) In embodiment (143) is presented a method of any one of embodiments (138), (139), (141), and (142), wherein the reaction vessel contains at least one
diketopiperazme unit of homoserine.
[0227] (144) In embodiment (144) is presented a method of any one of embodiments (84)-(137), wherein the reaction vessel contains at least one diketopiperazme unit of serine.
[0228] (145) In embodiment (145) is presented a method of any one of embodiments (84)-(137) and (144), wherein the reaction vessel contains at least one diketopiperazme unit of threonine.
[0229] (146) In embodiment (146) is presented a method of any one of embodiments (84)-(137), (144), and (145), wherein the reaction vessel contains at least one
diketopiperazme unit of homoserine.
[0230] (147) In embodiment (147) is presented a method of any one of embodiments (144)-(146), wherein the reaction vessel does not contain a diketopiperazme unit of either aspartic acid or glutamic acid.
[0231] (148) In embodiment (148) is presented a method of any one of embodiments (138)-(146), wherein the diketopiperazme units are of form (1, 1).
[0232] (149) In embodiment (149) is presented a method of any one of embodiments (138)-(146), wherein the diketopiperazme units are of form (d, d).
[0233] (150) In embodiment (150) is presented a method of any one of embodiments (138)-(147), wherein the diketopiperazme units are of form (1, d).
[0234] (151) In embodiment (151) is presented a method of any one of embodiments (138)-(147), wherein the diketopiperazme units are of form (d, 1).
[0235] (152) In embodiment (152) is presented a method of any one of embodiments (138)-(147), wherein the diketopiperazme units are of at least two different forms selected from (1, 1), (1, d), (d, 1), and (d, d).
[0236] (153) In embodiment (153) is presented a method of any one of embodiments (84) and (90)-(152), wherein the mole ratio of the diketopiperazme unit of aspartic acid and glutamic acid to the compounds of formula R1(OH)2 or R^OR6^ is about 0.01 to about 0.3 and/or the mole ratio of the diketopiperazme units of serine, homoserine, and threonine to the aliphatic glycols of formula R2(OH)2 is about 0.01 to about 0.3.
[0237] (154) In embodiment (154) is presented a method of any one of embodiments (84)- (152), wherein the mole ratio of the diketopiperazme unit of aspartic acid and glutamic acid to the compounds of formula R1(OH)2 or R1(OR6)2 is about 0.01 to about 0.3 and/or the mole ratio of the diketopiperazine units of serine, and threonine to the aliphatic glycols of formula R2(OH)2 is about 0.01 to about 0.3.
[0238] (155) In embodiment (155) is presented a method of embodiment (153), wherein the mole ratio of the diketopiperazine unit of aspartic acid and glutamic acid to the compounds of formula R1(OH)2 or R1(OR6)2 is about 0.01 to about 0.1 and/or the mole ratio of the diketopiperazine units of serine, homoserine, and threonine to the aliphatic glycols of formula R2(OH)2 is about 0.01 to about 0.1.
[0239] (156) In embodiment (156) is presented a method of embodiment (154), wherein the mole ratio of the diketopiperazine unit of aspartic acid and glutamic acid to the compounds of formula R1(OH)2 or Rx(OR6)2 is about 0.01 to about 0.1 and/or the mole ratio of the diketopiperazine units of serine and threonine to the aliphatic glycols of formula R2(OH)2 is about 0.01 to about 0.1.
[0240] (157) In embodiment (157) is presented a method of embodiment (155), wherein the mole ratio of the diketopiperazine unit of aspartic acid and glutamic acid to the compounds of formula R1(OH)2 or Rx(OR6)2 is about 0.02 to about 0.07 and/or the mole ratio of the diketopiperazine units of serine, homoserine, and threonine to the aliphatic glycols of formula R2(OH)2 is about 0.02 to about 0.07.
[0241] (158) In embodiment (158) is presented a method of embodiment (156), wherein the mole ratio of the diketopiperazine unit of aspartic acid and glutamic acid to the compounds of formula R1(OH)2 or Rx(OR6)2 is about 0.02 to about 0.07 and/or the mole ratio of the diketopiperazine units of serine and threonine to the aliphatic glycols of formula R2(OH)2 is about 0.02 to about 0.07.
[0242] (159) In embodiment (159) is presented a method of any one of embodiments (84)-(157), further comprising adding at least one of the compounds of formulas (XII) and (XIII)
Figure imgf000040_0001
to the reaction vessel, preferably prior to heating the reaction vessel.
[0243] (160) In embodiment (160) is presented a method of improving the
biodegradability and thermal properties of a polymer of formula
-[-R^O-R^O-]- (I)
comprising at least two monomer units of R1 and at least two monomer units of R2, wherein R1 is of formula
(II) (in) (IV) (V) (VI) wherein R is a Ci - C 19 straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group, and R2 is a C2 - Cg straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group, by (a) replacing about 0.01 to about 0.8 mole fraction of R1 by a diketopiperazine unit of formula (VII)
Figure imgf000040_0003
(VII) wherein R4 is -CH2C(0)- or -CH2CH2C(0)-, and/or (b) replacing about 0.01 to about 0.8 mole fraction of R2 by a diketopiperazine unit of formula (VIII)
Figure imgf000041_0001
(VIII)
wherein R5 is -CH2-, -CH2CH2-, or -CH(CH3)-.
[0244] (161) In embodiment (161) is presented a method of embodiment (160), wherein R5 is -CH2- or -CH(CH3)-.
[0245] (162) In embodiment (162) is presented a polymer of formula
-[-R^O-R^O-]- (I)
comprising at least two monomer units of R1, which can be the same or different, and at least two monomer units of R2, which can be the same or different, wherein R1 is an aliphatic or aromatic dicarboxylate unit, wherein the aliphatic dicarboxylate unit comprises a C3 - C36 straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group, and the aromatic dicarboxylate unit comprises a C5 - C2o aryl, heteroaryl, substituted, or unsubstituted aromatic dicarboxylate group, R2 is a C2 - Cs straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group, except that (a) about 0.01 to about 0.8 mole fraction of R1 is replaced by a diketopiperazine unit of formula (VII)
Figure imgf000041_0002
(VII)
wherein R4 is -CH2C(0)- or -CH2CH2C(0)-, and/or (b) about 0.01 to about 0.8 mole fraction of R2 is replaced by a diketopiperazine unit of formula (VIII)
Figure imgf000042_0001
(VIII)
wherein R5 is -CH2-, -CH2CH2-, or -CH(CH3)-.
[0246] (163) In embodiment (163) is presented a polymer of embodiment (162), wherein R5 is only -CH2-.
[0247] (164) In embodiment (164) is presented a polymer of embodiment (162), wherein R5 is only -CH(CH3)-.
[0248] (165) In embodiment (165) is presented a polymer of embodiment (162), wherein R5 is only -CH2CH2-.
[0249] Examples
[0250] The following examples further illustrate aspects of the invention but, of course, should not be construed as in any way limiting its scope.
EXAMPLE 1
[0251] This example demonstrates a method of preparing a homopolymer of polyethylene terephthalate (PET).
[0252] To a glass reaction vessel fitted with a stirrer, a Dean-Stark trap with a condenser, and a stainless steel thermocouple connected to a controller were added 388.38 g of dimethyl terephthalate (2 mole), 248.28 g of ethylene glycol (4 moles), 0.088 g zinc acetate dihydrate (65 ppm), and 0.48 g of dibutyltin diacetate (400 ppm). The vessel was purged with nitrogen for 5 minutes.
[0253] The reaction vessel was placed in an aluminum-housed heating mantle and, with stirring, was heated at a temperature of 190 °C for 1 hour, then at a temperature of 210 °C for 1.5 hour, and then at a temperature of 260 °C for 30 minutes. Vacuum was gradually applied over the next 30 minutes until a pressure of about 133.3 Pa (1 mm Hg) was obtained. After 10 minutes, the temperature was increased to 270 °C, and full vacuum was maintained for a total time of 1 hour. Upon completion, the pressure of the reaction vessel was brought to atmospheric pressure, and the hot contents of the flask were slowly poured into an aluminum container with ice water to form an amorphous strand of polymer. The intrinsic viscosity of the resulting homopolymer was measured in o-chlorophenol solvent as 0.576 dL/g.
EXAMPLE 2
[0254] This example demonstrates a method of preparing a copolymer from terephthalic acid, ethylene glycol, and diketopiperazine unit of serine.
[0255] To a glass reaction vessel fitted with a stirrer, a Dean-Stark trap with a condenser, and a stainless steel thermocouple connected to a controller were added 388.38 g of dimethyl terephthalate (2 moles), 10.33 g of serine diketopiperazine (0.06 moles), 161.38 g of ethylene glycol (2.6 moles), 0.088 g zinc acetate dihydrate (65 ppm), and 0.48 gram of dibutyltin diacetate (400 ppm). The vessel was purged with nitrogen for 5 minutes.
[0256] The reaction vessel was placed in an aluminum-housed heating mantle and, with stirring, was heated at a temperature of 190 °C for 1.5 hours, then at a temperature of 210 °C for 1.5 hour, and then at a temperature of 230 °C for 1 hour and 20 minutes. Vacuum was gradually applied over the next 30 minutes until a pressure of less than about 133.3 Pa (less than 1 mm Hg) was obtained. Full vacuum was maintained for another 50 minutes. Upon completion, the pressure of the reaction vessel was brought to atmospheric pressure. The hot contents of the flask, which had solidified on the stirrer, were removed from the reactor and collected on an aluminum sheet. The intrinsic viscosity of the resulting copolymer was measured in o-chlorophenol solvent as 0.123 dL/g.
EXAMPLE 3
[0257] This example demonstrates a method of preparing higher molecular weight copolymer containing diketopiperazine using the Solid State Polymerization process.
[0258] About 12 g of a low molecular weight copolymer from Example 2 was ground to small particles and evenly dispersed into an Erlenmeyer flask with a ground glass joint. The flask was purged with nitrogen gas for 5 minutes. Then the flask was placed into a hot oil bath controlled at 160 °C for 2 hours. In the solid state polymerization state, the flask was connected to a vacuum pump fitted with a dry ice-isopropanol cold trap. The pressure was reduced to about 60 Pa (about 0.5 mm Hg). The temperature of the hot oil bath was raised to 210 °C, and the reaction was allowed to proceed for 24 hours. The flask was then removed from the hot oil bath, and the polymer was allowed to cool to room temperature. The intrinsic viscosity (IV) of the resulting copolymer was measured in o-chlorophenol solvent as 0.375 dL/g.
EXAMPLE 4
[0259] This example demonstrates a method of preparing a copolymer of a terephthalate, ethylene glycol, and a diketopiperazine unit of aspartate.
[0260] To a glass reaction vessel fitted with a stirrer, a Dean Stark trap with a condenser, and a stainless steel thermocouple connected to a controller were added 376.73 g of dimethyl terephthalate (1.94 moles), 15.49 g of aspartate diketopiperazine (0.06 moles), 248.28 g of ethylene glycol (4.0 moles), 0.088 g of zinc acetate dihydrate (65 ppm), and 0.48 g of dibutyltin diacetate (400 ppm). The vessel was purged with nitrogen for 5 minutes.
[0261] The reaction vessel was placed in an aluminum-housed heating mantle and, with stirring, was heated at a temperature of 190 °C for 1 hour, then at a temperature of 210 °C for 1.5 hour, and then at a temperature of 250 °C for 30 minutes. Vacuum was gradually applied over the next 30 minutes until a pressure of 133.3 Pa (about 1 mm Hg) was obtained. After 10 minutes, the temperature was increased to 260 °C, and a full vacuum was maintained for a total time of 1 hour.
[0262] Upon completion, the pressure of the reaction vessel was brought to atmospheric pressure, and the hot contents of the flask were slowly poured into an aluminum container with ice water to form an amorphous strand of the polymer. A high molecular weight copolymer was produced, with intrinsic viscosity of 0.746 dL/g.
EXAMPLE 5
[0263] This example compares certain physical and thermal properties between a homopolymer of polyethylene terephthalate (PET) and a copolymer in which 0.03 mole fraction of the dialkoxy units were replaced with the diketopiperazine units of serine (serine- DKP (3 mol%)/PET copolymer).
[0264] PET prepared in accordance with Example 1 and serine-DKP (3 mol%)/PET copolymer prepared in accordance with Example 3 were each subjected to an analysis for the properties indicated in Table 1. The results are set forth in Table 1. The thermal properties were determined by differential scanning calorimetry (DSC). [0265] Table 1 : Comparison between the physical and thermal properties of polyethylene terephthalate (PET) and serine -DKP (3 mol%)/PET copolymer.
Figure imgf000045_0001
[0266] Compared to PET, serine-DKP (3 mol%)/PET copolymer had a lower glass transition temperature (Tg) and a higher melting temperature (Tm). In addition, serine-DKP (3 mol%)/PET copolymer had a lower temperature of crystallization on heating (Tch) from the amorphous state and a higher temperature of crystallization (Tec) on cooling from the melt. The heat of crystallization on heating (Hch) was also higher for serine-DKP (3 mol%)/PET copolymer as compared to PET, thereby indicating that serine-DKP (3 mol%)/PET copolymer had greater crystallinity than PET.
EXAMPLE 6
[0267] This example compares the physical and thermal properties of a homopolymer of polyethylene terephthalate (PET), a copolymer in which 0.03 mole fraction of the terephthalate monomer units were replaced with the diketopiperazme units of aspartic acid (aspartic acid-DKP (3 mol%)/PET copolymer), and a second copolymer in which 0.1 mole fraction of the terephthalate monomer units were replaced with the diketopiperazme units of aspartic acid (aspartic acid-DKP (10 mol%)/PET copolymer). [0268] PET prepared in accordance with Example 1 , aspartic acid-DKP (3 mol%)/PET copolymer prepared in accordance with Example 2, and aspartic acid-DKP (10 mol%)/PET copolymer were each subjected to an analysis for the properties identified in Table 2. The results are set forth in Table 2.
[0269] Table 2: Comparison between the physical and thermal properties of polyethylene terephthalate (PET), aspartic acid-DKP (3 mol%)/PET copolymer, and aspartic acid-DKP (10 mol%)/PET copolymer.
Figure imgf000046_0001
[0270] Aspartic acid-DKP (10 mol %)/PET copolymer became insoluble in typical solvents used to measure intrinsic viscosity, e.g., trifluoroacetic acid and
phenol/trichloroethane. As the mole fraction of the diketopiperazines increased in the copolymer, the glass transition temperature (Tg), the temperature of crystallization on heating (Tch), and the melting temperature (Tm) decreased. Aspartic acid-DKP (3 mol%)/PET copolymer showed an increase in the temperature of crystallization on cooling (Tec) as compared to PET, whereas aspartic acid-DKP (10 mol%)/PET copolymer showed a substantial decrease in the temperature of crystallization on cooling (Tec). EXAMPLE 7
[0271] This example compares the mechanical and thermal properties of a homopolymer of polyethylene terephthalate (PET) and a copolymer in which 0.03 mole fraction of the terephthalate monomer units were replaced with the diketopiperazine units of aspartate (aspartate-DKP (3 mol%)/PET copolymer).
[0272] Preparation of samples for dynamic mechanical analysis (DMA): Samples were prepared by compression molding using a press. Prior to applying the force, the material was heated to 255 °C in the press and kept at this temperature for 10 minutes. Then, the material was pressed into a sheet at a temperature of 255 °C under 2 tons of force for an additional 10 minutes. At the end of 10 minutes, the mold was removed from the press and allowed to cool at room temperature on a lab bench. The thickness of the material produced from this process was about 1.4 mm. The DMA samples were prepared by filing the fragments of the pressed material into a rectangular form using fine grain sandpaper. The final dimension of the test samples were approximately 15 mm long, 9 mm wide, and 1.4 mm thick.
[0273] DMA Run Conditions: All polymer samples were tested using the same test parameters. DMA measurements were performed in a Mettler Toledo DMA861e instrument but any suitable instrument may be used. The temperature program had a two-step profile. The temperature of the sample was held at 26 °C for three minutes and then heated from 26 °C to 150 °C at 5 °C/min. The force and displacement amplitude values were 1 Newton (N) and 2 μιη, respectively for both PET and aspartate-DKP (3 mol%)/PET copolymer samples.
[0274] Fig. 1 shows a comparison of storage modulus data for samples of polyethylene terephthalate (PET) and aspartate-DKP (3 mol%)/PET copolymer. The mechanical properties of PET are altered by the incorporation of low levels of aspartate DKP. At every measurement, the aspartate-DKP (3 mol%)/PET copolymer demonstrated a higher storage modulus, which means that the aspartate-DKP (3 mol%)/PET copolymer was stiffer than the base PET.
[0275] Fig. 2 shows a comparison of tan delta data for samples of PET and the aspartate- DKP (3 mol%)/PET copolymer as measured by DMA. The maximum value of tan delta is a measure of the glass transition temperature (Tg), which reflects the onset of the transition of the polymer from a glassy to a rubbery state. Fig. 2 shows that the glass transition
temperature (Tg) of the aspartate-DKP (3 mol%)/PET copolymer is lower than the base PET. EXAMPLE 8
[0276] This example demonstrates a method of preparing a homopolymer of polyethylene adipate (PEA).
[0277] To a glass reaction vessel fitted with a stirrer and a Dean-Stark trap with a condenser were added 304.85 g of dimethyl adipate (1.75 mole), 152.07 g of ethylene glycol (2.45 moles), 0.055 g zinc acetate dihydrate (54 ppm), and 0.40 g of dibutyltin diacetate (449 ppm). The vessel was purged with nitrogen for 5 minutes.
[0278] The reaction vessel was stirred at 60 rpm and placed in a hot oil bath, which was heated at a temperature of 170 °C for 1 hour, then at a temperature of 180 °C for 0.5 hour, then at a temperature of 190 °C with the stirrer speed set at 100 rpm for 0.5 hour, then at a temperature of 200 °C with the stirrer speed set at 150 rpm for 1 hour, and then at a temperature of 210 °C with the stirrer speed maintained at 150 rpm for 0.75 hour.
[0279] Vacuum was gradually applied over the next 40 minutes until a pressure of about 66.7 Pa (0.5 mm of Hg) was obtained. After 30 minutes, the temperature was increased to 220 °C for 1.75 hours, then to 230 °C for 1 hour, and then to 240 °C for 0.25 hour. During the period that the reaction was at full vacuum (i.e., 66.7 Pa (0.5 mm of Hg) or lower), the stirrer speed was gradually increased in 50 rpm increments until a final speed of 600 rpm was achieved. The stirrer speed of 600 rpm was maintained for the final hour of the reaction.
[0280] Upon completion, the pressure of the reaction vessel was brought to atmospheric pressure, and the hot contents of the flask were slowly poured into an aluminum container with ice water to form an amorphous strand of polymer.
EXAMPLE 9
[0281] This example demonstrates a method of preparing a copolymer of an adipate, ethylene glycol and diketopiperazine of aspartate at 5 mole %.
[0282] To a glass reaction vessel fitted with a stirrer and a Dean-Stark trap with a condenser were added 289.60 g of dimethyl adipate (1.663 mole), 22.60 g of aspartate diketopiperazine (0.0875 moles), 152.07 g of ethylene glycol (2.45 moles), 0.055 g zinc acetate dihydrate (54 ppm), and 0.40 g of dibutyltin diacetate (449 ppm). The vessel was purged with nitrogen for 5 minutes.
[0283] The reaction vessel was stirred at 60 rpm and placed in a hot oil bath, which was heated at a temperature of 170 °C for 1 hour, then at a temperature of 180 °C for 0.5 hour, then at a temperature of 190 °C with the stirrer speed set at 100 rpm for 0.5 hour, then at a temperature of 200 °C with the stirrer speed set at 150 rpm for 1 hour, and then at a temperature of 210 °C with the stirrer speed maintained at 150 rpm for 0.75 hour.
[0284] Vacuum was gradually applied over the next 40 minutes until a pressure of about 66.7 Pa (0.5 mm of Hg) was obtained. After 30 minutes, the temperature was increased to 220 °C for 1 hour, then to 230 °C for 0.75 hour, and then to 240 °C for 0.25 hour. During the period that the reaction was at full vacuum (i.e., 66.7 Pa (0.5 mm of Hg) or lower), the stirrer speed was gradually increased in 50 rpm increments until a final speed of 600 rpm was achieved. The stirrer speed of 600 rpm was maintained for the final hour of the reaction.
[0285] Upon completion, the pressure of the reaction vessel was brought to atmospheric pressure, and the hot contents of the flask were slowly poured into an aluminum container with ice water to form an amorphous strand of polymer.
EXAMPLE 10
[0286] This example demonstrates a method of preparing a copolymer of an adipate, ethylene glycol and diketopiperazine of aspartate at 10 mole %.
[0287] To a glass reaction vessel fitted with a stirrer and a Dean-Stark trap with a condenser were added 274.36 g of dimethyl adipate (1.575 moles), 45.19 g of aspartate diketopiperazine (0.175 moles), 152.07 g of ethylene glycol (2.45 moles), 0.055 g zinc acetate dihydrate (54 ppm), and 0.40 g of dibutyltin diacetate (449 ppm). The vessel was purged with nitrogen for 5 minutes.
[0288] The reaction vessel was stirred at 60 rpm and placed in a hot oil bath, which was heated at a temperature of 170 °C for 1 hour, then at a temperature of 180 °C for 0.5 hour, then at a temperature of 190 °C with the stirrer speed set at 100 rpm for 0.5 hour, then at a temperature of 200 °C with the stirrer speed set at 150 rpm for 1 hour, and then at a temperature of 210 °C with the stirrer speed maintained at 150 rpm for 0.75 hour. To the reaction mixture was then added 0.4 g of dibutyltin diacetate (449 ppm).
[0289] Vacuum was gradually applied over the next 40 minutes until a pressure of about 66.7 Pa (0.5 mm of Hg) was obtained. After 30 minutes, the temperature was increased to 220 °C for 1 hour, and then to 225 °C for 0.5 hour. During the period that the reaction was at full vacuum (i.e., 66.7 Pa (0.5 mm of Hg) or lower), the stirrer speed was gradually increased in 50 rpm increments until a final speed of 400 rpm was achieved. The stirrer speed of 400 rpm was maintained for the final hour of the reaction. During the final hour of the reaction, stirrer torque gradually increased to a final value of 33-lb-in.
[0290] Upon completion, the pressure of the reaction vessel was brought to atmospheric pressure, and the hot contents of the flask were slowly poured into an aluminum container with ice water to form an amorphous strand of polymer.
EXAMPLE 11
[0291] This example provides a method using proton nuclear magnetic resonance (NMR) spectroscopy to provide the relative molecular weight data for the polymers prepared in Examples 8, 9, and 10.
[0292] The solvent of the polymer was deuterochloroform (CDCI3). A synthetic sample of polyethylene adipate (PEA) was obtained from Sigma- Aldrich (#181919, Lot
MKBK3785V) and used as a control. The reported molecular weight of the synthetic PEA from Sigma- Aldrich was about 10,000 as determined by gel permeation chromatography (GPC).
[0293] As the reaction starting materials and products are all soluble in chloroform, the polymerization can be monitored using NMR analysis. NMR analysis of PEA showed a multiplet at a chemical shift of -2.35 ppm that represents the four methylene protons attached to the carboxylate carbon of the adipate moiety. In addition, at a chemical shift of -3.75 ppm is a multiplet that represents the four methylene protons attached to the alcohol end groups of ethylene glycol. The data from analysis of the synthetic PEA control, the PEA homopolymer and the two PEA copolymers containing aspartate DKP are provided in Table 3.
[0294] Table 3 : Comparison of proton NMR data from PEA of Sigma- Aldrich (control) of 10,000 molecular weight as determined by GPC to PEA homopolymer from Example 7 and PEA containing 5 mole% aspartate (Example 8), and 10 mole% aspartate (Example 9).
Figure imgf000051_0001
[0295] The data indicate that the ethylene glycol end group content of the three polymers prepared in Examples 8, 9, and 10 are two to three times lower than the Sigma-Aldrich PEA and thus are of higher molecular weight.
EXAMPLE 12
[0296] This example demonstrates a comparison between the mechanical and thermal properties of a homopolymer of polyethylene adipate (PEA) and a copolymer in which 0.10 mole fraction of the adipate monomer units were replaced with the diketopiperazine units of aspartate (aspartate -DKP (10 mol%)/PEA copolymer).
[0297] Preparation of samples for DMA: Samples were prepared by compression molding using a press. These materials were pressed into a sheet at a temperature of 55 °C under 4 tons of force for 10 minutes. The material was then cooled to room temperature using the water cooling system in the press. After cooling, the material was folded and subjected to a second compression molding step using the same parameters. The samples were kept at ambient conditions for a minimum time period of 24 hours before testing.
Rectangular DMA samples were prepared by cutting the sheet with a die cutter. The die had a dog bone shape, and the gage section was cut out to form the DMA sample. The nominal dimensions of the samples were 9 mm long, 3 mm wide, and 0.5 mm thick. [0298] DMA Run Conditions: The polyester samples were tested under the same temperature programs but at different force and displacement amplitude values to account for the differences in the mechanical properties observed while handling the samples.
Specifically, the base PEA polymer was brittle, and the PEA copolymer containing 10 mole% aspartate was more flexible.
[0299] DMA measurements were performed in a Mettler Toledo DMA861e instrument but any suitable instrument may be used. The temperature program had a three-step profile. First, the temperature was cooled from room temperature to -58 °C; then, it was held at -58 °C for three minutes; and finally the temperature was raised from -55 °C to 35 °C at 5 °C/min. The force and displacement amplitude values used for the two samples are given in Table 4. These values were found to be within the linear viscoelastic limit for each material.
[0300] Table 4: DMA testing parameters.
Figure imgf000052_0001
[0301] Fig. 3 shows a comparison of storage modulus data for samples of polyethylene adipate (PEA) and a PEA copolymer containing aspartate DKP- (10 mole %) (aspartate-DKP (10 mol%)/PEA copolymer) as measured by DMA. The mechanical properties of PEA are altered by the incorporation of low levels of aspartate DKP. The aspartate-DKP (10 mol%)/PEA copolymer demonstrated an increased stiffness at sub-ambient temperatures and reduced stiffness, i.e. increased flexibility, at temperatures closer to ambient conditions. In this particular case, the aspartate-DKP (10 mol%)/PEA copolymer had a significant improvement in structural integrity compared to the base PEA. At room temperature, while the base PEA is rigid and brittle the aspartate-DKP (10 mol%)/PEA copolymer was flexible. Fig. 4 shows a comparison of tan delta data for samples of PEA and the aspartate-DKP (10 mol%)/PEA copolymer as measured by DMA. The data presented in Fig. 4 show that the glass transition temperature (Tg) of the aspartate-DKP (10 mol%)/PEA copolymer is higher than that for the base PEA. EXAMPLE 13
[0302] This example demonstrates a method of preparing a copolymer from a
terephthalate, ethylene glycol, and diketopiperazine unit of threonine.
[0303] To a glass reaction vessel fitted with a stirrer, a Dean-Stark trap with a condenser, and a stainless steel thermocouple connected to a controller are added 388.38 g of dimethyl terephthalate (2 moles), 12.0 g of threonine diketopiperazine (0.06 moles), 161.38 g of ethylene glycol (2.6 moles), 0.088 g zinc acetate dihydrate (65 ppm), and 0.48 gram of dibutyltin diacetate (400 ppm). The vessel is purged with nitrogen for 5 minutes.
[0304] The reaction vessel is placed in an aluminum-housed heating mantle and, with stirring, is heated at a temperature of 190 °C for 1.5 hours, then at a temperature of 210 °C for 1.5 hour, and then at a temperature of 230 °C for 1 hour and 20 minutes. Vacuum is gradually applied over the next 30 minutes until a pressure of less than about 133.3 Pa (less than 1 mm Hg) is obtained. Full vacuum is maintained for another 50 minutes.
[0305] Upon completion, the pressure of the reaction vessel is brought to atmospheric pressure. The hot contents of the flask, which solidify on the stirrer, are removed from the reactor and collected in ice water.
EXAMPLE 14
[0306] This example illustrates the expected properties of a copolymer prepared from terephthalic acid as the dimethyl ester, ethylene glycol, and diketopiperazine unit of threonine (threonine -DKP/PET copolymer), as compared to the corresponding conventional polymer, polyethylene terephthalate (PET).
[0307] Threonine -DKP units replace the dialkoxy units in the conventional copolymer PET. Compared to PET, the threonine -DKP /PET copolymer shows a lower glass transition temperature (Tg), and a higher degree of crystallinity than the base PET. Threonine - DKP/PET copolymer also shows improved biodegradability.
EXAMPLE 15
[0308] This example demonstrates a method of preparing a copolymer of an adipate, ethylene glycol and diketopiperazine of threonine.
[0309] To a glass reaction vessel fitted with a stirrer and a Dean-Stark trap with a condenser are added 304.85 g of dimethyl adipate (1.75 mole), 24.66 g of threonine diketopiperazine (0.122 moles), 152.07 g of ethylene glycol (2.45 moles), 0.055 g zinc acetate dihydrate (54 ppm), and 0.40 g of dibutyltin diacetate (449 ppm). The vessel is purged with nitrogen for 5 minutes.
[0310] The reaction vessel is placed in hot oil bath and, with stirring set at 60 rpm, is heated at a temperature of 170 °C for 1 hour, then at a temperature of 180 °C for 0.5 hour, then at a temperature of 190 °C with the stirrer speed set at 100 rpm for 0.5 hour, then at a temperature of 200 °C with the stirrer speed set at 150 rpm for 1 hour, and then at a temperature of 210 °C with the stirrer speed maintained at 150 rpm for 0.75 hour.
[0311] Vacuum is gradually applied over the next 40 minutes until a pressure of about 66.7 Pa (0.5 mm of Hg) is obtained. After 30 minutes, the temperature is increased to 220 °C for 1 hour, then to 230 °C for 0.75 hour, and then to 240 °C for 0.25 hour. During the period that the reaction is at full vacuum, stirrer speed is gradually increased in 50 rpm increments until a final speed of 600 rpm is achieved. A stirrer speed of 600 rpm is maintained for the final hour of the reaction.
[0312] Upon completion, the pressure of the reaction vessel is brought to atmospheric pressure, and the hot contents of the flask are slowly poured into an aluminum container with ice water to form an amorphous strand of polymer.
EXAMPLE 16
[0313] This example illustrates the expected properties of a copolymer prepared from adipic acid as the dimethyl ester, ethylene glycol, and diketopiperazine unit of threonine (threonine -DKP/PEA copolymer), as compared to the corresponding conventional polymer, polyethylene adipate (PEA).
[0314] Threonine -DKP units replace the dialkoxy units in the conventional copolymer PEA. Compared to PEA, threonine-DKP/PEA copolymer shows a higher glass transition temperature (Tg), a higher melting temperature (Tm), an improved temperature of crystallization on heating (Tch) when heated from the amorphous state, and an improved temperature of crystallization (Tec) when cooled from the melt. Threonine-DKP/PEA copolymer also shows improved biodegradability. EXAMPLE 17
[0315] This example demonstrates a method of preparing a copolymer from a
terephthalate, ethylene glycol, and diketopiperazine unit of homoserine.
[0316] To a glass reaction vessel fitted with a stirrer, a Dean-Stark trap with a condenser, and a stainless steel thermocouple connected to a controller are added 388.38 g of dimethyl terephthalate (2 moles), 12.0 g of homoserine diketopiperazine (0.06 moles), 161.38 g of ethylene glycol (2.6 moles), 0.088 g zinc acetate dihydrate (65 ppm), and 0.48 gram of dibutyltin diacetate (400 ppm). The vessel is purged with nitrogen for 5 minutes.
[0317] The reaction vessel is placed in an aluminum-housed heating mantle and, with stirring, is heated at a temperature of 190 °C for 1.5 hours, then at a temperature of 210 °C for 1.5 hour, and then at a temperature of 230 °C for 1 hour and 20 minutes. Vacuum is gradually applied over the next 30 minutes until a pressure of less than about 133.3 Pa (less than 1 mm Hg) is obtained. Full vacuum is maintained for another 50 minutes.
[0318] Upon completion, the pressure of the reaction vessel is brought to atmospheric pressure. The hot contents of the flask, which have solidified on the stirrer, are removed from the reactor and collected in ice water.
EXAMPLE 18
[0319] This example illustrates the expected properties of a copolymer prepared from terephthalic acid as the dimethyl ester, ethylene glycol, and diketopiperazine unit of homoserine (homoserine-DKP/PET copolymer), as compared to the corresponding conventional polymer, polyethylene terephthalate (PET).
[0320] Homoserine-DKP units replace the dialkoxy units in the conventional copolymer PET. Compared to PET, the homoserine-DKP /PET copolymer shows a lower glass transition temperature (Tg), and a higher degree of crystallinity than the base PET.
Homoserine-DKP/PET copolymer also shows improved biodegradability.
EXAMPLE 19
[0321] This example demonstrates a method of preparing a copolymer of an adipate, ethylene glycol and diketopiperazine of homoserine.
[0322] To a glass reaction vessel fitted with a stirrer and a Dean-Stark trap with a condenser are added 304.85 g of dimethyl adipate (1.75 mole), 24.66 g of homoserine diketopiperazine (0.122 moles), 152.07 g of ethylene glycol (2.45 moles), 0.055 g zinc acetate dihydrate (54 ppm), and 0.40 g of dibutyltin diacetate (449 ppm). The vessel is purged with nitrogen for 5 minutes.
[0323] The reaction vessel is placed in hot oil bath and, with stirring set at 60 rpm, is heated at a temperature of 170 °C for 1 hour, then at a temperature of 180 °C for 0.5 hour, then at a temperature of 190 °C with the stirrer speed set at 100 rpm for 0.5 hour, then at a temperature of 200 °C with the stirrer speed set at 150 rpm for 1 hour, and then at a temperature of 210 °C with the stirrer speed maintained at 150 rpm for 0.75 hour.
[0324] Vacuum is gradually applied over the next 40 minutes until a pressure of about 66.7 Pa (0.5 mm of Hg) is obtained. After 30 minutes, the temperature is increased to 220 °C for 1 hour, then to 230 °C for 0.75 hour, and then to 240 °C for 0.25 hour. During the period that the reaction is at full vacuum, stirrer speed is gradually increased in 50 rpm increments until a final speed of 600 rpm is achieved. A stirrer speed of 600 rpm is maintained for the final hour of the reaction.
[0325] Upon completion, the pressure of the reaction vessel is brought to atmospheric pressure, and the hot contents of the flask are slowly poured into an aluminum container with ice water to form an amorphous strand of polymer.
EXAMPLE 20
[0326] This example illustrates the expected properties of a copolymer prepared from adipic acid as the dimethyl ester, ethylene glycol, and diketopiperazine unit of homoserine (homoserine-DKP/PEA copolymer), as compared to the corresponding conventional polymer, polyethylene adipate (PEA).
[0327] Homoserine-DKP units replace the dialkoxy units in the conventional copolymer PEA. Compared to PEA, homoserine-DKP/PEA copolymer shows a higher glass transition temperature (Tg), a higher melting temperature (Tm), an improved temperature of
crystallization on heating (Tch) when heated from the amorphous state, and an improved temperature of crystallization (Tec) when cooled from the melt. Homoserine-DKP/PEA copolymer also shows improved biodegradability. EXAMPLE 21
[0328] This example demonstrates a method of preparing a copolymer from a
terephthalate, ethylene glycol, and diketopiperazine unit of glutamate.
[0329] To a glass reaction vessel fitted with a stirrer, a Dean-Stark trap with a condenser, and a stainless steel thermocouple connected to a controller are added 376.73 g of dimethyl terephthalate (1.94 moles), 17.17 g of dimethyl ester of the glutamate diketopiperazine (0.06 moles), 161.38 g of ethylene glycol (2.6 moles), 0.088 g zinc acetate dihydrate (65 ppm), and 0.48 gram of dibutyltin diacetate (400 ppm). The vessel is purged with nitrogen for 5 minutes.
[0330] The reaction vessel is placed in an aluminum-housed heating mantle and, with stirring, is heated at a temperature of 190 °C for 1.5 hours, then at a temperature of 210 °C for 1.5 hour, and then at a temperature of 230 °C for 1 hour and 20 minutes. Vacuum is gradually applied over the next 30 minutes until a pressure of less than about 133.3 Pa (less than 1 mm Hg) is obtained. Full vacuum is maintained for another 50 minutes.
[0331] Upon completion, the pressure of the reaction vessel is brought to atmospheric pressure. The hot contents of the flask, which have solidified on the stirrer, are removed from the reactor and collected in ice water.
EXAMPLE 22
[0332] This example illustrates the expected properties of a copolymer prepared from terephthalic acid as the dimethyl ester, ethylene glycol, and diketopiperazine unit of glutamic acid (glutamate -DKP/PET copolymer), as compared to the corresponding conventional polymer, polyethylene terephthalate (PET).
[0333] Glutamate-DKP units replace the dicarboxy units in the conventional copolymer PET. Compared to PET, the glutamate-DKP /PET copolymer shows a lower glass transition temperature (Tg), and a higher degree of crystallinity than the base PET. Glutamate- DKP/PET copolymer also shows improved biodegradability.
EXAMPLE 23
[0334] This example demonstrates a method of preparing a copolymer of an adipate, ethylene glycol and diketopiperazine of glutamate. [0335] To a glass reaction vessel fitted with a stirrer and a Dean-Stark trap with a condenser are added 283.51 g of dimethyl adipate (1.628 mole), 35.05 g of dimethyl ester of glutamate diketopiperazine (0.122 moles), 152.07 g of ethylene glycol (2.45 moles), 0.055 g zinc acetate dihydrate (54 ppm), and 0.40 g of dibutyltin diacetate (449 ppm). The vessel is purged with nitrogen for 5 minutes.
[0336] The reaction vessel is placed in hot oil bath and, with stirring set at 60 rpm, is heated at a temperature of 170 °C for 1 hour, then at a temperature of 180 °C for 0.5 hour, then at a temperature of 190 °C with the stirrer speed set at 100 rpm for 0.5 hour, then at a temperature of 200 °C with the stirrer speed set at 150 rpm for 1 hour, and then at a temperature of 210 °C with the stirrer speed maintained at 150 rpm for 0.75 hour.
[0337] Vacuum is gradually applied over the next 40 minutes until a pressure of about 66.7 Pa (0.5 mm of Hg) is obtained. After 30 minutes, the temperature is increased to 220 °C for 1 hour, then to 230 °C for 0.75 hour, and then to 240 °C for 0.25 hour. During the period that the reaction is at full vacuum, stirrer speed is gradually increased in 50 rpm increments until a final speed of 600 rpm is achieved. A stirrer speed of 600 rpm is maintained for the final hour of the reaction.
[0338] Upon completion, the pressure of the reaction vessel is brought to atmospheric pressure, and the hot contents of the flask are slowly poured into an aluminum container with ice water to form an amorphous strand of polymer.
EXAMPLE 24
[0339] This example illustrates the expected properties of a copolymer prepared from adipic acid as the dimethyl ester, ethylene glycol, and diketopiperazine unit of glutamic acid (glutamate -DKP/PEA copolymer), as compared to the corresponding conventional polymer, polyethylene adipate (PEA).
[0340] Glutamate-DKP units replace the dicarboxy units in the conventional copolymer PEA. Compared to PEA, glutamate-DKP/PEA copolymer shows a higher glass transition temperature (Tg), a higher melting temperature (Tm), an improved temperature of crystallization on heating (Tch) when heated from the amorphous state, and an improved temperature of crystallization (Tec) when cooled from the melt. Glutamate-DKP/PEA copolymer also shows improved biodegradability. [0341] All references, including publications, patent applications, and patents, cited herein are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein.
[0342] The use of the terms "a" and "an" and "the" and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The terms "comprising," "having," "including," and "containing" are to be construed as open-ended terms (i.e., meaning "including, but not limited to,") unless otherwise noted. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., "such as") provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.
[0343] Preferred embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Variations of those preferred embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventors expect skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.

Claims

CLAIMS:
1. A polymer of formula
-[-R^O-R^O-]- (I) comprising at least two monomer units of R1, which can be the same or different, and at least two monomer units of R2, which can be the same or different, wherein
R1 is of formula
Figure imgf000060_0001
(II) (III) (IV) (V) (VI) wherein R3 is a Ci - C36 straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group, and
R2 is a C2 - Cg straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group, except that
(a) about 0.01 to about 0.8 mole fraction of R1 is replaced by a diketopiperazine unit of formula (VII)
Figure imgf000061_0001
(VII) wherein R4 is -CH2C(0)- or -CH2CH2C(0)- and/or
(b) about 0.01 to about 0.8 mole fraction of R2 is replaced by a diketopiperazine unit of formula (VIII)
Figure imgf000061_0002
(VIII) wherein R5 is -CH2-, -CH2CH2-, or -CH(CH3)-.
2. The polymer of claim 1, wherein R5 is only -CH2-.
3. The polymer of claim 1, wherein R5 is only -CH(CH3)-.
4. The polymer of any one of claims 1-3, wherein the polymer comprises at least two different monomer units of R1.
5. The polymer of claim 4, wherein at least one monomer unit of R1 is of formula
(II).
6. The polymer of claim 4 or 5, wherein at least one monomer unit of R1 is of formula (III).
7. The polymer of any one of claims 4-6, wherein at least one monomer unit of
R is of formula (IV).
8. The polymer of any one of claims 4-7, wherein at least one monomer unit of
R is of formula (V).
9. The polymer of any one of claims 4-8, wherein at least one monomer unit of
R1 is of formula (VI).
10. The polymer of any one of claims 4-9, wherein at least one monomer unit of R1 is of formula (VI), and R3 is -CH2CH2-.
11. The polymer of any one of claims 4-10, wherein at least one monomer unit of R1 is of formula (VI), wherein R3 is -CH2CH2CH2-.
12. The polymer of any one of claims 4-11, wherein at least one monomer unit of R1 is of formula (VI), wherein R3 is -CH2(CH2)2CH2-.
13. The polymer of any one of claims 4-12, wherein at least one monomer unit of R1 is of formula (VI), wherein R3 is of formula (IX)
Figure imgf000062_0001
(IX).
14. The polymer of any one of claims 4-13, wherein at least one monomer unit of R1 is of formula (VI), wherein R3 is -CH2(CH2)i4CH2-.
15. The polymer of any one of claims 4-14, wherein at least one monomer unit of R1 is of formula (VI), wherein R3 is -CH2(CH2)8CH2-.
16. The polymer of any one of claims 1-3, wherein each monomer unit of R is the same.
17. The polymer of claim 16, wherein R1 is of formula (II).
18. The polymer of claim 16, wherein R1 is of formula (III).
19. The polymer of claim 16, wherein R1 is of formula (IV).
20. The polymer of claim 16, wherein R1 is of formula (V).
21. The polymer of claim 16, wherein R1 is of formula (VI).
22. The polymer of claim 16, wherein R1 is of formula (VI), and R3 is -CH2CH2-.
23. The polymer of claim 16, wherein R1 is of formula (VI), and R3 is -CH2CH2CH2-.
24. The polymer of claim 16, wherein R1 is of formula (VI), and R3 is -CH2(CH2)2CH2-.
25. The polymer of claim 16, wherein R1 is of formula (VI), and R3 is of formula (IX)
Figure imgf000063_0001
(IX).
26. The polymer of claim 16, wherein R1 is of formula (VI), and R3 is
Figure imgf000063_0002
27. The polymer of claim 16, wherein R1 is of formula (VI), and R3 is -CH2(CH2)8CH2-.
28. The polymer of any one of claims 1-27, wherein the polymer comprises at least two different monomer units of R2.
29. The polymer of claim 28, wherein at least one monomer unit of R2 is -CH2CH2-.
30. The polymer of claim 28 or 29, wherein at least one monomer unit of R2 is -CH2CH(CH3)-.
31. The polymer of any one of claims 28-30, wherein at least one monomer unit of R2 is -CH2CH2CH2-.
32. The polymer of any one of claims 28-31 , wherein at least one monomer unit of R2 is -CH2(CH2)2CH2-.
33. The polymer of any one of claims 28-32, wherein at least one monomer unit of R2 is -CH2CH(CH3)CH2-.
34. The polymer of any one of claims 28-33, wherein at least one monomer unit of R2 is -CH2C(CH3)2CH2-.
35. The polymer of any one of claims 28-34, wherein at least one monomer unit of R2 is -CH2CH(CH2CH3)-.
36. The polymer of any one of claims 28-35, wherein at least one monomer unit of R2 is -CH2(CH2)3CH2-.
37. The polymer of any one of claims 28-36, wherein at least one monomer unit of R2 is -CH2(CH2)4CH2-.
38. The polymer of any one of claims 28-37, wherein at least one monomer unit of R2 is -CH2(CH2)5CH2-.
39. The polymer of any one of claims 28-38, wherein at least one monomer unit of R2 is -CH2(CH2)6CH2-.
40. The polymer of any one of claims 1-27, wherein each monomer unit of R2 is the same.
41. The polymer of claim 40, wherein R2 is -CH2CH2-
42. The polymer of claim 40, wherein R2 is -CH2CH(CH3)-
43. The polymer of claim 40, wherein R2 is -CH2CH2CH2-.
44. The polymer of claim 40, wherein R2 is -CH2(CH2)2CH2-.
45. The polymer of claim 40, wherein R2 is -CH2CH(CH3)CH2-.
46. The polymer of claim 40, wherein R2 is -CH2C(CH3)2CH2-.
47. The polymer of claim 40, wherein R2 is -CH2CH(CH2CH3)-.
48. The polymer of claim 40, wherein R2 is -CH2(CH2)3CH2-.
49. The polymer of claim 40, wherein R2 is -CH2(CH2)4CH2-.
50. The polymer of claim 40, wherein R2 is -CH2(CH2)5CH2-.
51. The polymer of claim 40, wherein R2 is -CH2(CH2)6CH2-.
52. The polymer of any one of claims 1-51, wherein at least one monomeric unit of R1 is replaced by the diketopiperazme unit of formula (VII), wherein R4 is -CH2C(0)-.
53. The polymer of any one of claims 1-51, wherein at least one monomeric unit of R1 is replaced by the diketopiperazme unit of formula (VII), wherein R4 is
-CH2CH2C(0)-.
54. The polymer of claim 52 or 53, wherein the monomeric unit of R2 is not replaced by a diketopiperazme unit.
55. The polymer of claim 52 or 53, wherein at least one monomeric unit of R2 is replaced by the diketopiperazme unit of formula (VIII), wherein R5 is -CH2-.
56. The polymer of any one of claims 52, 53, and 55, wherein at least one monomeric unit of R2 is replaced by the diketopiperazme unit of formula (VIII), wherein R5 is -CH(CH3)-.
57. The polymer of any one of claims 52, 53, 55, and 56, wherein at least one monomeric unit of R2 is replaced by the diketopiperazme unit of formula (VIII), wherein R5 is -CH2CH2-.
58. The polymer of any one of claims 1-51, wherein at least one monomeric unit of R2 is replaced by the diketopiperazine unit of formula (VIII), wherein R5 is only -CH2-.
59. The polymer of any one of claims 1-51, and 58, wherein at least one monomeric unit of R2 is replaced by the diketopiperazine unit of formula (VIII), wherein R5 is only -CH(CH3)-.
60. The polymer of any one of claims 1-51, 58, and 59, wherein at least one monomeric unit of R2 is replaced by the diketopiperazine unit of formula (VIII), wherein R5 is only -CH2CH2-.
61. The polymer of any one of claims 58-60, wherein the monomeric unit of R1 is not replaced by a diketopiperazine unit.
62. The polymer of any one of claims 1-61, wherein the diketopiperazine units are of form (1, 1).
63. The polymer of any one of claims 1-61, wherein the diketopiperazine units are of form (d, d).
64. The polymer of any one of claims 1-61, wherein the diketopiperazine units are of form (1, d).
65. The polymer of any one of claims 1-61, wherein the diketopiperazine units are of form (d, 1).
66. The polymer of any one of claims 1-61, wherein the diketopiperazine units are of at least two different forms selected from (1, 1), (1, d), (d, 1), and (d, d).
67. The polymer of any one of claims 1-53 and 62-66, wherein about 0.01 to about 0.3 mole fraction of one monomeric unit of R1 is replaced by a diketopiperazine unit of formula (VII).
68. The polymer of claim 67, wherein about 0.01 to about 0.1 mole fraction of one monomeric unit of R1 is replaced by a diketopiperazine unit of formula (VII).
69. The polymer of claim 68, wherein about 0.02 to about 0.07 mole fraction of one monomeric unit of R1 is replaced by a diketopiperazine unit of formula (VII).
70. The polymer of any one of claims 1-53 and 55-69, wherein about 0.01 to about 0.3 mole fraction of R2 is replaced by a diketopiperazine unit of formula (VIII).
71. The polymer of claim 70, wherein about 0.01 to about 0.1 mole fraction of one monomeric unit of R2 is replaced by a diketopiperazine unit of formula (VIII).
72. The polymer of claim 71, wherein about 0.02 to about 0.07 mole fraction of one monomeric unit of R2 is replaced by a diketopiperazine unit of formula (VIII).
73. The polymer of any one of claims 1-72, wherein at least one of the monomeric units of R2 is of the formula
Figure imgf000067_0001
(X) (XI).
74. The polymer of claim 73, wherein at least one of the monomeric units of R2 is of formula (X), and at least one of the monomeric units of R2 is of formula (XI).
75. The polymer of claim 73, wherein at least one of the monomeric units of R2 is of formula (X).
76. The polymer of claim 73, wherein at least one of the monomeric units of R2 is of formula (XI).
77. The polymer of any one of claims 1-76, wherein the polymer has a molecular weight of about 500 g/mol to about 1 million g/mol.
78. The polymer of claim 77, wherein the polymer has a molecular weight of about 20,000 g/mol to about 1 million g/mol.
79. The polymer of claim 78, wherein the polymer has a molecular weight of about 20,000 g/mol to about 100,000 g/mol.
80. The polymer of claim 77, wherein the polymer has a molecular weight of about 500 g/mol to about 100,000 g/mol.
81. The polymer of claim 80, wherein the polymer has a molecular weight of about 500 g/mol to about 20,000 g/mol.
82. The polymer of claim 81 , wherein the polymer has a molecular weight of about 500 g/mol to about 10,000 g/mol.
83. The polymer of claim 82, wherein the polymer has a molecular weight of about 500 g/mol to about 3,000 g/mol.
84. A method of preparing a polymer of any one of claims 1-83 comprising:
(i) combining in a reaction vessel (a) one or more compounds of formula R1(OH)2 or R1(OR6)2, wherein R6 is an alkyl group, (b) one or more aliphatic glycols of formula R2(OH)2, (c) one or more diketopiperazme units of aspartic acid and/or glutamic acid, wherein the mole ratio of the diketopiperazme units of aspartic acid and glutamic acid to the compounds of formula R1(OH)2 or R1(OR6)2 is about 0.01 to about 0.8, and/or one or more diketopiperazme units of serine, homoserine, and/or threonine, wherein the mole ratio of the diketopiperazme units of serine, homoserine, and threonine to the aliphatic glycols R2(OH)2 is about 0.01 to about 0.8, and (d) a catalyst,
(ii) purging the reaction vessel with an inert gas,
(iii) heating the reaction vessel to a first temperature of about 180 to about 270 °C at a pressure of about 0.5 to about 10 atmospheres (about 50 kPa to 1010 kPa),
(iv) raising the temperature of the reaction vessel to a second temperature of about 250 to about 320 °C,
(v) reducing the pressure in the reaction vessel to about 0.0001 and 0.01 atmospheres (about 10 Pa to about 1010 Pa), and (vi) thereby providing the polymer of any one of claims 1-83.
85. The method of claim 84, wherein subpart (c) only includes one or more diketopiperazine units of aspartic acid and/or glutamic acid.
86. The method of claim 84, wherein subpart (c) only includes one or more diketopiperazine units of of serine, homoserine, and/or threonine.
87. The method of claim 86, wherein subpart (c) only includes one or more diketopiperazine units of serine.
88. The method of claim 86, wherein subpart (c) only includes one or more diketopiperazine units of homoserine.
89. The method of claim 86, wherein subpart (c) only includes one or more diketopiperazine units of threonine.
90. The method of any one of claims 84-89, wherein the catalyst is zinc acetate dihydrate and dibutyltin diacetate.
91. The method of any one of claims 84-90, wherein the one or more compounds of formula R1(OH)2 or R1(OR6)2 comprises at least two different monomer units of R1.
92. The method of claim 90, wherein at least one monomer unit of R1 is of formula (II).
93. The method of claim 91 or 92, wherein at least one monomer unit of R1 is of formula (III).
94. The method of any one of claims 91-93, wherein at least one monomer unit of R1 is of formula (IV).
95. The method of any one of claims 91-94, wherein at least one monomer unit of R1 is of formula (V).
96. The method of any one of claims 91-95, wherein at least one monomer unit of R1 is of formula (VI).
97. The method of any one of claims 91-96, wherein at least one monomer unit of R1 is of formula (VI), and R3 is -CH2CH2-.
98. The method of any one of claims 91-97, wherein at least one monomer unit of R1 is of formula (VI), and R3 is -CH2CH2CH2-.
99. The method of any one of claims 91-98, wherein at least one monomer unit of R1 is of formula (VI), and R3 is -CH2(CH2)2CH2-.
100. The method of any one of claims 91-99, wherein at least one monomer unit of R1 is of formula (VI), and R3 is of formula (IX)
Figure imgf000070_0001
(IX).
101. The method of any one of claims 91-100, wherein at least one monomer unit of R1 is of formula (VI), wherein R3 is -CH2(CH2)i4CH2-.
102. The method of any one of claims 91-101, wherein at least one monomer unit of R1 is of formula (VI), wherein R3 is -CH2(CH2)8CH2-.
103. The method of any one of claims 84-89, wherein each monomer unit of R1 is the same.
104. The method of claim 103, wherein R1 is of formula (II).
105. The method of claim 103, wherein R1 is of formula (III).
106. The method of claim 103, wherein R1 is of formula (IV).
107. The method of claim 103, wherein R1 is of formula (V).
108. The method of claim 103, wherein R1 is of formula (VI).
109. The method of claim 103, wherein R1 is of formula (VI), and R3
Figure imgf000071_0001
110. The method of claim 103, wherein R1 is of formula (VI), and R3
CH2(CH2)2CH2-.
111. The method of claim 103, wherein R1 is of formula (VI), and R3
Figure imgf000071_0002
(IX).
112. The method of claim 103, wherein R1 is of formula (VI), and R3 is
Figure imgf000071_0003
113. The method of claim 103, wherein R1 is of formula (VI), and R3 is
-CH2(CH2)8CH2-.
114. The method of any one of claims 84-113, wherein the aliphatic glycols of formula R2(OH)2 comprises at least two different monomer units of R2.
The method of claim 114, wherein at least one monomer unit of R2
-CH2CH2-.
116. The method of claim 114 or 115, wherein at least one monomer unit of R2 is -CH2CH(CH3)-.
117. The method of any one of claims 114-116, wherein at least one monomer unit of R2 is -CH2CH2CH2-.
The method of any one of claims 114-117, wherein at least one monomer unit of R2 is -CH2(CH2)2CH2-
119. The method of any one of claims 114-118, wherein at least one monomer unit of R2 is -CH2CH(CH3)CH2-.
120. The method of any one of claims 114-119, wherein at least one monomer unit of R2 is -CH2C(CH3)2CH2-.
121. The method of any one of claims 114-120, wherein at least one monomer unit of R2 is -CH2CH(CH2CH3)-.
122. The method of any one of claims 114-121 , wherein at least one monomer unit of R2 is -CH2(CH2)3CH2-.
123. The method of any one of claims 114-122, wherein at least one monomer unit of R2 is -CH2(CH2)4CH2-.
124. The method of any one of claims 114-123, wherein at least one monomer unit of R2 is -CH2(CH2)5CH2-.
125. The method of any one of claims 114-124, wherein at least one monomer unit of R2 is -CH2(CH2)6CH2-.
126. The method of any one of claims 84-113, wherein each monomer unit of R2 is the same.
127. The method of claim 126, wherein R2 is -CH2CH2-.
128. The method of claim 126, wherein R2 is -CH2CH(CH3)-.
129. The method of claim 126, wherein R2 is -CH2(CH2)2CH2-.
130. The method of claim 126, wherein R2 is -CH2CH2CH2-.
131. The method of claim 126, wherein R2 is -CH2CH(CH3)CH2-.
132. The method of claim 126, wherein R2 is -CH2C(CH3)2CH2-.
133. The method of claim 126, wherein R2 is -CH2CH(CH2CH3)-.
134. The method of claim 126, wherein R2 is -CH2(CH2)3CH2-.
135. The method of claim 126, wherein R2 is -CH2(CH2)4CH2-.
136. The method of claim 126, wherein R2 is -CH2(CH2)5CH2-.
137. The method of claim 126, wherein R2 is -CH2(CH2)6CH2-.
138. The method of any one of claims 84-137, wherein the reaction vessel contains at least one diketopiperazine unit of aspartic acid.
139. The method of any one of claims 84-138, wherein the reaction vessel contains at least one diketopiperazine unit of glutamic acid.
140. The method of claim 138 or 139, wherein the reaction vessel does not contain any diketopiperazine unit of serine, homoserine, or threonine.
141. The method of claim 138 or 139, wherein the reaction vessel contains at least one diketopiperazine unit of serine.
142. The method of any one of claims 138, 139, and 141, wherein the reaction vessel contains at least one diketopiperazine unit of threonine.
143. The method of any one of claims 138, 139, 141, and 142, wherein the reaction vessel contains at least one diketopiperazine unit of homoserine.
144. The method of any one of claims 84-137, wherein the reaction vessel contains at least one diketopiperazine unit of serine.
145. The method of any one of claims 84-137 and 144, wherein the reaction vessel contains at least one diketopiperazine unit of threonine.
146. The method of any one of claims 84-137, 144, and 145, wherein the reaction vessel contains at least one diketopiperazine unit of homoserine.
147. The method of any one of claims 144-146, wherein the reaction vessel does not contain a diketopiperazine unit of either aspartic acid or glutamic acid.
148. The method of any one of claims 138-146, wherein the diketopiperazine units are of form (1, 1).
149. The method of any one of claims 138-146, wherein the diketopiperazine units are of form (d, d).
150. The methodof any one of claims 138-147, wherein the diketopiperazine units are of form (1, d).
151. The method of any one of claims 138-147, wherein the diketopiperazine units are of form (d, 1).
152. The method of any one of claims 138-147, wherein the diketopiperazine units are of at least two different forms selected from (1, 1), (1, d), (d, 1), and (d, d).
153. The method of any one of claims 84 and 90-152, wherein the mole ratio of the diketopiperazine unit of aspartic acid and glutamic acid to the compounds of formula R1(OH)2 or R1(OR6)2 is about 0.01 to about 0.3 and/or the mole ratio of the diketopiperazine units of serine, homoserine, and threonine to the aliphatic glycols of formula R2(OH)2 is about 0.01 to about 0.3.
154. The method of any one of claims 84-152, wherein the mole ratio of the diketopiperazine unit of aspartic acid and glutamic acid to the compounds of formula R1(OH)2 or R1(OR6)2 is about 0.01 to about 0.3 and/or the mole ratio of the diketopiperazine units of serine and threonine to the aliphatic glycols of formula R2(OH)2 is about 0.01 to about 0.3.
155. The method of claim 153, wherein the mole ratio of the diketopiperazine unit of aspartic acid and glutamic acid to the compounds of formula R1(OH)2 or R1(OR6)2 is about 0.01 to about 0.1 and/or the mole ratio of the diketopiperazine units of serine, homoserine, and threonine to the aliphatic glycols of formula R2(OH)2 is about 0.01 to about 0.1.
156. The method of claim 154, wherein the mole ratio of the diketopiperazine unit of aspartic acid and glutamic acid to the compounds of formula R1(OH)2 or R1(OR6)2 is about 0.01 to about 0.1 and/or the mole ratio of the diketopiperazine units of serine and threonine to the aliphatic glycols of formula R2(OH)2 is about 0.01 to about 0.1.
157. The method of claim 155, wherein the mole ratio of the diketopiperazine unit of aspartic acid and glutamic acid to the compounds of formula R1(OH)2 or R1(OR6)2 is about 0.02 to about 0.07 and/or the mole ratio of the diketopiperazine units of serine, homoserine, and threonine to the aliphatic glycols of formula R2(OH)2 is about 0.02 to about 0.07.
158. The method of claim 156, wherein the mole ratio of the diketopiperazine unit of aspartic acid and glutamic acid to the compounds of formula R1(OH)2 or R1(OR6)2 is about 0.02 to about 0.07 and/or the mole ratio of the diketopiperazine units of serine and threonine to the aliphatic glycols of formula R2(OH)2 is about 0.02 to about 0.07.
159. The method of any one of claims 84-157, further comprising adding at least one of the compounds of formulas (XII) and (XIII)
Figure imgf000075_0001
(XII) (XIII) to the reaction vessel prior to heating the reaction vessel.
160. A method of improving the biodegradability and thermal properties of a polymer of formula
-[-R^O-R^O-]- (I) comprising at least two monomer units of R1 and at least two monomer units of R2, wherein
R1 is of formula
Figure imgf000076_0001
(II) (in) (IV) (V) (VI) wherein R is a Ci - C 19 straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group, and
R2 is a C2 - Cg straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group, by
(a) replacing about 0.01 to about 0.8 mole fraction of R1 by a diketopiperazine unit formula (VII)
Figure imgf000076_0002
(VII) wherein R is -CH2C(0)- or -CH2CH2C(0)-, and/or
(b) replacing about 0.01 to about 0.8 mole fraction of R by a diketopiperazine unit of formula (VIII)
Figure imgf000077_0001
(VIII) wherein R5 is -CH2-, -CH2CH2-, or -CH(CH3)-.
161. A method of claim 160, wherein R5 is -CH2- or -CH(CH3)-.
162. A polymer of formula -[-R^O-R^O-]- (I) comprising at least two monomer units of R1, which can be the same or different, and at least two monomer units of R2, which can be the same or different, wherein
R1 is an aliphatic or aromatic dicarboxylate unit, wherein the aliphatic dicarboxylate unit comprises a C3 - C36 straight, branched, non- aromatic cyclic, saturated, substituted, or unsaturated aliphatic group, and the aromatic dicarboxylate unit comprises a C5 - C2o aryl, heteroaryl, substituted, or unsubstituted aromatic dicarboxylate group,
R2 is a C2 - Cg straight, branched, non-aromatic cyclic, saturated, substituted, or unsaturated aliphatic group, except that
(a) about 0.01 to about 0.8 mole fraction of R1 is replaced by a diketopiperazine unit of formula (VII)
Figure imgf000078_0001
(VII)
wherein R4 is -CH2C(0)- or -CH2CH2C(0)-, and/or
(b) about 0.01 to about 0.8 mole fraction of R2 is replaced by a diketopiperazine unit of formula (VIII)
Figure imgf000078_0002
(VIII)
wherein R5 is -CH2-, -CH2CH2-, or -CH(CH3)-.
163. A polymer of claim 162, wherein R5 is only -CH2-.
164. A polymer of claim 162, wherein R5 only is -CH(CH3)-
165. A polymer of claim 162, wherein R5 only is -CH2CH2-.
PCT/US2014/028816 2013-03-15 2014-03-14 Diketopiperazine containing copolymers and preparation methods WO2014144414A1 (en)

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