DE102009019852A1 - New polymer compound comprising amine structural elements, useful as synthetic resins, coatings, foams, liquid crystals, adhesives, paints, varnishes, composite materials, in cosmetics, and in polymer electronics - Google Patents

Abstract

Polymeric compound comprising at least ten amine structural elements in the backbone of the polymer, is new. Polymeric compound (A) comprising at least 10 amine structural elements of formula (-CO-NH-O-), (-CO-O-NH-) or (-O-CO-NH-O-) in the backbone of the polymer, is new. An independent claim is included for preparing (A).

Description

The This patent application relates to polymers having a plurality of structural elements -CO-NH-O-, -CO-O-NH- or -O-CO-NH-O- in the Polymer chain and process for its preparation.

Background and state of the technology

synthetic Polymers (plastics) determine our everyday life - areas of application are very diverse and often difficult to distinguish from each other.

The main customers for plastics (without chemical fibers) are z. B .: DIY store, Electrical engineering, electronics, vehicle construction, equipment construction, chemical Industry, consumer industry, agriculture. Our standard of living would be without the synthetic products, the organic chemical industry not nearly as high as it is today.

plastics consist of synthetic polymers. Polymers are synthetic Macromolecules consisting of many similar structural units, are constructed of the monomers. The invention Polymers are made of new structural units with new structural elements built up.

Synthetic polymers on Carbon-nitrogen base

monomers nitrogen-containing (N-containing) known polymers contain an amide - (- C-NH-CO-) or urethane - (- C-NH-CO-O-) unit as a structural element.

Definition of terms:

One Polymer is the n-mer of a monomer where n> 1 and covalently link the monomers together are (chain or branched molecules). A monomer is a molecule containing one or more polymerizable Owns groups. The number of polymerizable groups is determined by the functionality of the monomer.

you distinguishes bifunctional monomers, trifunctional monomers, tetrafunctional monomers.

polymers can be classified according to the number of basic monomers: Homopolymers, copolymers. In addition, one distinguishes organic and inorganic polymers. The organic polymers can be further differentiate into: biopolymers, chemically modified polymers and synthetic polymers.

In solid polymers, there are also "alloys" (polymer blends), the z. From the chains (A-A-A) n and (B-B-B) n. All aspects (degree of polymerization, co-polymers, polymer blends etc.) As a result, polymers have an extreme variety. In addition, between the polymer chains often Form bridges.

polymers are still divided according to their steric structure. Lie the side groups attached to the carbon chain (main chain) all on one side of the main chain, that is the polymer isotactic, they lie alternately on one side, then the polymer is called syndiotactic, they are on both sides Main chain statistically over the whole molecule distributed, then speaks of an atactic polymer. The tacticity of a polymer has significant impact on the chemical and physical Properties of the polymeric material.

is a polymer composed of uniform monomer units, then speaks one from a homopolymer, while one from different Monomeric polymers called co-polymers. The co-polymers will continue in block polymers, statistical and alternating Subdivided co-polymers. The thread-like or branched Macromolecules can chemically crosslink with each other become. Crosslinking may be by major valence or minor valence bonds (eg hydrogen bond). By networking a polymeric substance u. a. its mechanical and thermal Properties essentially determined.

polymer Chemistry

The chain formation of individual monomers is done by polyreactions, eg. As polymerization, poly condensation or polyaddition. Most plastics are polymers in which the carbon provides for molecular chain formation.

Synthetic polymers based on carbon-nitrogen

classifications: Polymers can be classified in several ways: according to origin and structure.

Construction:

• a) Nach Anzahl und Anordnung der Monomerbausteine unterscheidet man Homopolymere, Terpolymere, Copolymere. Die Copolymere unterscheidet man, gemäß der Anordnung der Strukturelemente, in: statistische, alternierende, blockförmige oder gepfropfte Polymere.
• b) Nach der Polymerstruktur unterscheidet man: lineare Polymere, verzweigte Polymere, vernetzte Polymere, sternförmige Polymere.

A distinction is made between thermoplastics (plastics made of long-chain, unbranched molecules that can be easily and reversibly deformed in the event of temperature changes) and thermosets (plastics made from cross-linked macromolecules that are extremely hard, they can not be remelted without decomposition).

• a) According to the number and arrangement of the monomer building blocks one distinguishes homopolymers, terpolymers, copolymers. The copolymers are distinguished, according to the arrangement of the structural elements, into: random, alternating, block-shaped or grafted polymers.
• b) According to the polymer structure, a distinction is made between: linear polymers, branched polymers, crosslinked polymers, star-shaped polymers.

polycondensates arise after a step growth mechanism, by reaction between at least two different functional groups.

Types of plastics

• – Herstellung: Additionspolymere entstehen durch wiederholte Addition einer Monomereinheit an die nächste – eine so genannte Kettenwachstumsreaktion.
• – Thermischen bzw. mechanischen Eigenschaften.

Plastics are differentiated

• - Preparation: Addition polymers are formed by repeated addition of one monomer unit to the next - a so-called chain-growth reaction.
• - Thermal or mechanical properties.

Distinguish after production

• 1. Polymers: z. Polyethylene, Polypropylene, polyvinyl chloride, etc.
• 2. polycondensates: z. As polyester (PET), polyamides, formaldehyde resins, Polycarbonates, polyethers.
• 3. polyadducts: z. B. Epoxides, polyurethane, epoxy resins, Perlon, polyether.

Classification according to other criteria:

• Thermoplastics (PE, PP, PMMA, polyacrylic).
• Thermosets (polycondensates such as bakelite, urea resins).
• Elastomers (rubber, Booner).
• Rubber-elastic plastics.
• silicones
• Polymer Blends

composites play an important role in technology. It is understood as Materials that are completely different from plastics and their combination is the highest have mechanical or thermal properties.

Properties and Technical Values

Mechanical properties

Electrical Properties

Thermal properties

Most synthetic polymers are thermoplastic and can be at temperatures above 60 ° C to form objects. Some polymers with fiber structure, e.g. B. Perlon must first be stretched before spinning so that the fiber is solidified by crystallite formation. Brittle or hard polymers become plastic by the addition of plasticizers and thus malleable.

foams is obtained by adding propellant-forming auxiliary substances the polymerization, polyaddition or polymer processing.

Amide bond and chain conformation

The Amide bond is a resonant structure. In this structure occur because of the electron displacement of nitrogen to oxygen a positive charge of nitrogen and a negative one Charge on oxygen. The C-O bond loses its pure Double bond character, while the C-N bond partial Double bond character wins. The result of the training of Resonance structure is the arrangement of all 6 atoms in one plane.

Tordierungen around the C-N single bonds require energy. The arrangement of C atoms in the plane are trans to each other. Due to the hydroxamate structure one obtains, compared to the amide (or urethane) structure another mesomeric resonance structure with amide and ether character.

In the hydroxamate structure, the partial double bond character of the CN bond is significantly altered compared to the amide structure. The enolic character is thus also changed.

6-atoms = planar but more rigid. This has an influence on the physical properties of the polymer.

Delocalized π electrons.

The cis arrangement is less favorable for steric reasons.

The stabilization of the structural elements by hydrogen bonding (secondary structure)

A Polyamide chain has due to the resonance structure of the planar amide bonds Degrees of freedom of rotation only at the two single bonds N-C and C-C. The threadlike molecular strands can be intra-molecular by training a maximum Number of hydrogen bonds to be stabilized. in this connection form each carbonyl oxygen atom with the N-H atom one after the other or more distant amide bond hydrogen bond out. Particularly stable is the alpha helix, since the hydrogen bonds can be produced almost stress-free. Hydrogen bonds can be in the single strand itself (intra) as well as between form the single strands (inter).

Parallel or antiparallel amide chains can be hydrogen-bonded be stabilized between the chains. By special procedural Measures can macromolecules in a desired spatial arrangement be brought. So can filamentous molecules obtained by "stretching" become.

Also can the stability z. B. by special Manufacturing process affect ("stretching" of the thread-like molecules)

Theoretical basics

Between the individual macromolecules that make up a plastic There are physical interactions that have typical properties such as mechanical, electrical and thermal properties, such as strength, Determine hardness or softening behavior. Depending on Order of the macromolecules in the solid state can be between semi-crystalline, liquid-crystalline and amorphous Differentiate plastics.

thermoplastics

Divide thermosets (also duromers)

elastomers

she consist of - mostly relatively weak - networked Macromolecules. This allows the elastomers the typical rubber-elastic behavior, at low at Strain strains up to 600% can be achieved.

plastics, Plastics or polymer materials consist of macromolecules; their characteristics are due to the unusual size or length of the chain-shaped molecules, and by functional groups (ester, amide, urethane).

designations

After their technical use, the plastics are divided into:

Thermoplastics go above the glass transition temperature from the hard to a plastically deformable state. The macromolecules are not or only slightly cross-linked.

Elastomers consist of widely meshed molecules. Above the glass transition temperature (about -50 ° C), these polymers are rubber-elastic and only limited deformable.

Thermoders show an extraordinary number of crosslinks between the molecules. Above a certain temperature, they can no longer be plastically deformed.

• – Lechner, Gehrke, Nordmeier: Makromolekulare Chemie, Verlag Birkhäuser, ISBN 3764329734
• – Calhoun, Peacock: Polymer Chemistry, Hanser Fachbuchverlag, ISBN 3446222839

Further basic information on the preparation, structure, properties and uses of polymers is contained in:

• - Lechner, Gehrke, Nordmeier: Macromolecular Chemistry, Verlag Birkhäuser, ISBN 3764329734
• - Calhoun, Peacock: Polymer Chemistry, Hanser Fachbuchverlag, ISBN 3446222839

On the contents of these standard works and the literature cited therein is hereby additionally referenced.

Polymers with hydroxamate functions

Out A number of polymers are already known in the art. which have hydroxamate functions. These are in particular to polymers with hydroxamate functions in the side chains. For this are usually provided with functional groups Polymers retrospectively with hydroxamic acid groups Mistake. These polymers have hydroxamate functions in the side chains Take advantage of the properties that hydroxamic acid has in a number of complexing metals. Those described in the prior art Polymers are particularly suitable as ion exchangers. In the however, the hydroxamate functions are described as Side chains designed.

Other Documents describe the solid phase reaction for the preparation of Hydroxamic acid derivatives.

• DE 4016543 A1
• EP 0347424 B1
• EP 0811019 B1 ( DE 69602016 T2 )
• EP 0891380 B1 ( DE 69703346 T2 )
• EP 0514648 B1 ( DE 69211224 T2 )

This prior art is particularly constituted by the following documents (and the literature cited therein):

• DE 4016543 A1
• EP 0347424 B1
• EP 0811019 B1 ( DE 69602016 T2 )
• EP 0891380 B1 ( DE 69703346 T2 )
• EP 0514648 B1 ( DE 69211224 T2 )

Description of the invention

It has now been found that - surprisingly - polymers with the new structural elements -CO-NH-O- or -O-CO-NH-O- in the polymer chain (ie in the backbone or backbone) outstanding properties which they identify as new materials.

It these are polymers where the linkage between individual monomers (repeating units) by said structural elements (derived from hydroxamic acid) is formed. The polymers of the invention contain at least 10 (preferably at least 50, more preferably at least 100) groups of the formula -CO-NH-O-, -CO-O-NH- or -O-CO-NH-O- as a coupling member between different monomers, that is in the backbone of the polymer.

The Connections differ from the state of the above Technique in that the groups -CO-NH-O-, -CO-O-NH- or -O-CO-NH-O- form the backbone of the polymer and not terminal are present in side chains.

The polymeric compounds according to the invention are in particular characterized by the general formula Ib, Ic, Id or Ie, - [OR ¹ -O-NH-CO-] _n - (Ia) - [R ¹ -O-NH-CO-] _n - (Ib) - [NH-R ¹ -O-NH-CO-NH-R ² -NH-CO-] _n - (Ic) - [OR ¹ -O-NH-CO-NH-R ² -NH-CO-] _n - (Id) - [NH-OR ¹ -O-NH-CO-NH-R ² -NH-CO-] _n - (Ie) wherein
R ^{1 represents} an organic radical which may contain alkyl, aryl or heteroaryl moieties which may contain one or more heteroatoms which may contain one or more double or triple bonds which may be fully or partially fluorinated and which may be one or more with halogen, pseudohalogen, with C ₁ -C ₄ alkyl or C ₁ -C ₄ alkoxy may be substituted
R ^{2 is} an organic radical which may contain alkyl, aryl or heteroaryl moieties which may contain one or more heteroatoms which may contain one or more double or triple bonds which may be wholly or partially fluorinated and which may be one or more with halogen, pseudohalogen, with C ₁ -C ₄ -alkyl or C ₁ -C ₄ -alkoxy may be substituted,
n is a number greater than or equal to 10.

Of course, the groups R ¹ and R ² may be the same or different.

The inventive polymeric compounds can also other functional groups for coupling different monomers such as urethane (-OCO-NH-) or urea groups (-NH-CO-NH-). By variation of these different functional coupling groups can properties of the invention Polymers are targeted.

This For example, it can be done in such a way that units which already carry urethane or urea groups, by means of the invention Methods are coupled with each other by Hydroxamatgruppen (Block polymerization) or mixtures of different monomers polymerized with each other.

The central construction sites of the monomers (R ¹ and R ^{2 of} the general formulas Ia, Ib, Ic, Id or Ic) may be alkyl groups, in particular C ₁ -C ₂₀ alkyl groups. These may be branched or unbranched and contain one or more double or triple bonds. Such alkyl groups may also be partially or fully fluorinated. Furthermore, the alkyl groups may also contain one or more oxygen atoms (in the sense of ether groups), these oxygen atoms may not be terminal. With the exception of the NO bond contained in the hydroxamate group, further NO or OO bonds should be avoided. Likewise, it is excluded that the hydroxamate connects directly to a carbonyl group.

The groups R ¹ and R ² may also denote C ₁ -C ₂₀ alkyl groups, which may be branched or unbranched and which contain one or more double or triple bonds and which further comprises one or more C ₆ -C ₁₄ aryl groups and / or one or more contain several C ₆ -C ₁₄ heteroaryl groups, wherein the Aryl or heteroaryl groups may be mono- or polysubstituted with C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxy, fluorine, chlorine, bromine, iodine or cyano.

Such aryl or heteroaryl groups may interrupt both the C ₁ -C ₂₀ alkyl group and be present in a side chain (in the case of a branched C ₁ -C ₂₀ aryl group).

The group R ¹ or R ² may also be a C ₆ -C ₁₄ aryl group which may be mono- or polysubstituted with C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxy, fluorine, chlorine, bromine, iodine or cyano ,

The groups R ¹ and / or R ² may also have the meaning of a C ₆ -C ₁₄ heteroaryl group which may contain one or more heteroatoms (N, O, S) and which may be mono- or polysubstituted with C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxy, fluorine, chlorine, bromine, iodine or cyano.

the It is clear to a person skilled in the art that the sulfur-containing polymer is also cross-linked can be (in the sense of vulcanization). this applies using modified cysteine monomers (see below) but also when using isothiocyanate-containing monomers.

A particularly preferred embodiment of the invention are polymers of the composition: - [O-NH-CHR ^A -CO-] _n wherein R ^{A is} the radical of an α-amino acid (for example -CH ₃ (Ala), -CH ₂ -CO-NH ₂ (Asn), -CH ₂ -SH (Cys), -CH ₂ -CH (CH ₃ ) ₂ (Leu)). These are inventively modified polyamino acids in which instead of the amide bond (-CO-NH-), a bond of the formula -CO-O-NH- is present (see below).

A particularly preferred embodiment of the invention are polymers of the composition: - [CO-O-NH-CH ₂ -] _n

It this is a modified according to the invention Polyglycine (polyaminoxyacetate).

In the modified polyamino acids according to the invention also a sequential structure is possible, for. B. by a correspondingly modified Merrifield synthesis. In this way, it is possible to produce polymers which, analogously to biopolymers (such as proteins), are not composed of the same monomers but combine the widest variety of monomers to form a total molecule. This is shown schematically below: -O-NH-CHR ^A1 -CO-O-NH-CHR ^A2 -CO-O-NH-CHR ^A3 -CO -...- O-NH-CHR ^to -CO-

In The framework of such a polymer is also the combination with classical Amino acids possible.

Process for the preparation the compounds of the invention

The Compounds according to the invention can be prepared by the methods described below.

The starting point of the process according to the invention is a compound of general formula III (HO-) _p R ¹ (-ONH ₂ ) _q (III) in which R ¹ has the meaning given in claim 1 and in which p is the integer zero, one, two or three, and q is the integer one, two, three, or four, and where the sum of p and q is two, three, or four. This compound can be reacted with a compound of general formula IV R ² (-C = N = O) _r (IV) wherein R ^{2 is} as defined in claim 1 and wherein r is the integer two, three or four , The reaction leads to the polymeric substance according to the invention. The invention therefore also relates to the method described above. In a simple form of the process, a compound of general formula III in which the sum of p and q is two is reacted with a compound of general formula IV in which r is two. Then a linear polymeric substance is obtained, which is coupled via hydroxamate functions. In other embodiments, the number of respective substituents (p + q) and r, respectively, may be increased. In this case, branched polymers with hydroxamate functions in the backbone result in which the mechanical stability is increased. Further process variants according to the invention can be found in the examples. It is clear to the person skilled in the art that this is only a selection of possibilities. The person skilled in the art knows of other possible variations that he can apply without having to be inventive.

Use of the invention polymers

The Polymers of the invention can be used in almost all areas are used on which known plastics be used. They can be used, for example, as synthetic resins, Casting compounds, foams, liquid crystals, adhesives, Paints, varnishes (also dispersion varnishes), composites, in the Cosmetics are used in polymer electronics, etc.

For this can in principle all mentioned in the beginning Plant of Peacock (Polymer Chemistry) Find use.

Examples

For the preparation of the monomer units (diaminooxy compounds), several known methods can be used. The following three methods have been found to be very suitable in addition to some other methods ( Etsuko Miyazawa et al., OPPI Briefs, 29, 5, 1997 ).

1. With aminating reagent

in this connection For example, an alcohol is preferably a phenol with an aminating reagent converted to the desired oxyamine. As suitable aminating reagents have 2,4-dinitrofluorobenzene or O-Mesitylensulfonylhydroxylamin exposed. An exemplary implementation is shown below.

2. Protected by Hydroxyphtalimid- or Boc hydroxylamine

in this connection is an activated aliphatic or aromatic compound, preferably an alkyl halide, alkyl tosylate or alkyl mesylate, with N-hydroxyphthalimide or a Boc protected hydroxylamine reacted. The Phthalimide derivatives are finally under Gabriel's conditions with hydrazine or the Boc-protected derivatives with TFA deprotected to the corresponding oxyamines. An exemplary Implementation is shown below.

3. With acetohydroxamic acid ethyl ester (Zinner's method) or acetoxime

in this connection is an activated aliphatic or aromatic compound, preferably an alkyl halide, alkyl tosylate or alkyl mesylate with acetohydroxamic acid ethyl ester or acetoxime converted to the corresponding hydroxamates, the then acid-catalytically cleaved. An exemplary Implementation is shown below.

1. Synthesis Scheme of the Monomer Building Blocks:

2. General Synthesis Options for the preparation of polyhydroxamic esters

2.1. As described in our examples:

A general overview of exemplary possibilities is the 1 refer to.

2.1. Other possible implementations from oxyamines to polymers:

Reaction of diaminooxy compounds to polyhydroxylamines:

Reaction with thiophosgene, or mixtures of several components:

Reaction with polyoxyimides:

Reactions with aminooxy alcohols:

• shown in 2

Reactions with tri-, tetra- or oligoaminooxy compounds to branched polymers:

• shown in 3 and 4

3. Experimental part

3.1. Synthesis of bis-N-hexyloxyphtalimide (CC-1859.6)

Reaction:

Approach CC-1859.6-1:

1,6-dibromohexane (EH-1377.2-1, 15 g, 61.5 mmol) and N-hydroxyphthalimide (EH-1078.2-1, 20.1 g, 123.2 mmol) under argon atmosphere at RT in 250 ml of dry DMF and triethylamine (EH-18.3-13, 35 ml, 24.6 mmol). Then heated one at 80 ° C and stirred overnight.

3.2. Synthesis of bis-N-hexyloxyphtalimide (CC-1859.7)

Reaction:

Approach CC-1859.7-1:

1,6-dibromohexane (EH-1377.2-1, 10 g, 41 mmol) and N-hydroxyphthalimide (EH-1078.2-1, 13.4 g, 82 mmol) are added under argon atmosphere RT was dissolved in 150 ml of dry DMF and incubated with DBU (EH-399.2-5, 12.26 ml, 82 mmol). Then you heat up 50 ° C and stirred for 72 h at this temperature. Subsequently is poured onto 450 ml of water, 3 × with 500 ml of ethyl acetate extracted and the combined organic phases with 2 × 500 ml each NaCl solution, dried over sodium sulfate and concentrated in vacuo. After drying in the HV you get CC-1859.7-1 as a light solid (8.88 g, 53%) without further Cleaning is used directly in the next stage.

3.3. Synthesis of 1,6-diaminooxyhexane (CC-1859.8)

Reaction:

Approach CC-1859.8-2:

• Ref.: Yu Lin Jiang et al., J. Am. Chem. Soc., 2005, 127, 17412–17420 .
• Jae Nyoung Kim et al., Synth. Comm., 1992, 22(10), 1427–1432 .

Dissolve CC-1859.7 (7.88 g, 19.3 mmol) in 240 mL of dry dichloromethane, cool to -20 ° C and slowly add dropwise 3.1 mL of methylhydrazine (EH-1160.2-1). After complete addition, allowed within Come to 0 ° C for 1.5 h, producing a white precipitate. The reaction mixture is filtered, concentrated in vacuo, taken up in 240 ml of ethyl acetate and washed with 120 ml of sat. NaCl solution washed. The aqueous phase is back-extracted with 120 ml of ethyl acetate, the combined organic phases dried over sodium sulfate and concentrated in vacuo. The residue is purified over flash silica gel (EE). Drying in HV gives CC-1859.8-2 as a colorless oil (1.19 g, 42%).

• Ref .: Yu Lin Jiang et al., J. Am. Chem. Soc., 2005, 127, 17412-17420 ,
• Jae Nyoung Kim et al., Synth. Comm., 1992, 22 (10), 1427-1432 ,

3.4. Synthesis of bis-N-ethyloxyphtalimide (CC-1859.29)

Reaction:

Approach CC-1859.29-2:

1,6-dibromoethane (25 ml, 0.29 mol) and N-hydroxyphthalimide (94.4 g, 0.58 mol) under an argon atmosphere at RT in 500 ml of dry DMF dissolved and treated with DBU (86.5 ml, 0.58 mol). Subsequently heated to 50 ° C and stirred for 24 h in this Temperature. Then it is poured onto 2.5 L of water, extracted with 2.7 L of ethyl acetate and the combined organic phases 2 × washed with 2 L of water, over sodium sulfate dried and concentrated in vacuo. After drying in the HV receives CC-1859.29-2 as a light solid (79 g, 78%).

3.5. Synthesis of 1,6-diaminooxyethane (CC-1859.30)

Reaction:

Approach CC-1859.30-2:

CC-1859.29 (30 g, 85.2 mmol) is dissolved in 240 ml of dry dichloromethane, cooled to -10 ° C and 13.7 ml of methylhydrazine slowly dropped. After complete addition leaves to come within 1.5 h at 0 ° C, with a white Precipitation occurs. The reaction mixture is filtered, in Vacuum concentrated, the residue in a little dichloromethane taken again filtered and concentrated in vacuo. desiccation HV gives CC-1859.30-2 as a colorless oil (g,%).

3.6. Synthesis of 3,5-bis [[(1-ethoxyethylidene) amino] oxy] benzonitrile (CC-1859.10)

Reaction:

Approach CC-1859.10-2:

Ethyl acetohydroxamate (EH-1088.5-5, 10.7 g, 103.76 mmol) is dissolved in 100 ml of absolute DMF (EH-83.3-8) and incubated at 0 ° CK ^t OBu (EH-671.2-4, 12.23 g , 108.95 mmol). After 30 min. Stirring at RT is added to 3,5-difluorobenzonitrile (EH-1366.4-1, 7.22 g, 51.88 mmol) and then stirred at 80 ° C. for 68 h. While cooling with ice, 850 ml of water are added, and the mixture is extracted 3 × with 600 ml of ethyl acetate each time, with 600 ml of sat. NaCl, dried over sodium sulfate and concentrated in vacuo. Chromatography on flash silica gel (tol / PE 1: 2) and drying in HV gives CC-1859.10-2 (5.6 g, 35%).

3.7. Synthesis of 3,5-diaminooxybenzonitrile (CC-1859.11)

Reaction:

Approach CC-1859.11-2:

Ethyl-2,5-dibromophenoxyacetohydroxamat (CC-1172.10-2, 5.56 g, 18.2 mmol) is dissolved in dioxane (EH-200.4-1, 40 ml) and cooled to 0 ° C. with an ice bath. With the help of a syringe is a 60% perchloric acid (EH-389.13-1, 28 ml) was added slowly. The ice bath is removed and after stirring at RT for 1 h, the reaction mixture is added to 400 ml of ice water and neutralized with a 10% sodium hydroxide solution (about 100 ml). The aqueous phase is 2 × with 400 ml of ethyl acetate extracted, with 400 ml of sat. NaCl solution washed, dried over magnesium sulfate and in vacuo concentrated. CC-1859.11-2 (3 g, quant) is obtained.

3.8. Synthesis of 2,2-bis- (4-aminooxyphenyl) -propane (CC-1859.26)

Reaction:

Approach CC-1859.26-2:

Bisphenol A (5.49 g, 24 mmol) is dissolved in 110 ml of dry DMF under an argon atmosphere, cooled to 0 ° C and treated with 0.87 g of NaH. The mixture is subsequently stirred at RT for 30 min. O- (2,4-dinitrophenyl) hydroxylamine (CC-1377.17, 4.79 g, 24 mmol) is dissolved in 70 ml of dry DMF, treated with molecular sieve and slowly added dropwise with the aid of a syringe within 2 h at RT to the reaction solution. After stirring for a further 2 h, 1.9 ml of TFA are added, and the mixture is added to 970 ml of sat. NaHCO ₃ solution and extracted 4 × with 970 ml of diethyl ether. The combined organic phases are washed 4 times with 970 ml of a 0.5 M NaOH solution. and dried over sodium sulfate. The reaction mixture is concentrated in vacuo. The residue is taken up again in 100 ml of diethyl ether and washed 4 times with 100 ml of 0.5 M NaOH solution. washed, evaporated and chromatographed on flash silica gel (EE / PE 1: 1 + 1% NEt ₃ ). After drying in the HV, CC-1859.26-2 (220 mg, 3.5%) is obtained as a brown solid.

3.9. Synthesis of polyhydroxamic acid ester / polypeptide analogs

Gen. Reaction for polymer reactions with diacid chlorides:

General procedure:

Diaminooxyverbindung / diamino (1 eq, 0.5 g) in dry dichloromethane (3 ml) under a Argon atmosphere dissolved, added with pyridine (3 eq), cooled to 0 ° C and slowly a solution from diacid chloride (1 eq, dissolved in 3 ml of dry Dichloromethane) is added dropwise. After complete addition, the ice bath removed and stirred at RT for 72 h. The solid polymer became filtered off, washed with dichloromethane and water and then dried in HV.

The DMSO soluble polymers were dissolved in DMSO, reprecipitated with four times the amount of water, filtered off and then dried in the HV.

at Reactions with 3,5-diaminooxybenzonitrile were used instead of dichloromethane used five times the amount of THF as a solvent.

Gen. Reaction for polymer reactions with 4-methyl-m-phenylene diisocyanate:

General procedure:

Diaminooxyverbindung / diamino (1 eq, 0.5 g) in dry dichloromethane (5 ml) under a Argon atmosphere dissolved, cooled to 0 ° C. and slowly added dropwise 4-methyl-m-phenylene diisocyanate (1 eq). To complete addition, the ice bath is removed and 72 h stirred at RT. The solid polymer was filtered off, with Washed dichloromethane and then dried in HV.

at Reactions with 3,5-diaminooxybenzonitrile were used instead of dichloromethane used five times the amount of THF as a solvent.

Gen. Reaction for polymer reactions with 4-methyl-m-phenylene diisothiocyanate:

General procedure:

Diaminooxyverbindung / diamino (1 eq, 0.25 g) in dry dichloromethane (5 ml) under a Argon atmosphere dissolved, cooled to 0 ° C. and slowly add 4-methyl-m-phenylenediisothiocyanate (1 eq, in 2 ml DCM dissolved) added dropwise. After complete addition The ice bath is removed and stirred at RT for 72 h. The solid Polymer was filtered off, washed with dichloromethane and then dried in HV.

Gen. Reaction for polymer reactions with phosgene:

General procedure:

Diaminooxyverbindung / diamino (1 eq, 0.5 g) in dry dichloromethane (5 ml) under a Argon atmosphere dissolved, cooled to 0 ° C. and slowly a phosgene solution (1 eq, 20% in toluene) dropwise. After complete addition, the ice bath is removed and stirred at RT for 72 h. The solid polymer was filtered off, washed with water and dichloromethane and then dried in HV.

at Reactions with 3,5-diaminooxybenzonitrile were used instead of dichloromethane used five times the amount of THF as a solvent.

Further methods for preparing the monomers - in particular for introducing the CNO bond are described by way of example in:
WO 2007/134578 . WO 2008/000252 . WO 2008/135041 . WO 2008/154905 . WO 2009/018807 . WO 2009/018811 . WO 2009/030224 . WO 2009/036753

the Those skilled in the art are further preparative methods for the preparation of the mono- and polymers known which he to their Production can be used without being inventive to have to.

QUOTES INCLUDE IN THE DESCRIPTION

This list The documents listed by the applicant have been automated generated and is solely for better information recorded by the reader. The list is not part of the German Patent or utility model application. The DPMA takes over no liability for any errors or omissions.

Cited patent literature

• DE 4016543 A1 [0034]
• - EP 0347424 B1 [0034]
• - EP 0811019 B1 [0034]
• - DE 69602016 T2 [0034]
• EP 0891380 B1 [0034]
• - DE 69703346 T2 [0034]
• - EP 0514648 B1 [0034]
• - DE 69211224 T2 [0034]
• - WO 2007/134578 [0078]
• - WO 2008/000252 [0078]
• WO 2008/135041 [0078]
• WO 2008/154905 [0078]
• WO 2009/018807 [0078]
• WO 2009/018811 [0078]
• WO 2009/030224 [0078]
• WO 2009/036753 [0078]

Cited non-patent literature

• - Lechner, Gehrke, Nordmeier: Macromolecular Chemistry, Verlag Birkhäuser, ISBN 3764329734 [0030]
• Calhoun, Peacock: Polymer Chemistry, Hanser Fachbuchverlag, ISBN 3446222839 [0030]
• Etsuko Miyazawa et al., OPPI Briefs, 29, 5, 1997 [0057]
• Yu Lin Jiang et al., J. Am. Chem. Soc., 2005, 127, 17412-17420 [0064]
• - Jae Nyoung Kim et al., Synth. Comm., 1992, 22 (10), 1427-1432 [0064]

Claims (7)

Polymer compound characterized by the presence of at least 10 structural elements of the formula -CO-NH-O- -CO-O-NH- or -O-CO-NH-O- in the backbone of the polymer. Polymeric compound according to claim 1, characterized by the general formula Ia, Ib, Ic, Id or Ie - [OR ¹ -O-NH-CO-] _n - (Ia) - [R ¹ -O-NH-CO-] _n - (Ib) - [NH-R ¹ -O-NH-CO-NH-R ² -NH-CO-] _n - (Ic) - [OR ¹ -O-NH-CO-NH-R ² -NH-CO-] _n - (Id) - [NH-OR ¹ -O-NH-CO-NH-R ² -NH-CO-] _n - (Ie) wherein R ^{1 is} an organic radical which may contain alkyl, aryl or heteroaryl moieties which may contain one or more heteroatoms which may contain one or more double or triple bonds which may be wholly or partially fluorinated and which may be one or more more times by halogen, pseudohalogen, C ₁ -C ₄ alkyl or C ₁ -C ₄ -alkoxy, R ² is an organic radical of the alkyl, aryl or heteroaryl moieties may contain, which may contain one or more heteroatoms which may contain one or more double or triple bonds which may be fully or partially fluorinated and which may be substituted one or more times by halogen, by pseudohalogen, by C ₁ -C ₄ -alkyl or C ₁ -C ₄ -alkoxy for a number greater than or equal to 10 stands. A polymeric compound according to claim 2, characterized in that it further urethane (-OCO-NH-) or urea groups (-NH-CO-NH-) in the backbone. Polymeric compound according to claim 2, characterized in that at least one of the groups R ¹ or R ^{2 is} selected from: a) a C ₁ -C ₂₀ -alkyl group which may be branched or unbranched and which contain one or more double or triple bonds can, b) a C ₁ -C ₂₀ alkyl group, which may be branched or unbranched and which may contain one or more double or triple bonds and which is fully or partially fluorinated, c) a C ₁ -C ₂₀ alkyl group, the may be branched or unbranched and which contains one or more oxygen atoms (ether groups), wherein the oxygen atoms are not terminal, d) a C ₁ -C ₂₀ -alkyl group which may be branched or unbranched and which contain one or more double or triple bonds and which contains one or more C ₆ -C ₁₄ -aryl groups and / or one or more C ₆ -C ₁₄ -heteroaryl groups, where the aryl or heteroaryl groups may be monosubstituted or polysubstituted en with C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, fluorine, chlorine, bromine, iodine or cyano, e) a C ₆ -C ₁₄ -aryl group which may be mono- or polysubstituted with C ₁ C ₄ alkyl, C ₁ -C ₄ alkoxy, fluoro, chloro, bromo, iodo or cyano; f) a C ₆ -C ₁₄ heteroaryl group which may contain one or more heteroatoms (N, O, S) and which may be mono- or polysubstituted by C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, fluorine, chlorine, bromine, iodine or cyano. Polymeric compound according to claim 1, characterized by the formula - [CO-O-NH-CH ₂ ] _n where n is at least 10. A process for the preparation of polymeric compounds according to any one of claims 1-4, characterized in that a compound of general formula III (HO-) _p R ¹ (-ONH ₂ ) _q (III) wherein R ^{1 is} as defined in claim 1 and wherein p is the integer zero, one, two or three and wherein q is the integer one, two, three or four and wherein the sum of p and q is two , three or four, is reacted with a compound of general formula IV R ² (-N = C = O) _r (IV) wherein R ² , which has the meaning mentioned in claim 1 and wherein r is the integer two, three or four, to the polymeric substance according to the invention. Process for the preparation of polymeric compounds according to Claim 6, characterized in that a compound of the general formula IIa or IIb or IIc HO-R ¹ -ONH ₂ (IIa) H ₂ NR ¹ -ONH ₂ (IIb) H ₂ NOR ¹ -ONH ₂ (IIc) wherein R ¹ , which has the meaning given in claim 1, is reacted with a compound of general formula V O = C = NR ² -N = C = O (V) wherein R ² having referred to in claim 1, according to the invention for the polymeric substance.