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• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
  • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
  • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
  • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
  • C07D307/40—Radicals substituted by oxygen atoms
  • C07D307/42—Singly bound oxygen atoms
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
  • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
  • C07D493/04—Ortho-condensed systems
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C67/00—Preparation of carboxylic acid esters
  • C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C67/00—Preparation of carboxylic acid esters
  • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
  • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
  • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C68/00—Preparation of esters of carbonic or haloformic acids
  • C07C68/06—Preparation of esters of carbonic or haloformic acids from organic carbonates
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
  • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
  • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
  • C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
  • C07D307/12—Radicals substituted by oxygen atoms
• • 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
  • C08G64/00—Macromolecular compounds obtained by reactions forming a carbonic ester link in the main chain of the macromolecule
  • C08G64/20—General preparatory processes
  • C08G64/30—General preparatory processes using carbonates

Definitions

• the present invention is in the field of art that relates to cyclic bi-functional materials useful as monomers in polymer synthesis and as intermediates generally, and to the methods by which such materials are made.
• the present invention pertains to a method of preparing anhydrosugar ethers and carbonates.
• carbohydrates One of the most abundant kinds of biologically-derived or renewable alternative feedstock for such materials is carbohydrates.
• Carbohydrates are generally unsuited to current high temperature industrial processes.
• carbohydrates such as polysaccharides are complex, multi-functionalized hydrophilic materials.
• researchers have sought to produce biologically-based chemicals that can be derived from carbohydrates, but which are less highly functionalized, including more stable bi-functional compounds.
• One class of such compounds include anyhydrosugars, such as 1,4:3,6-dianhydrohexitols.
• 1,4:3,6-Dianhydrohexitols are derived from renewable resources from cereal-based polysaccharides.
• Isohexides embody a class of bicyclic furanodiols that derive from the corresponding reduced sugar alcohols (D-sorbitol, D-mannitol, and D-iditol respectively).
• D-sorbitol, D-mannitol, and D-iditol Depending on the chirality, three isomers of the isohexides exist, namely: A) isosorbide, B) isomannide, and C) isoidide, respectively; the structures of which are illustrated in Scheme 1.
• the isohexides are composed of two cis-fused tetrahydrofuran rings, nearly planar and V-shaped with a 120° angle between rings.
• the hydroxyl groups are situated at carbons 2 and 5 and positioned on either inside or outside the V-shaped molecule. They are designated, respectively, as endo or exo.
• Isoidide has two exo hydroxyl groups, while the hydroxyl groups are both endo in isomannide, and one exo and one endo hydroxyl group in isosorbide.
• the presence of the exo substituents increases the stability of the cycle to which it is attached.
• exo and endo groups exhibit different reactivities since they are more or less accessible depending on the steric requirements of the derivatizing reaction.
• ethers of isohexides A kind of derivative that can be made is ethers of isohexides.
• ethers of dianhydrosugars are prepared by contacting alkyl halides and dialkylsulfates with an anhydrosugar, in the presence of a base or phase transfer catalysts (PTC's, e.g., tetra-n-butylammonium bromide, benzyltriethyammonium bromide or N-methyl-N,N-dioctyloctan-1-aminium chloride).
• PTC's phase transfer catalysts
• the present disclosure describes a method for alkylation of anhydrosugar alcohols (isohexides) using a carbonate reagent.
• the alkylation method involves: a) contacting an isohexide with a dialkyl, diallyl, or diaryl carbonate, and a Br ⁇ nsted base; and b) producing at least an alkyl ether or alkyl carbonate of the isohexide compound.
• the alkylation reaction is in situ, that is, performed without an extrinsic catalyst.
• the Br ⁇ nsted base has a pKa of at least 4, which helps deprotonates the isohexide compound.
• the isohexide is at least one of the following: isosorbide, isomannide, and isoidide.
• the dialkyl, diallyl, or diaryl carbonate has an R-group having 1 to 20 carbon atoms. When the R-group is at least a methyl, ethyl, propyl group, an ether is produced, and when the R-group is at least a C 4 -C 20 group, a carbonate is generated.
• the resultant ether or carbonate, respectively can be either: a mono-alkyl ether or dialkyl ether, or mono-alkyl, mono-allyl, mono-aryl carbonate, or dialkyl, diallyl, or diaryl carbonate.
• the present disclosure pertains to certain ethers and carbonates synthesized according the foregoing method.
• the alkylated ether of the isohexide compound is at least one of the following: mono-ether of isoidide; mono-ether of isomannide; mono-ether of isosorbide; di-ether of isoidide; di-ether of isomannide; and di-ether of isosorbide, wherein the resultant ether has at least one of the following alkyl groups: a mono-methyl, mono-ethyl, mono-propyl, di-methyl, di-ethyl, or di-propyl.
• the alkylated carbonate of the isohexide compound is at least one of the following: mono-carbonate of isoidide; mono-carbonate of isomannide; mono-carbonate of isosorbide; di-carbonate of isoidide; di-carbonate of isomannide; and di-carbonate of isosorbide, wherein the resultant carbonate has at least one of the following alkyl, allyl or aryl groups: a mono-butyl, mono-pentyl, mono-hexyl, mono-benzyl, mono-phenyl, mono-allyl, di-butyl, di-pentyl, dihexyl, di-benzyl, di-phenyl, di-allyl, or a mono- or di-alkyl group from C 7 -C 20 carbon atoms.
• 1,4:3,6-dianhydrohexitols are a class of bicyclic furanodiols that are valued as renewable molecular entities.
• 1,4:3,6-dianhydrohexitols will be referred to as “isohexides” in the Description hereinafter.
• the isohexides are good chemical platforms that have recently received interest because of their intrinsic chiral bi-functionalities, which can permit a significant expansion of both existing and new derivative compounds that can be synthesized.
• Isohexide starting materials can be obtained by known methods of making respectively isosorbide, isomannide, or isoidide.
• Isosorbide and isomannide can be derived from the dehydration of the corresponding sugar alcohols, D-sorbitol and D mannitol respectively.
• isosorbide is also available easily from a manufacturer.
• the third isomer, isoidide can be produced from L -idose, which rarely exists in nature and cannot be extracted from vegetal biomass. For this reason, researchers have been actively exploring different synthesis methodologies for isoidide.
• the isoidide starting material can be prepared by epimerization from isosorbide. In L. W. Wright, J. D. Brandner, J.
• L-iditol precursor for isoidide
• L-sorbose U.S. Patent Publication No. 2006/0096588; U.S. Pat. No. 7,674,381 B2
• L-iditol is prepared starting from sorbitol.
• sorbitol is converted by fermentation into L-sorbose, which is subsequently hydrogenated into a mixture of D-sorbitol and L-iditol.
• This mixture is then converted into a mixture of L-iditol and L-sorbose. After separation from the L-sorbose, the L-iditol can be converted into isoidide. Thus, sorbitol is converted into isoidide in a four-step reaction, in a yield of about 50%. (The contents of the cited references are incorporated herein by reference.)
• molecular entities hold significant potential as “green”, renewable solvents derived from biomass, as well as platform chemicals (monomethyl ethers) for the production of surfactants, dispersants, and emollients (personal care products). Furthermore, the reagents used in the aforementioned preparation are non-toxic, environmentally friendly substances.
• benign, environmentally friendly carbonate e.g., diethyl carbonate or potassium carbonate
• Schemes 1 and 2 are generalized illustrations of embodiments of the present synthesis process.
• Scheme 1 depicts an embodiment in which an isohexide is reacted with a carbonate having C 1 -C 3 alkyl R-groups using a Br ⁇ nsted base to generate a corresponding ether.
• Scheme 2 shows an alternate embodiment in which an isohexide is reacted with a carbonate having C 4 and greater alkyl, phenyl, allyl R-groups using a Br ⁇ nsted base to produce a corresponding carbonate.
• the base serves to deprotontate the isohexide intermediate to generate the ether or carbonate compounds.
• the base should be reasonably soluble in solution to afford satisfactory mixing and subsequent reactivity.
• the reaction time for each synthesis can be within about 24 hours.
• the reaction time is within about 6 hours to about 12 hours (e.g., 7 or 8 hours to about 9 or 10 hours).
• the yields respectively of mono-ether and di-ether products will increase to full conversion of the di-ether species.
• the mono-carbonate species quickly converts to the di-carbonate species within about 1-2 hours.
• the Br ⁇ nsted base should have a minimal pKa of about 4 (e.g., pyridine). Typically, the base pKa is about 7-14, usually about 8 or 10 to about 12 or 13. In alternative embodiments, some bases may have a greater pKa, up to about 40-55 (e.g., alkyl-lithium).
• the base can be one of the following: a carbonate (e.g., sodium or potassium carbonate); a hindered amine (e.g., triethylamine, tributylamine, diisopropylethylamine (DIEA), dibutylamine); a nucleophilic base (e.g., pyridine, pyrimidine, dimethyl-aminopyridine, imidazole, pyrrolidine, morpholine); a sodium, potassium, or calcium hydride; or an organometallic compound (e.g., alkyl-lithium or alkyl-magnesium).
• a carbonate e.g., sodium or potassium carbonate
• a hindered amine e.g., triethylamine, tributylamine, diisopropylethylamine (DIEA), dibutylamine
• DIEA diisopropylethylamine
• a nucleophilic base e.g.
• the minimum stoichiometric equivalents of base to the staring materials is about 1 for mono-ether or mono-carbonate, and about 2 equivalents depending on the solubility of the carbonate or miscibility of the base (e.g., amines) in solution.
• a non-nucleophilic amine that is sterically hindered such as diisopropylethylamine (DIEA)
• DIEA diisopropylethylamine
• the Br ⁇ nsted base in some embodiments is a solid compound, such as a mineral carbonate, which would make the removal and purification of the final product from solution easier.
• hindered amines owing to their innate liquidity and ease of segregation by mild acid treatment comprise other salutary bases for this process.
• the liquid hindered amine allows for better mixing and miscibility but removal is more complex involving a titration with acid and then liquid-liquid extraction.
• isosorbide diallyldicarbonate separates in the form of viscous oil, and can be stored indefinitely, with negligible degradation, in an inert atmosphere.
• the alkylation reaction can be conducted at a temperature in a range from about 70° C. or 80° C. to about 180° C. or 200° C., inclusive, depending on the boiling point temperature of the particular carbonate solvent used in the reaction (e.g., 75° C. for dimethyl carbonate, or 120° C. for diethyl carbonate).
• the reaction temperature is in a range from about 85° C. or 90° C. or 100° C. to about 160° C., 170° C. or 175° C., inclusive of various combinations of ranges therein.
• Particular temperature ranges for example may be from about 110° C. or 120° C. to about 140° C. or 150° C., inclusive of combination of ranges therein.
• the reaction is performed at a temperature between about 115° C., 117° C. or 120° C. to about 125° C., or 130° C., or 135° C.
• the reaction should use at least 1 to 2 equivalents of carbonate for each equivalent of isohexide consumed. For diethers, at least 2 equivalents are used.
• an alcohol having the same R-species as that which is displaced from the carbonate molecule such as, an ethanol when reacting with diethylcarbonate, or an allyl alcohol when using diallylcarbonate, such in Scheme 3. It is believed that in surplus alcohol the carbonate is activated.
• the reactions can be executed in a neat solution of dimethyl or ethylcarbonate, or as previously detailed, can be generated in situ via transesterification.
• the isohexide compound and the dialkyl, diallyl, or diaryl carbonate are reacted respectively in a neat solution of at least the dialkyl, diallyl, or diaryl carbonate.
• the present etherification reactions can simplify and make the purification and recovery process relatively easy.
• An illustration of an advantage of the present synthesis process is the employment of relatively mild conditions and safe non-toxic reagents is, for example, the preparation of (3R,3aR,6S,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl diphenyl dicarbonate, isosorbide diphenylcarbonate, as discussed in Example 4, below.
• the conventionally way of preparing the same compound can involve several reaction steps, and uses harsh conditions and some reagents such as diphosgene or triphosgene, which are toxic (see, e.g., Noordover, Bart A.
• organic bases all linear and cyclic amines, such as triethylamine, Hunig's base, DBU, and piperidine;
• alkali and alkali earth metal carbonates such as cesium carbonate, calcium carbonate
• alkyl carbonates transesterification of carbonates that can be implimented with relatively inexpensive dimethyl or diethyl carbonates in an excess alcohol and with a Lewis acid catalyst.
• isoidide mono and dibenzylethers can be generated from the in situ production of dibenzyl carbonate (dimethyl carbonate, a surfeit of benzyl alcohol, and catalyst) using the present method.
• the alkylated isohexide compound prepared by the present method is either an ether or a carbonate.
• the isohexide ether can be at least one of the following: a mono-alkyl ether or dialkyl ether.
• the ether compound can be, for example: an isoidide monoethylether, with a structure:
• the alkylated isohexide ether can be one of the following: mono-methyl ether of isoiodide; mono-ethyl ethers, of isosorbide, isommanide, or isoiodide, respectively; diethyl ester of isoiodide; mono-propyl ether of isomannide; dipropyl ether of isomannide; mono-propyl ether of isoidide; dipropyl ether of isoiodide; mono-benzyl ether of isoidide; monoallyl ethers of isosorbide, isommanide, or isoiodide, respectively; and diallyl ethers of isosorbide, isommanide, or isoiodide, respectively.
• Isoidide monoethylether (IUPAC: (3S,3aR,6S,6aR)-6-ethoxyhexahydrofuro[3,2-b]furan-3-ol) and isoidide diethylether (IUPAC: (3S,3aR,6S,6aR)-6-ethoxyhexahydrofuro[3,2-b]furan-3-ol).
• Diethyl ethers of isomannide and isosorbide, as well as the corresponding monoethyl ethers can be formed in high yields. It is believed that the monomethyl ethers of isomannide and isosorbide are new compositions of matter.
• the carbonate compound can be at least one of the following: a mono-alkyl carbonate, dialkyl carbonate, mono- or di-aryl carbonate, mono- or di-allyl carbonate, or a carbonate with an alkyl group from 4-20 carbon atoms.
• the carbonate compound is: isosorbide diallyldicarbonate, with a structure:
• the isohexide carbonate can be one of the following: mono-methylcarbonate of isomannide; mono-methylcarbonate of isoidide; dimethylcarbonate of isomannide; dimethylcarbonate of isoidide; monoethylcarbonates of isosorbide, isommanide, or isoiodide, respectively; diethylcarbonate of isomannide; diethylcarbonate of isoidide; mono-propyl or dipropylcarbonates of isosorbide, isommanide, or isoiodide, respectively; mono- or dicarbonates having an alkyl R-group of C 4 to C 20 of isosorbide, isommanide, or isoiodide, respectively; mono-benzyl or dibenzyl carbonates of isosorbide, isommanide, or isoiodide, respectively; monophenylcarbonates of isosorbide, isommanide, or isoiodide, respectively; monopheny

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