Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
  • C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
  • C07C51/36—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by hydrogenation of carbon-to-carbon unsaturated bonds
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
  • C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
  • C07C51/353—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by isomerisation; by change of size of the carbon skeleton
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C55/00—Saturated compounds having more than one carboxyl group bound to acyclic carbon atoms
  • C07C55/02—Dicarboxylic acids
• • 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
  • C07C67/303—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by hydrogenation of unsaturated carbon-to-carbon bonds
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C67/00—Preparation of carboxylic acid esters
  • C07C67/475—Preparation of carboxylic acid esters by splitting of carbon-to-carbon bonds and redistribution, e.g. disproportionation or migration of groups between different molecules
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
  • C07C69/34—Esters of acyclic saturated polycarboxylic acids having an esterified carboxyl group bound to an acyclic carbon atom
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
  • C07C69/52—Esters of acyclic unsaturated carboxylic acids having the esterified carboxyl group bound to an acyclic carbon atom
  • C07C69/593—Dicarboxylic acid esters having only one carbon-to-carbon double bond
• • 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
  • C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
  • C08G69/02—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids
  • C08G69/26—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids derived from polyamines and polycarboxylic acids
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
  • C12P7/00—Preparation of oxygen-containing organic compounds
  • C12P7/40—Preparation of oxygen-containing organic compounds containing a carboxyl group including Peroxycarboxylic acids
  • C12P7/44—Polycarboxylic acids

Definitions

• the invention relates generally to the production of dodecanedioic acid from renewable feedstock and subsequent uses thereof, such as for forming polyamides.
• Nylon is a generic designation for a family of synthetic thermoplastic polyamides that are used to make fabrics, musical strings, rope, screws and gears, to name just a few examples. Nylon is available with fillers too, such as glass- and molybdenum sulf ⁇ de-f ⁇ lled variants.
• Nylon 6 is the most common commercial grade of molded nylon. The numerical suffix specifies the numbers of carbon atoms donated by the monomers; the diamine first and the diacid second. For nylon 6,6, the diamine typically is hexamethylenediamine and the diacid is adipic acid. Each of these monomers donates 6 carbons to the polymer chain.
• nylon 6,12 is a copolymer of a 6-carbon diamine and a 12-carbon dicarboxylic acid.
• One method for making nylon 6,12 comprises forming a polycondensation product of 1,6-hexamethylene diamine and dodecanedioic acid.
• the starting materials are virtually solely obtained from hydrocarbon sources.
• Dodecanedioic acid is thus a very important chemical. It is used in a variety of industrial applications, such as plasticizers for polymers, epoxy curing agents, adhesive and powder coatings, engineering plastics, perfumery and pharmaceutical products, etc. Annually, 15,000,000,000 pounds of dodecanedioic acid are synthesized from petrochemical feedstock. Such petrochemical feedstocks are a predominantly depleting natural resource, and the use of such feedstocks has been linked to detrimental changes to the environment on a global scale. [007] Such feedstock materials useful for the production of nylon have therefore limited availability and are subject to substantial price fluctuations. As a result, there has been a growing interest and need for alternative methods to produce dodecanedioic acid as well as polyamides that are renewable, sustainable and less harmful for the environment.
• aspects of the invention relate to the production of useful commercial product, such as polyamides, starting with materials produced by a biological process from renewable feedstock, as opposed to using starting materials derived from non-renewable feedstock such as petroleum or other fossil carbon resources.
• aspects of the invention relates more particularly to the production of dicarboxylic acid, as well as derivatives thereof, from renewable biomass-derived carbon source. More particularly, some aspects of the invention relate to the production of dodecanedioic acid, as well as precursors and derivatives thereof, from renewable biomass-derived carbon source.
• the methods of the invention make use of a metathesis step with olefinic compounds in order to produce biosourced dicarboxylic acid such as dodecanedioic acid from renewable biosourced feedstock.
• the resulting renewable dodecanedioic acid can be separated from other products of the metathesis reaction and from any remaining starting materials.
• Dodecanedioic acid and derivatives thereof have utility in the production of polyamides and other polymers.
• the invention provides a method of producing first muconic acid biologically from renewable feedstock.
• the muconic acid is reduced to an isomer or isomers of hexenedioic acid.
• Reduction of the muconic acid can be performed using methods known in the art such as a zinc halide reagent, electrochemical reduction, or selective hydrogenation.
• the hexenedioic acid may be present as a derivative such as an ester, amide, or salt.
• the hexenedioic acid is reacted with an unsaturated fatty acid in a metathesis reaction to produce dodecenedioic acid, which is then reduced to dodecanedioic acid.
• the reaction typically involves using a metathesis catalyst, such as a Grubbs catalyst, including benzylidene-bis(tricyclohexylphosphine)dichlororuthenium or benzylidene[1,3- bis(2,4,6- trimethylphenyl)-2- imidazolidinylidene]dichloro(tricyclohexylphosphine)ruthenium.
• a metathesis catalyst such as a Grubbs catalyst, including benzylidene-bis(tricyclohexylphosphine)dichlororuthenium or benzylidene[1,3- bis(2,4,6- trimethylphenyl)-2- imidazolidinylidene]dichloro(tricyclohexylphosphine)ruthenium.
• Forming muconic acid biologically may comprise forming the muconic acid bacterially using prokaryotes belonging to the genera Escherichia, Klebsiella, Corynebacterium, Brevibacterium, Arthrobacter, Bacillus, Pseudomonas, Streptomyces, Staphylococcus, or Serratia, or by using yeasts of the genus Saccharomyces or Schizosaccharomyces.
• Muconic acid is reduced to an isomer of hexenedioic acid, such as 3-hexenedioic acid, using any suitable reagent.
• One suitable reagent is a zinc halide reagent, such as zinc chloride in pyridine.
• the hexenedioic acid or derivative thereof is reacted with an unsaturated fatty acid to form an unsaturated dicarboxylic acid or derivative thereof.
• the unsaturated fatty acid is first reacted in a self metathesis reaction to produce ⁇ 9 octadecenedioic acid.
• ⁇ 9 octadecenedioic acid then reacts with the hexenedioic acid to produce dodecenedioic acid.
• the unsaturated fatty acid is a ⁇ 9 unsaturated fatty acid.
• Examples, without limitation, of the ⁇ 9 unsaturated fatty acid include myristoleic acid, palmitoleic acid, elaidic acid, and oleic acid.
• the unsaturated dicarboxylic acid or derivative thereof which is produced by the metathesis reaction can then be reduced to a saturated dicarboxylic acid.
• the unsaturated dicarboxylic acid which is formed is dodecenedioic acid is then reduced to its saturated analog dodecanedioic acid. This can be accomplished by, for example, hydrogenating the dodecenedioic acid using a precious metal hydrogenation catalyst.
• the ⁇ 9 unsaturated fatty acid is first transformed to the symmetric ⁇ 9 unsaturated dicarboxylic acid octadecenedioic acid via a self-metathesis reaction.
• the symmetric ⁇ 9 octadecenedioic acid can then be used in a cross-metathesis reaction with the symmetric 3-hexenedioic acid to give the desired dodecenedioic acid as a single product of the metathesis reaction.
• the dodecanedioic acid is used for forming polymers, such as polyamides.
• polyamides include a nylon, such as nylon 6,12.
• Nylon 6,12 can be formed by reacting 1,6-hexamethylene diamine with dodecanedioic acid.
• a particular embodiment of the disclosed invention comprises first forming muconic acid biologically using prokaryotes belonging to the genera Escherichia, Klebsiella, Corynebacterium, Brevibacterium, Arthrobacter, Bacillus, Pseudomonas, Streptomyces, Staphylococcus, ox Serratia or yeasts of the genus Saccharomyces or Schizosaccharomyces.
• the muconic acid is reduced to 3-hexenedioic acid using a zinc halide reagent.
• the 3-hexenedioic acid is reacted with a ⁇ 9 unsaturated fatty acid, such as myristoleic acid, palmitoleic acid, elaidic acid, oleic acid, or combinations thereof, in a metathesis reaction using a metathesis catalyst, to produce dodecenedioic acid.
• a ⁇ 9 unsaturated fatty acid such as myristoleic acid, palmitoleic acid, elaidic acid, oleic acid, or combinations thereof
• a metathesis reaction using a metathesis catalyst to produce dodecenedioic acid.
• the dodecenedioic acid is reduced by hydrogenation to form dodecanedioic acid.
• the dodecanedioic acid is then used to form a poly amide, such a nylon 6,12, by reaction with a suitable diamine, such as 1,6-hexamethylene diamine.
• compositions comprising biosourced unsaturated dicarboxylic acid or derivative thereof and their saturated analogs which have been produced from renewable feedstock derived from biomass.
• the composition comprises a biosourced dodecenedioic acid or dodecenedioic acid derivatives thereof.
• biosourced products with a carbon isotope distribution or a 14 C/ 12 C ratio characteristic of product synthesized from renewable carbon sources.
• the renewable isolated dodecenedioic acid or dodecenedioic acid derivatives thereof are characterized by a 14 C/ 12 C ratio greater than 0, greater than 0.9 x 10 '12 , or of about 1.2 x 10 '12 .
• the dodecenedioic acid derivative is a dimethyl dodecenedioic acid.
• compositions comprising biosourced dodecanedioic acid or derivatives thereof are disclosed.
• Other aspects of the invention relates to compositions comprising a renewable isolated 3- hexenedioic and 3-hexenedioic derivatives thereof.
• the biosourced 3- hexenedioic and 3-hexenedioic derivatives thereof is characterized by a 14 C/ 12 C isotopic ratio of about 1.2 x 10 -12 .
• Further aspects of the invention relate to compositions comprising biosourced polyamide.
• the polyamide is a nylon 6,12 polymer and at least 12 carbon atoms per monomer units derived from renewable carbon sources.
• the nylon 6,12 comprises detectable traces of carbon 14.
• the renewable compounds disclosed herein contains up to about 1 part per trillion of carbon 14.
• compositions comprising a dodecenedioic acid or dodecenedioic acid derivative and at least one unsaturated dicarboxylic acid or unsaturated dicarboxylic acid derivative byproduct derived from the dodecenedioic acid or dodecenedioic acid derivative .
• the composition comprises at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9 byproducts derived from the dodecenedioic acid or dodecenedioic acid derivative.
• the at least one unsaturated dicarboxylic acid or unsaturated dicarboxylic acid derivative byproduct comprises an alkene chain having from about 7 to about 16 carbon atoms.
• the compositions comprises at least 9 byproducts derived from the dodecenedioic acid or dodecenedioic acid derivative, the byproducts comprising an alkene chain having from about 7 to about 16 carbon atoms.
• the dodecenedioic acid derivative is a dodecenedioic acid diester.
• the dodecenedioic acid or dodecenedioic acid derivative contains up to about 1 part per trillion of Carbon 14.
• the alkene chain comprises a carbon double bond in a position of C3-C4.
• Other aspects of the invention relate to compositions comprising 9-octadecenedioic acid or 9-octadecenedioic acid derivative and at least one octadecenedioic acid or octadecenedioic acid derivative byproduct derived from 9-octadecenedioic acid or 9-octadecenedioic acid derivative.
• the composition comprises at least 1, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 15, at least 16 byproducts derived from 9- octadecenedioic acid or 9-octadecenedioic acid derivative.
• the octadecenedioic acid or octadecenedioic acid derivative byproducts comprise a carbon double bond in Cl-C2, C2-C3, C3-C4, C4-C5, C5-C6,, C6-C7, C7-C8, C8-C9, ClO-CI l, C11-C12, C12-C13, C 13-Cl 4, C 14- Cl 5, C 15-Cl 6, C 16-Cl 7, or C 17-Cl 8 position.
• the 9- octadecenedioic acid or 9-octadecenedioic acid derivative contains up to about 1 part per trillion of Carbon 14.
• FIG. 1 shows the common pathway of aromatic amino acid biosynthesis and the divergent pathway synthesizing cis,cis-muconic acid from 3-dehydroshikimate.
• FIG. 2 shows a process flow diagram of an embodiment of the dodecanedioic acid synthesis.
• Fig. 2 shows the self-metathesis reaction forming the symmetric ⁇ 9 octadecenedioic acid and the subsequent cross metathesis reaction with 3-hexenedioic acid.
• FIG. 3 shows the effect of double bond migration on self metathesis reaction.
• FIG. 4 shows the effect of double bond migration on cross metathesis reaction.
• aspects of the invention relates to methods and compositions to produce dodecenedioic acid derivatives thereof and/or dodecanedioic acid and derivatives thereof.
• the invention relates to the methods and compositions for the production of dodecenedioic acid from 3-hexenedioic acid and octadecenedioate.
• dodecenedioic acid is produced from dimethyl hexenedioates and dimethyl octadecenedioate.
• reduction of dimethyl dodecenedioic acid produces dimethyl dodecanedioic acid.
• hexenedioic acid and hexanedioate are used interchangeably and refer to a molecule comprising six carbon atoms, eight hydrogen atoms and four oxygen atoms having the formula
• dodecenedioic acid and dodecenedioate are used interchangeably and refer to a molecule comprising twelve carbon atoms, twenty hydrogen atoms and four oxygen atoms having the formula COOH .
• dodecanedioic acid and dodecanedioic acid are used interchangeably and refer to a molecule comprising twelve carbon atoms, twenty two hydrogen atoms and four oxygen atoms having the formula [0027]
• Dodecanedioic acid can be produced from epoxidation of the 1,5,9 cyclodecatriene using hydrogen peroxide and acetic acid to form the corresponding epoxy compound which is subsequently hydrogenated to form the alcohol and oxidized to form the desired product.
• the dodecanedioic acid is prepared by the epoxidation of 1,5,9 cyclododecatriene with an organic hydroperoxide to form 1,2-epoxy-5,9-cyclododecadiene followed by conversion of this compound to a cycloderivative oxidizable to dodecanedioic acid.
• the invention uses oils or fats and muconic acid as an alternative starting material for the production of dicarboxylic acids, oxo chemicals such as oxo aldehydes and oxo esters.
• aldehyde refers to a carbonyl-bearing functional group having a formula
• R is virtually any group including, by way of example and without limitation, aliphatic, substituted aliphatic, aryl, arylalkyl, heteroaryl, etc.
• aliphatic refers to a substantially hydrocarbon-based compound, or a radical thereof , for a hexane radical), including alkanes, alkenes and alkynes, and further including straight- and branched-chain arrangements, and as well as all stereo and position isomers.
• alkyl refers to a hydrocarbon arranged in a chain in a homologous series having the general formula Alkyl substituents include methyl, and so on.
• the structure of an alkyl group is like that of its alkane counterpart, but with one less hydrogen atom.
• aryl refers to a substantially hydrocarbon-based aromatic compound, or a radical thereof as a substituent bonded to another group, particularly other organic groups, having a ring structure as exemplified by benzene, naphthalene, phenanthrene, anthracene, and the like.
• arylalkyl refers to a compound, or a radical thereof (e.g.
• carboxylic acid refers to a compound having a formula R-
• R can be virtually any group including, by way of example and without limitation, aliphatic, substituted aliphatic, aryl, arylalkyl, heteroaryl, and the like.
• cyclic refers to a substantially hydrocarbon, closed-ring compound, or a radical thereof. Cyclic compounds or substituents also can include one or more sites of unsaturation. Exemplary cyclic compounds include compounds typically having 3 or more, more typically 4 or more, and even more typically 5 or more carbon atoms in the ring including, without limitation, cyclopentene, cyclopentadiene, cyclohexene, cyclohexadiene, and conjugated derivatives thereof, such as compounds having olefins conjugated with carbonyl functionalities, such as carboxylic acids, amides and esters.
• derivative refers to a molecule that differs in chemical structure from a parent compound.
• derivatives include, without limitation: homologs, which differ incrementally from the chemical structure of the parent, such as a difference in the length of an aliphatic chain; molecular fragments; structures that differ by one or more functional groups from the parent compound, such as can be made by transforming one or more functional groups of a parent, such as by changing an acid functional group of a parent molecule into an acid halide, amide, or ester; a change in ionization state of a parent, such as ionizing an acid to its conjugate base; isomers, including positional, geometric and stereoisomers; and combinations thereof.
• esters refers to a compound having a formula
• R and R 1 are independently selected from virtually any group, including aliphatic, substituted aliphatic, aryl, arylalkyl, heteroaryl, etc.
• heteroaryl refers to an aromatic, closed-ring compound, or radical thereof as a substituent bonded to another group, particularly other organic groups, where at least one atom in the aromatic ring is other than carbon, such as oxygen, sulfur and/or nitrogen.
• heterocyclic refers to a cyclic, i.e. closed-ring, aliphatic compound, or radical thereof as a substituent bonded to another group, particularly other organic groups, where at least one atom in the ring structure is other than carbon, such as oxygen, sulfur and/or nitrogen.
• ketone refers to a compound having a formula
• R and R' are independently selected from virtually any group including, without limitation, aliphatic, substituted aliphatic, aryl, arylalkyl, heteroaryl, etc.
• lower organic compounds refers to organic compounds or radicals thereof having 10 or fewer carbon atoms in a chain, including all branched and stereochemical variations thereof, particularly including methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, and decyl.
• substituted refers to a fundamental compound, such as an aliphatic, aryl, arylal ⁇ phatic, heterocyclic, heteroaryl, or heteroarylaliphatic compound, or a radical thereof, having coupled thereto, typically in place of a hydrogen atom, a second atom, substituent, functional group, etc.
• substituted aryl compounds or substituents may have an aliphatic group coupled to the closed ring of the aryl base, such as with toluene, which has a methyl group substituted for a hydrogen atom of benzene.
• a long-chain hydrocarbon may have, without limitation, an atom or substituent bonded thereto, such as a halide, a heteroatom, a functional group, an aryl group, a cyclic group, a heteroaryl group or a heterocyclic group.
• unsaturated fatty acid refers to compounds that have an alkene chain with a terminal carboxylic acid group.
• unsaturated dicarboxylic acid refers to a compound with a carboxylic acid at each end of an unbranched carbon chain, which also includes at least one double bond in the carbon chain.
• Muconic acid refers to chemical species in which both carboxylic acid functions are protonated, and the molecule is formally a neutral species.
• moconate refers to the chemical species in which one or both of the carboxylic acid functions is deprotonated to give the anionic or doubly-anionic form of muconic acid which would be the predominate chemical species at physiological pH values.
• moconic acid and “muconate” refer to the protonated or deprotonated forms of the same molecule, the terms are used synonymously where the difference between protonated and deprotonated (e.g., non-ionized and ionized) forms of the molecule is not usefully distinguished.
• Cis cis-muconic acid and trans, trans-muconic acid are available commercially in small quantities (e.g., from Sigma- Aldrich), but are quite expensive. However, cis.cis-muconic acid also is produced by some bacteria through the enzymatic degradation of aromatic compounds. In some embodiments, cis.cis-muconic acid is synthesized biologically in certain bacteria as disclosed in U.S. Patent Nos. 5,487,987 and 5,616,496, which are incorporated herein by reference. Industrial-scale quantities of Cis cis-muconic acid can be produced by such biosynthesis.
• Bacteria that are capable of the biosynthesis of Cis cis-muconic acid are members of genera having an endogenous common pathway of aromatic amino acid biosynthesis.
• Suitable bacteria include prokaryotes belonging to the genera Escherichia, Klebsiella, Corynebacterium, Brevibacterium, Arthrobacter, Bacillus, Pseudomonas, Streptomyces, Staphylococcus, or Serratia.
• Eukaryotic host cells can also be utilized, particularly yeasts of the genus Saccharomyces or Schizosaccharomyces.
• Suitable prokaryotic species include Escherichia coli, Klebsiella pneumonia,
• the methods include microbial biosynthesis of biosourced muconic acid from readily available, renewable carbon sources (see, for example U.S. Patent No. 5,616,496 which is incorporated herein by reference).
• biosourced refers to a material derived using a biological process as opposed to a non-biological process such as a synthetic, chemical process.
• biosourced muconic acid is derived from a fermentation process utilizing a fermentable carbon source.
• a “biosourced” compound or product refers to a product comprised in whole or in part from biosourced material.
• preferred host cells for use in this invention are able to convert carbon sources into D-erythrose-4- phosphate (E4P) and phosphoenolpyruvate (PEP).
• E4P and PEP are subsequently converted to amino acids via a metabolic pathway ultimately producing aromatic amino acids.
• Fermentable carbon sources can include essentially any carbon source capable of being biocatalytically converted into D-erythrose 4-phosphate (E4P) and phosphoenolpyruvate (PEP), two precursor compounds to the common pathway of aromatic amino acid biosynthesis.
• Suitable carbon sources include, but are not limited to, biomass-derived, renewable sources such as starches, cellulose, polyols such as glycerol, pentose sugars such as arabinose and xylose, hexose sugars such as glucose, and fructose, disaccharides such as sucrose and lactose, as well as other carbon sources capable of supporting microbial metabolism, for example, carbon monoxide.
• Exemplary carbon sources include glucose, glycerol, sucrose, xylose and arabinose.
• D-glucose is the biomass-derived carbon source.
• Host cells suitable for use in the present invention include members of genera that can be utilized for biological production of desired intermediates in the biosynthesis of aromatic compounds such as amino acids.
• such host cells are suitable for industrial- scale biosynthetic or biological production of industrially useful aromatic compounds, and intermediates leading to such useful compounds.
• One intermediate in the pathway of aromatic amino acid biosynthesis is 3-dehydroshikimate (DHS).
• DHS 3-dehydroshikimate
• suitable host cells can have an endogenous common pathway of aromatic amino acid biosynthesis that is functional at least to the production of DHS.
• Common pathways for the biosynthesis of aromatic amino acids are endogenous in a wide variety of microorganisms, and can be used for the production of various aromatic compounds.
• auxotrophic mutant cell lines having a mutation blocking the conversion of 3-dehydroshikimate (DHS) to chorismate are used.
• Such mutants have a mutation in one or more of the genes encoding shikimate dehydrogenase, shikimate kinase, EPSP synthase or chorismate synthase. These mutants accumulate elevated intracellular levels of DHS.
• Suitable mutant cell lines include Escherichia coli strains AB2834, AB2829 and AB2849.
• E. coli AB2834 has a mutation in the aroE locus which encodes shikimate dehydrogenase, preventing the cells from converting DHS into shikimic acid.
• E. coli AB2829 accumulates DHS because it cannot convert shikimate 3-phosphate (S3P) into 5-enoipyruvylshikimate-3-phosphate (EPSP) due to a mutation in the aroA locus which encodes EPSP synthase.
• S3P shikimate 3-phosphate
• EPSP 5-enoipyruvylshikimate-3-phosphate
• E. coli AB2849 is unable to catalyze the conversion of EPSP into chorismic acid due to a mutation in the aroC locus which encodes chorismate synthase also result in increased intracellular levels of DHS.
• Host cells can be transformed so that the intracellular DHS can be used as a substrate for biocatalytic conversion to catechol, which can thereafter be converted to muconic acid.
• host cells can be transformed with recombinant DNA to force carbon flow away from the common pathway of aromatic amino acid biosynthesis after DHS is produced and into a divergent pathway to produce muconic acid.
• a mechanism for transforming the host cell to direct carbon flow into the divergent pathway can involve the insertion of genetic elements including expressible sequences coding for 3- dehydroshikimate dehydratase, protocatechuate decarboxylase, and catechol 1,2-dioxygenase. Regardless of the exact mechanism utilized, it is contemplated that the expression of these enzymatic activities will be effected or mediated by the transfer of recombinant genetic elements into the host cell. Genetic elements as herein defined include nucleic acids (generally DNA or RNA) having expressible coding sequences for products such as proteins, apoproteins, or antisense RNA, which can perform or control pathway enzymatic functions.
• the expressed proteins can function as enzymes, repress or derepress enzyme activity, or control expression of enzymes.
• the nucleic acids coding these expressible sequences can be either chromosomal (e.g., integrated into a host cell chromosome) or extrachromosomal (e.g., carried by plasmids, cosmids, and the like).
• the genetic elements of the present invention can be introduced into a host cell by plasmids, cosmids, phages, yeast artificial chromosomes or other vectors that mediate transfer of the genetic elements into a host cell. These vectors can include an origin of replication along with cis- acting control elements that control replication of the vector and the genetic elements carried by the vector.
• Selectable markers can be present on the vector to aid in the identification of host cells into which the genetic elements have been introduced.
• selectable markers can be genes that confer resistance to particular antibiotics such as tetracycline, ampicillin, chloramphenicol, kanamycin, or neomycin.
• Plasmid borne introduction of the genetic element into host cells involves an initial cleaving of a plasmid with a restriction enzyme, followed by ligation of the plasmid and genetic elements in accordance with the invention.
• transduction or other mechanism e.g., electroporation, microinjection, and the like
• plasmid transfer is utilized to transfer the plasmid into the host cell.
• Plasmids suitable for insertion of genetic elements into the host cell include, but are not limited to, pBR322, and its derivatives such as pAT153, pXf3, pBR325, pBr327, pUC vectors, pACYC and its derivatives, pSClOl and its derivatives, and CoIEl.
• cosmid vectors such as pLAFR3 are also suitable for the insertion of genetic elements into host cells.
• plasmid constructs include, but are not limited to, p2-47, pKDS.243A, pKD8.243B, and pSUaroZYl 57-27, which carry the aroZ and aroY loci isolated from Klebsiella pneumoniae, which respectively encode 3-dehydroshikimate dehydratase and protocatechuate decarboxylase.
• Additional examples of plasmid constructs include pKDS.292, which carries genetic fragments endogenous to Acinetobacter calcoaceticus catA, encoding catechol 1 ,2-dioxygenase.
• Methods for transforming a host cell can also include insertion of genes encoding for enzymes, which increase commitment of carbon into the common pathway of aromatic amino acid biosynthesis.
• the expression of a gene is primarily directed by its own promoter, although other genetic elements including optional expression control sequences such as repressors, and enhancers can be included to control expression or derepression of coding sequences for proteins, apoproteins, or antisense RNA.
• recombinant DNA constructs can be generated whereby the gene's natural promoter is replaced with an alternative promoter to increase expression of the gene product. Promoters can be either constitutive or inducible.
• a constitutive promoter controls transcription of a gene at a constant rate during the life of a cell, whereas an inducible promoter's activity fluctuates as determined by the presence (or absence) of a specific inducer.
• control sequences can be inserted into wild type host cells to promote overexpression of selected enzymes already encoded in the host cell genome, or alternatively can be used to control synthesis of extrachromosomally encoded enzymes.
• DHS is synthesized in the common pathway by the sequential catalytic activities of the tyrosine-sensitive isozyme of 3-deoxy-D-arabinoheptulosonic acid 7-phosphate (DAHP) synthase (encoded by aroF) and 3-dehydroquinate (DHQ) synthase (encoded by aroB) along with the pentose phosphate pathway enzyme transketolase (encoded by tkt).
• DAHP 3-deoxy-D-arabinoheptulosonic acid 7-phosphate
• DHQ 3-dehydroquinate
• DAHP synthase the first enzyme of the common pathway
• levels of DAHP synthase catalytic activity are reached beyond which no further improvements are achieved in the percentage of D-glucose that is committed to aromatic biosynthesis.
• amplification of the catalytic levels of the pentose phosphate pathway enzyme transketolase achieves sizable increases in the percentage of D-glucose siphoned into the pathway.
• one method for amplifying the catalytic activities of DAHP synthase, DHQ synthase and DHQ dehydratase is to overexpress the enzyme species by transforming the microbial catalyst with a recombinant DNA sequence encoding these enzymes.
• Amplified expression of DAHP synthase and transketolase can create a surge of carbon flow directed into the common pathway of aromatic amino acid biosynthesis, which is in excess of the normal carbon flow directed into this pathway. If the individual rates of conversion of substrate into product catalyzed by individual enzymes in the common aromatic amino acid pathway are less than the rate of DAHP synthesis, the substrates of these rate-limiting enzymes can accumulate intracellularly.
• DHQ synthase is an example of a rate-limiting common pathway enzyme. Amplified expression of DHQ synthase removes the rate-limiting character of this enzyme, and prevents the accumulation of DAHP and its nonphosphorylated analog, DAH. DHQ dehydratase is not rate-limiting.
• Escherichia coli expressing genes encoding DHS dehydratase, protocatechuate decarboxylase, and catechol 1,2-dioxygenase was constructed enabling the biocatalytic conversion of D-glucose to cis.cis-muconic acid. Efficient conversion of D-glucose to DHS was accomplished upon transformation of the host cell with pKD136. The strain E. coli AB2834/pKD136 was then transformed with plasmids pKD8.243A and pKDS.292. The result was E.
• E. coli AB2834/pKD136/pKDS.243A/pKDS.292 that expresses the enzymes 3-dehydroshikimate dehydratase (aroZ), protocatechuate decarboxylase (aroY) and catechol 1,2-dioxygenase (catA).
• This bacterial cell line was deposited with the American Type Culture Collection, 12301 Parklawn Drive, Rockville MD 20852, on Aug. 1, 1995 and assigned accession number 69875.
• E. coli AB2834/pKD 136 is transformed with plasmids p2-47 and pKD8.292 to generate E. coli AB2834/pKD136/p2-47/pKDS.292.
• E. coli AB2834/pKD136 is transformed with plasmids pKD8.243B and pKDS.292 to generate E. coli AB2834/pKD136/p2-47/pKDS.292.
• Each of these heterologous host cell lines catalyzes the conversion of D-glucose into cis,cis-muconic acid. Synthesized cis,cis-muconic acid accumulates extracellularly and can be separated from the cells. Subsequently, the cis.cis-muconic acid can be isomerized into cisjrans-muconic acid and further to trans,trans-muconic acid as desired.
• Some aspects to the invention thus relates to a transformant of a host cell having an endogenous common pathway of aromatic amino acid biosynthesis.
• the transformant is characterized by the constitutive expression of heterologous genes encoding 3-dehydroshikimate dehydratase, protocatechuate decarboxylase, and catechol 1,2-dioxygenase.
• the cell transformant is further transformed with expressible recombinant DNA sequences encoding the enzymes transketolase, DAHP synthase, and DHQ synthase.
• the host cell is selected from the group of mutant cell lines including mutations having a mutation in the common pathway of amino acid biosynthesis that blocks the conversion of 3-dehydroshikimate to chorismate.
• the genes encoding 3-dehydroshikimate dehydratase and protocatechuate decarboxylase are endogenous to Klebsiella pneumoniae.
• the heterologous genes encoding catechol 1,2-dioxygenase are endogenous to Acinetobacter calcoaceticus.
• the intermediates in the divergent pathway are protocatechuate, catechol, and Cis cis-muconic acid.
• the enzyme responsible for the biocatalytic conversion of DHS to protocatechuate is the enzyme 3-dehydroshikimate dehydratase, labeled "aroZ" in FIG. 1.
• the enzyme responsible for the decarboxylation of protocatechuate to form catechol is protocatechuate decarboxylase, labeled "aroY" in FIG. 1.
• the enzyme catalyzing the oxidation of catechol to produce cis.cis-muconic acid is catechol 1,2-dioxygenase, labeled "catA" in FIG. 1.
• host cells may exhibit constitutive expression of the genes aroZ, aroY, and catA.
• host cells may exhibit constitutive expression of any one or more of the genes aroZ, aroY and catA; or any combination of two thereof
• host cells may exhibit constitutive expression of none of aroZ, aro Y and catA.
• the enzymes 3-dehydroshikimate dehydratase and protocatechuate decarboxylase are recruited from the ortho cleavage pathways which enable microbes such as Neurospora, Aspergillus, Adnetobacter, Klebsiella, and Pseudomonas to use aromatics (benzoate and p-hydroxybenzoate) as well as hydroaromatics (shikimate and quinate) as sole sources of carbon for growth.
• DHS dehydratase plays a critical role in microbial catabolism of quinic and shikimic acid.
• Protocatechuate decarboxylase was formulated by Patel to catalyze the conversion of protocatechuate into catechol during catabolism of p-hydroxybenzoate by Klebsiella aerogenes. Reexamination of Patel's strain (now referred to as Enterobacter aerogenes) [(a) Grant, D. J. W.; Patel, J. C. Antonie van Leewenhoek 1969, 35, 325. (b) Grant, D. J. W. Antonie van Leewenhoek 1970, 36, 161] recently led Ornstonto conclude that protocatechuate decarboxylase was not metabolically significant in catabolism of p-hydroxybenzoate [Doten, R. C; Ornston, N. J. Bacteriol. 1987, 169, 5827].
• Compounds of interest comprising at least one carbon atom, such as muconic acid, dodecanedioic acid, dodecenedioic acid, 3-hexenedioic acid and derivatives thereof produced from renewable, biologically derived carbon sources will be composed of carbon from atmospheric carbon dioxide which has been incorporated by plants (e.g., from a carbon source such as glucose, sucrose, glycerin, or plant oils). Therefore, such compounds include renewable carbon rather than fossil fuel-based or petroleum-based carbon in their molecular structure.
• the biosourced dodecanedioic acid or products synthesized from dodecanedioic acid, and associated derivative products will have a smaller carbon footprint than dodecanedioic acid and associated products produced by conventional methods because they do not deplete fossil fuel or petroleum reserves and because they do not increase the amount of carbon in the carbon cycle (e.g., life cycle analysis shows no net carbon increase to the global carbon balance).
• the biosourced dodecanedioic acid and associated products as well as the starting compounds (such as muconic acid) or intermediate products (such as 3-hexenedioic acid) can be distinguished from products produced from a fossil fuel or petrochemical carbon source by methods known in the art, such as dual carbon-isotopic finger printing. This method can distinguish otherwise chemically-identical materials, and distinguishes carbon atoms in the material by source, that is biological versus non-biological, using the 14 C and 13 C isotope ratios.
• the carbon isotope 14 C is unstable, and has a half life of 5730 years.
• t (-5730/0.693)ln(A/Ao)
• a and A 0 are the specific 14 C activity of the sample and of the modern standard, respectively (Hsieh, Y., Soil ScL Soc. Am J., 56, 460, (1992)).
• 14 C has acquired a second, geochemical time characteristic. Its concentration in atmospheric CO 2 , and hence in the living biosphere, approximately doubled at the peak of nuclear testing, in the mid-1960s.
• f M is defined by National Institute of Standards and Technology (NIST) Standard Reference Materials (SRMs) 4990B and 4990C, known as oxalic acids standards HOxI and HOxII, respectively.
• SRMs Standard Reference Materials
• the fundamental definition relates to 0.95 times the 14 C/ 12 C isotope ratio HOxI (referenced to AD 1950).
• fM ⁇ 1.1.
• the ratio of the stable carbon isotopes 13 C and 12 C provides a complementary route to source discrimination and apportionment.
• the 13 C/ 12 C ratio in a given biosourced material is a consequence of the 13 C/ 12 C ratio in atmospheric carbon dioxide at the time the carbon dioxide is fixed and also reflects the precise metabolic pathway. Regional variations also occur. Petroleum, C 3 plants (the broadleaf), C 4 plants (the grasses), and marine carbonates all show significant differences in 13 C/ 12 C and the corresponding differences in the 13 C values, that is the ⁇ 13 C values.
• the 13 C measurement scale was originally defined by a zero set by pee dee belemnite (PDB) limestone, where values are given in parts per thousand deviations from this material. The values are in parts per thousand (per mil), abbreviated % 0 , and are calculated as follows:
• the major cause of differences in the carbon isotope ratio in plants is closely associated with differences in the pathway of photosynthetic carbon metabolism in the plants, particularly the reaction occurring during the primary carboxylation (e.g., the initial fixation of atmospheric CO 2 ).
• Two large classes of vegetation are those that incorporate the C 3 (or Calvin-Benson) photosynthetic cycle and those that incorporate the C 4 (or Hatch-Slack) photosynthetic cycle.
• C 3 plants, such as hardwoods and conifers, are dominant in the temperate climate zones.
• the primary CO 2 fixation or carboxylation reaction involves the enzyme ribulose-1,5-diphosphate carboxylase and the first stable product is a 3-carbon compound.
• C 4 plants include such plants as tropical grasses, corn and sugar cane.
• C 4 plants an additional carboxylation reaction involving another enzyme, phosphoenol-pyruvate carboxylase, is the primary carboxylation reaction.
• the first stable carbon compound is a 4-carbon acid, which is subsequently decarboxylated.
• the CO 2 thus released is refixed by the C 3 cycle.
• Both C 4 and C 3 plants exhibit a range of 13 C 12 C isotopic ratios, but typical values are ca. -10 to -14 per mil (C 4 ) and -21 to -26 per mil (C 3 ) (Weber et al, J. Agric. Food Chem., 45, 2942 (1997)). Coal and petroleum fall generally in this latter range.
• the biosourced muconic acid, the dodecanedioic acid and compositions including dodecanedioic acid of the invention can be distinguished from their ancient fossil-fuel and petrochemical derived counterparts on the basis of 14 C (fM) and dual carbon-isotopic fingerprinting, indicating new compositions of matter (e.g., U.S. Patent Nos. 7,169,588, 7,531,593, and 6,428,767).
• the ability to distinguish these products is beneficial in tracking these materials in commerce. For example, products comprising both new and old carbon isotope profiles can be distinguished from products made only of ancient materials.
• the biosourced dodecanedioic acid and derivative materials can be followed in commerce on the basis of their unique profile.
• a molecule or compound containing at least one carbon atom such as muconic acid or derivatives thereof, fatty acid or derivative thereof, 3- hexenedioic acid or derivatives thereof, dodecenedioic acid or derivatives thereof, dodecanedioic acid or derivatives thereof, dicarboxylic acids or derivatives thereof, polyamides or derivatives thereof, nylon or derivatives thereof can be described by their carbon isotope distribution (for example, 14 C, 13 C, or 12 C) or by their 14 C/ 12 C ratio. As each single carbon atom within compound comes from a naturally occurring carbon isotope, the source of carbon atoms will affect the carbon isotope distribution of the compound or the 14 C/ 12 C ratio.
• the carbon isotope distribution or 14 C/ 12 C ratio of a compound synthesized from petrochemical feedstock is distinguishable form the carbon isotope distribution or 14 C/ 12 C ratio of a compound produced from renewable carbon sources.
• the basic assumption is that the constancy of 14 C concentration in the atmosphere leads to the constancy of 14 C in living organisms whereas in inorganic carbon sources (such as petrochemical feedstock) all the 14 C has decayed.
• inorganic carbon sources such as petrochemical feedstock
• the 14 C/ 12 C ratio is measured using a ASTM test method D 6866-05 Determining the Biobased Content of Natural Range Materials Using Radiocarbon and Isotope Ratio Mass Spectrometry Analysis, incorporated by reference. Assessment of the renewably based carbon in a compound can be performed through standard test methods. Using radiocarbon and isotope ratio mass spectrometry analysis, the biobased content of materials can be determined. ASTM International, formally known as the American Society for Testing and Materials, has established a standard method for assessing the biobased content of materials. The ASTM method is designated ASTM-D6866. This test method measures the 14 C/ 12 C isotope ratio in a sample and compares it to the 14 C/ 12 C isotope ratio in a standard 100% biosourced material to give percent biosourced content of the sample.
• the compositions including biosourced dodecanedioic acid, dodecenedioic acid, 3-hexenedioic acid, polyamide can be distinguished from non-renewable corresponding compounds using a 14 C distribution or a 14 C/ 12 C ratio.
• the 14 C/ 12 C ratio is indicative of the fraction of carbon atoms coming from renewable carbon source.
• the starting materials for the production of dodecanedioic acid are muconic acid and ⁇ 9 unsaturated fatty acid such as oleic acid.
• muconic acid is produced from biologically derived carbon sources and the ⁇ 9 unsaturated fatty acid is derived from a vegetable or animal source.
• the resulting dodecanedioic acid product from cross metathesis reaction will therefore has a 14 C/ 12 C ratio indicative that all carbon atoms are coming from renewable carbon sources and no carbon atoms are coming from ancient carbon (e.g. carbon from coal, oil, or natural gas).
• Synthesis of compounds from starting materials coming from a renewable carbon source containing 14 C and from an ancient carbon source containing no radiocarbon will result in a decrease of the 14 C/ 12 C ratio when compared to a 14 C/ 12 C ratio of a compound comprised in whole from biosourced material.
• nylon 6, 12 results in the condensation of 1 ,6- hexamethylene diamine and dodecanedioic acid. If 1,6-hexamethylene diamine is produced from petrochemical feedstocks (e.g. from coal, oil, and natural gas) and doceanedioic acid is formed in whole from biosourced materials, two third of the carbon atoms content will come from renewable carbon source.
• the desired product's 14 C/ 12 C ratio is greater than 0, greater than 0.9x 10 -12
• the biosourced carbon content of a compound can be analyzed and a ratio of the amount of 14 C can be reported to that of a biosourced reference standard (percent of modern carbon).
• the carbon content of a biosourced product is 100%, at least 90%, at least 80%, at least 70%, at least 60%, at least 50%, at least 40%, at least 30%.
• the resulting products of the process contain a significant percentage of carbon derived from renewable resources. Such products are unique because the products contain a detectable trace or amount of carbon 14, and preferably up to about 1 part per trillion, as determined according to ASTM D6866- 08.
• the resulting products preferably contain 3 or greater carbons, more preferably 9 or greater carbons, more preferably 12 carbons or greater carbons derived from renewable resources, such as biomass, preferably by microbial synthesis.
• the resulting products are prepared from renewable resources prepared by microbial synthesis under fermentor-controlled conditions.
• the monomer units preferably contain 12 or greater carbons, derived from renewable resources, such as biomass.
• muconic acids are reduced to 3-hexenedioic acid.
• Cis cis-muconic acid and derivatives thereof produced biologically by a recombinant host cell culture are first reduced to 3-hexenedioic acid.
• 3- hexenedioic acid is used in a metathesis reaction to form desired compounds.
• General Formula 1 exemplifying muconic acids and muconic acid derivatives within the scope of the present invention is provided below.
• Ri-R 6 typically are independently selected from aliphatic, substituted aliphatic, alkoxy, amino, amines, substituted amines, protected amines, aryl, substituted aryl, arylalkyl, substituted arylalkyl, carbonyl-containing moieties (such as aldehydes, amides, carboxylic acids, esters, ketones and thioesters), cyclic, substituted cyclic, ethers, substituted ethers, halide, heteroaryl, substituted heteroaryl, heterocyclic, substituted heterocyclic, hydrogen, hydroxyl, hydroxylamine, and nitrogen-containing moieties, such as nitrile (RCN), nitro (NO 2 ) and nitroso (RNO).
• RCN nitrile
• NO 2 nitro
• RNO nitroso
• Ri-R 6 are independently selected from aliphatic, typically lower aliphatic, and even more preferably lower alkyl, and hydrogen. Ri and R 6 are most typically independently hydrogen or lower alkyl. R 2 -R 5 are most typically hydrogen.
• Formula 1, and certain other structural formulas provided herein, includes bonds indicated by a wavy, as opposed to a straight line, to indicate that all possible stereoisomers are included in that particular general formula.
• the primary derivatives made from muconic acids are (1) conjugate bases, (2) various stereoisomers produced by an isomerization reaction of a parent compound, and/or (3) compounds formed by transforming one or more carboxylic acid functional groups to another functional group.
• cis,cis-muconic acid can be isomerized to trans,trans-muconic acid by dissolving Cis cis-muconic acid in methanol along with traces of iodine and exposing the reaction mixture to light.
• the methane solubilities of cis,cis-mxxcom ' c acid and trans, trans-mucomc acid differ substantially.
• trans, trans-mucomc acid precipitates from solution as it forms.
• the Cis cis-muconic acid can be isomerized to cisjrans- muconic acid using methods known in the art.
• cis, trans- mucomc acid is more soluble in both organic solvent and aqueous media than either of the cis, cis- or trans, trans- isomers
• cisjrans-muconic acid is an advantageous starting compound allowing easy processing and recovery.
• the method includes culturing recombinant cells that express 3-dehydroshikimate dehydratase, protocatechuate decarboxylase and catechol 1,2- dioxygenase in a medium comprising a renewable carbon source and under conditions in which such renewable carbon source is converted to DHS by enzymes found in the common pathway of aromatic amino acid biosynthesis of the cell, and the resulting DHS is biocatalytically converted to cis.cis-mucor ⁇ c acid.
• the fermentation broth is provided in a vessel such as a fermenter vessel and the isomerization reaction may be carried out in the vessel.
• the production of Cis cis-muconic acid by the fermentation of the renewable carbon source can produce a broth comprising the recombinant cells and extracellular cis,c is-muconic acid.
• the production can also include the step of separating the recombinant cells, cell debris, insoluble proteins and other undesired solids from the broth to give a clarified fermentation broth containing substantially all, or most of, the cis,cis-mucox ⁇ c acid formed by the fermentation.
• muconic acid After muconic acid has been produced it may accumulate in the extracellular medium (e.g. fermentation broth) and can be separated from the cells by centrifugation, filtration, or other methods known in the art.
• cic, cis-muconic acid is first isomerized to cis,trans-muconic acid and which is then separated from the fermentation broth or cell free fermentation broth by precipitation, extraction, filtration, or other methods known in the art
• the carboxylic acid functional group of the muconic acid is converted to various different functional groups that facilitate the cycloaddition reaction.
• This conversion promotes desired physical properties of compounds made by the cycloaddition reaction, or derivatives or polymers made therefrom using the compounds produced by cycloaddition as monomers, or both.
• Exemplary carboxylic acid functional group transformations include forming an acid halide, such as an acid chloride, using suitable reagents known to a person of ordinary skill in the art, such as thionyl chloride, phosphorous pentachloride or pentbromide.
• the carboxylic acid functional group of the muconic acid also can be converted to an ester, such a methyl or ethyl ester.
• esters particularly lower alkyl esters
• methods for forming esters, particularly lower alkyl esters include: the alcohol/H* protocol, such as using methanol or ethanol and catalytic sulfuric acid to form the corresponding methyl and ethyl esters, which is convenient to execute, but may be accompanied by double bond isomerization; methylation with diazomethane to form the methyl ester; or treating the acid with an alkyl iodide, such as MeI/ Et 4 NOH, in a dark protocol.
• a dimethyl ester derivative is obtained starting from cis,cis-rmiconic acid and using dimethyl sulfate and potassium carbonate.
• Table 1 provides a partial list of exemplary muconic acids and lower alkyl muconic acid esters, particularly methyl and ethyl muconic acid esters, as well as their melting points and solvents useful for purification by recrystallization.
• Scheme 1 illustrates one embodiment of a method for reducing muconic acid, or a muconic acid derivative, to 3-hexenedioic acid, or a derivative thereof, such as a mono- or diester.
• the muconic acid diene can be reduced to 3-hexenedioic acid using a zinc halide reagent in a suitable solvent, such as pyridine.
• a suitable solvent such as pyridine.
• olefin refers to is an unsaturated chemical compound containing at least one carbon-to-carbon double bond.
• the simplest olefin with only one double bond and no other functional groups form a homologous series of hydrocarbons with the general formula C n H 2n .
• the term "lower olefin” refers to an organic compound having less than about 10 carbon atoms and containing at least one carbon-carbon double bond. Lower olefin may have one, two or more unsaturated bonds. Preferably, the lower olefin has a single unsaturated bond.
• Lower olefins may be substituted at any position along the carbon chain with one or more substituents, provided that the one or more substituents are substantially inert with respect to the metathesis reaction.
• Suitable substituents include, but are not limited to alkyl, preferably methyl, as well as hydroxy, ether, keto, and aldehyde.
• Olefin metathesis is an important reaction used in organic synthesis. Olefin metathesis is also known as transalkylidenation organic reaction and entails cleavage of alkene double bond followed by redistribution of alkylene fragments. The reaction was developed by Yves Chauvin, Richard R. Schrock and Robert H. Grubbs, who shared a Nobel Prize in Chemistry in 2005. Olefin metathesis reactions proceed in the presence of a catalytically effective amount of metathesis catalyst.
• Exemplary metathesis catalysts include metal carbene catalysts based upon catalytic transition metals, such as ruthenium, nickel, tungsten, osmium, chromium, rhenium, and molybdenum.
• Metathesis catalysts which can be employed in the process according to the invention, are all metathesis catalysts which are known to the person skilled in the art and which are suitable for metathesis reactions, or a mixture of at least two catalysts.
• the olefin metathesis reaction uses first generation Grubbs catalysts, variant or derivative of the first generation Grubbs-type catalyst.
• the olefin metathesis reaction uses second generation Grubbs catalysts, variant or derivative of the Grubbs-type catalyst.
• Grubbs catalysts include but are not limited to, benzylidene-bis(tricyclohexylphosphine)dichlororuthenium and benzylidene[1,3- bis(2,4,6-trimethylphenyl)-2- imidazolidinylidene]dichloro(tricyclohexylphosphine)ruthenium.
• Schrock catalysts or a variant or derivative of the Schrock catalysts are used as catalysts for the metathesis reactions.
• the catalyst is a Hoveyda-Grubbs catalyst or variant of the Hoveyda-Grubbs catalyst.
• At least one metathesis catalyst selected from carbene or carbyne complexes or a mixture of these complexes is employed.
• the term "complex” as used herein refers to a metal atom with at least one ligand or complexing agent bound thereto. Metathesis catalysts are used using techniques known to those skilled in the art.
• 3-hexenedioic acids, or derivatives thereof, such as their lower alkyl esters may be reacted with an unsaturated dicarboxylic acid, particularly a ⁇ 9 dicarboxylic fatty acid, in the presence of a metathesis catalyst to produce dodecenedioic acid.
• an unsaturated dicarboxylic acid particularly a ⁇ 9 dicarboxylic fatty acid
• a metathesis catalyst to produce dodecenedioic acid.
• any suitably unsaturated fatty acid can be suitably employed in the process of this invention.
• the alkene chain of the unsaturated fatty acid may be a linear or branched and may optionally include one or more functional groups in addition to the carboxylic acid group.
• some carboxylic acids include one or more hydroxy 1 groups.
• the alkene chain typically contains about 4 to about 30 carbon atoms, more typically about 4 to about 22 carbon atoms. In many embodiments, the alkene chain contains 18 carbon atoms (i.e., a Cl 8 fatty acid).
• the unsaturated fatty acids have at least one carbon-carbon double bond in the alkene chain (i.e., a monounsaturated fatty acid), and may have more than one double bond (i.e., a polyunsaturated fatty acid) in the alkene chain.
• the unsaturated fatty acid is a ⁇ 9 unsaturated fatty acid.
• ⁇ 9 unsaturated fatty acids have a carbon-carbon double bond located between the C9 and ClO in the alkene chain of the unsaturated fatty acid. In determining this position, the alkene chain is numbered beginning with the carbon atom in the carbonyl group of the unsaturated fatty acid.
• the ⁇ 9 unsaturated starting materials have a straight alkene chain.
• suitable ⁇ 9 unsaturated fatty acids include myristoleic acid, palmitoleic acid, , elaidic acid, and oleic acid, each of which has a C9-C10 unsaturated bon ( ⁇ 9 olefin).
• useful ⁇ 9 unsaturated fatty acids are derived from natural oils such as plant-based oil or animal fats.
• Representative examples of renewable plant based oils include olive oil, peanut oil, grape seed oil, sea buckthorn oil, and sesame oil, poppyseed oil, nutmeg butter, palm oil, coconut oil, Macadamia oil, Sea Buckthorn oil.
• animal fats include lard and tallow fats.
• Unsaturated fatty acids can be obtained commercially or synthesized by saponification of fatty acid esters using methods known to those skilled in the art.
• dodecenedioic acid or derivative thereof e.g. (Z)- dimethyldodecenedioic acid
• a cross-metathesis reaction using a metathesis catalyst as shown in Fig. 2.
• oleic acid is converted to dimethyl octadecenedioate in a two-step synthesis process as described inNgo and Foglia (JAOCS, 1985, 84:777-784).
• oleic acid is placed in presence of a metathesis catalyst to form dimethyl 9- octadecenedioate.
• Octadecenedioic acid can then be purified using techniques known in the art.
• the starting materials include dimethyl-hexenedioate and dimethyl-octadecenedioate.
• dimethyl-dodecenedioate After the cross metathesis reaction of dimethyl-hexenedioate in presence of dimethyl-octadecenedioate, dimethyl-dodecenedioate is formed.
• the dodecenedioic acid can be converted into dodecanedioic acid by hydrogenation to saturate the olefin.
• dimethyl dodecenedioate is reduced to form dimethyl dodecanedioate.
• biosourced dimethyl-hexenedioate is produced by reduction of muconic acid derivatives.
• the resulting product from the metathesis reaction is a composition comprising a biosourced dimethyl dodecanedioate compound.
• Metathesis reactions are conducted under appropriate conditions to produce the desired metathesis product(s).
• metathesis reactions may be performed under an inert atmosphere.
• the inert atmosphere is an inert gas that does not interfere with the metathesis catalyst.
• inert gases include, but are not limited to, nitrogen, argon, neon, helium and combination thereof.
• the metathesis reactions are processed under any desired pressure.
• the metathesis reactions are conducted in an inert solvent that does not impede catalysis.
• inert solvent include, but are not limited to, aromatic hydrocarbon such as benzene or toluene, halogenated aromatic hydrocarbons, aliphatic hydrocarbons such as methanol.
• a solvent may be desirable where the reactants are not entirely miscible and both can be solubilized in a suitable solvent.
• the solvent is thermally stable, and does not decompose at the process temperature.
• metathesis reactions proceed in a solvent-free reaction.
• the metathesis reactions are performed at a temperature selected to form the desired product(s) and lower the formation of undesired products.
• the temperature is above O°C, above 2O°C, above 4O°C, above 5O°C.
• the metathesis temperature reaction is from about 2O°C to about 100°C.
• the process temperature may be about 45°C or about 50°C.
• the amount of catalyst used in the metathesis reaction is selected to form the desired product and lower the formation of undesired products.
• the molar ratio of the dioic acid to the catalyst may rage from 5:l to 20:1 or to 100:1 or to 1,000:1, or to 100,000: 1.
• the reaction time is about 1 hour, about 2 hours, about 4 hours, about 5 hours, about 10 hours, about 15 hours or longer.
• Useful techniques to separate and purify the desired product(s) from starting material or other undesired product(s) include, but are not limited to, distillation, chromatography, fractional crystallization, liquid/liquid extraction, or any combination thereof.
• the desired products are purified to a high degree, for example to 90% or greater.
• the conversion can be checked by gas chromatography-mass spectrometry.
• filtrate of the reaction mixture cross metathesis of dimethyl hexenedioate and dimethyl octadecenedioates and subsequent hydrogenation
• gas chromatography-mass spectrometry can be checked by gas chromatography-mass spectrometry and compared with standard dimethyl dodecanedioates calibration curve.
• oleic acid, octadoc-9-enedioic acid and the 3-hexenedioic acid are symmetric molecules with respect to the carboxylic or ester terminal groups and therefore self metathesis reactions of the oleic acid or cross metathesis of the octadoc-9-enedioic acid and the 3-hexenedioic acid will result, theoretically, in the formation of fewer products than if an asymmetric molecule was used.
• cross metathesis reaction of 3-hexenedioic acid with dimethyl octadoc-9-enedioic acid will form theoretically only dimethyl dodecenedioic acid.
• Whether a cis isomer or trans isomer is formed in this type of reaction is determined by the orientation the molecules assume when they coordinate to the catalyst, as well as the sterics of the substituents on the carbon-carbon double bond of the newly forming molecule. [0098] If the metathesis catalyst used for metathesis processes promotes double bond migration, that is, if the metathesis catalyst causes the double bond to move from its original position in the unsaturated fatty acid to a position either closer to, or further from, the carboxylic acid function, the metathesis reaction will produce a mixture of dicarboxylic acid products.
• reaction conditions are modified to prevent double bond migration.
• the ratio of lower olefin to unsaturated fatty acid or derivative thereof is selected to prevent double-bond migration.
• the dimethyl hexenedioic acid is added in excess of the dimethyl octadecendioic acid.
• the molar ratio of reactants dimethyl hexenedioate/ dimethyl octadecenedioate can be 2:1, 3:1, 4:1 or greater.
• an acidic additive is added to inhibit double bond migration and undesired product formation. Examples of acidic additive include, but are not limited to, benzoic acid and salts, phosphoric acid and salts.
• compositions comprising a dodecenedioic acid or dodecenedioic acid derivative and at least one unsaturated dicarboxylic acid or unsaturated dicarboxylic acid derivative byproduct derived from the dodecenedioic acid or dodecenedioic acid derivative .
• the composition comprises at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9 byproducts derived from the dodecenedioic acid or dodecenedioic acid derivative.
• the at least one unsaturated dicarboxylic acid or unsaturated dicarboxylic acid derivative byproduct comprises an alkene chain having from about 7 to about 16 carbon atoms.
• the compositions comprises at least 9 byproducts derived from the dodecenedioic acid or dodecenedioic acid derivative, the byproducts comprising an alkene chain having from about 7 to about 16 carbon atoms.
• the dodecenedioic acid derivative is a dodecenedioic acid diester.
• the alkene chain comprises a carbon double bond in a position of C3-C4.
• compositions comprising 9-octadecenedioic acid or 9-octadecenedioic acid derivative and at least one octadecenedioic acid or octadecenedioic acid derivative byproduct derived from 9-octadecenedioic acid or 9-octadecenedioic acid derivative.
• the composition comprises at least 1, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 15, at least 16 byproducts derived from 9- octadecenedioic acid or 9-octadecenedioic acid derivative.
• the octadecenedioic acid or octadecenedioic acid derivative byproducts comprise a carbon double bond in position.
• a "polyamide” is a polymer containing amide monomers joined by amide bonds that are produced by reacting an amine and a carboxylic acid or derivative thereof.
• industrial polyamides have many uses, including aramids, nylons, and polyaspartates.
• Aramid (pictured below) is an aromatic polyamide that is made by polymerizing terephthalic acid or a derivative thereof, such as terephthaloyl chloride, and a diamine, such as 1 ,4- phenyldiamine (para-phenylenediamine).
• Nylon is a generic designation for a family of synthetic thermoplastic polyamides that are used to make fabrics, musical strings, rope, screws and gears, to name just a few examples.
• Nylon is available with fillers too, such as glass- and molybdenum sulfide-filled variants.
• Nylon 6 is the most common commercial grade of molded nylon. The numerical suffix specifies the numbers of carbon atoms donated by the monomers; the diamine first and the diacid second.
• the diamine typically is hexamethylenediamine and the diacid is adipic acid. Each of these monomers donates 6 carbons to the polymer chain.
• Another example of a useful nylon is nylon 6,12, which has a glass transition temperature of 46 °C, and a molecular weight of repeat units of 310.48 g/mol. The structural formula of nylon 6,12 is as shown below.
• One method for making nylon 6, 12 comprises forming a polycondensation product of
• nylon 6,12 can be prepared by combining decanedioic and an aqueous 1,6-hexane diamine solution in water with stirring in an autoclave for 30 minutes at 90 °C such that a 55 % by weight salt solution is obtained.
• Water is removed by distillation by first raising the temperature in 10 minutes to 180 °C, removing half of the amount of water through distillation and then raising the temperature to 200 °C and removing an amount of water through distillation such as to obtain a 90 % by weight aqueous salt solution.
• the reactor is completely closed, the distillation is stopped and the temperature is raised to 227 °C and prepolymerization begins.
• the water present and the high temperature cause the pressure to rise slowly .
• the pressure at the end of the prepolymerization is about 12x105 Pa.
• the prepolymerization is performed during 1/2 hour at a constant temperature, after which the content of the autoclave is flashed in a nitrogen atmosphere.
• the prepolymer is cooled in a nitrogen atmosphere.
• the prepolymer granules obtained are sieved so that the fraction having a diameter of between 1 and 2 mm is obtained.
• This fraction is introduced into either a static bed (capacity approximately 50 g of solid substance) or a tumble dryer (capacity approximately 10 liters) and postcondensed at an elevated temperature (about 25 °C below the polymer's melting point) in a nitrogen/water vapor (75/25 % by volume) atmosphere for 24 hours. Then the polymer granules were cooled to room temperature. From the polymer thus prepared a number of rods and plates were injection-molded.

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