AND POLYAMIDES THEREFROM

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and the benefit of U.S. Provisional Application No. 61/473,753, filed April 9, 2011, U.S. Provisional Application No. 61/473,754, filed April 9, 2011, and U.S. Patent Application No. 13/442,306, filed on April 9, 2012, each of which is incorporated herein by reference in its entirety.

FIELD OF THE INVENTION

[0002] The present invention provides improved processes for the preparation of hexamethylenediamine (HMDA) from muconate diester and novel intermediates made in these processes. The described processes also enable HMDA to be made from renewable biomass.

BACKGROUND OF THE INVENTION

[0003] Hexamethylenediamine (HMDA) is an important industrial chemical that has a wide range of applications, especially in the area of making polymers, such as nylon-6,6. Methods available for making HMDA are well known in the literature (see U.S. Patent Nos. 3,152,186 and 3,398,195). In general, the industrial process for making HMDA involves first converting material derived from petroleum feedstock, i.e., cyclohexanone 2, to adipic acid 3, followed by reductive amination of adipic acid to adiponitrile 4 using a dehydrating agent such as H ₃ P04/silica, and subsequent hydrogenation of the resulting adiponitrile to HMDA 1. Scheme 1 below illustrates this industrial process.

Petro-chemical

Feedstock

cyclohexanone adipic acid

2 3

Scheme 1 [0004] In Scheme 1 the conversion of adipic acid 3 to adiponitrile 4 is problematic due to adiponitrile's labile nature and high reactivity. As such, many attempts have been made to improve the yield of adiponitrile. Some examples of this effort involve reacting the adipic acid 3 with ammonia at elevated temperatures in the gas phase over a bed of heterogeneous dehydrating catalysts as a way to minimize the residence time of adiponitrile in the reaction. For example, a process described in U.S. Patent No. 3,607,906 generated adiponitrile 4 with good yield by having adipic acid and ammonia react in a trickle bed reactor over a bed of silica/phosphoric acid (18%) catalyst at 320°C. Other processes described in U.S. Patent Nos. 3,629,316; 3,393,222; 4,599,202; and 3,671,566 disclose similar approaches to the synthesis of adiponitrile 4 from adipic acid 3.

[0005] The reduction of adiponitrile 4 to HMDA 1 is facile and well established in the literature. U.S. Patent Nos. 3, 152, 186 and 3,398,195 describe continuous processes for making HMDA by mixing adiponitrile with a large excess of ammonia and hydrogen, and passing the mixture over a bed of catalyst usually composed of copper, nickel, cobalt, zinc, or palladium.

[0006] However, all industrial processes available to date involve using petroleum-derived chemicals or petrochemicals as a starting material. Because of the reliance of these processes on non-renewable petroleum, there is an urgent need to find processes for making chemicals from renewable sources such as biomass, as a way to reduce mankind's dependence on crude oil, to increase the use of renewable energy sources, and to reduce air and water pollution from the petrochemical industry.

[0007] Although making HMDA from a feedstock derived from renewable biomass for environmental and commercial reasons is highly desirable, until now it has not been possible. Clearly, it would be advantageous to have a better process to make HMDA, with higher yield, with fewer by-products, and from a feedstock derived from renewable biomass.

BRIEF SUMMARY OF THE INVENTION

[0008] The present invention, in one aspect, provides novel processes using carbon atoms derived from renewable biomass to make hexamethylenediamine. The renewable biomass can contain detectable ¹⁴ C content determined according to ASTM D6866 and optionally can contain a ¹⁴ C content up to 0.0000000001% (one part per trillion). In some embodiments, the present invention provides a process for preparing hexamethylenediamine (HMDA, 1) of the formula:

HMDA

1

which includes reacting one or more of the three double-bond isomers of muconate diester (e.g., dimethyl muconate (Q, g-DMM), structure as shown below in Structure Scheme 2), structures 5a, 5b, and 5c, to form one or more of the three double-bond isomers of

muconamide (Q,Q-MCA), structure as shown below in Structure Scheme 2, structures 6a, 6b and 6c. The Q,Q-MCA can then be either directly converted to HMDA, or be subject to dehydration to form one or more double-bond isomers of the intermediate mucononitrile (Q,Q- MN), structure as shown below in Structure Scheme 2, structures 7a, 7b and 7c. The Q,Q-MN can then be hydrogenated to yield HMDA 1. The muconate diester starting material (e.g., Q,Q-OMM) can be derived from muconic acid, which itself has been derived from renewable biomass sources containing up to 1 part per trillion of ¹⁴ C.

Structure Scheme 2

c/s,c/ ^' s-DMM 5a cis,trans-DMM 5b trans,trans-D MM 5c cis, cis-, cis, trans-, and trans,trans- double-bond isomers of DMM 5a-c (Qg-DMM)

H ₂ NOC /=\ CONH,

CONH ₂

CONH ₂ ^H 2 ^N °C =* H ₂ NOC

cis, c/s-MCA 6a cis,trans-MCA 6b trans,trans-MCA 6c cis,cis-, cis,trans-, and trans,trcins- double-bond isomers of MCA 6a-c (β,β-MCA)

j _C/ s-MN 7a cis,trans-MN 7b trans,trans-MN 7c cis, cis-, cis, trans-, and trans, trans- double-bond isomers of MN 7a-c (β,β-ΜΝ)

[0009] The present invention, in another aspect, provides a process for the preparation of HMDA 1. The process includes reacting muconate diester (e.g., Q,Q-OMM) with one or more reagents which provide for one or more of amidation, dehydration, reduction, and hydrogenation, and obtaining HMDA therefrom. In various embodiments, the muconate diester (e.g, Q,Q-OMM) contains detectable ¹⁴ C content determined according to ASTM D6866. In some embodiments, the muconate diester (e.g, Q,Q-OMM) contains a ¹⁴ C content up to 0.0000000001% (one part per trillion). The muconate diester (e.g., ββ-DMM) can be prepared from biomass-derived muconic acid (MA). The biomass-derived MA can contain detectable ¹⁴ C content determined according to ASTM D6866. In some embodiments, the biomass-derived MA contains a ¹⁴ C content up to 0.0000000001% (one part per trillion). The biomass-derived MA can be prepared into muconate diester (e.g., Q,Q-OMM) using any methods known in the art (e.g., alkyl esterification such as methyl esterification). Some examples of preparing Q,Q-OMM from MA are illustrated in Starting Materials, Examples A through G. The Q,Q-OMM can then be prepared into HMDA via any of the following routes, or combinations, variations and modifications thereof.

[0010] Route 1 (2 steps) includes: (1) ami dating one or more of cis,cis-, cis, trans-, and trans, trans- muconate diester (e.g., Q,Q-OMM 5a-5c) to one or more of cis, cis-, cis, trans- and trans, trans -muconamide (β,β-MCA, 6a-6c); and (2) reducing the Q,Q-MCA 6a-6c to HMDA 1 by reacting with ¾ gas and ¾ gas in the presence of a reduction catalyst and an aprotic polar solvent. In some embodiments, Route 1 step(2) is carried out at a total gas pressure from about 300 to about 3,000 psi, at a temperature from about 150 to about 350°C.

[0011] In certain embodiments, Route 1, step (1) includes: (a) forming the cis,cis-MCA or cis, trans-MCA in aq. Ν¾, either (i) at a temperature from about 20 to about 25°C, or (ii) at a temperature of about 70 to about 100°C; or (b) forming the trans, trans-MCA in aq. ¾ and an alcohol, at a temperature from about 20 to about 25°C. In some embodiments, Route 1, step (l)(a)(i) can take about 1 to 10 days, 2 to 8 days, or about 4 days. Route 1, step (l)(a)(ii) can take from about 1 to about 48 hours, 4 to 30 hours, 4 to 20 hours, or about 20 hours. In Route 1, step (l)(b) a ratio of the aq. NH ₃ to the alcohol can be about 1 : 1. In Route 1, step (l)(b) the alcohol can be methanol, ethanol or any other suitable organic solvent. In Route 1, step (l)(b) can take about 5 to 20 days, about 10 to 16 days, or about 14 days.

[0012] In some embodiments, in Route 1, step (2) the reduction catalyst can be about 15- 99 mol%, about 20-50 mol%, or about 22 mol% of 2CuO-Cr ₂ 0 ₃ . The aprotic polar solvent can be tetrahydrofuran or dioxane, or any suitable aprotic polar solvent. In certain embodiments, Route 1, step (2) takes about 1 to 10 hours, about 2 to 5 hours, or about 3 hours. The temperature in Route 1, step (2) can be from about 100 to about 500°C, from about 150 to about 350°C, from about 200 to about 300°C, or about 250°C. In some embodiments, Route 1 step (2) is conducted at about 150-350°C for about 3 hours to yield HMDA 1. [0013] Route 2 (3 steps) includes: (1) amidating one or more of cis,cis-, cis, trans- and trans, trans- muconate diester (e.g., Q,Q-OMM 5a-5c) to one or more of cis, cis-, cis, trans- and trans, trans -muconamide (Q,Q-MCA, 6a-6c); (2) dehydrating the Q,Q-MCA 6a-6c to one or more of cis,cis-, cis, trans- and trans, iraws-mucononitrile (Q,Q-MN, 7a-7c) using a dehydrating agent; and (3) hydrogenating the Q,Q-MN 7a-7c to HMDA 1, using H ₂ gas in the presence of a hydrogenation catalyst and a solvent. In some embodiments, Route 2 step (3) is carried out at a pressure of about 300 to about 1,500 psi.

[0014] In certain embodiments, Route 2, step (1) includes: (a) forming the cis,cis-MCA or cis, trans-MCA in aq. Ν¾, either (i) at a temperature from about 20 to about 25°C, or (ii) at a temperature of about 70 to about 100°C; or (b) forming the trans, trans-MCA in aq. ¾ and an alcohol, at a temperature from about 20 to about 25°C. In some embodiments, Route 2, step (l)(a)(i) can take about 1 to 10 days, 2 to 8 days, or about 4 days. Route 2, step (l)(a)(ii) can take from about 1 to about 48 hours, 4 to 30 hours, 4 to 20 hours, or about 20 hours. In Route 2, step (l)(b) a ratio of the aq. NH ₃ to the alcohol can be about 1 : 1. In Route 2, step (l)(b), the alcohol can be methanol, ethanol or any other suitable organic solvent. Step (l)(b) can take about 5 to 20 days, about 10 to 16 days, or about 14 days.

[0015] In some embodiments, in Route 2, step (2) the dehydrating agent can be P2O5, POCI ₃ or PdC¾. For example, the dehydrating agent can be PdC¾ in a solvent that is a mixture of water and acetonitrile. Route 2, step (3) can include using a mixture of H ₂ gas and NH ₃ gas at a total pressure from about 300 to about 1,500 psi, about 500 to about 1500 psi, about 500 to about 1,200 psi, or about 1,000 psi. In certain embodiments, in Route 2, step (3) the hydrogenation catalyst can be Raney Ni. Any suitable hydrogenation catalyst may be used in Route 2, step (3). In some embodiments, in Route 2, step (3) the solvent can be

tetrahydrofuran. Any suitable solvent may be used in Route 2, step (3). Route 2, step (3) can be carried out at a temperature of about 80 to about 150°C, about 100 to about 120°C, or about 1 10°C. In some variations, Route 2, step (3) is carried under a total pressure of about 500 to about 1500 psi and a temperature of about 1 10°C for about 3 hours to yield HMDA 1.

[0016] Route 3 (4 steps) includes: (1) amidating one or more of cis,cis-, cis, trans- and trans, trans- muconate diester (e.g., Q,Q-OMM) to one or more of cis, cis-, cis, trans- and trans, trans -muconamide (Q,Q-MCA, 6a-6c); (2) hydrogenating the Q,Q-MCA 6a-6c to adipamide 8, using H ₂ gas in the presence of a first hydrogenation catalyst; (3) dehydrating the adipamide 8 to adiponitrile 4 using a dehydrating agent; and (4) hydrogenating the adiponitrile 4 to HMDA 1, using ¾ gas in the presence of a second hydrogenation catalyst and a solvent. In some embodiments, Route 3 step (2) is carried out using H ₂ gas at a pressure from about 300 to 2000 psi, at a temperature from about 25 to about 100°C. In some embodiments, Route 3 step (4) is carried out using H ₂ gas at a pressure from about 100 to about 800 psi.

[0017] In certain embodiments, Route 3, step (1) includes: (a) forming the cis,cis-MCA or cis, trans-MCA in aq. NH ₃ , either (i) at a temperature from about 20 to about 25°C, or (ii) at a temperature of about 70 to about 100°C; or (b) forming the trans, trans-MCA in aq. NH ₃ and an alcohol, at a temperature from about 20 to about 25°C. In some embodiments, Route 3, step (l)(a)(i) can take about 1 to 10 days, 2 to 8 days, or about 4 days. Route 3, step (l)(a)(ii) can take from about 1 to about 48 hours, 4 to 30 hours, 4 to 20 hours, or about 20 hours. In Route 3, step (l)(b) a ratio of the aq. NH ₃ to the alcohol can be about 1 : 1. In Route 3, step (l)(b), the alcohol can be methanol, ethanol or any other suitable organic solvent. Step (l)(b) can take about 5 to 20 days, about 10 to 16 days, or about 14 days.

[0018] In some embodiments, in Route 3, step (2) the first hydrogenation catalyst can be a Pd/C catalyst. In Route 3, step (2), any suitable hydrogenation catalyst may be used. In Route 3, step (3) the dehydrating agent can be PdCl ₂ , P2O5 or POCl ₃ . For example, the dehydrating agent can be PdC¾ in a solvent that is a mixture of water and acetonitrile. In certain embodiments, in Route 3, step (4) the second hydrogenation catalyst can be Raney Ni. In Route 3, step (4), any suitable hydrogenation catalyst may be used. The solvent in Route 3, step (4) can be tetrahydrofuran or w-butanol, or any suitable solvent.

[0019] Another aspect of the present invention relates to a process for preparing one or more of cis, cis-, cis, trans- and trans, iraws-muconamide (Qg-MCA). The process includes amidating one or more of cis,cis-, cis, trans- and trans,trans- muconate diester (e.g., Q,Q- DMM) to Q,Q-MCA. The amidating includes (a) forming the cis,cis-MCA or cis, trans-MCA in aq. NH ₃ , either (i) at a temperature from about 20 to about 25°C, or (ii) at a temperature of about 70 to about 100°C; or (b) forming the trans, trans -MCA in aq. NH ₃ and an alcohol, at a temperature from about 20 to about 25°C. In some embodiments, step (a)(i) can take about 1 to 10 days, 2 to 8 days, or about 4 days. Step (a)(ii) can take from about 1 to about 48 hours, 4 to 30 hours, 4 to 20 hours, or about 20 hours. In step (b), a ratio of the aq. NH ₃ to the alcohol can be about 1 : 1. In step (b), the alcohol can be methanol, ethanol or any other suitable organic solvent. Step (b) can take about 5 to 20 days, about 10 to 16 days, or about 14 days.

[0020] The present invention, in another aspect, also provides a compound derived from biomass. The compound contains detectable ¹⁴ C content determined according to ASTM D6866. Such compound is selected from the group consisting of: trans, iraws-muconamide, cis, iraws-muconamide, czs,czs -muconamide, trans, trans-vauc n mtnlQ, cis rans- mucononitrile, czs,czs -mucononitrile, adipamide, and adiponitrile. In various embodiments, the compound can contain up to 0.0000000001% ¹⁴ C.

[0021] Further aspects of the present invention relate to a process for preparing polyamides and copolymers thereof, and polyamides and copolymers thereof prepared therefrom. The process includes reacting hexamethylenediamine (HMD A) with one or more compounds having at least two amide-forming groups, wherein the HMDA is prepared from a biomass-derived muconate diester and contains a detectable amount of ¹⁴ C determined according to ASTM D6866. In some embodiments, the process can further include: reacting one or more of cis,cis-, cis, trans- and trans, trans- muconate diester containing carbon atoms derived from a renewable biomass with one or more reagents which provide for one or more of amidation, dehydration, reduction, and hydrogenation, wherein the renewable biomass contains detectable ¹⁴ C content determined according to ASTM D6866; and obtaining HMDA therefrom. In some examples, the muconate diester is dimethyl muconate. In various embodiments, the HMDA can contain up to 0.0000000001% ¹⁴ C. In some instances, the compound having at least two amide-forming groups comprises one or more of aliphatic or aromatic dicarboxylic acids, or salts or halides or esters thereof. The polyamides and copolymers thereof prepared according to any one of these processes is also included in the present invention. Such polyamides and copolymers thereof can contain a detectable amount of ¹⁴ C determined according to ASTM D6866, e.g., up to 0.0000000001% ¹⁴ C.

ABBREVIATIONS AND DEFINITIONS

[0022] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Reference is made here to a number of terms that shall be defined to have the following meanings.

[0023] AHN means 6-aminohexanenitrile.

[0024] "Alcohol" as used herein means an alcohol that comprises a C _1-20 alkyl moiety substituted at one, two or more hydrogen atoms with one, two or more hydroxyl groups.

Alcohols include methanol, ethanol, w-propanol, z ^' -propanol, w-butanol, z ^' -butanol, s-butanol, t- butanol, w-pentanol, z ^' -pentanol, w-hexanol, cyclohexanol, w-heptanol, w-octanol, w-nonanol, n- decanol, ethylene glycol and glycerol. The carbon atoms in alcohols can be straight, branched or cyclic. Alcohol includes any subset of the foregoing, e.g., Ci_6 alcohols (alcohols having 1, 2, 3, 4, 5 or 6 carbon atoms). [0025] "Alkyl" refers to a group having the general formula C _n H _2n+ i derived from a saturated, straight chain or branched aliphatic hydrocarbon, where n is an integer. In certain embodiments, n is from 1 to about 30, from 1 to about 20, or from 1 to about 10. Non-limiting examples of alkyl groups include Ci-Cs alkyl groups such as methyl, ethyl, propyl, isopropyl, 2-methylpropyl, 2-methylbutyl, 3-methylbutyl, 2,2,-dimethylpropyl, 2-methylpentyl, 3- methylpentyl, 4-methylpentyl, 2-2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl, n-butyl, isobutyl, tert-butyl, isopentyl, n-pentyl, neopentyl, n-hexyl, isohexyl, n-heptyl, isoheptyl, n- octyl, isooctyl, n-nonyl, isononyl, n-decyl and isodecyl. An alkyl group may be unsubstituted, or may be substituted. In some embodiments, the alkyl group is straight chain having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbons. In some embodiments, the alkyl group is branched having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 or 12 carbons. Non-limiting examples of moieties with which the alkyl group can be substituted are selected from the group consisting of halogen (fluoro, chloro, bromo or iodo), hydroxyl, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, or phosphonate, either unprotected, or protected as necessary, as known to those skilled in the art, for example, as taught in Greene, et ah, Protective Groups in Organic Synthesis, John Wiley and Sons, Second Edition, 1991, hereby incorporated by reference.

[0026] "aq." means aqueous.

[0027] "Aryl" refers to an organic radical derived from a monocyclic or polycyclic aromatic hydrocarbon by removing a hydrogen atom. Non-limiting examples of the aryl group include phenyl, naphthyl, benzyl, or tolanyl group, sexiphenylene, phenanthrenyl, anthracenyl, coronenyl, and tolanylphenyl. An aryl group can be unsubstituted or substituted with one or more suitable substituents. Furthermore, the aryl group can be monocyclic or polycyclic. In some embodiments, the aryl group contains at least 6, 7, 8, 9, or 10 carbon atoms. Non- limiting examples of moieties with which the aryl group can be substituted are selected from the group consisting of halogen (fluoro, chloro, bromo or iodo), hydroxyl, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, or phosphonate, either unprotected, or protected as necessary, as known to those skilled in the art, for example, as taught in Greene, et ah, Protective Groups in Organic Synthesis, John Wiley and Sons, Second Edition, 1991, hereby incorporated by reference.

[0028] The ASTM D6866 specifications, "Standard Test Methods for Determining the Biobased Content of Solid, Liquid, and Gaseous Samples Using Radiocarbon Analysis" as published by ASTM International, are incorporated herein by reference in its entirety. [0029] Biomass refers to the carbon atoms in the form of cellulose, lignocellulose, hemicellulose, starch and other carbohydrate polymers contained in nonfood and food plants, for example but not limited to, corn, sweet sorghum and sugar cane, and the waste materials produced from growing or processing them which cannot be used as a food source, but which can be broken down to simple sugars which can be converted into cis,c w-muconic acid and other compounds described herein. Such compounds contain detectable ¹⁴ C content determined according to ASTM D6866 and optionally contain a ¹⁴ C content up to

0.0000000001% (one part per trillion).

[0030] BuOH means w-butanol.

[0031] A catalyst support refers to a material, usually a solid with a high surface area, to which a catalyst is affixed. The support may be inert or participate in the catalytic reactions. Examples of suitable supports include various forms of carbon (e.g., charcoal), alumina (e.g., AI2O ₃ ) and silica (e.g., Davisil ^® 635). Any catalysts described herein, or combinations thereof, can be provided on a catalyst support.

[0032] DMM means dimethyl muconate.

[0033] EtOH means ethanol.

[0034] "g" means gram(s).

[0035] GCMS means gas chromatography mass spectroscopy.

[0036] HMDA means hexamethylenediamine.

[0037] HMI means hexamethylenimine.

[0038] HPLC means high pressure liquid chromatography.

[0039] hr(s) means hour(s).

[0040] L means liter.

[0041] MA means muconic acid.

[0042] MCA means muconamide.

[0043] MeOH means methanol.

[0044] min(s) means minute(s).

[0045] mL means milliliter.

[0046] M means mucononitrile.

[0047] "mol" means the mole unit. "mol%" in the context of catalyst amount, means the molar percentage of the actual metal of a given catalyst relative to the moles of reactant.

[0048] "m.p." means melting point.

[0049] NMR means nuclear magnetic resonance. [0050] The term "optional" or "optionally" means that the subsequently described feature or structure may or may not be present, or that the subsequently described event or

circumstance may or may not occur, and that the description includes instances where a particular feature or structure is present and instances where the feature or structure is absent, or instances where the event or circumstance occurs and instances where the event or circumstance does not occur.

[0051] Q,Q-OMM means one or more of the cis,cis-, cisjrans-, or trans, trans-double- bond isomers of dimethyl muconate. In should be understood that in the synthesis routes provided herein, dimethyl muconate can be replaced by any muconate diester as described herein.

[0052] Q,Q-MCA means one or more of the cis,cis-, cis, trans-, or trans, trans-double-bond isomers of muconamide.

[0053] Q,Q-MN means one or more of the cis, cis-, cis,trans-, or trans, trans -double-bond isomers of mucononitrile.

[0054] RBF means round bottom flask.

[0055] RT means ambient temperature or room temperature, from about 20 to about 25°C.

[0056] Unless otherwise noted, a "solvent" used herein refers to organic solvents.

Organic solvents include protic polar solvents, aprotic polar solvents, and non-polar solvents. Non-limiting examples of protic polar solvents include methanol, ethanol, w-butanol, isopropanol, w-propanol, acetic acid, formic acid, hydrogen fluoride, and ammonia. Non- limiting examples of aprotic polar solvents include dimethylformamide, dimethylsulfoxide (DMSO), methoxymethyl ether, ethyl ether, diethyl ether, tert-butyl methyl ether (TBME), diglyme (bis(2-methoxyethyl) ether), tetraglyme (tetraethylene glycol dimethyl ether), cyclopentyl methyl ether, ethyl acetate, tetrahydrofuran (THF), methyl THF, dioxane, acetone, acetonitrile and propionitrile. Non-limiting examples of non-polar organic solvents include benzene, toluene, pentane, hexane, cyclohexane, heptane, octane, nonane and decane. A mixture of two or more of any of these can also used.

[0057] "Substituted" as used to describe a compound or chemical moiety refers to where at least one hydrogen atom of that compound or chemical moiety is replaced with a second chemical moiety. The second chemical moiety can be any desired substituent that does not adversely affect the desired activity of the compound. Examples of substituents are those found in the exemplary compounds and embodiments disclosed herein, as well as halogen; alkyl; heteroalkyl; alkenyl; alkynyl; aryl, heteroaryl, hydroxyl; alkoxyl; amino; nitro; thiol; thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; acyl; formyl; acyloxy; alkoxycarbonyl; oxo; haloalkyl (e.g., trifluoromethyl); carbocyclic cycloalkyl, which can be monocyclic or fused or non-fused polycyclic (e.g., cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl) or a heterocycloalkyl, which can be monocyclic or fused or non-fused polycyclic (e.g., pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl or thiazinyl); carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic aryl (e.g., phenyl, naphthyl, pyrrolyl, indolyl, furanyl, thiophenyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, triazolyl, tetrazolyl, pyrazolyl, pyridinyl, quinolinyl, isoquinolinyl, acridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, benzimidazolyl, benzothiophenyl or benzofuranyl); amino (primary, secondary or tertiary); o-lower alkyl; o-aryl, aryl; aryl-lower alkyl; -C0 ₂ CH ₃ ; -CONH ₂ ; -OCH ₂ CONH ₂ ; -NH ₂ ; -S02NH ₂ ; -OCHF ₂ ; -CF ₃ ; -OCF ₃ ; - NH(alkyl); -N(alkyl) ₂ ; -NH(aryl); -N(alkyl)(aryl); -N(aryl) ₂ ; -CHO; -CO(alkyl); -CO(aryl); - C0 ₂ (alkyl); and -C0 ₂ (aryl); and such moieties can also be optionally substituted by a fused- ring structure or bridge, for example -OCH ₂ 0-. These substituents can optionally be further substituted with a substituent selected from such groups. All chemical groups disclosed herein can be substituted, unless it is specified otherwise.

[0058] THF means tetrahydrofuran.

[0059] TLC means thin-layer chromatography.

[0060] In the following description, all numbers disclosed herein are approximate values, regardless whether the word "about" or "approximate" is used in connection therewith. They may vary by 1 percent, 2 percent, 5 percent, or, sometimes, 10 to 20 percent. Whenever a numerical range with a lower limit, R ^L , and an upper limit, R ^u , is disclosed, any number falling within the range is specifically disclosed. In particular, the following numbers within the range are specifically disclosed: R=R ^L +k*(R ^u -R ^L ), wherein k is a variable ranging from 1 percent to 100 percent with a 1 percent increment, i.e., k is 1 percent, 2 percent, 3 percent, 4 percent, 5 percent, . . . , 50 percent, 51 percent, 52 percent, . . . , 95 percent, 96 percent, 97 percent, 98 percent, 99 percent, or 100 percent. Moreover, any numerical range defined by two R numbers as defined in the above is also specifically disclosed.

DETAILED DESCRIPTION

[0061] It is understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. As used in this specification, the singular forms "a", "an", and "the" include plural referents unless the content clearly indicates otherwise. [0062] Also, certain patents and published applications have been incorporated by reference. However, the text of such patents is only incorporated by reference to the extent that no conflict exists between such text and other statements set forth herein. In the event of such conflict, then any such conflicting text in such incorporated by reference patent or application is specifically not so incorporated herein.

[0063] The conversion of biomass to cis,cis -muconic acid can be found in U.S. Patent Nos. 4,879,987 and 5,487,987, both of which patents are incorporated herein by reference in their entirety. The biomass-derived cis,cis-, cis, trans-, and trans, trans -muconic acid materials may be converted to the various double-bond isomers of muconate diester (e.g., Qg-DMM) according the methods described in WO 2010/148063, WO 2010/148080, WO 2010/148049, WO 2010/148081 and WO 2010/148070, all of which applications are incorporated herein by reference in their entirety.

Hexamethylenediamine

[0064] In contrast to the known processes for the commercial production of HMDA from petrochemical-derived starting materials, the present invention, in certain embodiments, provides processes for HMDA production having a renewable starting material derived from biomass. The starting material muconate diester (e.g., Q,Q-OMM) can be produced from biomass-derived muconic acid, MA, such that at least a significant percentage of the carbon is derived from renewable resources. Such products prepared using muconate diester (e.g., Q,Q- DMM) are unique because the products can contain a detectable ¹⁴ C content determined according to ASTM D6866 and optionally contain a ¹⁴ C content up to 0.0000000001% (one part per trillion).

[0065] As disclosed in U.S. Patent No. 5,487,987, cis,cis-muconic acid (cis,cis-MA) may be hydrogenated to give adipic acid 3. It would be clear to those skilled in the art that this adipic acid 3 may be converted to HMDA 1 using the known synthetic routes, e.g., those synthetic routes described herein. It would also be clear to those skilled in the art that the cis, trans- and trans, trans- double bond isomers of muconic acid, MA, may also be

hydrogenated to adipic acid 3, which may be converted to HMDA 1 using any known synthetic route.

[0066] One of the syntheses of biomass-derived HMDA of the present invention starts from biomass-derived muconic acid (MA), which is converted to the corresponding diester and then to diamide. In some variations, the diester can be DMM made from methyl esterification of MA. The muconate diester has formula R'OOC-C^-C^-COOR ² , where R ¹ and R ² can be the same or different, and R ¹ and R ² are each individually any alkyl, alkenyl, alkynyl, aryl, cyclalkyl, cycloalkenyl, alkaryl and aralkyl group that is unsubstituted or substituted. In some variations, the diamide can be MCA made from amidation of the diester. Any esterification and amidation methods known in the art may be used for the conversion. The MCA can subsequently be converted (e.g., via dehydration) to mucononitrile (M ), which can then be hydrogenated to HMDA.

[0067] As alternative syntheses of biomass-derived HMDA in the present invention, muconamide (MCA) can be directly hydrogenated to HMDA 1, or the MCA may first be reduced to adipamide, which may subsequently be reduced to HMDA 1. In either alternative, the reduction or reductions may be performed using methods available in the literature for converting amides to amines. One such method is described in U.S. Patent No. 7,504,540 which converts Ν,Ν-dimethyldodecylamide to Ν,Ν-dimethyldodecylamine with copper chromite in greater than 97% yield. However, this process requires the use of gas-phase reaction conditions and the major product is Ν,Ν-dimethyldodecylamine that is contaminated with by-products such as N-methyldodecylamine and N-didodecylamine. U.S. Patent No. 4,448,998 also describes the reduction of Ν,Ν-disubstituted amides to amines using a co- catalyst of copper chromite with zeolite in a batch reactor having a conversion to the following product mixture: dialkylmethylamine 9.2 wt %, unreacted amine 8.4 wt %, alkyldimethylamine 72.4 wt %, and lauryl alcohol 8.3 wt %, with selectivity of the product of 80.5%.

[0068] Various routes to make biomass-derived HMDA 1 are provided by the present invention, where each can have different advantages. For example, the 3 -step route (stated as Route 2) incorporating the dehydration of muconamide (Q,Q-MCA) to mucononitrile (Q,Q- MN) and then reduction of the mucononitrile (MN) to HMDA 1 is a higher yielding process with minimal amount of by-products formed. The 2-step route (stated as Route 1) in which Q,Q-MCA is directly reduced to HMDA 1 has fewer steps and uses fewer reagents, but gives a lower yield of HMDA 1 than Route 2, and forms larger amounts of by-products such as caprolactam and hexamethylenimine (HMI 9). In comparison, the 3 -step Route 2 utilizing the Q,Q-MN intermediate provides cleaner HMDA 1 with the minimum amount of by-products.

[0069] It should be noted that when any of the double bond isomers (e.g., cis,cis-) are converted to another double bond isomer (e.g., cis, trans-) in a process of the present invention, the conversion provides predominantly the isomer indicated, although it is understood that some of the other isomer(s) could be present.

[0070] All of the double-bond isomers of the muconate diester (e.g., Q,Q-OMM) starting material used to make biomass-derived HMDA 1 can be prepared from cis,cis-muconic acid (cis,cis-MA). cis,cis-MA can be produced, for example, via fermentation of sugars derived from biomass containing detectable ¹⁴ C content determined according to ASTM D6866 and optionally containing a ¹⁴ C content up to 0.0000000001% (one part per trillion). The biomass- derived cis,cis-MA can be converted to the various double-bond isomers of the muconate diester (e.g., Q,Q-OMM) starting material according to the methods described herein (see Examples A through G in Starting Materials). Thus, all the double-bond isomers of the muconate diester (e.g., Q,Q-OMM) starting material used in the present invention can be derived from biomass and are not derived from petrochemical feedstock. Such starting material derived from biomass has not been previously available.

[0071] Certain embodiments of the present invention for the production of biomass- derived HMDA 1 is illustrated by Scheme 3 below. It should be noted that any suitable diesters of MA can be used as the starting material in place of DMM in reactions illustrated in Scheme 3, such as diethyl muconate, or any suitable dialkyl muconate. In some cases, DMM may be less expensive or cheaper to make from MA than other MA diesters. The MA diester has formula R'OOC-C^-C^-COOR ² , where R ¹ and R ² can be the same or different, and R ¹ and R ² are each individually any alkyl, alkenyl, alkynyl, aryl, cyclalkyl, cycloalkenyl, alkaryl and aralkyl group that is unsubstituted or substituted.

Scheme 3

Route and Example Number for each step are indicated

^ common step in all routes

Me0 ₂ C C0 ₂ Me

C0 ₂ Me ► Route 1 (2-step route)

C0 ₂ Me Me0 ₂ C Me0 ₂ C

Route 2 (3-step route) c/s,c/s-DMM 5a cis,trans-DMM 5b trans, trans-DMM 5c

Route 4-ste route

d

[0072] As shown in Scheme 3, the first reaction in each of Route 1, Route 2 and Route 3 is the formation of one or more of the double-bond isomers of Q, g-MCA from one or more of the double-bond isomers of Q,Q-OMM. This can be accomplished by: (a) forming the cis,cis- MCA 6a or cis,trans-MCA 6b (Examples 11 and 7, respectively) in aq. NH ₃ , either (i) at a temperature from about 20 to about 25°C, or (ii) at a temperature of about 70 to about 100°C ; or (b) forming the trans, trans -MCA 6c (Example 1) in aq. ¾ and an alcohol, at a temperature from about 20 to about 25°C. In some embodiments, step (a)(i) can take about 1 to 10 days, 2 to 8 days, or about 4 days. Step (a)(ii) can take from about 1 to about 48 hours, 4 to 30 hours, or about 20 hours. The temperature in step (a)(ii) can be from about 60 to about 80°C, about 70°C, or about 100°C. In step (b), a ratio of the aq. NH ₃ to the alcohol can be about 1 : 1. In step (b), the alcohol can be methanol, ethanol or any other suitable organic solvent. Step (b) can take about 5 to 20 days, about 10 to 16 days, or about 14 days.

[0073] The route for making HMDA 1 in the fewest steps is provided by Route 1, as shown by the dashed arrow in Scheme 3. Following formation of Q,Q-MCA from Q,Q-OMM, the Q,Q-MCA is then reacted with H ₂ plus NH ₃ , in the presence of a reduction catalyst and an aprotic polar solvent (e.g., THF or dioxane). The total gas pressure can be from about 300 to about 3,000 psi, from about 1,000 to about 2,000 psi, or about 1,500 to about 1,800 psi (e.g., in a Parr reactor). The reduction catalyst can be about 15-99 mol%, about 15-50 mol%, or about 20 mol% of 2Οι0-(¾(¾. The reduction reaction can be carried out at from about 150 to about 350°C, from about 200 to about 300°C, or at about 250°C. The reaction can take about 1-10 hr, 2-5 hr, about 3 hr, or shorter or longer times. Some exemplary results are shown in Example 14, for example entries 4 through 8 in Table 3. It should be noted that under these conditions caprolactam may also be produced.

[0074] Another synthesis route is provided by Route 2 as shown by regular solid arrows in Scheme 3. In Route 2, the reaction following the formation of Q,Q-MCA from Q,Q-OMM is the dehydration of ββ-MCA to form Q,Q-MN. The Q,Q-MCA may be dehydrated using a dehydrating agent. Any dehydrating agent known in that art suitable for the dehydration reaction may be used. For example, P2O5 (Example 3), POCI ₃ (Example 2), or PdC¾ (Example 4) can be used to dehydrate trans, trans -MCA 6c to form the trans, trans-MN 7c in about 65- 80% yield. The cis,cis-MCA 6a and cis, trans-MCA 6b may be dehydrated with POCl ₃ (Examples 12 and 8 respectively) and the cis,trans-MCA 6b may also be dehydrated with PdCi ₂ in aq. acetonitrile (1 : 1) (Example 9).

[0075] The third step in Route 2 is the hydrogenation of each of the double-bond isomers (cis,cis- or cis, trans- or trans, trans-) Q,Q-MN 7a-7c with H ₂ gas at about 300 to about 1500 psi, in the presence of a hydrogenation catalyst and a solvent. Optionally NH ₃ gas can be included. The gas pressure can be from about 300 to about 1,500 psi, from about 800 to about 1,200 psi, or about 1,000 psi. The hydrogenation catalyst can be any catalyst known in that art suitable for the hydrogenation reaction. For example, the catalyst can be Raney Ni catalyst. The solvent can be THF. The reaction can be carried out at from about 50 to about 200°C, from about 80 to about 150°C, or at about 1 10°C. The reaction can take about 1-10 hr, 2-5 hr, about 3 hr, or shorter or longer times. For example, hydrogenation of cis,cis-MN 7a is shown in Example 13; cis,tram-MN 7b shown in Example 10; and trans, trans-MN 7c shown in Example 6. These examples give an overall yield of about 55 to about 75%. The yield can be increased by further converting the by-products into HMDA (e.g., by hydrogenating the adiponitrile of Example 6, Entries 3-4 of Table 2 to produce HMDA as described herein). It should also be noted that all three MCA and MN isomers can be used to produce HMDA, while the trans,trans-isomer of both MCA 6c and MN 7c may be preferred, as the trans, trans- isomers, under the conditions in Examples 6, 10, and 13 provide the highest yield of HMDA and lowest amount of by-products. Furthermore, while it is not necessary to include NH ₃ gas with the H ₂ in the reduction of ββ-ΜΝ to HMDA 1, without NH ₃ gas the yield of HMDA 1 may be lower than optimal and oligomeric by-products can form (see Example 5). When NH ₃ gas is used, it can be introduced at about 50 psi, and the H ₂ can be added to give a total gas pressure in the reactor of about 500 psi or higher.

[0076] Other reactions may also be used in the production of HMDA 1 from the Q, Q- DMM starting material. As provided by Route 3 and shown in Scheme 3 by bold solid arrows, the reaction following the formation of Q, g-MCA from Q, g-DMM is the hydrogenation of β,β-MCA 6a-c to adipamide 8. For example, trans, trans-MCA 6c can be reduced with Pd/C, ¾ to generate adipamide 8 (Example 14, see entries 1 through 3 in Table 3), which can then be dehydrated to adiponitrile 4 using POCl ₃ as dehydrating agent (Example 15). Other or alternative dehydrating agents such as PdCl ₂ and P ₂ O ₅ can be used. Other isomers of Q,Q- MCA can also be converted into adiponitrile 4 using similar methods. Hydrogenation of the adiponitrile 4 over a hydrogenation catalyst can be used to produce HMDA 1. The

hydrogenating catalyst can be any catalyst known in that art suitable for the hydrogenation reaction. For example, the catalyst can be Raney Ni catalyst in a solvent (e.g., BuOH or THF). H ₂ pressures can be from about 300 to about 1,000 psi, from about 400 to about 600 psi, or about 500 psi. The reaction temperature can be at from about 50 to about 200°C, from about 80 to about 150°C, or at about 110°C. The reaction can take about 1-10 hr, 2-5 hr, about 2-3 hr, or shorter or longer. Adiponitrile 4 hydrogenation can be carried out as shown in Examples 16 and 17; conditions in Example 17 may be preferred given the higher yield. This Route 3 has the most number of steps, but provides the product HMDA 1 with the least byproducts and may be preferred for that reason. All of the double-bond isomers (cis,cis- or cis, trans- or trans, trans-) of MCA 6a-c can be used in this process.

[0077] As demonstrated, all three isomers of Q, g-DMM can be converted to the final desired product, HMDA 1. In some embodiments, the use of the trans, trans -double-bond isomer of the DMM 5c as starting material and proceeding through the trans, trans -MCA 6c intermediate as the first step in each of Route 1, Route 2 or Route 3 may be preferred over the other double-bond isomers for its stability and ease of product isolation. All of the double-bond isomers of the Q,Q-OMM starting material and the Q,Q-MCA and Q,Q-MN intermediates are soluble in organic solvents and can be used in the present invention. In some embodiments, some double-bond isomers will give higher yield or form fewer by-products. Thus for these various process routes, the preferred double-bond isomer may be the trans, trans-, then the cis, trans- and then the cis, cis- isomer (i.e., the order of preferred isomers may be trans, trans > cis, trans > cis, cis). For these reasons the cis, cis- and cis, trans -double-bond isomers of DMM 5a and 5b can be sometimes converted to the trans, trans -double-bond isomer of DMM 5c. In some variations, cis, cis -muconic acid, as well as the cis, trans isomer can be converted to the trans, trans -muconic acid isomer prior to further chemistry.

Polyamides

[0078] Compounds prepared according to methods of the present invention can be used as monomers to prepare a variety of polymers such as polyamides and copolymers thereof. A polyamide is a polymer containing monomers of amides joined by peptide bonds. Polyamides are useful in a variety of commercial products, such as fibers, textiles, high performance plastics and the like, and may be prepared from a variety of amines and carboxylic acids. In general, the amide link can be produced from the condensation reaction between an amino group and a carboxylic acid, acid halide or carboxylate group. Polyamides are traditionally prepared from starting materials derived from petroleum feed stocks.

[0079] In certain embodiments, HMDA prepared according to methods of the present invention can be reacted with one or more compounds having at least two amide-forming groups such as carboxylic acid, acid halide and/or carboxylate groups, under suitable conditions to form polyamides. Any processes for preparing such polyamides known in the art can be used, such as those disclosed in U.S. Patent Nos. 6,846,868; 5,763,561 ; 6,291,633; 5,665,854; 5,194,577; 5,276, 131 ; 5,218,082; 3,627,736 and 7,053, 169, and Kirk-Othmer Encyclopedia of Chemical Technology, 3d Ed., 1982 John Wiley and Sons, Inc., Vol. 18, pp. 353-357, all of which are incorporated herein by reference in their entirety. The resulting polyamides contain at least about 6 carbons per monomer unit, and preferably at least about 6 carbon atoms that are from muconic acid precursors derived from renewable resources. In some embodiments, the resulting polyamides contain a detectable amount of ¹⁴ C and optionally up to about 1 part per trillion ¹⁴ C.

[0001] Compounds having amide-forming groups can include aliphatic or aromatic dicarboxylic acids, or salts or halides or esters thereof, or any combination thereof. In some embodiments, dicarboxylic acids can be derived from renewable resources such as biomass. In some embodiments, suitable aliphatic dicarboxylic acids can contain from 3 to 30 carbon atoms, cyclic or non-cyclic, saturated or unsaturated, and optionally having one or more substituents such as halogen atoms, hydroxy groups, mercapto groups, alkyl groups containing 1 to 12 carbon atoms, alkenyl groups containing 2 to 12 carbon atoms, alkoxy groups containing from 1 to 12 carbon atoms, alkoxycarbonyl groups containing 2 to 24 carbon atoms, alkenyloxycarbonyl groups containing 4 to 24 carbon atoms, phenyl, benzyl, phenoxy, naphthyl or cyclohexyl groups, the ring moieties of which are optionally substituted by one or more substituents such as halogen atoms, hydroxy groups, alkyl groups containing 1 to 6 carbon atoms, or alkoxy groups containing 1 to 6 carbon atoms. Suitable aromatic

dicarboxylic acids can contain any aryl group optionally having one or more substituents, and can include but not limited to isophthalic acid; terephthalic acid; 1,4-, 1,5-, 2,6-, and 2,7- naphthalenedicarboxylic acid; 4,4'-diphenyl ether dicarboxylic acid or 4,4'- benzophenonedicarboxylic acid; 4,4'-diphenyl sulfone dicarboxylic acid; 2-phenoxy- terephthalic acid; 4,4-biphenyldicarboxylic acid; or mixtures thereof. Heterocyclic carboxylic acids can also be used, for example, those derived from pyridine, furan, thiophene, pyrrole and pyran, optionally having one or more substituents. Non-limiting examples of dicarboxylic acids are disclosed in U.S. Patent No. 6,846,868, incorporated herein by reference. In some embodiments, a mixture of two of more dicarboxylic acids (e.g., a main dicarboxylic acid and one or more alternative dicarboxylic acid) can be used. For example, the amount of alternative dicarboxylic acids (e.g., isophthalic acid and/or 1,5-furandicarboxylic acid) may be about 40 mole percent or less based on the total moles of dicarboxylic acids, about 30 mole percent or less or about 20 mole percent or less.

[0080] Non-limiting examples of dicarboxylic acid include adipic acid, sebacic acid, glutaric acid, terephthalic acid, 2-methylterephthalic acid, isophthalic acid,

naphthalenedicarboxlic acid, 1,5-furandicarboxylic acid, cyclopentane dicarboxylic, cyclopentene dicarboxylic, cyclohexane dicarboxylic, and cyclohexene dicarboxylic acids, each optionally having one or more substituents. No limiting examples of polyamide (PA) products include:

PA 6T: made from hexamethylenediamine and terephthalic acid; terephthalic acid can be provided by any available source, including but not limited to the methods of preparation disclosed in U.S. Patent Application No. 12/816,73 and PCT International Patent Application Nos. PCT/US201 1/064621 and PCT/US201 1/064618, all incorporated herein by reference;

PA 61: made from hexamethylenediamine and isophthalic acid;

PA 66: [NH-(CH ₂ ) ₆ -NH-CO-(CH ₂ )4-CO] _n made from hexamethylenediamine and adipic acid;

PA 6/12: [NH-(CH ₂ ) ₆ -NH-CO-(CH ₂ )io-CO] _n made from hexamethylenediamine and dodecanedioic acid; dodecanedioic acid can be provided by any available source, including but not limited to the methods of preparation disclosed in U.S. Patent Application No. 13/145,621, incorporated herein by reference;

PA 6/66: [NH-(CH ₂ ) ₆ -NH-CO-(CH ₂ )4-CO] _n -[NH-(CH ₂ ) ₅ -CO] _m made from caprolactam, hexamethylenediamine and adipic acid; caprolactam can be provided by any available source, including but not limited to the methods of preparation disclosed in PCT International Patent Application entitled "Process for Preparing Caprolactam and Polyamides Therefrom", Attorney Docket No. 136556-013102/PCT filed with the U.S. Receiving Office on April 9, 2012, and U.S. Patent Application No.13/442,306 entitled "Process for Preparing Caprolactam and Polyamides Therefrom", Attorney Docket No. 136556-013103/US filed on April 9, 2012, both incorporated herein by reference;

PA 66/610:

[NH-(CH ₂ ) ₆ -NH-CO-(CH ₂ ) ₄ -CO] _n -[NH-(CH ₂ ) ₆ -NH-CO-(CH ₂ ) ₈ -CO] _m made from hexamethylenediamine, adipic acid and sebacic acid.

[0081] In some examples, polyamides can be prepared in a multistep reaction sequence. In general, one or more dicarboxylic acids (or diesters or other derivatives) can be contacted with one or more diamines (e.g., HMD A) to form a salt. The salt can then be subject to a polycondensation step to form a prepolymer. The prepolymer can be optionally subjected to a solid phase polymerization, solution polymerization, or melt polymerization to form a polyamide of a desired molecular weight.

[0082] In the salt formation step, one or more diamines and dicarboxylic acids (or diesters) are contacted. This step can be conducted in water, for instance from 20 to 150 weight percent of water based on the weight of the reactants. Optionally this step is conducted in the absence of free oxygen or under an inert atmosphere, e.g., under nitrogen. The one or more diamines and one or more dicarboxylic acids are preferably contacted at water reflux, for example, at about 90°C to 100°C. The reaction can be performed at superatmospheric pressures, e.g., about 100 kPa to about 1000 kPa, about 200 kPa to about 600 kPa, or greater or less. Preferably the volatiles are removed during this process and if one or more of reactants volatilize away during the condensation step additional quantities of that reactant(s) may need to be added to maintain the desired stoichiometry. The formed salt may be recovered by cooling to precipitate the salt and performing a standard separation, such as filtration or centrifugation. Impurities may be removed by contacting with an adsorbant such as active carbon. Alternatively the formed salt may be exposed to polycondensation conditions without recovery from the reaction medium.

[0083] Next, during polycondensation of the salt to a prepolymer, the salt can be exposed to temperatures at which the salt condenses to form an amide linkage. In some embodiments, the reactants are contacted in an aqueous reaction mixture at a temperature of about 200°C to about 330°C , about 250°C to about 310°C, about 270°C to about 300°C, or greater or less. This contacting step can be conducted in water, for instance from about 20 to about 150 weight percent of water based on the weight of the salt. The reaction can be conducted in the absence of free oxygen or under an inert atmosphere, e.g., under nitrogen. The reaction can be performed at superatmospheric pressures, e.g., about 100 kPa to about 1000 kPa, about 200 kPa to about 600 kPa, or greater or less. Once the desired molecular weight has been achieved, water can be removed and the product can be granulated or transferred to an extruder.

[0084] If the resulting product does not have the desired molecular weight it can be subjected to solid state or melt polymerization. In this step the polymer can be exposed to conditions under which the polymer continues to polymerize. This can be performed at reduced pressure and/or under an inert atmosphere. The polymerization can be conducted in a polymerization apparatus, for example, a batch-type reactor, a single-tank or multi-tank continuous polymerization apparatus, a tubular continuous polymerization apparatus, or a kneading reaction extruder. The polymerization can be conducted with agitation. In a solid state polymerization the agitation is typically performed by an impeller. In melt

polymerization the polymer can be fed through an extruder where the screws of the extruder can provide the agitation. The reaction temperature can be about 200°C to about 370°C, about 250°C to about 300°C, about 270°C to about 280°C, or greater or less. The polymerization step may be performed in the presence of a phosphorous catalyst or any other suitable catalyst known in the art. Exemplary phosphorous catalysts include phosphoric acid, phosphorous acid or hypophosphoric acid or a salt or ester thereof, such as those disclosed in U.S. Patent No. 6,846,868, incorporated herein by reference. The phosphorous catalyst can be used in a sufficient amount such that a reasonable rate of condensation and reasonable yield are achieved, for example, in an amount of about 0.01 to 5 wt%, about 0.05 to 2 wt%, about 0.07 to 1 wt%, or greater or less. The reaction mixture may also contain one or more monoamines or monocarboxylic acids to control the molecular weight of the polyamide (e.g., by adding to the end of the extending polymer chain thereby stopping the polymerization). Exemplary monoamines or monocarboxylic acids are disclosed in U.S. Patent No. 7,053,169, incorporated herein by reference.

[0085] The polyamides of the present invention can be formulated with known additives. For example, the polyamides are formulated to contain one or more copper and/or alkali metal stabilizers, e.g., as disclosed U.S. Patent Nos. 6,846,868 and 5,763,561, both incorporated herein by reference. Other additives such as fillers, fibers, pigments, stabilizers, flame retardants, nucleating agents, lubricants, impact modifiers, thermoplastic polymers and the like may be used in combination with the polyamides described herein, e.g., as disclosed in U.S. Patent Nos. 5,194,577; 6,846,868; and 6,291,633, all incorporated herein by reference. The polyamide compositions of the invention can be formed by blending in a suitable mixer or extruder.

[0086] The polyamides can be formed into fibers, films or molded products using known processes. The polyamides can be formed into the desired shape by thermoforming, melt extrusion, injection molding and the like. The polyamides can be formed or molded into automobile engine parts, electrical connectors, electrical equipment parts, etc. Specific examples of these molded objects include mechanism elements such as an oil strainer, timing chain cover, rocker cover, timing chain tensioner, thrust washer, power steering tank, oil level gauge, brake fluid subtank, brake master cylinder, brake piston rod, automatic -transmission stator, bearing retainer, governor gear, and sensor, electrical equipment parts such as a relay box and connector, and electrical/electronic parts such as a terminal board, connector, and relay.

EXAMPLES

[0087] The present invention will be further clarified by a consideration of the following examples, which are intended to be purely exemplary of the present invention. Those of ordinary skill in the art will readily recognize a variety of non-critical parameters that could be changed or modified to yield essentially similar results. Materials and Methods

[0088] Solvents were purified and dried prior to use by distillation from an appropriate drying agent. Tetrahydrofuran (THF) was distilled from sodium/benzophenone under a nitrogen atmosphere.

[0089] Solvents were removed at water aspirator pressure by rotary evaporation, and residual solvent was removed by vacuum pump at less than 2 mmHg. Glassware and syringes were dried in an oven at 100°C overnight and cooled in a desiccator over CaS0 ₄ prior to use.

Alternatively, flasks were flame-dried under a stream of argon.

[0090] Analytical thin-layer chromatography (TLC) was performed on E. Merck precoated TLC plates (silica gel 60 F-254, layer thickness 0.2 mm).

[0091] Melting points (m.p.) were determined using a Mel-Temp II melting-point apparatus and are uncorrected.

[0092] Nuclear magnetic resonance (NMR) spectra were obtained on a Varian spectrometer; chemical shifts are expressed as parts per million (ppm) downfield from tetramethylsilane.

[0093] High Pressure Liquid Chromatography (HPLC) was performed using Agilent 1100 series system using the following method: Column = Prevail Organic Acid (150 mm x 4.6 mm, Grace Davison Discovery Sciences). Mobile Phase: potassium phosphate buffer (25 mM, pH 1.5) : acetonitrile (85: 15). Detection wavelength = 257 nm.

[0094] Gas Chromatography Mass Spectra (GCMS) was analyzed using Agilent 6890 GC system with Agilent 5973 inert Mass Selective Detector and the following method: Column = J&W Sci 112-2132; 220°C Max CAM Capillary 30.0m x 250 μΜ x 0.25 μιη nominal.

Temperature profile = 90°C initially and hold for 2 min; ramp up to 200°C at a rate of

10°C/min and hold for 15 min. Inlet temperature = 250°C.

Starting Materials

[0095] DMM, or other muconic acid esters, can be used as the starting material for the production of biomass-derived HMDA. Such muconic acid esters can be prepared from muconic acid (MA). Muconic acid used in the methods described herein can be obtained from any available source or prepared by any technique known by or apparent to one of skill in the art. In some cases, muconic acid is derived from a microbial organism that has been modified to produce muconic acid. Microbially-derived muconic acid may contain any one of or any combination of the the cis,cis-, cis-trans-, and trans,trans- isomers of muconic acid. In some instances, the most prevalent isomer in microbially-derived muconic acid is cis,cis -mucomc acid. In some instances, the most prevalent isomer in microbially-derived muconic acid is cis, trans -mucomc acid. In some instances, the most prevalent isomer in microbially-derived muconic acid is trans, trans -muconic acid. The muconic acid present in a cell culture medium or fermentation broth used in the microbial synthesis may be used as-is, purified, or isolated before undergoing amidation reaction. Non- limiting examples of purification or isolation methods include extraction, washing, filtration, centrifuge, and combinations thereof.

[0096] In certain variations, muconic acid is microbially synthesized from readily available carbon sources capable of biocatalytic conversion to erythrose 4-phosphate (E4) and phosphoenolpyruvate (PEP) in microorganisms having a common pathway of aromatic amino acid biosynthesis. Carbon sources used in the synthesis are advantageously renewable, being derived from starch, cellulose and sugars found, for example, in corn, sugar cane, sugar beets, wood pulp and other biomass. One carbon source that can be used to make muconic acid is D- glucose.

[0097] Any suitable method for microbial synthesis of muconic acid may be used. A host microbial organism is selected such that it produces the precursor of a muconate pathway, either as a naturally produced molecule or as an engineered product that produces the precursor or increases production of the precursor naturally produced by the host organism. In some cases, an engineered organism is generated from a host that contains the enzymatic capability to synthesize muconate. Increased synthesis or accumulation of muconate can be

accomplished by overexpression of nucleic acids encoding one or more muconate pathway enzymes or proteins. Engineered organisms may be designed to produce muconate through overexpression of any number of the nucleic acids enconding muconate biosynthetic pathway enzymes or proteins.

[0098] In certain embodiments, MA can be produced via fermentation of sugars derived from biomass. The conversion of biomass to cis,cis-mucomc acid can be found in U.S. Patent Nos. 4,879,987 and 5,487,987, both of which patents are incorporated herein by reference in their entirety.

[0099] Host microbial organisms suitable for synthesizing muconic acid may be selected from genera possessing an endogenous common pathway of aromatic amino acid biosynthesis. In certain embodiments, the host cells are recombinantly modified to produce the muconic acid, or a precursor thereof. Illustrative examples of suitable host cells include any archae, prokaryotic, or eukaryotic cell. Examples of an archae cell include, but are not limited to those belonging to the genera: Aeropyrum, Archaeglobus, Halobacterium, Methanococcus, Methanobacterium, Pyrococcus, Sulfolobus, and Thermoplasma. Illustrative examples of archae strains include but are not limited to: Aeropyrum pernix, Archaeoglobus fulgidus, Methanococcus jannaschii, Methanobacterium thermoautotrophicum, Pyrococcus abyssi, Pyrococcus horikoshii, Thermoplasma acidophilum, Thermoplasma volcanium.

[00100] Examples of a procaryotic cell include, but are not limited to those belonging to the genera: Agrobacterium, Alicyclobacillus, Anabaena, Anacystis, Arthrobacter, Azobacter, Bacillus, Brevibacterium, Chromatium, Clostridium, Corynebacterium, Enterobacter, Erwinia, Escherichia, Lactobacillus, Lactococcus, Mesorhizobium, Methylobacterium, Microbacterium, Phormidium, Pseudomonas, Rhodobacter, Rhodopseudomonas, Rhodospirillum, Rhodococcus, Salmonella, Scenedesmun, Serratia, Shigella, Staphlococcus, Strepromyces, Synnecoccus, and Zymomonas.

[00101] Illustrative examples of prokaryotic bacterial strains include but are not limited to:

Bacillus subtilis, Bacillus amyloliquefacines, Brevibacterium ammoniagenes, Brevibacterium immariophilum, Clostridium beigerinckii, Enterobacter sakazakii, Escherichia coli,

Lactococcus lactis, Mesorhizobium loti, Pseudomonas aeruginosa, Pseudomonas mevalonii, Pseudomonas pudica, Rhodobacter capsulatus, Rhodobacter sphaeroides, Rhodospirillum rubrum, Salmonella enterica, Salmonella typhi, Salmonella typhimurium, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Staphylococcus aureus, and the like.

[00102] In general, if a bacterial host cell is used, a non-pathogenic strain is preferred. Illustrative examples of non-pathogenic strains include but are not limited to: Bacillus subtilis, Escherichia coli, Lactibacillus acidophilus, Lactobacillus helveticus, Pseudomonas aeruginosa, Pseudomonas mevalonii, Pseudomonas pudita, Rhodobacter sphaeroides, Rodobacter capsulatus, Rhodospirillum rubrum, and the like.

[00103] Examples of eukaryotic cells include but are not limited to fungal cells. Examples of fungal cell include, but are not limited to those belonging to the genera: Aspergillus, Candida, Chrysosporium, Cryotococcus, Fusarium, Kluyveromyces, Neotyphodium,

Neurospora, Penicillium, Pichia, Saccharomyces, Trichoderma and Xanthophyllomyces (formerly Phaffia).

[00104] Illustrative examples of eukaryotic strains include but are not limited to:

Aspergillus nidulans, Aspergillus niger, Aspergillus oryzae, Candida albicans, Chrysosporium lucknowense, Fusarium graminearum, Fusarium venenatum, Kluyveromyces lactis,

Neurospora crassa, Pichia angusta, Pichia flnlandica, Pichia kodamae, Pichia

membranaefaciens, Pichia methanolica, Pichia opuntiae, Pichia pastoris, Pichia pijperi, Pichia quercuum, Pichia salictaria, Pichia thermotolerans, Pichia trehalophila, Pichia stipitis, Streptomyces ambofaciens, Streptomyces aureofaciens, Streptomyces aureus, Saccaromyces bayanus, Saccaromyces boulardi, Saccharomyces cerevisiae, Streptomyces fungicidicus, Streptomyces griseochromogenes, Streptomyces griseus, Streptomyces Uvidans, Streptomyces olivogriseus, Streptomyces rameus, Streptomyces tanashiensis, Streptomyces vinaceus, Trichoderma reesei and Xanthophyllomyces dendrorhous (formerly Phaffla rhodozyma).

[00105] In general, if a eukaryotic cell is used, a non-pathogenic strain is preferred.

Illustrative examples of non-pathogenic strains include but are not limited to: Fusarium graminearum, Fusarium venenatum, Pichia pastoris, Saccaromyces boulardi, and

Saccaromyces cerevisiae.

[00106] The muconic acid (MA) can be present as the cis,cis-, cis, trans-, or trans,trans- double-bond isomer, as illustrated in Scheme 4.

Scheme 4

cis,cis-MA 9a cis,trans-M A 9b trans,trans-MA 9c

[00107] In some variations, the methods may comprise isomerizing the muconic acid or muconic acid ester prior to the amidation reaction. In some instances, it may be desired to isomerize muconic acid to form predominantly the cis, cis-, cis, trans-, or trans, trans- isomer. For example, in some cases muconic acid produced via microbial synthesis may be the cis,cis- muconic acid isomer or a mixture of cis, cis-muconic acid and cis, trans -muconic acid, and it may be desired to isomerize the c/s,c/s-muconic acid (or ester) to form cis, trans -muconic acid (or ester) or trans, trans -muconic acid (or ester), or to isomerize cis, trans- muconic acid (or ester) to form cis, cis -muconic acid (or ester) or trans, trans-muconic acid (or ester) before the amidation reaction. Isomerization may occur using any suitable isomerization conditions and appropriate isomerization conditions and catalysts (if needed). For example, the cis, cis- isomer can be isomerized to the cis, trans- isomer in boiling water without a need for a catalyst. In some variations, iodine is used as a catalyst for isomerization, and in some variations iodine- catalyzed photochemical isomerization of cis,cis- or cis, trans- isomers to trans, trans- isomers can be used. Non-limiting examples of methods for isomerizing muconic acid are provided in International Patent Publication No. WO 2010/148063 and in Elvidge J A et al., Journal of the Chemical Society, Chemical Society, Letchworth, GB, 1 Januaray 1950 (1950-01-01), pages 2235-2241, each of which is incorporated by reference herein in its entirety. It should be understood that esterification of muconic acid may occur prior to isomerization to form desired isomers, or isomerization to form desired isomers may occur prior to esterification.

[00108] For example, the cis,cis-MA 9a may be converted to cis,trans-MA 9b in a discrete step. In such discrete step, the cis,cis-MA 9a can be dissolved or dispersed in water and exposed to elevated temperatures to convert the cis,cis-MA 9a to the cis,trans-MA double- bond isomer 9b. Temperatures which may be used for this process step include any temperature at which the isomerization proceeds, this process step being performed as long as required to convert the desired amount of cis,cis-MA 9a to the cis,trans-MA double-bond isomer 9b.

[00109] Both cis,cis-MA 9a and cis,trans-MA 9b may be converted to trans, trans -MA 9c with one or more isomerization catalysts, a source of ultraviolet radiation or both, in solvent to form the trans, trans -MA 9c.

[00110] Muconic acid can be prepared to muconic acid esters by any method apparent to those of skill in the art. Muconic acid esters may also be obtained from any source. In some embodiments, muconcic acid esters are prepared by esterification of muconic acid. Any suitable esterification method known in the art may be used to obtain the desired monoester or diester. Muconic acid may be contacted with an esterifying agent under conditions suitable to form the desired ester. Non- limiting examples of esterifying agents include alkanols (e.g., Ci- Cio alkanols, polyols, polyalkylene glycols having one or more hydroxyl groups and one or more ether groups, aryl alcohols (e.g. phenol or isomers of dihydroxyl benzene), and aryl substituted alcohols (e.g., benzyl alcohol). In some cases, muconic acid is contacted with one or more esterifying agents in the presence of one or more acids. Non-limiting examples of suitable acids include sulfuric acid, nitric acid, phophoric acid, hydrochloric acid, p-toluene sulfonic acid, and Lewis acids. The esterification reaction may be carried out in the presence of acid at an elevated temperature, e.g., about 50°C, 60°C, 70°C, 80°C, 90°C, 100°C, 110°C, 120°C, 130°C, 140°C, or 150°C. As another example, muconic acid may be esterified by reacting with an alcohol in the presence of a base (e.g., pyridine, a tertiary amine, or aqueous NaOH). Further non-limiting examples of esterification reactions for muconic acid are provided in International Patent Publication Nos. WO 2010/148063, WO 2010/148080, WO 2010/148049, WO 2010/148081 and WO 2010/148070, all of which applications are incorporated herein by reference in their entirety.

[00111] Muconic acid ester can have the formula R'OOC-C ^-C X^OOR ² , where R ¹ and R ² can be the same or different, and R ¹ and R ² are each individually any alkyl, alkenyl, alkynyl, aryl, cyclalkyl, cycloalkenyl, alkaryl and aralkyl group that is unsubstituted or substituted. In certain variations, one or both of R ¹ and R ² are Ci-Cio alkyl groups. For example, one or both of R ¹ and R ² may be selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, isopentyl, 2-methylpentyl, 3- methylpentyl, 2-ethylbutyl, n-hexyl, isohexyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, n-heptyl, isoheptyl, 2-methylheptyl, 3-methylheptyl, 4-methylheptyl, 5-methylheptyl, 2- ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 5-ethylhexyl, 6-ethylhexyl, n-octyl, isooctyl, 2- methyloctyl, 3-methyloctyl, 4-methyloctyl, 5-methyloctyl, 6-methyloctyl, 2-ethylheptyl, 3- ethylheptyl, 4-ethylheptyl, 5-ethylheptyl, n-nonyl, isononyl, 2-methylnonyl, 3-methylnonyl, 4- methylnonyl, 5-methylnonyl, 6-methylnonyl, 7-methylnonyl, 2-ethyloctyl, 3-ethyloctyl, 4- ethyloctyl, 5-ethyloctyl, 6-ethyloctyl, n-decyl, and isodecyl. In one embodiment, both R ¹ and R ² can be methyl and the ester is dimethyl muconate (DMM).

[00112] Any muconic acid ester can be used as the starting material and replace DMM in Route 1, 2 or 3 in Scheme 3. The following lettered Examples, A-G, are directed to the preparation of DMM. It should be understood that MA can also be directly amidated to form MCA, without the DMM or other intermediate. Using the DMM intermediate can be more cost saving.

Example A: Isomerization of cis, cis -Muconic Acid \cis,cis-MA] to cis, trans -Muconic Acid \ cis, trans -MA] in Water

cis,cis-MA 9a

cis,trans-MA 9b

[00113] cis,cis-MA 9a (265 g) was suspended in water (2 L) and the pH of the solution was adjusted to 5.1 with 10 M NaOH (250 mL). The mixture was heated at 90°C for 2 hr and the progress of the isomerization monitored by HPLC. After 2 hr of heating at 90°C, the mixture was treated with charcoal (20 g) for 30 min and the hot solution filtered through a thin bed of Celite™. The solution was adjusted to a pH of 2 with concentrated sulfuric acid (50 mL) and allowed to cool to 0°C in an ice-bath. The precipitate was recovered by filtration and dried under reduced pressure overnight to yield 71 g of cis, trans-MA 9b as light yellow solid. The remaining filtrate was concentrated to 600 mL and allowed to incubate at 0°C overnight. More precipitate was formed; this was recovered by filtration and dried to yield an additional 152 g of cis, trans -MA 9b; thus an overall yield of 84% was achieved.

Example B: Isomerization of cis, trans-MA to trans, trans-Maco ic Acid \trans,trans-MA\ in Tetrahydrofuran (THF)

cis,t ns-MA 9b trans,trans-MA 9c

[00114] cis,trans-MA 9b (38.3 g, 269.7 mmol) was dissolved in THF (400 mL) at RT and a single crystal of iodine (247 mg, 0.972 mmol) was added. The reaction mixture was heated at reflux for 4 hr. The precipitate thus obtained was collected by filtration, washed with ice-cold THF (2X) and dried under reduced pressure to yield 33.2 g (a 86% yield) of trans, trans -MA 9c.

Example C: Synthesis of cis,cis-OMM from cis,cis-MA

cis,cis-MA 9a c/s,c/ ^' s-DMM 5a

[00115] Purified cis,cis-MA 9a (10.0 g, 70.4 mmol) was suspended in aq. NaOH (42.2 mL, 5.0 M, 21 1 mmol, 3.0 equivalents). At RT, dimethyl sulfate (18.4 ml, 194 mmol, 2.75 equivalents) was added after 15 min and the mixture rapidly stirred for 6 hr. The mixture was taken up in ethyl acetate and shaken until all solid was dissolved. The organic phase was extracted 3 times with 1 M (molar) aq. NaOH and once with saturated aq. sodium chloride (NaCl). Drying with magnesium sulfate (MgS0 ₄ ), filtering, and evaporation of all solvent gave cis,cis-DMM 5a as an off-white crystalline solid (6.2 g, 36.4 mmol, 52% yield).

Example D: Synthesis of cis, trans -DMM from cis, trans-MA

cis,trans-DMM 5b [00116] Purified cis,trans-MA 9b (10.0 g, 70.4 mmol) was suspended in aq. NaOH (42.2 ml, 5.0 M, 211 mmol, 3.0 equivalents). At RT, dimethyl sulfate (18.4 ml, 194 mmol, 2.75 equivalents) was added after 15 min and the mixture rapidly stirred for 5 hr. The mixture was taken up in ethyl acetate and shaken until all solid was dissolved. The organic phase was extracted three times with 1 M aq. NaOH and once with saturated aq. NaCl. Drying with magnesium sulfate (MgSC^), filtering, and evaporation of all solvent gave cis, trans-DMM 5b as an off-white crystalline solid (6.0 g, 35.3 mmol, 50% yield).

Example E: Synthesis of trans, trans-DMM from trans, trans -MA rat H ⁺

H0 ₂ C * Me0 ₂ C ^^^^ ² t trmanns, t rramnns- MMAA Q arc MeOH, reflux _{trans^ trans} . _{DM M} 5 _C

[00117] trans, trans -MA 9c (4.6 g, 32.4 mmol) was suspended in MeOH (125 mL). A catalytic amount of sulfuric acid, H ₂ SO ₄ (0.3 mL) was added and the reaction mixture was refluxed for 18 hr. After concentration, the remaining brown residue is taken up in ethyl acetate and extracted three times with saturated aq. K ₂ CO ₃ . Drying over sodium sulfate ( a ₂ S0 ₄ ), filtering, and evaporation of all solvent yields trans, trans-DMM 5c as an off-white solid (5.2 g, 30.6 mmol, 94% yield).

Example F: Synthesis of mixed double-bond isomers of DMM from cis,cis-MA u Hn0 ₂ rC _=/ = _x ^{ca H+} ^ _/ C0 ₂ Me

^C ° ^2H MeOH, reflux

cis,cis-MA 9a Q,Q-DMM 5a,5b

[00118] cis,cis-MA 9a (10.0 g, 70.4 mmol) was suspended in MeOH (250 mL). A catalytic amount of H ₂ SO ₄ (0.6 mL) was added and the reaction mixture was refluxed for 18 hr. After concentration, the remaining brown residue was taken up in ethyl acetate and extracted three times with sat. aq. K ₂ C0 ₃ . Drying (Na ₂ S0 ₄ ), filtering, and evaporation of all solvent gave a light brown solid (10.8 g, 63.5 mmol, 90% yield), consisting mainly of cis,cis- and cis, trans- double-bond isomers of DMM 5a and 5b. Example G: Synthesis of trans, trans-DMM from a mixture of cis, cis- and cis, trans-DMM isomers

c/s,c/s-DMM 5a

[00119] A mixture of cis,cis- and cis, trans-DMM 5a and 5b (10.8 g, 63.5 mmol) and a catalytic amount of L_ (300 mg, 1.9 mol %) in MeOH (250 mL) were heated to reflux for 60 hr, at which time TLC and GC-MS confirmed complete conversion. The reaction mixture was then cooled to 0°C, and the resulting precipitate collected by filtration, washed with ice-cold MeOH, and dried under high vacuum (8.2 g, 48.2 mmol, 76% yield). This material was trans, trans-DMM 5c.

Exemplary Reactions

[00120] The following numbered Examples illustrate various reaction conditions for preparing various intermediates and HMDA 1.

Example 1 : Preparation of trans, trans -muconamide \ trans, trans -MCA] from trans, trans-

DMM

trans, trans- DMM 5c trans,trans-MCA 6c

[00121] trans, trans -DMM 5c (27g, 159 mmol) was suspended in aq. ammonia (200 mL) and EtOH (200 mL) and the mixture was allowed to stir at RT for 14 days. The white precipitate formed was filtered, washed with MeOH, and dried under reduced pressure to provide 17.23 g (77% yield) of trans, trans -MCA 6c as white solid. *H and ¹³ C NMR data of trans, trans -MCA 6c is:

¾-NMR (300 MHz, DMSO-d6): δ 7.62 (s, 2H), 7.18 (s, 2H), 7.08 (dd, J = 11.3, 3.3 Hz, 2 H), 6.29 (dd, J = 1 1.3, 3.3 Hz, 2H); and

¹³ C-NMR (75 MHz, DMSO-d6): δ 166.2, 136.8, 130.8. m.p. = 276 C - 280 C

(decomposed). Example 2: Preparation of trans, fraws-mucononitrile \ trans, trans-MN from trans, trans- muconamide \ trans, trans-MCA] using POC as dehydrating agent.

H ₂ NOC

trans,t ns-MCA 6c Reflux; 20 min

trans,trans-MN 7c

[00122] trans, trans -MCA 6c (4 g, 28.5 mmol) was suspended in phosphorus oxychloride (30 mL) and the mixture was brought to reflux for 30 min. Excess phosphorus oxychloride was removed under reduced pressure. The resulting residue was quenched with 100 g of ice and the black precipitate was filtered. The isolated black solid was dissolved in ethyl acetate (100 mL), treated with charcoal (1 g) and filtered through a Whatman # 2 filter paper. The filtrate was concentrated to dryness to provide 2.1 g (70%) of trans, trans -MN 7c as a white solid. ^! H and ¹³ C NMR data of trans, trans -MN 7c is:

¾-NMR (300 MHz, DMSO-d6): δ 7.35 (dd, J = 12.2, 3.0 Hz, 2H); 6.21 (dd, J = 12.2, 3.0 Hz, 2H); and

¹³ C-NMR (75 MHz, DMSO-d6): δ 147.0, 1 17.5, 107.3; MP = 160°C - 162°C.

Example 3 : Preparation of trans, fraws-mucononitrile \ trans, trans-MN ^~ \ from trans, trans- muconamide \ trans, trans-MCA] using P?(¾ as dehydrating agent. Kugelrhor, 120°C;

trans,trans-MCA 6c 90 min; 2 mmHg trans,trans-MN 7c

[00123] trans, trans -MCA 6c (0.5 g) was mixed with phosphorus pentoxide in a 25 mL RBF and placed in the Kugelrohr apparatus to perform bulb-to-bulb distillation. The mixture was heated to 120°C under reduced pressure (2 mmHg) and provided 0.1 g (27%) of trans, trans -MN 7c as a white solid.

Example 4: Preparation of trans, fraws-mucononitrile \ trans, trans-MNI from trans, trans- muconamide \ trans, trans-MCA ^' ] using PdCl? as catalyst.

trans,trans-MCA 6c trans,trans-MN 7c

[00124] trans, trcins-MCA 6c (1 g, 7.17 mmol) was suspended in a 1 : 1/CH ₃ CN:H ₂ 0 (40 mL) solvent mixture along with PdCl2 (0.1 g, 0.563 mmol, 7.9 mol %). The reaction mixture was heated to 50°C for 24 hr under 2 atmosphere.

[00125] The insoluble material was filtered and the filtrate was analyzed by HPLC showing that trans, trans-MN 7c was the major product. Overall 61% of the starting material was consumed to provide 26% of trans, trans-MN 7c with 42% selectivity.

[00126] In an effort to optimize the reaction conditions for converting trans, trans '-MCA 6c to trans, trans-MN 7c using PdCl2 as catalyst, a series of reactions with different amount of solvent constituents were carried out.

[00127] These results are shown in Table 1 below.

Table 1

These results showed that, when the water content was less than 13% as in the case of entry 3 in Table 1 , the rate of conversion was low with only 9% for entry 3.

Example 5: Reduction of trans, trans -muconomtrile \ trans, trans-MN] with Raney Ni catalyst in THF

+ oligomeric NH ₂ material trans,trans-MN 7c HMDA 1

[00128] Into a 500 mL Parr reactor, equipped with a glass liner, trans, trans-MN 7c (2 g, 19.2 mmol) was dissolved in THF along with Raney Nickel (2 g wet). The reactor was pressurized with hydrogen (530 psi) and heated at 1 10°C for 3 hr. The catalyst was filtered and THF was removed under reduced pressured. The resulting black viscous residue was bulb-to- bulb distilled under reduced pressure (2 mmHg) at 70°C using Kulgerhor apparatus to provide 150 mg (6.7%) of HMDA 1 as white solid. The NMR data for the HMDA product matched with the authentic sample obtained from commercial sources. While the reaction conditions in this example do produce HMDA 1, the yield is low and the conditions lead to the production of oligomeric by-products.

Example 6: Reduction of trans, trans- uconomtrile \ trans, trans-MN ^~ \ to

hexamethylenediamine [HMDA] with Raney Ni catalyst in THF in the present of ammonia.

[00129] Into a 500 mL Parr reactor, equipped with a glass-liner, trans, trans-MN 7c (0.5 g, 4.8 mmol) was dissolved in THF along with Raney Nickel (0.8 g wet). The reactor was purged with H ₂ (3X) and pressurized with ammonia (50 psi) and H ₂ (1000 psi), heated for 3hr at 1 10°C. The catalyst was filtered and the filtrate was analyzed by GCMS, which indicated that HMDA (68%) was the only major product with trace amount of 6-aminohexanenitrile (6- AHN).

[00130] Other reaction parameters in the Raney Nickel reduction of trans, trans-MN 7c, such as hydrogen pressure and temperature, were also investigated and the results are sumarized in the table below, Table 2, below. When the reaction was carried out at 80°C, only 18.4% of HMDA 1 was observed along with 75.2% of adiponitrile formed along with 6- aminohexanenitrile (6-AHN) intermediate, entry 3. Similar phenomenon was observed when the reaction was carried out under 300 psi of hydrogen pressure, with 32% of HMDA 1 observed along with 26.3% of adiponitnle and 6-aminohexanenitrile (6-AHN) intermediate (Table 2, entry 4).

Table 2

6-AHN = 6-amino-hexanenitrile; Yes = large amount was observed but was not quantified

Example 7: Preparation of cis rans-muconamide \ cis, trans -MCA] from cis,trans-OMM

cis,trans-MCA 6b

[00131] cz ^' s,iraws-DMM 5b (5 g, 29.5 mmol) was suspended in aq. ammonia (50 mL) and the mixture was allowed to stir at RT for 4 days. The reaction mixture was concentrated until white solid began to precipitate out of the solution. The concentrated solution was chilled in an ice-bath for 1 hr and the precipitate was obtained by filtration, dried under reduced pressure to yield 2.5 g (60% yield) of cis, trans -MCA 6b, as a white solid. ^! H and ¹³ C NMR data of cis, trans-MCA 6b is:

¾-NMR (300 MHz, DMSO-d6) δ 8.22 (ddd, J = 15.5, 1 1.7, 0.9 Hz, 1H), 7.57 (d, J = 4.8 Hz, 2H), 7.14 (d, J = 10.5 Hz, 2H), 6.50 (t, J = 11.7 Hz, 1H), 6.13 (d, J = 15.3 Hz, 1H), 5.95 (d, J = 11.4 Hz, 1H); and

¹³ C-NMR (75 MHz, DMSO-d6) δ 166.8, 166.4, 137.1, 135.2, 130.9, 127.0.

m.p. = 190 C - 192 C (decomposed).

Example 8: Preparation of mucononitrile ΓΜ 1 isomers from cis, trans -muconamide

\cis,trans-MCA] using POCl^as dehydrating agent.

[00132] cis,trans-MCA 6b (2g, 14.2 mmol) was suspended in POCI ₃ (15 mL) and the mixture was brought to reflux for 15 min. Excess POCI ₃ was removed under reduced pressure and the resulting residue was quenched with ice (50g) and extracted with ethyl acetate (3X). The organic fractions were combined, washed with NaHCC (IX), dried with MgS0 ₄ and concentrated to yield a black residue, which was distilled to give mixture of cis, trans-MN 7b and trans, trans-MN 7c (250 mg, 17% yield) as white solid. Example 9: Preparation of cis rans-muconomtrile \cis,trans-MN ^~ \ from cis rans- muconamide \cis,trans-MCA] using PdCl?_as dehydrating agent.

[00133] In order to minimize the isomerization of the cis, trans-MN to trans, trans-MN as observed when POCI ₃ was used as the dehydrating agent in the process of converting cis,trans- MCA to cis, trans-MN, milder reaction condition and PdC¾ was used as dehydrating agent for converting cis,trans-MCA to MN. With silica-gel chromatography, pure cis, trans-MN was isolated and characterized and the process is described below.

cisJran MCA 6b cis,trans-MN 7b

[00134] cis,trans-MCA 6b (3 g, 21.4 mmol) was suspended inl : l/CH ₃ CN:H ₂ 0 solvent mixture (40 mL) along with PdC¾ (0.2 g, 1.1 mmol). The reaction mixture was heated at 50°C and the progress of the reaction was monitored by TLC. After 18 hr of stirring at 50°C, the reaction mixture was filtered and CH ₃ CN was removed under reduced pressure. The resulting aq. fraction was extracted with ethyl acetate (3X). The organic fractions were combined, dried (MgS0 ₄ ), and concentrated to yield yellowish residue, which was purified by silica-gel chromatography (3: l/hexane:ethyl acetate) to yield 0.5 g of cis, trans-MN 7b as a white solid, which turns grayish as being exposed to air indicating that cis, trans-MN 7b may not be a stable compound. ^J H and ¹³ C NMR data of cis, trans-MN 7b is:

¾-NMR (300 MHz, DMSO-d6) δ 7.45-7.32 (m, 1H), 7.31-7.18 (m, 1H), 6.45-6.32 (m, 1H), 6.15-6.05 (m, 1H); and

¹³ C-NMR (75 MHz, DMSO-d6) δ 145.5, 144.2, 1 17.3, 115.6, 108.5, 105.7.

Example 10: Reduction of cis, fraws-mucononitrile \ cis, trans-MN] to hexamethylenediamine

[HMDA] with Raney Ni catalyst in THF in the present of ammonia.

cis,trans-MN 7b HMDA 1 [00135] Into a 500 niL Parr reactor, equipped with a glass-liner, cis,trans-MN 7b (0.5 g, 4.8 mmol) was dissolved in THF along with Raney Nickel (0.8 g wet). The reactor was purged with nitrogen (3X) and pressurized with ammonia (50 psi) and H ₂ (1000 psi), heated for 3hr at 1 10°C. The catalyst was filtered and the filtrate was analyzed by GCMS, which indicated that 75% of HMDA 1 formed as the only major product, its physical and spectra data matched with that of the authentic HMDA obtained from commercial sources.

Example 11 : Preparation of czs.czs-muconamide \cis,cis-MCA]

[00136] cis,cis-OMM 5a (6.2 g, 36.4 mmol) was suspended in aq. ammonia (50 mL) and the mixture was allowed to stir at RT for 4 days. The white precipitate was obtained by filtration, dried under reduced pressure to yield 3.0 g (59% yield) of white solid cis,cis-MCA 6a. ^! H and ¹³ C NMR data of cis,cis-MCA 6a is:

Ή-NMR (300 MHz, DMSO-d6): δ 7.72 (dd, J = 8.1, 2.1 Hz, 2 H), 7.57 (s, 2H), 7.10 (s, 2H), 5.91 (dd, J = 8.2, 2.1 Hz, 2H); and

¹³ C-NMR (75 MHz, DMSO-d6): δ 167.1, 134.3, 126.3. m.p. = 244 C - 246 C

(decomposed).

Example 12: Preparation of czs.czs-mucononitrile l cz ^' s.cz ^' s-MNI and cis, trans -mucono tdle \cis, trans -MN ^~ \ from cis,cis- uconamide\cis,cis-MCA]

cis,cis-MCA 6a cis,cis-MN 7a cis,trans-MN 7b

[00137] cis,cis-MCA 6a (3 g, 21.4 mmol) was suspended POCI ₃ (15 mL) and the mixture was brought to reflux for 15 min. Excess POCI ₃ was removed under reduced pressure and the resulting residue was quenched with ice (50 g) and extracted with ethyl acetate (3X). The organic fractions were combined, dried (MgS0 ₄ ), and concentrated to yield a black viscous residue that was distilled at 80°C under reduced pressure (2 mmHg) to provide 200 mg of white solid. The ^! H and ¹³ C-NMR data showed this product was a mixture of cis,cis-MN 7a and cis,trans-MN 7b.

Example 13 : Reduction of czs.czs-mucononitrile fez ^' s, cz ^' s-MNI to hexamethylenediamine ΓΗΜΡΑ1 with Raney Ni catalyst in THF in the presence of ammonia.

c/s.c/s-MN 7a

[00138] Into a 500 mL Parr reactor, equipped with a glass-liner, cis,cis-MN 7a (0.5 g, 4.8 mmol) was dissolved in THF along with Raney Nickel (0.8 g wet). The reactor was purged with nitrogen (3X) and pressurized with ammonia (50 psi) and H ₂ (1000 psi), and then heated for 3hr at 110°C. The catalyst was filtered and the filtrate was analyzed by GCMS, which indicated that 63% of HMDA 1 formed as the only major product; its physical and spectra data matched with that of the authentic HMDA obtained from commercial sources.

Example 14: Reduction of trans, trans-muconamide \ trans, trans-MCA] to adipamide over copper chromite and zeolite co-catalyst in THF

H,N .

CONH THF; H ₂ , NH ₃ HMDA 1

H ₂ NOC ² + 2 CuO-Cr ₂ 0 ₃ ¹ - +

200°C; 6 hr

trans,trans-MCA 6c .CONH,

H ₂ NOC'

adipamide 8

[00139] trans, trans -MCA 6c (1 g, 7.1 mmol) plus copper chromite (0.5 g) and zeolite (0.5 g) were suspended in THF (100 mL). The mixture was heated to 200°C under hydrogen pressure (300 psi) for 6 hr. The catalyst was filtered along with other insoluble solids and dried under reduced pressure. Analysis of the filtrate by GCMS showed no detectable amount of HMDA. The isolated solid was analyzed by NMR, which indicated that it contained mainly adipamide 8 (Table 3, entry 1).

[00140] Other conditions were also assayed for the reduction of trans, trans-MCA 6c to

HMDA 1 and the results are summarized in Table 3. In a related application, U.S. Patent

Application entitled "Process for Preparing Caprolactam and Polyamides Therefrom", Attorney Docket No. 136556-013102/US, filed on April 9, 2012, various processes are described to make caprolactam.

Table 3

Under the reaction conditions tested in entries I, 2 and 3, adipamide 8 was detected. 1 ,6-hexanediol was detected when the reaction was carried out for 18 hr (entry 2). HMDA was detected when the reaction was carried out at 250°C in the presence of ammonia and under high pressure of hydrogen (entries 4 through 8).

Example 15: Preparation of biomass-derived adiponitrile from biomass-derived adipamide using POC as dehydrating agent.

H ₂ NO

a pam e adiponitrile 4

[00141] Adipamide 8 (4 g, 27.7 mmol) that was prepared from biomass-derived MCA, was suspended in phosphorus oxychloride (30 mL) and the mixture was brought to reflux for 30 min. Excess phosphorus oxychloride was removed under reduced pressure. The resulting residue was quenched with 100 g of ice and the mixture was extracted with ethyl acetate (3X, 100 mL). The organic fractions were combined, dried (MgSC^), and concentrated. The resulting residue was distilled at 80°C under reduced pressure (2 mmHg) to obtain 1.8 g (60%) of adiponitrile 4. The physical and spectra data of the product matched those of authentic sample obtained from commercial sources.

Example 16: Reduction of biomass-derived adiponitrile to hexamethylenediamine ΓΗΜΡΑ1 in Butanol using Raney Nickel as catalyst.

H N .

adiponitrile 4

[00142] Biomass-derived adiponitrile 4 (5 g, 48 mmol) was suspended in w-BuOH (80 mL) and Raney Nickel (1.7 g). The mixture was heated at 110°C for 2hr under ¾ atmosphere (530 psi) in a high pressure, high temperature Parr reactor. The catalyst was then removed by filtration. The filtrate was analyzed by GCMS, which indicated that 5% of HMDA 1 formed and 4% of adiponitrile 4 remained unreacted along with other uncharacterized by-products.

Example 17: Reduction of adiponitrile to hexamethylenediamine [HMDA] in THF using Raney Nickel as catalyst. N H ₂

[00143] Into a 500 niL Parr reactor, equipped with a glass-liner, biomass-derived adiponitrile 4 (5 g, 46.2 mmol) was dissolved in THF (100 mL) along with Raney Nickel (1.7 g wet). The reactor was pressurized with hydrogen (530 psi) and heated at 1 10°C for 2 hr. The catalyst was filtered through a Whatman #2 filter paper after the reaction solution has been cooled down to RT. The filtrate was analyzed by GCMS showing that HMDA 1 was the main product with trace amount of adiponitrile remained unreacted. THF was removed under reduced pressured and the resulting residue, a brown viscous oil, was distilled at 70°C using a Kugelrohr apparatus to provide 2.44 g (45%) of HMDA 1 as white solid material, and the NMR data matched with that of the authentic material obtained from Sigma-Aldrich.

[00144] Although the invention has been described with reference to its preferred embodiments, those of ordinary skill in the art may, upon reading and understanding this disclosure, appreciate changes and modifications which may be made which do not depart from the scope and spirit of the invention as described above or claimed hereafter.

Accordingly, this description is to be construed as illustrative only and is for the purpose of teaching those skilled in the art the general manner of carrying out the invention.

INCORPORATION BY REFERENCE

[00145] Reference is made to PCT International Patent Application entitled "Process for Preparing Caprolactam and Polyamides Therefrom", Attorney Docket No. 136556- 013102/PCT filed with the U.S. Receiving Office on April 9, 2012, and U.S. Patent

Application No. 13/442,306 entitled "Process for Preparing Caprolactam and Polyamides Therefrom", Attorney Docket No. 136556-013103/US filed on April 9, 2012, the entire content of both of which is hereby incorporated by reference. All publications, patent applications and patents mentioned herein are hereby incorporated by reference in their entirety as if each individual publication, patent application and patent was specifically and individually indicated to be incorporated by reference.