Patent Application
20210214298
The disclosure provides methods for deoxydehydration of sugar-based derivatives using hydrogen gas as a reducing agent.
Lignocellulosic biomass is the most abundant resource of organic carbon on Earth and is the only renewable resource that is cheap enough to replace fossil fuels and sustain energy demands in the transportation sector. Such biomass is composed of three major polymeric components: cellulose, hemicellulose, and lignin. Cellulose is crystalline in structure and is comprised of linear β-1,4 linked glucose units known as glucan. Hemicellulose is amorphous in structure and is often primarily comprised of polymeric chains of β-1,4 linked xylose units known as xylan, a major hemicellulose component in most hardwood species, agricultural residues, and herbaceous energy crops. Lignin is a cross-linked heterogeneous complex covalently bonded to hemicellulose involving polymers of phenyl propanol units called monolignols.
The disclosure provides a method for the deoxydehydration of vicinal diols allowing for access of deoxygenated analogues of sugar-based derivatives. The methods of the disclosure allow for the use of carboxylic acids and esters derived from sugars as substrates and hydrogen gas as a reducing agent.
In a particular embodiment, the disclosure provides a method for the deoxydehydration (DODH) of a sugar derivative comprising: (a) incubating a reaction mixture for a sufficient period of time to allow for formation of one or more deoxydehydrated products, wherein the reaction mixture comprises: (i) a reactant selected from the group consisting of an aldaric acid, an aldaric acid derivative, an aldonic acid, aldonic acid derivative, a sugar lactone, and a sugar lactone derivative; (ii) a catalyst selected from the group consisting of a vanadium-based catalyst, a molybdenum-based catalyst, a rhenium-based catalyst, and any combination thereof; (iii) a reducing agent comprising hydrogen gas; (iv) a solvent system; and (v) optionally an acid.
In another embodiment, the reaction is carried out by incubating the reaction mixture at a temperature greater than 20° C. In yet another embodiment, the reaction mixture is incubated at a temperature between 120° C. to 300° C. In a further embodiment, the reaction is carried out for up to 72 hours. In yet a further embodiment, the reaction mixture is incubated at about 150° C. for up to 4 hours.
In accordance with an important feature of the present invention, it was found that only vicinal diols in an α, β-position to an electron withdrawing group, such as a carbonyl group, undergo a DODH reaction. Examples of electron withdrawing groups are carboxylic acid, ester, and lactone.
In a certain embodiment, for a method disclosed herein, the catalyst can be regenerated and reused (e.g., step (a)) by exposing the catalyst to an oxidizing agent comprising oxygen gas. In a further embodiment, after performing step (a), the method further comprises: (b′) adding to the reaction mixture a catalyst selected from the group consisting of a vanadium-based catalyst, a palladium-based catalyst, a platinum-based catalyst, a nickel-based catalyst, a molybdenum-based catalyst, a lithium-based catalyst, an aluminum based-catalyst, an iron-based catalyst, an iridium-based catalyst, a rhodium-based catalyst, a rhenium-based catalyst, and any combination thereof; and subsequently or simultaneously increasing the pressure of the hydrogen gas up to 300 psi and heating the reaction mixture at a temperature between 120° C. to 160° C.
In a particular embodiment, a method disclosed herein can be repeated one or more times. In another embodiment, a method disclosed herein further comprises separating the product from any remaining reactant and reaction intermediates. In yet a further embodiment, a method disclosed herein is performed using a one pot synthesis strategy.
In a certain embodiment, a method disclosed herein produces one or more reduced product(s) comprising at least one reduced product that comprises a structure selected from the group consisting of formula I, formula II, formula III, and formula IV:
wherein, R1, R2, and R3 are each independently selected from the group consisting of H, optionally substituted (C1-C12)alkyl, optionally substituted (C1-C11)heteroalkyl, optionally substituted (C2-C12)alkenyl, optionally substituted (C2-C11)heteroalkenyl, optionally substituted (C2-C12) alkynyl, optionally substituted (C2-C11)heteroalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycle, and optionally substituted aryl. In a further embodiment, a reduced product of formula IV is produced from the reduced products of formula I, or from formula II that is produced from the compound of formula I, or from formula III that is produced from formula II that is produced from formula I.
In a certain embodiment, the disclosure provides for a method for the deoxydehydration (DODH) of a sugar derivative comprising: (a) incubating a reaction mixture for a sufficient period of time to allow for formation of one or more deoxydehydrated products, wherein the reaction mixture comprises: (i) a reactant selected from the group consisting of an aldaric acid, an aldaric acid derivative, an aldonic acid, aldonic acid derivative, a sugar lactone, and a sugar lactone derivative; (ii) a catalyst selected from the group consisting of a vanadium-based catalyst, a molybdenum-based catalyst, a rhenium-based catalyst and any combination thereof; (iii) a reducing agent comprising hydrogen gas; (iv) a solvent system; and (v) optionally an acid; (b) adding to the reaction mixture one or more catalysts suitable for the hydrogenation of an alkene and/or increasing the pressure of hydrogen gas up to 300 psi; followed by (c) repeating step (a); followed by (d) repeating step (b); and (e) optionally repeating steps (a) and (b) until the majority of the sugar derivatives has been converted to a reduced product having the structure of formula IV:
wherein, R2 and R3 are independently selected from the group consisting of H, optionally substituted (C1-C12)alkyl, optionally substituted (C1-C11)heteroalkyl, optionally substituted (C2-C12)alkenyl, optionally substituted (C2-C11)heteroalkenyl, optionally substituted (C2-C12) alkynyl, optionally substituted (C2-C11)heteroalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycle, and optionally substituted aryl. In a further embodiment, steps (a), (b), (c), (d) and/or (e) are carried out at a temperature from 20° C. to 300° C.
In a particular embodiment, a method disclosed herein comprises an aldaric acid reactant and the deoxydehydrated product is an unsaturated dicarboxylic acid compound. In an alternate embodiment, a method disclosed herein comprises a glucaric acid reactant and the one or more deoxydehydrated products is adipic acid.
In yet another embodiment, a method disclosed herein uses a rhenium-based catalyst. Examples of rhenium-based catalyst include, but are not limited to, HReO4, KReO4, NH4ReO4, ReO2, ReIO2(Ph3P)2, ReCl3O(Ph3P)2, CH3ReO3 (MTO), and ReCl3. In a certain embodiment, a method of the disclosure uses MTO or HReO4 catalyst. In an alternate embodiment, a method disclosed herein uses a vanadium-based catalyst. Examples of vanadium-based catalysts include, but are not limited to, NBu4VO3, NBu4VO2(CA)2, HC(PZ)VO2BF4, TpaVO2PF6, NaVO2(acac)2, and Bu4N(dipic)VO2. In yet another embodiment, a method disclosed herein uses molybdenum-based catalysts. Examples of molybdenum-based catalysts include, but are not limited to, MoO3, Mo(CO)6, Mo(CO)4(bipy), MOO2Cl2(bipy), MoO2Br2(bipy), MoO2(CH3)2(bipy),(NH4)6Mo7O24.4H2O, and H3PMo12O40.
In a further embodiment, a method disclosed herein comprises palladium on carbon (Pd/C), sodium sulfite, triphenylphospine, and/or secondary alcohols. In yet a further embodiment, a method disclosed herein comprises Pd/C.
Surprisingly, it was found that the addition of a second component to the catalyst system, e.g., Pd/C, improved the DODH capabilities of the catalyst system. For example: the addition of Pd/C increases the reaction speed (4 hours to 0.75 hours) and the yield to 90% from 55%. Thus, in a further embodiment, the method disclosed herein additionally comprises Pd/C.
In a certain embodiment, a method disclosed herein comprises a solvent system which comprises ones or more polar solvents. Examples of polar solvents include but are not limited to water, methanol, ethanol, n-propanol, n-butanol, isopropanol, acetic acid, and formic acid. In another embodiment, a method disclosed herein comprises a solvent system which comprises ethanol and/or methanol.
In a particular embodiment, the disclosure also provides a method to produce (C4-C7)-linear saturated carboxylic acids from polysaccharides and/or disaccharides comprising: (A) polysaccharides and/or disaccharides with enzymes to hydrolyze the polysaccharides and/or disaccharides into simple sugars; (B) oxidizing the simple sugars to form aldonic acids or aldaric acids; and (C) deoxydehydrating the aldonic acids or aldaric acids using any one of the preceding methods to produce (C4-C7)-linear saturated carboxylic acids; or optionally (B′) derivatize the aldonic acid or aldaric acid of step (B), and (C′) deoxydehydrating the aldonic acid derivatives or aldaric acid derivatives using any one of the preceding methods to produce (C4-C7) linear saturated carboxylic acids and/or (C4-C7)-linear saturated carboxylic acid derivatives, which may be hydrolyzed to the (C4-C7)-linear saturated carboxylic acids.
In yet another embodiment, the disclosure provides a method to produce (C4-C7)-linear saturated carboxylic acids from a lignocellulosic biomass comprising: (A) pretreating the lignocellulosic biomass with one or more physical processes, one or more chemical processes, and/or one or more biological agent(s) or any combination thereof to generate solubilized lignocellulosic polymers; (B) hydrolyzing the lignocellulosic polymers using enzymes and/or chemical treatment to obtain simple sugars; (C) oxidizing the simple sugars to form aldaric acids or aldonic acids; and (D) deoxydehydrating the aldaric acids or aldonic acids using any one of the disclosed methods to produce (C4-C7)-linear saturated carboxylic acids; or optionally (C′) derivatize the aldonic acid or aldaric acid of step (C); and (D′) deoxydehydrating the aldonic acid derivatives or aldaric acid derivatives using any one of the preceding methods to produce (C4-C7)-linear saturated carboxylic acids and/or (C4-C7)-linear saturated carboxylic acids derivatives, which may be hydrolyzed to the (C4-C7)-linear saturated carboxylic acids. In yet another embodiment, the lignocellulosic biomass is pretreated with one or more physical processes and/or with acid; the lignocellulosic polymers are hydrolyzed by enzymatic action; and/or the simple sugars are oxidized by treating with nitric acid. In a further embodiment, the aldaric acids using in the reaction mixture comprises glucaric acid, and wherein the (C4-C7)-linear saturated carboxylic acid derivative comprises adipic acid esters and wherein the (C4-C7)-linear saturated carboxylic acid comprises adipic acid.
In a particular embodiment, a method disclosed herein comprises a reaction mixture that comprises an aldaric acid derivative reactant having the structure of:
wherein, R10 and R11 are independently selected from the group consisting of H, optionally substituted (C1-C12)alkyl, optionally substituted (C1-C11)heteroalkyl, optionally substituted (C2-C12)alkenyl, optionally substituted (C2-C11)heteroalkenyl, optionally substituted (C2-C12)alkynyl, optionally substituted (C2-C11)heteroalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycle, and optionally substituted aryl, wherein at least one of R10 or R11 is not H. In a further embodiment, the reaction mixture which comprises the aldaric acid derivative is incubated at a temperature greater than 20° C. In yet a further embodiment, the reaction mixture which comprises the aldaric acid derivative is incubated at a temperature between 120° C. to 300° C. In another embodiment, the reaction mixture which comprises the aldaric acid derivative is incubated for up to 72 hours. In yet another embodiment, the reaction mixture which comprises the aldaric acid derivative is incubated at about 150° C. for up to 4 hours. In a further embodiment, the reaction mixture which comprises the aldaric acid derivative comprises a rhenium-based catalyst (e.g., MTO). In yet a further embodiment, the reaction mixture which comprises the aldaric acid derivative comprises a solvent system which comprises an alcohol (e.g., ethanol). In another embodiment, the reaction mixture which comprises the aldaric acid derivative comprises palladium on carbon (Pd/C).
In yet a further embodiment, the reaction mixture which comprises the aldaric acid derivative produces a deoxydehydrated product which comprises a lactone derivative having a structure of:
wherein, R10 is selected from the group consisting of H, optionally substituted (C1-C12)alkyl, optionally substituted (C1-C11)heteroalkyl, optionally substituted (C2-C12)alkenyl, optionally substituted (C2-C11)heteroalkenyl, optionally substituted (C2-C12)alkynyl, optionally substituted (C2-C11)heteroalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycle, and optionally substituted aryl. In yet a further embodiment, a method disclosed herein comprises a reaction mixture that comprises the lactone derivative with one or more reducing agents comprising hydrogen gas. In another embodiment, the hydrogen gas is used at a pressure up to 300 psi. In another embodiment, a reaction mixture that comprises the lactone derivative is incubated at a temperature greater than 20° C. in a solvent system comprising a catalyst suitable for the hydrogenation of an alkene. In yet a further embodiment, a reaction mixture that comprises the lactone derivative comprises a solvent system comprising an alcohol (e.g., ethanol). In yet another embodiment, a reaction mixture that comprises the lactone derivative further comprises a catalyst comprising Pd/C.
In yet a further embodiment, a reaction mixture that comprises the lactone derivative produces a reduced product having a structure of:
wherein, R10 is selected from the group consisting of H, optionally substituted (C1-C12)alkyl, optionally substituted (C1-C11)heteroalkyl, optionally substituted (C2-C12)alkenyl, optionally substituted (C2-C11)heteroalkenyl, optionally substituted (C2-C12)alkynyl, optionally substituted (C2-C11)heteroalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycle, and optionally substituted aryl.
In a certain embodiment, a method of deoxydehydrating a reduced lactone product having the structure of
comprises incubating a reaction mixture comprising the reduced product for a sufficient period of time to allow for formation of a deoxydehydrated product, wherein the reaction mixture comprises: a catalyst selected from the group consisting of a vanadium-based catalyst, a molybdenum-based catalyst, a rhenium-based catalyst and any combination thereof; a reducing agent comprising hydrogen gas; a solvent system; and optionally an acid, wherein R10 is selected from the group consisting of H, optionally substituted (C1-C12)alkyl, optionally substituted (C1-C11)heteroalkyl, optionally substituted (C2-C12)alkenyl, optionally substituted (C2-C11)heteroalkenyl, optionally substituted (C2-C12)alkynyl, optionally substituted (C2-C11)heteroalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycle, and optionally substituted aryl. In another embodiment, a reaction mixture comprising the reduced lactone product is incubated at a temperature greater than 20° C. In yet another embodiment, a reaction mixture comprising the reduced lactone product is incubated at a temperature between 120° C. to 300° C. In a further embodiment, a reaction mixture comprising the reduced lactone product is incubated for up to 72 hours. In yet a further embodiment, a reaction mixture comprising the reduced lactone product is incubated at about 150° C. for up to 4 hours. In a certain embodiment, a reaction mixture comprising the reduced lactone product comprises a rhenium-based catalyst. Examples of rhenium-based catalysts include, but are not limited to, HReO4, KReO4, NH4ReO4, ReO2, ReIO2(Ph3P)2, ReCl3O(Ph3P)2, CH3ReO3 (MTO), and ReCl3. In a particular embodiment, a reaction mixture comprising the reduced lactone product comprises MTO. In another embodiment, a reaction mixture comprising the reduced lactone product comprises an alcohol (e.g., ethanol). In yet another embodiment, a reaction mixture comprising the reduced lactone product further comprises Pd/C. In a further embodiment, a reaction mixture comprising the reduced lactone product produces hex-2-enedioic acid diethyl ester.
In a particular embodiment, the disclosure also provides a method of reacting hex-2-enedioic acid diethyl ester with one or more reducing agents comprising hydrogen gas. In a further embodiment, the hydrogen gas is used at a pressure of up to 300 psi. In yet a further embodiment, the hex-2-enedioic acid diethyl ester is reduced at a temperature greater than 20° C. in a solvent system comprising a catalyst suitable for the hydrogenation of an alkene. In another embodiment, the solvent system comprises an alcohol (e.g., ethanol). In yet another embodiment, the catalyst comprises Pd/C. In a further embodiment, the method of reducing hex-2-enedioic acid diethyl ester produces diethyl adipate.
In a certain embodiment, the disclosure also provides a method for the deoxydehydration (DODH) of a sugar derivative, comprising:(a) incubating a reaction mixture at 220 to 295° C. for a sufficient period of time to allow for formation of one or more deoxydehydrated products, wherein the reaction mixture comprises a reactant having the structure of
catalysts comprising (NH4)6Mo7O24 and Pd/C; a reducing agent comprising hydrogen gas; a solvent system comprising ethanol, wherein, R10 is selected from the group consisting of H, optionally substituted (C1-C12)alkyl, optionally substituted (C1-C1)heteroalkyl, optionally substituted (C2-C12)alkenyl, optionally substituted (C2-C11)heteroalkenyl, optionally substituted (C2-C12)alkynyl, optionally substituted (C2-C11)heteroalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycle, and optionally substituted aryl.
In a certain embodiment, a method disclosed herein comprises a reaction mixture which comprises a sugar lactone derivative having the structure of Formula V or Formula V(a):
wherein, v is an integer selected from the group consisting of 1, 2, 3, 4, and 5; w is an integer selected from the group consisting of 0, 1, 2, 3, 4, 5 and 6; z1 is an integer selected from κ or 1; R4, R5, R6, R1, R8, and R9 are each independently an H, hydroxyl, halo, ester, alkoxy, alkenyloxy, thiol, optionally substituted (C1-C12)alkyl, optionally substituted (C1-C1)heteroalkyl, optionally substituted (C2-C12)alkenyl, optionally substituted (C2-C11)heteroalkenyl, optionally substituted (C2-C12)alkynyl, optionally substituted (C2-C11)heteroalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycle, and optionally substituted aryl; and R10 is selected from the group consisting of H, optionally substituted (C2-C12)alkyl, optionally substituted (C1-C11)heteroalkyl, optionally substituted (C2-C12)alkenyl, optionally substituted (C2-C11)heteroalkenyl, optionally substituted (C2-C12)alkynyl, optionally substituted (C2-C11)heteroalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycle, and optionally substituted aryl. In a further embodiment, the reaction mixture comprising the lactone of Formula V or Formula V(a) is incubated at a temperature between 120° C. to 300° C. In yet a further embodiment, the reaction mixture comprising the lactone of Formula V or Formula V(a) is incubated for up to 72 hours. In another embodiment, the reaction mixture comprising the lactone of Formula V of Formula V(a) is incubated at about 150° C. for up to 4 hours. In yet another embodiment, the reaction mixture comprising the lactone of Formula V of Formula V(a) comprises a rhenium-based catalyst (e.g., MTO). In yet another embodiment, the reaction mixture comprising the lactone of Formula V of Formula V(a) comprises a solvent system comprising an alcohol (e.g., ethanol). In a certain embodiment, the reaction mixture comprising the lactone of Formula V of Formula V(a) further comprises palladium on carbon (Pd/C).
In another embodiment, the reaction mixture comprising the lactone of Formula V or Formula V(a) produces a structure of Formula VI or Formula VI(a):
wherein, v is an integer selected from the group consisting of 1, 2, 3, 4, and 5; w is an integer selected from the group consisting of 0, 1, 2, 3, 4, 5 and 6; z and z2are independently selected integers from 0 or 1; R4, R5, R6, R7, R8, and R9 are each independently an H, hydroxyl, halo, ester, alkoxy, alkenyloxy, thiol, optionally substituted (C1-C12)alkyl, optionally substituted (C1-C1)heteroalkyl, optionally substituted (C2-C12)alkenyl, optionally substituted (C2-C11)heteroalkenyl, optionally substituted (C2-C12)alkynyl, optionally substituted (C2-C11)heteroalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycle, and optionally substituted aryl; and R10 and R11 are independently selected from the group consisting of H, optionally substituted (C1-C12)alkyl, optionally substituted (C1-C11)heteroalkyl, optionally substituted (C2-C12)alkenyl, optionally substituted (C2-C11)heteroalkenyl, optionally substituted (C2-C12)alkynyl, optionally substituted (C2-C11)heteroalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycle, and optionally substituted aryl.
In yet another embodiment, the method further comprises reducing the deoxydehydrated product of Formula VI or Formula VI(a) using one or more reducing agents comprising hydrogen gas. In a further embodiment, the hydrogen gas is used at pressure of up to 300 psi. In yet a further embodiment, the deoxydehydrated product of Formula VI or Formula VI(a) is reduced at a temperature greater than 20° C. in a solvent system comprising a catalyst suitable for hydrogenating an alkene. In another embodiment, the solvent system comprises an alcohol (e.g., ethanol). In yet another embodiment, the catalyst comprises Pd/C. In a particular embodiment, the reduction of the deoxydehydrated product of Formula VI or Formula VI(a) produces a reduced product having a structure of Formula VII:
wherein, v is an integer selected from the group consisting of 1, 2, 3, 4, and 5; w is an integer selected from the group consisting of 0, 1, 2, 3, 4, 5 and 6; z1 and z2 are integers independently selected from 0 or 1; R4, R5, R6, R7, R8, and R9 are each independently an H, hydroxyl, halo, ester, alkoxy, alkenyloxy, thiol, optionally substituted (C1-C12)alkyl, optionally substituted (C1-C11)heteroalkyl, optionally substituted (C2-C12)alkenyl, optionally substituted (C2-C11)heteroalkenyl, optionally substituted (C2-C12)alkynyl, optionally substituted (C2-C11)heteroalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycle, and optionally substituted aryl; and R10 and R1 are independently selected from the group consisting of H, optionally substituted (C1-C12)alkyl, optionally substituted (C1-C11)heteroalkyl, optionally substituted (C2-C2)alkenyl, optionally substituted (C2-C11)heteroalkenyl, optionally substituted (C2-C12)alkynyl, optionally substituted (C2-C11)heteroalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycle, and optionally substituted aryl.
As used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a catalyst” includes a plurality of such catalysts and reference to “the reducing agent” includes reference to one or more reducing agents or equivalents thereof known to those skilled in the art, and so forth.
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 disclosure belongs. Although many methods and reagents similar to or equivalent to those described herein can be used in the practice of the disclosed methods and compositions, the exemplary methods and materials are now described.
All publications mentioned herein are incorporated herein by reference in their entirety for the purposes of describing and disclosing methodologies that might be used in connection with the description herein. Moreover, with respect to any term that is presented in the publications that is similar to, or identical with, a term that has been expressly defined in this disclosure, the definition of the term as expressly provided in this disclosure will control in all respects.
As used herein, the term “alkyl” refers to straight chain and branched saturated Cn-p hydrocarbon groups. Nonlimiting examples of alkyl groups include methyl, ethyl, and straight chain and branched propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, and decyl groups. The term Cn means the alkyl group has “n” carbon atoms. The term Cn-p means that the alkyl group contains “n” to “p” carbon atoms. The term “alkylene” refers to an alkyl group having a substituent. An alkyl, e.g., methyl, or alkylene, e.g., —CH2—, group can be unsubstituted or substituted with halo, trifluoromethyl, trifluoromethoxy, and alkoxy, for example.
As used herein, the terms “alkenyl” and “alkynyl” refer to unsaturated aliphatic groups analogous in length and optional substitution to the alkyls described above, but that contain at least one double or triple bond, respectively.
As used herein, the terms “heteroalkyl”, “heteroalkenyl”, and “heteroalkynyl” refer to an alkyl, alkenyl, or alkynyl group as defined above, wherein one to four carbon atoms are replaced by an oxygen, nitrogen, or sulfur atom, optionally substituted as described for an alkyl group.
As used herein, the term “cycloalkyl” and “cycloalkenyl” mean a monocyclic or bicyclic aliphatic ring system containing three to ten carbon atoms. A cycloalkenyl group contains at least one carbon-carbon double bond. The terms “heterocycloalkyl” and “heterocyclo” mean a monocyclic or bicyclic ring system containing three to ten total atoms and at least one nitrogen, oxygen, or sulfur atom in the ring system.
These ring systems are optionally substituted as described above for an alkyl group.
As used herein, the term “aryl” refers to a monocyclic or polycyclic aromatic group, preferably a monocyclic or bicyclic aromatic group, e.g., phenyl or naphthyl. Unless otherwise indicated, an aryl group can be unsubstituted or substituted with one or more, and in particular one to four, groups independently selected from, for example, halo, alkyl, —OCF3, —CF3, alkoxyl, aryl, and heteroaryl.
As used herein, the term “heteroaryl” refers to a monocyclic or bicyclic ring system containing one or two aromatic rings and containing at least one and up to four nitrogen and/or oxygen and/or sulfur atom in an aromatic ring. Unless otherwise indicated, a heteroaryl group can be unsubstituted or substituted with one or more, and in particular one to four, substitutents selected from, for example, halo, alkyl, —OCF3, —CF3, alkoxy, aryl, and heteroaryl.
As used herein, the term “halo” is defined as encompassing fluoro, chloro, bromo, and iodo.
The term “hydroxy” is defined as —OH.
The term “alkoxy” is defined as —OR, wherein R is alkyl.
The term “alkenoxy” is defined as —OR, wherein R is alkenyl.
The term “amino” is defined as —NH2 and the term “alkylamino” is defined as —NR2, wherein at least one R is alkyl and the second R is alkyl or hydrogen.
The term “nitro” is defined as —NO2.
The term “cyano” is defined as —CN.
The term “trifluoromethyl” is defined as —CF3.
The term “trifluoromethoxy” is defined as —OCF3.
The term “thiol” is defined as —SR, wherein R is defined as alkyl.
The term “ester” is defined as —C(═O)OR, wherein R is alkyl or aryl.
As used herein, a “sugar compound” refers to sweet, short-chain, soluble carbohydrate comprised of hydrogen, oxygen and carbon atoms. A “sugar compound” will typically have a chemical formula of Cx(H2O)x, where x is an integer from 3 to 7. Specific examples of sugar compounds include erythrose, threose, erythrulose, arabinose, lyxose, ribose, xylose, ribulose, xylulose, allose, altrose, glucose, mannose, gulose, idose, galactose, talose, psicose, fructose, sorbose, tagatose, sedoheptulose, and mannoheptulose.
As used herein, the term “sugar derivative” refers to a sugar compound in which one or more functional groups of the sugar compound have been substituted, removed or modified. Examples of “sugar derivatives” would include, but are not limited to, aldaric acids, aldonic acids, and sugar lactones, or a derivative of any of the foregoing. In a particular embodiment, a “sugar derivative” refers to an ester or a carboxylic acid derivative of a sugar compound (e.g., a hydroxyl group and/or a ketone/aldehyde group of a sugar compound has been replaced with an ester or carboxylic group). In a further embodiment, a “sugar derivative” comprises 4 to 7 carbon atoms.
As used herein, an “aldaric acid” refers to a compound in which a terminal hydroxyl and aldehyde group of a sugar compound has been replaced with a carboxylic acid group Generally, an “aldaric acid” is characterized by the formula HOOC—(CHOH)n—COOH. Examples of aldaric acids include, but are not limited to, tartaric acid, arabinaric acid, ribaric acid, xylaric acid, allaric acid, altraric acid, glucaric acid, talaric acid.
As used herein, an “aldaric acid derivative” refers to an aldaric acid compound in which one or more functional groups has been substituted, removed, or modified. For example, an “aldaric acid derivative” could include an aldaric acid compound where one or more of the terminal carboxylic acid groups are replaced with ester groups.
As used herein, an “aldonic acid” refers to compound in which an aldehyde or hydroxyl group of a sugar compound has been replaced with a carboxylic acid group. Examples of aldonic acids include, but are not limited to, arabinonic acid, ribonic acid, glyceric acid, gluconic acid, galacturonic acid, glucoronic acid, iduronic acid, threonic acid, and xylonic acid.
As used herein, an “aldonic acid derivative” refers to an aldaric acid compound in which a hydroxyl and/or a carboxylic acid group has been replaced or substituted with a different group. For example, an “aldonic acid derivative” could include an aldonic acid compound where a terminal carboxylic acid group was replaced with an ester.
As used herein, a “sugar lactone” refers to a cyclic ester compound that has formed from the dehydration of a sugar compound.
As used herein, a “sugar lactone derivative” refers to a sugar lactone that is derived from aldonic acid, aldonic acid derivative, aldaric acid, and an aldaric acid derivative. In a particular embodiment, a sugar lactone derivative comprises the structure of Formula V:
v is an integer selected from the group consisting of 0, 1, 2, 3, 4, and 5;
w is an integer selected from the group consisting of 0, 1, 2, 3, 4, 5 and 6;
R4, R5, R6, R7, R8, and R9 are each independently an H, hydroxyl, halo, ester, ether, sulfide, optionally substituted (C1-C12)alkyl, optionally substituted (C1-C11)heteroalkyl, optionally substituted (C2-C12)alkenyl, optionally substituted (C2-C11)heteroalkenyl, optionally substituted (C2-C12) alkynyl, optionally substituted (C2-C11)heteroalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycle, and optionally substituted aryl; and
R10 is selected from the group consisting of H, optionally substituted (C1-C12)alkyl, optionally substituted (C1-C1)heteroalkyl, optionally substituted (C2-C12)alkenyl, optionally substituted (C2-C11)heteroalkenyl, optionally substituted (C2-C12) alkynyl, optionally substituted (C2-C11)heteroalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycle, and optionally substituted aryl; wherein the dash line indicates that the bond may be a single covalent bond or double covalent bond, and wherein if the bond is double covalent bond then R4 and R6 are absent.
In an alternate embodiment, the disclosure provides for a sugar lactone derivative comprising the structure of Formula V(a):
wherein,
v is an integer selected from the group consisting of 0, 1, 2, 3, 4, and 5;
w is an integer selected from the group consisting of 0, 1, 2, 3, 4, 5 and 6;
R4, R5, R6, R7, R8, and R9 are each independently an H, hydroxyl, halo, ester, ether, sulfide, optionally substituted (C1-C12)alkyl, optionally substituted (C1-C11)heteroalkyl, optionally substituted (C2-C12)alkenyl, optionally substituted (C2-C11)heteroalkenyl, optionally substituted (C2-C12) alkynyl, optionally substituted (C2-C11)heteroalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycle, and optionally substituted aryl; and
R10 is selected from the group consisting of H, optionally substituted (C1-C12)alkyl, optionally substituted (C1-Cu)heteroalkyl, optionally substituted (C2-C12)alkenyl, optionally substituted (C2-C11)heteroalkenyl, optionally substituted (C2-C12) alkynyl, optionally substituted (C2-C11)heteroalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycle, and optionally substituted aryl; wherein the dash line indicates that the bond may be a single covalent bond or double covalent bond, and wherein if the bond is double covalent bond then R4 and R6 are absent. In a particular embodiment, the lactone ring of Formula V and Formula V(a) does not contain a doubly covalent carbon to carbon bond.
Lignocellulosic biomass is the most abundant resource of organic carbon on Earth and is a renewable resource that can economically replace fossil fuels for production of liquid fuels and sustain future energy demands in the transportation sector. Additionally, conversion of the lignocellulosic biomass to industrially desirable compounds, such as adipic acid, would also provide a great benefit. A feasible conversion strategy requires efficiently overcoming the recalcitrance of lignocellulose to maximize the yield of reactive sugar intermediates and their derivatives that are suitable for transformation to final products by targeted conversion technologies. The chemical transformation of lignocellulosic biomass provides an intriguing route to access C3-C6 commodities (e.g., malonic acid, succinic acid, glutaric acid, and adipic acid).
Cellulosic and lignocellulosic biomass residues and wastes, such as agricultural residues, wood, forestry wastes, sludge from paper manufacture, and municipal and industrial solid wastes, provide a potentially large renewable feedstock for the production of chemicals, plastics, fuels, and feeds. Cellulosic and lignocellulosic biomass residues and wastes, composed of carbohydrate polymers comprising cellulose, hemicellulose, and lignin can be generally treated by a variety of chemical, mechanical, and enzymatic means to release primarily hexose and pentose sugars, which are typically fermented to useful products including ethanol or dehydrated by acids to furfural, 5-HMf, and levulinic acid, which can then be catalytically upgraded to gasoline, diesel, and jet range fuels.
Pretreatment methods are used to make the carbohydrate polymers of cellulosic and lignocellulosic materials more readily available to saccharification enzymes or acid catalysts. Standard pretreatment methods have historically utilized primarily strong acids at high temperatures; however due to high energy costs, high equipment costs, high pretreatment catalyst recovery costs and incompatibility with saccharification enzymes, alternative methods are being developed, such as enzymatic pretreatment, or the use of acid or base at milder temperatures where decreased hydrolysis of biomass carbohydrate polymers occurs during pretreatment, requiring improved enzyme systems to saccharify both cellulose and hemicellulose. Additionally, carbohydrate polymers of cellulosic and lignocellulosic materials can be accessed by using one or more physical approaches, including, milling, chipping, grinding, pyrolysis, extrusion, explosion (e.g., steam explosion, ammonia fiber explosion, carbon dioxide explosion) and irradiation (e.g., gamma rays, electron beam, ultrasounds, microwaves). Chemical pretreatment methods for lignocellulosic material, include but are not limited to, ozonolysis, acid hydrolysis, alkaline hydrolysis, oxidative delignification, and organosolv process. Additionally, pulsed electric-field pretreatment may also be employed. It should be further understood that the pretreatment of cellulosic and lignocellulosic materials may be accomplished by using any of the foregoing processes alone or alternatively in combination, e.g., pretreating the lignocellulosic materials with steam explosion, acid hydrolysis, and enzymatic treatment.
Glucaric acid is a member of a larger group of compounds known as sugar acids, and more specifically, aldaric acids. Glucaric acid has garnered attention because it was identified as one of the top 12 renewable building block chemicals by a 2004 US Department of Energy (DoE) report: Top value added chemicals from biomass. It can be prepared in one step from abundant and inexpensive glucose and has numerous potential applications, both as a building block chemical and in direct end uses. The unique molecular structure of glucaric acid, a carbohydrate diacid, provides for a range of technical applications that require varying levels of solubility, biodegradability, and safe dispersal in the environment. Conventionally, glucaric acid is made from glucose using nitric acid as the oxidizing agent. Other aldaric acids are created from aldoses in a similar manner. In recent years, other oxidation methods for preparing glucaric acid have been developed. Nitric acid, however, remains superior with respect to versatility, reaction efficiency, both in time and energy, and in raw material cost.
The high degree of oxygenation of sugar derivatives, like aldaric acids, creates a synthetic challenge. Deoxydehydration (DODH) reactions provide a potential solution. Traditionally, DODH reactions have been implemented for the conversion of vicinal diols to olefin products using high valent oxo-rhenium catalysts with various reducing agents (e.g., see
The application of DODH to industrially relevant processes, however, requires further modifications, namely the incorporation of H2 gas as the reducing source. The main advantage of using H2 gas is the generation of H2O as the sole byproduct of the catalytic cycle. While DODH has been shown to be reduced by H2, the results have been greatly limited by substrate scope, modest yields, and the over-reduction of the resulting olefin. In addition to the incorporation of H2 gas, the ability to perform DODH in the presence of carboxylic acids and ester motifs is also advantageous. The DODH reaction with sorbitol, the reduced derivative of glucose, provides hexatriene, which to date, has not found much industrial utility (see
The disclosure provides for DODH methods capable of reducing a sugar derivative to a reduced DODH olefin adduct which can be further reduced to an unsaturated dicarboxylic acid product or an unsaturated di-ester product. In particular embodiments, the DODH methods disclosed herein provide for a reaction mixture comprising a sugar derivative or a sugar compound, a catalyst, a reducing agent, and a solvent system. Typically, the reaction is heated and maintained at an elevated temperature for a sufficient period of time to allow for product formation. However, depending upon the components of the reaction mixture, such as the sugar derivative used or the catalyst used, product formation may still result without the use of supplemental heating, by maintaining the reaction at or around ambient temperature or at a lower temperature. In further embodiments, the reaction is maintained at temperature from 20° C. to 300° C., 50° C. to 250° C., from 100° C. to 180° C., or from 120° C. to 160° C. In a particular embodiment, the reaction mixture is heated and maintained at a temperature around 150° C. Generally, the reaction is performed up to 72 hours, up to 48 hours, up to 24 hours, up to 12 hours, up to 6 hours, up to 3 hours, from 30 minutes to 3 hours, from 1 to 2 hours at a certain temperature (e.g., around 150° C.).
In some embodiments, it is preferred to first apply a lower temperature, i.e., about 20° C. to about 130° C., then raise the temperature to complete the reaction. In particular, certain substrates cannot withstand an initial high temperature and decompose. For these substrates, a “thermal posttreatment” significantly increased the yield of the desired product.
In a particular embodiment, the DODH methods disclosed herein utilize a sugar derivative as a substrate. Examples of sugar derivatives, include, but are not limited to, aldaric acids, derivatives of aldaric acids (e.g., ester substituted aldaric acids), aldonic acids, derivatives of aldonic acids (e.g., ester substituted aldonic acids), sugar lactones (e.g., ribonolactone), and derivatives of sugar lactones.
In a certain embodiment, the DODH methods disclosed herein utilizes a catalyst (e.g., a transition metal-based catalyst). In a further embodiment the catalyst is an oxorhenium based catalyst. Examples of oxorhenium based catalysts, include, but are not limited to, HReO4, KReO4, NH4ReO4, ReO2, ReIO2(Ph3P)2, ReCl3O(Ph3P)2, CH3ReO3 (MTO), and ReCl3. In a further embodiment, the catalyst used in the methods of the disclosure is MTO. In an alternate embodiment, the catalyst used in methods disclosed herein is a vanadium-based catalyst. Examples of vanadium-based catalysts include, but are not limited to, NBu4VO3, NBu4VO2(CA)2, HC(PZ)VO2BF4, TpaVO2PF6, NaVO2(acac)2, and Bu4N(dipic)VO2. In a particular embodiment, the vanadium-based catalyst is Bu4N(dipic)VO2 (dioxovanadium(v)dipicolinate). In yet another alternate embodiment, the catalyst used in methods disclosed herein is a molybdenum-based catalyst. Examples of molybdenum-based catalysts include, but are not limited to, MoO3, Mo(CO)6, Mo(CO)4(bipy), MOO2Cl2(bipy), MoO2Br2(bipy), MoO2(CH3)2(bipy),(NH4)6MoO24.4H2O, H3PMo12O40, and (NH4)6MO7O24.4H2O. In a certain embodiment, the molybdenum-based catalyst is Mo(CO)4(bipy) or (NH4)6Mo7O24.4H2O. In a further embodiment, the catalyst can be loaded as low as 2.5% and still provide acceptable yields.
In one preferred embodiment, the catalyst comprises KReO4 in combination with Pd/C. The KReO4—Pd/c combination allows the use of a low H2 pressure, which generate a saturated lactone.
The DODH methods disclosed herein can further utilize one or more additional reducing agents in addition to hydrogen gas. Examples of such reducing agents, include, but are not limited to, sodium sulfite, triphenylphospine, and secondary alcohols.
The DODH methods of the disclosure typically use a solvent system. Examples of solvents that can be used in the methods disclosed herein, include, but are not limited to, alcohols (e.g., methanol, ethanol, isopropanol, n-propanol, and n-butanol), carboxylic acids (e.g., formic acid, acetic acid, p-toulenesulfonic acid), water, nonpolar organic solvents (e.g., toluene, benzene, xylene, hexane, diethyl ether, dichloromethane, and 1,4-dioxane), polar organic solvents (e.g., tetrahydrofuran, ethyl acetate, acetone, dimethylformamide, acetonitrile, and dimethyl sulfoxide).
In further embodiments, it has been shown that the addition of an acid to the reaction mixture described herein may allow for the full conversion of a reactant (e.g., a sugar lactone derivative) to a desired product (e.g., diethyl adipate) without having to use differential H2 pressures. Examples of acids that can be used include but are not limited to, phosphoric acid, hydrochloric acid, hydrofluoric acid, nitric acid, nitrous acid, acetic acid, sulfuric acid, citric acid, carbonic acid, oxalic acid, and formic acid. It is a particular benefit of this embodiment that the acidic additive allows opening of the saturated lactone obtained formed after the first DODH/hydrogenation cycle, and thus adipic acid or its ester is formed be formed after a second DODH/hydrogenation cycle.
In further embodiments, it has been shown that the addition of an activated charcoal to the reaction mixture described herein may allow for the full conversion of a reactant (e.g., a sugar lactone derivative) to a desired product (e.g., diethyl adipate) without having to use differential H2 pressures and improved yields. An example of a charcoal that can be used is C270C purchased from Fischer.
In a certain embodiment, the DODH methods disclosed herein utilize an oxorhenium catalyst (KReO4) and a hydrogen activating catalyst (Pd/C) in an alcoholic solvent (methanol) to convert a reactant (e.g., a sugar lactone derivative) to a desired product (e.g., dialkyl adipate) with hydrogen as the reducing agent at a temperature of 150° C. in yields>85%.
The following examples are intended to illustrate, but not limit, the disclosure. While they are typical of procedures that might be used, other procedures known to those skilled in the art may alternatively be used.
Development of an effective DODH strategy to produce a DODH adduct lactone product from oxidized derivatives of glucose using H2 as a reducing agent. It was found that the unsaturated analog of levulinic acid could be isolated in moderate to good yield by performing a reaction with ribonolactone, a catalytic amount of HReO4 in dioxanes at 150° C. and under 150 psi of H2 gas (see
Modifying the previous DODH reaction conditions in view of the ribonolactone reduction findings. In view of the foregoing results with ribonolactone, it was concluded that H2-driven DODH is plausible with sugar-based derivatives. Unfortunately, the relative abundance of ribose is much lower than glucose.
In a series of experiments, it was found that lowering the H2 pressure of the reaction mixture facilitated increased yields of a DODH adduct resulting from glucaro-6,3-lactone (see
Development of a one-pot strategy to form adipic acid from the DODH adduct lactone product. After the successful production of the DODH lactone adduct, a process amenable to the formation of adipic acid from the DODH lactone adduct was devised. The unsaturated lactone generated from the first DODH event could be hydrogenated with fresh Pd/C under H2 in quantitative yield. The saturated lactone was then subjected to nearly identical DODH conditions as previously utilized, which facilitated lactone ring opening and subsequent DODH with the resulting diol to provide an enoate in 95% yield. Lastly, olefin hydrogenation generated diethyl adipate in 97% yield (e.g., see
Based upon the synthetic route above, the similarity of the reaction conditions facilitated a one-pot sequence for the chemical transformation of diethyl glucarate to diethyl adipate. Palladium and rhenium catalysts added at various times during the reaction course led to complicated reaction mixtures. It was found, however, that modulation of the H2 pressure combined with one additional loading of rhenium (i.e. MTO), provided diethyl adipate in 72% overall yield (NMR yield) (see
DODH reactions: A solution of the DODH substrate, MTO, and 10% Pd/C (4.25:1 Re:Pd, i.e. equal wt % of MTO to Pd/C) in EtOH (typically about 0.08M w/respect to a sugar derivative) was introduced into a Parr reactor or pressure sealed glass tube and purged with H2 (1 atm), closed, and heated to 150° C. The reaction times vary depending on catalyst loadings, e.g., for 10 mol % MTO leads to about 1 hour, or 2 hours. The reaction was monitored by NMR analysis following the concentration of small reaction aliquots. When the reaction was observed to be complete, the reaction mixture was filtered through celite. The celite was rinsed with MeOH and the resulting liquid was concentrated.
All-in-one pot synthesis: A solution of diethyl glucarate, MTO, Pd/C in EtOH in a Parr reactor was setup as stated above. When the reaction was observed to be complete, the H2 pressure was increased to 300 psi and reheated to 150° C. The reaction mixture was again monitored by NMR. Once olefin hydrogenation was complete, an additional loading of MTO was added to the reaction mixture. Typically, twice the loading of MTO compared to the initial loading was found to be sufficient DODH reactivity. The reaction was subjected to 1 atm H2 and heated to 150° C. Again, the reaction mixture was monitored by NMR. Once complete, the reaction was pressurized to 300 psi H2 and reheated to 150° C. When completed by NMR analysis, the reaction mixture was filtered through celite, rinsed with MeOH, and concentrated.
NMR yield analysis: the crude mixtures were evaluated with a known amount of mesitylene. Purification by column chromatography was typically performed with 0-3% MeOH:DCM, depending the extent of oxygenation of the product.
To further demonstrate the present DODH method, a series of experiments was performed to show that under the disclosed reactions conditions, only vicinal diols that are in α,β-position to an electron-withdrawing group, preferably a carbonyl group, and still more preferably a carboxylic acid, ester, or lactone moiety, undergo DODH.
The following three starting materials (SM) individually were subjected to the following reaction condition.
It was found that when no carboxylate group is present, then no conversion to DODH products occurred.
In another experiment, the mixture below was subjected to the indicated reaction conditions.
It was found that the disclosed catalyst system and reaction conditions selectively convert only vicinal diols that are a, to a carboxylate group. The sorbitol was not converted.
The following substrates were subjected to the following DODH reaction. A solution of the DODH substrate, MTO, and 10% Pd/C (4.25:1 Re:Pd, i.e. equal wt % of MTO to Pd/C) in EtOH (typically about 0.08M with respect to a sugar derivative) was introduced into a Parr reactor or pressure sealed glass tube and purged with H2 (1 atm), closed, and heated to 150° C. The reaction times vary depending on catalyst loadings, e.g. for 10 mol % MTO leads to about 1 hour, or 2 hours. The reaction was monitored by NMR analysis following the concentration of small reaction aliquots. When the reaction was observed to be complete, the reaction mixture was filtered through celite. The celite was rinsed with MeOH and the resulting liquid was concentrated.
The above further illustrates the substrate selectivity of the disclosed DODH method.
In another experiment, a transformation to adipic acid in one pot was acheived, without adding additional catalyst, by regenerating the catalyst in situ by reoxidation with oxygen. As shown in the following reaction scheme, iteratively repeating the atmosphere exchange cycles, the yield of adipic acid was improved. The hydrogenation step is conducted at elevated H2 pressure; whereas the DODH chemistry is conducted at low H2 pressure.
The headspace above a solution of 1 (132 mg), MTO (15 mg), and 10% Pd/C (15 mg) in EtOH (7.5 mL) in a Parr reactor was purged with H2 and maintained under 1 atm of H2. The reaction was heated to 150° C. After 1.5 hours, the reaction was cooled to room temperature and the reactor was pressurized to 300 psi with H2. The reaction was re-heated to 150° C. for 1.5 hours. The reaction was cooled to room temperature. The headspace was purged with N2 to facilitate removal of residual H2. The headspace was then purged with 1 atm O2, capped, and stirred at room temperature overnight. The reaction was purged with N2 to remove residual O2. The process described above (i.e., heating at 1 atm H2, heating at 300 psi H2, followed by O2 treatment) was repeated 3 times.
The reaction mixture was collected, centrifuged, and the supernatant was removed by pipet. The remaining solids were washed and re-centrifuged with EtOH (2×10 mL). The combined supernatant was collected and concentrated to provide 5 in 74% yield (NMR analysis with mesitylene as a standard).
The following examples utilizes KReO4 as a DODH catalyst. It was found that potassium perrhenate demonstrated a significant improvement compared to MTO in the DODH reaction.
After 4 hours, full conversion of the starting material was achieved. In contrast to the MTO-Pd/C catalyst system, the hydrogenation activity was retained at low H2 pressure leading to formation of the saturated lactone. Both the DODH reaction and the hydrogenation reaction occur with a H2 pressure of 75-100 psi. Essentially only the desired product was observed in NMR analysis.
It therefore is possible to directly transform a glucaric acid derivative to adipic acid under one set of conditions, if the saturated lactone can be ring-opened and the second DODH performed.
A Parr reactor charged with polyol (7.5 mmol), KReO4 (22 mg), 10% Pd/C (60 mg), 85% H3PO4 (26 mg), and EtOH (7.5 mL) was pressurized to 75 psi with H2. The reaction was placed in a preheated oil bath set to 150° C. for a 4 hours. The reaction mixture was cooled to room temperature, filtered, rinsed with ethanol, and concentrated.
Mesitylene was added to the crude residue as a standard for the determination of yields by NMR.
The effect of including an acidic additive also was investigated. It was hypothesized that an acidic additive would allow opening of the saturated lactone obtained above, and thus adipic acid would be formed after a second DODH/hydrogenation cycle.
The effect of phosphoric acid addition is illustrated in the above reaction system. Under these acidic conditions, the hypothesis was proved correct. The saturated lactone reacts further, and diethyl adipate was formed in 70% overall yield from the starting material.
A Parr reactor charged with polyol (7.5 mmol), KReO4 (22 mg), 10% Pd/C (60 mg), 85% H3PO4 (26 mg), and EtOH (7.5 mL) was pressurized to 75 psi with H2. The reaction was placed in a preheated oil bath set to 150° C. until the reaction was complete (typically from a few hours up to three days). The reaction mixture was cooled to room temperature, filtered, rinsed with EtOH, and concentrated.
Mesitylene was added to the crude residue as a standard for the determination of yields by NMR.
In another example, it was found that activated charcoal as an additive significantly promoted the DODH/hydrogenation reaction. The exemplary charcoal is C270C purchased from Fischer. The experiments were performed on a series of substrates shown in the following table.
The table above demonstrates the significant yield improvements achieved by the addition of charcoal. The yield of adipate was improved to 91% from 70% by addition of activated charcoal, while the same ease of use (no atmosphere exchange, all reactions to the adipate carried out under the same set of conditions) was maintained. The catalyst system is also competent in the transformation of other diols in α,β-position to carboxylate moieties as demonstrated in the table above. The final example in the table, i.e., 1,5-gluconolactone, demonstrates this selectivity within a single molecule: only the α,β-diol group is transformed. The other hydroxy functionalities are not affected.
A Parr reactor charged with polyol (7.5 mmol), KReO4 (22 mg), 10% Pd/C (60 mg), 85% H3PO4 (26 mg), granular activated carbon (450 mg, C270C, purchased from Fisher), and MeOH (7.5 mL) was pressurized to 75 psi with H2. The reaction was placed in a preheated oil bath set to 150° C. for a given amount of time until the reaction was complete (typically from a few hours up to three days). The reaction mixture was cooled to room temperature, filtered, rinsed with MeOH, and concentrated.
Mesitylene was added to the crude residue as a standard for the determination of yields by NMR.
The effect of temperature and substrate on activity and catalyst loading also was investigated. Using the conditions disclosed above, the influence of an increase in temperature was examined. When using 6,3-glucarolactone monoethyl ester as the starting material, the temperature can be increased with essentially no loss of yield (90% vs. 91%) and with a decrease in reaction to 7 hours from 18 hours as shown below. The reaction at lower temperature was carried out with KReO4 as the rhenium source, whereas the higher temperature reaction used (NBu4)ReO4.
When using glucarodilactone as the starting material, direct application of 170° C. led to significant product decomposition. This was overcome by first applying a lower temperature (120° C.) to the reaction mixture and subsequently raising the temperature to 170° C. Using this “thermal pre-treatment” approach, dimethyl adipate was obtained in 90% yield compared to 70% when the reaction was carried out at 150° C. Using the thermal pre-treatment reaction conditions, the catalyst loading can be reduced from 1 mol % KReO4 to 0.25 mol % with only a moderate decrease in yield (75% vs. 90%).
Representative procedure: A Parr reactor charged with polyol (7.5 mmol), KReO4 (22 mg), 10% Pd/C (60 mg), 85% H3PO4 (26 mg), granular activated carbon (450 mg, C270C, purchased from Fisher), and MeOH (7.5 mL) was pressurized to 75 psi with H2. The reaction was placed in a preheated oil bath set to the appropriate temperature for a given amount of time. The reaction mixture was cooled to room temperature, filtered, rinsed with MeOH, and concentrated.
Mesitylene was added to the crude residue as a standard for the determination of yields by NMR.
In another example, a Parr reactor charged with polyol (7.5 mmol), KRe04 (22 mg), 10% Pd/C (60 mg), 85% H3PO4 (26 mg), and EtOH(7.5 mL) was pressurized to 75 psi with H2. The reaction was placed in a preheated oil bath set to 150° C. until the reaction was complete (typically from a few hours up to three days). The reaction mixture was cooled to room temperature, filtered, rinsed with EtOH, and concentrated.
Mesitylene was added to the crude residue as a standard for the determination of yields by NMR. It was found that diethyl adipate was formed in 70% overall yield from the starting material.
The effect of solvent and substrate also was investigated. It was found that the choice of solvent has a strong effect on the yield of the reaction when glucarodilactone is used as the substrate.
Using methanol as the solvent improves the yield by about 10% (78% vs 67%). It is theorized, but not relied upon, that, in methanol, glucarodilactone is rapidly converted into either the monolactone monoethyl ester species or the dimethyl glucarate. These compounds are theorized to be less thermally sensitive than the dilactone, thus reducing decomposition over time. To test this theory, the dilactone was reacted for 1.25 h at 120° C. in ethanol and methanol, respectively, and the product distribution analyzed.
When methanol was used as the solvent, a stronger shift of the product distribution towards the diester and the monoesters was detected compared to the use of ethanol. Thus, a low temperature thermal pre-treatment is advantageous when using glucarodilactone as the starting material with an alcohol as the solvent. Methanol is a preferred alcoholic solvent.
DODH reaction: Representative procedure: A Parr reactor charged with polyol (7.5 mmol), KReO4 (22 mg), 10% Pd/C (60 mg), 85% H3PO4 (26 mg), granular activated carbon (450 mg, C270C, purchased from Fisher), and MeOH (7.5 mL) was pressurized to 75 psi with H2. The reaction was placed in a preheated oil bath set to the appropriate temperature for a given amount of time. The reaction mixture was cooled to room temperature, filtered, rinsed with MeOH, and concentrated.
Mesitylene was added to the crude residue as a standard for the determination of yields by NMR.
As demonstrated above, an important feature of the present invention is the discovery that the addition of a second component to the catalyst system, e.g., Pd/C, surprisingly improved the DODH capabilities of the catalyst system.
The above reactions demonstrate that the addition of the Pd/C increases the reaction speed (4 hours to 0.75 hours) and the yield to 90% from 55%.
The same results were obtained when using the 6,3-glucarolactone monomethyl ester (lactone 2 below) as the substrate. It was found that omitting either the hydrogen or the hydrogenation catalyst results in significantly lower yields.
Another important feature of the present invention is the discovery of a four step route to diethyl adipate. In particular, diethyl adipate can be obtained from lactone 1 in a four step reaction sequence coupling DODH reaction steps and hydrogenation steps.
A 350 mL glass schlenk tube was charged with 1(450 mg), MTO (21 mg), 10% Pd/C (21 mg), and EtOH (21 mL). The tube was purged with H2 and capped with 1 atm of H2. The reaction was placed in a preheated oil bath at 150° C. After 2.5 hours, the reaction was cooled to room temperature. The mixture was filtered through celite, rinsed with MeOH, and concentrated. The crude residue was purified by column chromatography (2.5% MeOH:DCM) to provide compound 2 (282 mg, 74%) as a white solid.
A solution of compound 2 (100 mg) and 10% Pd/C (15 mg) in EtOH (5 mL) was stirred under 1 atm of H2 (balloon) for 2 hours at room temperature. The reaction was filtered through celite, rinsed with EtOH, and concentrated to provide 3 (100 mg, 99%) as a white solid.
A 100 mL glass schlenk tube was charged with 3 (80 mg), MTO (10 mg), 10% Pd/C (4 mg), and EtOH (5 mL). The tube was purged with H2 and capped with 1 atm of H2. The reaction was placed in a preheated oil bath at 150° C. After 4 hours, the reaction was cooled to room temperature, filtered through celite, rinsed with DCM, and concentrated. The crude residue was purified by column chromatography (DCM) to provide 4 (81 mg, 95%) as a colorless oil.
A solution of 4 (68 mg) and 10% Pd/C (5 mg) in EtOH (2 mL) stirred under 1 atm of H2 (balloon) overnight. The reaction was filtered through celite, rinsed with DCM, and concentrated to provide 5 (63 mg, 97%) as a colorless oil.
A number of embodiments have been described herein. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of this disclosure. Accordingly, other embodiments are within the scope of the following claims.
This application claims the benefit of U.S. Provisional Application No. 62/300,008, filed Feb. 25, 2016, and Provisional Application No. 62/311,488, filed Mar. 22, 2016, the disclosures of which are incorporated herein by reference in their entirety.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2017/018779 | 2/22/2017 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 62300008 | Feb 2016 | US | |
| 62311488 | Mar 2016 | US |
