RU2801218C2 - Dehydration and splitting of alpha-, beta-dihydroxycarbonyl compounds to lactic acid and other products - Google Patents

Abstract

FIELD: chemical industry.

SUBSTANCE: invention relates to a method for the synthesis of pyruvic acid or its salt, including (a) dehydration of the starting compound in the form of glucaric acid or its salt, or a stereoisomer of glucaric acid or its salt, with the formation of a dicarbonyl intermediate compound 2-keto-3-deoxyglucaric acid or a salt thereof, or a stereoisomer of 2-keto-3-deoxyglucaric acid or a salt thereof by converting the alpha hydroxy group to a second carbonyl group and removing the beta hydroxy group, and (b) cleaving the dicarbonyl intermediate to give pyruvic acid or a salt thereof.

EFFECT: method for the synthesis of pyruvic acid or pyruvate from substrates that are obtained from renewable carbohydrate resources.

5 cl, 2 dwg, 1 tbl, 5 ex

Description

FIELD OF THE INVENTION

The present invention relates to methods for the synthesis of cleavage products, using pyruvic acid and glyceraldehyde as precursors for a number of valuable end products, and the cleavage products and end products contain fewer carbon atoms relative to α-, β-dihydroxycarbonyl starting compounds, including α-, β- dihydroxycarboxylic acids and carboxylates, such as products derived from glucose.

PRIOR ART

The depletion of fossil fuels has created a strong incentive to look for alternative sources of petroleum carbon to produce so-called "platform" molecules with low carbon numbers, such as propylene glycol and other 3 carbon (C ₃ ) products. Biomass, from which many of these well-known valuable petroleum-based chemicals can be derived, is currently being considered as a potential replacement, but developing sustainable technologies to produce such chemicals from renewable resources remains a major challenge. In recent years, the biodiesel industry has provided large quantities of crude glycerol as a by-product of refining triglycerides from vegetable oils and animal fats. This glycerin can serve as a feedstock for these same valuable lower carbon chemicals, such as propylene glycol. However, significant costs are inherent in the steps required to properly purify glycerol for this purpose, and the biodiesel industry is highly dependent on tax credits and other forms of government subsidies for its profitability.

The current state of the art will greatly benefit from the development of synthetic routes designed to produce valuable intermediates such as pyruvic acid and glyceraldehyde and/or their derived transformation products such as lactic acid, glycerol and propylene glycol from readily available or readily available substrates. and in particular from substrates that are derived from renewable carbohydrate resources.

BRIEF DESCRIPTION OF THE INVENTION

Aspects of the present invention relate to the discovery of synthetic methods that can use substrates such as gluconic acid and glucaric acid, which are easy to obtain, for example, from the oxidation of glucose. Such substrates generally exhibit higher stability under high temperature conditions than their aldehyde precursors (e.g., glucose), which can result in increased reaction selectivity and yield in the desired reaction sequence to one or more specific products. This reduces the loss of products due to unwanted side reactions. Of particular interest are the "cleavage" products formed by breaking the carbon-carbon bond and thus containing fewer carbon atoms compared to the substrate used. The preparation of suitable substrates from the oxidation of aldehyde precursors to carboxylates is straightforward and inexpensive, usually requiring only air as an oxidizing agent. Particular aspects relate to the ability of carboxylate anion-containing substrates to undergo a series of reaction steps in solution, resulting in the formation of the desired 3-carbon cleavage products, such as pyruvic acid and glyceraldehyde, which can be further converted under the same reaction conditions (e.g., by hydrogenation/reduction) into desired end products such as lactic acid, glycerol and even propylene glycol (1,2-propanediol).

Particular aspects relate to synthetic routes that use a cleavage step after the formation of the dicarbonyl intermediate from the α-,β-dihydroxycarbonyl starting compound. Cleavage can be initiated using a cleavage catalyst under the reaction conditions described herein. Cleavage products with fewer carbon atoms include, for example, compounds with 3 carbon atoms, such as those described above, which can be synthesized from any substrates or starting compounds with 4-, 5-, or 6 carbon atoms. Such substrates may, for example, typically form pyruvic acid as a cleavage product. More specific aspects relate to identifying such synthetic pathways or individual reaction steps of such pathways that can be carried out non-enzymatically, which means without the use of an enzyme (eg, polypeptide) in the reaction mixture. In the case where the methods described herein are carried out non-enzymatically, for example, using only one or more chemical catalysts, and not biological catalyst(s), the advantages are to provide a wider range of possible reaction conditions, such as temperature and/or pH conditions that will be unfavorable for biological agents (for example, will cause denaturation of proteins, including enzymes), but which, nevertheless, provide high performance values in relation to the desired intermediate and/or end product. Other advantages may result from lower operating costs, and especially the costs otherwise associated with separating the enzyme from the product, compared to the relatively low cost associated with separating a heterogeneous or homogeneous chemical catalyst. According to some embodiments, at least one of the synthetic steps described herein: (i) dehydration of the starting compound to form the dicarbonyl intermediate, (ii) cleavage of the dicarbonyl intermediate to form the cleavage product, (iii) hydrogenation of the cleavage product with the formation of the final product and (iv) the conversion of the second cleavage product into an additional amount of the final product, is a non-enzymatic reaction step (ie, catalyzed without the use of an enzyme). Preferably at least two of (i), (ii), (iii) and (iv) are not enzymatic reaction steps, more preferably at least three of (i), (ii), (iii) and (iv ) are not enzymatic reaction steps, and even more preferably all of (i), (ii), (iii) and (iv) are not enzymatic reaction steps.

Embodiments of the present invention relate to methods for synthesizing a cleavage product containing fewer carbon atoms relative to the parent compound. The parent compound or substrate contains a carbonyl functional group (C=O) with hydroxy-substituted carbon atoms in the alpha (α) and beta (β) positions relative to the carbonyl functional group. In accordance with one stage of the reaction, this is the starting compound, namely α-, β-dihydroxycarbonyl compound, i.e. a general class of compounds that encompasses α-, β-dihydroxycarboxylic acids and carboxylates are dehydrated to form a dicarbonyl intermediate by converting the α-hydroxy group to a second carbonyl group (adjacent to the carbonyl group of the parent compound) and removing the β-hydroxy group. The dicarbonyl intermediate is then cleaved to form a cleavage product which is itself a dicarbonyl but which contains fewer carbon atoms than the dicarbonyl intermediate and retains the first and second carbonyl groups. This cleavage usually results in a second cleavage product, such as an aldehyde or carboxylate, which is different from the (dicarbonyl) cleavage product. Often in the case of 6 carbon substrates, both the (dicarbonyl) cleavage product and the second cleavage product (eg aldehyde or carboxylate) can be 3 carbon products such as glyceraldehyde or 2-hydroxy-3-oxopropanoic acid. In the case of 5 carbon substrates (dicarbonyl) the cleavage product may be a 3 carbon product and the second cleavage product (e.g. aldehyde or carboxylate) may be a 2 carbon product such as 2-hydroxyacetaldehyde or 2-oxoacetic acid. In the case of 4 carbon substrates (dicarbonyl), the cleavage product may be a 3 carbon product and the second cleavage product (eg aldehyde or carboxylate) may be a one carbon product such as formaldehyde or formic acid.

Either or both of the cleavage product and the second cleavage product can be further converted, eg by hydrogenation/reduction under reducing conditions (eg, elevated hydrogen partial pressure), which may be present in the reaction medium, into hydrogenated end products. Such hydrogenated end products in the case of pyruvic acid as the (dicarbonyl) cleavage product may include lactic acid or in the case of glyceraldehyde or 2-hydroxy-3-oxopropanoic acid as the second cleavage product (e.g. aldehyde or carboxylate) may include glycerol or glyceric acid respectively. Other valuable end products may include lactic acid obtained from glyceraldehyde via reactions involving 1,2-hydride shift or hydride transfer (Cannizzaro reaction).

These and other aspects, embodiments and associated advantages will become apparent from the following detailed description.

BRIEF DESCRIPTION OF GRAPHICS

Figure 1 shows the general mechanism of the reaction, including the steps for the synthesis of cleavage products and final products in accordance with the methods of synthesis described in this document.

The figure 2 shows the specific reaction mechanism, according to which gluconic acid is the starting material or substrate.

The figures are to be understood as representing embodiments of the present invention to aid understanding of the principles and reaction chemistry involved, and not to limit the scope of the present invention as defined in the appended claims. As will be apparent to one of ordinary skill in the art having knowledge of the present invention, the synthetic methods in accordance with various other embodiments of the present invention will use specific reactants and certain reaction conditions, at least in part in accordance with the specific objectives.

DETAILED DESCRIPTION OF EMBODIMENTS

As used herein, the term "substrate" or alternatively "parent compound" refers to a parent compound that is subjected to one or preferably a series of transformation steps, such as "dehydration", "cleavage" and optionally "hydrogenation" transformation steps, to give one or more cleavage products and/or end products. These conversion steps do not preclude the use of pre-conversion steps, e.g. under the same reaction conditions (e.g. in the same reactor) or under different reaction conditions (e.g. in a separate reactor) as those used to obtain the cleavage products and/or final products. . Such preliminary conversion steps may include the conversion of a readily available precursor, such as glucose, to gluconic acid or glucaric acid as the starting compound, for example, by oxidation. Similarly, the steps carried out "to obtain the cleavage product" or "to obtain the final product" do not exclude the use of subsequent conversion steps, for example under the same reaction conditions (for example, in the same reactor) or under different reaction conditions (for example, in a separate reactor) as used to obtain products) splitting and/or end product(s), to obtain one or more other desired end products. For example, lactic acid as a hydrogenated end product may be further converted to propylene glycol or acrylic acid. Glyceric acid as a hydrogenated end product may be further converted to glycerol.

The terms "mole %" and "wt %" are used to refer to amounts or concentrations in terms of mole percentages and weight percentages, respectively. Yields given in terms of "mole %" refer to the number of moles of a given product (eg, a cleavage product such as pyruvic acid) obtained, based on the number of moles of substrate used (introduced or fed into the reactor).

The term "alkyl", when used alone or in combination with other moieties, for example, when used in combination in "alkoxy", "alkoxyalkyl", "hydroxyalkyl", "carboxyalkyl", "alkanoyl" and "alkanoylalkyl", represents a hydrocarbon moiety that derived from an alkane. When used alone, "alkyl" therefore includes "methyl" (CH ₃ -), "ethyl" (C ₂ H ₅ -), etc. When used in combination, the alkyl portion of the "alkoxy" moiety is linked at the end of the moiety to the rest of the molecule via an intermediate oxygen bond, -O- as in the case of "methoxy" (CH ₃ -O-), "ethoxy" (C ₂ H ₅ -O -), etc., which are covered by the term "alkoxy". The alkyl portion of the "alkanoyl" moiety is linked at the end of the moiety to the rest of the molecule via an intermediate carbonyl bond, -(C=O)-, with "methanoyl" (HC=O-) being the terminal aldehyde moiety, "ethanoyl" (CH ₃ - (C=O-) is carbonyl-bonded methyl, etc., which are encompassed by the term "alkanoyl".

The term "hydroxy" represents the -OH moiety, and the term "carboxy" represents the -(C=O)OH moiety. The term "hydroxyalkyl" is hydroxy linked at the end of the moiety to the rest of the molecule via an intermediate divalent alkyl moiety, as in the case of "hydroxymethyl" (HO-CH ₂ -), "hydroxyethyl" (HO-C ₂ H ₅ -) and t .d., which are covered by the term "hydroxyalkyl". The term "carboxyalkyl" is a carboxy bonded at the end of the moiety to the rest of the molecule via an intermediate divalent alkyl moiety, as in the case of "carboxymethyl" (HO-(C=O)-CH ₂ -), "carboxyethyl" (HO-(C =O)-C ₂ H ₅ -), etc., which are covered by the term "carboxyalkyl". The term "alkoxyalkyl" includes both the terminal alkoxy moiety (i.e. attached at the end of the moiety) as defined above and indicated by the notation "alkoxy" and the intermediate divalent alkyl moiety through which the "alkoxy" is linked to the rest of the molecule. Thus "alkoxyalkyl" encompasses "methoxymethyl" (CH ₃ -O-CH ₂ -), "methoxyethyl" (CH ₃ -O-C ₂ H ₄ -), "ethoxymethyl" (C ₂ H ₅ -O-CH ₂ -), "ethoxyethyl" (C ₂ H ₅ -O-C ₂ H ₄ -), etc. The term "alkanoylalkyl" includes both the terminal alkanoyl moiety (i.e., linked at the end of the moiety) as defined above and shown by the notation "alkanoyl" and the intermediate divalent alkyl moiety through which the "alkanoyl" is bonded to the rest of the molecule. Thus "alkanoylalkyl" encompasses "methanoylmethyl" (H(C=O)-CH ₂ -), "methanoylethyl" (H(C=O)-C ₂ H ₄ -), "ethanoylmethyl" (CH ₃ -(C =O)-CH ₂ -), "ethanoylethyl" (CH ₃ -(C=O)-C ₂ H ₄ -) _{, etc.}

The term "optionally substituted" with respect to "alkyl" or with respect to terminal or intermediate alkyl portions of moieties as defined above, means substituting a hydrogen substituent on one or more carbon-hydrogen bonds in the alkyl or alkyl portion with the specified substituent. In the case of a hydroxy (-OH) or methyl (-CH ₃ ) substituent, one, two or three hydrogen substituents on the carbon-hydrogen bonds of the terminal carbon atom in the alkyl may be replaced by the corresponding substituents -OH and/or CH ₃ , and one or two the hydrogen substituent in the carbon-hydrogen bonds of the intermediate carbon atom in the alkyl (alkylene) may be substituted by the corresponding substituents -OH and/or -CH ₃ . For example, in the case of an alkyl terminal moiety, its terminal carbon atom may be substituted with two -CH ₃ substituents to form an isopropyl terminal moiety, or may be substituted with three -CH ₃ substituents to form a tert-butyl terminal moiety. In the case of an intermediate alkyl moiety or an intermediate carbon atom in a terminal alkyl moiety: one or two hydrogen substituents on the carbon-hydrogen bonds of the carbon atom in the alkylene can be replaced by —CH ₃ substituents to give the corresponding methyl-substituted or dimethyl-substituted derivatives. In accordance with this description, similar substitutions of a terminal carbon atom in an alkyl or an intermediate carbon atom in an alkyl with one or more substituents -OH can be obtained. In the case of a carbonyl substituent (=O): hydrogen substituents at two carbon-hydrogen bonds of any terminal carbon atom in alkyl or intermediate carbon atom in alkyl (alkylene) can be substituted with =O to give a terminal aldehyde moiety (or group) or carbonyl moiety ( or group) respectively.

Given the possible moieties and the manner in which they may be substituted, it should be noted that there may be overlap in the moiety definitions, for example in the case of "methanol" and the terminal "methyl" substituted with =O, both of which represent a terminal aldehyde moiety. (or group). Specific fragments are mentioned, however, in order to emphasize their precise inclusion in this connection. In addition, if "alkyl" or "alkyl part" is further defined with respect to its corresponding number of carbon atoms (e.g., alkyl or alkyl part "containing 1-5 carbon atoms"), optional substituents -CH ₃ , if any, are not included in this the number of carbon atoms. Those. the phrase "containing 1-5 carbon atoms" and other phrases defining the number of carbon atoms in the alkyl refer to the number of carbon atoms in the backbone of the alkyl, which may be additionally substituted by substituents -CH ₃ or other substituents in accordance with the specific definitions given.

The carboxylic acid compounds include their respective salt forms. In the case where the parent compound or substrate contains a carboxylic acid functional group, the salt form is typically used in aqueous solution to carry out the synthetic methods described herein. Suitable carboxylic acid salt forms include, for example, alkali metal salts (eg sodium salt form), alkaline earth metal salts (eg calcium salt form) and ammonium salts. Thus, compounds such as "gluconic acid", "glucaric acid", "tartaric acid", "pyruvic acid", "lactic acid", "2-hydroxy-3-oxopropanoic acid", "glyceric acid", etc. e are understood to include the salt forms of "gluconate", "glucarate", "tartrate", "pyruvate", "lactate", "2-hydroxy-3-oxopropanoate", "glycerate", etc. Both general and specific structures illustrating carboxylic acid compounds are similarly understood to encompass their salt forms or ionized forms, thus the structure of gluconic acid, for example, when shown with its non-ionized carboxyl group, is understood to encompass the structure with its ionized carboxyl group, and vice versa, with non-ionized and ionized carboxyl group of the equivalent structures of this compound shown below:

Compounds may have one or more stereocenters, and the structures are illustrated without reference to any particular stereochemistry, with the understanding that the reactions described with respect to substrates such as "gluconic acid", "glucaric acid" and "erythronic acid" are, in accordance with their nomenclature designate a specific stereochemistry can be similarly carried out in a similar manner using the corresponding non-stereospecific substrates "2,3,4,5,6-pentahydroxyhexanoic acid", "2,3,4,5-tetrahydroxyhexanedioic acid" and "2,3,4 -trihydroxybutanoic acid", as well as using all stereoisomers of such compounds. Thus, unless otherwise specified, "gluconic acid" is intended to encompass "gluconic acid and its stereoisomers", as provided for other compounds, denoting a specific stereochemistry. General and specific compounds described in this document, you can use or get in the form of pure or purified (enriched) optical isomers, or in the form of their racemic mixtures. The use of optically active substrates or starting compounds may result in the formation of optically active products using the synthetic methods described herein, which will be appreciated by those skilled in the art in conjunction with the knowledge of the present invention. If desired, purification of a particular optical isomer or enrichment of one optical isomer relative to another can be achieved, for example, by the formation of diastereomeric salts by treatment with an optically active acid or base. Examples of suitable acids are tartaric, diacetyltartaric, dibenzoyltartaric, ditoluoyltartaric and camphorsulfonic acids. Examples of suitable bases are chiral alkaloids of plant origin. Mixtures of diastereomers are then separated by crystallization, followed by the release of optically active bases or acids from these salts. Another method for separating optical isomers involves using a chiral chromatography column chosen to maximize the degree of separation of the enantiomers. Another available method involves the synthesis of covalent diastereomeric molecules by reaction with an optically pure acid in activated form or an optically pure isocyanate. The synthesized diastereomers can be separated by conventional methods such as chromatography, distillation, crystallization or sublimation and then hydrolyzed to give an enantiomerically pure compound.

The general reaction mechanism for the synthesis of cleavage products and final products is shown in FIG. 1. As shown, the starting material of general formula I is broadly α-, β-dihydroxycarbonyl compound, which covers the preferred class of compounds, namely α-, β-dihydroxycarboxylates, if R ¹ represents hydroxy (OH), to provide terminal carboxyl group on the left side of the illustrated compound. The starting material of general formula I from FIG. 1 contains an α-hydroxy group substituted at the α-carbon atom relative to the carbonyl (C=O) group shown, as well as a β-hydroxy group substituted at the β-carbon atom relative to this carbonyl group. According to the synthesis mechanism illustrated, the first step of dehydration (removal of water) causes the removal of the β-hydroxy group along with the formation of a site of unsaturation, i.e. carbon-carbon double bond between α-carbon atom and β-carbon atom. The resulting ethylenically unsaturated, dehydrated compound shown as Compound A generally maintains tautomeric equilibrium with the dicarbonyl intermediate shown as having the general formula IIA. The dehydration step may thus involve the formation of water from the combination of the β-hydroxy group and the α-hydroxy hydrogen in the parent compound or substrate of general formula I.

The dicarbonyl intermediate of general formula IIA can then be cleaved to form a cleavage product of general formula IIB.

Due to cleavage, the moiety represented as R ^2B in this cleavage product has fewer carbon atoms relative to the moiety represented as R ^2A in the dicarbonyl intermediate of general formula IIA. Therefore, the cleavage product generally has fewer carbon atoms relative to this dicarbonyl intermediate. Optional hydrogenation of the cleavage product can then provide the final product - in this case, the corresponding hydrogenated final product is characterized by the general formula IIIB, as shown in FIG. 1. Cleavage to form a cleavage product further provides for the formation of a second cleavage product having the general formula IIC and hence containing an aldehyde group. Depending on the substrate or parent compound, this second cleavage product may contain other functional groups, such as a carboxylic acid functional group, as a moiety represented as R ^{2 C} , or otherwise included at the end of this moiety, which is associated with an aldehyde functional group. Such a second cleavage product can be obtained, for example, when the moiety represented by R ^2A in the dicarbonyl intermediate of general formula IIA is linked via a hydroxy-substituted carbon atom. That is, the parent compound may further contain a gamma-hydroxy group substituted at the gamma carbon atom relative to the first carbonyl group, such that cleavage produces, in addition to the first (dicarbonyl) cleavage product, a second cleavage product containing the aldehyde group resulting from the cleavage. bonds between the beta carbon atom and the gamma carbon atom of the dicarbonyl intermediate corresponding to the beta carbon atom and gamma carbon atom of the parent compound. In a specific embodiment, the second cleavage product of the general formula IIC may be formed in the case of R ^2A or at least the terminal part of R ^2A representing the fragment:

in which case the cleavage product will have fewer carbon atoms relative to both the dicarbonyl intermediate and the substrate. The cleavage product may then optionally be subjected to hydrogenation, whereby further transformations of the second cleavage product (eg also via hydrogenation) may provide the formation of other desired compounds, eg as described in relation to the more specific embodiment shown in FIG. 2. According to some methods, the moiety represented by R ^2C in the second cleavage product having the general formula IIC may have one carbon atom less than the moiety represented by R ^2A and the second cleavage product may be the corresponding aldehyde or the corresponding carboxylic acid formed from R ^2A and containing the same number of carbon atoms as R ^2A . In this case, the cleavage product may be pyruvic acid, which can be hydrogenated to lactic acid. Thus, it can be noted that the route of synthesis to lactic acid through the cleavage of a dicarbonyl intermediate to form pyruvic acid can be carried out using a number of α-, β-dihydroxycarbonyl compounds as substrates, including α-, β-dihydroxycarboxylic acids and carboxylates containing less than four carbon atoms.

Therefore, typical methods may include, in addition to obtaining a cleavage product that is a dicarbonyl compound, hydrogenating some or all of this cleavage product to obtain an end product that retains the first carbonyl group of the starting compound and the dicarbonyl intermediate, and also contains the adjacent hydroxy group obtained hydrogenation of the second carbonyl group of the cleavage product. Thus, the consumption of the cleavage product of general formula IIB by its hydrogenation shifts the cleavage reaction forward, ultimately giving an additional yield of the dicarbonyl compound from compound A by shifting the tautomeric equilibrium in this direction. The rate at which the (dicarbonyl) cleavage product becomes hydrogenated can be controlled using an optional cleavage catalyst as well as reaction conditions as described herein. As a result of the cleavage step, a 3-carbon cleavage product such as pyruvic acid can be prepared from available α-, β-dihydroxycarboxylic acids and 4-, 5-, or 6-carbon carboxylates as starting compounds such as erythronic acid ( or usually 2,3,4-trihydroxybutanoic acid); 2,3-dihydroxy-4-oxobutanoic acid; wine acid; 2,3,4,5-tetrahydroxypentanoic acid; 2,3,4-trihydroxy-5-oxopentanoic acid; 2,3,4-trihydroxypentanedioic acid; gluconic acid (or usually 2,3,4,5,6-pentahydroxyhexanoic acid); 2,3,4,5-tetrahydroxy-6-oxohexanoic acid and glucaric acid (or usually 2,3,4,5-tetrahydroxyhexanedioic acid). Thus, typical synthesis methods may involve the conversion of available C ₄ -C ₆ substrates, such as readily available carbohydrates, to produce C ₃ compounds as cleavage products and end products. In such embodiments, if the substrate is a 6 carbon compound (C ₆ substrate), then the second cleavage product of the synthesis process is also a C ₃ compound. For example, each of the 6 carbon substrates, gluconic acid and glucaric acid, can produce pyruvic acid as a cleavage product and lactic acid as the end product of lactic acid hydrogenation. In the case of gluconic acid, the second cleavage product may be glyceraldehyde, which may be hydrogenated to give glycerol as the final product. In the case of glucaric acid, the second cleavage product may be 2-hydroxy-3-oxopropanoic acid, which may be hydrogenated to give glyceric acid as the final product.

With regard to the connections in FIG. 1 having the general formulas I, IIA, IIB and IIIB, as well as compounds having the general formulas shown for compound A, R ¹ may be selected from the group consisting of alkyl, alkoxy, alkoxyalkyl, hydroxy and hydroxyalkyl, where alkyl and alkyl the alkoxy, alkoxyalkyl, and hydroxyalkyl portions contain from 1 to 5 carbon atoms optionally substituted with one or more substituents (i.e., may optionally have hydrogen substituents on carbon-hydrogen bonds substituted, as defined herein, with one or more substituents), selected from the group consisting of -OH, -CH ₃ and =O. According to specific embodiments, in these respective compounds, including the parent compound of general formula I, the dicarbonyl intermediate, and the cleavage products of general formulas IIA and IIB, respectively, and/or the final product of general formula IIIB, R ¹ may be alkyl (for example , containing 1-3 alkyl carbon atoms) and may result in a terminal ketone functional group in the corresponding compounds; R ¹ may be alkoxy (eg, having 1-3 alkyl carbons) and may result in an ester terminal functional group in the corresponding compounds; or R ¹ may be hydroxy and may result in a terminal carboxyl functional group in the respective compounds. Preferably, R ¹ is hydroxy, wherein the parent compound and the dicarbonyl intermediate are carboxylic acids. For example, as described above with respect to terms commonly used herein, the starting compound, dicarbonyl intermediate, cleavage product, and/or end product may be in the form of (e.g., present in the reaction mixture as) carboxylates, which means compounds containing a carboxylate -anion and likely present in salt form in the aqueous reaction mixture (eg, in the form of their corresponding ammonium salt) that is used to carry out the synthetic methods described herein.

With regard to the connections in FIG. 1 characterized by the general formulas I and IIA, as well as compounds characterized by the general formula given for compound A, R ^2A can be selected from the group consisting of alkyl, alkoxy, alkoxyalkyl, hydroxy, hydroxyalkyl, carboxy, carboxyalkyl, alkanoyl and alkanoylalkyl, where the alkyl and alkyl moieties of alkoxy, alkoxyalkyl, hydroxyalkyl, carboxyalkyl, alkanoyl and alkanoylalkyl contain 1-5 carbon atoms, optionally substituted with one or more substituents selected from the group consisting of —OH, —CH ₃ and =O. In accordance with a specific embodiment, R ^2A may be selected from the group consisting of alkyl, alkoxy, hydroxy, hydroxyalkyl, carboxy, carboxyalkyl, alkanoyl and alkanoylalkyl, where the alkyl and alkyl moieties of alkoxy, alkoxyalkyl, hydroxyalkyl, carboxyalkyl, alkanoyl and alkanoylalkyl contain 1 -3 carbon atoms optionally substituted with one or more -OH and/or one or more -CH ₃ . In a more specific embodiment, R ^2A may be alkyl, carboxy, carboxyalkyl, alkanoyl, or alkanoylalkyl, where the alkyl and alkyl moieties of carboxyalkyl, alkanoyl, and alkanoylalkyl contain 1-3 carbon atoms, optionally substituted with one or more -OH. Specific substrates containing 4-6 carbon atoms include erythronic acid (or usually 2,3,4-trihydroxybutanoic acid); 2,3-dihydroxy-4-oxobutanoic acid; tartaric acid; 2,3,4,5-tetrahydroxypentanoic acid; 2,3,4-trihydroxy-5-oxopentanoic acid; 2,3,4-trihydroxypentanedioic acid; gluconic acid (or usually 2,3,4,5,6-pentahydroxyhexanoic acid); 2,3,4,5-tetrahydroxy-6-oxohexanoic acid and glucaric acid (or usually 2,3,4,5-tetrahydroxyhexanedioic acid).

In the case of a specific 4 carbon substrate, when R ¹ is hydroxy and R ^2A is hydroxymethyl, the parent compound is erythronic acid (or typically 2,3,4-trihydroxybutanoic acid). In this case, the cleavage step may thus provide pyruvic acid, in addition to a second single carbon cleavage product such as formaldehyde. Thus, hydrogenation of the cleavage products will result in lactic acid and methanol, respectively. This example and other examples of 4 and 5 carbon substrates and their respective cleavage products, second cleavage products, and hydrogenation products are shown in Table 1 below.

Specific examples of 6-carbon substrates and their respective cleavage products, second cleavage products, and hydrogenation products are described below along with substrates having specific structures of formulas IV and VI that are within the scope of formula I.

With regard to compounds characterized by the general formulas IIB and IIIB, R ^2B may be selected from the group consisting of the substituent hydrogen, alkyl, alkoxy, alkoxyalkyl, hydroxy, hydroxyalkyl, carboxy, carboxyalkyl, alkanoyl and alkanoylalkyl, where alkyl and alkyl parts of alkoxy, alkoxyalkyl , hydroxyalkyl, carboxyalkyl, alkanoyl and alkanoylalkyl contain 1-4 carbon atoms, optionally substituted with one or more substituents selected from the group consisting of -OH, -CH ₃ and =O. In accordance with a specific embodiment, R ^2B may be selected from the group consisting of a substituent of hydrogen, alkyl, alkoxy, hydroxy, hydroxyalkyl, carboxy, carboxyalkyl, alkanoyl and alkanoylalkyl, where alkyl and alkyl parts of alkoxy, alkoxyalkyl, hydroxyalkyl, carboxyalkyl, alkanoyl and alkanoylalkyl contain 1-3 carbon atoms optionally substituted with one or more —OH and/or one or more —CH ₃ . In a more specific embodiment, R ^2B may be a hydrogen substituent, alkyl, carboxy, carboxyalkyl, alkanoyl, or alkanoylalkyl, where the alkyl and alkyl moieties of carboxyalkyl, alkanoyl, and alkanoylalkyl contain 1 or 2 carbon atoms, optionally substituted with one or more -OH. In accordance with another specific embodiment, R may be a hydrogen substituent or alkyl containing 1-3 carbon atoms, optionally substituted with one or more -OH.

In addition, it can be understood from the present disclosure that when R ¹ is hydroxy and R ^2B is a hydrogen substituent, the cleavage product is pyruvic acid, which can hydrogenate to lactic acid, theoretically from various possible α-, β-hydroxycarboxylate substrates as described above. In addition, the second cleavage product of the general formula IIC can be formed in the case of R ^2A or at least the terminal part of R ^2A , which is a fragment

Therefore, R ^2C in compounds of general formula IIC may represent moieties as defined above with respect to R ^2A , but containing at least one less carbon atom. Thus, R ^2C may be selected from the group consisting of the substituent hydrogen, alkyl, alkoxy, alkoxyalkyl, hydroxy, hydroxyalkyl, carboxy, carboxyalkyl, alkanoyl, and alkanoylalkyl, where the alkyl and alkyl moieties of alkoxy, alkoxyalkyl, hydroxyalkyl, carboxyalkyl, alkanoyl, and alkanoylalkyl contain 1-4 carbon atoms optionally substituted with one or more substituents selected from the group consisting of —OH, —CH ₃ and ═O. In accordance with a specific embodiment, R ^2C may be selected from the group consisting of a substituent of hydrogen, alkyl, alkoxy, hydroxy, hydroxyalkyl, carboxy, carboxyalkyl, alkanoyl and alkanoylalkyl, where alkyl and alkyl parts of alkoxy, alkoxyalkyl, hydroxyalkyl, carboxyalkyl, alkanoyl and alkanoylalkyl contain one or two carbon atoms, optionally substituted with one or more -OH and/or one or more -CH ₃ . In accordance with a more specific embodiment, R ^2C may be a hydrogen substituent or alkyl with one or two carbon atoms, optionally substituted with one or more -OH.

In a more specific embodiment, the R ^2C fragment of the compounds in FIG. 1 could represent

so that the parent compound and the dicarbonyl intermediate are characterized by the general formula IV and formula VA, respectively,

wherein the compounds may optionally be in their respective salt forms as described above. With regard to these compounds, R ¹ may be as defined above. R ^3A may be selected from the group consisting of a substituent of hydrogen, alkoxy, hydroxy and carboxy, where the alkyl part of the alkoxy contains 1-5 carbon atoms, which may be optionally substituted with one or more substituents selected from the group consisting of -OH, - CH ₃ and =O. Preferably R ^3A is a hydrogen substituent, methyl, methoxy, hydroxy or carboxy. R ^4A may be selected from the group consisting of the substituent hydrogen, alkyl, alkoxy, alkoxyalkyl, hydroxy, hydroxyalkyl, carboxy, carboxyalkyl, alkanoyl and alkanoylalkyl, where the alkyl and alkyl moieties of alkoxy, alkoxyalkyl, hydroxyalkyl, carboxyalkyl, alkanoyl and alkanoylalkyl contain 1- 5 carbon atoms which may be optionally substituted with one or more substituents selected from the group consisting of —OH, —CH ₃ and =O. Preferably R ^4A is a hydrogen substituent, methyl, methoxy, hydroxy or carboxy.

In the case of a particular 6 carbon substrate, R ¹ and R ^3A can both be hydroxy and R ^4A can be carboxy, resulting in glucaric acid (or typically 2,3,4,5-tetrahydroxyhexanedioic acid) as the substrate of general formula IV and 2-keto-3-deoxyglucaric acid (2,3-dihydroxy-5-oxohexanedioic acid) as a dicarbonyl intermediate of general formula VA. In this case, the cleavage product of general formula IIB may be pyruvic acid, which can be hydrogenated to lactic acid as the final product of general formula IIIB, as described above. The second cleavage product of general formula IIC may be 2-hydroxy-3-oxopropanoic acid, which can be hydrogenated to give glyceric acid as described above. In the case of another particular 6 carbon substrate, R ¹ and R ^3A may both be hydroxy and R ^4A may be methanol, resulting in 2,3,4,5-tetrahydroxy-6-oxohexanoic acid as the total substrate formula IV; and 4,5-dihydroxy-2,6-dioxohexanoic acid as a dicarbonyl intermediate of the general formula VA. In this case, the cleavage product of general formula IIB may be pyruvic acid, which can be hydrogenated to lactic acid as the final product of general formula IIIB, as described above. The second cleavage product of general formula IIC may be 2-hydroxymalonic aldehyde, which can be hydrogenated to give glyceraldehyde.

According to still more specific embodiments, the R ^2A fragment of the compounds in FIG. 1 could represent

which is obtained when, in the compounds of general formula IV above, R ^4A contains a methylene carbon atom (-CH ₂ -), so that R ^4A can be selected from the group consisting of alkyl, alkoxyalkyl, hydroxyalkyl, carboxyalkyl and alkanoylalkyl. According to such embodiments, it is possible that the parent compound of general formula IV and the dicarbonyl intermediate of general formula VA have more specific structures corresponding to general formula VI and general formula VIIA, respectively:

The R ¹ and R ^3A moieties may be as defined above, and the R ^5A moiety may be selected from the group consisting of hydrogen, alkyl, alkoxy, alkoxyalkyl, hydroxy, hydroxyalkyl, carboxy, carboxyalkyl, alkanoyl, and alkanoylalkyl, where alkyl and the alkyl moieties of alkoxy, alkoxyalkyl, hydroxyalkyl, carboxyalkyl, alkanoyl and alkanoylalkyl contain 1-4 carbon atoms which may optionally be substituted with one or more substituents selected from the group consisting of —OH, —CH ₃ and ═O. Preferably R ^5A is a hydrogen substituent, methyl, methoxy, hydroxy or carboxy.

In another example of a particular 6 carbon substrate, R ¹ , R ^3A and R ^5A can be hydroxy, resulting in gluconic acid (or typically 2,3,4,5,6-pentahydroxyhexanoic acid) as a substrate of general formula VI and 2-keto-3-deoxygluconic acid (4,5,6-trihydroxy-2-oxohexanoic acid) as a dicarbonyl intermediate of general formula VIIA. In this case, the cleavage product of general formula IIB may be pyruvic acid, which can be hydrogenated to lactic acid as the final product of general formula IIIB, as described above. The second cleavage product of general formula IIC may be glyceraldehyde, which can be hydrogenated to give glycerol as described above.

A typical reaction environment associated with the synthesis of the cleavage product and/or the final product, in accordance with the methods described herein, provides for an increased hydrogen partial pressure, such as a hydrogen partial pressure of at least 3 megapascals (MPa) (435 pounds /square inch), optionally in combination with a hydrogenation catalyst. In this hydrogenation/reduction medium, the terminal aldehyde group in the second cleavage product of the general formula IIC can be converted to an alcohol or hydroxy(-OH) terminal group. Other possible conversion products of the cleavage product and the second cleavage product are possible, as described in more detail below, with respect to the more specific embodiment shown in FIG. 2.

FIG. 2 shows the synthesis method shown in FIG. 1 using gluconic acid as the starting compound or a compound of formula I in which R ^2A is a moiety

In this embodiment, the formula IIA dicarbonyl intermediate as shown is 2-keto-3-deoxygluconic acid (2-keto-4,5,6-trihydroxyhexanoic acid). This dicarbonyl intermediate can then be cleaved to yield a Formula IIB cleavage product which, in the embodiment shown in FIG. 2 is pyruvic acid. In addition, a second cleavage product of formula IIC is obtained, which in this embodiment is glyceraldehyde, according to which R ^2C in the general formula for this compound, as shown in FIG. 1 is a fragment

which corresponds to the fragment R ^2A as shown above, however, containing one less carbon atom.

The final product and additional conversion products can also be formed under the reaction conditions described herein, as shown in FIG. 2. For example, hydrogenation/reduction of pyruvic acid, a cleavage product of formula IIB, may yield lactic acid. Hydrogenation/reduction of glyceraldehyde, the second cleavage product of Formula IIC, has been shown to yield glycerol. In addition, the resulting glyceraldehyde can be subjected to additional reactions, such as those involving 1,2-hydride shift or hydride transfer (Cannizzaro reaction), to cause it to be converted to lactic acid, as shown in FIG. 2. Thus, according to specific embodiments, lactic acid can be obtained in a molar amount that exceeds the molar amount of glyceraldehyde produced, despite the fact that the first part of this lactic acid can be obtained by hydrogenation of pyruvic acid, which is obtained by a cleavage reaction in equimolar amount with glyceraldehyde. That is, glyceraldehyde can be converted to the second part of lactic acid, so that the reaction mixture can contain combined first and second parts of lactic acid, which exceed the amount of glyceraldehyde in a molar ratio. For example, the ratio of total (combined) molar amount of lactic acid to net molar amount of glyceraldehyde (eg, in the reaction mixture after completion of the synthesis process) may be at least 1.2, at least 1.5, or at least 2.0. This excess may result, at least in part, from the conversion of glyceraldehyde to lactic acid. As also shown in FIG. 2, lactic acid can also react to form propylene glycol and acrylic acid as additional conversion products under the reaction conditions described herein.

Thus, exemplary methods are described herein for synthesizing an α-hydroxycarboxylate end product containing fewer carbon atoms relative to the α-,β-dihydroxycarboxylate starting compound. The methods involve reacting an α-,β-dihydroxycarboxylate starting compound in a reaction mixture that preferably contains a cleavage catalyst, i.e. the catalyst or promoter of the reaction step shown as "cleavage" in FIG. 1 and 2. Preferred cleavage catalysts provide one or more active cleavage metals such as tungsten, molybdenum and/or vanadium, which may be present in the reaction mixture as appropriate salts such as tungstates, molybdates or vanadates, which include the metatungstate salt, paratungstate salt, metamolybdate salt, paramolybdate salt, metavanadate salt or paravanadate salt. Typical tungstates are Group 1 (alkali) or Group 2 (alkaline earth) metal salts, as well as ammonium salts. Salts of ammonium metatungstate and ammonium paratungstate are typical. The cleavage catalyst (for example, ammonium metatungstate) may be present in the reaction mixture in an amount of from 0.1 mol. % up to 30 mol. %, from 0.5 mol. % up to 10 mol. % or from 1 mol. % up to 5 mol. % relative to the number of moles of the substrate, for example, in accordance with the initial composition for loading the reactor in the case of a batch reaction or in accordance with the composition in a steady state in the case of a continuous reaction. The cleavage catalyst may also, or may alternatively, be present in the reaction mixture in such an amount that the number of moles of active metal to be cleaved (eg tungsten, molybdenum or vanadium) can be from 6 mol. % up to 50 mol. % or from 10 mol. % up to 35 mol. % relative to the number of moles of the substrate. Other cleavage catalysts may contain solid acids and/or Lewis acids (eg, organometallic compounds, including organotin compounds).

According to these methods, an α-hydroxycarboxylate end product, such as lactic acid, is formed from a combination of cleavage and hydrogenation. Additional aspects of the present invention relate to the discovery that the use of a base, such as a hydroxide, can help convert at least a portion of the aldehyde cleavage product, such as glyceraldehyde, into an additional amount of the final product. For example, glyceraldehyde can be subjected to additional reactions, including reactions involving 1,2-hydride shift or hydride transfer (Cannizzaro reaction), so that it can be converted or isomerized to additional lactic acid. This additional amount of the final product can be expressed relative to the amount at the original level, in which the base is absent or otherwise in a nominal amount. An additional amount of the final product may be an increase of at least 10 mol. %, at least 20 mol. % or at least 50 mol. % relative to the amount at the initial level. Thus, the reaction mixture may contain a base, such as a hydroxide, to help produce such an additional amount of the final product. Typical hydroxides include ammonium hydroxide, as well as alkali and alkaline earth metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide, etc., with lithium hydroxide being preferred.

Particular methods are directed to the synthesis of lactic acid from an α-,β-dihydroxycarboxylate starting compound with more than 3 carbon atoms, such as a salt of gluconate (or usually 2,3,4,5,6-pentahydroxyhexanoate); 2,3,4,5-tetrahydroxy-6-oxohexanoate; glucarate (or usually 2,3,4,5-tetrahydroxyhexanedioate); 2,3,4,5-tetrahydroxypentanoate; 2,3,4-trihydroxy-5-oxopentanoate; 2,3,4-trihydroxypentanedioate; erythronate (or usually 2,3,4-trihydroxybutanoate); 2,3-dihydroxy-4-oxobutanoate or tartrate. As described herein, exemplary methods include dehydrating this parent compound to form a dicarbonyl intermediate by converting the alpha hydroxy group to a second carbonyl group and removing the beta hydroxy group, and cleaving this dicarbonyl intermediate by breaking the bond between the beta carbon atom and the gamma carbon atom of the dicarbonyl intermediate, corresponding to the beta carbon atom and the gamma carbon atom, relative to the carboxylate group of the parent compound to form pyruvate. The methods further include hydrogenation or reduction of pyruvate to produce lactic acid and optionally additional conversion products such as propylene glycol or acrylic acid.

In accordance with specific embodiments, the overall yield(s) of the cleavage product, the second cleavage product, or any particular end product and/or additional conversion product, as described herein, based on the theoretical yields through the respective pathways, which is also described in this document, can usually be at least 25 mol. % (for example, from 25 mol.% to 90 mol.%), usually at least 35 mol. % (for example, from 35 mol.% to 80 mol.%) and often at least 50 mol. % (for example, from 50 mol.% to 75 mol.%). These yields may refer, for example, to (i) any cleavage product of general formula IIB, such as pyruvic acid or any other specific cleavage product of this general formula described herein, (ii) any second cleavage product of general formula IIC, such as glycerin or any other specific second cleavage product of this general formula described herein, (iii) any end product of general formula IIIB such as lactic acid or any other specific end product of this general formula described herein, (iv) any product resulting from the conversion (for example, hydrogenation) of the second cleavage product of general formula IIC, such as glycerol or any other such specific conversion product described herein, and/or (v) any additional conversion product, such as propylene glycol or acrylic acid described in this document.

The reaction mixture, which is preferably an aqueous reaction mixture, may further contain a hydrogenation catalyst such as a solid (heterogeneous) catalyst. A typical hydrogenation catalyst may contain one or more hydrogenation active metals selected from groups 8-11 of the Periodic Table, such as, for example, ruthenium (Ru), cobalt (Co), nickel (Ni), platinum (Pt), palladium (Pd ) or gold (Au). The preferred active metal for hydrogenation is ruthenium. The catalyst may also comprise a solid support for the active metal(s) to be hydrogenated, the metals being dispersed on the solid support in a distribution pattern, such as preferably near the outer surface of the solid support or otherwise substantially evenly throughout the porous solid support. , depending on the specific technique used to prepare the catalyst (for example, impregnation by means of evaporation of the active metal solution for hydrogenation). Preferably, the hydrogenation active metal, or such metals in combination, is/are present in an amount of from 1 wt. % up to 15 wt. % or from 2 wt. % up to 10 wt. %, based on the total weight of the hydrogenation catalyst.

Active(s) metal(s) for hydrogenation may be present in the reaction mixture in such an amount that the number of moles of active(s) metal(s) for hydrogenation (for example, ruthenium) is from 1 mol. % up to 20 mol. % or from 2 mol. % up to 10 mol. % relative to the number of moles of the substrate, for example, in accordance with the initial composition for loading the reactor in the case of a batch reaction or in accordance with the composition in a steady state in the case of a continuous reaction. The solid support is preferably refractory in the reaction mixture and under the synthesis reaction conditions described herein. Typical solid substrates contain one or more metal oxides such as alumina (alumina), silicon oxide (silicon dioxide), titania (titanium dioxide), zirconium oxide (zirconia), magnesium oxide (magnesium oxide), strontium oxide ( strontium oxide), etc. The preferred solid support is carbon. According to a specific embodiment, the hydrogenation catalyst contains ruthenium on a carbon support, the ruthenium being present in the above range based on the total weight of the catalyst and/or in the above range relative to the number of moles of the substrate.

The reaction conditions under which the reaction mixture is maintained during the synthesis of the cleavage product(s) and/or final product(s) include elevated pressure and hydrogen partial pressure. Typical reactor absolute pressures typically range from 2.07 MPa (300 psi) to 24.1 MPa (3500 psi), typically from 3.45 MPa (500 psi . inch) up to 20.7 MPa (3000 psi) and often from 10.3 MPa (1500 psi) to 17.2 MPa (2500 psi). The pressure in the reactor may be derived primarily or in fact from hydrogen, so that these total pressure ranges may also correspond to hydrogen partial pressure ranges. However, the presence of gaseous particles evaporated from the reaction mixture, such as ammonia and/or water vapor, may result in a reduction in the hydrogen partial pressure relative to these total pressures, so that, for example, the hydrogen partial pressure may typically be in the range of 1.38 MPa (200 psi) to 22.4 MPa (3250 psi), typically 2.41 MPa (350 psi) to 19.0 MPa (2750 psi) and often from 8.62 MPa (1250 psi) to 15.5 MPa (2250 psi).

Other reaction conditions include temperatures from 100°C to 350°C and preferably from 130°C to 230°C. Response time, i.e. the time that the reaction mixture is maintained under pressure and temperature conditions at any of the target values or within the target sub-ranges in any of the pressure and temperature ranges above (for example, a total pressure target of 13.8 MPa (2000 psi) and target temperature 160°C) is from 0.5 hour to 24 hours and preferably from 1 hour to 5 hours in case of batch reaction. For a continuous reaction, this reaction time corresponds to the residence time in the reactor. Continuous mode can be carried out, for example, under the conditions of pressure and temperature described above with continuous supply of substrate and hydrogen and continuous withdrawal of the reaction mixture containing the product(s) of the split and/or end product(s). Continuous operation may also include continuous purification of cleavage products and/or end products, continuous separation of process streams containing unreacted gaseous and/or liquid products, and/or continuous recycling of one or more such process streams back to the reaction mixture located in the synthesis reactor. . In the case of a recycle operation, the yields of the cleavage product(s) and/or final product(s) as described above will correspond to a "single" or "per pass" yield, with higher overall yields being possible due to for recycling.

Example 1

Sodium gluconate (10 grams) was combined with 100 ml of water, 2.5 mol. % commercial catalyst ruthenium on carbon relative to the substrate sodium gluconate, 2.5 g or 2 mol. % tungstate in the form of ammonium metatungstate hydrate and 1 equivalent of lithium hydroxide in 450 cc. high pressure Parr reactor Hastelloy® C2000. The reactor was purged three times with nitrogen at 6.9 MPa (1000 psi), then three times with hydrogen at 6.9 MPa (1000 psi). After a third hydrogen purge, the reactor was pressurized to 3.4 MPa (500 psi) with hydrogen and agitation started at 700 rpm. with heating up to 180 degrees Celsius. Once the reaction temperature was reached, additional hydrogen was added to produce 9.0 MPa (1300 psi) of hydrogen in the vessel. After two hours, the contents of the reactor were cooled to room temperature by quenching in an ice water bath, the pressure in the reactor was reduced and the contents were filtered to recover the catalyst, and then the samples were silylated for analysis by GC/MS using N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and trimethylchlorosilane (TMCS) in pyridine. Analysis showed greater than 99% substrate conversion, yielding 14.1 weight percent lactic acid (38.4 mole percent yield), 1.6 weight percent glycerol (4.3 mole percent yield), 3.4 wt. percent ethylene glycol (yield 13.5 mole percent) and 5.2 weight percent propylene glycol (yield 16.8 mole percent).

Example 2

The apparatus and protocol of Example 1 was used, except that hydrogen was used at 13.8 MPa (2000 psi) and no lithium hydroxide was added. More than 98% of the substrate was converted to products, including 0.6 wt% lactic acid (yield 1.6 mole percent), 3.3 wt% glycerol (yield 8.8 mole percent), 1.2 wt% ethylene glycol ( yield 4.8 mole percent) and 1.0 weight percent propylene glycol (yield 3.2 mole percent).

Example 3

The conditions of Example 2 were repeated except that no tungstate was used and nitrogen was used instead of hydrogen to pressurize the reactor. The molar conversion of the substrate was reduced to 92.7%. Products included 4.97 weight percent lactic acid (yield 13.1 mole percent), 5.3 weight percent glycerol (yield 13.7 mole percent), 1.5 weight percent ethylene glycol (yield 5.7 mole percent) and 2.1 weight percent propylene glycol (yield 6.5 mole percent).

Example 4

For this example, neither tungstate nor commercial ruthenium-carbon catalyst was used, and nitrogen was used again in place of hydrogen, except that it was used at 1.0 MPa (150 psi). Complete conversion of the substrate occurred, with the products comprising 1.29 weight percent lactic acid (yield 3.4 mole percent), 4.8 weight percent pyruvic acid (yield 13.11 mole percent) and 0.3 weight percent 5- hydroxymethyl-2-furancarboxylic acid (HMFCA) (yield 4.7 mole percent), but no glycerol, ethylene glycol or propylene glycol was noticeable.

Example 5

For this example, 10 g calcium erythronate was used as substrate, hydrogen was used again at 13.8 MPa (2000 psi) and 2.5 mol % was used again in relation to substrate. percent commercial catalyst ruthenium on coal and 2 mol. percent tungstate. After 2 hours at 180 degrees Celsius, all of the substrate was converted and the products included 0.9 weight percent lactic acid (yield 1.7 mole percent), 11.7 weight percent glycerol (yield 22.2 mole percent), 0.7 wt. percent ethylene glycol (yield 2.0 mole percent) and 1.8 weight percent propylene glycol (yield 4.1 mole percent).

In general, aspects of the present invention relate to the use of the synthetic methods described herein to obtain cleavage product(s) and/or final product(s) from readily available or readily obtainable substrates. End products and optionally additional conversion products, as described herein, can be obtained from further conversion of cleavage products (including second cleavage products, as described herein) either in situ or in an additional, separate reaction step. The cleavage product(s) and/or final product(s) have a lower number of carbon atoms relative to the substrates used to obtain these products. These methods can advantageously overcome various disadvantages of conventional methods. Those skilled in the art, with the knowledge derived from the present invention, will recognize that various modifications can be made to these methods to achieve these and other benefits without departing from the scope of the present invention. Thus, it should be understood that the features of the present invention are subject to modifications and/or substitutions without deviating from the scope of the present invention. The specific embodiments shown and described herein are for illustrative purposes only and do not limit the present invention as set forth in the appended claims.

Claims (9)

1. A method for the synthesis of pyruvic acid or its salt, including: (a) dehydration of the parent compound in the form of glucaric acid or a salt thereof, or a stereoisomer of glucaric acid or a salt thereof, to form the dicarbonyl intermediate 2-keto-3-deoxyglucaric acid or a salt thereof, or a stereoisomer of 2-keto-3-deoxyglucaric acid or its salts by converting the alpha hydroxy group to a second carbonyl group and removing the beta hydroxy group; And (b) cleaving the dicarbonyl intermediate to give pyruvic acid or a salt thereof. 2. The method of claim. 1, further comprising (c) hydrogenating pyruvic acid or a salt thereof to obtain lactic acid or a salt thereof. 3. The method of claim 1 wherein the dehydrogenation comprises generating water from a combination of a beta hydroxy group and an alpha hydroxy hydrogen. 4. Process according to claim 1, wherein the cleavage step (b) additionally produces a second cleavage product in the form of 2-hydroxy-3-oxopropanoic acid or a salt thereof. 5. The method of claim 4 further comprising hydrogenating 2-hydroxy-3-oxopropanoic acid or a salt thereof to glyceric acid or a salt thereof.

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