WO2006101473A1

WO2006101473A1 - Process and catalysts for the conjugation of double bonds in fatty acids and derivatives thereof

Info

Publication number: WO2006101473A1
Application number: PCT/US2005/008639
Authority: WO
Inventors: Joseph C. Rongione
Original assignee: Stepan Company
Priority date: 2005-03-15
Filing date: 2005-03-15
Publication date: 2006-09-28

Abstract

A process to manufacture conjugated fatty acids or their derivatives, in particular long chain polyunsaturated fatty acids (e.g., CLAs) or their derivatives, using an improved catalyst system that isomerizes the fatty acids and their derivatives in an efficient, cost-effective manner. The improved catalyst system includes a metal alkoxide or amide catalyst chelated with an appropriate chelating agent or a metal alkoxide formed from another metal alkoxide in the described process.

Description

PROCESS AND CATALYSTS FOR THE CONJUGATION OF DOUBLE BONDS IN FATTY ACIDS AND DERIVATIVES THEREOF

FIELD OF THE INVENTION

[0001] The invention relates to a process for the manufacture of conjugated fatty acids or their derivatives, in particular long chain polyunsaturated fatty acids, using an improved catalyst system that isomerizes the fatty acids and their derivatives in a more efficient and cost-effective manner. The improved catalyst system includes a metal alkoxide or metal amide catalyst chelated with an appropriate chelating agent or a metal alkoxide formed from another metal

alkoxide in the described process.

BACKGROUND OF THE INVENTION

[0002] Most fatty acids and fatty acid derivatives are straight-chain molecules having from three to eighteen carbon atoms. A significant fraction of these fatty acid molecules are polyunsaturated, meaning that they contain two or more double bonds. In most instances, the double bonds in naturally occurring polyunsaturated fatty acid molecules are separated from each other by two single bonds (e.g., with the structure -CH=CH-CH₂-CH=CH-), and such molecules are sometimes referred to as unconjugated polyenes or methylene-interrupted polyenes. In more limited instances, naturally occurring polyunsaturated fatty acid molecules contain double bonds separated from each other by a lone single bond, having the structure -CH=CH-CH=CH-, and such molecules are generally referred to as conjugated polyenes or conjugated fatty acids. Among the naturally occurring conjugated polyenes, conjugated dienes and trienes are the most prevalent.

[0003] In the area of health and nutrition, materials comprising conjugated isomers of long chain polyunsaturated fatty acids are known for their health enhancing qualities, when used in food products. Researchers have shown that ingestion of conjugated polyenes may inhibit tumor growth, prevent heart disease, and reduce body fat. One important category of conjugated long chain polyunsaturated fatty acids are conjugated linoleic acids (CLAs). There is presently a great deal of interest in the apparent health benefits imparted by certain conjugated linoleic acids (CLAs).

[0004] CLAs, originally isolated from the fat and milk of ruminants, refer to a mixture of positional and geometric isomers of linoleic acids, which are unsaturated fatty acids considered essential to the human diet and found preferentially in dairy products and meat. "CLA(s)" is a general or collective term used to describe one or a mixture of conjugated octadecadienoic fatty acids. In a variety of chemical forms, including but not limited to free fatty acids (FFA) and fatty acid methyl esters (FAME), CLA reportedly has antidiabetic properties, leads to reduced carcinogenesis and atherosclerosis, and increases bone and lean muscle mass. CLAs have generated much interest in the academic and business communities because of their nutritional, therapeutic, and pharmacological properties, and have exhibited impressive physiological effects in animal studies.

[0005] There are known CLA compositions, along with various known routes to prepare such compositions. See, e.g., U.S. Pat. Nos. 6,479,683 (Abney, et al.);

6,420,577 (Reaney, et al.); 6,060,514 (Jerome, et al.); 6,015,833, 6225,486 and 6,333,353 (all to Saebo, et. al.); 6,160,140 (Bhaggan, et. al.); 6,034,132 and 6,019,990 (both to Remmereit, J.); and U.S. Pat. App. Pub. No. 2004/0058998 Al (Saebo, et al.). CLAs have become biologically and commercially important, as they have been observed to inhibit mutagenesis and to provide unique nutritional value.

[0006] Typically, CLAs are a mixture of positional isomers of linoleic acid (C18:2) having conjugated double bonds. The cis-9, trans-11 (c9,tll) and trans- 10, cis-12 (tlθ,cl2) isomers are present in greatest abundance in typical CLA compositions, but it is not absolutely certain which isomers are responsible for the biological and heightened nutritional activity previously observed. From labeled uptake studies, it has been noted that the c9,tll-isomer appears to be somewhat preferentially taken up and incorporated into the phospholipid fraction of animal tissues, and to a lesser extent the tlO,cl2-isomer. (See Ha, et. al., Cancer Res., 50: 1097 (1991)). Others have reported that virtually all of the biological activity of the mixed CLA isomers could be attributed to the tlθ,cl2- CLA isomer while very little activity could be ascribed to the c9,tll-CLA isomer. See Sebedio, et al., Inform Vol. 10, No. 5.

[0007] A factor hampering commercialization and research interests in CLAs and other conjugated fatty acids is that such compounds are not naturally abundant. Conjugated fatty acids typically are present in animal fats only at a level of about 0.5 percent. See U.S. Pat. 6,479,683 (Albany, et al.). In plant sources, conjugated fatty acids do not occur widely. Thus, investigators continue to seek ways to obtain conjugated fatty acids by partial or total synthesis.

[0008] One of the existing methods for preparing conjugated fatty acids is isomerization. The properties of unsaturated fatty acids and their derivatives can be altered by rearrangement, i.e., isomerization, of the structure of the double bond, either with respect to the steric position or the position in the carbon chain of the molecule of the fatty acid. As noted above, conjugated fatty acids and their derivatives are of great technical and commercial interest and, therefore, many attempts have been made to isomerize unconjugated fatty acids to conjugated ones.

[0009] Synthesis of conjugated fatty acids via isomerization typically proceeds from an unconjugated fatty acid or fatty acid ester as a precursor. Probably the most common unconjugated fatty acid precursor employed in such methods is linoleic acid. Linoleic acid can be expressed as an all-cis-9,12- octadecadienoic acid, or a c9,cl2-octadecadienoic acid, where c indicates the cis- configuration (the orientation that typically occurs in linoleic acid derived from natural sources) and the numbers 9 and 12 indicate the position of the double bonds relative to the carboxyl carbon of the acyl chain (-COOH). This nomenclature can be abbreviated in several ways, including: 18:2 (Δ9,12); 18:2- c9,cl2; 9-cis,12-cis-18:2; and c9,cl2-18:2, where c indicates the cis- configuration, 18 indicates the total number of carbon atoms, and 2 represents the number of double bonds in the molecule. Using alternative nomenclature, linoleic acid can be expressed in the (n-6) or omega (oo) system as 18:2 (n-6) or 18:2 ω6, where (n-6) or ω6 indicates the position of the first double bond beginning from the methyl end.

[0010] Previously known methods to produce conjugated unsaturated compounds include, for example, hydrogenation of fats using a variety of catalysts. Such methods, however, often lead to incomplete isomerization and unwanted side reactions, such as polymerization and intramolecular cyclization. Other known methods, for example, include isomerization with an excess of alkali metal hydroxide in an aqueous or alcoholic medium, which leads to a quantitative isomerization. See, e.g., U.S. Pat. No. 2,343,644 (Cawley). However, this particular method typically suffers from the limitation that a considerable excess of alkali metal hydroxide must be utilized so that the conjugated fatty acids or fatty acid compounds are obtained from the process in the form of alkali soaps. Moreover, the resultant conjugated fatty acids or fatty acid compounds have to be recovered and isolated from the soap mixture. These techniques also differ in their use of a particular solvent, temperature and pressure. See, e.g., U.S. Pat. No. 3,162,658 (Baltes, et. al).

[0011] Alternatively, the rearrangement of the double bonds of linoleic acids to conjugated positions can occur during treatment with catalysts such as nickel or alkali at high temperatures, and during autooxidation. It is theoretically possible that eight geometric isomers of 9,11 and 10,12 octadecadienoic acid (c9,cll; c9,tll; t9,cll; t9,tll; clθ,cl2; clθ,tl2; tlθ,cl2 and tlθ,tl2) could result from the isomerization of c9,cl2-octadecadienoic acid. Again, without being bound by any particular theory, a general mechanism for the isomerization of linoleic acids has been described by J. C. Cowan in JAOCS 72:492-99 (1950). The formation of certain isomers of CLAs is thermo-dynamically favored as described therein. The relatively higher distribution of 9,11 and 10,12 isomers apparently results from the further stabilization of the c9,tl 1 or tlθ,cl2 geometric isomers.

[0012] U.S. Pat. No. 6,420,577 (Reaney, et al.) describes a process for making CLAs by reacting a linoleic acid-rich oil with a base, in the presence of a catalytic amount of such a base, in an aqueous medium via simultaneous saponification and quantitative isomerization. Polyethylene glycol is used in the process as a phasing aid at the end of the process. However, this process utilizes a heightened temperature (>170 ⁰C). Higher temperatures lead to the formation of undesirable CLA isomers, including the trans, trans-CLA isomers.

[0013] U.S. Pat. No. 6,160,140 (Bhaggan, et al.) describes the conversion of a linoleic acid-containing oil, free fatty acid, or alkyl ester to CLA by treating it with a base in an alcohol solution, where the alcohol has at least 3 carbons and at least 2 hydroxyl groups. The allegedly preferred embodiment of the Bhaggan patent utilities potassium hydroxide in propylene glycol. However, the use of solvent in the conjugation (isomerization) step gives rise to the potential formation of unwanted CLA-alcohol esters (e.g., CLA-propylene glycol esters) as well as reduces overall process productivity by lowering reactor efficiency and adding processing steps for solvent removal.

[0014] U.S. Pat. No. 3,162,658 (Baltes, et al.) provides for the use of alkali metal hydrocarbyl alcoholates or alkali metal amides to isomerize esters of unconjugated polyethylene acids such as linoleic acids. This patent appears to indicate metal alkoxides and their effectiveness in isomerizing esters of unconjugated polyethylene acids. The patent further appears to indicate that potassium alcoholates may be useful as isomerization catalysts for technical purposes not only because of their adequate catalytic activity, but also for their partial solubility. According to the Baltes patent, decreasing cation size decreases catalytic effectiveness.

[0015] U.S. Pat. No. 3,984,444 (Ritz, et al.) describes the isomerization of an ester of an alcohol having 1 to 12 carbon atoms and a fatty acid or its methyl ester having 10 to 24 carbon atoms with isolated double bonds (to the corresponding compound having conjugated double bonds) using alkaline metal alcoholates in strongly polar aprotic solvents. As noted above, the use of solvents in the conjugation step is undesirable because it gives rise to the potential formation of unwanted CLA-alcohol esters (e.g., CLA-propylene glycol esters) and reduces process efficiency.

[0016] U.S. Pat. No. 2,343,644 (Cawley) and WO 01/51597 (Reaney, et al.) describe the use of glycol polyethers as solvents for the concurrent saponification and isomerization of linoleic acid-rich oils. These processes employ excess base and yield conjugated linoleic acid streams. This patent suffers from the same decreased efficiency by the use of solvents that was noted previously. Thus, there is a need to improve the effectiveness of a metal alkoxide as a conjugation catalyst.

[0017] U.S. Pat. Nos. 3,162,658, 3,984,444, 6,479,683, 6,743,931 and 6,333,353 all teach that potassium methoxide is the catalyst of choice in solvent- free isomerization processes. These patents span 40 years and contain 28 isomerization examples, 27 of which use potassium alkoxides. The 28th example utilizes a cesium alkoxide. Compared to potassium alkoxides, sodium methoxide is cheaper and more readily available at commercial scale. As a result, there is a need for a system that can efficiently use sodium methoxide or other sodium alkoxides to isomerizes unconjugated fatty acids. There is also a need for cost- effective generation of metal alkoxides that are currently expensive or not commercially available. Such metal alkoxides would be useful for isomerization and other processes. BRIEF SUMMARY OF THE INVENTION

[0018] One objective of the presently described technology is to improve catalytic effectiveness of metal alkoxides or amides used to isomerize unconjugated fatty acids, especially those having less effective metal ions.

[0019] Another objective of the presently described technology is to exchange the less effective counter ions of metal alkoxide or amides with more effective counter ions.

[0020] Still another objective of the presently described technology is to provide a system which can avoid the use of a solvent in the conjugation step of the isomerization process to reduce or eliminate the potential formation of unwanted CLA-alcohol esters (e.g., CLA-propylene glycol esters).

[0021] A further objective of the presently described technology is to economically generate metal alkoxides that are not commercially available or are relatively expensive to produce conventionally.

[0022] A still further objective of the present technology is to decrease the cost to produce conjugated fatty acids and their derivatives, most notably CLAs and their derivatives.

[0023] In one aspect, the presently described technology provides a process to improve the performance of a suitable catalyst system for conjugating unsaturated fatty acids or their derivatives by providing a metal alkoxide or amide catalyst comprising a cation; providing a chelating agent; and chelating the cation of the metal alkoxide or metal amide catalyst with the chelating agent. The chelated metal alkoxide or amide has an improved catalytic effectiveness to isomerize unconjugated fatty acids and/or their derivatives (e.g., fatty acid esters). [0024] The chelating step can be performed before the metal alkoxide or amide catalyst is added to a composition containing an unconjugated fatty acid and/or a derivative of the fatty acid, or can be performed in situ by first adding the chelating agent to the composition containing unconjugated fatty acid starting material and then adding the metal alkoxide or amide catalyst to the reaction mixture.

[0025] In another aspect, the presently described technology provides a process for the formation of a second metal alkoxide for conjugating unsaturated fatty acids or their derivatives from a first metal alkoxide by exchanging cations between the first metal alkoxide and a salt of the second metal by dissolving the salt of the second metal in a first solvent to make a first solution; mixing the first metal alkoxide with the first solution; forming a salt of the first metal and an anion from the first solution; and forming a second solution comprising the second metal alkoxide. In doing so, a catalytically more effective metal alkoxide can be obtained from a less effective metal alkoxide . Further, currently commercially unavailable or expensive metal alkoxides can also be obtained in a more cost-effective manner.

[0026] In accordance with one embodiment of this aspect of the presently described technology, the first metal is sodium and the second metal is an alkali, alkaline earth or transition metal other than sodium.

DETAILED DESCRIPTION OF THE INVENTION

Definitions And Conventions

[0027] As used herein, the term "conjugated linoleic acid(s)" or "CLA(s)" refers to any conjugated linoleic acid or octadecadienoic free fatty acid. It is intended that this term encompass all positional and geometric isomers of linoleic acid with two conjugated carbon-carbon double bonds at any position in the respective molecule. A CLA differs from an ordinary linoleic acid in that an ordinary linoleic acid has double bonds at carbon atoms 9 and 12 while a CLA has conjugated double bonds. Examples of CLAs include, but are not limited to, cis- and trans- isomers ("E/Z isomers") of the following positional isomers: 2,4- octadecadienoic acid, 4,6-octadecadienoic acid, 6,8-octadecadienoic acid, 7,9- octadecadienoic acid, 8,10-octadecadienoic acid, 9,11-octadecadienoic acid, 10,12-octadecadienoic acid, and 11,13-octadecadienoic acid. As used herein, the term "CLA(s)" encompasses a single isomer, a selected mixture of two or more isomers, and a non-selected mixture of isomers obtained from natural sources, as well as synthetic and semi-synthetic CLAs.

[0028] The term "CLA derivatives" refers to moieties of CLAs recognized by one skilled in the art as structures that can be readily converted to carboxylic acids. Examples of such moieties are carboxylic acids, salts of carboxylic acids, carboxylic anhydrides, amides, carboxylic esters, ortho esters, 1,3-dioxolanes, dioxanones, oxazoles and hydrazides.

[0029] As used herein, it is intended that the term "esters" of CLA (or "CLA esters") include any and all positional and geometric isomers of CLA bound through an ester linkage to an alcohol or any other chemical group including, but not limited to physiologically acceptable, naturally occurring alcohols (e.g., methanol, ethanol, or propanol). Therefore, an ester of CLAs or an esterified CLA or a CLA ester may contain any of the positional and geometric isomers of CLAs. [0030] It is further intended that the term "undesirable isomers" of CLAs includes, but is not limited to, cll,tl3-; tll,cl3-; tll,tl3-; cll,cl3-; c8,tlθ-; t8,tlθ-; and c8,clθ- isomers of octadecadienoic acids, but does not include tlθ,cl2- and c9,t 11 -isomers of octadecadienoic acids. Undesirable isomers may also be referred to as "minor isomers" of CLAs as these isomers are generally produced in low amounts when CLAs are synthesized by alkali isomerization. [0031] As used herein, the term "c" encompasses a chemical bond in the cis orientation, and the term "t" refers to a chemical bond in the trans orientation. If a positional isomer of CLA is designated without a "c" or a "t", then that designation includes all four possible isomers. For example, 10,12 octadecadienoic acid encompasses clθ,tl2-; tlθ,cl2-; tlθ,tl2-; and clθ,cl2- octadecadienoic acid, while tlO,cl2-octadecadienoic acid or tlO,cl2-CLA refers to just the single isomer. [0032] As used herein, the term "oil" refers to a free flowing liquid containing long chain fatty acids (e.g., linoleic acids and CLAs) or other long chain hydrocarbon groups, which can comprise triglycerides of CLAs and linoleic acids. The long chain fatty acids, include, but are not limited to, the various isomers of CLAs. [0033] Additionally, as used herein, it is intended that the term "triglycerides" of CLAs (or linoleic acids) may contain CLAs (or linoleic acids) at any or all of the three positions on the triglyceride backbone. Moreover, a triglyceride of CLA may contain any of the positional and geometric isomers of CLAs. [0034] Moreover, as used herein, a "linoleic acid-rich/containing" (or "CLA- rich/containing") material is a material — which can be an oil, an ester, a salt or other derivatives thereof — that is rich in or contains linoleic residues (or CLA residues). A "linoleic acid residue" (or "CLA residue") means a component which has a fatty carbon chain length and isomer distribution that resembles linoleic acids (or CLAs). [0035] It should also be understood that the fatty acid distributions in the examples of the instant application were determined by gas chromatography (GC) using a Chrompack CP-SiI 88 capillary column (100 m x 0.25 mm, df = 0.2 microns) using a helium carrier at approximately 1.0 mL/minute. Further, the following temperature parameters were used: injector at 250 ⁰C; detector at 250 ⁰C; oven temperature at 75 ⁰C for 2.0 minutes (min), then increased at 5 °C/min to 185 ⁰C and held for 30.0 min, then increased at 4 °C/min to 225°C and held for 36.0 min. Description Qf The Invention

[0036] While the presently described technology will be described in connection with one or more preferred embodiments, it will be understood that the technology is not limited to those embodiments, and the improved catalyst systems of the presently described technology are not limited to the production of only CLAs or CLA derivatives. To the contrary, the presently described technology includes all alternatives, modifications, and equivalents as may be included within the spirit and scope of the appended claims.

[0037] The presently described technology relates to a process to manufacture conjugated fatty acids and/or their derivatives, in particular long chain polyunsaturated fatty acids (e.g., CLAs) or their derivatives using an improved catalyst system. The improved catalyst system includes a metal alkoxide or amide catalyst chelated with an appropriate chelating agent or a suitable metal alkoxide (e.g., potassium alkoxide) formed from another alkoxide (e.g., sodium alkoxide).

[0038] By using the improved catalyst system of the presently described technology, isomerization of nonconjugated fatty acids and their derivatives can be performed at a lower temperature with minimal or no solvent, which improves both productivity and isomer ratio. An ensuing saponification reaction can be performed in an aqueous medium at significantly lower temperature than the conventional art (e.g., 75 °C vs. 200 ⁰C), and thereby removing the need for a pressure vessel, improving process safety, and decreasing environmental hazards while still preserving desirable product isomer ratios. Some of the salt can be pre-formed in the reaction mix, which can significantly decrease the reaction time.

[0039] When isomerizing unconjugated fatty acids and their derivatives (e.g., fatty acid esters) in according to the present technology, the isomerization step is typically catalyzed by a base in a nonaqueous system, and the catalyst can be an alkali, alkaline earth or transition metal alkoxide salt of an alkyl group alcohol, i.e., alkyl alcoholates, or an alkali, alkaline earth or transition metal amide. Any alkali, alkaline earth or transition metal compound of any alcohol, preferably, monohydric alcohol, or any alkali, alkaline earth or transition metal amide that is used in the prior art as a catalyst for the isomerization of unconjugated fatty acids, can be improved by the present technology described herein.

[0040] Examples of metal alkoxide catalysts useful in the performance of the presently described technology are alcoholates of monohydric alcohols with 1-18 carbon atoms of the alkali, alkaline earth or transition metals. Such alkali, alkaline earth or transition metal alkoxides include, but are not limited to alcoholates of methyl, ethyl, propyl, butyl, tertiary butyl, lauryl, stearyl, oleyl, or benzyl alcohols. The specific metal alkoxides set forth in this paragraph except those derived from benzyl alcohol can be termed as alkali, alkaline earth or transition metal alcoholates. Alkali, alkaline earth or transition metal alcoholates can also be called "alkali," "alkaline earth" or "transition metal hydrocarbyl alcoholates."

[0041] Cesium, rubidium, potassium, sodium, calcium, lithium, magnesium, copper, iron or zinc alkoxides or amides can be utilized, for example, along with mixtures of such alkoxides or amides, in the presently described technology. [0042] Alkali, alkaline earth or transition metal alkoxide salts of lower alkyl group alcohols (about 1-6 carbons) are preferred. Sodium methoxide is likely the least expensive to acquire among the metal alcoholates that are suitable for the isomerization of unconjugated fatty acids according to the presently described technology. However, under current conventional practices, the more expensive potassium alkoxides (e.g., potassium methoxide) are most often used as an isomerization catalyst for technical purposes because of their adequate catalytic activity and partial solubility. Many other known metal alkoxides, including sodium methoxide, are viewed in the prior art as less effective than potassium alkoxides. Further, some conventional isomerization process descriptions provide that decreasing cation size decreases catalytic effectiveness.

[0043] In accordance with one embodiment of the present technology, a composition comprising an unconjugated fatty acid and/or a derivative thereof, for example an alkyl linoleate composition, is treated with a metal alcoholate and a chelating agent at temperatures low enough to suppress formation of undesirable isomers, but sufficient to cause rearrangement of the double bonds. After neutralization of the catalyst, the chelating agent can be washed from the conjugated fatty aid derivative solution by using any conventional washing technique known in the art.

[0044] The unconjugated fatty acid derivatives in accordance with the presently described technology can include, but are not limited to esters, amides, carboxylic acids, salts of carboxylic acids, carboxylic anhydrides, ortho esters, 1,3-dioxolanes, dioxanones, oxazoles and hydrazides of various unconjugated fatty acids. [0045] Suitable chelating agents include, but are not limited to polyethers and polyether derivatives. For example, poly(ethylene glycol), poly(propylene glycol), fatty alcohol (C₁-C₁₂) mono-ethers of poly(ethylene glycol), fatty alcohol (C₁-C₁₂) mono-ethers of poly(propylene glycol), fatty acid esters (C₂-C₁₂) of poly(ethylene glycol), fatty acid esters (C₂-C₁₂) of poly(propylene glycol), dialkyl ethers (C₁-C₁₂) of poly(ethylene glycol), dialkyl ethers (C₁-C₁₂) of poly(propylene glycol), poly(trimethylene glycol), fatty alcohol (C₁-C₁₂) mono- ethers of poly(trimethylene glycol), fatty acid esters (C₂-C₁₂) of poly(trimethylene glycol) or dialkyl ethers (C₁-C₁₂) of poryøximethylene glycol), poly(tetramethylene glycol), fatty alcohol (C₁-C₁₂) mono-ethers of poly(tetramethylene glycol), fatty acid esters (C₂-Ci₂) of poly(tetramethylene glycol) or dialkyl ethers (Ci-C₁₂) of poly(tetramethylene glycol) can be used as chelating agents for the presently described technology. Preferably, the molecular weight of the polyethers and polyether derivatives used as chelating agents in the presently described technology range from about 150 to about 8000 atomic mass units. [0046] Preferably, the charge quantity of the chelating agent is from about 0.5% to about 25%, alternatively from about 0.5% to 9%, alternatively from about 0.75% to about 6% of the weight of the unconjugated fatty acid and/or its derivative. [0047] Preferably, the chelating agent in accordance with at least one embodiment of the presently described technology is a nitrogen-containing compound such as triethanolamine or tris[2-(2-methoxyethoxy)ethyl]amine. [0048] In accordance with at least one other embodiment of presently described technology, the chelating agent (e.g., a polyether) is added to the composition comprising the unconjugated fatty acid and/or its derivative followed by the addition of the isomerization catalyst (e.g., a metal alkoxide or amide) to the reaction mixture.

[0049] In accordance with yet another embodiment of the presently described technology, the chelating agent and the isomerization catalyst (e.g., a metal alkoxide or amide) are premixed; then the mixture comprising the chelated isomerization catalyst is added to the composition comprising the unconjugated fatty acid and/or its derivative in an isomerization reaction vessel. [0050] In accordance with the presently described technology, the catalyst loading can be from about 0.3% to about 7% by weight, alternatively from about 0.3% to about 4% by weight, alternatively from about 0.5% to about 3 % by weight, based on the weight of the fatty acid and/or its derivative in the composition. When being added directly to the unconjugated fatty acid composition or being mixed with the chelating agent to form a premix, the metal alkoxide or amide catalyst can be delivered as a solid or as a solution, for example, in the conjugate alcohol of the metal alkoxide when a metal alkoxide is used.

[0051] The isomerization step can be performed at temperatures low enough to suppress formation of undesirable CLA isomers, but sufficient to cause rearrangement of the double bonds. Such temperatures can be at or below about 140 °C, alternatively between about 90 ⁰C to about 130 ⁰C, alternatively between about 110 ⁰C to about 120 ⁰C, and alternatively at about 120 ⁰C. The catalyst, either before or after chelated with the chelating agent, can be added to the composition of the fatty acid and/or its derivative at about 140 ⁰C or below. [0052] In a preferred embodiment, no solvent is added for the isomerization step. The catalyst for the isomerization step may be added in a solvent, but the starting composition of the unconjugated fatty acid and/or its derivative is not dissolved in a solvent. Relative to the fatty acid or its derivative quantity, the catalyst solvent may be present in a minimal and/or negligible amount at any given time since the catalyst solvent is distilled from the reactor soon after it is added. By avoiding the use of solvent in the isomerization step, the potential formation of unwanted isomers, e.g., CLA-alcohol esters, can be reduced or prevented and process efficiency is improved. [0053] However, a person of ordinary skill in the art would understand that the process of the invention can optionally, although less preferably, be carried out in the presence of solvents which do not interfere with the overall conjugation reaction. Examples of such optional solvents, which are used preferably in an amount of from about 10 to about 50 percent, alternatively from about 15 to about 40 percent, alternatively from about 20 to 30 percent based on the weight of the starting fatty acid material, are for example, methyl, ethyl, isopropyl, butyl, amyl alcohol, pentane, hexane, heptane, heptylene-(l), octylene-1, benzene, toluene, or a combination thereof.

[0054] In accordance with a further embodiment of the presently described technology, a second metal alkoxide can be formed from a first metal alkoxide, e.g., a sodium alkoxide, and a salt of the second metal, e.g., a carboxylate or halide of the first metal, by for example, the precipitation of the salt of the first metal, e.g., a sodium carboxylate or halide from the cation exchange solvent.

The newly formed solution containing the second metal alkoxide can then be used to conjugate double bonds of a fatty acid and/or its derivative in a manner similar to that as described above.

[0055] Preferably, the first metal in accordance with this embodiment of the present technology is sodium, and the second metal is an alkali, alkaline earth or transition metal other than sodium. Examples of the salts of the second metals include, but are not limited to aliphatic carboxylate (C₁-C₁₂) salts of calcium, magnesium, potassium, lithium, copper or zinc and halides of calcium, magnesium, iron, copper or zinc. Examples of halide counter ions in the salts of the second metals include, but are not limited to chloride, bromide and iodide ions.

[0056] In accordance with this embodiment of the presently described technology, the salt of the second metal is preferably first dissolved in a first solvent. More preferably, the first solvent used to dissolve the salt of the second metal is capable of causing the salt of the first metal and the anion from the salt of the second metal or another anion from the first solution to precipitate. In accordance with this embodiment of the present technology, the first metal alkoxide can be added to the salt of the second metal dissolved in the first solvent as a solid, as a solution in the first solvent or as a solution in a second solvent. Examples of suitable solvents for the presently described technology include, but are not limited to aliphatic alcohols having from about 1 to about 6 carbons, aliphatic polyols having from about 1 to about 6 carbons and from about 2 to about 6 hydroxyls, dimethylformamide and tetrahydrofuran.

[0057] All documents, e.g., patents and journal articles, cited above are hereby incorporated by reference in their entirety.

[0058] The invention is illustrated further by the following examples which are not to be construed as limiting the invention or scope of the specific procedures or compositions described herein. In the following examples, all weight percentage amounts are stated in percent by weight of active material unless indicated otherwise. One skilled in the art will recognize that modifications may be made in the invention without deviating from the spirit or scope of the invention. AU levels and ranges, temperatures, results etc., used herein are approximations unless otherwise specified.

[0059] The following examples exemplify some of the advantages of the presently described technology:

Examples

Comparative Example 1: CLME trial using potassium methoxide catalyst

[0060] Methyl esters derived from safflower oil (175 g, 0.594 mol) (i.e., methyl linoleate) were treated with a 25% solution of potassium methoxide (15.2 g, 0.054 mol) in methanol at 110 ⁰C. After a 1-hour feed and a 3-hour hold period of time at 110 ⁰C, 97.6% of the available methyl linoleate had been isomerized to conjugated linoleic acid methyl ester (CLME). The fatty acid distribution was determined by GC.

Comparative Example 2: CLME trial using sodium methoxide catalyst

[0061] Methyl esters derived from safflower oil (176 g, 0.598 mol) were treated with a 25% solution of sodium methoxide (13.7 g, 0.063 mol) in methanol at 110 ⁰C. After a 1-hour feed and a 3-hour hold period of time at 110 ⁰C, only 2.5% of the available methyl linoleate had been isomerized to CLME. The fatty acid distribution was determined by GC.

Example 3: CLME trial using potassium methoxide generated from sodium methoxide

[0062] Potassium acetate (3.98 g, 0.041 mol) was dissolved in methanol (14.1 g). Next, a 25% solution of sodium methoxide (8.28 g, 0.0383 mol) in methanol was added to the clear solution. A precipitate formed within 5 minutes of the sodium methoxide addition. Methyl esters derived from safflower oil (100.7 g, 0.342 mol) were added to the slurry. The mix was heated to 120 ⁰C. After 8 hours of time at 120 ⁰C, 75.6% of the available methyl linoleate had been isomerized to CLME. The fatty acid distribution was determined by GC.

Example 4: CLME trial using sodium methoxide catalyst with ρoly(ethvlene

[0063] Methyl esters derived from safflower oil (504 g, 1.71 mol) and poly(ethylene glycol) (35.5g, 0.09 mol, avg. MW 400) were combined and heated to 120 ⁰C. Mo this solution was fed a 25% solution of sodium methoxide (56.3 g, 0.261 mol) in methanol at 120 ⁰C. After 8 hours of time at 120 ⁰C, 98% of the available methyl linoleate had been isomerized to CLME. The fatty acid distribution was determined by GC.

Example 5: CLME trial using reduced potassium methoxide catalyst charge with PEG 400

[0064] Methyl esters derived from sunflower oil (100.13 g, 0.346 mol) and poly(ethylene glycol) (1.12g, 0.0028 mol, avg. MW 400) were combined and heated to 120 ⁰C. Into this solution was fed a methanolic solution of potassium methoxide (KOMe) (25 wt.%, 1.2 g) over 1 hour at 120 ⁰C. After 2 hours of time at 120 ⁰C, the residual methyl linoleate content was 9.1% (starting linoleate content: 62.1%). Another portion of KOMe solution (1.45 g; 2.65 g total, 0.0094 mol; 0.66 wt% based on starting ester) was then added. After 1.5 hours of time, the residual methyl linoleate was determined to be 0.5%. The KOMe loading represents 32% of the typical industry standard charge. Free fatty acid for this sample after workup was 1.7%. Typical values for material made with higher catalyst loadings range from 8-10%. The fatty acid distribution was determined by GC.

[0065] The present technology is now described in such full, clear, concise and exact terms as to enable any person skilled in the art to which it pertains, to practice the same. It is to be understood that the foregoing describes preferred embodiments of the presently described technology and that modifications may be made therein without departing from the spirit or scope of the invention as set forth in the claims. A person of ordinary skill in the art will also understand that besides manufacture of the desired CLA product, the invention can be used to efficiently and economically isomerize other unconjugated fatty acids or their derivatives while reducing the formation of undesired isomers in long chain polyunsaturates.

Claims

CLAIMS WHAT IS CLAIMED IS:

1. A process to improve the performance of a suitable catalyst system for conjugating unsaturated fatty acids or their derivatives, comprising: providing a metal alkoxide or amide catalyst comprising a cation; providing a chelating agent; and chelating the cation of the metal alkoxide or amide catalyst with the chelating agent.

2. The process of claim 1, wherein the chelating agent comprises a polyether or a polyether derivative.

3. The process of claim 1, wherein the chelating agent comprises a nitrogen- containing compound.

4. The process of claim 3, wherein the nitrogen-containing compound is triethanolamine or tris[2-(2-methoxyethoxy)ethyl]amine.

5. The process of claim 1, further comprising: providing a first composition comprising an unsaturated fatty acid or a derivative thereof; treating the first composition with said chelated metal alkoxide or amide catalyst to isomerize the unconjugated fatty acid or the derivative thereof; and producing a second composition comprising a conjugated fatty acid or a derivative thereof.

6. The process of claim 5, wherein the isomerization is performed in a nonaqueous system.

7. The process of claim 1, wherein the metal alkoxide catalyst is an alkali, alkaline earth or transition metal alkoxide salt of a lower alkyl group alcohol having from about 1 to about 6 carbons.

8. The process of claim 1, wherein the cation is sodium, potassium, lithium, calcium, magnesium, cesium, iron, copper, zinc or cobalt.

9. The process of claim 1, wherein the metal alkoxide catalyst is provided as a solid or as a solution in a conjugate alcohol of the metal alkoxide.

10. The process of claim 5, wherein the first composition comprises an alkyl ester of the fatty acid, and wherein the second composition containing less than about 5% by weight of free fatty acid content .

11. The process of claim 5, wherein the fatty acid derivative is an ester, an amide, a carboxylic acid, a salt of carboxylic acid, a carboxylic anhydride, an ortho ester, a 1,3-dioxolane, a dioxanone, an oxazole, or an hydrazide of the fatty acid.

12. The process of claim 2, wherein the polyether or polyether derivative is a poly(ethylene glycol), a poly(propylene glycol), a fatty alcohol (C₁-C₁₂) mono-ether of poly(ethylene glycol), a fatty alcohol (C₁-C₁₂) mono-ether of poly(propylene glycol), a fatty acid ester (C₂-C₁₂) of ρoly(ethylene glycol), a fatty acid ester (C₂-C₁₂) of poly(propylene glycol), a dialkyl ether (C₁-C₁₂) of poly(ethylene glycol), a dialkyl ether (C₁-C₁₂) of poly(propylene glycol), a poly(trimethylene glycol), a fatty alcohol (C₁- C₁₂) mono-ether of poly(trimethylene glycol), a fatty acid ester (C₂-C₁₂) of poly(trimethylene glycol), a dialkyl ether (C₁-C₁₂) of poly(trimethylene glycol), a poly(tetramethylene glycol), a fatty alcohol (C₁-C₁₂) mono- ether of poly(tetramethylene glycol), a fatty acid ester (C₂-C₁₂) of poly(tetramethylene glycol), or a dialkyl ether (C₁-C₁₂) of ρoly(tetramethylene glycol).

13. The process of claim 2, wherein the molecular weight of the polyether or polyether derivative ranges from about 150 to about 8000 atomic mass units.

14. The process of claim 5, further comprising: adding the chelating agent to the first composition; and subsequently adding the metal alkoxide or amide catalyst to the first composition.

15. The process of claim 5, wherein the chelating agent is premixed with the metal alkoxide or amide catalyst to form the chelated metal alkoxide or amide before being added to the first composition.

16. The process of claim 14, wherein the chelating agent is added in an amount of from about 0.5% to about 25% of the weight of the fatty acid or the derivative thereof in the first composition.

17. A process for the formation of a second metal alkoxide from a first metal alkoxide by exchanging cations between the first metal alkoxide and a salt of the second metal, comprising: dissolving the salt of the second metal in a first solvent to make a first solution; mixing the first metal alkoxide with the first solution; forming a salt of the first metal and an anion from the first solution; and forming a second solution comprising the second metal alkoxide.

18. The process of claim 17, wherein the first metal is sodium and the second metal is an alkali, alkaline earth, or transition metal other than sodium.

19. The process of claim 17, wherein the salt of the second metal is selected from the group consisting of aliphatic carboxylate salts of calcium, magnesium, potassium, lithium, copper or zinc, wherein the carboxylate comprises from about 1 to about 12 carbons.

20. The process of claim 17, wherein the first solvent causes the salt of the first metal and the anion from the first solution to precipitate.

21. The process of claim 20, wherein the first solvent comprises an aliphatic alcohol having from about 1 to about 6 carbons, an aliphatic polyol having from about 1 to about 6 carbons and from about 2 to about 6 hydroxyls, dimethylformamide, or tetrahydrofuran.

22. The process of claim 17, wherein the salt of the second metal is selected from the group consisting of halides of calcium, magnesium, iron, copper or zinc.

23. The process of claim 22, wherein the halide counter ion is chloride, bromide or iodide.

24. The process of claim 17, wherein the first metal alkoxide is provided as a solid, as a solution in the first solvent, or as a solution in a second solvent.