EP1544282A1 - Process for the preparation of triglycerides of conjugated linoleic acid - Google Patents

Abstract

Method for preparing triglyceride-conjugated linoleic acid (I) by transesterification of a 1-5C linear or branched alkyl linoleic acid ester (II) with triacetin (III). An independent claim is also included for (A) prepared by the new method.

Description

Field of the invention

The invention is in the field of fatty acid esters and relates to a new process for the preparation of esters of conjugated linoleic acid with glycerol by transesterification.

State of the art

The compound class of "conjugated linoleic acids" (CLA) comprises numerous isomers of C18: 2 fatty acids whose double bonds form a conjugated p system. Analytical separation of the isomers has recently been described in ANALYTICA CHIMICA ACTA Chromatography separation and identification of conjugated linoleic acid isomers: Roach JAG, Mossoba MM, Yurawecz MP, Kramer JKG; 465 (1-2): 207-226 AUG 16 2002. While natural sources such as dairy products mainly contain the c9, t11 isomer (rumen acid), commercial syntheses usually provide a 1: 1 mixture of c9, t11 and t10, c12 isomers. Both isomers show specific physiological activities, for example, preference of building muscle over the creation of adipose tissue, strengthening of the immune system, positive influence on bone structure and anticancerogenic effect. The properties described make a mixture of these two isomers highly interesting for use as a food additive. However, a basic prerequisite for use in this area is a high isomer purity, ie the absence of undesired CLA isomers-in particular the c11, t13-CLA and trans, trans-CLAs. These form at temperatures above 130 ° C by isomerization of c9, t11 and t10, c12-CLA.
All currently commercially used methods for the preparation of CLA provide these in the form of the free acid or its esters. Naturally, however, fatty acids are mainly absorbed as fats and oils, and triglyceride is the preferred CLA derivative in food supplements. In addition to its sensorially superior properties, its very high structural and physical similarity to conventional triglycerides, especially high-linoleic acid-containing oils Thistle and sunflower oil - a light formulation in a variety of fatty preparations. In addition, triglycerides prove to be much more stable to oxidation than the corresponding free fatty acids.
Since no process for the isomerization of linoleic acid groups of an oil with preservation of the triglyceride structure is known so far. CLA triglycerides currently represented by the transesteric transesterification of CLA / CLA-Estem and glycerol. For the reasons described above, relatively mild conditions are required under which presently only enzymatic catalysts show sufficient activity. Significant disadvantages of these enzyme-catalyzed reactions, however, are the high reaction time of several days, very high enzyme costs and the unproblematic handling of the enzyme. The lipase-catalyzed interesterification of long-chain fatty acids or their alkyl esters with triglycerides of short-chain fatty acids is known, for example, from WO 90/12858 .

Various methods for the preparation of acetoglycerides, in particular stearylacetylglycerides, based on the transesterification of corresponding fats with triacetin (triacetylglyceride). The main catalysts used are metal soaps. Some of the reactions are carried out at 200-260 ° C as US 6,124,486 can be seen. At lower temperatures, the low miscibility of triacetin with triglycerides bearing long-chain fatty acids (C16-C22) leads to significant decreases in reactivity and thus yield. This restriction can be overcome by the addition of C3-C10 triglycerides. International Application WO 94/18290 and US 5,434,278 disclose interesterification of triacetyls and triglycerides with C16 - C22 long chain fatty acid residues to mixed triglycerides with long chain and short chain fatty acid residues, characterized in that the reaction comprises triglycerides with saturated C3 - C10 fatty acid residues is added. This ensures that the reaction is single-phase, solvent-free, fast and without high-performance mixture.
The object of the present invention was therefore to provide a process for the preparation of CLA triglycerides, which is characterized by a good profitability characterized by short reaction times, high yields and inexpensive starting materials. The resulting CLA triglycerides should have a high isomer purity synonymous with a low content of trans, trans isomers and c11, t13 - isomers.

Description of the invention

The invention relates to a chemical process for the preparation of triglycerides conjugated linoleic acid (CLA triglycerides), in which one Linolsäurealkylester with a linear or branched alkyl radical having 1 to 5 carbon atoms in the presence of Triacetin (triacetylglyceride) transesterified.

The synthesis is carried out by transesterification of a CLA-alkyl ester, preferably methyl and ethyl esters, corresponding quality (food grade) with triacetin. Suitable catalysts are bases, preferably alkali metal alkoxides, more preferably sodium methoxide. The latter can be used both solid and dissolved in the corresponding alcohol. While the reaction is successful even when using stoichiometric amounts of the starting materials, the yield of CLA triglyceride can be increased by using an excess of CLA ester based on the amount of triacetin. Preferred is a 10-30%, more preferably a 20% excess of the CLA ester.
Surprisingly, the required amount of triacetin proves to be completely soluble in the CLA ester and the process can be carried out in a single phase. High reaction temperatures, the use of strong stirrers or the use of solubilizers or solvents, as known from the prior art, thus becomes superfluous even at low reaction temperatures.
The chemical representation of the CLA triglyceride by transesterification of triacetin and a CLA alkyl ester proceeds within a few hours in the presence of catalytic amounts of an alkoxide. The reaction temperature is 90 to 160 ° C, preferably 100 to 140 ° C, more preferably 120 to 130 ° C. At a reaction temperature of 130 ° C, the reaction is complete after about 3 hours. After working up, unreacted CLA ester can be almost completely separated from CLA glycerides by short path distillation.

Surprisingly, it was also found that the isomeric pattern in the CLA triglyceride corresponds to the used CLA alkyl ester (see Table 1), although Alkoxides at 130 ° C effective isomerization catalysts. Among the elected Conditions obviously do not find unwanted secondary isomerizations instead of; the isomeric pattern of the fatty acid remains unchanged. This means that the Content for each of the C 18: 2 isomers after the transesterification reaction no longer as 3, preferably 1, more preferably 0.5 area% measured by the method by Eulitz et al. (see Table 3c) differ from the value of the isomers used should.

This is noteworthy, since alkoxides - methoxide and ethanolate in particular - are among the most efficient isomerization catalysts ever and are used commercially for the synthesis of CLA methyl and ethyl esters. The absence of unwanted CLA isomers in the product is a crucial quality criterion.
Undesirable isomers are to be understood as meaning C 18: 2 trans, trans isomers whose increase by the process according to the invention is not more than 0.5, preferably 0.3 and in particular 0.2 area% (see Table 3 c) Area%) should be compared to the starting product.
Also undesirable are c11, t13 - isomers - in animal experiments could be an accumulation of these isomers in the pig heart detect. They are determined by silver ion HPLC methods according to Eulitz et al. determined (see Table 3c) and should be present in the CLA triglyceride at most in an amount of 0.5, preferably 0.3, more preferably 0.1 area%.
In contrast to enzymatic processes, their multiple use is not necessary due to the low catalyst costs, which considerably simplifies handling. In addition, a considerably shorter reaction time is required.
Optimized reaction yields of over 80% CLA triglyceride can be achieved. Remarkably, the only other major component of the product was not the expected di-CLA-monoacetyl-triglyceride - the result of the double transesterification of triacetin and CLA-ester - but the CLA-diglyceride: Acetyl groups and free acetic acid could only be obtained by HPLC detect in extremely small amounts in the reaction product. This has a decisive positive effect on the product quality: on the one hand, it avoids the risk of releasing acetic acid under unfavorable storage conditions, which, among other things, would severely impair the sensory properties of the product. On the other hand, a mixture of CLA di- and triglyceride corresponds largely to natural oils, which makes use as a food supplement unproblematic.
After short-path distillation and Aufreiningung on thin-film evaporator gives a CLA glyceride mixture of tri- and diglycerides with very small traces of monoglyceride, the amount of triglycerides at least 70% preferably 75% and the amount of monoglycerides maximum 1%, preferably at most 0.5% based on the total amount of CLA glycerides should be.

The starting materials for the process according to the invention are conjugated linoleic acid alkyl esters, which preferably follow the formula (I), R ¹ CO-OR ² in which R ¹ CO is the acyl radical of a conjugated linoleic acid and R ^{2 is} a linear or branched alkyl radical having 1 to 5 carbon atoms. In particular, conjugated linoleic acid methyl and / or ethyl esters are used.
Among conjugated linoleic acid according to the invention are preferably the main isomers 9cis, 11trans octadecadienoic acid and 10trans, 12cis and, however, any isomeric mixtures, such as are usually obtained in the preparation of conjugated linoleic acid.

The catalysts selected are bases, preferably alkali metal alkoxides, such as, for example, sodium methoxide, sodium ethanolate, sodium propanolate, sodium butoxide, potassium methoxide, potassium ethanolate, potassium propoxide, potassium butoxide
The alcoholates can be used both solid and dissolved in the corresponding alcohol.

Examples Preparation of triglycerides of conjugated linoleic acid example 1

Reaction of CLA methyl ester with triacetin using methanolate solution starting materials material amount of substance
[mol] Weight
[G] CLA Methylester 1.0 292.4 triacetin 0.3 65.5 Sodium methoxide solution (30% in methanol) 00:04
(NaOMe) 7.2
(Solution) citric acid 00:02 4.2

After drying of methyl ester and triacetin (vacuum, 120 ° C, 30 min) catalyst solution is added at 90 ° C under a nitrogen atmosphere. Upon subsequent heating to 130 ° C, methyl acetate distils off. After about 1 hour, vacuum is applied and stirred for a further 3 h. It is then neutralized with citric acid at 80 ° C, washed several times with 150 ml of hot water, dried (vacuum, 120 ° C, 30 min) and filtered. Key figures CLA triglyceride unit acid number 2.1 mg KOH / g saponification 189 mg KOH / g oleochem. Key figures hydroxyl 15.7 mg KOH / g iodine Value 134 composition CLA Methylester 26.5 % Mono- / di- / triglyceride 0.8 / 14.6 / 55.7 %

Example 2

Reaction of CLA methyl ester with triacetin using solid methoxide starting materials material amount of substance
[mol] Weight
[G] CLA Methylester 1.0 292.4 triacetin 0.3 65.5 Sodium methoxide 00:04 2.2 citric acid 00:02 4.2

After drying of methyl ester and triacetin (vacuum, 120 ° C, 30 min) catalyst is added at 90 ° C under a nitrogen atmosphere. Upon subsequent heating to 130 ° C, methyl acetate distils off. After about 1 hour, vacuum is applied and stirred for a further 3 h. It is then neutralized with citric acid at 80 ° C, washed several times with 150 ml of hot water, dried (vacuum, 120 ° C, 30 min) and filtered. Key figures CLA triglyceride unit acid number 3.2 mg KOH / g oleochem. Key figures hydroxyl 8.1 mg KOH / g composition CLA Methylester 25.9 % Mono- / di- / triglyceride 0.9 / 9.5 / 61.6 %

Example 3

Reaction of CLA ethyl ester with triacetin using methanolate solution, including short path distillation for purification. starting materials material Amount of substance [mol] Weight [g] CLA ethyl ester 15.1 4637 triacetin 4.6 995 Sodium methoxide solution (30% in methanol) 0.63
(NaOMe) 112.6
(Solution) Citric acid, anhydrous 0.3 60 Water, demin. 120 Becolite® 5000 filter aid Source: Begerow, Germany 23

After drying of ethyl ester and triacetin (<30 mbar, 80 ° C, 30 min) is added at 80 ° C under nitrogen atmosphere catalyst. Upon subsequent heating to 130 ° C distilled ethyl acetate. After about 1 hour, vacuum is applied (to <30 mbar) and stirred for a further 3 h. It is then neutralized at 80 ° C with citric acid dissolved in 120 g of demineralized water, stirred at 80 ° C for 10 min and added filter aid. The crude product is obtained after drying (<30 mbar, 80 ° C, 30 min) and filtration as a yellow oil. The CLA ethyl ester contained therein is separated by short path distillation and the resulting oil is purified on a thin-film evaporator.
After these refining steps, triglyceride levels of at least 70% based on the total amount of CLA glycerides are obtained. Key figures CLA triglyceride value unit in general. yield 3237 G oleochem. Key figures acid number 00:06 mg KOH / g saponification 190.6 mg KOH / g iodine Value 165.7 peroxide 0.2 Gardner 4 unsaponifiables <0.1 % composition Mono- / di- / triglyceride 0.3 / 18.9 / 77.8 Area% Glycerin free <0.1 Area% fatty acid ethyl esters 0.8 Area% oligomers 0.4 Area% Acetic acid free <0.2 % By weight Bound acetic acid <0.1 % By weight Comparison of the fatty acid distribution in the educt (CLA ethyl ester) and product (CLA di / triglyceride in the process with triacetin (according to Example 3) The isomer distribution of CLA triglycerides was determined by HPLC methods according to LIPIDS,
Preparation, separation, and confirmation of the eight geometric cis / trans conjugated linoleic acid isomers 8,10-through 11,13-18: 2; Eulitz K, Yurawecz MP, Sehat N, Fritsche J, Roach JAG, Mossoba MM, Kramer JKG, Adlof RO, Ku Y, 34 (8): 873-877 AUG 1999. fatty acid Starting material (CLA-EE) Product (CLA-TG) unit C16: 0 1.3 1.2 area% C18: 0 2.7 2.8 area% C18: 1 c9 14.0 12.8 area% C18: 2 c 9, c 12 0.2 0.1 area% C18: 2 conj., Total 80.5 80.8 area% C18: 2 conj., C 9, t 11 39.8 39.8 area% C18: 2 conj., T 10, c 12 38.7 38.7 area% C18: 2 conj., T 8, c 10 - <0.1 area% C18: 2 conj., C 11, t 13 - 0.1 area% C18: 2 konj., C, c isomers 0.9 1.0 area% C18: 2 konj., T, t isomers 1.0 1.1 area%

Claims (8)

Process for the preparation of triglycerides of conjugated linoleic acid (CLA triglycerides), in which
Conjugated Linolsäurealkylester having 1 to 5 carbon atoms in a linear or branched alkyl radical in the presence of triacetin transesterified. Process according to Claim 1, characterized in that the transesterification is catalyzed by alkali alkoxylates. A process according to claim 2, characterized in that alkali alcoholates are selected from the group formed by sodium methoxide, sodium ethanolate, sodium propanolate, sodium butoxide, potassium methoxide, potassium ethanolate, potassium propoxide and potassium butanolate. A method according to any one of claims 2 and / or 3, characterized in that one uses as the alkali metal alcoholates sodium methoxide in solid or dissolved form. A method according to any one of claims 1 to 4, characterized in that one carries out the transesterification at temperatures of 90 to 160 ° C. Method according to at least one of claims 1 to 5, characterized in that one uses a 10 to 30% excess of CLAalkylester based on the amount of triacetin. A method according to any one of claims 1 to 6, characterized in that followed by a short path distillation for purifying the CLA triglycerides. CLA triglycerides obtainable by the process according to claims 1 to 7.