CS276881B6 - Process for preparing fatty acids diacylglycerols - Google Patents

Abstract

Process for the preparation of fatty diacylglycerols acids by reacting monoacylglycerol with the oxide phosphorous in a non-polar liquid medium. Diacylglycerols are formed in addition to glycerolphosphoric acid by disproportionation unstable intermediate. Final products containing about 95 wt. diacylglycerols and are useful as biologically active additives pharmaceutical and cosmetic preparations and as starting materials for preparation glycerophospholipids.

Description

The present invention relates to a process for the preparation of fatty acid diacylglycerols by reacting monoacylglycerols with phosphorus pentoxide in a non-polar liquid medium. Another product of this reaction is glycerol phosphoric acid.

Diacylglycerols are used as biologically active lipids in pharmaceutical and cosmetic products, as cosmetic and food non-toxic emulsifiers, as enhancing additives. plasticity of food fats, raw materials for the preparation of glycerophospholipids and the like (Beridge M., et al., Nature 312, 315 (1984), Moolenaar WH, et al., Nature 323, 6084 (1986), JP 63-104917 (1986), Ranny M ., doctoral dissertation, ICT Prague / 1990 /). Technical diacylglycerols are commonly produced by glycerolysis of fats in the presence of alkaline catalysts, for example KOH and Ca (OH) ₂ / a, at a temperature of 200 to 240 ° C (Czech Author's Certificate No. 261 170 (1989)). However, the glycerolysis products contain, in addition to the desired diacylglycerols (40 to 50% by weight), unreacted triacylglycerol (20 to 40% by weight) and monoacylglycerol (15 to 25% by weight) and are particularly suitable as raw materials for the production of acylglycerophosphates (e.g. author's certificate No. 173 220/1978 /, Czechoslovak author's certificate No. 203 421/1982 / and Czechoslovak author's certificate No. 256 690/1989 /). Also, more modern enzymatic processes for the preparation of diacylglycerols essentially lead to mixtures of partial acylglycerols, triacylglycerols and unreacted fatty acids (e.g. Jap. Pp. 51-7754 (1976), J. America. Oil Chemist s Soc., 61, 776 (1984)). . Newer biotechnological methods based on the use of large amounts of selective lipases (2 to 20% by weight, based on a starting mixture of fatty acids and glycerol) are expensive and the final products contain a maximum of 80% by weight of diacylglycerols (EP 307 154 (1988)). On the other hand, processes for the preparation of more concentrated (i.e. about 90% by weight, diacylglycerols) or pure diacylglycerols (more than 95% by weight, diacylglycerol) are too complex, require difficult to obtain chemicals and are usually only applicable to small amounts of diacylglycerols. for scientific work. For example, the preparation of structurally defined diacylglycerols is based on 3,4-isopropylidene-D-mannitol, which is converted in a multi-step synthesis to 1,2-isopropylidene-3-benzyl-sn-glycerol and then acylated with a fatty acid in the presence of 4- dimethylaminopyridine and dicyclohexylcarbodiimide; the benzyl protecting group is removed by catalytic hydrogenolysis in the presence of palladium on carbon (Eibl H., Phospholipid Synthesis, in Liposomes / Knight CG, ed./Elsevier, Amsterdam 1981).

The described disadvantages are eliminated by the process for the preparation of diacylglycerols of fatty acids according to the invention, which consists in the reaction of monoacylglycerols of fatty acids having 8 to 22 carbon atoms in the fatty acid chain with phosphorus pentoxide in a nonpolar liquid medium at 30 to 100 ° C. The molar ratio between monoacylglycerol and phosphorus pentoxide is 1: 0.5 to 1.0. After reacting 95 to 99.5% by weight of the starting monoacylglycerols, the solution of the diacylglycerol formed by the reaction is separated from the precipitated glycerol phosphoric acid, which is insoluble in a non-polar medium. The diacylglycerol solution is then neutralized with a suitable base, preferably calcium hydroxide or ammonia gas, and the precipitated insoluble phosphates are removed either by filtration or by centrifugation. In the final stage, the solvent is removed from the clarified solution by distillation, • / /

CS 276881 B6 / *

preferably under reduced pressure.

The advantage of the process for the preparation of diacylglycerols according to the invention lies in particular in the high yield of diacylglycerols, since the final products contain 95 to 99% by weight of diacylglycerols. The method does not require hard-to-reach chemicals, it is not technologically demanding. It makes it possible to obtain pure diacylglycerol in sufficient quantities.

In developing this method of preparation, we based on our knowledge of the mechanism of phosphorylation of monoacylglycerols in a non-polar environment. This can be briefly described as follows: Monoacylglycerol is imperfectly soluble in a non-polar liquid medium and, due to its polar-non-polar structure, accumulates at the phase interface between the solvent and the dispersed phosphorus pentoxide particles. The reaction of both components produces lysophosphatidic acid (LPA), which forms with monoacylglycerol a reaction intermediate (I) which is unstable and disproportionates to protonated diacylglycerol and the glycerol phosphoric acid anion (GPA). The transfer of a proton from diacylglycerols to said anion then produces both final products, i.e. diacylglycerol and glycerol phosphoric acid:

0.5 H ₂ O (-) (+)

MG + 0.5 P ₂ 0 ₅ —--------- LPA. MG ---------- (-) (+)

-------- GPA + DG --------- DG + GPA

The reaction in the product direction is promoted by the fact that glycerol phosphoric acid is insoluble in a non-polar medium and forms a separate phase.

As monoacylglycerol, the products of molecular distillation of a mixture of partial acylglycerols obtained by glycerolysis of vegetable and / or animal fats can be advantageously used. These lipids are now commonly produced in thousands of tons as food emulsifiers and baking additives. Depending on the type of starting fat, they contain both saturated and unsaturated fatty acids with 8 to 22 carbon atoms in the fatty acid chain. The reaction non-polar medium can be solvents with a relative permittivity of 1.8 to 6, preferably simple hydrocarbons such as n-pentane, n-hexane, n-heptane, isooctane and cyclohexane.

The reaction rate is directly proportional to the temperature, the corresponding activation energy is around 40 to 50 kJ.mol ^-1 . The maximum reaction temperature is given by the boiling point of the solvent and depends on the solubility of the starting monoacylglycerols in the reaction medium. In general, unsaturated fatty acid derivatives, such as molecularly distilled rapeseed oil monoacylglycerol, dissolve in hydrocarbons at normal temperatures, while saturated fatty acid monoacylglycerol, such as hydrogenated tallow monoacylglycerol, is soluble in non-polar environments only at temperatures of 50 to 70 ° C.

The ratio between the reactants is given by the above reaction mechanism; when using the theoretical amount of phospho3, the reaction is completed after a few hours, in excess and at higher temperatures it may take only a few minutes; in this case, however, the concomitant glycerol phosphoric acid is contaminated with polyphosphoric acids.

The progress of the reaction can be monitored by the determination of unreacted monoacylglycerol by one of the flash quantitative chromatographic procedures, for example by TLC-FID on commercial Chromarods with benzene: ethyl acetate: acetic acid: water (100: 4: 0.6: 0.2 v / v). ).

After completion of the reaction, i.e., as soon as 95 to 99.9% by weight of monoacylglycerol has reacted, the diacylglycerol solution is discharged from the reactor and neutralized with a suitable base. The neutralization temperature is again limited by the boiling point of the solvent, the temperature during filtration or blasting by the solubility of diacylglycerol. In general, diacylglycerol solutions should be filtered or centrifuged at a temperature several degrees above the cloud point of the solution in question. flow.

The solvent is removed from the centrifuged or filtered diacylglycerol solutions by distillation, preferably under reduced pressure, and the diacylglycerols obtained are either used directly or can be refined by crystallization, optionally on active adsorbent columns. Another reaction product, i.e. glycerol phosphoric acid, can be used as a nutrient in food, feed or cosmetics after neutralization.

The process for the preparation of the diacylglycerols of fatty acids according to the invention is further illustrated in the following examples. Reference examples 1 and 2 are given for comparison.

Example 1.

100 g (0.47 mol) of molecularly distilled monoacylglycerol from coconut fat were dissolved at elevated temperature (50-60 ° C) in 550 ml of cyclohexane. The resulting solution was added to a reactor in which 35 g (0.25 mol) of phosphorus pentoxide was dispersed in 50 ml of the same solvent. The mixture was stirred at 50 ° C and samples were taken every hour for TLC-FID analysis. After 5 hours, when 95% of the starting monoacylglycerol had reacted, the liquid phase was discharged from the reactor into the neutralizer and 40 g of powdered calcium hydroxide were added. The mixture was stirred at 45 to 50 ° C for 15 minutes and then filtered at the same temperature. The filtrate was evaporated on a rotary evaporator at 60-65 ° C. 75 g of product were obtained (i.e. about 90% of theory), the composition of which is given in Table 1.

Example 2

Following the procedure of Example 1, 100 g (i.e. 0.27 mol) of distilled hydrogenated tallow monoacylglycerol (ref. 3) were reacted with 33 g of phosphorus pentoxide (i.e. 0.23 mol) in n-heptane (500 ml) at boiling point (around 98 ° C). About 98% by weight of the starting monoacylglycerol reacted within 15 minutes. The separated liquid phase was neutralized with ammonia gas at 60 ° C and the precipitated solids were removed by centrifugation. After distilling off n-heptane on a rotary evaporator at 70 [deg.] C., 80 g of product were obtained (i.e. about 93% of theory). The composition of the product is given in Table 1.

Example 3

Following the procedure of Example 1, diacylglycerol was prepared from rapeseed oil, low in erucic acid, from 100 g (i.e. 0.27 mol) of the corresponding monoacylglycerol and 24 g of phosphorus pentoxide (i.e. 0.17 mol) in an extraction gasoline (boiling point 65 to 72 ° C, 400 ml) at 35 ° C. Analysis of the reaction samples by TLC-FIS showed that after 8 hours, 97% by weight of the starting monoacylglycerol had reacted. 28 g of calcium hydroxide were used for neutralization. 76 g of final product were obtained (i.e. 89% of theory), the corresponding analysis of the product is given in Table 1.

Reference Example 1

A mixture of 100 g of hydrogenated tallow (ref. 3), 12 g of glycerol and 0.02 g of Ca (OH) 2 was heated under nitrogen at 220 ° C for 3 h. After lowering the temperature to 170 ° C, the catalyst was neutralized with 75% phosphoric acid, and the formed inorganic phosphate was separated by centrifugation. The composition of the product is given in Table 1.

Reference Example 2 g of immobilized lipase Lipozyme 3 A (Novo Ind.), 85 g of a mixture of low erucic acid rapeseed oil and 15 g of glycerol were stirred at 38 ° C for 15 h. The resulting water was continuously removed by distillation. under reduced pressure. The product was then separated from the enzyme by centrifugation. The composition of the product is given in Table 1.

The reaction products obtained according to Examples 1 to 3 and according to both reference examples were analyzed by TLC-FID on Chromarods S III layers and evaluated on a latroscan TH-10 instrument. The results of the analyzes in the table indicate the advantages of our approach.

Table 1

Example Component (% by weight) monoacyl-diacyl-triacyl-inorganic glycerol glycerol glycerol phosphate 1 CM O rd O Μ * in σι cn '2 1.9 98.0 - 0.1 3 1 ω ό σι σι ο ω ω RF 1 19.5 48.1 33.1 0.3 RF 2 14.8 75.1 4.5 5.6

Claims (2)

PATENT CLAIMS A process for the preparation of fatty acid diacylglycerols, characterized in that monoacylglycerol having 8 to 22 carbon atoms in the fatty acid chain is treated in a non-polar liquid medium at 30 to 100 ° C with phosphorus pentoxide in a molar ratio of 1: 0.5 to 1. After reacting 95 to 99.5% by weight of the starting monoacylglycerol, the diacylglycerol solution formed is separated from the precipitated glycerol phosphoric acid, made neutral, filtered or centrifuged, and the diacylglycerol is obtained from the solution thus evaporated by evaporating the solvent. 2. The process according to item 1, characterized in that the diacylglycerol solution is neutralized with ammonia gas or calcium oxide before filtration or centrifugation.