ES2334536A1 - Procedure for the selective obtaining of 12-hydroxy-9-cis-octadecenoate from (1,4: 3,6-dianhydro-d-glucitol) using immobilized lipas as a catalyst (Machine-translation by Google Translate, not legally binding) - Google Patents

Abstract

The preparation of 12-hydroxy-9-cis-octadecenoate from (1,4: 3,6-dianhydro-d-glucitol) is carried out by selective esterification of ricinoleic acid (12-hydroxy-9-cis-octadecenoic acid) and (1), 4: 3,6-dianhydro-d-glucitol) using as a catalyst immobilized lipases in anion exchange resins or porous or other acrylics that give the obtained catalyst a pore diameter between 50 and 400º a, and a specific surface area between 10 and 40º c. And 150 m 2 /gr. The lipases used come from the fungal species mucor miehi and candida antarctica. The esterification reaction is carried out at pressures between atmospheric and 1 mm hg at a temperature comprised between 20 and 90º c. It is noteworthy that the monoster resulting from the esterification of isosorbide is mainly obtained by the process object of this invention. In position 2 and as the cis isomer. (Machine-translation by Google Translate, not legally binding)

Description

Procedure for the selective obtaining of 12-hydroxy-9-cis-octadecenoate from (1,4: 3,6-dianhydro-D-glucitol) using immobilized lipases as a catalyst.

The present invention relates to a Selective esterification procedure of ricinoleic acid with isosorbide using immobilized lipases as a catalyst.

Isosorbide (1,4: 3,6-dianhydro-D-glucitol) (Formula I) is a type of diols whose structure is a heterocycle bicyclic derived from sugars, which in recent years has received a considerable interest, particularly for his great biological activity

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State of the art

The synthesis of the isosorbide esters and fatty acids are not abundantly reflected in the scientific literature

Seemayer et al in 1991 ("Enzymatic Preparation of Isomerically Pure 1,4: 3,6-Dianhydro-D-Glucitol Monoacetates precursors for Isoglucitol 2 and 5 mononitrates", Tetrahedron: Asymmetry , vol. 3, no. 9 (1991), pg. 1123-1126) and in US Patent 5,538,891 describe the synthesis of two-stage isosorbide 2-monoacetate. In the first one the isosorbide diacetylate derivative is obtained using acetic anhydrous and pyridine followed by enzymatic hydrolysis using flourishing pseudomonas as catalysts.

Stoss et al in 1987 ("Regioselective acylation of 1,4: 3,6-Dianhydro-D-Glucitol" Synthesis vol. 2 (1987), pg. 174-176) and in European patent EP 0 057 847 obtain the monoacetate of isosorbide by the acylation reaction with anhydrous acetyl, followed by distillation on the basis, hydroxides carbonates or alkali alkoxides obtaining a yield of 70%. The process is not economically profitable due to the high energy costs of the distillation operation.

Cetovic et al in 1989 ("Selective Esterification of 1,4: 3,6-Dianhydro-D-Glucitol" Synthesis vol. 8 (1989), pg. 610-611), describe a selective method for esterification of isosorbide with derivatives of carboxylic acids in the presence of 4-demethylamino pyridine (DMAP). The yields of 2-esterdiol were between 68% and 85%.

Another approach to the synthesis of the monoester is described by Abenhaim et al in ("Selective Alkylations of 1,4: 3,6-Dianhydro-D-glucitol (isosorbide)" Carbohydrate Reseach , vol. 261, no. 2 (1994), pg 255-266) using protective agents such as allyl, propyl or benzoyl groups.

Mukesh et al in 1993 ("Lipase catalysed esterification of isosorbide and sorbitol". Biotechnology Letters vol. 15, no. 12 (1993), pg. 1243-1246), describe the esterification reaction of oleic acid and isosorbide using as catalyst the commercial enzyme immobilized lipozime IM-20 and silica gel. Isosorbide mono ester oleate is obtained as the only reaction product in a tubular reactor. The maximum conversion was 95% with an operating time of 13 hours.

In 1992, Ghoshray et al . ("Enzymatic prepanohydric alcohols and properties of the esters". J. Am. Oil Chem. Soc. , Vol. 69, no. 1 (1992), pg. 85-88) describe the reaction of obtaining esters of ricinoleic acid by the transesterification reaction of castor oil with monoalcohols such as decanol, dodecanol, tetradecanol, hexadecanol and octadecanol using a soluble lipase from Mucor miehi at a temperature of 60 ° C.

EP 0 320 132 describes an enzyme fixed assets comprising an insoluble macroporous carrier and a lipolytic enzyme adsorbed on it that is obtained by treatment of the carrier with a fatty acid. This enzyme has application in esterification and transestirification processes where the immobilization in the presence of a fatty acid leads to greater enzyme yield, obtaining conversions close to 90% in the esterification of fatty acid with a monoalcohol or a polyol. This patent refers to the use of the enzyme in processes of esterification in general, not being oriented to obtain a specific product, as is the case with the present invention.

The process of the present invention is characterized by using as immobilized lipase catalysts on resins without prior treatment with a fatty acid, in the esterification reaction between isosorbide (polyol) and acid ricinoleic (acid 12-hydroxy-9-cis-octadecenoic acid), achieving conversions higher than 95% and selectivity at desired monoester close to 90% in just two hours of reaction.

The effectiveness of the present procedure lies in that, first there is no bibliographic reference for the selective obtaining of monoester (isosorbide monoricinoleate) from Ricinoleic acid by direct esterification in yields almost quantitative, second with this procedure you get specifically the cis isomer of the final monoester without existing cis-trans isomerization and third this procedure  allows to filter the enzyme catalyst when the reaction has concluded, reuse it and isolate the monoester in a single step purification.

Description of the invention

In the present invention a esterification procedure of ricinoleic acid, 12-hydroxy-9-cis-octadecenoic with 1,4: 3,6-Dianhydro-D-Glucitol, in which they are used as lipase catalysts of different fungal species and catalytic activity immobilized in resins anion exchange or macroporous acrylics, with different pore diameters and specific surfaces, obtaining high yields and selectivities of the corresponding monoesters

The present invention relates to the use of enzymes, of certain characteristics, to direct the esterification between ricinoleic acid with the isosorbide to obtain a proportion greater than 90% of monoester The esterification reaction takes place according to conventional procedures in a continuous or discontinuous reactor, stirred tank type or in a basket reactor or in reactors Continuous type fixed bed or fluidized bed, in which Find the enzyme catalyst. The reaction is carried out in the temperature range of 60ºC and 80ºC.

The reaction is convenient to carry out under pressure Atmospheric or vacuum (1 mm Hg) when interested in eliminating evaporation of the water formed. In the event that the balance is move by removing one of the reaction products, by water, for example, conversions of over 85% are achieved, being the time needed to reach this conversion from 10 to 120 minutes, although normally this time is between 10 and 60 minutes.

The catalytic systems referred to in the present invention are enzymatic preparations consisting of lipases, triacylglycerol hydrolases (EC 3.1.1.3), produced by the fungal species Mucor miehi or the fungal species Candida antarctica , and immobilized on anionic or acrylic exchange resins macroporous, with different properties for each of them, and different The two enzymatic species can exert with high effectiveness the action of lipase or the action of carboxylesterase and, also in both cases, the specificity of said enzymes can be positional or not depending on the type of substrate that you want to modify with them. Catalytic systems have an average pore diameter that is in the range of 50 and 400 Å, preferably between 120 and 300 Å. Being the range in which the specific surface area of 10 and 150 m2 / g, preferably between 25 and 100 m2 / g, is located.

Catalytic systems produced from the fungal species Mucor miehi have an activity that is in the range of 20 to 80 BIUS (number of µmoles of palmitic acid transformed with triolein per minute using the immobilized enzyme at a temperature of 40 ° C).

Catalytic systems produced from the fungal species Candida antarctica have an activity that is in the range of 5000 to 12000 PLUS / g (number of n-propyl laurate obtained from lauric acid and 1-propane1 during a reaction time of 15 minutes, at a temperature of 60 ° C).

The objective of the present invention is the selective obtaining of 12-hydroxy-9-cis-octadecenoate of isosorbide. Qualitative and quantitative identification has been carried out by a combination of techniques such as IR (infrared), 1 H-NMR (Magnetic resonance 1 H nuclear), 1 C-NMR (Resonance 13 C nuclear magnetic), mass spectrometry and gas chromatography.

Embodiment of the invention

The present invention is further illustrated. by the following examples:

Example 1

In this example the influence of the activity of an enzymatic catalyst obtained from the fungal species Mucor miehi , immobilized in an anion exchange resin, with an average pore diameter of 176 Å is shown. A specific surface area 60 m2 / g. and an activity of 60 BIU.

The reaction is carried out in a reactor of complete mix of 250 ml capacity, provided with a system of vacuum distillation. Ricinoleic acid is introduced into it and isosorbide in a 1: 1 molar ratio, with an initial concentration of 5% by weight enzyme catalyst. The temperature of reaction was maintained at 70 ° C, the working pressure at 55 mm Hg and the stirring speed was 600 r.p.m.

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After 2 hours of reaction, the conversion of acid was 45%, with a selectivity in the formation of 92% monoester, the rest is formed by diester.

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Example 2

This example shows the influence of the activity of an enzymatic catalyst obtained from the fungal species Candida antarctica , immobilized in a macroporous acrylic resin, with an average pore diameter of
180 Å, a specific surface area 95 m2 / g. and an activity of 7000 PLUS / g.

The reaction is carried out in a reactor of complete mix of 250 ml capacity, provided with a system of vacuum distillation. Ricinoleic acid is introduced into it and isosorbide in a 1: 1 molar ratio, with an initial concentration of 5% by weight enzyme catalyst. The temperature of reaction was maintained at 70 ° C, working pressure at 55 mm Hg, and stirring speed at 600 r.p.m.

After two hours of reaction, the conversion of acid was 97%, with a selectivity in the formation of 91% monoester the rest is formed by diester.

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Example 3

This example shows the influence of the activity of an enzymatic catalyst obtained from the fungal species Candida antarctica immobilized in a macroporous acrylic resin with an average pore diameter of
210 Å, a specific surface area 67 m2 / g. and an activity of 7800 PLUS / g.

The reaction is carried out in a reactor of complete mix of 250 ml capacity, provided with a system of vacuum distillation. Ricinoleic acid is introduced and isosorbide in a 1: 1 molar ratio, being initial concentration of 5% by weight enzyme catalyst. The temperature of reaction was maintained at 70 ° C, working pressure at 55 mm Hg, and stirring speed at 800 r.p.m.

After two hours of reaction, the conversion of acid was 49%, with a selectivity in the formation of 94% monoester, the rest is formed by diester.

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Example 4

This example shows the influence of the reaction temperature Example 2 was repeated with the same catalyst and operating conditions, except the temperature of reaction, which was maintained at 80 ° C.

After two hours of reaction, the conversion of acid was 100%, with a selectivity in the formation of 87% monoester, the rest is formed by diester.

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Example 5

This example shows the influence of the initial catalyst concentration. Example 2 was repeated, with the same catalyst and operating conditions, except the initial catalyst concentration, which was set at 7.8% in weight.

After two hours of reaction, the conversion of acid was 93%, with a selectivity in the formation of 91% monoester, the rest is formed by diester.

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Example 6

This example shows the influence of the work pressure. Example 5 was repeated, with the same catalyst and operating conditions, except working pressure,  which was maintained at 380 mm Hg.

After 2 hours of reaction, the conversion of acid was 71%, with a selectivity in the formation of 92% monoester, the rest is formed by diester.

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Example 7

This example shows the influence of the molar ratio alcohol: acid. Example 5 was repeated, with the same catalyst and operating conditions, except the molar ratio alcohol: acid, which was set at 3.

After 2 hours of reaction, the conversion of acid was 96%, with a selectivity in the formation of 91% monoester, the rest is formed by diester.

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Example 8

This example shows the influence of the stirring rate. Example 2 was repeated, with the same catalyst and operating conditions, except the speed of reaction that was set at 100 r.p.m.

After two hours of reaction, the conversion of acid was 45%, with a selectivity in the formation of 92% monoester, the rest is formed by diester.

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Example 9

This example shows the influence of the activity of an enzymatic catalyst obtained from the fungal species Candida antarctica , immobilized in a macroporous acrylic resin, with an average pore diameter of 180 Å, a specific surface 95 m 2 / g. and an activity of 7000 PLUS / g.

The reaction is carried out in a type reactor 250 ml capacity basket and a 300 µm mesh light, provided with a vacuum distillation system. Is introduced into it ricinoleic acid and isosorbide in a 1: 1 molar ratio, and the Initial concentration of enzyme catalyst of 5% by weight. The reaction temperature was maintained at 70 ° C, the working pressure at 55 mm Hg, and stirring speed at 700 r.p.m. After two hours of reaction, the acid conversion was 85%, with a selectivity in the formation of monoester of 92%, the rest is formed by diester.

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Example 10

This example shows the influence of the Mesh light. Example 9 was repeated, with the same catalyst and operating conditions, except for the mesh light that was set at 400 \ mum.

After two hours of reaction, the conversion of acid was 94%, with a selectivity in the formation of 92% monoester, the rest is formed by diester.

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Example 11

In a fixed bed of extensible capacity, with a diameter of 1.6 cm. and a height of 6 cm., provided with a jacket to thermostatize the operation, 4.5 g are introduced. of immobilized enzyme. Through it, a mixture of ricinoleic acid and isosorbide is circulated in a 1: 1 molar ratio at a flow rate of 1 ml / min. The enzymatic catalyst used is that obtained from the fungal species Candida antarctica , immobilized in a macroporous acrylic resin, with an average pore diameter of 180 Å, a specific surface area 95 m2 / g. and an activity of 7000 PLUS / g. The reaction temperature was maintained at 70 ° C and the working pressure at 760 mm Hg.

The average residence time was 1.3 hours and the acid conversion was 16%, with a selectivity in the 93% monoester formation, the rest is formed by diester

Claims (11)

1. Method to produce 12-hydroxy-9-cis-octadecenoate from (1,4: 3,6-dianhydro-D-glucitol) comprising selective esterification of ricinoleic acid with isosorbide using immobilized lipases as a catalyst in resins 2. Method for producing 12-hydroxy-9-cis-octadecenoate of (1,4: 3,6-dianhydro-D-glucitol), according to claim 1, wherein the lipases come from the fungal species Mucor miehi and Candida antarctica . 3. Method to produce 12-hydroxy-9-cis-octadecenoate from (1,4: 3,6-dianhydro-D-glucitol), according to claims 1 and 2, wherein the catalyst obtained has a  pore diameter between 50 and 400 Å. 4. Method to produce 12-hydroxy-9-cis-octadecenoate of (1,4: 3,6-dianhydro-D- glucitol) r, according to claim 1, wherein the resins are of anion exchange or porous acrylics. 5. Method to produce 12-hydroxy-9-cis-octadecenoate from (1,4: 3,6-dianhydro-D-glucitol), according to previous claims, wherein the reaction of esterification is performed at a temperature between 20 and 90 ° C. 6. Method to produce 12-hydroxy-9-cis-octadecenoate from (1,4: 3,6-dianhydro-D-glucitol), according to previous claims, wherein the reaction of esterification is performed at a pressure between 1 and 760 mmHg. 7. Method to produce 12-hydroxy-9-cis-octadecenoate from (1,4: 3,6-dianhydro-D-glucitol) r, according to previous claims, where the reaction time varies between 10 and 120 minutes to achieve an 85% conversion. 8. Method to produce 12-hydroxy-9-cis-octadecenoate from (1,4: 3,6-dianhydro-D-glucitol), according to previous claims, where the esterification has place in a stirred tank reactor, continuous or discontinuous. 9. Method to produce 12-hydroxy-9-cis-octadecenoate from (1,4: 3,6-dianhydro-D-glucitol), according to claims 1 to 7, wherein the esterification takes place in a basket reactor, continuous or discontinuous. 10. Method to produce 12-hydroxy-9-cis-octadecenoate from (1,4: 3,6-dianhydro-D-glucitol), according to claims 1 to 7, wherein the esterification takes place in a fixed or fluidized bed reactor. 11. Acid isosorbide monoester ricinoleic obtainable by the claimed process.