Title of Invention

A PROCESS FOR THE LIPASE CATALYSED PREPARATION OF ALKYL AND ARYL ESTERS OF HYDROCINNAMIC ACID

Abstract

ABSTRACTA process for lipase catalyses preparation of alkyl and aryl esters of hydrocinnamic acid comprising the steps of incubating hyilrocinnnmic acid, alcohol an lipase organic solvent at 3()°C 1o 50°C (ns in Fig. 1) under agitation, the ratio of the alcohol to acid being 1:4 to 1:10 (mole/mole) and that of the acid to onsite being 1:0.5 to 1:5 (wt/ wt), (he enzyme being filtered off after conflation of the reaction and the organic layer washed with sodium bicarbonate, dried and concentrated to yield the esters.

Full Text

This invention relates to a process for lipase catalyzed preparation of alkyl and aryl esters of hydrocinnnamic acid. Hydrocinnamic acid esters among its various uses find application in the flavour and fragrance industry. Hydrocinnamates are generally prepared by the esterification of hydrocinnamic acid. Esterification is an important organic reaction, which has been widely used, in both chemical synthesis and industrial processes. Chemical esterifications are equilibrium reactions that are performed in the presence of an acid or base catalyst at high temperatures. The equilibrium can be shifted to the right by: • Addition of an excess of alcohol or acid (usually the alcohol). • Removal of ester or water by distillation • Removal of water by azeotropic distillation. • Removal of water by use of a dehydrating agent like silica gel, molecular sieves, DCC & aminopyridine, amberlyst-15, diethylazodicarboxylate & Ph3P (Mitsunobu esterification reaction). • High temperature. In general, when acid, alcohol and ester is nonvolatile the esterification reaction is done by heating the mixture to 200°C or higher, or by bubbling inert gas or by performing the reaction in vacuum. When either acid or alcohol is volatile the water formed during the reaction is removed by azeotropic distillation using benzene or toluene. A number of catalysts have been employed for esterification reactions like sulphuric acid (most favoured in chemical plants because of its low cost and lower corrosive effect on metal but can cause dehydration of alcohol), hydrochloric acid, phosphoric acid, sulphonic acid, perchloric acid, p- chlorosulphonic acid, Twitchell's reagent (complex formed from naphthalene, oleic acid and sulphuric acid), ion-exchange resin, boron and silicon fluoride. Esterification of hydrocinnamic acid has been done using hydrochloric acid, sulphuric acid, trichloroacetic acid, trichlorobutyric acid, and picric acid. 3-Phenylpropylhydrocinnamte was prepared from the corresponding silyl deivative of the acid and alcohol in the presence of p-trifluromethyl benzoic anhydride and Sn(0Tf)2-Ethylhydrocinnamate has been prepared in 70% yield from cinnamic acid and ethanol in the presence of nickel at 100°C and 60kg/cm hydrogen and heating of equimolar amounts of free carboxylic acid and alcohol in the presence of 2-chloro-l-methylpyridinium iodide and coupling agent BU3N. Hydrocinnamate esters can be prepared from the corresponding acid and alcohol in THF using quaternary ammonium salts like 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride. Diphenylammonium triflate has been used as a catalyst for the esterification of hydrocinnamic acid and also for the transesterification of hydrocinnamate esters. Methylhydrocinnamate has been prepared by the transesterification of ethylhydrocinnamte by methanol in the presence of hydrochloric acid as the catalyst and vice versa. iso-Propyl and tert- butylhydrocinnamate have been prepared by the transesterification of the methylhydrocinnamte with the corresponding alcohols using indium triiodide as the catalyst. Similarly methyhydrocinnamte has been prepared by the transesterification of iso-propylhydrocinnmate with methanol using indium triiodide as the catalyst. . Irrespective of the nature of the catalyst used, chemical esterification employs harsh reaction conditions viz., high temperature. SOME OF THE NOTEWORTHY FEATURES OF THIS INVENTION ARE: ♦ Esterification of hydrocinnamic acid by different alcohols can be achieved by using the biocatalytic approach viz., using lipase as the catalyst. ♦ The reaction can be done at room temperature with minimum input of energy using mild chemicals to obtain high yields of the product esters. ♦ This enzymatic route is an attractive, environment friendly and clean alternative to the chemical esterification with negligible waste management problems. ♦ The other highlight of this methodology is the simple work up. After completion of the reaction, the enzyme is filtered, the organic layer is washed with sodium bicarbonate to remove any unreacted acid, followed by distillation of the organic solvent to get the product. ♦ The enzyme and the solvent thus recovered can be reused. SOME OF THE ADVANTAGES OF THIS INVENTION ARE: ♦ Environment friendly - "Green Method" i.e. mild reaction conditions ♦ Clean reaction ♦ Simple work up ♦ Reuse of recovered solvent and enzyme The process, according to this invention, for lipase catalyzed preparation of alkyl and aryl esters of hydrocinnamic acid comprises the steps of incubating hydrocirmamic acid, alcohol and lipase in organic solvent at 30°C to 50°C (as in Fig. 1) under agitation, the ratio of the alcohol to acid being 1: 4 to 1:10 (mole/mole) and that of the acid to enzyme being 1:0.5 to 1:5 (wt/ wt), the enzyme being filtered off after completion of the reaction and the organic layer washed with sodium bicarbonate, dried and concentrated to yield the esters. The reaction takes about 24-48 hours to complete. The yield of the esters at the end of the reaction is 70% - >95% and 100% purity. The solvent and the enzyme recovered can be reused. EXAMPLE I A mixture of hydrocinnamic acid, cyclohexylmethyl alcohol and lipase in hexane was incubated at 50°C in an orbital shaker set at 250rpm. The ratio of acid to alcohol was 1:5 (mole/mole) while that of acid to enzyme was 1:1 (wt/wt). After 48h, the enzyme was filtered off, the organic layer was washed with sodium bicarbonate, dried over anhydrous sodium sulphate and concentrated to get the pure ester in 82% yield. • Reaction can also be done in a magnetic stirrer instead of a shaker. • The term "alcohol" in this specification includes aliphatic (primary, secondary and tertiary), substituted aliphatic (primary, secondary and tertiary), aromatic, substituted aromatic, polyaromatic methyl alcohols, substituted polyaromatic methyl alcohols, cyclohexyl, cyclohexylmethyl and their substituted derivatives. The term "solvent" in this specitlcation will include halogenated (e.g. chloroform, methylene chloride) simple alkanes (e.g. hexane. heptane) ethers (e.g. diethyl ether, diisopropyl ether) or aromatic hydrocarbons (e.g. benzene, toluene). The term hydrocinnamic acid" in this specification includes its derivatives. α- or β- substitution in the alkyl chain; o, m, p substitution in the aromatic ring. Such derivatives can also be esterified by the process proposed herein. We Claim: 1. A process for lipase catalyzed preparation of alkyl and aryl esters of hydrocinnamic acid comprising the steps of incubating hydrocinnamic acid, alcohol and lipase in organic solvent at 30 deg. C to 50 deg. C (as in Fig.l) under agitation, the ratio of the alcohol to acid being 1 ;4 to 1.10 (mole/mole) and that of the acid to enzyme being 1:0.5 to 1:5 (wt./wt.), the enzyme being filtered off after completion of the reaction and the organic layer washed with sodium bicarbonate, dried and concentrated to yield the esters. 2. The process as claimed in Claim 1 wherein the alcohol is aliphatic (primary, secondary' and tertiary) substituted aliphatic (primary', secondary' and tertiary), aromatic, substituted aromatic, polyaromatic methyl alcohols, substituted polyaromatic methyl alcohols, cyclohexyl, cyclohexylmethyl, and their substituted derivatives. 3. The process as claimed in Claim 1 and Claim 2 wherein the solvent is halogenated (e.g. chloroform, methylene chloride) simple alkanets (e.g. hexane, heptane’s) ethers (e.g. diethyl ether, isopropyl ether) or aromatic hydrocarbons (e.g. benzene, toluene). 4. The process as claimed in Claim 1 wherein the agitation is carried out in an orbital shaker at 200 - 250 rpm. 5. The process as claimed in Claim 1 wherein the agitation is carried out using a magnetic stirrer. 6. The process as claimed in any one of the preceding Claims wherein the solvent and the enzyme recovered are reused in the said process. 7. The process as claimed in any one of the preceding Claims wherein the organic layer is washed with sodium bicarbonate, dried and concentrated to yield the esters of 70% - >95% and 100% punt}'. 8. The process for lipase catalyzed preparation of alkyl and aryl esters of hydrocinnamic acid, substantially as herein described with reference to, and as illustrated by, the Examples. 9. Alkyl and aryl esters of hydrocinnamic acid whenever prepared by a process as claimed in any one of the preceding Claims.

Documents:

319-mas-2002 abstract duplicate.pdf

319-mas-2002 abstract.pdf

319-mas-2002 claims duplicate.pdf

319-mas-2002 claims.pdf

319-mas-2002 correspondecne others.pdf

319-mas-2002 correspondecne po.pdf

319-mas-2002 description (complete) duplicate.pdf

319-mas-2002 description (complete).pdf

319-mas-2002 form-1.pdf

319-mas-2002 form-19.pdf

319-mas-2002 form-26.pdf