CS201749B1 - Process for preparing 6-hydroxy-bicyclo-/2,2,1/-heptan-3,5-carbolacton-2-carboxylic acid - Google Patents

Abstract

The invention relates to a method of preparation 6-hydroxy-bioykX © - / 2,2,1 / "lieptAn-3,5-carbolactone-2-carboxylic acid acid hydrolysis and hydratAoleu bioyklo ~ / 2,2,1-hept- -5-E, -2,3-dicarboxylic acid anhydride And subsequent lactonization, the resulting the product is obtained in high yield, as well as β of a high degree of purity. The reaction is carried out at a temperature of 40 to 40 ° C 90 ° C for 3-5 hours in the presence a hydrogenation agent and a hydrating agent prepared from a salt of transient elements mooenstvom 5th and 6th group Mendelejeva periodic «constituent elements, hydrogen peroxide, water and tero. butanol, being atollic ratio of feedstock to peroxide the hydrogen is in the range of 1 to 1.1 to 1 ton 1.6 and forming the product from the reaction mixture separated.

Description

The invention relates to a method of preparation

6-hydroxy-bioykX © - / 2,2,1 / "lieptAn-3,5-carbolactone-2-carboxylic acid by hydrolysis and hydratAoleu bioyklo ~ / 2,2, L / hept-5-b '2 _s 3 dicarboxylic acid anhydride followed by lactonization, the resulting product being obtained in high yield as well as β with a high degree of purity. The reaction is carried out at a temperature of 40 to 90 ° C for 3-5 hours in the presence of a hydrogenation agent and a hydrating agent prepared from a salt of elements of transition groups 5 and 6 of Mendeleyev's periodic constituent elements, hydrogen peroxide, water and tero. butanol, wherein the atoll ratio of the starting material to hydrogen peroxide is between 1 and 1.1 to 11.6 and the product formed is separated from the reaction mixture.

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SUMMARY OF THE INVENTION The present invention provides a process for the preparation of 6-hydroxy-bioyclo- [2,2,1] -heptane-3,5-carbolactone-2-carboxylic acid by hydrolysis and hydration of bioclo- [2,2,1] -hept-5- ene-2,3-dicarboxylic acid anhydride followed by lactonization, the resulting product being obtained in high yield as well as a high degree of purity of δ-hydroxy-bioyclo- [2,2,1] heptane-3,5- Carbolactone-2-carboxylic acid was prepared by reacting bioyclo [2.2.1] hept-5-ene-2,3-dicarboxylic acid anhydride with a mixture of oic acid and hydrogen peroxide for 4 hours at 85 ° C (Alder) K., Mttlle HHi Ann. Chem., 11, 7 (1958). 6-Hydroxy-bicyclo [2.2.1] -heptane-3,5-carbolactone-2-carboxylic acid spontaneously falls out of the reaction medium and has a melting point of 196-197 ° C after recrystallization from acetonitrile. A disadvantage of this process is the necessity of distilling off water and regenerating in the process of circulating oic acid, which is highly corrosive.

According to the invention, a process for the preparation of 6-hydroxy-bioyclo- (2,2,1) -heptane-3,5-carbo-lactone-2-carboxylic acid of the formula 1

by reacting the hydroxylating agent on bioyclo [2.2.1] hept-5-ene-2,3-enhydride-dlcarbonic acid by carrying out the reaction at a temperature of 40 to 90 ° C for 3 to 5 hours in the presence of a hydroxylating agent. and a hydrating agent prepared from a salt of the Group 5 and 6 transition elements of the Mandeleyev periodic array of elements, preferably tungsten, molybdenum and vanadium, hydrogen peroxide, water and tero. butanol, wherein the molar ratio of the starting material to hydrogen peroxide is in the range of 1: 1.1 to 1: 1.6 and the product formed is separated from the reaction mixture.

Thus, according to the invention, 6-hydroxy-bioyclo- (2,2,1) -heptane-3,5-carbolactone-2-carboxylic acid (i) is prepared by hydration and bipyclo- (2,2,1) -hqpt-5 hydroxylase. -en-2,3-dicarboxylic anhydride (li). The hydrating and hydroxylating agent used is a mixture of hydrogen peroxide, water, tero. butanol (t-BuOH) and transition metal salts of metal acids, followed by the subsequent lactonization of 5,6-dihydroxy-bioylpheno [2,2,1] heptane-2,3-dicarboxylic acid (III) to 6- hydroxy-bioyclo- (2,2,1) -heptane-3,5-harbolactone-2-carboxylic acid (1) t

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II III i

The molar ratio of bicyclo [2.2.1] hept-5-ene-2,3-aatoydride-dicarboxylic acid to hydrogen peroxide is from 1 to 1.1 to 1: 1. 1.6. The advantage of the process is the possibility of using a commercially available 30% solution of hydrogen peroxide in water, which does not need to be concentrated. The temperature optimum of the reaction lies in the range of from 40 to 90 ° C and in which the reaction purity and thermo-catalytic decomposition of hydrogen peroxide are in optimal theological and economic consistency. The reaction time is in the range of 3 to 5 hours. Termination of the reaction® generally indicates that the oxidation potential of the reaction system is exhausted. Upon completion of the reaction, by cooling the reaction precipitate to a temperature close to 0 ° C, the reaction product precipitates in crystalline form; it is usually isolated by filtration.

As reaction catalyst, alkali and ammonium salts of transient moieties of Groups 3 and 6 of the Mendeleyev Periodic Table of the Elements, preferably tungsten, molybdenum and vanadium, may be used in an amount of 0.7 to 3 calculated on the basis weight of the reaction mixture. .

Salts of transition metal salts of tungsten, molybdenum and vanadium with hydrogen peroxide and water provide the corresponding peroxy acids which have been used as hydroxylating agents for the hydroxylation of linear and cyclic alkenes and unsaturated carboxylic acids / Mugdan M., Young DPi J. Chem, Soc., 2888 (1949)]. The resulting peroxyacid epoxidizes the double bond of bioyclo [2,2,1] -hept-5-ene-2,3-anhydride-dicarboxylic acid or the bicyclo [2.2.1] hept-5-ene-formed by hydrolysis thereof. 2,3-dicarboxylic acid. The corresponding epoxy derivatives in the aqueous medium hydrolyze to the common product 5,6-dihydroxy-bioyclo- [2,2,1] -heptene-2,3-dicarboxylic acid, which, by intramolecular esterification, gives 6-hydroxy-bioylo- [2,2], 1 H -heptane-3,5-carbolactone-2-dicarboxylic acid.

The product obtained was identified by melting point 196-197 ° C, by infrared, mass and NMR spectrometry. The product is of interest both for its configuration and for its functional groups, which allow interesting polymorphic, condensation and other reactions, the resulting substances having rare mechanical-physical properties, taking into account the configuration. The product can also be used as an intermediate for Saler synthesis.

The advantage of the invention is, in particular, that the high purity of the product reaches up to 99.9, the high product yield reaches up to stoichiometric values, a simple and technologically undemanding process.

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The invention is illustrated in more detail in the examples below, and the present invention is not limited to these examples.

Example 1 wt. parts of bioyclo- [2,2,1] -hept-5-ene-2,3-dicarboxylic anhydride,

23.73 wt. parts by weight of 30% hydrogen peroxide, 33.75 wt. parts tero. butanol and 0.96 wt. parts at 70 ° C did not react for 5 hours. Addition of hydrogen peroxide per stirring takes 15 minutes and is conducted to maintain the temperature at the desired value. Thereafter, the reaction mixture was cooled to 4 [deg.] C. and 24.83 wt. parts of 6-hydroxy-bioyclo [2.2.1] heptane-3,5-carbolactone-2-carboxylic acid in the form of crystals, which represents 82.5% yield. The melting point of the product thus obtained is 196 ° C and its purity according to chromatographic analysis is 99.6%.

Example 2 wt. parts by weight of bioyclo [2.2.1] hept-5-ene-2,3-anhydride-dicarboxylic acid, 27.65 wt. parts by weight of 30% hydrogen peroxide, 33.75 wt. parts tero. butanol and 0.96 wt. parts of Na ₂ SO 4 · 2H ₂ O by reaction at 75 ° C for 5 hours afforded 29.53 wt. parts

6-hydroxy-bioyclo [2.2.1] heptane-3,5-carbolactone-2-carboxylic acid, which represents

98.2% yield. Melting point 196 ° C purity 99.8 ¢.

Example 3 wt. parts by weight of bioyclo [2.2.1] hept-5-ene-2,3-dicarboxylic anhydride, 20.73 wt. parts by weight of 30% hydrogen peroxide, 33.75 wt. parts tero. butanol and 0.75 wt. parts per ₂ Mo0 _{t | 2} H ₂ O reacted at 50 ° C for 4 hours to give 17.45 wt. 12.68 wt. parts by weight represented 6-hydroxy-bioyclo [2.2.1] heptane-3,5-carbolactone-2-carboxylic acid, which is 72.7% by weight, the remainder being 4.77 wt. Part of the block is blockyclo- [2,2,1] -hept-5-ene-2,3-dicarboxylic acid.

Example 4

Roakoia as in Example 1 except that the molar ratio of bioyclo [2.2.1] hept-5-ene-2,3-dicarboxylic anhydride to hydrogen peroxide is 1: 1.5, 70 ° C C, 4 hours and 1 $ NagMoO4 gave a yield of 6-hydroxy-biayclo [2.2.1] heptone-3,5-carbolactone-2-carboxylic acid of 78.5%, purity 99.5 ° C. .

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Example 5

As in Example 4, except that the molar ratio is equal to 1; 1.2} temperature 70 ° C} for 4 hours and 1 ° (NH4 / v / v) yield 75.5%, purity 99.6%.

Example 6

As in Example 4, with the difference that the molar ratio is 1: 1.4, the temperature is 75 ° C for 5 hours, and the yield is 99.81 $, purity 99, 5 fy ·

Example 7

As in Example 4 with the difference that the molar ratio is 1: 1.5} temperature 80 ° C} for 4 hours and 1% Na 2 Mo 2 O 2 · 2 O 2} yield 98.7 phy> purity 99.5 phy ·

Example 8

As in Example 4, with the difference that the molar ratio is equal to 1: 1.2} temperature 80 ° C} for 4 hours and 1 phy NagMoO4 · HgO} yield 99.8 phy, purity 99.9 phy ·

Example 9

As in Example 4, with the difference that the molar ratio is 1: 1.4} temperature 75 ° C} for 5 hours and 1 phy Na ₂ SO 4 · 2H ₂ O yield 99.9 phy> purity 99.9 phy ·

6-Hydroxy-bicyclo [2.2.1] heptene-3,5-carbolactone-2-carboxylic acid can be used for further synthesis.

OBJECT OF THE INVENTION

Claims (1)

OBJECT OF THE INVENTION A process for the preparation of 6-hydroxy-bicyclo [2.2.1] -heptene-3,5-carbolactone-2-carboxylic acid of the formula by reacting the hydroxylating agent to bioyclo [2.2.1] hept-5-ene-2. , 3-dicarboxylic anhydride 201 749, characterized in that the reaction is carried out at a temperature of 40 to 90 ° C for 3 to 5 hours in the presence of a hydroxylating and hydratading agent prepared from salts of transition elements of Group 5 and Group 6 of the Mandeleyev periodiho preferably tungsten, molybdenum and vanadium, hydrogen peroxide, water and tero. butanol, wherein the molar ratio of the feedstock to hydrogen peroxide is between 1 and 1.1 to 1: 1.6 and the product formed is separated from the reaction mixture.