US2466588A - Process of preparing pimelic acid esters - Google Patents

Description

Patented Apr. 5, 1949 UNliE was new? orrlce rnocnss or rename rnunric Aorn ns'rans poration of France No Drawing.- Application June 15, 1946, Serial No. 677,099. In France January 11, 1943 2 Claims. (or. 260 485) This invention relates to an improved process of preparing pimelic acid esters. The com pounds, after, conversion into pimelic acid, are useful as intermediates in the preparation of plasticisers, synthetic materials and other technical products. I l

Few satisfactory methods. are known for the production of pimelic acid esters. According to one method, salicylic acid is reduced with nascent hydrogen formed by action of metallic sodium on amyl alcohol. This mode of preparation requires the use and handling of considerable amounts of sodium metal. It has also been proposed to treat the ethyl-ester of cyclohexanone- (D-carboxylic acid-(2) with a large amount of sodium in amyl alcohol itself which process involves the same inconvenience and hazard. Still another procedure, leading directly to pimelic acid, consists in reacting the ethyl ester of cycloheXanone-(l) -carboxy1ic acid-(2) with potassium methylate and results in a poor yield of pimelic acid. According to a, fourth method, also conducive to pimelic acid but without passing through the intermediate stage of esterification, 2-ch1oro-cyclohexanone-(1) is converted by potassium cyanide into its corresponding nitrile which is then saponified to form pimelic acid under reasonable conditions. The big disadvantage of this method, however, resides in the use of potassium cyanide which is expensive and a. dangerous poison.

It is one object of this invention to devise a new and improved method of preparing esters of pimelic acid which will avoid all the aforesaid risks and shortcomings.

It is another object of the present invention to provide a process of producing pimelic acid esters which will ensure a product of great purity and in an excellent yield.

These objects are attained by the novel process hereinafter described and illustrated by examples, and more particularly defined by the appended claims, setting forth the basic features of our invention.

We have found that it is possible to obtain 'pimelic acid esters with a hitherto unequalled yield :by treating esters of cyclohexanone(l) carboxylic acid-(2) with an alcohol at elevated temperature in the presence of catalytic quantitles of an alkaline agent. The optimum temperature for this reaction lies in the vicinity and within the range of 130 to 150 C. It can easily be reached by running the process under pressure if the alcohol employed has a boiling point far below the optimum reaction temperature .2 1: a t os h estr asure In e he casesdt might be more advantageous towwork witho anypressure To this. effect an alcohol is -selected as reaction medium, whose boiling oin i sit ei de nn e viuei r the e pe att re o t m wis m cd any event the new method in .ac cordahce with this invention shall not be .limited to the specific aforesaid temperature range as, the.,yield rises gradually wi th progression of temperature. If the reaction, e. g., takes place in ethanol with sodium as alkaline agent, the yield will rise from 4% of the theory at 83 C. to more than at a temperature of 140 C.

The alkaline agent will act as a. catalyst of the alcohol for the opening up of the cyclohexanone carboxylic acid ester nucleus. It may be an alkali alcoholate, a. caustic alkali or an alkali carbonate. Its amount to be applied may vary within vast ranges. However, it is not preferred to employ excessive amounts and without establishing a definite rule, it ma be assumed that a, proportion of about 10% of the cyclohexanone carboxylic acid ester is to be considered as a maximum that should not be exceeded.

Examples 1. 1000 parts of ethanol are added with 20 parts of metallic sodium and, after the evolution of i=1- hydrogen has ceased, 1000 parts of cyclohexanone-(l) -carboxylic acid-(2) -ethy1ester are introduced. The mixture is heated to 140 in a closed vessel for '7 hours under the proper pressure of the alcohol. The product is thereupon poured into Water acidulated with sulphuric acid, decanted and washed with water by several decantations. By fractionation one obtains 1090 parts of ethylpimelate which represents a yield of 85.7%.

If the reaction takes place under atmospheric pressure, that is at the boiling temperature of the reaction mass which is approximately 83, the yield of diethylpimelate is but 4% of the theory.

2. 1000 parts of cyclohexanone-(l)-carboxylic acid-(2) ethylester are dissolved in 2000 parts of anhydrous amyl alcohol. and added with 40 parts anhydrous potassium carbonate. The mixture is brought to ebullition and maintained at boiling temperature with simultaneous distillation of a small quantity of amyl alcohol to permit the elimination of the ethanol formed by the substitution of the ethyl radical in the ester group. The temperature starting from C. rises progressively up to 147 C. After 3 to 4 hours the reaction is completed. The product is washed to remove the catalyst and then fractionated. The yield is 1650 parts of diamylpimelate which represents 96% of the theory.

An identical result is obtained if 20 parts of metallic sodium are employed in place of potassium carbonate.

Having thus described the invention, we desire it to be understood that the foregoing examples have been given by way of illustration only and that we do not wish to limit ourselves to the specific amounts or temperatures or periods of treatment mentioned therein. It will also be obvious that numerous changes and modifications of the process may be made without departing from the spirit of our novel and improved process, and that all equivalents of the reactants used and described will fall within the scope of our invention.

What is claimed as new and sought to secure by Letters Patent is:

1. A process for preparing pimelic acid esters, comprising the steps of treating cyclohexanone (1)-carboxylic acid (2) esters with an alcohol containing less than 8 atoms of carbon, and selected from the group consisting of primary aliphatic and arylaliphatic alcohols, at 100-180 in the presence of an alkaline reagent selected from the group consisting of alkali-alcoholate, caustic alkali and alkali carbonate, said alkaline reagent being present in a proportion of less than 10% of the weight of the cyclohexanone carboxylic acid ester, removing said alkaline catalyst from the reaction mixture, and washing and isolating the thus formed pimelic acid ester.

2. A process for preparing pimelic acid esters comprising the steps of treating at a temperature within the range. of to C. cyclohexanone- (1) -carboxylic acid-(2) -esters with an alcohol containing less than 8 atoms of carbon, and selected from the group consisting of primary aliphatic and arylaliphatic alcohols, in the presence of an alkaline reagent selected from the group consisting of alkali-alcoholate, caustic alkali, and alkali carbonate, said alkaline reagent being present in a proportion of less than 10% of the weight of the cyclohexanone carboxylic acid ester, removing said alkaline catalyst from the reaction mixture and washing and isolating the thus formed pimelic acid ester.

MAXIM'ILIEN GRUNFELD. MARC EDMOND BATIGNE.

REFERENCES CITED The following references are of record in the file of this patent:

Einhorn et al., Annalen der Chem. volume 286 (1895) page 266.

Snyder et al., Organic Synthesis Collective Volume 2 (1943), pages 53l534.