GB556044A - A process for the manufacture of ketotetrahydropyridine derivatives and hydroxypyridine derivatives - Google Patents

Abstract

556,044. Pyridine ketocarboxylic acids and esters. ROCHE PRODUCTS, Ltd., BERGEL, F., and COHEN, A. March 9, 1942, No. 3088. [Class 2 (iii)] Pyridine keto-carboxylic esters are prepared by treating compounds of the general formula first with alkali metals or their alcoholates and then with acids. In the formula R is alkyl or aryl or substituted alkyl group which does not react with an alkali metal or alcoholate or with an acid under the conditions of the reaction, R<SP>1</SP> is alkyl or aralkyl, R<SP>11</SP> is hydrogen or alkyl and X, Y, and Z which are not necessarily identical are lower alkyl groups. The reaction is preferably carried out in an inert solvent in an inert atmosphere. The products may be converted by treatment with an acid such as hydrochloric acid into a salt which, on dehydrogenation by exposure to an oxygencontaining gas such as air, or to oxygen, forms a quaternary pyridinium salt. In the case of the pyridinium salt where R' is benzyl, treatment with hydrogen in the presence of a hydrogenation catalyst such as palladized charcoal results in the formation of a 3-hydroxy pyridine derivative. Treatment of the pyridinium salts with one equivalent of cold alkali results in the formation of the corresponding phenol betaine. The compounds of the present invention are useful in the synthesis of vitamin B 6 . In examples: (1) The condensation product of N-methyl alanine and α-formyl succinate prepared as described in Specification 551,216 is treated in benzene solution and in an atmosphere of nitrogen with powdered sodium. The product on treatment with sulphuric acid is 1 : 2 - dimethyl - 3 - hydroxy - 4:5 - dicarbethoxy - dihydropyridine. The hydrochloride of this compound on dehydrogenation gives 1:2- dimethyl - 3 - hydroxy - 4:5 -dicarbethoxypyridinium chloride. Treatment with caustic soda yields the phenolic betaine which may be saponified to 1:2-dimethyl-3-hydroxy-4:5-dicar boxy pyridinium hydroxide. (2) The condensation product of methyl α-benzylaminopropionate and α-formyl succinate is treated with' powdered sodium and then with acid as in example (1) to give 1-benzyl-2-methvl-3- hydroxy-4:5-dicarbmethoxypyridinium chloride. This yields a phenolic betaine as in example (1), and also on reduction with hydrogen and palladised charcoal, gives 2-methyl-3-hydroxy- 4:5 - dicarbomethoxypyridine hydrochloride. (3) This is identical with example (2) but using in the condensation sodium methoxide instead of powdered sodium.