Patent GB-825058-A (GB)
Title: Process for the production of dioxopyrazolidines
Filed: 1956-03-02
Abstract: Dioxo-pyrazolidines of the general formula <FORM:0825058/IV (b)/1> wherein R1 represents an aryl radical which may be substituted by halogen or an alkoxy or alkyl group, R2 represents hydrogen or an alkyl or aryl radical or an aryl radical substituted by halogen or by an alkoxy or alkyl group and R1 represents an alkyl, cycloalkyl, aralkyl or aryl group which may each be substituted by an alkoxy, aryloxy, acetal and/or tertiary amino group are prepared according to one method by reacting at 80-160 DEG  C. a mono-acyl aryl hydrazine of the general formula <FORM:0825058/IV (b)/2> wherein R1, R2 and R3 are as above defined with a carbonic acid alkyl ester or alkyl haloformate in the presence of an alkaline condensing agent and in the absence of water. Condensing agents specified include alkali metals and their hydrides, amides and alcoholates.  Inert solvents may be present, e.g. alcohols, aromatic hydrocarbons, ethers and excess of the alkyl carbonate reagent.  In a modification, the mono-acyl aryl hydrazine is heated with the alkyl haloformate at a temperature of 80-160 DEG  C. in the absence of both water and a condensing agent and then, after removal of liberated hydrogen halide and any unchanged alkyl haloformate, cyclizing the resulting product in the presence of an alkaline condensing agent and, if desired, an inert solvent, in the absence of water at a temperature between 80 DEG  and 160 DEG  C.; the alkyl haloformate is preferably used in excess and the intermediates, N-acyl-N1-carbalkoxy hydrazines need not be purified before their cyclization.  In examples: (1) a mixture of diethyl carbonate and phenacetyl-hydrazo benzene is refluxed in alcoholic sodium ethoxide at 120 DEG  C. and then, after removal of alcohol, at 150 DEG  C.; the resulting 1,2,4-triphenyl - 3,5 - dioxopyrazolidine is isolated by dissolving the product in aqueous alkali, washing with chloroform and then acidifying; (2) n - capronyl - N : N1 - diphenyl hydrazine is heated with excess ethyl chloroformate under reflux, then unchanged chloroformate is distilled from the resulting N-carbethoxy-n-capronyl - N:N1 - diphenyl hydrazine and the latter cyclized to yield 1,2-diphenyl-3,5-dioxo-4-n-butyl-pyrazolidine by refluxing in benzene in the presence of sodamide or (3) of potassium; (4) phenacetyl N:N1-diphenyl hydrazine is reacted with ethyl chloroformate and the product cyclized as in (2) to give the pyrazolidine of (1); (3) n-valeryl-N,N1-diphenyl hydrazine is reacted as in (2) with ethyl chloroformate and the product cyclized in benzol containing sodium hydride, yielding 1,2-diphenyl-3,5-dioxo-4-n-propyl pyrazolidine; (6) phenyl propionyl-N:N1-diphenyl hydrazine is similarly reacted with ethyl chloroformate and the product cyclised as in (5) yielding 1:2-diphenyl-3,5 - dioxo - 4 - benzyl - pyrazolidine.  Other specified reagents are methyl chloroformate and dimethyl carbonate. The mono acyl hydrazides are prepared by reacting the appropriate hydrazine and carboxylic acid chloride together in the presence of a tertiary base in an inert solvent.  Reference has been directed by the Comptroller to Specification 732,820.