Patent GB-793968-A (GB)
Title: Process for the production of 4-substituted 1.2-diaryl-3.5-dioxo-pyrazolidines
IPC: C07D231/34
Filed: 1956-08-14
Abstract: The invention comprises 4-substituted 1:2-diaryl - 3:5 - dioxopyrazolidines of the general formula <FORM:0793968/IV (b)/1> (wherein Ar1 and Ar2 represent phenyl radicals which may be substituted by alkyl, alkoxy or alkylmercapto groups of 1-4 carbon atoms or by halogen, R represents a heterocyclic radical in the lowest stage of hydrogenation, and n is an integer from 1 to 4) and their salts with organic or inorganic bases, and the preparation thereof by reacting a diarylhydrazine of the general formula <FORM:0793968/IV (b)/2> or a derivative thereof carrying on one or each nitrogen atom a substituent easily split off (e.g. an acyl radical, an alkali metal atom or a halomagnesium radical) with (a) a substituted malonic acid ester of the general formula <FORM:0793968/IV (b)/3> (wherein X represents a radical easily split off as -OX, especially a lower alkyl radical) in the presence of a condensing agent, or with (b) a substituted malonic acid derivative of the general formula <FORM:0793968/IV (b)/4> wherein Y represents chlorine, bromine or an acyloxy radical) in the presence of an acid-binding agent, or with (c) a substituted malonic acid ester derivative of the general formula <FORM:0793968/IV (b)/5> or a dimer of the latter, if necessary first in the presence of an acid-binding agent and then, for the ring-closure, in the presence of a condensing agent, and, if desired, converting the products into salts with organic or inorganic bases, or by condensing a 1:2-diaryl-3:5-dioxopyrazolidine of the general formula <FORM:0793968/IV (b)/6> with a heterocyclic oxo compound R-(CnHm-1)=0 and simultaneously or subsequently reacting with catalytically activated hydrogen.  The products have antiphlogistic and antipyretic activity, and may be used in the form of salts, e.g. with sodium or other alkali metals or organic bases such as diethylaminoethanol. Examples describe the preparation of 4-(a - and g -picolyl)-, 4 - [b - pyridyl - (41) - ethyl] -, 4 - thenyl -, 4 - [indolyl - (31) - methyl] - and 4 - [furyl - (21) - methyl] - 1:2 - diphenyl - 3:5 - dioxopyrazolidine, 4 - (a  - picolyl) - 1:2 - bis - (p - methyl - and p - methoxy - phenyl) - 3:5 - dioxopyrazolidine, 4 - [b  - pyridyl - (41) - ethyl] - 1:2 - bis - (p - chlorophenyl) - 3:5 - dioxopyrazolidine and 4 - [furyl - (21) - methyl] - 1:2 - bis - (p - methylphenyl) - 3:5 - dioxopyrazolidine. Lists are given of additional starting materials for the various processes, including mono- and di-bromo- and di-(methyl- and ethyl-mercapto)-substituted hydrazobenzenes and 4-ethoxy-41-bromohydrazobenzene.  Starting materials.  Substituted malonic acid diesters of the third general formula above may be prepared by condensing sodium malonic acid diesters with heterocyclic-aliphatic halides R-(CnH2n)-halogen, or malonic or mesoxalic acid diesters with heterocyclic aldehydes with subsequent hydrogenation.  They may be converted into the corresponding dihalides by alkaline saponification, liberation of the acids and treatment thereof with inorganic acid halides such as SOCl2, PCl5 or PBr3.  Specificatio 646,597 is referred to.ALSO:Medicines for the treatment of rheumatic diseases contain dioxopyrazolidines of the general formula p  <FORM:0793968/VI/1> (wherein Ar1 and Ar2 represent phenyl radicals which may be substituted by alkyl, alkoxy, or alkylmercapto groups of 1-4 carbon atoms or by halogen, R represents a heterocyclic radical in the lowest stage of hydrogenation, especially a pyridyl, thienyl, or furyl radical, and n is an integer from 1 to 4) or their salts.  They may be administered perorally, e.g. in the form of tablets or coated tablets, or parenterally, e.g. by intramuscular injection of aqueous solutions of the sodium or other alkali metal salts or salts with organic bases such as diethylaminoethanol.  Specification 646,597, [Group IV (b)], is referred to.