Patent GB-781551-A (GB)
Title: N-carboxy-3,5-pyrazolidine-dione derivatives
Filed: 1956-01-10
Abstract: The invention comprises N-carboxy-3:5-pyrazolidinedione derivatives of the formul : <FORM:0781551/IV (a)/1> and <FORM:0781551/IV (a)/2> (wherein R1 represents phenyl, o -chlorohexyl, cyclohexyl or 4-ethoxyphenyl, R2 and R3 hydrogen, n-butyl or phenyl, and R4 an ethoxy or anilino radical), and their alkali metal salts, and a process for the preparation of amide derivatives of N-carboxy- and N-carbothionyl-3:5-pyrazolidinediones by reacting malonic acid halides and C-substituted malonic acid halides with semi-carbazides and thiosemicarbazides, or otherwise according to the following examples: (1) 1-phenyl-2-anilino-carbonyl - 3:5 - pyrazolidinedione is prepared by stirring malonic acid dichloride with 1:4-diphenylsemicarbazide in benzene, or by heating 1-phenyl-3:5-pyrazolidinedione with phenyl isocyanate; (2) 1 - phenyl - 2 - anilinocarbonyl-4 - n - butyl - 3:5 - pyrazolidinedione is analogously produced from the corresponding n-butyl-substituted starting materials; (3) 1-phenyl - 3:5 - pyrazolidinedione is heated with o -chlorohexyl isocyanate to form 1-phenyl - 2 - o  - chlorohexylaminocarbonyl-3:5 - pyrazolidinedione; (4) cyclohexyl isocyanate similarly yields 1-phenyl-2-cyclohexylaminocarbonyl - 3:5 - pyrazolidinedione; (5) 4-ethoxyphenyl isocyanate similarly yields 1-phenyl - 2 - (4 - ethoxyanilinocarbonyl) - 3:5-pyrazolidinedione; (6) 1-ethoxycarbonyl-4-phenyl - 3:5 - pyrazolidinedione is heated with phenyl isocyanate to give 1-ethoxycarbonyl-2-anilinocarbonyl - 4 - phenyl - 3:5 - pyrazolidinedione; (7) 4 - phenyl - 3:5 - pyrazolidinedione similarly yields 1:2 - bis - anilinocarbonyl - 4-phenyl - 3:5 - pyrazolidinedione; (8) 1:4 - diphenyl - 3:5 - pyrazolidinedione similarly yields 1:4 - diphenyl - 2 - anilinocarbonyl - 3:5-pyrazolidinedione; (9) malonic acid dichloride is stirred with 1-phenyl-4:4-dimethylsemicarbazide in benzene to produce 1-phenyl-2 - dimethylaminocarbonyl - 3:5 - pyrazolidinedione; (10) C-phenylmalonic acid dichloride similarly yields 1:4-diphenyl-2-dimethylaminocarbonyl - 3:5 - pyrazolidinedione, also obtained by carrying out the reaction in the presence of dimethylaniline, or from C-phenylmalonic acid in the presence of PCl3; (11) C-n-butylmalonic acid dichloride is reacted as in (9) to form 1 - phenyl - 2 - dimethylaminocarbonyl-4 - n - butyl - 3:5 - pyrazolidinedione; (12) malonic acid dichloride is stirred with 1:4-diphenylthiosemicarbazide in benzene to give 1-phenyl - 2 - anilinothiocarbonyl - 3:5 - pyrazolidinedione; (13) 1 - phenyl - 3:5 - pyrazolidinedione is heated with dimethylcarbamic acid chloride to produce 1-phenyl-2-dimethylaminocarbonyl - 3 - (N:N - dimethylcarbamoyloxy) - 2:5 - dihydropyrazolone - 5. Additional starting materials specified are b -ethoxyethylmalonic acid dichloride; 1-phenyl-4-a -pyridyl- and 1:4:4-triphenyl-semicarbazide. The products are useful as analgesics.  Starting materials. 1-Phenyl-4-n-butyl-3:5-pyrazolidinedione is prepared by reacting C-n-butylmalonic acid dimethyl ester with phenylhydrazine in ethanolic sodium ethoxide solution. 1-Ethoxycarbonyl-4-phenyl-3:5-pyrazolidinedione is prepared by reacting 1-ethoxycarbonylhydrazine with phenylmalonic acid dichloride in ether.  4-Phenyl-3:5-pyrazolidinedione is prepared from C-phenylmalonic acid and hydrazine hydrate in ethanolic sodium ethoxide solution.