Patent GB-778128-A (GB)
Title: Process for the production of 4-substituted 1.2-diaryl-3.5-dioxopyrazolidines
Filed: 1955-12-14
Abstract: The invention comprises compounds of the general formula <FORM:0778128/IV(b)/1> (or tautomeric forms thereof), wherein R represents a hydrocarbon radical which may be interrupted by O or S (as chain or ring members) or by -CO-O- and which may contain halogen atoms or hydroxy groups, and Ar1 and Ar2 represent phenyl radicals which may be substituted by alkyl or alkoxy groups of at most 4 carbon atoms, aralkoxy or hydroxy groups, halogen atoms or radicals R1-CO-O-(R1 being a hydrocarbon radical), and the manufacture thereof by reacting a malonyl hydrazobenzene of the general formula <FORM:0778128/IV(b)/2> with a carboxylic acid R-COOH or a reactive functional derivative thereof (if necessary in the presence of a condensing agent), followed, if desired, by hydrogenolysis of any aralkoxy groups or hydrolysis of any R1-CO-O-radicals present in Ar1 and/or Ar2.  As functional derivatives of the acids R-COOH may be used acid halides in the presence of basic condensing agents or of AlCl3, FeCl3 or BF3, and preferably in inert organic solvents, or acid anhydrides in the presence of basic condensing agents, usually in the absence of a solvent.  The products, which possess antiphlogistic and antipyretic activity, form salts with inorganic and organic bases.  In examples: (1) malonyl hydrazobenzene is warmed with acetic anhydride and pyridine, and 1 : 2-diphenyl-4-acetyl-3 : 5-dioxopyrazolidine is liberated from the resulting pyridine salt thereof by heating under reduced pressure; the same compound is obtainable by boiling the reactants in the absence of a condensing agent; (2) malonyl hydrazobenzene is stirred with butyryl chloride and pyridine in benzene to produce 1 : 2-diphenyl - 4 - butyryl - 3 : 5 - dioxopyrazolidine, the semicarbazone of which is described; (3) phenylacetyl chloride similarly yields 1 : 2-diphenyl - 4 - phenacetyl - 3 : 5 - dioxopyrazoli - dine, and analogously prepared are 1 : 2-diphenyl - 4 - (g  - phenylmercaptobutyryl)- and -4-(m:p - dimethylphenacetyl)-, 1 : 2 - bis - p - tolyl - 4 - phenacetyl- and -4-isobutyryl-, 1 : p - methoxy-, -p-benzyloxy- and -p-acetoxyphenyl-2 - phenyl - 4 - butyryl- and 1 : 2 - bis - p - chlorophenyl - 4 - butyryl - 3 : 5 - dioxopyrazolidine; (4) caproyl chloride is reacted as in (2) to give 1 : 2 - diphenyl - 4 - caproyl - 3 : 5 - dioxo - pyrazolidine the 2 : 4-dinitrophenylhydrazone of which is described; there may similarly be prepared 1 : 2 - diphenyl - 4 - valeryl-, -isova - leryl-, -b -phenylpropionyl-, -cinnamoyl-, -a -thenoyl-, -a -furoyl- and -isobutyryl- and 1 : 2-bis - p - chloro- and -p-methyl - phenyl - 4 - benzoyl - 3 : 5 - dioxopyrazolidine; (5) di - n - butylacetyl chloride is reacted as in (2) to produce 1 : 2 - diphenyl - 4 - (di - n - butylacetyl)-3 : 5-dioxopyrazolidine; similarly obtainable are 1 : 2 - diphenyl - 4 - a  - cycloheptenylbutyryl-, -homoveratroyl- and -o -undecenoyl - 3 : 5 - di - oxopyrazolidine; (6) p-benzyloxy malonyl hydrazobenzene and benzoyl chloride are reacted as in (2) and the product is dissolved in aqueous alcohol caustic soda and shaken with Raney nickel in a hydrogen atmosphere to form 1 - p - hydroxyphenyl - 2 - phenyl - 4 - benzoyl - 3 : 5-dioxopyrazolidine; the corresponding 4-phenacetyl compounds may be similarly prepared; (7) p-hydroxy malonyl hydrazobenzene and butyryl chloride are reacted as in (2) to give 1 - p - hydroxyphenyl - 2 - phenyl - 4 - butyryl - 3 : 5-dioxopyrazolidine; which is also obtainable by hydrogenolysis of the corresponding p-benzyloxy compound or hydrolysis of the corresponding p-acetoxy or p-benzoyloxy compound; (8) p-chlorobenzoyl chloride is reacted as in (2) to produce 1 : 2-diphenyl-4-p-chlorobenzoyl-3 : 5-dioxopyrazolidine; (9) malonyl hydrazobenzene is heated with benzoyl chloride and pyridine in chloroform (or benzene), yielding 1 : 2 - diphenyl - 4 - benzoyl - 3 : 5 - dioxopyrazolidine, the 2 : 4-dinitrophenylhydrazone of which is described; (10) malonyl hydrazobenzene is heated with butyryl chloride and AlCl3 in chloroform to produce 1 : 2-diphenyl-4-butyryl-3 : 5-dioxopyrazolidine; (11) malonyl hydrazobenzene is stirred with p-methoxybenzoyl chloride in benzene, with or without pyridine, producing 1 : 2-diphenyl-4-p-methoxybenzoyl-3 : 5-dioxopyrazolidine; (12) the reaction of (9) is carried out in benzene in the presence of K2CO3 as condensing agent; (13) acetoxymethyl chloride is reacted as in (2) to give 1 : 2-diphenyl - 4 - acetoxyacetyl - 3 : 5 - dioxopyrazolidine. Additional starting materials are listed.  Starting materials. p-Benzyloxy malonyl hydrazobenzene is prepared from p-benzyloxy hydrazobenzene and malonic acid diethyl ester, and yields p-hydroxy malonyl hydrazobenzene by catalytic hydrogenolysis.