Patent GB-766714-A (GB)
Title: New 2-and 3-substituted 1-phenyl-5-pyrazolones and processes for the production thereof
Filed: 1954-08-13
Abstract: The invention comprises 5-pyrazolones of the general formula: <FORM:0766714/IV(b)/1> wherein R1 is hydrogen or an aliphatic hydrocarbon radical of 1 to 5 carbon atoms, R2 is an alkyl or alkenyl radical of 1 to 3 carbon atoms and R3 is hydrogen, one or more alkyl groups of 1 to 4 carbon atoms or an alkoxy group, and their preparation by condensing a compound of the general formula: <FORM:0766714/IV(b)/2> wherein X is an alkoxy radical with an aryl hydrazine: <FORM:0766714/IV(b)/3> wherein R12 is hydrogen or an alkyl or alkenyl radical of 1 to 3 carbon atoms, to form a 5-pyrazolone, then, if desired, converting said pyrazolone containing hydrogen atoms in the 2-and 4-positions into the corresponding 4-alkyl compound by condensation with a low molecular aliphatic oxo compound and simultaneous or subsequent reduction, and, after or instead of introducing the radical R1, introducing an alkyl or alkenyl radical R2 into compounds in which R2 is hydrogen by treatment with an alkylating or alkenylating agent and a basic agent.  In the pyrazolone formation a solvent such as methanol, ethanol or aqueous ethanol may be added and the reaction may be completed by refluxing. Aliphatic oxo compounds used in the optional second stage are aldehydes or, preferably, ketones, and the hydrogenation is performed at normal or elevated pressure in the presence of a catalyst such as Raney nickel or platinum on barium sulphate with an excess of the ketone or an alcohol as solvent.  Specified alkylating or alkenylating agents for introduction of R2 are dimethyl or diethyl sulphate methyl iodide, ethyl, propyl or allyl bromide and the basic agent, e.g. caustic soda, may be incorporated in the reaction mixture or used to treat the initial quaternary reaction product formed in the absence of a base.  In examples: (1) cyclopropane carbonyl acetic acid ethyl ester and phenyl hydrazine give 1-phenyl-3-cyclopropyl - pyrazol - 5 - one which is then methylated with dimethyl sulphate to 1-phenyl-2-methyl - 3 - cyclopropyl - pyrazol - 5 - one; (2) 1 - phenyl - 3 - cyclopropyl - 4 - isopropyl-pyrazol - 5 - one, prepared either as in Example (1) using cyclopropane carbonyl a -isopropyl acetic acid ethyl ester or by hydrogenating condensation of 1-phenyl-3-cyclopropyl-pyrazol-5-one with acetone, is methylated as in Example (1) giving 1-phenyl-2-methyl-3-cyclopropyl - 4 - isopropyl - pyrazol - 5 - one; (3) ethyl cyclopropane carbonyl acetate and p-methylphenyl hydrazine give 1-(p-methyl-phenyl) - 3 - cyclopropyl - pyrazol - 5 - one from which 1 - (p - methyl - phenyl) - 2 - methyl - 3-cyclopropyl - pyrazol - 5 - one is prepared by methylation as in Example (1); 1-(m-methoxyphenyl) - 2 - methyl - 3 - cyclopropyl - pyrazol-5 - one is prepared similarly; (4) ethyl cyclopropane carbonyl-a -allyl acetate and phenyl hydrazine give 1 - phenyl - 3 - cyclopropyl - 4-allyl - pyrazol - 5 - one which is then methylated to the 2-methyl compound as in Example (1); (5) 1 - phenyl - 3 - cyclopropyl - pyrazol-5-one and allyl bromide give 1-phenyl-2-allyl-3-cyclopropyl-pyrazol-5-one.  A list of further starting materials is also given.  Starting materials.  Aliphatic hydrocarbon substituted cyclopropane carbonyl acetic acid esters are prepared by reacting the appropriate aliphatic hydrocarbon halides with the sodio derivatives of the cyclopropane carbonyl acetic acid esters.