Patent GB-1225225-A (GB)
IPC: C07D295/15
Filed: 1969-03-03
Abstract: 1,225,225. Imidoylurea and imidoylthiourea derivatives. STERLING DRUG Inc. 3 March, 1969 [7 March, 1968], No. 11308/69. Heading C2C. [Also in Division A5] The invention comprises novel 1-phenyl-3- alkanimidoylureas of the Formula I wherein R is alkyl or R 1 R 2 N-Y-, where Y is alkylene, and R 1  and R 2  each are C 1-6  alkyl or benzyl or R 1  and R 2  taken together with the nitrogen atom form a morpholino, thiamorpholino, piperidino, pyrrolidino, piperazino, N-C 1-6 - alkylpiperazino or N-phenylpiperazino radical; R<SP>1</SP> and R<SP>111</SP> are each H or C 1-6  alkyl; Q is alkyl, C 1-6  alkoxy, phenyl-C 1-6  alkoxy, C 1-6  alkanoyloxy, OH, di(C 1-6 )alkylamino, C 1-6  alkanoylamino, NH 2 , C 1-6  alkylsulphonyl, C 1-6  alkylsulphinyl, ..C 1-6  alkylthio, trihalomethyl, NO 2 , CN or halogen and n is 0 to 5; novel alkanimidoyl-thioureas of the Formula II wherein R is alkyl, Q<SP>1</SP> is C 1-6  alkoxy, C 1-6  alkanoyloxy, di(C 1-6  alkyl)amino, C 1-6  alkanoylamino, trihalomethoxy, trihalomethyl, NO 2  or halogen and n is 1 to 5; novel imidoylureas of the Formula III wherein R 3  is alkyl, phenyl or 5-nitro-furyl and R 4  is alkyl, halophenyl, nitrophenyl, 2-thienyl or cyclohexyl, but excluding halophenyl or nitrophenyl when R 3  is alkyl; and the acid addition salts of compounds of the above Formulas I, II and III. Compounds of the above Formula I, except those in which Q is OH or NH 2 , are prepared by reacting amidines of the formula RC( = NH).NHR<SP>1</SP> with either the appropriate phenyl isocyanates or with the corresponding N - phenyl - N - (C 1-6  alkyl) - carbamyl chlorides, and, if desired, hydrogenating the compounds thus obtained wherein Q n  includes one or more NO 2  and/or benzyloxy substituents to reduce said substituents to amino and/or hydroxy substituents respectively; compounds of Formula II by reacting amidines of the formula R-C(=NH).NH 2  with the corresponding phenyl isothiocynates; and compounds of FormulaIII by reacting amidines of the formula R 3 C( = NH)NH 2  with isocyanates of the formula R 4 NCO. Substituted phenyl isocyanates are obtained by treating the corresponding substituted anilines with phosgene. Amidines of the formula R(C = NH)NHR<SP>1</SP> are prepared by treating the salts of the corresponding imino-ethers, resulting from the treatment of a mixture of cyanides of the formula RCN, methanol and ether with hydrogen chloride, with amines of the formula R<SP>1</SP>NH 2 . Nitriles of the formula R 1 R 2 N-Y-CN are obtained by reacting iodonitriles of the formula I-Y-CN with amines of the formula R 1 R 2 NH. N - Phenyl - N - methylcarbamyl chloride, N - (4 - chlorophenyl) - N - methylcarbamyl chloride, N - phenyl - N - hexylcarbamyl chloride and N - phenyl - N - isopropylcarbamyl chloride are obtained by treating phosgene with N-methylaniline, N-methyl-p-chloraniline, N-hexylaniline, and N-isopropylaniline, respectively. 4-Amino-2-chlorobenzonitrile is obtained by reducing 2-chloro-4-nitrobenzonitrile resulting from the dehydration of 2-chloro-4-nitrobenzamide with phosphorus pentachloride. 5-Iodovaleronitrile is made by reacting 5- bromovaleronitrile with potassium iodide.