Patent GB-800869-A (GB)
Title: Substituted amino-guanidines
Inventor: BIRTWELL STANLEY
IPC: C07C281/16
Filed: 1955-09-28
Abstract: The invention comprises substituted amino-guanidines of the formula: <FORM:0800869/IV (b)/1> and acid addition salts thereof, wherein of A and B one represents phenyl, naphthyl or a tetrahydronaphthyl radical which may be optionally substituted and the other represents hydrogen or an alkyl radical, R, R1 and R11 represent hydrogen or alkyl radicals and R111 represents hydrogen, an alkyl or an aralkyl radical, provided that when B, R, R1, R11 and R111 are hydrogen, A is not phenyl, or p- or o-methoxyphenyl, and when B is methyl and R, R, R11 and R111 are hydrogen then A is not phenyl; and processes for the manufacture thereof by (a) reacting a compound (II) <FORM:0800869/IV (b)/2> or its hydrate or its salts with a compound (III): <FORM:0800869/IV (b)/3> or its salts, preferably in the presence of an inert solvent or diluent; (b) (when B is hydrogen) reacting compound (II) or its salts with a compound: <FORM:0800869/IV (b)/4> preferably in the presence of an inert solvent or diluent; (c) (when R is hydrogen) reacting a compound (II) with a compound: A-N = C = N-B (V) (d) (when R is hydrogen and B is hydrogen or alkyl) reacting a compound: <FORM:0800869/IV (b)/5> with ammonia or an alkylamine; (e) (when R11 is hydrogen) catalytic hydrogenation of a compound <FORM:0800869/IV (b)/6> preferably in the presence of an inert solvent or diluent; wherein X is an alkyl or an aralkyl group, R2 is an alkyl or aryl radical and R3 is hydrogen, an alkyl or an aryl radical.  In examples, compounds of the general formula (I), wherein A represents m- and p-chloro- and o-methoxy-phenyl groups, B, R, R1, R11 and R111 being hydrogen, and wherein A represents p-chlorophenyl, R methyl and B, R1, R11 and R111 hydrogen, are prepared by reacting hydrazine monohydrochloride (obtained by mixing hydrazine hydrate and dihydrochloride) with an isothiourea of the general formula (III), wherein A and R represent the groups above and X is a methyl group, in methanol, the products being isolated or converted into the mono- or di-hydrochlorides; compounds wherein A represents 2:4-dimethylphenyl and wherein A represents 2:3-dimethyl phenyl are similarly prepared but using an isothiourea wherein X is, respectively, an ethyl and a benzyl group.  In further examples, compound (I) wherein A is 2:4-dichloro-, p-bromo-, p-nitro-, 2-methoxy-5-chloro-, p-iodo, 2:5-dimethyl-, p-n-butyl-, 3-chloro-4-methyl-, 2 - methyl - 4 - chloro -, 3 - methyl - 4 - chloro-, 3:4 - dimethyl -, 2:4:5 - trimethyl -, 2:4 - dichloro - 5 - methyl -, 2 - methoxy - 5 - chloro-, 2 - methyl - 5 - chloro -, p - hydroxy - and 3:4-dichloro-phenyl, a - and b -naphthyl, m- and p-tolyl, diphenylyl, and a - and b -tetrahydronaphthyl, B, R, R1, R11 and R111 being hydrogen; wherein A is phenyl, R methyl and B, R1, R11 and R111 hydrogen; A is p-chlorophenyl, B methyl, and R, R1, R11 and R111 hydrogen; and A is methyl, B phenyl, R methyl and R1, R11 and R111 hydrogen, are prepared by reacting hydrazine hydrate with the hydriodide of an isothiourea (III), wherein A and R represent the groups above and X is a methyl group, in methanol, the product being isolated as the hydriodide or the hydrochloride after treatment with hydrogen chloride.  Compounds (I) wherein A is p-chlorophenyl and R11 and R111 methyl; A is p-chlorophenyl and R methyl; and A is p-chlorophenyl and R1 and R111 methyl, the other symbols representing hydrogen, are prepared by reacting a correspondingly substituted cyanamide (IV) with a substituted or unsubstituted hydrazine (II) or its salts, in methanol, the product being isolated as the base or its hydrohalide salt, the base being prepared from the salt by basification. N1-Dimethylamino-N2-p-chlorophenyl - N1:N3 - dimethylguanidine is prepared by reacting an acetone solution of p-chlorophenyl methylcarbodiimide with N1:N1: N2 - trimethylhydrazine; N1 - dimethyl amino-N1 - methyl - N2 - n - butyl - N3 - p - chlorophenylguanidine by reacting N1dimethylamino-N1:S - dimethyl - N2 - p - chlorophenyliso - thiourea hydroidide with n - butylamine, and N1-dimethylamino - N2 - phenylguanidine by reacting N1 - dimethylamino - N2 - phenyl - S-methylisothiourea hydroiodide with ammonia.  N1 - benzylamino -, N1 - isopropylamino -, and N1 - nonylamino - N2 - p - chlorophenyl guanidinen hydrochlorides are prepared by catalytic hydrogenation of the corresponding compounds of formula (VII), in methanol, using a platinum catalyst.  Starting materials.  Isothioureas (III) are prepared by treatment of the corresponding thioureas with a molecular proportion of an alkyl or aralkyl halide, and isolated as the halide salt from which the base may be obtained.  The corresponding thioureas are prepared by interaction of the corresponding amine and benzoyl isothiocyanate followed by hydrolysis.  N1-p-chlorophenyl - N1:N2:S - trimethylisothiourea is prepared from methyl isothiocyanate and N - methyl - p - chloroaniline to form N1 - p-chlorophenyl - N1:N1 - dimethylthiourea which is treated with methyl iodide. p-Chlorophenylmethyl carbodiimide (acetone solution) is obtained by heating acetone with a small quantity of sulphur, followed by further heating with mercuric oxide and N1-p-chlorophenyl-N2-methyl - thiourea and filtration.  N1 - Dimethylamino - N1 - S - dimethyl - N2 - p - chlorophenyl iso thiourea hydroiodide is prepared by reaction of methyl iodide with N1-dimethylamino-N1-methyl - N2 - p - chlorophenylthiourea which is prepared by reacting trimethyl hydrazine with p-chlorophenylisothiocyanate.