Patent GB-1476503-A (GB)
Title: 1-arylamino-and 1-arylimino-pyrroles and preparation thereof
IPC: C07D207/50
Filed: 1974-06-10
Abstract: 1476503 1-Arylamino or 1-aryliminopyrroles STERLING DRUG Inc 10 June 1974 [21 June 1973] 25599/74 Heading C2C  Novel compounds of the Formulae Ia, Ib, Ic and Id wherein R 1  and R 2  are hydrogen or alkyl or R 1  is hydrogen and R 2  is carboxyl; R 3  is hydroxy, benzyloxy, fluorine, chlorine, bromine or alkyl; R 4  is hydrogen, alkanoyl benzoyl or alkyl, X is the grouping -CH=CH-CH=CH- fused to the phenyl ring at the positions indicated or it represents two hydrogen atoms, or one hydrogen atom and one of the groups R 3 , or two of the groups R 3 ; R 5  is hydrogen, alkyl, alkanoyl, benzoyl or benzyl; R 7  is hydrogen; R 8  is alkyl, phenyl or 1-pyrrolyl or in Formula Ic R 7  and R 8  together with the nitrogen to which they are attached represent nitroso; n is 0, 1 or 2 and where the phenyl ring of the groups R 4  and R 5 , when benzoyl or of the R 8  group when phenyl, can be substituted by alkyl, alkoxy, fluorine, chlorine or bromine; in which the alkyl groups in alkyl, alkoxy and alkanoyl are C 1-4  alkyl groups, may be prepared by reacting a compound having the Formula IIa or IVa or a compound having the Formula IIc or IVc with a compound having the Formula III wherein R 6  is lower-alkyl, to prepare a compound of the Formula Ia or Ic, respectively, wherein R 1  and R 2  are each hydrogen, or reacting a compound having the Formula IIa or a compound having the Formula IIc with a compound of the Formula V. wherein R 1  and R 2  are each lower-alkyl to prepare the corresponding compound of Formula Ia or Ic, respectively, wherein R 1  and R 2  are each lower-alkyl, if desired, subjecting a compound of Formula Ia or Ic obtained, wherein R 4  is lower-alkanoyl, benzoyl or substituted benzoyl to alkaline hydrolysis to obtain the corresponding compound wherein R 4  is hydrogen, if desired, reacting a compound of Formula Ia obtained, wherein R 1 , R 2  and R 4  are each hydrogen with an oxalyl halide and reacting the resulting compound of Formula VI with hydrogen peroxide in the presence of aqueous alkali to obtain the corresponding compound wherein R 1  is hydrogen and R 2  is carboxyl, if desired, subjecting a compound of the Formula Ia obtained, wherein R 3  is benzyloxy and/or R 5  is benzyl to catalytic hydrogenolysis to obtain the corresponding compound wherein R 3  is hydroxy and/or R 5  is hydrogen, if desired, reacting a compound of Formula Ia obtained, wherein R 5  is hydrogen with a lower-alkanoylating or benzoylating or substituted benzoylating agent to prepare a corresponding compound wherein R 5  is lower-alkanoyl, benzoyl or substituted benzoyl respectively, if desired, reacting a compound of the Formula Ia or Ic obtained, wherein R 4  is hydrogen with a loweralkanoylating, benzoylating or substituted benzoylating agent to prepare the corresponding compound wherein R 4  is lower-alkanoyl, benzoyl or substituted benzoyl respectively, if desired, oxidizing a compound of the Formula Ia or Ic obtained, wherein R 4  is hydrogen, R 5 O is 4-OH with respect to the imino bridge, and R 7  is hydrogen to prepare the corresponding compound of Formula Ib or Id, respectively. Alternative processes include (1) reacting a compound IX with a compound X to produce a compound Ib and a compound Id wherein R 8  is 1-pyrrolyl (R 1  and R 2  = hydrogen); (2) reducing, with alkali metal hydrosulphite, a compound Id to produce a compound Ic wherein R 4  and R 7  are hydrogen; (3) reacting a compound Ib or Id wherein n is zero with anhydrous hydrohalic acid to produce a compound Ia, in which OR 5  is in the 4 position relative to the amine group, or a compound Ic, wherein R 4  and R 5  are hydrogen, R 3  is halogen and n is 1; (4) reacting a compound IX with a compound XI to produce a compound Ic, wherein R 4  is hydrogen and R 7  and R 8 , taken together with the nitrogen to which they are attached, are nitroso. Acetaldehyde N - benzoyl - 4 - benzyloxy phenylhydrazone is prepared by reacting 4- benzyloxyphenylhydrazine with acetaldehyde to give acetaldehyde 4-benzyloxyphenylhydrazone, which is acylated with benzoyl chloride. Acetaldehyde N - benzoyl - 4 - methoxyphenylhydrazone hydrochloride is prepared by an analogous process. N - methyl - N - (4 - benzyloxyphenyl)hydrazine is prepared by reacting N-methyl-4-hydroxyaniline hemisulphate with nitrous acid formed in situ to give N-methyl-N-nitroso-4-hydroxyaniline, which with benzyl chloride and strong base yields N-methyl-N-nitroso-4-benzyloxyaniline, which with lithium aluminium hydride gives the required hydrazine. Numerous N - benzoyl - N - (substituted phenyl) hydrazines, in which the substituents are 2,3 or 4- benzyloxy, 3,4 - dibenzyloxy or 4- phenylamino, are prepared by reacting the corresponding N-benzoyl aniline with sodium hydride then sodium hypochlorite and concentrated ammonium hydroxide to form the hydrazine group. These N-benzoyl anilines are prepared by acylation of the aniline or etherification of the corresponding N-benzoyl hydroxyaniline. Similarly N - benzoyl - 4 - benzyloxy - 1 - naphthylamine is prepared by etherification of N- benzoyl-4-hydroxy-1-naphthylamine. N - benzoyl - N - (4 - methylaminophenyl)- hydrazine is prepared by reacting N-methyl-4- nitroaniline with trifluoroacetic anhydride to yield N - methyl - N - trifluoroacetyl - 4 - nitroaniline, which is hydrogenated to N-methyl-N- trifluoroacetyl - p - phenylenediamine, acylated to N - methyl - N - trifluoroacetyl - N<SP>1</SP> - benzoylp-phenylenediamine, hydrolysed to N-methyl- N<SP>1</SP> - benzoyl - p - phenylenediamine and finally reacted with sodium hydride and chloramine. N - benzoyl - N - (4 - chlorophenylaminophenyl) hydrazine is prepared by reacting 4-nitrosophenol with 4-chloroaniline in the presence of p-toluene sulphonic acid to yield 4-chloro-4<SP>1</SP>- nitrosodiphenylamine, which is catalytically reduced to N-(4-chlorophenyl)-p-phenylene diamine, acylated to N - benzoyl - N<SP>1</SP> - (4 - chlorophenyl)-p-phenylenediamine, which is converted by the action of sodium hydride and chloramine to the required compound. The compounds of the Formulae Ia to Id have bactericidal activity and may be applied as solutions, creams or aerosol sprays or foams. Some compounds are useful against urinary tract infections.