Patent GB-1088095-A (GB)
Title: N-halo- n' -aryl amidines
IPC: C07D235/18
Filed: 1964-10-12
Abstract: The invention comprises (1) compounds of the formula PhNH.C(R) = NX, where X is Cl or Br, Ph is phenyl or substituted phenyl, and R is an alkyl, aralkyl, aryl or heterocyclic aromatic radical, with the proviso that if Ph is unsubstituted phenyl or a 2- or 3-(C1- 5 alkyl or C1- 5 alkoxy) phenyl radical, then R is not aryl or a five-membered heterocyclic ring attached by a carbon atom and containing nitrogen and sulphur as hetero atoms; (2) their production by reacting PhNH.C(R) = NH with a positive chlorinating or brominating agent in the absence of a substantial quantity of base; (3) processes for making 2-R-substituted benzimidazoles BzR as follows: (a) treating PhNH.C(R) = NH with a positive chlorinating or brominating agent in the presence of at least an equimolar quantity of base; Ph and R are defined as in (1) above, but with the proviso that if Ph is unsubstituted phenyl or a 2- or 3-(C1- 5 alkyl or C1- 5 alkoxy) phenyl radical, then R is not aryl; (b) treating PhNH.C(R) = NH with a positive chlorinating or brominating agent in the absence of substantial amounts of base to form an N - halo - N1 - phenyl (R-amidine), and then contacting the latter with at least an equimolar quantity of base; here Ph and R are as defined in (1) with the same proviso; (c) intimately contacting a halo-amidine PhNH.C(R) = NX with at least an equimolar quantity of base; here X is Cl or Br, Ph is phenyl or substituted phenyl, and R is a heterocyclic aromatic radical in which the heteroatoms are selected from O, S and N, with the proviso that if Ph is unsubstituted phenyl or a 2-or 3-(C1- 5 alkyl or C1- 5 alkoxy) phenyl radical, then R is not a five-membered heterocyclic ring attached by a carbon atom and containing N and S as heteroatoms; (d) exposing a solution or suspension of a compound PhNH.C(R) = NX in an inert organic solvent to irradiation with ultraviolet light; here X, Ph and R are as defined in (1) above, but with the proviso as in (c) above; and (4) preparing <FORM:1088095/C2/1> by treating <FORM:1088095/C2/2> with a positive chlorinating or brominating agent in the presence of at least an equimolar quantity of base; here A is phenylene or ethylene.  Ph may be substituted by e.g. alkyl, aryl or halogen.  Specified chlorinating or brominating agents are N-haloamides and N-haloimides such as N-chloro- or N-Bromo-succinimide, -acetamide, and N-chlor-propionamide and N-bromglutarimide; chlorine water and bromine water; and hypochlorous and hypobromous acids, which may be obtained in situ by adding an alkali or alkaline earth metal hypochlorite or hypobromite to a solution of the N-phenylamidine acid addition salt.  Solvents are used, and the temperature may be 0-40 DEG  C.  Specified bases for the cyclization step are ammonium hydroxide, alkali metal carbonates, bicarbonates, cyanides, hydroxides, alkoxides and hydrides, and alkaline earth metal hydroxides; solvents are used.  Preferably the temperature is 40-100 DEG  C.  Examples are given.  Starting materials.-N-R-N1-(4-thiazolyl) amidines are prepared from 4-cyanothiazole and RNH2 in the presence of AlCl3.  In examples R is p-biphenylyl, 4-chlorobiphenyl, 4-fluorophenyl, 4 - nitrophenyl, and p - (4 - thiazolyl) - phenyl. Similarly reaction of aniline with ethyl succinimidate dihydrochloride or ethyl terephthalimidate dihydrochloride gives ethane - 1,2-and phenylene -1,4 - di - (N- phenylamidine) dihydrochlorides.  Reference has been directed by the Comptroller to Specification 948,635.