Patent GB-587673-A (GB)
Title: Improvements in or relating to the manufacture of phenanthridine compounds
Filed: 1944-01-03
Abstract: Quaternary salts of 2 : 7-diamine-9-phenylphenanthridine, having the general formula <FORM:0587673/IV/1> wherein R represents an alkyl or aralkyl group and Y represents the anion of an acid, and showing pronounced trypanocidal action, are prepared from the corresponding 2 : 7-dinitro, or 2 : 7-dicarbalkoxyamino compounds, (a) in manner preferred, by quaternating 2 : 7-dinitro-9-phenylphenanthridine, e.g. by treatment with an appropriate alkylating-agent, and ultimate reduction to amino groups of the nitro groups in the product; (b) by reduction of the dinitro-phenanthridine and quaternation of the resultant derivative, preferably after protection of the amino groups, e.g. by acetylation, and subsequent removal of the acetyl groups by hydrolysis; (c) from the corresponding dicarbalkoxyamido compound, replacing by a step of hydrolysis the reduction step of (a).  In examples: (1) 2-amino-4 : 41-dinitrodiphenyl in boiling chlorobenzene is treated with benzoylchloride, and the resultant acyl derivative is then cyclised by heating at 170-190 DEG  C. in admixture with phosphorus oxychloride and nitrobenzene; alternatively, the condensation with benzoylchloride or benzoic anhydride may be effected in nitrobenzene, the acyl derivative then being cyclised in situ after addition of phosphorus oxychloride. Quaternation is conveniently effected by heating the resulting 2 : 7-dinitro-9-phenylphenanthridine with nitrobenzene and methyl sulphate.  The quaternary chloride is obtained (a) by crystallising from dilute hydrochloric acid the pseudo base precipitated on rendering alkaline the foregoing aqueous solution, or (b) by salting out an aqueous solution of the methosulphate.  The quaternary chloride, in aqueous solution, is boiled with iron powder until reduction of the nitro groups is complete, and the resulting liquor is rendered slightly alkaline with ammonia, the filtrate being neutralized with acid prior to adding potassium bromide and isolating 2 : 7 - diamino - 9 - phenyl - 10 - methylphenanthridinium bromide; alternatively, by treatment with sulphuric acid, the acid sulphate is crystallised from the cold filtered aqueous liquor produced on reduction, and it is then neutralized in aqueous solution with ammonia and treated with an appropriate bromide to effect crystallisation of the diamino-quaternary bromide; 2 : 7 - diamino - 9 - phenyl - 10 - methyl - phenanthridinium chloride is isolated on boiling with alcohol the residue obtained by evaporating to dryness the aqueous liquor from the cold reduction mixture.  (2) 2-Amino-4 : 41-dicarbethoxyaminodiphenyl is condensed with benzoyl chloride by heating the reactants in chlorobenzene and the product is cyclised by heating with phosphorus oxychloride, followed by decomposition of the reaction-mixture with water and heating with methyl sulphate in nitrobenzene to yield 2 : 7-dicarbethoxyamino-9 - phenyl - 10 - methylphenanthridinium methosulphate, from which 2 : 7-diamino-9-phenyl-10-methylphenanthridinium bromide is obtained by sulphuric acid hydrolysis, neutralization with ammonia and addition of potassium bromide.  Specifications 372,859, 511,353 and 578,226 are referred to.