Patent GB-610915-A (GB)
Title: Process for the preparation of dihydrophenanthridine compounds
IPC: C07D221/12
Filed: 1946-04-09
Abstract: Substituted 9,10 - dihydrophenanthridines having the formula <FORM:0610915/IV(b)/1> are prepared by the reduction under mild reduction conditions of phenanthridinium salts of the formula <FORM:0610915/IV(b)/2> in which the ring A or B or both may be substituted by one or more halogen, hydroxyl, alkyloxyl, aryloxy, amino, alkylamino, acylamino or carbalkoxylamino radicals or other radicals unaffected by mild reduction condition, R and R1 are alkyl, aryl or aralkyl radicals in which the aryl or aralkyl radicals (if any) may be similarly substituted, and X is an acid radical. Reduction may be effected at room temperature in aqueous or alcoholic solution, by means of hydrogen at atmospheric or elevated pressure and in presence of a hydrogenation catalyst and, if desired, in the presence of an alkali.  Quaternary compounds of the formula <FORM:0610915/IV(b)/3> wherein R2 is an alkyl, aryl or aralkyl radical are prepared by treating the above specified dihydrophenanthridine with an alkyl, aryl or aralkyl halide or other quaternizing agent.  When one or both of the rings A and B contains or contain amino or hydroxy substituents, these substituents are protected by a preliminary acylation or equivalent protective reaction before treatment with the quaternizing agent.  The quaternization may be carried out in a high boiling solvent such as anisole or a low boiling solvent such as ethyl alcohol, if desired, under pressure. The following examples are given: (1) 9-phenylphenanthridine is treated with methyl sulphate and then with potassium iodide to produce 9-phenyl-10-methyl-phenanthridinium iodide which is converted to the corresponding chloride by means of silver chloride.  The latter is reduced with hydrogen in the presence of palladized charcoal to yield 9-phenyl-10-methyl-9,10-dihydrophenanthridine.  The same product is obtained by hydrogenating 9-phenyl-10-methyl-phenanthridinium methosulphate; (2) 9-benzyl-phenanthridine is methylated with dimethyl sulphate and then treated with hydrochloric acid to give 9-benzylphenanthridine methochloride.  This is hydrogenated and treated with hydrochloric acid to yield the hydrochloride of 9-benzyl - 10 - methyl - 9,10 - dihydrophenanthridine; (3) 2 - p - methoxyphenyl-acetamidodiphenyl prepared from p-methoxyphenyl-acetyl chloride and 2-aminodiphenyl, is heated with phosphorous oxychloride to give 9-p-methoxybenzylphenanthridine.  This is converted to methochloride and hydrogenated to yield 9-p-methoxybenzyl - 10 - methyl - 9,10 - dihydrophenanthridine hydrochloride; (4) 2-nitro-41-methoxydiphenyl is reduced with iron filings in the presence of ferric chloride to the corresponding amino compound which is then reacted with anisoyl chloride to give 2-anisamido-41-methoxydipheny.  By treatment with phosphorous-oxychloride the latter is converted to 7 - methoxy - 9 - (p - methoxyphenyl) - phenanthridine which is treated with dimethyl sulphate to form 7-methoxy-9-(p-methoxyphenyl)-phenanthridine methochloride.  The latter is reduced with hydrogen to give 7-methoxy-9-(p - methoxyphenyl) - 10 - methyl - 9,10 - dihydrophenanthridine. (5) 7-carbethoxyamino-9,10-dimethylphenanthridinium methosulphate (prepared according to Specification 578,226) is hydrogenated and treated with hydrochloric acid to yield the hydrochloride of 7-carbethoxyamino - 9,10 - dimethyl - 9,10 - dihydrophenanthridine; (6) 2-nitro-41-carbethoxyhydroxydiphenyl, prepared from 2-nitro-41-hydroxydiphenyl and ethyl chloroformate, is reduced with iron filings and the product acetylated to give 2 - acetamino - 41 - carbethoxyhydroxy-diphenyl, which is converted by means of phosphorous oxychloride to 7-carbethoxyhydroxy-9-methylphenanthridine.  This is treated with dimethyl sulphate and potassium bromide and the quaternary salt formed is hydrogenized to yield 7 - carbethoxyhydroxy - 9,10 - dimethyl-9,10-dihydrophenanthridine; (7) 7-carbethoxyhydroxy-9-methylphenanthridine is converted successively into 7 - hydroxy - 9 - methylphenanthridine, 7 - hydroxy - 9 - methylphenanthridine methochloride and 7-hydroxy-9,10-dimethyl-9,10-dihydrophenanthridine; (8) 7-Acetamido - 9,10 - dimethylphenanthridinium chloride is hydrogenated and the 7-acetamido-9,10 - dimethyl: 9,10 - dihydrophenanthridine formed is deacetylated; (9) 2,7-diacetamido-9-9-phenyl-10-methylphenanthridine is hydrogenated as in (1).  Other examples show the preparation of the quaternary salts; (10) 9-phenyl - 10,10 - dimethyl - 9,10 - dihydro phenanthridinium iodide; (11) and (12) 9-benzyl - 10 - methyl - 9,10 - dihydrophen anthridine methiodide; (13) 9-benzyl-10-methyl - 9,10 - dihydrophenanthridine methochloride; (14) 9-p-methoxybenzyl-10-methyl-9,10 - dihydrophenanthridine methochloride; (15) 7 - methoxy - 9 - p - methoxyphenyl - 10 - methyl - 9,10 - dihydrophenanthridine methiodide; (16) 7-carbethoxyhydroxy-9,10-dimethyl - 9,10 - dihydrophenanthridine methiodide, and (17) 7 - carbethoxyamino-9,10,10-trimethyl - 9,10 - dihydrophenanthridinium iodide and the hydrochloride of 7-amino-9,10,10-trimethyl - 9 - 10 - dihydrophenanthridinium chloride.