Patent GB-813507-A (GB)
Title: Substituted 2:3-diphenyl-1:4-dioxotetrahydrophthalazines and a process for preparing them
Filed: 1955-08-08
Abstract: The invention comprises substituted phthalazine derivatives of the general formula: <FORM:0813507/IV (b)/1> wherein R is a substituent in the 5 or 6 position and is a hydroxyl, amino, acyloxy, basically substituted alkoxy, basically substituted alkylamino, basically substituted acyloxy or basically substituted acylamino group, and acid salts and quaternary ammonium salts thereof, together with a process for their preparation by condensing a phthalic chloride or anhydride substituted in position 3 or 4 by a nitro or a hydroxyl group, in an anhydrous medium and in the presence of a tertiary amine, with hydrazobenzene, reducing the nitro group if present in the product to an amino group, and if desired submitting the 5- or 6-amino- or 5- or 6 - hydroxy - 2,3 - diphenyl - 1,4 - dioxotetrahydrophthalazine so obtained to an alkylation by a halide yielding a basically substituted alkyl radical or to an acylation with a halide yielding an unsubstituted or basically substituted acyl radical and, if desired, forming an acid addition or quaternary ammonium salt.  The acylation may be performed in two stages by use of a haloacyl halide and subsequent reaction with a secondary or tertiary amine.  In examples: (1) 4-nitrophthalyl chloride is added dropwise to hydrazobenzene in dimethylaniline, benzene is added and after heating the mixture is acidified, giving 6-nitro-2,3-diphenyl - 1,4 - dioxo - tetrahydrophthalazine (also prepared using 4-nitrophthalic anhydride in pyridine) which is hydrogenated over Raney nickel to 6 - amino - 2,3 - diphenyl - 1,4 - dioxotetrahydrophthalazine; (2) 3 - nitrophthalyl chloride similarly yields the 5-amino isomer, which (3) is heated with diethylaminoethyl chloride giving the hydrochloride of 5-(b -diethylaminoethylamino) 2,3-diphenyl-1,4-dioxotetrahydrophthalazine; (4) 4-hydroxyphthalic anhydride and hydrazobenzene in pyridine give 6 - hydroxy - 2,3 - diphenyl - 1,4 - dioxo - tetrahydrophthalazine which (5) in toluene is treated with ethanolic sodium ethylate and then diethylaminoethyl chloride, yielding the 6-(b -diethylaminoethoxy)-derivative; (6) and (7) similarly are prepared the 5-hydroxy isomer and using N-chlorobetainyl) chloride the 5-dimethylaminoacetoxy compound as its methochloride; (8) the sodium salt of the 5-hydroxy compound is treated with bromoacetyl bromide in toluene and then with triethylamine giving the ethobromide of 5 - diethylaminoacetoxy - 2,3 - diphenyl - 1,4 - dioxo - tetrahydrophthalazine; (9) the sodium salt of the 5-hydroxy compound is reacted with the ethochloride of chloroformic acid b -diethylaminoethyl ester the product precipitated with KI and then treated with ethanolic silver nitrate giving [2,3-diphenyl-1,4-dioxo - tetrahydrophthalazinyl - 5) - [b  - diethylaminoethyl] carbonate etho nitrate; (10) [2,3 - diphenyl - 1,4 - dioxo - tetrahydrophthalazinyl - 5] - [b  - dimethylaminoethyl) carbonate methiodide is similarly prepared; (11) to (20) other derivatives of 2,3-diphenyl-1,4 - dioxotetrahydrophthalazine described include: 6 - nicotinoyloxy -, 5 - nicotinoyloxy (as its methiodide, methyl methosulphate, and ethobromide), 5 - diethylaminoacetylamino-, 5 - diethylaminoacetoxy -, its ethobromide, 5-acryloyloxy-, 5-stearoyloxy- and 5-oleoyloxy-.