Patent GB-642134-A (GB)
Title: Preparation of quinazolones
Filed: 1947-07-28
Abstract: Substituted 4-quinazolones are obtained by heating an N-acyl-o-amino cyclic carboxylic acid derived from an aromatic carboxylic acid or from a heterocyclic carboxylic acid containing a carbocyclic ring, the N-acyl-o-amino group in the latter case being attached to a carbocyclic ring, with a primary aliphatic, aromatic, or araliphatic amine, the aromatic amine when containing a condensed ring system bearing the amino group in the b -position thereof, in the presence of phosphorus trichloride or phosphorus oxychloride.  The products have the general formula <FORM:0642134/IV (b)/1> in which R is an aromatic nucleus or a heterocyclic nucleus containing a carbocyclic ring.  The aromatic or heterocyclic nucleus may be substituted by monovalent groups, e.g. nitro, halogen such as chlorine, bromine, alkyl such as methyl, ethyl, propyl, butyl, amyl, lauryl or octadecyl, alkoxy such as methoxy, ethoxy or propoxy, Z is alkyl, e.g. methyl, ethyl, propyl, butyl, amyl, octyl or decyl, and Y is an aliphatic radical such as alkyl or alkylamino such as methylamino or ethylamino, an aromatic radical such as phenyl, tolyl, anisyl, phenetyl, o-nitro-phenyl, m-nitro-phenyl, p-nitrophenyl, p-chlorophenyl, naphthyl or phenylamino or araliphatic such as benzyl or menaphthyl.  The nucleus R may be benzene or of the benzene series or may be naphthalene, anthracene, anthraquinone, dibenzo-furane, carbazole, diphenylene sulphide.  The reaction may be effected by heating the reactants in an inert solvent, e.g. a normally liquid organic solvent, e.g. a liquid aromatic hydrocarbon such as benzene or toluene, the chlorine derivatives thereof, e.g. monochlorbenzene, monochlorotoluene, normally liquid aliphatic hydrocarbons such as octane, solvent naphtha, kerosene and their chlorine derivatives such as ethylene chloride, butyl chloride and chlorkerosene, and normally liquid nitrogeneous heterocyclic bases such as pyridine or quinoline. The reactants are generally used in equimolar proportions and about one third of a mole. of phosphorus trichloride or phosphorus oxychloride is generally employed for one mole. of each reactant.  In examples, N-acetyl anthranilic acid is heated, using toluene as diluent, with (1) p-chloroaniline; (2) lauryl amine; and (3) phenyl hydrazine.  The acid, amine and toluene mixture is agitated in each case and then treated slowly with phosphorus trichloride in toluene. The mixture is then heated to reflux temperature and after treating p with a sodium carbonate solution the toluene is removed by steam distillation and the residue is removed by filtration, washed and dried to yield 2 - methyl - 3 - p - chlorophenyl - 4 - quinazolone, 2-methyl-3-lauryl-4-quinazolone and 2-methyl-3-anilino-4-quinazolone respectively; (4) the procedure of (1) is repeated using N-acetyl-o-amino naphthoic acid instead of the N-acetylanthranilic acid, 2-methyl-3-p-chloro-phenyl-6,7-benzo-quinazolone being obtained; (5) N-acetyl-5-chloroanthranilic acid is heated with aniline as in (1), 2-methyl-3-phenyl-6-chloro-4-quinazolone being obtained; (6) example (1) is repeated using o-nitro-aniline instead of the p-chloro-aniline, the product being 2-methyl-3-o-nitro-phenyl-4-quinazolone.  Other acids specified as starting materials are N-propionyl- (or N-butyryl-) anthranilic acid, N-acetyl-5-nitroanthranilic acid, N-acetyl-6-methyl-anthranilic acid and N-acetyl-5-ethoxy-anthranilic acid, and other amines specified are methyl (ethyl, butyl, octyl, and octadecyl) amines, methyl (or ethyl) hydrazine; p-toluidine, p-anisidine, p-phenetidine, m- (or p-) nitraniline, b -naphthylamine, benzylamine and menaphthylamine.  The amine starting material when aromatic may be substituted by, e.g. halogen, nitro, alkyl and alkoxy groups.