From Rings with an Amino Group Adjacent to a Replaceable Hydrogen Atom

From Rings with an Amino Group Adjacent to a Replaceable Hydrogen Atom 

This section brings together a miscellaneous set of reactions all of which require a parent nucleus that is aromatic, rc-excessive, and electronically equipped to support an electrophilic attack adjacent to the amino group. Understandably, rather severe conditions are often required. Common substituents found in the product are alkyl, aryl, amino, and oxo groups. For example, 2-aminonaphthalene hydrochloride, when refluxed for 2 days with an excess of sodium dicyanimide [NaN(CN)2] in octanol, gave 1,3-diamino-benzo[/]quinazoline (54) in good yield the method was also suitable for 

Acetanilide, heated with urethane and phosphorus pentoxide, gave 2-methylquinazolin-4-one (see 1) benzanilide similarly furnished the 2-phenyl analog (yields not reported).38 The intermediate is apparently the amidine 55, because this produced 2-phenylquinazolin-4-one, in moderate yield, when heated at 185°C.39 

In the first of a series of new reactions, Meerwein heated JV-phenylbenz-imidoyl chloride (56) with acetonitrile and aluminum chloride to obtain 4-methyl-2-phenylquinazoline (see 1). He postulated that the nitrilium salt (57) (not isolated) was the intermediate. Aromatic nitriles could also be used. The imidoyl chloride could be replaced by a mixture of benzanilide and thionyl chloride other Lewis acids could replace the aluminum chloride. The solvent could be tetrachloroethane, nitrobenzene, or an excess of the nitrile. Best reaction temperatures ranged from 90° to 160°C and yields were usually excellent. Imidate esters, e.g., PhNC(Ph)OEt, could replace the imidoyl chloride.41 

In the same program, phenyldiazonium tetrafluoroborate was allowed to react with two molecules of a nitrile (RCN) at 20°-50°C to obtain 2,4-disubstituted (phenyl or benzyl) quinazolines in good yields. The nitrilium salt 58 was thought to be the first stage 41,42 Somewhat similarly, phenyldiazonium tetrafluoroborate reacted with methyl isothiocyanate to give 2,4-di(methylthio)quinazoline.41 

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