By Reaction of Benzyl Cyanides with Nitroarenes

The base-catalyzed reaction of benzyl cyanides with p-chloronitro-benzenes is widely used as a preparative route to 3-arylanthranils (Eq. 8), and hence, by reductive ring opening, o-aminobenzophenones, the valuable precursors of the pharmacologically important benzodiazepinones. By this method 3-phenylanthranils bearing trifluoromethoxy,173 (trifluoromethyl)-thio,173 sulfonamido,174 methoxy- and ethoxycarbonyl,175,176 cyano,175 methylsulfonyl,175 halo,176 difluoromethoxy,177 and acetyl (protected as the 

Occasionally, the reaction is complex and affords a multitude of products. For example, 2,4-dichloronitrobenzene and benzyl cyanide produce a mixture containing bis(4-chloro-2-benzoyl)azoxybenzene, 2-benzoyl-4-chlo-ronitrobenzene, 5,7-dichloroanthranil, and a-(5-chloro-2-nitrophenyl) benzyl cyanide.180 Using sodium hydride in dimethylsulfoxide as the base, the substituted benzyl cyanide, formed by direct nucleophilic displacement of chloride, becomes the major product (48%), whereas with sodium hydroxide and benzyltriethylammonium chloride the dichloroanthranil (33%) predominates. 

Nucleophilic displacement of halogen rather than anthranil formation is generally observed with o-nitrochlorobenzenes.1 Of interest, therefore, is the formation of 5-benzoyl-7-chloro-3-phenylanthranil from 4-benzoyl-2-chloronitrobenzene and benzyl cyanide in the presence of potassium hydroxide.181 

Attempts to prepare 3-(p-aminophenyl)-5-chloroanthranil from p-amino-benzyl cyanide and p-chloronitrobenzene failed. However, protection of the amino function as the dichloroacetyl derivative permits direct cyclization to the anthranil.182 

5-Difluoronitrobenzene and ethyl cyanoacetate furnish 3-cyano-6-fluoroanthranil, albeit in poor yield (26%). 83 2-Chloro-5-fluoronitrobenzene behaves similarly. 

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