Birch Reduction and Reductive Alkylation of Benzonitriles and Benzamides

Article abstract of DOI:10.1021/jo00375a043

In contrast to literature suggestions, benzonitriles and N,N-dialkylbenzamides are excellent substrates for Birch reduction and reductive alkylations.Thus, o-methoxybenzonitrile (1a) and benzonitrile (1b) give 1,4-cyclohexadienes 2a-2d from alkali-metal reduction in NH3-THF with tert-butyl alcohol (1 equiv), followed by sequential addition of an alkyl halide and excess NH4Cl.The product of HCN elimination is obtained if NH4Cl is not added prior to an aqueous workup.Birch reduction of 1a followed by NH4Cl quench gives 2-cyano-1-methoxy-1,3-cyclohexadiene (4), while benzonitrile (1b) gives the dimeric dinitrile 8, isolated as a 7:5 mixture od diastereoisomers.Hydrogenation of the mixture, 8, gives chromatographically separable 9a and 9b; a single-crystal X-ray diffraction study provided the molecular structure of 9b.Birch reduction of N,N-dimethylbenzamide (12a) gives 1,4-cyclohexadiene 13a, while reductive benzylation gives 13b.The effect of alkali metal (type and quantity), the availability of a proton source, and variation in reaction temperature on the course of Birch reduction of N,N-dimethylbenzamide (12a) is reported.