Benzilic acid with benzonitrile

The isolation in poor yield of 2,5,5-triphenyl-4(5f )-oxazolone (82) by reaction of benzilic acid with benzonitrile in concentrated sulfuric acid was claimed by Japp and Findlay. Cornforth, however, suggested that the reactions of this product, m.p. 136°, could be accounted for more satisfactorily by the isomeric 5(4i ) structure 83. 

The reaction of benzil 135 with benzonitrile in the presence of the trifluoromethane-sulfonic acid leads to the bis-Af-benzoylimine 136. Under the same conditions benzoyla-cetone 137 reacts to give the bis-Af-benzoylimine 138s6 (equation 46). 

Benzilic acid (81) also reacts with benzonitrile in the presence of sulfuric acid however, it does not yield 2,5,5-triphenyl-oxazolin-4-one (82) as indicated originally,81 but the 2,4,4-triphenyl isomer (83).62,63... 

Japp also found that benzilic acid gave a triphenyloxazolone product with benzonitrile," and later woik " demonstrated that this material was (55 Scheme 26). The internal nucleophile in this case is the carbonyl oxygen. More recently, extensions of this type of reaction have been applied to the synthesis of stericaUy hindered peptides." A further interesting oxazolone synthesisfrom (56) involves nucleophilic attack by the nitrile on a cyclopropenium intermediate and leading ultimately to formation of the spiro derivative (57 Scheme 27). 

Reports have appeared claiming that triperoxo vanadates behave as nucleophilic oxidants. In particular, triperoxo vanadium complexes, A[V(02)3]3H20 (A=Na or K), are proposed as efficient oxidants of a,-unsaturated ketones to the corresponding epoxide, benzonitrile to benzamide and benzil to benzoic acid, reactions which are usually carried out with alkaline hydrogen peroxide. Subsequent studies concerning the oxidation of cyclobutanone to 4-hydroxybutanoic acid, carried out with the above-cited triperoxo vanadium compound, in alcohol/water mixtures, clearly indicated that such a complex does not act as nucleophilic oxidant, but only as a source of HOO anion. 

The reaction of amines with 1,2-diketo substrates led to a variety of substituted imidazole derivatives. Treatment of various substituted anilines 88 with glyoxals 89 gave the imine intermediate 90, which was then cyclized to the 1-arylimidazoles 91 with paraformaldehyde and ammonium chloride under acidic conditions <0382661>. A one-pot, three-component condensation of benzil 92, benzonitrile derivatives and primary amines on the surface of silica gel under solvent-free conditions and microwave irradiation provided tetrasubstituted imidazoles 93<03TL1709>. 

Cyanocarboxylic acid esters. 2-Oximinocyclohexanone dimethyl ketal, trimethyl orthoformate, and a little methanesulfonic acid added at -70° under Ng to liq. SO2, and refluxed 0.5 hr. at ca. -10° methyl 5-cyanopentanoate. Y 97%. -Similarly at 72° Benzil monoxime and triethyl orthoformate -> benzonitrile (Y 95%) and ethyl benzoate (Y 98%). M. M. Rogic et al., J. Org. Chem. 39, 3424 (1974) Beckmann fragmentation with tetrakis(triphenylphosphine)palladium cf. K. Maeda et al., Chem. Commun. 1975, 689. 

Balalaie et al. (2003) reported a one-pot, three-component condensation of benzil, benzonitrile derivatives, and primary amines on the surface of silica gel with acidic character under microwave irradiation as a new and efficient method to produce 1,2,4,5-tetrasubstituted imidazoles (Scheme 6.14). This methodology offers several advantages, such as solvent-free conditions, the use of substances without any modi-hcation or activation, high yields, shorter reaction times, and reusability of solid catalysts, and it is environmentally benign compared to the existing methodologies. 

---