1.2.4- Triazines, synthesis from oximes

The 1,2,3-triazine ring was constructed from o-aminophenyl oximes in the conditions of nitrosation (NaN02/HCl) , while hydrazinooximes were used for the synthesis of the 1,2,4-triazine ring Thus, cyclization of a-hydrazinooxime 342 with Pb304 in the presence of acetic acid afforded 1,2,4-triazines 343 in 44-54% yields (equation 149) . Interaction of oxime 344 with hydrazine leads to the spiro compound product 345 in 73% yield (equation 150) °. 

An in situ method for the preparation of N-methyleneamines has been devised by Overman and Osawa for use in condensation reactions with enolates and organometallic reagents. These species, with the exception of very hindered N-methyleneamines, cannot be isolated in the condensed phase because they rapidly trimerize to hexahydro-l,3,5-triazines. In this in situ method, A -methyleneamines (230) are generated from N-(cyanomethyl)amines (228) by deprotonation with an equivalent of enolate to give an intermediate amide (229) which loses LiCN (equation 22). When two equivalents of enolate are present, addition to the N-methyleneamine occurs and 3-lactams (233) are obtained in 60-70% yield upon warming the reaction mixture to 25 C (Scheme 48 Table 26). Uncyclized 3-amino esters can be isolated if the reaction is quenched at lower temperature a possible cycloaddition mechanism is thus ruled out. It is not clear to what extent, if any, the reaction is limited to a,a-disubstituted enolates. N-Methyleneamines, like oxime ethers, are useful for the synthesis of 4-unsubstituted 3-lactams and should also have important applications in the synthesis of monobactam antibiotics. 

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