AMIDES AND RELATED FUNCTIONS

This Chapter deals with the stereoelectronic effects which control the cleavage of tetrahedral intermediates during the formation or the hydrolysis of the amide function (1-4). These electronic effects will he examined in the amide function first. 

In amides, the nitrogen electron pair is n-x conjugated with the carbonyl group and this electronic delocalization is normally expressed by resonance structures and 3. As a result, the amide function is essentially planar and it is assuuted that the three atoms (C, M, and 0) of this function are sp hybridized. The amide function can be illustrated in three dimensions by structure 4. The electronic distribution can also be viewed as the result of the delocalization of tvio n electron pairs, one from the oxygen atom and one fro.a the nitrogen atom (cfj 1 versus 2) and on that basis, it is referred to here as the primary electronic delocalization of the amide function. 

Furthermore, the oxygen atom of the carbonyl group in the amide function has an electron pair oriented antiperiplanar to the polar C-N bond there is therefore an electronic delocalization caused by the overlap of that oxygen electron pair orbital with the antibonding orbital of the C-N sigma bond (o ) as shown in two dimensions by structure 5 and in three dimensions by structure 6. This additional n-o delocalization is referred to here as a secondary electronic delocalization. Thus, amides are similar to E esters because they both have the primary electronic effect and one secondary electronic effect. This is in contrast with Z esters which have two secondary electronic effects besides the primary electronic effect. 

The principle of microscopic reversibility predicts that the reverse process must follow the same path which is indeed stereoelectronically allowed the oxygen atom in T has two secondary electronic effects (n-o ) (one electron pair of the oxygen atom is antiperiplanar to the C-N bond while the other is antiperiplanar to C—Y bond) and the nitrogen has one (the nitrogen electron pair is antiperiplanar to the C— Y bond). Thus, there are three secondary electronic effects (n-o ) in 1 and by the ejection of Y to form A. two of these (due to the two electron pairs antiperiplanar to the C-Y bond) have been transformed into primary electronic effects (n-v ) in the product 4. The third secondary electronic effect remains a n-a interaction in the product. The ejection of Y can therefore take place with the help of the primary and one secondary electronic effects. 

In cases where Y is an alkoxy group, there is the possibility of forming either an ester or an amide function, and the proportion of each will depend on the conformation of the tetrahedral intermediate. The nine different gauche conformers for such a hemi-orthoamide tetrahedral intermediate are shown in Fig. 1, and the stereoelectronically controlled cleavages are described in Table 1. 

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Amides and Related Functions 125 this possibility must be eliminated. These ions can exist either exclusively in the syn or as a mixture of syn and anti isomers. These two possibilities are likely because both predict the same results which correspond to the experimental observation. Indeed, if these ions are syn, it means that the intermediate 59 will first be produced and then, it would give different conformers which would yield the mixture of ester and amine plus amide and alcohol products. If these ions are a mixture of anti and syn, the former will give the ester and amine products whereas the latter would give a mixture of ester and amine plus amide and alcohol products. 

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