Amidines dipole moments

Configuration of A. /V-disubstituted amidines is thus regularly E, reversed rather than in amidines with a free NH2 group which are Z95. Derivatives with only one substituent at the amino group are in the middle and their conformation may be sensitive to small steric effects. In 24 a tautomeric equilibrium would be degenerate, hence the problem is simplified. In the case of IV,-diaryl derivatives, three forms are possible (24a-c) the fourth would be very improbable for steric reasons. From dipole moments an equilibrium... 

FIGURE 1. Determination of the configuration (E or Z) and of die electron distribution (the mesomeric dipole moment /xm) of file amidine 23 on the basis of the experimental dipole moment [Pg.271]

It remains to mention derivatives with just one substituent on the NH2 group. Concerning the configuration, they should take an intermediate position in addition, one has to deal with the conformation on C—N. These compounds have been less studied. Compared to structurally very similar amidines, a remarkable difference was found101. While AW -dimethyl-d-nitrobenzamidine in the crystal is in the form E,sp (41), A -methyl-4-nitrobenzamidoxime is Z.ap (42). Dipole moments in solution are compatible with a conformational equilibrium, but analysis is made imprecise by the mesomeric moments which are not known exactly102. In a previous analysis129 of /z of derivatives similar to 42 (H and Cl in place of NO2) the form Z.ap was also preferred, although the presence of a minor conformer could not be completely excluded. 

In the histaminic H2 receptor antagonist series, the classical urea-thiourea-guanidine progression was successfully completed by the use of the V-nitro and V-cyanoguanidines and, later on, by l,l-diamino-2-nitroethylene groups (Fig. 13.19). Cyano amidines and carbamoyl amidines were also used, and structure-activity relationship patterns were rationalized in terms of dipole moment orientation of related bioisosteric groups. ... 

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