4‐Methyl‐ and 4‐(Halophenyl)pyrimidinium (4‐Halobenzoyl)methylides. Correlation of Structure, Stability, Reactivity, and Biological Activity

For the first time in the cycloimminium ylide series, we present a theoretical and experimental study concerning the correlation between structure, stability, reactivity, and biological activity of 4‐(R)‐pyrimidinium (4‐halobenzoyl)methylides (R = Me and 4‐chlorophenyl; hal = X = F, Cl, Br, I; see 5 and 6 in Scheme 1). The 4‐methylpyrimidinium (4‐halobenzoyl)methylides 5 are relatively stable compounds, while the (4‐chlorophenyl)pyrimidinium (4‐halobenzoyl)methylides 6 are more unstable. Their stability varies with the nature of the substituents at the ylide carbanion and pyrimidinium cation moieties as confirmed by quantum‐chemical calculations. The latter also disclose the possibility to use pyrimidinium ylides as nucleophilic reagents as well as 1,3‐dipoles in reactions with appropriate reagents. The experimental data obtained confirm the calculations concerning the nucleophilicity and reactivity of the ylides 5 and 6. Moreover, the influence of microwave irradiation on the synthesis of the pyrimidinium salts 3 and 4 from pyrimidine and an organic halide is studied and reveals a remarkable reaction‐rate increase under microwave irradiation as compared to classical conditions; this allows the general and facile synthesis of the salts 3 and 4 (Scheme 1, Table 1). The in vitro biological activity of the newly obtained 4‐methylpyrimidine compounds is also tested. Some of them exhibit a remarkable activity against different microorganisms (germs and fungi) which allows to establish structure–activity correlations.