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. 1; 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 pyrimidiniurn 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.