ALKALINE CARBONS AS BASE CATALYSTS - ALKYLATION OF IMIDAZOLE WITH ALKYL-HALIDES

Anionic alkylation of imidazole with alkyl halides to produce intermediates in the synthesis of pharmaceutically important antiviral products, such as famciclovir and acyclovir, have been carried out using alkaline carbons as base catalysts. Previously to the alkylation of imidazole, the condensation of benzaldehyde with malonic esters has been used as test reaction of basicity on a series of lithium, sodium, potassium and cesium exchanged Norit RX 1 Extra activated carbon. The importance of active sites and the measurement of surface basicity have been emphasized. Under reaction conditions, it has been found that most of the basic sites in alkaline carbons have 10.7 less-than-or-equal-to pK(a) less-than-or-equal-to 13.3, but there is a considerable number of sites able to abstract protons of 13.3 less-than-or-equal-to pK(a) less-than-or-equal-to 16.5. Norit RX 1 Extra which was not subject to alkaline exchange retains most of its basic sites capable of abstracting protons of 9 less-than-or-equal-to pK(a) less-than-or-equal-to 10.7. Taking into account that the pK(a) of the NH group of imidazole is 14.5, the alkaline carbons present the required basic strength to catalyze the alkylation of this N-heterocycle with alkyl halides.