Alquilação seletiva na posição N1 de timina e uracil em sistema de Mitsunobu

Abstract

Selectivity of alkylation at the N1 position in pyrimidines (thymine and uracil) was achieved by the application of N3-benzoyl thymine and N3-benzoyl uracil as substrates, where the N3 atom was temporarily protected, exposing the N1 atom as the alkylation site. The N3-benzoylated compounds were obtained by double benzoylation at the N1 and N3 positions, and selective basic hydrolysis at the N1 atom. Using the Mitsunobu conditions (iPrO2CN=NCO2iPr, Ph3P, ROH) both pyrimidines were reacted with allyl and propargyl alcohol. To avoid difficulties during purification of the N1-alkyl N3- benzoylated intermediates, basic hydrolysis was realized to remove the N3-benzoyl group, since this facilitates the separation of final products from triphenylphosphine oxide and iPrO2CNHNHCO2iPr. N1-Allyl and –propargyl thymine and uracil are the substrates for future transformations.