Comparative Study of the Chemoselectivity and Yields of the Synthesis of N ‐Alkyl‐4‐(trihalomethyl)‐1 H ‐pyrimidin‐2‐ones

This paper reports a comparative study of the chemoselectivity and yields of the synthesis of N ‐alkyl‐4‐(trihalomethyl)‐1 H ‐pyrimidin‐2‐ones carried out by the cyclocondensation of 4‐alkoxy‐1,1,1‐trihalo‐3‐alken‐2‐ones (enones) with methyl‐ and allylureas with the N ‐alkylation of 4‐(trihalomethyl)‐1 H ‐pyrimidin‐2‐ones with methyl iodide and allyl bromide. To determine the chemoselectivity of the products obtained, all compounds were fully analyzed by 1 H and 13 C NMR and 2D HMBC spectroscopy. This study has demonstrated that the cyclocondensation reactions give better yields and furnish either N 1 ‐ or N 3 ‐alkylated products depending on both the reaction conditions and the substituents on the enones, whereas the alkylation of pyrimidin‐2‐ones gives lower overall yields and either an N 1 ‐alkylated product or a mixture of N 1 ‐ and O ‐alkylated products.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)