A. Gondela, K. Walczak
Jul 3, 2006
Citations
0
Influential Citations
11
Citations
Journal
Tetrahedron Letters
Abstract
Nitrophenyl)- and 1-(2,4-dinitrophenyl)uracil derivatives have been obtained by direct arylation of uracil and its 5-substituted derivatives using 1-fluoro-4-nitrobenzene or 1-fluoro-2,4-dinitrobenzene in the presence of a base. The application of the newly obtained uracil derivatives in further synthesis is also presented. 2006 Elsevier Ltd. All rights reserved. Many N-substituted uracil derivatives possess biological activity. 1 N-Glycosides of substituted uracils are widely used in therapy, mainly as antiviral and antineoplastic agents. The most prominent representatives are 5-fluo- rouracil and thymine derivatives. 2,3 Uramustine, 5- (N,N 0 -bis(2 0 -chloroethyl)amino)uracil, is used orally in the treatment of several leukemias, 4 and 5-nitrouracil derivatives exhibit macrophage growth inhibition. 5 1- Aryl-5-substituted uracils are also useful intermediates in the synthesis of other uracil derivatives. 6-8 It has been demonstrated that 3-methyl-1-(4-nitrophenyl)- uracil derivatives possessing an electron-withdrawing group, such as nitro, cyano, or carbamoyl group, at the 5-position, when treated with different N-centered nucleophiles readily undergo ring transformation according to the ANRORC type reaction. 6-8 The 1-(4- nitrophenyl)-5-substituted uracils were obtained using known condensation methods. Thus, 3-methyl-5-nitro- 1-(4-nitrophenyl)uracil was obtained by the condensa- tion of 1-phenylurea with methyl 3,3-dimethoxypropan- oate and subsequent ring closure under acidic conditions, followed by N-3 methylation and nitration, which occurred on both rings (at C-5 of the uracil ring and C-4 of the benzene ring). 9 A similar procedure was used for the synthesis of 5-cyano-3-methyl-1-(4- nitrophenyl)uracil. 7 In both cases, the final products were obtained in moderate yields. The other 1-arylura- cils have been synthesized from substituted ureidoprop- anoic acids or 1-acryloyl-3-arylureas. 10 6-Methyl-1,3-