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J.MAR.CHIM.HETEROCYCL. Volume 1, N° 1 Décembre 2002 DIRECT ONE STEP PREPARATION FOR QUINAZOLINES DERIVATIVES Abdelhakim El Ouali Lalami, 1,2 Saïd Boukhris, 1 Nouzha Habbadi, 1 Najib Ben Larbi 2 and Abdelaziz Souizi 1* 1. Laboratoire de Synthèse Organique et d’Agrochimie. Département de Chimie. Faculté des Sciences. Université Ibn Tofaïl. B.P 133- Kénitra. Maroc 2. Laboratoire de chimie Organique . Département de Chimie. Faculté des Sciences DHM, Université Sidi Mohammed Ben Abdellah B.P 1796-Atlas, Fès. Maroc Abstract : The double addition of anthranilamide 2 on epoxides 1 is observed when the reaction is carried out at room temperature in acetonitrile while 2-alkyl-quinazolin-4-ones 4 are obtained at higher temperature. Résumé : La double addition de l’anthranilamide 2 sur les époxydes 1 est observée quand la réaction est réalisée à température ambiante, tandis que les 2-alkyl-quinazolin-4-ones 4 sont obtenues à reflux de l’acétonitrile. Key words : anthranilamide , gem-diyano epoxides, quinazolinones The quinazolin-4-ones constitute a class of compounds of very important medicinal chemists interest and has acquired commercial success as drugs for various kinds of CNS(central nervous system) disturbances [1], they are, for example, used as tranquillizers [2], antidepressive [3], analgesic [4], antithrombic [5], antifibrillatory [6], drugs for the treatment of arteriosclerosis [7], Several derivatives have also been used in the industry [8]. Indeed, the epoxides 1 are widely used as precursors in the synthesis of new heterocyclic systems [9-15]. Contrary to the reactivity of the anthranilamide with epoxydes cyano esters [16] , in this paper we will show that the reaction of epoxides 1 with anthranilamide 2 follows a different route and leads to compounds 3 and quinazolinones 4 depending on the reaction conditions (Scheme 1). It appears that the temperature has an important effect on the outcome of the reaction. Indeed, when the epoxide 1 was reacted with anthranilamide 2 at room temperature during 20 hours in acetonitrile, products 3 were obtained and characterized. 37
J.MAR.CHIM.HETEROCYCL. Volume 1, N° 1 Décembre 2002 Ar H O 1 CN CN + 2 CONH2 NH2 CH3CN, r.t., 20h CH3CN,reflux, 20h 45-52 % 38 50-56 % Scheme 1 H2NOC Ar H NH O HN 3a-c reflux, 16h CH3CN H N NH Ar H O 4a-b CONH2 This reaction proceed first by the opening of the epoxide cycle by the most nucleophile site of the anthranilamide which leads to the unstable cyanhydrine 5 that evolues to a very reactive derivative cyanoformyle 6 [17], which then immediately reacts with the second molecule of anthranilamide to yield the compounds 3 (scheme 2). Ar H O 1 - HCN CN CN + H N C O 6 Ar O NH2 CONH2 NH2 CN CONH2 NH2 Scheme 2 H N C O HO 5 Ar CN NH2 CN H2NOC Ar H NH HN 3 O CONH2 Compounds 4, were formed when the reaction was performed in refluxing acetonitrile. Compounds 3 was also the early formed derivative when an excess of anthranilamide was used. It is noted that the thermolysis of Compound 3 under the reaction conditions did not give 3aryl-quinazolin-4-ones 4. The structure of 4, in agreement with spectral data was confirmed by comparing these derivatives with their isomers quinoxalin-2-ones 8 previously described in the literature [18-19].
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