Chemical reactivity of 6-methylchromone-3- carbonitrile towards some nucleophilic reagents

Abstract

The subject of this research work aimed to study the chemical transformations of 6-methylchromone-3-carbonitrile (1) with a variety of active methylene compounds bearing –CH2-CN and –CH2-CO- groups. Reaction of 6-methylchromone-3- carbonitrile (1) with malononitrile in absolute ethanol containing 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as a basic catalyst, afforded 2-amino-7-methyl-5-oxo-5H-chromeno[2,3-b]pyridine-3- carbonitrile (2). CN CN O O N NH2 H C CN 3 O O H C 3 CN OH O CN N N O O H C 3 CN H CN CN H EtOH/DBU 2 1 B :DBU A -DBUH+ +H+ 65% Scheme 1: Reaction of carbonitrile 1 with malononitrile. Compound 2 was used as a good precursor to synthesize a novel series of heteroannulated chromones identified as Summary ii chromeno[3',2':5,6]pyrido[2,3-d]pyrimidines 3-5. Consequently, condensation of compound 2 with formamide under fusion condition afforded 4-amino-8-methyl-6H-chromeno[3',2':5,6] pyrido[2,3-d]pyrimidin-6-one (3) (Scheme 2). Moreover, reaction of compound 2 with formic acid under fusion condition afforded 8-methyl-6H-chromeno[3',2':5,6]pyrido[2,3-d]pyrimidine- 4,6(3H)-dione (4). Further, refluxing compound 1 with acetic anhydride produced 2,8-dimethyl-6H-chromeno[3',2':5,6]pyrido [2,3-d]pyrimidine-4,6(3H)-dione (5) (Scheme 2). O H NH2 O O N H C 3 N N NH2 O O N NH2 H C CN 3 O H OH O O N H C 3 N NH O O O N H C 3 N NH O CH3 3 2 4 Ac2O 5 56% 52% 61% Fusion Scheme 2: Formation of chromeno[3',2':5,6]pyrido[2,3-d] pyrimidines 3-5. On the other hand, reaction of carbonitrile 1 with ethyl cyanoacetate in boiling ethanol containing DBU afforded ethyl 2- amino-7-methyl-5-oxo-5H-chromeno[2,3-b]pyridine-3- Summary iii carboxylate (6) (Scheme 3). In the same manner, treatment of carbonitrile 1 with N-benzyl-2-cyanoacetamide and N-phenyl-2- cyanoacetamide afforded 2-aminochromeno[2,3-b]pyridine-3- carboxamide derivatives 7 and 8, respectively (Scheme 3). Compounds 7 and 8