A fast and green way to preparation of a new series of triazole derivatives is reported using the three-component reaction between arylglyoxals, acetylacetone and sodium azide in water as solvent.
INTRODUCTION1,2,3-Triazoles are important heterocyclic scaffolds of interesting chemical and biological applications and are present as the key substructure in therapeutically active compounds such as antimicrobials, anti-HIV agents and kinase inhibitors. [1][2][3][4] In that respect, the development of new methods for their synthesis have gained special importance in triazole chemistry. 1,3-Dipolar cycloaddition of azides to carbon-carbon multiple bonds is a common method to obtain 1,2,3-triazoles. [5][6][7][8][9][10] An important criterion of green chemistry is replacing hazardous organic solvents with environmentally favorable solvents. Water is the most desirable solvent in the green context and many successful examples of reactions in an aqueous medium are known. [11][12][13][14] Arylglyoxals with a carbonyl group adjacent to the aldehyde functionality, are reactive and versatile species which have been widely used for the synthesis of different heterocyclic and carbocyclic compounds. [15][16][17] Recently we focused our attention on the application of multi-component reactions of arylglyoxals for synthesis of different carbocyclic and heterocyclic organic compounds. [18][19][20] In continuation of these works, we report here a simple method for synthesis of some new 1,2,3-triazole derivatives by a three-component reaction between arylglyoxals, acetylacetone and sodium azides in water as solvent.
RESULTS AND DISCUSSIONIn order to investigate the reaction of arylglyoxals, acetylacetone and sodium azide, at first we studied the reaction between 3-nitrophenylglyoxal monohydrate 1a, acetylacetone and sodium azide in water as solvent (Scheme 1). A mixture of 3-nitrophenylglyoxal monohydrate and acetylacetone was stirred in water at 100 o C for 20 min. After cooling the reaction mixture to room temperature, sodium azide was added. The reaction mixture became quickly light-red and TLC of the reaction mixture showed the presence of only one product. After extracting the mixture with dichloromethane and evaporating the solvent a solid was obtained which was washed with diethyl ether to afford triazole derivative 4a in 90% yield. Then the synthesis of 4a was examined in different solvents (H2O, EtOH, MeOH, THF, MeCN, CH2Cl2). The results are shown in Table 1. First, we tested the reaction in water at 25 o C under air atmosphere for 48 h, but no product was isolated (Table 1, entry 1). Stirring the reaction mixture in EtOH for 5 h at 25 o C, afforded the product 4a in 56% yield (Table 1, entry 2). Using H2O: EtOH (1:1) as a solvent at 25 o C lead to the desired product 4a in 68% yield after 2 h, but refluxing the mixture for 20 min gave the product 4a in 88% yield (Table 1, entries 3-4). The best result was obtained when water was used as solvent at 100 o C and compound 4a was isolated after 20 min in 90% yield (Table 2, en...
