Heteropoly Acid Catalyzed Selective Cyclization of 6-Alkyl-3-propargylmercapto-1 , 2 , 4-triazin-5 ( 2 H )-one

Cyclization of 6-alkyl-3-propargylmercapto-1,2,4-triazin-5(2H)one, derivatives (2) in the presence of Keggin heteropoly acids, H3PW12O40, H3PMo12O40, H4SiW12O40 and lacunary Keggin structure (K7PMo2W9O40) afforded 3 (3a = 6-dimethyl-7H-thiazolo[2,3-b][1,2,4]-triazin-7-one and 3b=6ethyl-3-methyl-7H-thiazolo[2,3-b][1,2,4]-triazin-7-one) in high yields and short reaction times


Introduction
Thiones of nitrogen-containing heterocycles have excited the attention of researchers because of their synthetic possibilities and useful properties.Many compounds containing sulfur and nitrogen atoms are anti-inflammatory 1 , sedative 2 , antibacterial 3,4 , antiviral 5,6 or antitumor 7,8 .Synthesis of the corresponding heterocyclic compounds could be of interest from the viewpoint of chemical reactivity and biological activity.Heteropoly acids are widely used in variety of acid catalyzed reactions [9][10][11][12][13][14] .Heteropoly acids as solid acid catalysts are green with respect to corrosiveness, safety, quantity of waste and separability and it is well known that the use of heteropoly acid catalysts for organic synthesis reactions can give a lot of benefits.One of the unique features that make solid heteropoly acids economically and environmentally attractive is their stability and bronsted acidity.Because of interesting importance of nitrogen-sulfur containing heterocycles and in continuation of our interest in application of heteropoly acids in organic synthesis [15][16][17][18] , in this article we wish to report our results for the selective heterocyclization of 6-alkyl-3-propargyl-mercapto-1,2,4-triazin-5(2H)one (2) using different keggin type heteropoly acid catalysts in various conditions.The effects of various parameters such as amount of catalysts, solvent and time were studied.

Results and Discussion
Compound 1 is well known heterocyclic thiones derived from thiosemicarbazide and it exists in two thione and thiol tautomeric forms.Condensation reaction of 1 with propargyl bromide (equation 1) in the presence of sodium ethoxide led to corresponding 6-alkyl-3-propargyl-mercapto-1,2,4-triazin-5(2H)-one (2) 21 .Cyclization of 2 could not be undertaken in either aprotic or protic solvents at their refluxing temperature.We recently have described the use of sulfuric acid for cyclization of 2a.Compound 2a had been heated in warm sulfuric acid to give compound 3a.Herein, we wish to report the use of keggin type heteroploy acids (HPA) for intermolecular cyclization of 6-alkyl-3-propargyl-mercapto-1,2,4-triazin-5(2H)-one (2).Compound 2 was refluxed in acetic acid with catalytic amounts of HPA to afford a single (TLC) compound.Heteropoly acids are separated by filtration and the products were purified by recrystalization from ethanol.The yields are shown in Table 1.Comparison of physical and spectroscopic data of obtained product with those of authentic compounds 21 proved the selective formation of 3. As shown in scheme 2, heteropoly acid play important role to protonation and activation of acetylenic carbon for nucleophilic attack of NH group, followed by isomerization to convert the methylene moiety to a methyl group.1).In study of reaction progress with TLC, we found that the conversion rate and yield were affected by amounts of catalyst and a single (TLC) compound was observed in the presence of 4% (mol/mol) of catalyst after 30 min.Reactions were done in various solvent and we find that the catalytic system composed of acetic acid as solvent shows best catalytic behaviors for heterocyclization reaction.

1 Heterocycization of 2
can lead to the formation of two isomers (3 and 4) according to Scheme 1.
Scheme 11 H NMR of 3a showed signals at 2.27 δ and 2.34 δ for the two methyl groups and 7.05 δ for one vinyl proton, these signals are observed at 1.14, 2.20 and 6.95 δ for 3b.Comparison of physical and spectroscopic data of obtained product with those of authentic compounds21 proved the selective formation of 3. As shown in scheme 2, heteropoly acid play important role to protonation and activation of acetylenic carbon for nucleophilic attack of NH group, followed by isomerization to convert the methylene moiety to a methyl group.

2
Scheme 2The results of the comparison among the Keggin HPAs (H 3 PW 12 O 40 , H 3 PMo 12 O 40 and H 4 SiW 12 O 40 ) and Lacunary Keggin structure (K 7 PMo 2 W 9 O 40 ) showed, they are almost the same regarding the yields and reaction times (Table1).In study of reaction progress with TLC, we found that the conversion rate and yield were affected by amounts of catalyst and a single (TLC) compound was observed in the presence of 4% (mol/mol) of catalyst after 30 min.Reactions were done in various solvent and we find that the catalytic system composed of acetic acid as solvent shows best catalytic behaviors for heterocyclization reaction.