New Synthesis of 5-Aryl-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones

Abstract

The acylation of 4,5-dihydro-1,2,4-triazole-5thiones with carboxylic acid chlorides is known to occur at the nitrogen atom in position 1 of the heteroring [1, 2], while compounds having an activated double bond readily add at the 5-thioxo group at 20oC [3]. Taking these data into account, we proposed a new procedure for synthesizing poorly studied 5-aryl-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones by condensation of triazolethione I with substituted cinnamoyl chlorides IIa3IIc (Scheme 1). The heterocyclization occurs under mild conditions, on heating the reactants in a benzene3pyridine mixture for 1 h under reflux. Products III were formed in good yields, and no by-products were detected. The structure of compounds III was established on the basis on the H NMR spectra. The double bond of initial cinnamoyl chloride II (two doublets at d 6.80 and 7.50 ppm) is transformed into a single bond (d 3.3035.50 ppm) which gives rise to an ABX system. The composition of products III was confirmed by the data of mass spectrometry and elemental analysis. 5-Phenyl-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-one (IIIa). A solution of 1.66 g (10 mmol) of cinnamoyl chloride (IIa) in 4 ml of benzene was added at 20oC to a solution of 1.01 g (10 mmol) of 4,5-dihydro-1,2,4-triazole-5-thione (I) in 4 ml of pyridine. The mixture was refluxed for 1 h, cooled, and diluted with 50 ml of water. The precipitate was filtered off and dried. Yield 1.62 g (70%), mp 163oC. H NMR spectrum (acetone-d6), d, ppm: 3.47 m (1H, 6-H), 3.88 m (1H, 6-H), 5.40 m (1H, 5-H), 7.4637.58 m (5H, Harom), 8.10 s (1H, 2-H). Mass spectrum, m/z (Irel, %): M + . 231 (27). Found, %: C 56.66; H 3.95; N 18.20. C11H9N3OS. Calculated, %: C 57.14; H 3.89; N 18.18. Compounds IIIb and IIIc were synthesized in a similar way. 5-(4-Methoxyphenyl)-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-one (IIIb). Yield 72%, mp 143oC. H NMR spectrum (acetone-d6), d, ppm: 3.41 m (1H, 6-H), 3.78 m (1H, 6-H), 3.83 s (3H, CH3O), 5.36 m (1H, 5-H), 7.00 d (2H, Harom), 7.53 d (2H, Harom), 8.06 s (1H, 2-H). Mass spectrum, m/z (Irel, %): M + . 261 (41). Found, %: C 55.12; H 4.10; N 16.12. C12H11N3O2S. Calculated, %: C 55.17; H 4.21; N 16.09. 5-(3-Nitrophenyl)-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-one (IIIc). Yield 81%, mp 202oC. H NMR spectrum (DMSO-d6), d, ppm: 3.41 m (1H, 6-H), 3.99 m (1H, 6-H), 5.60 m (1H, 5-H), 7.76 d.d (1H, Harom, J = 8.3, J` = 8.3 Hz), 7.95 d (1H, Harom, J = 8.3 Hz), 8.25 d (1H, Harom,