Visible-light mediated regioselective approach towards synthesis of 7-aroyl-6-methyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines

• Published in: Tetrahedron 2019-12, Vol.75 (50), p.130728, Article 130728
• Main Authors: Aggarwal, Ranjana, Sharma, Shilpa, Hooda, Mona, Sanz, Dionisia, Claramunt, Rosa M., Twamley, Brendan, Rozas, Isabel
• Format: Article
• Language: English
• Subjects: 4-Amino-[1,2,4]triazole-3-thiols; 7-Aroyl-6-methyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines; Heteronuclear 2D NMR; Regioselective synthesis; Unsymmetrical diketones; Visible-light
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2019.130728

The first visible-light mediated, simple, efficient and ecofriendly protocol for the regioselective synthesis of novel [1,2,4]triazolo[3,4-b][1,3,4]thiadiazines has been developed by the reaction of α-bromodiketones, generated in situ by the bromination of a diverse array of β-diketones with N-bromosuccinimide, with 4-amino-[1,2,4]triazole-3-thiols. The methodology does not require the presence of any additives and this reaction proceeded in the presence of EDG (OMe), EWG (Cl) and heteroarenes (thiophenyl) giving the expected products in good to excellent yields. A solvent free protocol was also established to accomplish the synthesis of target compounds but it required PTSA as a catalyst and yields are comparatively poor. The structure of the regioisomer has been confirmed unambiguously by heteronuclear 2D-NMR [(1H-13C) HMBC, (1H-15N) HMBC, (1H-13C) HMQC] spectroscopic and X-ray crystallographic studies. [Display omitted] ••Unique and novel protocol for regioselective synthesis of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine without any catalyst.•Introduction of Acyl group at 7-position of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazines with excellent regioselectivity.•Comparative study of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine synthesis under CFL and solvent free conditions.•One-pot greener reaction approach without isolation of lachrymatory α-halocarbonyl compound.•Assignment of the regioisomer by heteronuclear 2D-NMR [ HMBC, HMQC] spectroscopic and X-ray crystallographic studies.