Bromination and Diazo-Coupling of Pyridinethiones; Microwave Assisted Synthesis of Isothiazolopyridine, Pyridothiazine and Pyridothiazepines

Abstract

Isothiazolopyridines, pyridothiazines and pyridothiazepines are important compounds that possess valuable biological activities. This paper reports on the synthesis of these compounds using both conventional chemical methods and modern microwave techniques. 3-Bromo-6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-carboxamide, 5-arylazo-6-hydroxy-4-methyl-2-thioxo-1,2-dihydropyridine-3-carboxamides, 3,5-bis-arylazo-6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-caboxamide, 4-methyl-2,3,6,7-tetra-hydroisothiazolo[5,4-b]-pyridine-3,6-dione, 2,2'-(methylene-bis-(sulfanediyl))bis(4-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide), 2-hydroxy-5-methyl-4H-pyrido[3,2-e][1,3]-thiazine-4,7(8H)-dione and 2-arylmethylene-8-hydroxy-6-methyl-2,3,4,5-tetrahydropyrido-[3,2-f][1,4]thiazepine-3,5-diones have been prepared from 6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-carboxamide. Some of these compounds were prepared using microwave-assisted reaction conditions, that provided higher yields in shorter times than the conventional methods.

Microwave Assisted Synthesis of Some New Thiazolopyrimidine, Thiazolodipyrimidine and Thiazolopyrimidothiazolopyrimidine Derivatives with Potential Antioxidant and Antimicrobial Activity

“…Our research group has recently [ 22 , 23 , 24 , 25 ] been interested in performing synthesis of some heterocyclic compounds under environmentally friendly, time saving microwave-assisted conditions. Accordingly, we re-synthesized the previously described compounds 1a – d , 3a – d , 5a – d , and 7a – c under microwave conditions, aiming to increase reaction yields and reduce the reaction times.…”

Emerging green synthetic routes for thiazole and its derivatives: Current perspectives

“…Youssef et al [84] reported the reaction between 3-amino-3thioxopropanamide and ethyl acetoacetate to obtain 6-hydroxy-4methyl-2-thioxo-2,3-dihydropyridine-3-carboxamide followed by the Saini et al [85] developed an eco-friendly and catalyst-free method for synthesizing benzo[d]thiazol-2(3H)-ylidene benzamides by the one-pot reaction. They utilized o-haloanilines, aroyl isothiocyanates, and acrylates as starting materials, with Et 3 N as the base and water as a green solvent.…”

“…T A B L E 3 Outline for green solvent-mediated synthesis of thiazole derivatives. [77] 2 -Ethanol 80 12 h 82 [78] 3 Nanochitosan Ethanol Reflux 2.5-4.5 h 75-97 [79] 4 Sulfamic acid Water Reflux 3-6 h 64-89 [80] 5 -Ethanol Reflux 6 h 90-95 [81] 6 F e 3 O 4 @SiO 2 @KIT-6 Water RT 1-2 h 85-97 [82] 7 -PEG-600 RT 4 h 87 [83] 8 K 3 [Fe(CN) 6 ] Ethanol and KOH RT 2 h 80 [84] 9 -Water 90 20 h 65-85 [85] 10 CTAB Glycerol 40 1-3 h 82-96 [86] 11 Fe 3 O 4 @vitamin B 1 Water 80 30-45 min 79-93 [87] 12 -PEG-400 100 2-3.5 h 87-96 [88] 13 GAA PEG-300 70-75 1-1.5 h 82-96 [89] 14 -Water 135 35 min 50-89 [90] 15 Pyridine Water 150 20 h 40-84 [91] 16 -Water 60 1-6 h 65-90 [92] 17 -Glycerin RT 1-2.5 h 87-92 [93] 18 Ca/4-MePy-IL@ZY-Fe 2 O 3 and TCCA Ethanol 80 25 min 85-92 [94] 19 γ-Fe 2 O 3 @HAp@CPTMS@AT@Cu(ӀI) Ethanol RT 20-28 min 88-95 [95] 20 -Ethanol and water RT 60 min 90-98 [96] 21 Citric acid Ethanol and water Reflux 15-40 min 0-96 [97] 22 -Water Reflux 6 h 84-93 [98] 23 ZnO NP Ethanol/neat RT 2-8 min 90-99 [99] 24 PTSA PEG-400 80 2 h 79-95 [100] 25 Fe 2 O 3 NP Water RT 10-32 min 77-90 [101] 26 2-Hydroxypropyl-β-cyclodextrin Water and acetone 50 6 h 41-70 [102] 27 GAA PEG-400 70-75 1-5 h 80-95 [103] 28 Triton X-100 Water RT 5-10 min 85-98 [104] Abbreviations: CTAB, cetyl trimethyl ammonium bromide; GAA, glacial acetic acid; PEG, polyethylene glycol; PTSA, p-toluenesulfonic acid; TCCA, trichloroisocyanuric acid.…”

Synthesis and Characterization of Thiazepine/Benzothiazepine Derivatives Through Intramolecular C‐2 Ring Expansion Pathway

“…They can be easily obtained as five‐ or six‐membered analogs. Thiazepines and benzothiazepines are important structural scaffolds of seven‐membered heterocycles and contain sulfur and nitrogen heteroatoms, due to which they possess a broad spectrum of pharmacological activities . The distinctive feature of the thiazepine core is that it is active against different families of targets, making them interesting heterocyclic ring systems 9b .…”