title: Synthesis of fused 1,2,4-dithiazines and 1,2,3,5-trithiazepines.
abstract: Reacting (Z)-N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-1H-pyrazol-5-amines 5 with Et2NH and then with concd H2SO4 gives 5H-pyrazolo[3,4-e][1,2,4]dithiazine-3-carbonitriles 7 in good yields (74-85%) and 6H-pyrazolo[3,4-f][1,2,3,5]trithiazepine-4-carbonitriles 9 as minor products (0-6%). Furthermore, the 1,3-dimethylpyrazole analogue 5a was transformed into the dithiazine 7a in two discrete steps, allowing the isolation of a disulfide intermediate (Z)-2-[(diethylamino)disulfan-yl]-2-[(1H-pyrazol-5-yl)imino]acetonitrile (8a). The one-pot, two-step reaction also worked with electron-rich hydroxy- and methoxy-substituted anilines. Thermolysis of the pyrazolo[3,4-e][1,2,4]dithiazines 7 gave the ring-contracted 1H-pyrazolo[3,4-d]thiazole-5-carbonitriles 6 (94-100%). With active sulfur, 1,3-dimethyl-5H-pyrazolo[3,4-e][1,2,4]dithiazine-3-carbonitrile (7a) gave 1,3-dimethyl-6H-pyrazolo[3,4-f][1,2,3,5]trithiazepine-4-carbonitrile (9a), but on prolonged reaction times, it gave 5,7-dimethyl-5H-[1,2,3]dithiazolo[4,5-b]pyrazolo[3,4-e][1,4]thiazine (13). Finally, in the absence of acid, heating a solution of (Z)-2-[(diethylamino)disulfanyl]-2-[(1,3-dimethyl-1H-pyrazol-5-yl)imino]acetonitrile (8a) gave 4,6,10,12-tetramethyl-6H-pyrazolo[3,4-f]pyrazolo[3',4':4,5]pyrimido[6,1-d][1,2,3,5]trithiazepine-8,12b(10H)-dicarbonitrile (19) (67%).
authors.affiliation: Department of Chemistry, University of Cyprus , P.O. Box 20537, 1678 Nicosia, Cyprus.
authors.forename: Maria
authors.initials: M
authors.lastname: Koyioni
authors.forename: Maria
authors.initials: M
authors.lastname: Manoli
authors.forename: Panayiotis A
authors.initials: PA
authors.lastname: Koutentis
mesh_terms: D000097:Acetonitriles / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D013841:Thiazepines / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: C000597363:2-((diethylamino)disulfan-yl)-2-((1H-pyrazol-5-yl)imino)acetonitrile; C000597364:4,6,10,12-tetramethyl-6H-pyrazolo(3,4-f)pyrazolo(3',4'-4,5)pyrimido(6,1-d)(1,2,3,5)trithiazepine-8,12b(10H)-dicarbonitrile; D000097:Acetonitriles; D009570:Nitriles; D011720:Pyrazoles; D013841:Thiazepines