Synthesis of Fused 1,2,4-Dithiazines and 1,2,3,5-Trithiazepines

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%).