Pyrazolo 1,2,4-thiadiazines

The first synthesis of pyrazolo[5,l-c]-l,2,4-thiadiazines 116 and pyrazolo[3,4-c]-l,2-thiazines 118 was reported by Aiello and co-workers <76JHC615>. Compound 115 was heated five degrees above its melting point to afford the novel ring system 116. However, compound 117 gave compound 118 when treated with triethylamine. 

In all the reported agrochemical applications a sulfur heterocycle is used. The 2,2-dioxo-pyrazolo[3,4-c][l,2,5]thiadiazines <90MI 713-01) and the 5,6-dipyridyl[l,2,5]thiadiazolo[3,4-6]pyr-azine (183) <84BRP2122492> are fungicidal. The 2,2-dioxopyrazolo[3,4-c][l,2,6]thiadiazines are herbicides <80USP4182623). 

In a related reaction, isopropylsulfamoyl chloride (123) reacts with the enamino esters 32 and 38 to give the sulfonyl analogues of ureas, e.g., 124. Basic ring closure leads then to a benzo[h]thieno[3,4-e]-2,l,3-thiadiazine 2,2-dioxide (125) and a pyrazolo [3,4-e]-2,l, 3-thiadiazine 2,2-dioxide (126), respectively86 (Scheme 30). Similarly, chlorosulfonyi isocyanate (127)87 affords with several enamino esters (after saponification and ring closure... 

A recently developed related sequence is shown in Scheme 5 <87CPB156>. The structure of the final product was found to be independent of the nature of R (R = Et, Ph, NEtz, OEt, SMe) but to be strongly influenced by the nature of R . The involvement of 1,3,4-thiadiazine intermediates was demonstrated by NMR spectroscopy and, in a few cases, by isolation. Synthesis of the previously inaccessible pyrazolo[l,5-a]pyridine-2-thiols was achieved following this route, by initially protecting the thiol as, for example, the 2-cyanoethylthio group <90CPB2662>. 

In the base-induced conversion of pyridinium salts (199) to pyrazolo[l,5-a]pyridines, 4,4a-di-hydropyrido[l,2-t ][l,3,4]thiadiazine intermediates (200) could be identified by H NMR, but were not isolable. Their subsequent oxidation may afford 127t antiaromatic systems (201) which upon disrotatory cyclization to tricyclic thiiranes (202), followed by desulfurization or acyl migration, gave differently substituted pyrazolo[l,5-a]pyridines, (203) and (204), respectively (Scheme 14) <85BCJ1432,84H(22)2237>. A similar desulfurization reaction of this ring system has also been reported <73CPB2146>. 

Intramolecular ring-closure of 6-(thiosemicarbazido)uracils (368) to pyrimido-thiadiazines (369) is achieved in 32—75% yield by oxidation with Af-chloro- or N-bromo-succinimide. On heating the thiadiazines, sulphur is extruded and pyrazolo-pyrimidines (370) are formed (Scheme 142). ... 

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