Unequivocal synthesis of 2,3,6‐triazaphenothiazine and two new tetraazaphenothiazine heterocycles

Abstract

This paper describes the unequivocal synthesis of three new heterocycles: 2, 3, 6‐triazaphenothiazine (7) and 2, 3, 6, 9‐tetraazaphenothiazine (18), both parents of the respective ring systems and the 6, 8‐dihydro‐7, 9‐di‐oxo derivative of 2, 3, 6, 8‐tetrahydrophenothiazine (12). These compounds were obtained by base‐catalysed condensation of 4, 5‐dichloropyridazine (8) with the appropriate o‐amino‐heterocyclic thiols 9, 11, 16. In contrast, reaction of 2, 3, 5‐trichloropyrazine (20) with 4, 6‐diaminopyrimidine‐5‐thiol (21) and 2‐amino‐6‐picoline‐3‐thiol (28) gave 5‐chloro‐2, 3‐bis(diaminopyrimidinyl‐5‐thio)pyrazine (33) and 5‐chloro‐2, 3‐bis(2‐amino‐6‐picolinyl‐3‐thio)pyrazine (29), respectively. Chloropyrazine (34) and 3‐aminopyridine‐2(1H)‐thione (9) followed the latter reaction path to 2‐(3‐amino‐2‐pyridyl) pyrazinyl sulfide (35) in good yields. Structural assignments were based on their infrared, ultraviolet, nmr and mass spectra.

Synthesis and properties of diaza‐, triaza‐, and tetraazaphenothiazines

“…The reaction of the betaine 261 with trichloropyrazine 267 in DMA (with sodium hydroxide) aimed at obtaining triazaphenothiazines 268 or 269 gave unexpectedly the bis‐sulfide 270 in 82% yield. The formation of the second sulfide function proceeded more smoothly than the thiazine ring closure (Scheme ) [126].…”

“…Reaction of 3‐aminopyridine‐2(1 H )‐thione 277 with 4,5‐dichloropyridazine 278 in ethanol (with potassium hydroxide) under nitrogen atmosphere led to 2,3,6‐triazaphenothiazine 279 in 63% yield (Scheme ) [126]. Later, Baltrop and Owen repeated this reaction and questioned the previous result.…”

“…Reaction of 4,6‐diaminopyrimidine‐5‐thiol 289 with trichloropyrazine 267 in DMA did not lead to tetraazaphenothiazine 290 or 291 but unexpectedly to the bis‐sulfide 292 in high yield (93%, Scheme ) [126].…”

“…Reaction of 5‐aminouracil‐6‐thiol 299 with dichloropyridazine 278 in ethanol (with potassium hydroxide) led to 2,3,6,8‐tetraazaphenothiazine‐7,9(6 H ,8 H )‐dione 300 in 50% yield (Scheme ) [126].…”