Dithieno‐ and thienobenzothiazines

Abstract

The synthesis of some isomeric dithienothiazine systems has been described. These thiazines were made by an Ullman type cyclization reaction, starting with the appropriate dithienyl‐sulphides. During the ring closure reaction hydrogen chloride was eliminated from the β‐chloro‐propionyl side chain resulting in the formation of the acryloylthiazines 5, 7 and 11. This reaction was studied under various conditions and some of the byproducts were identified. The general applicability of the reaction was demonstrated by the synthesis of two isomeric thienobenzothiazines 14 and 16. Addition of N‐methylpiperazine afforded the (N‐methylpiperazinyl)propionylthienothiazines, which were isolated as their hydrochloride salts. The latter compounds were tested for neuroleptic and antidepressive properties, but were shown to be devoid of activity. This lack of activity is discussed in terms of the hampered formation of the radicalcations, as was shown by the electrochemical oxidation of these compounds. Efforts to reduce the carbonyl function to give the propyl chain failed, due to an elimination of the side chain.

Dithieno[1,4]thiazines and Bis[1]benzothieno[1,4]thiazines—Organometallic Synthesis and Functionalization of Electron Density Enriched Congeners of Phenothiazine

“…Similarly, thieno [1,4]benzothiazines have been synthesized. An analogous procedure also provided the first synthesis of the functionalized syn-syn regioisomer 2a-a [32]. As for the syn-anti isomer 2d-a, the final anellation mode is predetermined by the position of the nitro group.…”

“…In addition, by this methodology three further N-acryl dithieno [1,4]thiazines 2a-b, 2d-b and 2dc were synthesized, which were further functionalized by a Michael addition of N-methylpiperazine ( Figure 2). However, reducing the carbonyl group was not successful, so that according to Grol the intended pharmacological activity could not be achieved [32]. An analogous procedure also provided the first synthesis of the functionalized syn-syn regioisomer 2a-a [32].…”

“…However, reducing the carbonyl group was not successful, so that according to Grol the intended pharmacological activity could not be achieved [32]. An analogous procedure also provided the first synthesis of the functionalized syn-syn regioisomer 2a-a [32]. As for the syn-anti isomer 2d-a, the final anellation mode is predetermined by the position of the nitro group.…”

“…Syn-syn and anti-anti dithieno[1,4]thiazines 2a-b, 2d-b and 2d-c synthesized by Michael addition[32].…”