Benzo thiazepine

The reaction of diketene with 2-aminobenzenethiol was reported to yield 4-methyl-l,5-benzo-thiazepin-2(3//)-one (1A),52 which exists in tautomeric equilibrium with the hydroxy form IB.53... 

In general, 1,4-oxazepines and 1,4-thiazepine derivatives are stable compounds. Many of the (di)benzo derivatives are crystalline, while some of the more flexible monocyclic derivatives may be liquids. Conjugated (benzo)thiazepine derivatives can lose sulfur on heating, forming (fused) pyridines. This aspect of their reactivity is treated in Section 13.09.5. The completely or partially reduced derivatives of the title heterocycles and the benzo analogues may adapt different conformations, which has already been discussed in Section 13.09.2. The study of the tautomerism of lactams 9 has also been mentioned in Section 13.09.2. 

As is the case with other five-membered rings condensed to 1,5-benzo-thiazepines, pyrrolo derivatives have received intensive study and several synthetic routes have appeared. Although it would be possible to obtain several pyrrolo-l,5-benzothiazepines, only two types of fusion have been reported. 

Chimirri, A., Gitto, R., Grasso, S., Montforte, A. M., Zappala, M., Annelated 1,5-Benzo thiazepines,... 

A wide variety of photoreactions have been reported in sulphur-containing compounds, with particular attention being paid to the photochemistry of thiones. Electrocyclic ring closure to the eyelobutabenzo[b]thiophenes (131) is the principal reaction observed on irradiation of the mono-substituted 1-benzo-thiepines (132). Photorearrangement of the 2-methyl-1,5-benzo-thiazepines (133) takes a different course and affords the isomeric... 

Internal standard (+)-cis-5-acetyl-2,3-dihydro-3-hydroxy-2-(p-metho3Qq)henyl)-1,5-benzo-thiazepin-4(5H)-one (acetylthiazepin) (24)... 

Substituted 1,2-benzisothiazole 1,1-dioxides form benzo-1,2-thiazepines (86) with 1-diethylaminoprop-l-yne (76H(5)95). 2,1-Benzisothiazole does not react with maleic... 

Dichloro-10-dioxo-11 -methyldi-benzo [c,f] thiazepine (1 Tianeptine... 

Intramolecular electrophilic cyclization of methyl selenoate gives only a 12% yield of benzo[/]pyrrolo[2,l- ][l,3]thiazepin-9(10H)-one 285, while cyclization of an acetate derivative under a variety of the conditions failed (Scheme 61 (1998JMC3763)). An alternate route from pyrrole ketones 286 by oxidation and TFAA induced cyclization proved to be advantageous providing a 40% yield of 285. 

Benzo[c]thieno[3,2-/][l,2]thiazepin-4(9H)-one 313 is the product obtained from acid 312 on dehydration (Scheme 67 (1997JHC1191, 1998PHA130, 1993JHC1509)). A similar transformation has been reported for the preparation of an isomeric to 313 benzo[c]thieno[3,4-/][l,2]thiazepin-10(5fJ)-one (not depicted in the Scheme). 

Syntheses of benzo[/]thieno[3,2-i7][l,4]thiazepin-9(10H)-one 323 (2001BMC1123) and thieno[3,4- 7]-[l,4]benzothiazepine 324 (Figure 5 (1999JHC659)) start from the corresponding open chain amino acids. 

A number of monocyclic and benzo-annelated examples of 1,2- and 1,3-thiazepines have been prepared but there has been little systematic study of these systems. The interesting photochemical interconversions of pyridine N-imides into 1,2- and 1,3-diazepines and of pyridine Af-oxides into 1,2- and 1,3-oxazepines regrettably lack parallels in thiazepine chemistry. There has been more interest in 1,4-thiazepines, as both rearrangement products and possible biogenetic precursors for penicillins and because of the pharmacological value of the benzo- and dibenzo-[l,4]thiazepines as antidepressants and coronary vasodilators. The only review (70ZC361) is excellent but not very recent. 

An example of the photodecomposition of a dithiin to give a stable dithiet, with elimination of ethylene, has been reported.206 A different reaction is preferred in the dithiins (261), which on irradiation, are converted to benzene derivatives (262) via the 1,4-dithiocins (263).207 The cyclic trimer of thio-acetophenone on irradiation in cyclohexane yields thioacetophenone.208 An initial carbon-sulfur bond homolysis is also responsible for the conversion, on irradiation in methanol, of a 3-cephem to two thiazoles,209 whereas a 1,2-alkyl migration followed by a further photochemically induced carbon-sulfur bond homolysis has been proposed to account for the photorearrangement of the sulfonium ylides (264) to the pyrimido-l,4-benzo[h]thiazepines (265).210 The novel photorearrangemenl of a 1,3-thiazine to a cyclopro-pathiazolidine has also been rationalized in terms of an initial carbon-sulfur... 

Actually, treating the two related ring systems in one chapter makes sense since in many cases they appear side by side in the same article or in a series of follow-up articles by the same author. There has been considerable activity concerning these two ring systems and this is certainly due to the large medicinal interest in 1,4-oxazepines and 1,4-thiazepines and their benzo derivatives. In this chapter, we have compiled the data abstracted from selected recent publications (since 1995) focusing on aspects of synthesis and reactivity as also has been the case in the previous treatments. The most important medicinal applications are mentioned at the end of the text. 

Pyrimido[5,4-/]benzo[l,4]thiazepines 105 were alkylated by the Vorbruggen reaction at the pyrimidine nitrogen. The resulting uracil derivatives 106 are inhibitors of HIV-1 reverse transcriptase (Equation 10) <1995JME2145>. 

In this case, the seven-membered ring is formed from the reaction of an electrophilic carbon atom with an electron-rich component, such as an aromatic ring to afford di- or tricyclic benzo-l,4-thiazepine derivatives. 

This technique can also be used to build up benzo condensed pyrimido[4,5-6][ 1,4]thiazines and pyrimido[4,5-6][l,4]thiazepines. 

Hiramii.su. T. tricyclic system. Synthesis, 177, 1977. 

---