1.4- Benzothiazepines 2,3,4,5-tetrahydro

Ring expansion of thiochroman-4-ones to 5-oxo-2,3,4,5-tetrahydro-1,4-benzothiazepines is accomplished by the Schmidt reaction, cf. Eq. (10).64... 

The reduced pyrido[4,3-g][l,4]benzothiazepine 133 has been detected by HPLC as a novel metabolite in some human urine samples. It arises from Pictet-Spengler condensation of 5-S-cysteinyldopa with formaldehyde. This chemistry also underpins a facile synthesis of the 2,3,4,5-tetrahydro[l,4]benzothiazepine 134 via reaction of formaldehyde with a cysteinylcatechol . 

The 2,3-benzoxazepin-l-one system (436) is prepared by the reaction of benzonitrile oxide with the benzopyranone (435) (80JCS(P1)846). The tetrahydro-3,2-benzothiazepine 3,3-dioxide (438) was prepared from (437) by intramolecular sulfonamidomethylation (76CC470). 

Amination of 2,2-disubstituted thioindoxyls followed by treatment with base results in ring opening to the sulfenamide (451). This can either cyclize to a benzisothiazole (when R=Me) or to a tetrahydro-l,2-benzothiazepin-5-one (when R = aryl), as shown in Scheme 153 (80JCS(Pi)2830). 3-Methoxybenzo[6]thiophene undergoes ring expansion to 3-chlorothiochromone on treatment with dichlorocarbene (70AHC(11)177). 

Dimethyl-2,3,4,10-tetrahydro-l//-pyrrolo[3,4-c][l,5]benzothiazepin-1-ones (10) were prepared by a reaction between 2-aminothiophenol (5) and 3-arylmethylene-5,5-dimethyltetramic acids (9) in 81-%% yields (Scheme 4) (84YZ1004). 

Condensation of 5 with methyl tetrahydro-4-oxothiophene-3-carboxyl-ate (64) led to the formation of the ring-closed enamino thiolactone 65. Chemical transformation of 65 with sodium hydride/methyl iodide gave 67, whereas 4H, 10//-thieno[3,4-c][l,5]benzothiazepin-10-one (66) was obtained upon aromatization of the thiophene ring by the action of sulfuryl chloride (Scheme 18) (80JOC497). 

The Ulmann reaction of 4-bromo-3-(2-aminophenyl)thiomethyl-3-pyra-zolin-5-ones (74) in a nonpolar solvent such as xylene and in the presence of a small amount of pyridine afforded 1,2,4,10-tetrahydro-3//-pyrazolo[3,4-c][l,5]benzothiazepin-3-ones (75). However, when the same reaction was... 

There have been a number of reports on the preparation and chemistry of fused thiazepine derivatives. Toda el al. have noted the stereocontrolled synthesis of tetrahydro-1,5-benzothiazepines, trans- and c/s-263, on reaction of o-aminothiophenol with the epoxide 262 in the presence of magnesium perchlorate the overall yield of 263 was 94% and the trans.cis ratio was 24 76 and the factors controlling the stereochemical outcome were discussed [01H1451 ]. 

Die Reaktion von 2-Amino-thiophenolmit Benzyliden-malonsaure-diethylester ergibt ein chro-matographisch trennbares Gemisch aus 3-Ethoxycarbonyl-4-oxo-2-phenyI-2,3,4,5-tetrahydro-1,5-benzothiazepin (38%) und 2-Phenyl-l,3-benzothiazol (30%)258 ... 

Two research groups have published methods for the synthesis of the benzothiazepine class of molecule this year. Ishibashi et al. have prepared a 1,2,3,5-tetrahydro-4,1-benzothiazepine via intramolecular Friede1-Crafts reaction of the ortho-chloro intermediate (82) or acid-catalysed cyclization of the sulphoxide... 

A soln. of 7-chlorO 2,3-dihydrO 5-phenyl-l,4-benzothiazepine in tetrahydrofuran added slowly at room temp, to a stirred suspension of LiAlH4in tetrahydrofuran, and refluxed 2 hrs. 7-chloro-2,3,4,5-tetrahydro-5-phenyl-l,4-benzothiazepine. Y 88%. F. e. s. L. H. Sternbach et al., J. Org. Chem. 30, 2812 (1965). 

Scheme 4.15 Regio and stereocontrolled synthesis of substituted 2,3,4,5-tetrahydro-l, 5-benzothiazepines through domino S. reaction.

Base-promoted ring-enlargement of the sulphimide (57) to tetrahydro-1,2-benzothiazepine-5-one (59) has been confirmed to proceed via incipient formation of the sulphenamide (58) as an intermediate. However, similar treatment of the aminosulphonium salt (60) affords the ring-contracted isothiazole (61). ... 

Cl8Hi9BrN2S CH O, 11-Phenyl-3,4,6,11-tetrahydro-2H-pyrimido[2,1-c](2,4)benzothiazepine hydrobromide methanolate, 43B, 492 Cl8H20CIF3N2S, Triflupromazine, 40B, 357 C18H20N2S2, Bis(2,3-dimethylbenzothiazoline), 39B, 281 Cl8H20N4S, 4-Ethyl-5-ethylimino-2-phenyl-3-phenylimino-1,2,4-thiadi-azolidine, 46B, 414... 

---