Benzo benzothiazepines

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. 

Formylation of 5H-benzo[/]pyrrolo[l,2-d][l,4]diazepin-6(7H)-one 180 pyrrole ring with POCI3/DMF is known (Scheme 36, Section 3.1.1.1 (1992BMCL1639)). Formyation of pyrrolo-benzothiazepine can be accomplished using POCI3/ PhNMeCHO (Scheme 76 (2004JMC143)). The monoaldehyde 375 (R = H) is... 

Benzo[e]thieno[3,2- ]thiepin-10(5Ef)-one 388 can be smoothly reduced with sodium borohydride to the corresponding alcohol, which forms the chloro substituted compound under standard treatment with thionyl chloride (1991CPB2564). Dihydro derivatives of pyrrolo-benzothiazepine 377 have been reported starting from ketone 373 by a carbonyl reduction, bromination and amination sequence (Scheme 76, Section 5.1.1 (1998JMC3763, 2002JMC344, 2004JMC143)). 

In a similar fashion 2-aminothiophenol can be reacted with 1,3-bis carbon electrophiles to give various types of 1,5-benzothiazepine. Thus the benzo analogues of (408) and (409), e.g. (410), are prepared by parallel routes, reaction with 1,3-diphenylpropynone gives (411), reaction with /3-ketoesters gives products of type (412), reaction with diketene gives (413), and the reaction with methyl 3-arylglycidates gave (414) which could not be dehydrated. 

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. 

The synthetic approach reported in Scheme 50 has also been applied to the synthesis of 6a, 7-dihydro-6//[l]benzothiopyrano[3,4-c][l,5] benzothiazepine (162) starting from 5 and 3-phenylmethylene-4//-1 -benzo-thiopyran-4-one (161) (Scheme 52) (81MI1 820MR133 83MI1). >H-NMR investigations proved that the phenyl group at C-7 exists in a quasi-equatorial position, analogous to that in the isosteric benzopyrano derivatives. 

The photocycloaddition reactions of 3-aryl-1,2-benzisothiazole with alkenes is regio- and stereospecific and yields 2,3-dihydro-1,4-benzothiazepines (Scheme 10) <8IT3377>. When electron-rich alkynes are used, then substituted 3,4-benzo-2,6-thiazabicyclo[3.2.3]hepta-3,6-dienes are the major product (Scheme 10) <83JOCi275>. 

Reaction of the chalcone analogues of dehydroacetic acid with o-aminothiophenol provided a convenient route to 1,5-benzothiazepines <05T6642>. Bis ring fused thiazepines have continued to attract attention including the dihydropyrido[3,4-6]benzo[/][l,4]thiazepin-1-one 195, which was prepared from 193 via 194, and the dione 199 from 196 via 197 and 198<05TL2919>. 

Reactions. - Photoreactions. 3-Phenyl-1,2-benzisothiazoles (21 X=H, Cl) and electron-rich alkynes (ethoxyacetylene, ethoxy-propyne, and diethylaminopropyne) undergo photocycloaddition to give substituted 3>4-benzo-2,6-thiazabieyclo[3 2.0Jhepta-3,6-dienes (22 R=H,CHj,R =0Et R=NEt2,R =CH, respectively), and smaller amounts of other products. 1,4-Benzothiazepine... 

A gallium(III) triflate-catalyzed [4 + 3] cydoaddition of 1,3-diarylpropanones and OPD has been developed for the synthesis of 2,4-disubstituted-3H-benzo[b][l,4]diazepines using ethanol as a green solvent at room temperature. The product was collected by filtration and the catalyst was directly used for the next cycle. The process was repeated 10 times and the catalyst was found to maintain consistent activity [104,105]. Several approaches to benzodiazepinone and benzothiazepine ring systems xmder solvent-free conditions and using other greener techniques such as MW, US or solid acid catalysis, organocatalysis, and so on are also known [106,107]. 

---