Pyrrolo benzothiadiazepine acids

Reduction of nitro glyoxylic ester 334 with iron powder in acetic acid into pyrrolo-benzothiadiazepine 335 represents a type (i) intramolecular cyclization (Equation (39) (1996JHC2019)). 

Oxidation on the sulfur atom of pyrrolo-benzothiazepine 175 (Scheme 34, Section 2.3.1 (1994MI283)), indolo benzothiazepine (Scheme 65, Section 3.3.1.2 (1998MI139)) and pyrrolo-benzothiadiazepine (Scheme 74, Section 4.2 (1994SC2685)) proceeds smoothly with hydrogen peroxide in acetic acid or with MCPBA to afford cyclic sulfones in good yields. 

Lithium hydroxide hydrolysis of the ester of pyrrolo[l,2-l7][l,2,5]benzothia-diazepine 5,5-dioxide 346 afforded the acid, subsequently reduced with lithium aluminum hydride-aluminum chloride to alcohol 348 (Scheme 73, Section 4.2 (2006JMC5840)). Pyrrolo[l,2- 7][l,2,5]benzothiadiazepine acid 347 gives easy access to a variety of esters and amides 407, while treatment with TFAA produces fused lactam 408 (Scheme 85 (1996FES425)). 

Type (ii) cyclizations are more common. Thus, acid derivatives of pyrrolo[l,2-f>]-[l,2,5]benzothiadiazepine 5,5-dioxide 346 and 347 have been prepared from amino sulfonyl pyrrole 345 with acetal (2006JMC5840) or the semiacetal (1994JHC867) of ethyl glyoxalate or ethyl 2,2-diethoxy propionate (1996FES425) in the presence of PTSA catalyst in boiling absolute ethanol by a Pictet-Spengler type of reaction (Scheme 73). 

Pyrrolo[l,2- >]-l,2,5-benzothiadiazepine 1,1-dioxide (105) has been obtained by cyclization of the A(-formamide derivative (104), derived from l-(2-aminobenzenesulfonyl)pyrrole (103) and acetic formic anhydride, with phosphorus oxychloride via a Bischler-Napieralski reaction in 47% yield, or by iron powder-acetic acid reduction of the nitro-aldehyde derivative (106) and subsequent ring closure of the resulting aminoaldehyde intermediate in 92% yield <94JHC1033>. The reaction of (103) with ethyl glyoxylate hemiacetal via a Pictet-Spengler type condensation afforded the benzo-thiadiazepine (107) in a high yield (94%) <94JHC867> (Scheme 17). 

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