Pyrrolo benzothiadiazepine 5,5-dioxide

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). 

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)). 

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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