1,2,5-Benzothiadiazepine 1,1-dioxides

The reactions of 2-benzoylbenzenesulfonyl chlorides (533) with amidines, guanidine or S-alkylthioureas give benzenesulfenylamidines (534 R = Ph, NH2 or SMe) which cyclize on heating in xylene in the presence of acid to give 1,2,4-benzothiadiazepine 1,1-dioxides (535) (68JHC719). 

In MeCN, anodic oxidation of < -toluenesulfonamides yields 3-methyl-4,5-dihydro-1,2,4-benzothiadiazepine-1,1-dioxides, probably by an initial Ritter reaction followed by ring closure [138]. 

A number of thiadiazepine and benzothiadiazepine dioxides have been obtained using amino-exchange reactions (i.e., from [6 -I- l]-atom fragments). Dilution techniques were found to be necessary in the preparation of compound 233 from tetramethylenediamine and sulfamide (78CB1915) the product claimed to be 233 by other authors (76IJC(B)766) seems to be a polymeric or open-chain material. 

Benzothiadiazepine dioxides (351) have been obtained by reaction of o-bromomethyl-iV-(n-hexyl)benzenesulphonamide with alkyl nitriles in the... 

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)). 

The 1,2,5-benzothiadiazepine 1,1-dioxide (545) and its 3,4-dihydro analogue have been prepared by the reaction of 2-nitrobenzenesulfonyl chloride with w-aminoacetophenone to give (544) followed by reductive cyclization (79JHC835). 

The benzothiadiazepine 1-oxides (550), formed by the reaction of the diaryl sulfoxides (549) with hydrazoic acid, rearrange on treatment with sodium hydroxide to give (551) (72CB757). The benzothiadiazine 1,1-dioxide (552) also undergoes base-induced ring expansion to give (553) (71JOC2968). 

The pyrrole[2,l- /][l,2,5]benzothiadiazepin-7(677)-one 5,5-dioxide 103 upon reaction with ethyl iodide in the presence of anhydrous potassium carbonate gives the iV-ethyl derivative 104 (Scheme 22) <1997FES375>. 

Benzothiadiazepine 3,3-dioxides 234 have been prepared following the same pattern from a,a -diamino-o-xylenes and sulfamides (74M114 76IJC(B)766), or by reaction of a,a -dibromo-o-xylene with sulfamides ([4 + 3]), and a,a -diamino-o-xylenes with sulfuryl chloride ([6-1- 1]) (74M114). 

This interesting transformation is represented by the oxidative desulfurization of 7,8-dimethoxy-l,2,3,4-tetrahydro-3,2,4-benzothiadiazepine 3,3-dioxide (183) to... 

Controlled potential oxidation of o-toluenesulfonamides (180) at a platinum anode in acetonitrile using a divid cell provided 4,5-dihydro-l,2,4-benzothiadiazepine 1,1-dioxides (182) in generally good yields via (181) (Scheme 33). The scope and limitation of this one-step heterocyclization... 

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). 

Reactions with ketene and sulfur dioxide 2,l,5-Benzothiadiazepin-4-one 2-oxides... 

Bianchi et have prepared a new class of heterocycles—the 1,2-dihydro-5//-2,l,4,5-benzothiatriazepine-2,2-dioxides (348), by diazotization and intramolecular coupling of ethyl-A (o-aminophenylsulphamoyl) acetate (347). Cycliz-ation of the corresponding acid gave a 2,1,5-benzothiadiazepin derivative (349). 

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