1.4- Thiazepine 1,1-dioxide

In a substrate-dependent, palladium-catalyzed domino N-benzylation/ intramolecular direct arylation process, tosylamides 133 and 2-bromobenzyl bromides 134 reacted to form dibenzo-l,2-thiazepine dioxides 135 exclusively, or gave mixtures that also contained 6,7-dihydro-5H-dibenzo[c,e] azepines 136 (14JOC10899). 

A pair of sulfonamides 137 underwent a palladium-catalyzed intramolecular double C(sp )-H oxidative coupling reaction to form optically pure dibenzo-l,2-thiazepine dioxides 138 (14JOC8010). 

A set of exocyclic methylene benzo-l,2-thiazepine dioxides underwent 1,3-dipolar cycloaddition reactions with benzonitrile oxide to give isoxazo-line Spiro adducts 139 in a regioselective, and for specific dipolarophiles, diastereoselective manner (14AJC381). Guided by X-ray crystallographic analysis, a pair of benzo-l,2-thiazepine dioxides 140 was designed, prepared, and found to be picomolar inhibitors of HIV-1 protease (14T2894). 

Substituted 1,2-benzisothiazole 1,1-dioxides form benzo-1,2-thiazepines (86) with 1-diethylaminoprop-l-yne (76H(5)95). 2,1-Benzisothiazole does not react with maleic... 

The formation of thiazine systems by ring contractions of 2,3-dihydro-l,4-thiazepine 303 (Equation 108) <1971CC698>, 2,3>4,7-tetrahydro-l,4,5-thiadiazepin-3-one 3, 3 -dioxide 304 (Equation 109) <1972T2307>, 2,3-dihy-drobenzo[ ][l,4]thiazepin-4(57/)-ones 305 and 306 (Scheme 78) <1992LA403>, and 6,7-dihydro-1,4-thiazepin-5(477)-one. -oxide 307 (Equation 110) <1999H(51)1639> has been published. 

As with 1,4-oxazepines the Schmidt reaction of cyclic ketones and the Beckmann rearrangement of their oximes can be applied to the synthesis of monocyclic 1,4-thiazepines, 1,4- and 1,5-benzothiazepines and their 1-oxides and 1,1-dioxides (75CJC276). 

Thioxanthen-9-one 10,10-dioxides with sodamide undergo ring expansion to dibenzo [/>,/]-[l,4]thiazepin-l 1-one 5,5-dioxides (75JHC1211). 

There has been a modest interest in the chemistry of these systems over the past decade. In this chapter, the 1,2-oxazepines and 1,2-thiazepines are grouped together due to their sparseness in the literature. There is a general review of these systems that appeared in CHEC-II(1996) <1996CHEC-II(9)183>. The parent systems 1 and 2, respectively, are shown below however, most of the known compounds are based on their reduced derivatives. Oxidized forms of the 1,2-thiazepine system are also treated, in particular derivatives of 1,2-thiazepine 1,1-dioxide 3. 

Chemical Name 6,ll-Dihydro-6-methyl-U-[(laH,5aH-tropan-3a-yl)-oxy]dibenzo[c,f][l,2]thiazepine 5,5-dioxide... 

Dihydro-10,10-dioxo-l l-methyldibenzo[c,f][l,2]thiazepin-5-yloxy)tropane and the hydrogen maleate salt thereof. (This name was given by the authors of U. S. Patent No 3 700 633. It corresponds to endo-6,11-dihydro-6-methyl-ll-[(8-methyl-6-azabicyclo[3.2.1]oct-3-yl)oxy]dibenzo[c,f] [l,2]thiazepine 5,5-dioxide and 6,ll-dihydro-6-methyl-ll-(8-methyl-8-azabicyclo[3.2.1]octan-3a-yloxy)dibenzo[cf][l,2]thiazepin-5,5-dioxide). 

Compound 425, prepared from pyrrole according to a similar method described in the literature <1975MI43>, was hydrolyzed to give the corresponding acid 426, which was cyclized by treatment with PPA at 80 °C (Equation 102) <2000TL6605>. These sequential reactions produced two products. X-ray crystal analysis has shown that the major one is 2-methyl-3,4-dihydro-2//-pyrrolo[2,3y ][l,2]thiazepin-5(6//)-one 1,1-dioxide 427, and the minor one is 2-methyl-3,4-dihydro-27/-pyrrolo[3,4 ][l,2]thiazepin-5(7//)-one 1,1-dioxide 428. No amount of the 2-sulfonyl derivative 429 was detected. 

Flash vacuum pyrolysis (FVP) of 2-arylethanesulphonyl azides leads to good yields of -sultams, such as 4 -methyl-3,4-dihydro-2,l-benzothiazine-2,2-dioxide 108 (equation 190)248, provided the pyrolysis temperature is no higher than 300 °C and is carried out in Freon 113. More recently, using similar techniques, Abramovitch and coworkers have synthesized unusual seven-membered benzo-sultams249 from 3-arylpro-panesulphonyl azides and 2-aryloxyethanesulphonyl azides, as illustrated in equation 191 for the formation of the e-sultam 2,3,4,5-tetrahydro[c]-l,2-thiazepine 1,1-dioxide (109)... 

Intramolecular nitrene cyclization from thermolysis of 2-azidosulfonylbenzophenone affords the dibenzo[c/][l,2]thiazepine 5,5-dioxide system (47) in low yield, together with other products. The 2-methyl and 8-methyl analogues of (47) are prepared similarly, also in low yields <78JOCi2i8>. 

Initial 1,3-dipolar cycloaddition of the mesoionic compound (87) to (86), followed by extrusion of carbon dioxide, leads to the 1,2-thiazepine derivatives (88) and (89) in low yields (Equation (13)) <85MI 907-01>. 

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