Benzothiazepines rearrangement

Pyrrolo[2,l-c][l,4]benzothiazepine 297 (R=Ph) has been prepared by an intramolecular nucleophilic displacement of acetyl derivative 296 (Scheme 64 (1992H51)). The same compound and its aryl (R = Ar (1992H51)) and carboethoxy or cyano (R = C(30Et or CN (1990H1291)) analogs can also be obtained by a Pummerer rearrangement-cyclization of sulfinyl precursor 298. 

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). 

The oxime (60) (Scheme 11) undergoes the Beckmann rearrangement to 3.5-dihydro-4,l-benzothiazepin-2(l//)-one.247... 

The reaction of oxime 385 with polyphosphoric acid results in ring expansion via Beckmann rearrangement leading to the fused 1,4-benzothiazepine derivative 386 (Scheme 207) <1997JHC921, CHEC-III(13.09.10.2)286>. 

Several [ 1,2,4]triazolobenzothiadiazocin-l 1-ones 174 were prepared via ring expansion of [l,2,4]triazolo[3,2-A -[2,4]benzothiazepin-10(5//)-ones in presence of sodium azide. The intermediate aryl isocyanate 173, formed as a result of Curtius rearrangement, was isolated and characterized by elemental analysis, IR, H NMR, and mass spectroscopies (Scheme 45 <2002PS2303>). 

Chloro-5-formyl-l,3-dimethyluracil reacts, furthermore, with 2-aminothiophenole in the presence of l,5-diazabicyclo-[4,3,0]non-5-ene (DBN) via a Smiles rearrangement to afford pyrimido[4,5-6][l, 4]benzothi-azine, while, without base, a simple condensation-substitution step leads to the formation of pyrimido[4,5- ]-[ 1,5]benzothiazepines (85UP1) (Scheme 104). 

Sulphonium methanides, e.g. (167), which are prepared by the reaction of thiachroman-4-ones with dimethyl diazomalonate, rearranged in the presence of base to give 1-benzothiepins, e.g. (169). This reaction parallels the recent conversion of sulphonyUmines into 1,2-benzothiazepines (e.g., see ref. 104). 

Thiazepines. - The full report has now appeared on the preparation of 1,2-benzothiazepines by the rearrangement of thiochroman-4-one N-tosylsulphimides [cf. the preparation of 1-benzothiepins (169)]. 

Thiochromanone-2-acetate (79), on treatment with NaNj in presence of cone. H2SO4 underwent a Schmidt rearrangement to give 2,3-dihydro-l,4-benzothiazepin-4(5/0-one-2-acetate (80) in 55-... 

Alkylation of 1,4-benzothiazepin-5(4//)-one (82) with methyl iodide/silver tetrafluoroborate gave the sulfonium salt, which rearranged to l-methoxy-4-(methylthio)isoquinoline (83) on heating in acetonitrile (Scheme 27) <88CB2147>. 

Triazole Derivatives. Triazole derivatives are known to possess tumor necrosis factor-a (TNF-a) production inhibitor activity. The synthesis of triazole derivatives can be achieved from alkynes or diynes by a tandem cascade reaction involving 1,3-dipolar cycloaddition, anionic cyclization and sigmatropic rearrangement on reaction with sodium azide. Some of the benzoyl triazole derivatives were considered to be potent local anaesthetics and are comparable with Lidocaine. The triazoles can also be prepared from benzoyl acetylenes,triazoloquina-zoline derivatives, 2-trifluoromethyl chromones, aliphatic alkynes, 2-nitroazobenzenes, ring opening of [ 1,2,4]triazolo [5,1-c] [2,4]benzothiazepin-10 (5//)-one, alkenyl esters and dendrimers. A number of these reactions are outlined in eqs 44 8. 

An interesting rearrangement was observed in the Thorpe-Ziegler reaction of 19. Aimed at the synthesis of a benzothiazepine, treatment of 19 with sodium hydride resulted in the formation of intermediate 20. While protonation of 20 would have provided the desired benzothiazepine, instead, intramolecular attack by the enolate resulted in the formation of 21. Subsequent expulsion of sulfur and aromatization provided the 2-morpholinoquinoline 22 in good yield. 

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