Thiepine 2,7-dihydro

According to the Hantzsch-Widman system, the seven-membered unsaturated hcterocyclc with one sulfur atom is named thiepin (1). The three different benzothiepins are assigned by the position of sulfur 1-benzothiepin (2), 2-benzothiepin (3) and 3-benzothiepin (4). Of the four possible dibenzothiepins only dibenzo[6,r/]thiepin (5) and dibenzo[A,/]thiepin (6) are of importance for synthesis, while the other two isomers, which contain unfavorable o-quinoid structures, exist mainly as the stable dihydro compounds, i.c. 5,7-dihydrodibenzo[c,t ]thiepin (7) and 6,1 l-dihydrodibenzo[6,c ]thiepin (8). Benzannulation over all double bonds results in tri-benzo[6,(7,/]thiepin (9). 

The Pummerer reaction has successfully been applied to the synthesis of some novel thiepins (13) starting from the 4,5-dihydro derivatives 11 and proceeding via the sulfoxide 12 u I2). 

Cyclization of l,6-dibromo-2,4-dienes with sulfide ion results in the formation of dihydro-1/f-thiepins, which were characterised in turn as their sulfones <00H(53)897>. 

Benzo[e]thieno[3,2- ]thiepin-10(5Ef)-one 388 can be smoothly reduced with sodium borohydride to the corresponding alcohol, which forms the chloro substituted compound under standard treatment with thionyl chloride (1991CPB2564). Dihydro derivatives of pyrrolo-benzothiazepine 377 have been reported starting from ketone 373 by a carbonyl reduction, bromination and amination sequence (Scheme 76, Section 5.1.1 (1998JMC3763, 2002JMC344, 2004JMC143)). 

Theoretical studies on thiepine-thianorcaradiene (benzene sulfide) valence isomerization have been of continuous interest. In addition, hypervalency of sulfur in thiepines has been theoretically studied. The interest in fused systems, such as dibenzo[/)/]thiepines, toward pharmacologically active compounds is growing. In the last decade, many reports on the synthesis, characterization, and utilization of enantiomerically pure dihydro- and tetrahydrothiepines and thiepanes have appeared. 

Racemic l,ll-dimethyl-5,7-dihydrodibenzo[c,< ]thiepine A-oxide 24 and A,A-dioxide 25 and 10,12-dihydro-4/7,6/7-[2]benzothiepino[6,5,4- i/][2]benzothiepine 30, based on bridged biphenyl structures, were resolved into enantiomers by chromatography on swollen microcrystalline TAC <2000HCA479>. The first-eluted enantiomers were assigned to have the (A)-configuration by comparison of the experimental CD spectra with spectra calculated by the CNDO/S method (see also Sections 13.03.3.1 and 13.03.3.3). 

The sulfur atom of (—)-(i )-3,9-bis[4-(dodecyloxy)benzoyloxy]-5,7-dihydro-l,lTdimethyldibenzo[c/]thiepine 80 was... 

Carbon-carbon bond formation by Friedel-Crafts reactions was a versatile procedure for benzo- and dibenzothie-pines. Some new methods to synthesize thiepine rings by Friedel-Crafts-type reactions have been reported. Carbon-sulfur bond formation has been used for dihydro-, tetrahydrothiepines, and thiepanes. New cyclization methods involving carbon-sulfur and carbon-carbon bond formation have been added. 

The useful ring closure providing benzothiepines involved the formation of both S-C bonds by reaction of diaryllithium or divinyllithium organometallic species with S2+ equivalents. Another method for formation of both S-C bonds toward dihydro- and tetrahydrothiepines and thiepines is the nucleophilic substitution reaction of S2 equivalents (Na2S or Li2S) with dibromides. Synthesis of thiepines by the related stepwise formation of two S-C bonds was also described. 

The enantiomerically pure bridged biphenyl, (—)-(R)-3,9-bis[4-(dodecyloxy)benzoyloxy]-5,7-dihydro-l,ll-dimethyl-dibenzo[c,( ]thiepine 80, was prepared from enantiomerically pure diiodide 197 (Scheme 25) <1998JOC3895>. The synthesis of the precursor 197 was based on Ullmann coupling reaction of the chiral oxazoline (-)-(S)-195. 

Recently, enantiomerically pure dihydro- and tetrahydrothiepines and thiepanes have been of more interest. In this section, the syntheses of chiral thiepines by various routes described in Sections 13.03.9 and 13.03.10 are summarized. 

Chemical Name Dibenzo[b,f]thiepin-2-acetic acid, 10,11-dihydro-a-methyl-10-oxo-... 

Preparation of 2-(10,ll-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid [i.e., Zaltoprofen] ... 

Dihydro-dibenzo[c.e]thiepine und 10.11-Dihydro-dibenzo-[b.f]thiepine... 

Die absolute Konfiguration mehrerer optisch aktiv vorliegender Dihydro-oxepine und -thiepine konnte mit Hilfe von ORD- und CD-Kurven bestimmt werden 38>13°). 

Dihydro-1-benzothiepin is converted into 2,3-dihydro-l-benzo-thiepin 1-oxide with sulfuryl chloride in 79% yield or with sodium periodate in 77% yield (equation 562) [5%]. 

The reaction of the complex (157) with divinyl sulphone gave the dihydro-thiepin 1,1-dioxide (159) instead of the expected triene (158) the latter is probably the primary product, and is converted into (159) by an intramolecular Diels-Alder reaction and subsequent isomerizations/° ... 

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