Thiochromans preparation

Scheme 6.144 Thiochromanes prepared from the 121-catalyzed enantioselective tandem Michael-Knoevenagel reaction between 2-mercaptobenzaldehydes and diethyl methylenemalonates. The product configurations were not determined.

An intramolecular hetero-Diels-Alder reaction of o-thiobenzoquinone methides, generated in situ from bis(2-formyl-phenyl)disulfide and alkenols in the presence of iodine, has been used to prepare thiochromans (Scheme 22) <2003TL6513>. 

Thiochromans (1 R = H2) result from disproportionation of 2H- -benzothiopyrans (4) and also from thio-Claisen rearrangements of phenyl allyl sulfides. The first pathway was discovered by Tilak and Vaidya,24 who attempted to prepare one benzothiopyran (15) by cyclizing the /S-ketosulfide (14) in polyphosphoric acid (PPA), but obtained the thiochroman (16) and a benzothiopyrylium salt as in Eq. (5). This reaction involves25,26 an acid-promoted disproportionation... 

A variety of thiochromans possess biological activity. For example, 7-sulfamoylthiochroman 1,1-dioxides are effective diuretics 130-134 thiochroman-6-acetic acids possess antiinflammatory, antipyretic, and analgesic activity 135-136 phenethylamines from the Mannich reaction on thiochroman-4-ones are a-sympatliolytic137 and antidepressant 138 4-substituted aminothiochromans are active as antihypertensives, as antidepressants, and as agents against angina pains 139-142 3,3-dibromo-6-halothiochroman-4-one S-oxides exhibit antitumor characteristics 143 substituted 4-phenylthiochroman-4-ols have been prepared... 

Thiochrom-4-ones have also been prepared by the amine-promoted elimination of hydrogen halide from 3-haIothiochroman-4-ones,188 by the Puinmerer reaction on thiochroman-4-one S-oxides [Eq. (20)],98 from a ring expansion of activated benz[6]thiophenes [Eq. (21)],189 by the reaction of o-mercaptoaryl alkyl ketones with ethyl esters of... 

Dehydration of thiochroman-4-ols, generally with potassium hydrogen sulfate, is the most convenient preparation of 2/f-l-benzothio-pyrans,266,267 [Eq. (29)]. Further methods to derivatives of 4 involve the Vilsmeier formylation of thiochroman-4-one to (8-chlorovinyl aldehydes... 

The 1-benzothiopyrylium salts are best prepared from the easily accessible thiochroman-4-one [Eq. (35)].6,51,52,302-304 The common dehydrating agents include potassium hydrogen sulfate8 and phosphorus pentoxide51,302-304while sulfuryl chloride/perchloric acid51,302-304 and trityl perchlorate 6 have been useful as hydride extractors. Another method involves the cyclization of /1-ketosulfides (e.g., 81) or j8-arylthio-acroleins (82) with perchloric acid [Eq. (36)].305,306... 

Thiochromans and thiochroman 1,1-dioxides are readily prepared from the corresponding thiochroman-4-one by catalytic hydrogenation in acetic acid/perchloric acid or via the Wolff-Kishner and Clemensen methods. Thermal decomposition of 21 produced thiochroman in 85% yield. Thiochroman and isothiochroman occur in petroleum, and the completely saturated analog of the former (1-thiadecalin) was obtained from propenyl 1-cyclohexenyl ketones in the presence of hydrogen sulfide and sodium acetate in ethanol. 

The 1-benzothiopyrylium salts are best prepared from the easily accessible thiochroman-4-one [Eq. (35)].6,51,52.302-304 common... 

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)]. 

Synthesis of tetramethylchroman analogue (64) was similar to that of thiochroman (63) except that the key ethynyl intermediate (72) was prepared from acetophenone (70). Formation of a phosphoester from the lithium enolate salt of (70) was followed by elimination of the phosphate group to give acetylene (72). Coupling of (72) with ethyl 4-iodobenzoate proceeded as with (71) and gave (64). 

Geranyl phenyl sulphides or sulphones, Me2C=CHCH2CMe=CHCHXY (33 X = H Y = SPh or SOjPh), cyclized to cyclocitral derivatives under acid conditions, whereas the corresponding dithioacetal (33 X = Y = SPh) gives the thiochroman (34). The novel heterocycles (35) have been prepared by standard methods from the corresponding tellurochromanones. The critical step in the synthesis of the latter consists of reduction of the appropriate diaryl ditelluride with borohydride and subsequent reaction with 3-chloropropionic acid under carefully controlled conditions. 

Further details of the rearrangement-ring contraction of the ketone ArSCMeaCHaCOMe, which gives benzothiophens with polyphosphoric acid, have been reported. Additional analogues of thiochroman clathrate hosts have been prepared in order to test their inclusion properties. The thermolysis of 2,2-dimethyl-l-(toluene-/j-sulphonylimino)thiochroman has been investigated. In benzene it gives A -[2-(3-methylbut-3-enyl)phenylthio]-iV-(2 -methyI-thiochroman-2 -ylmethyl)toluene-p-sulphonamide. 

---