Thiochroman-4-ones reactions

The photochemical behavior of a number of substituted derivatives of thiochroman-4-one 1-oxides has been examined by Still and coworkers192-194. These authors also report that rearrangement to cyclic sulfenates, with subsequent reaction by homolysis of the S—O bond, appears to be a particularly favorable process. For example, ultraviolet irradiation of a solution of 8-methylthiochroman-4-one 1-oxide (133) in benzene for 24h afforded a single crystalline product which was assigned the disulfide structure 134 (equation 54). More recently, Kobayashi and Mutai195 have also suggested a sulfoxide-sulfenate rearrangement for the photochemical conversion of 2,5-diphenyl-l,4-dithiin 1-oxide (135) to the 1,3-dithiole derivatives 136 and 137 (equation 55). 

Thiochroman-4-ones result from the Pd-catalysed reaction of iodothiophenols with allenes and carbon monoxide <99JOC9646> and various thioflavonoids are accessible from acetoquinone via derived chalcones <99JOC359>. 

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... 

Scheme 3 demonstrates similar reactions for thiochroman-4-one 1,1-dioxide (available from hydrogen peroxide oxidation of thiochroman 4-one).49... 

Ring expansion of thiochroman-4-ones to 5-oxo-2,3,4,5-tetrahydro-1,4-benzothiazepines is accomplished by the Schmidt reaction, cf. Eq. (10).64... 

Thiochroman-4-ones fragment on treatment with dimethylsulfox-onium methylide [Eq. (14)].86 When R3 = H, both 40 and 41 are produced at 50° whereas only 40 is obtained at room temperature the process is believed to involve 42. In a mechanistically similar reaction, 3-inethylthiochroman-4-one yields 3,4,5,()-tetrahydro-3,5,5-trimethyl-3-[o-(methylthio)benzoyl]-2//-l-benzotliiocin-6-one (43).87... 

Photochemical reactions of thiochroman-4-one give mainly polymeric products,88 but irradiation of the corresponding sulfoxides89 (44) and sulfones90 ( 45) forms disulfides and pinacols [Eqs. (15) and (16)]. 

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... 

Thiochroman-4-one 1-oxide also fragments by a rDA reaction though now with the loss of ethene to afford a putative ketene sulfine 227. It is likely that a second fragmentation pathway of the molecular ion operates to afford the base peak, mlz 136 which subsequently eliminates CO to give mlz 108 (28%) rather than the direct loss of an oxygen atom from 227 (Scheme 16) <2002CH400>. 

The enantiomers of thiochroman 1-oxide have been obtained by oxidation of thiochroman in the presence of (R,R)-l,2-diphenylethane-l,2-diol (DPED) or L-diethyl tartrate. In the case of the enantioselective oxidation of thiochroman-4-one, (R,R)-DPED and (V,V)-DPED were used as the chiral inducers <2002CH400>. Fligh yields of both (—)-(R)-thiochroman 1-oxide and (—)-(R)-thiochroman-4-one 1-oxide and with enantioselectivities of 98% and 96%, respectively result from the reaction of H202 with the heterocycles when significant amounts of chloroperox-idase are used as catalyst <1998CH246>. 

A base-promoted cleavage of the hetero ring of the 4-oxo-3,4-dihydro-2/7-thiochromenium salt 299 results in the formation of an ethylsulfanylaryl vinyl ketone, while reaction with thiourea produces the thiochroman-4-one (Scheme 45) <1998T5599>. 

Thiochroman-3,4-diones react with various diamines to create the thiopyrano[c]pyrazine ring system, and reaction with />-anisaldehyde and NH4OAC gives a thiopyrano[c]imidazole. The base-catalyzed condensation with dibenzyl ketone yields a red [Amax = 495nm, = 8.4 X 103moldm 3cm 1] cyclopenta[c][l]-benzothiopyran-2-one 386 which gives a dibenzo[A/]thiopyran on reaction with DMAD (Scheme 101) <1994T7865>. 

Reaction of thiochroman-3,4-diones with NaBH4 affords a mixture of the as- and trans- 3,4-diols and two keto alcohols result from reaction with MeMgl. Attempts to separate the latter mixture by preferential dehydration of the thiochroman-4-ol gave unchanged 3-hydroxythiochromanA-one, but no 4-methylenethiochroman-3-one was detected. Instead, a spiro-linked adduct arising from a hetero Diels-Alder cycloaddition between two molecules of the expected dehydration product was isolated (Scheme 102) <1994T7865>. 

Optically pure (+)-(i )-3-phenylsulfanyl-l,3-diarylpropan-l-ones are readily available by the enantioselective Michael addition of thiophenols to chalcones. After reduction, acidic dehydration of the racemic alcohol affords a mixture of the racemic cis- and trans- 2,4-disubstituted thiochromans (Scheme 164). A detailed consideration of the stereochemical outcome of the reaction with unsymmetrically substituted diaryl derivatives suggests the involvement of a [1,3] PhS shift via a four-membered sulfonium intermediate and this is backed up by theoretical calculations <2003T3621>. 

Thiochroman-4-ones are converted to thiochromones by conversion to their trifropropylsilyl enol ethers and dehydrogenation with ceric ammonium nitrate. It is proposed that the reaction proceeds via a radical cation which undergoes desilylation. (l-Elimination from the cation generated by single-electron transfer completes the sequence (Scheme 206) <1995TL3985>. 

The alkylidene malononitrile derived from chroman-4-one adds to /ra .v-P-nitrostyrcne to give (5, /< )-2-[3-(2-nitro-l-phcnylcthyl)chroman-4-ylidene]malononitrile under dihydroquinine catalysis (Scheme 39) <06OBC63> and a similar reaction of both the chromanone and thiochroman-4-one dicyanoalkenes with a,P-unsaturated aldehydes proceeds with even better ee <06CC1563>. 

On treatment with a Lewis acid, a-(benzotriazolyl)methyl thioethers generate a-ihionium ions which can be trapped by styrenes in a [4 + 2] cationic cycloaddition to produce thiochromans 38. The reaction proceeds in high yield and allows good variation in substitution pattern. The stereoselectivity is variable, though often only one isomer is obtained and seldom more than two <01JOC5595>. 

The base-catalysed reaction of 6-aryl-3-carbomcthoxy-4-methylthio-2//-pyran-2-one 39 with tetrahydrothiopyran-4-onc affords the isothiochroman 40. Similarly, reaction with thiochroman-4-one gives a benzo[c]thiochromene. The carbanion derived from the thiopytanone attacks the pyranone at the electrophilic 6-position with concomitant ring cleavage and loss of CO2. Cyclisation involves nucleophilic attack at the 4-carbonyl function (Scheme 44) <01JOC5333>. 

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