Thiopyran 1,1-Dioxides

Sulphones of the thiopyran series continue to receive attention. The acidities of compounds (34 R = H) and (34 R = Me) have been measured the former is a stronger acid than the acyclic disulphone MeS02CH2S02Me, but a weaker acid than the keto-sulphone MeCOCH2S02Me. Several conjugated systems of types (35) and (36) have been prepared. The electronic situation in the thiopyran rings of these compounds should 

X-Ray crystallographic data have been reported for two compounds of this series/ one of each type. In both examples, the thiopyran ring is not planar but is boat-shaped the bond lengths indicate appreciable contributions from the dipolar structures, and suggest that the sulphone groups are involved in the ir-electron delocalization. 

Substitution and condensation reactions of a series of benzo- and dibenzo-thiopyran dioxides have been studied. Methylation of compounds 

A different aspect of thiopyran dioxide chemistry is reflected in the Diels-Alder addition which leads to compound (18) (see p. 525). 

Although not a sulphone, the (formally) sexivalent sulphur compound (41) is included here a new synthesis for thiabenzene oxides of this type has been reported.  

Photolysis of the diones o-RCHaCgH COCOMe (R = H or Me) in benzene-sulphur dioxide afforded the base-sensitive compound (26). 

A number of heterocyclic derivatives (27 X = S, O, or NR) and their benzologues have been synthesized in order to examine the involvement of the SOg group in the conjugation of the molecule. Investigation of their spectral and chemical properties led to the conclusion that these compounds (27) could not be considered as pseudo-azulenes, and that there was little interaction of the S—O bond with the conjugated system. 

The Diels-Alder reaction was used as a probe for aromaticity in the ketones 

CH=CHXCH=CHCO (X = O, S, SO2, or NR). Thiopyran-4-one 1,1-dioxide was the only compound to react with a diene.  

Evidence has been provided that photolysis of 2/f-thiopyran 1,1-dioxides and their benzo-derivatives does involve sulphene intermediates. Details of the synthesis of a thiabenzene oxide have appeared.  

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Hydroxy-2//-thiopyran as a pseudobase was determined by UV spectrophotometry and discussed with HMO calculations together with other heterocycles.287 Ionization constants of 2//-thiopyran 1,1-dioxides 484 (R = H R1 = Ph R2 = H, Me) were determined spectrophotometrically in H20 and MeOH at 25°C.4S8a... 

Both the sulfone-tethered enyne 426 and diene 427 undergo RCM to give 5,6-dihydro-2//-thiopyran 1,1-dioxides when treated with a second generation Grubbs mthenium catalyst 425 tagged with an ionic liquid (Scheme 136) <2005JOM(690)3577>. 

Certain thiin derivatives undergo similar transformations. The formation of the sulfonate ester (31) on irradiation of 3-phenyl-2//-thiopyran 1,1-dioxide (32) in methanol strongly supports the intermediacy of the sulfene (33). Initial formation of a sulfene has also been proposed to account for... 

Hoffmann-La Roche s (Q-6-[l-(4-carboxyphenyl)propen-2-yl]-4,4-dimethyl-7-heptyl-oxy-3,4-dihydrobenzo[2//]thiopyran-1,1-dioxide (Ro41-5253) was one of the first RAR subtype-selective antagonists reported. Ro41-5253 was originally synthesized by the Klaus group... 

Probably a general approach to 2//-thiopyran dioxides 118 is the reaction of mesyl chloride with enamino ketone 117 (Scheme 8).159... 

Ring expansion reactions are much better known and sulfolene substrates have received considerable investigation. Cyclopropanation with dichlorocarbene affords 6,6-dichloro-3-thiabicyclo[3.1.0]hexane 3,3-dioxides which may readily be ring enlarged by base or acid treatment. Base treatment, especially with LDA, cleanly affords 2//-thiopyran dioxides hydrochloric acid does likewise, but less cleanly, while hydrobromic acid treatment causes a more complex set of reactions leading to thiopyranones containing bromine in which the sulfur has been reduced. The intermediacy of thiopyrylium oxides has been invoked to rationalize the observations (Scheme 27) (81JOC4502). 

Diphenyl-4//-thiopyran (9) was oxidized to its S,S-dioxide 141g with Ru04 (82CJC574). 2,4,4,6-Tetraphenyl-4//-thiopyran-S-oxide (143) was obtained from 56 (R = Ph) with H202-Ac0H under mild conditions [92JCS(P2) 1301 ]. 

Further 4//-thiopyrans as well as 2//-analogs were reduced mainly to their corresponding tetrahydro derivatives. In addition, the hydrogenation of 4//-thiopyran-5,5-dioxides have been described. 

Thiopyran-S,5-dioxide 140c underwent hydrogenation to its tetrahy-dro derivative 159 under the same conditions as the annulated substrates 160b and 161 (83KGS1058). 

Crystal and molecular structures of 2,4,4,6-tetraphenyl-4//-thiopyran-1-oxide (143) and the corresponding 1,1-dioxide 141a were investigated to show the boat conformations of the heterocycles as well as an interesting... 

The pKa values for 3-phenyl- and 6-methyl-3-phenyl-2//-thiopyran-S,S-dioxides have been discussed in connection with the aromatic stabilization energies of their corresponding anions (91JOC4218). 

S,4aR, 9aR )-decahvdro-9a-hydroxy-4-phenylcyc ohept[Pg.1032]

Ried and Bopp76 have shown that the photolysis of 3,5-diphenyl-4H-thiopyran-4-one 1,1-dioxide (58) in chloroform very rapidly leads to a trimer, or to photoadducts with... 

CN (4iS-rrani)-4-(ethylamino)-5,6-dihydro-6-methyl-4//-thieno[2,3-( ]thiopyran-2-sulfonamide 7,7-dioxide trans-base... 

A number of fused thiopyranopyrazolopyrimidines with potential as potassium channel openers have been prepared by a three-component Hantzsch-type reaction between a ketone, an aldehyde, and an aminopyrazole. These reactions give a mixture of isomers, with and without ring junction heteroatoms (Equation 49) <2002BML1481> among the compounds of particular interest are those in which the ketone is a derivative of thiopyran or its A,A-dioxide. 

Tetrahydro-4H-thiopyran-4-one [ 1072-72-6] M 116.2, m 60-62 , 61-62 , 64-65 , 65-67 . Purified by recrystn from diisopropyl ether or pet ether and dried in air. If too impure then dissolve in Et2O, wash with aq NaHCO3, then H2O, dried (MgSO4), filtd, evapd and the residue recrystd as before. [Cardwell JCS 715 7949], The oxime can be recrystd from CHCl3-pet ether (at -20°) and has m 84-85° [Barkenbus et al. JOC 20 871 7955]. The 2,4-dinitrophenylhydrazone has m 186° (from EtOAc) [Barkenbus et al. JOC 16 232 7957]. The S-dioxide is recrystd from AcOH, m 173-174° [Fehnel and Carmack JACS 70 1813 7945]. 

The preparation of unsubstituted 2//-thiopyran (6, up to 82%) from 3-propynyl vinyl sulfide seems to be the simplest example.21,23 Similarly, homologs 101a,21 cyanides 101b,146 ketones 101c,141 and ethyl esters lOld148 were prepared in satisfactory yields. The same approach was subsequently explored for the synthesis of 15 and similar condensed systems21,43,137 (see also 5,5-dioxides in Section V,G,3). 

The preparation of thiopyrans from dihydro- and tetrahydrothiopyrans, based on elimination reactions, appears to be effective especially for the preparation of different 2//-thiopyrans and corresponding S,S-dioxides. 

Dihydrothiopyran dioxide 284 disproportionates to a mixture of 2H-thiopyran 285 and its tetrahydro derivative 286 in the presence of piperidine,300 as shown in Eq. (14). 

Dehydration procedures have led to 2//-thiopyrans. Thus unsubstituted parent heterocycle 6 was prepared by the dehydration of hydroxy derivative 287 with potassium hydrogen sulfate.20 The same procedure applied to a mixture of isomeric hydroxy 2-methyl-5,6-dihydro-2//-thiopyrans and 3,5-dihydroxy-2,4,5,6-tetrahydrothiopyran gives all the corresponding thio-pyrans.91 3-Phenylthiopyran dioxide 289 was obtained after the dehydration of hydroxy derivative 288a with phosphoric acid at elevated temperatures.300,301 The same approach was explored for the preparation of furano-2//-thiopyran 14.42... 

Dehydrochlorination with diethylaniline was explored for the preparation of 4//-thiopyran (7) and its 3-methyl and 4-isopropyl derivatives from 2,6-dichloro-l-thiacyclohexanes7,l9,24 303a (see Section III,B). Chlorosulfone 288b undergoes dehydrochlorination to 289.300 Chloro derivative 296 was similarly dehydrochlorinated with triethylamine to 4//-thiopyran sulfoxide (10).27 On the other hand, debromination of 2,3,5,6-tetrabromo derivative 297 with zinc surprisingly gives 2//-dioxide 9 instead of expected 10,46 probably due to an isomerization of 10 with ZnBr2. 

The rearrangement of dihydropyran sulfoxide 290 to 2//-thiopyran derivative 291302 was mentioned in Section IV,E. An unusual dehydrochlorination of 3-thiabicyclo[3.1.0]hexane S,5-dioxides 364 aifording 2H-... 

Thiopyran S-dioxides equilibrate with their isomers by deprotonation with sodium alkoxides according to Scheme 23, e.g., 484 4854,° and 484 486 for R = R2 = H and R = Ph.300 The equilibrium 484 485 was also observed during the flash vacuum thermolysis of 3-phenyl-2f/-thiopyran S-dioxide (289).411... 

Unsaturated ketone 545 was obtained in a 98% yield by acid hydrolysis of a mixture of isomeric 2//-thiopyran S,S-dioxides 543 and 544 generated382 as shown in Scheme 28 (see Section III,F,6). 

Thiopyran 5,5-dioxide (9) accepted several amines RR NH by addition in the presence of triethylamine to give cyclic sulfones 589a in variable yields.26 Similarly, 3-phenyl derivative 289 gave 589b with piperidine, whereas no addition took place with sodium methoxide.300... 

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