Thiopyran-4-ones

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... 

Tiifluoromethyl derivatives of tetrahydrothiopyran-4-ols result from the Michael addition of hydrosulfide to a, -unsaturated trifluoromethyl ketones <96JOC1986> and tetrahydro-thiopyran-4-ones arise from the reaction of H2S with l,5-diaryl-2-chloropenta-l,4-dien-3-ones <96PS(108)93>. 

Radical promoted reactions feature in a synthesis of 3-substituted derivatives of 2,3-dihydro- and tetrahydro- thiopyran-4-ones from the 3-methylene compounds <96SL261> and in the formation of 2-methyltetrahydroselenopyran from a selenoalkyl (phenyltelluro)formate <96JOC5754>. 

Treatment of the thiopyran-4-ones 450 with triethylphosphite gave the bisfuranothiopyran-4-ones 451 in excellent yields (Equation 123) <2000J(P1)1467>. 

Simple large scale syntheses of 4-hydroxythiocoumarin and 2-methylthiochromone from 2-mercaptobenzoic acid have been devised <00SC1193> and efficient syntheses of various simple and fused thiopyran-4-ones and 4-thiones have been achieved through the reaction of ethylene trithiocarbonate and dibenzoylacetylene (Scheme 58) <00JCS(P1)1467>. 

An interesting case of the reaction of tetramethylthiourea with DMAD has been reported by Winterfeldt. The products formed in this reaction are tetracarbomethoxythiophene (327), 2,3,5,6-tetracarbo-methoxy-4H-thiopyran-4-one (376), and an open-chain 1 2 adduct (377) (Scheme 58). 

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]. 

However, in the sulfone analogues of the thiopyrans the transannular interaction has been shown to extend to the 4-position, in that thiopyran-4-one 1,1-dioxide is electrochemi-cally reduced more readily than the sulfide (72MI22500). 

AH- Thiopyrans are directly accessible only in relatively poor yield, and then only by condensation of a suitable 1,5-dicarbonyl compound with sulfide (690PP21). As has been described earlier, this particular reaction is bedevilled with the problem of disproportionation to tetrahydrothiopyrans and thiopyrylium compounds. Thiopyran-4-ones may be prepared in a related manner by addition of sulfur dichloride to divinyl ketones, followed by base treatment (76MI22500). 

Few carbonyl-containing sulfur heterocycles have been studied. Cyclo-pentadienones (277) have been obtained by irradiation of thiopyran-4-ones (278), possibly via the thiirans (279).230 A cyclic sulfenate (280) has again... 

The cycloaddition of a variety of sulfur heterocycles to alkenes has also been reported. Dibromomaleic anhydride undergoes [ 2 + 2] cycloaddition to thiophen295 and to benzo[b]thiophen.296 The photoaddition of benzo-[(>]thiophen 1,1-dioxides to alkenes also affords cyclobutane derivatives.297 Of particular interest is the addition of 3-acetoxybenzo[6]thiophen (350) to cyclohexene to give the adduct (351), which on treatment with base, undergoes a retro-aldol ring opening to benzo[6]thiepinone (352).298 A mixture of stereoisomeric cyclobutane derivatives were obtained on irradiation of 2,6-diphenyl-4//-thiopyran-4-one 1,1-dioxide in cyclohexene.299 The [ 2 + 2] cycloaddition of sulfolen to maleic anhydride and to maleimide has been reported.300... 

The synthetic approach reported in Scheme 50 has also been applied to the synthesis of 6a, 7-dihydro-6//[l]benzothiopyrano[3,4-c][l,5] benzothiazepine (162) starting from 5 and 3-phenylmethylene-4//-1 -benzo-thiopyran-4-one (161) (Scheme 52) (81MI1 820MR133 83MI1). >H-NMR investigations proved that the phenyl group at C-7 exists in a quasi-equatorial position, analogous to that in the isosteric benzopyrano derivatives. 

An analog of the (6S)-methylketosulfone towards Trusopt , 5,6 dihydro-(6S)-pro-pyl-4H-thieno[2,3fc]thiopyran-4-one 7,7-dioxide ( ketosulfone , Figure 13.28), the precursor to the carbonic anhydrase inhibitor L-683393 (Merck), could be reduced to the trans-hydroxysulfone 5,6 dihydro-(4S)-hydroxy-(6S)-propyl-4H-thieno[2,3F] thiopyran 7,7-dioxide by whole cells of the yeast Rhodotorula rubra MY 2169 from the Merck collection (Lorraine, 1996). Low water-solubility limited the optimum substrate concentration to 2 g L, as organic solvents added to increase solubility resulted in lower rates, which at 0.04 g (g dew)-1 h 1 were not high to start with. Diastereomeric excess ranged from 89 to 94% d.e., and decreased with increasing conversion. 

Ward, D. E. Gai, Y. Lai, Y. A general method for the synthesis of 3-substituted tetrahydro-and 2,3-dihydro-4H-thiopyran-4-ones. Synlett 1996, 261-262. 

The ketones derived from thiopyrans are 2//-thiopyran-2-one 25 and 47/-thiopyran-4-one 26 and the benzologues are 2//-1 -benzothiopyran-2-one or thiocoumarin 27, 4//-l-benzothiopyran-4-one (thiochromone) 28, and 9//-thiox-anthen-9-one or simply thioxanth-9-one 29. The trivial names dihydrothiocoumarin and thiochroman-4-one are used for the partially reduced derivatives. l//-2-Benzothiopyran-l-one 30 is usually known as isothiocoumarin. The 2- and 3- aryl derivatives of 10, 28, and 31 are generally referred to as the thioflavonoids. 

Amino-4//-thiopyran-4-one HF/6-31G, HF/6-31G", B3LYP/6-31G" Rotation about C-N bond, geometry 2001JST(535)257... 

Figure 10 Bond lengths (pm) for thiopyranothiopyrandione, tetrahydrothiopyranothiopyrandione and 4H-thiopyran-4-one.

Figure 33 Selected 1H NMR data for substituted thiopyran-4-ones.

The 4-keto function of 3-ethoxycarbonyltetrahydrothiopyran-4-one resonates at 5 205.2 with the ester CO at 5170.8 <1999SL735> and the 4-CO group 2,2-dimethyltetrahydrothiopyran-4-one appears at 5208.9 <2005HCA1922>. The exomethylene C atoms resonate at 5121.2 and 139.0 in the thiopyran-4-ones 203 and 204, respectively <1996SL261>. 

Figure 43 Selected 13C NMR data for some thiopyran-4-ones and corresponding thiopyran-4-thiones.

Thiopyran-4-one fragments by way of a retro Diels-Alder (rDA) reaction followed by loss of CO. An alternative decomposition involves initial loss of CO which leads to the thiophene radical cation (Scheme 13) . 

Infrared stretching frequencies for a range of 2-aryl-6-phenyl-47/-thiopyran-4 -ones, -thiones, and oximes and some related 1-oxides and 1,1-dioxides have been reported (Table 14) <1993PS(81)101>. 

Aromaticity indices for 4/7-thiopyran, thiopyran-4-one, and the related imine and methylene compounds are listed in Table 18 <1997JST(412)115>. 

Although methyl 4-oxotetrahydrothiopyran-3-carboxylate and the corresponding 2,3-dihydro-4//-thiopyran-4-one exist as a mixture of keto and enol forms in solution, the 2,3-dihydro sulfoxide is present only as the ketone. However, the sulfone and the tetrahydro sulfoxide and sulfone are present exclusively in the enolic form. The picture is further complicated in the solid state, where the dihydro compound and its sulfoxide exist exclusively as the keto structure but the sulfone is found as the enol (Table 27) <1986J(P2)1887>. The related 2-esters of tetrahydrothiopyran-3-one 268 exist as a ca. 1 2 mixture of keto and enol <1981T2633>. 

Protected 5,6-dihydro-477-thiopyran-4-one is lithiated at the 2-position allowing the introduction of a 2-SnMe3 function to give compound 312. Sequential reactions with propenoyl chloride and H2S yield the thiopyrano[3,2-4]-thiopyran system (Scheme 53) <1998EJO 989>. 

The 3-methylene derivatives of both 2,3-dihydro- and tetrahydro- 4/7-thiopyran-4-ones undergo a radical-promoted addition of alkyl and aryl halides producing 3-substituted thiopyran l-ones (Equations 52 and 53) <1996SL261>. 

Sulfones derived from tetrahydrothiopyran-4-ones are dehydrogenated to the corresponding thiopyran-4-one 1,1-dioxides by treatment with I2 in DMSO-H2SC>4 the reaction is particularly efficient when aryl groups, with the exception of furyl, are present at the 2- and 6-positions (Equation 93). For the formation of 4//-thiopyran 1,1-dioxide from the tetrahydro precursor a higher yielding three-step sequence (Scheme 100) is preferred <1995JOC1665>. 

The reduction of benzo- and naphtho-thiopyran-4-ones to thiopyrans has been accomplished in high yield by hydrogenation under pressure over M0S3 <1995JHC687>. 

Two sequential thio-Claisen condensations convert dialkyl ketones into thiopyran-4-ones in a rapid, high-yielding process. Initial reaction with an aromatic dithioester produces an a, 3-unsaturated ketone which, after alkylation at sulfur, undergoes reaction with a second dithioester and cyclization to the substituted thiopyranone follows (Scheme 200) <1993JOC3042>. 

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