Thiopyrans intermediates

No addition products with S-nucleophiles have yet been reported except for the reaction of 2-methylthio-4,6-diphenylthiopyrylium iodide with sodium thiophenolate involving a 2//-thiopyran intermediate (86S916). 

Diels-Alder cycloaddition reactions of enaminothiones153 155 or enamino thioesters154,156,157 as nucleophilic dienes with electrophilic dienophiles R4CH = CHX lead to appropriate 4-amino-2,3-dihydro-2//-thiopyran intermediates 110, which easily eliminate amines R2R3NH to give the corresponding 2//-thiopyrans 111. 

Pentasubstituted tricyclic 4//-thiopyran 48 ( = 2, R = Me) was also prepared by the reduction of the corresponding thiopyrylium salt 227b with LiAlH4.269 The reduction with zinc proceeds via a dimeric 4//-thiopyran intermediate.272 Ion 229 (R = Ph, n = 2) was reduced with zinc in hydrochloric acid to a mixture of 2//-thiopyran 230 (R = Ph, n = 2), 4//-thio-pyran 232, and the corresponding perhydrothiopyran.100... 

The cyclization of saturated 1,5-pentanediones with H2S and HCl is one of the most exploited reactions for the synthesis of thiopyrylium salts. These are generally formed together with the corresponding dihydro- or, more frequently, tetrahydro-thiopyrans, as a result of the disproportionation of 4//-thiopyran intermediates (Scheme I). The reaction is frequently performed in AcOH, which appears to facilitate the disproportionation processes (76KFZ80 81 KGS 1604). 

Halo-l-benzothiepins 4 can be synthesized by the treatment of 7a-halobenzo[fe]cyclopropa-[e]thiopyran-7-ols 2 with hydrogen bromide and subsequent hydrogen bromide elimination from the 2,4-dihalo-2,3-dihydro-l-benzothiepins 3 by l,5-diazabicyclo[4.3.0]non-5-ene (DBN).9 The alcohols 2 are prepared by Grignard reaction of the corresponding 7a-halobenzo[ft]cyclopropa[c]thiopyran-7-ones l18 and are used for the synthesis without purification. The intermediate dihalodihydro-l-benzothiepins 3 are not isolated due to their thermal lability related and more stable compounds are described in Section 2.1.2.1. 

Treatment of 2,7-di-/ert-butylthiepin (1) either directly with bromine at — 78 °C, or with pyridinium bromide perbromide at room temperature, gives the thiophene compound 2. In contrast, bromination with bromine-1,4-dioxane complex or pyridinium bromide perbromide in the presence of acetic acid leads to the thiopyran derivative 3.87 To account for these results a homothiopyrylium ion has been proposed as a common intermediate, formed by electrophilic bromination at C4 in the first step. 

Diphenyl-4/7-thiopyran (9) was prepared by application of the known two-step procedure involving the 2,6-dichloro intermediate from the corresponding bis-dimethylacetal (82CJC574). 

Diels-Alder cycloadditions of enaminothiones with electrophilic die-nophiles (83AHC145, section III,G) have been widely used for the preparation of various thiopyran derivatives. In addition to expected 2H-thiopyrans, 4//-isomers were trapped as intermediates or even as final products. Nitroolefines (90T1951), olefinic carbonyl derivatives [80JH405 85JOC1545 92JCS(P1)2603] allenedicarboxylic esters... 

Two principle approaches from thiopyrylium salts to thiopyrans accompanied by C-substitution have been found, e.g., the one-step additions of C-nucleophiles or the two-step procedures involving primary conversions of the salts to nucleophilic intermediates followed by attacks with appropriate electrophiles. 

Two examples involving as key intermediates the corresponding thio- or selenopyran anions are mentioned in Section IV,A,2, e.g., 48e — 60 + 56 (R = /-Bu) and 54d + 55d -> 59 (85CL1119 90ACS524). A deuteriode-protonation of 2,6-diphenyl-2//-thiopyran (87) to 4-deuterio-2,6-diphenyl-4//-thiopyran (51) took place after the initial reaction with BuLi-THF at... 

In this section, compounds are described that differ from 6 by the replacement of one or more methylene groups by heteroatoms or heteroatom groups. Quantum-chemical calculations on such species have not been carried out. However, on the basis of the results discussed in the above sections and depicted in Schemes 6.42 and 6.64, there is no doubt that all reactive intermediates under consideration are genuine allenes. After all, the tether across the allene subunit is larger in the corresponding compounds in this section than in 3<52-lH-pyridine (179), 3<52-pyran (180) and 3<52-thiopyran (299) owing to the absence of a double bond. Thus, compared with these models, the allene structures in this section suffer from less strain and are hence stabilized relative to their zwitterionic states. 

Subsequent studies on thioamide pyrans with application of the competitive reactions method contribute to our understanding of the mechanisms of heterocyclizations with cyanothioacetamide 114 (89ZOR1331). 2,6-Diaminothiopyrans 115, on heating in benzene, open their thiopyran ring reversibly forming intermediate 116, which can eliminate cyanothioacetamide 114 or malononitrile 27a with formation of UNs 30 or 117, respectively. The direction of the subsequent reaction with... 

The first synthesis starting with glutaric dialdehydes and involving intermediates 42 succeeded in preparing unsubstituted 4//-thiopyran (7)19,24 as well as alkylated derivatives.7,90,91... 

The first approach to 2//-thiopyrans from acetylenes resembles the synthesis of oxa analogs 92a,b. In contrast to the latter, intermediates like 100 have been directly used as starting compounds. 

Hexasubstituted 4//-thiopyrans 250 were easily prepared from 3,5-dimethyl-2,4,6-triphenylthiopyrylium tetrafluoroborate with phenyl-and p-tolyllithium via thermal decomposition of corresponding thiabenzene intermediates.277... 

The elimination of the RS02 group may also be used in the synthesis of 6-arylthio-2//-thiopyrans 299a-c via intermediates 298a-c elimination takes place by means of bases.304... 

The agents used for oxidative aromatization of 2/f-thiopyrans were trityl perchlorate,42-155,156 tetrafluoroborate,267 and iodide.267 Thus 3,5-diphen-yl-2//-thiopyran (222) was found to aromatize either on its own to thiopyrylium salts 396 or by S-methylation to l-methyl-3,5-diphenylthiabenzene (398) via intermediate 397,267 as shown in Scheme 18. 

The desulfurization of 2-substituted 4-methyl-2//-thiopyrans, accompanied by dimerization of primary intermediates, is caused by ZnHg. This approach was explored for the synthesis of polyenes,183-186 including / -carotene (Eq. 24a). 

Azido-2f/-pyran derivatives 212a (R = H) eliminates nitrogen on standing to give azirine 579 (Eq. 39). When R = Ph, intermediate 579 was too labile to be trapped.254 Analogous azido-2//-thiopyrans 212b decomposed only at elevated temperature to provide thiophene and pyridine derivatives,254 as shown in Scheme 35. 

Thiopyrans have, in general, been less thoroughly investigated. The isothiochroman-4-one (245) on irradiation in basic methanol is converted to the indanone (246)199 a pathway involving electrocyclic ring opening and the formation of the intermediate (247) may be implicated. An alternative... 

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