The solution reactivity of benzyne in thiophenes; Tetrahydrothiopyran-4-ols

Abstract

Part A. Benzyne was generated from diphenyliodonium-2-carboxylate at 220(DEGREES) in solutions of substituted thiophenes. The Diels-Alder reaction was found to be the major process, giving naphthalenes. Methoxy groups gave higher yields (30-54%), and methyl groups slightly lower yields (19-25%) than parent thiophene (27-29%). Halogens decreased the yields (0-18%), with the exception of 3-bromothiophene which was comparable to thiophene (26%). 2 + 2-Cycloadditions were generally observed to occur to a small extent (0.5-2.5%), but to be very relevant with bromothiophenes (9-12%), a result explained in terms of bond polarization. Benzothiophenes are formed in low yields (0.5-3%) but are very significant in that they represent the first evidence of a 2 + 3-cycloaddition to the thiophene ring. Ene and double ene reactions analogous to those reported for alkylbenzenes are significant side-reactions in methyl-thiophenes (3-20%). (alpha)-Halogens are found to give extensive C-Hal cleavage under the reaction conditions. Thienyl sulfides were formed from, and only from, halogenated thiophenes (2-10%). In thiophene, both (alpha)- and (beta)-naphthyl phenyl sulfides were formed (9 and 6% respectively), and are regarded as resulting from the 4 + 2 addition of benzyne to a thiophene-benzyne adduct formed by nucleophilic addition of the thiophene sulfur to benzyne. The reactivity of thiophene toward electrophiles interferes with benzyne formation by trapping the decomposition intermediates, as indicated by the formation of o-(2-thienyl) benzoic acid and its phenyl ester (16% total). The spectroscopic properties of diphenyliodonium-2-carboxylate were found to be more consistent with a closed structure than with the commonly shown open zwitterionic one. Part B. The reaction of trans-dibenzoylethylene with Na(,2)S or H(,2)S gave 4-phenyl-2,4,6-tribenzoyltetrahydrothiopyran-4-ol rather than the reported isomeric bis-1,2-dibenzoylethyl sulfide. In what appears to be a rather general reaction, both diastereomers of bis-1-phenyl-2-benzoyl sulfide cyclized to the same 3-benzoyl-2,4,6-triphenyltetrahydrothiopyran-4-ol upon treatment with Na(,2)S. The same cyclic compound was also formed by reaction of 1-benzoyl-2-mercapto-2-phenylethane with NH(,3). This is again at variance with a previous report, as is the fact that benzalacetophenone gave 2,4-dibenzoyl-3,5-diphenyltetrahydrothiophene in a saturated solution of sodium polysulfide in EtOH. Bis-3-ketopropyl sulfide was cyclized by Na(,2)S to the two 4-epimers of 3-acetyl-4-methyltetrahydrothiopyran-4-ol. A strong H-bond is observed in all cases between the axial OH group and the adjacent carbonyl.