Thiophens, from alkynes

Thiophenes from alkynes 48 The alkyne is dissolved in methanol, ethanol, or acetone and the solution is adjusted to pH 9-10 by adding N-sodium hydroxide solution in the proportion 9 1. Hydrogen sulfide is then led in at 20-80° until a sample of the mixture no longer shows acetylene bands in its UV spectrum (4-20 h). The mixture is then treated with water, and the product is taken up in ether, dried over sodium sulfate, freed from solvent, and distilled or recrystallized. Thus were prepared 2,5-dimethylthiophene, b.p. 134-136° (70%), 2,5-dlethyl-thiophene, b.p. 180-181° (65%), and 2,5-diphenylthiophene, m.p. 152-153° (85%). 

A brief review of the cotrimerization of alkynes with nitriles to give pyridines has appeared. Pyridine itself is produced from C2H2 and HCN in benzene at 110 C/60 min under 23 bar pressure. The borabenzene complex (54) as the catalyst gives 103 turnovers. The catalytic formation of substituted thiophenes from alkynes and elemental sulfur in the presence of [CPC0L2] catalysts is also mentioned. Analogous rhodium complexes [Cp RhL2] also catalyze the formation of pyridines. 

The direct combination of selenium and acetylene provides the most convenient source of selenophene (76JHC1319). Lesser amounts of many other compounds are formed concurrently and include 2- and 3-alkylselenophenes, benzo[6]selenophene and isomeric selenoloselenophenes (76CS(10)159). The commercial availability of thiophene makes comparable reactions of little interest for the obtention of the parent heterocycle in the laboratory. However, the reaction of substituted acetylenes with morpholinyl disulfide is of some synthetic value. The process, which appears to entail the initial formation of thionitroxyl radicals, converts phenylacetylene into a 3 1 mixture of 2,4- and 2,5-diphenylthiophene, methyl propiolate into dimethyl thiophene-2,5-dicarboxylate, and ethyl phenylpropiolate into diethyl 3,4-diphenylthiophene-2,5-dicarboxylate (Scheme 83a) (77TL3413). Dimethyl thiophene-2,4-dicarboxylate is obtained from methyl propiolate by treatment with dimethyl sulfoxide and thionyl chloride (Scheme 83b) (66CB1558). The rhodium carbonyl catalyzed carbonylation of alkynes in alcohols provides 5-alkoxy-2(5//)-furanones (Scheme 83c) (81CL993). The inclusion of ethylene provides 5-ethyl-2(5//)-furanones instead (82NKK242). The nickel acetate catalyzed addition of r-butyl isocyanide to alkynes provides access to 2-aminopyrroles (Scheme 83d) (70S593). 

Sonogashira reactions of both a-halothiophenes [117] and P-halothiophenes [118] proceed smoothly even for fairly complicated molecules as illustrated by the transformation of brotizolam (134) to alkyne 135 [119]. Interestingly, 3,4-bis(trimethylsilyl)thiophene (137), derived from the intermolecular cyclization of 4-phenylthiazole (136) and bis(trimethylsilyl)acetylene, underwent consecutive iodination and Sonogashira reaction to make 3,4-bisalkynylthiophenes [120], Therefore, a regiospecific mono-i/wo-iodination of 137 gave iodothiophene 138, which was coupled with phenylacetylene to afford alkynylthiophene 139. A second iodination and a Sonogashira reaction then provided the unsymmetrically substituted 3,4-bisalkynylthiophene 140. 

Compound 99 reacts with alkynes to generate thieno[2,3-f]thiopyranthiones and thieno[3,2-f]thiopyranthiones. The ratio of isomers is typically 1 1. The reaction proceeds via a cycloaddition reaction and an unprecedented molecular rearrangement (Equation 35) <20050L791>. Thieno[2,3-f]- and [3,2-f]thiopyrans can be prepared from thiophene-2-carbaldehyde in a multistep synthesis that leads to the thienothiopyrans in excellent yields <1999J(P1)2639>. 

Incidentally, a 1,3-cycloaddition of benzyne to thiophene has been postulated (81CC124) to account for the small, but reproducible amount of benzo[ >]thiophene formed in this reaction (Scheme 79). Reactive alkynes have been successfully used as dienophiles to cycloadd with thiophenes benzene derivatives are obtained after extrusion of sulfur from the adduct (Scheme 80) (72TL605, 72TL1909, 73CB674). 

Evidence has been presented591 that favours the involvement of thiirane intermediates in the formation of ( , )-divinyl sulfides (455) from the reaction of thiocarbonyl ylides (454) with activated alkynes, while the reaction of l-alkynyl-2,3-epithio alcohols (456) with a catalytic amount of Hg(II) has been shown to afford592 substituted thiophenes (457) (see Scheme 117). 

Although obtained only in low yields upon troublesome chromatography of product mixtures that contained much polymeric material, the tricyclic benzofuran and benzothiophene lactones (61) were shown to be isolable products from attempted Diels-Alder reactions on the allene ester precursors shown in Equation (32) <85JCS(Pl)747>. Although it was noted in the case of the two thiophenes that the tricyclics appeared to be forming from a precursor (presumably a dihydro form) on the chromatographic column, it was not possible to convert the crude suspected cycloaddition adducts directly into the aromatics by dehydrogenation with DDQ. Complex mixtures were obtained instead. It is possible that the actual dienophiles in these Diels-Alder reactions are alkynes. In a related study, the bis-lactone (62) was also obtained (Equation (33)) <86H(24)88l>. 

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