Fluorinated benzo thiophenes

Based on the same mechanistic concept, syntheses of perfluoro-benzo[ ]thiophenes and partially fluorinated indoles are described [67JCS(C)865, 67JCS(C)869, 67JCS(C)1189 68JCS(C)1225, 68TL4049]. 

Perfluorothiophenol and acetylene react at 600°C to yield tetrafluoro-benzo[ )]thiophene (89JOU201). Similarly, 2,3,4,5,6-pentafluoro-l-thionaphtholate and dimethyl acetylene dicarboxylate give fluorinated naphtho[fe]thiophenes [89JFC(43)393]. 

In 1967, two reactions that proceeded by the intramolecular cyclization mechanism and led to fluorinated benzo[Z>]thiophenes were carried out. The first is based on the reaction of the lithium salt of pentafluorothiophenol and diethyl acetylenedicarboxylic ether (67JCS(C)1225) (Scheme 148). Here the intermediate species is a carbanion. In the second process, the starting compound is a benzylidene rhodanine derivative, giving benzo[Z>]thiophene carboxylic acid 157 in alkaline media. This reaction occurs via the intermediate S-nucleophile (Scheme 149). 

Fluorinated benzo[fc]thiophene derivative 70 was synthesized in 93 % yield by the intramolecular cychzation of anodicaUy fluorinated open-chain sulfide 69 containing the 2-cyanophenyl group [41],... 

Yin B, Inagi S, Fuchigami T (2011) Electrosynthesis of fluorinated benzo[l>]thiophene derivatives. Synlett 2011 1313-1317... 

The first successful Diels-Alder addition of thiophene appears to have been with tetrafluorobenzyne (66CC143). The adduct apparently loses sulfur, resulting in the isolation of the tetrafluoronaphthalene in 40% yield (Scheme 78). Other thiophene derivatives (69T25) and fluorinated benzynes <71JCS(C)604) have been similarly reacted. Subsequently it was found (80H 14)647) that unsubstituted benzyne, generated from diphenyliodonium-2-carboxylate, could be trapped with thiophene to form naphthalene in 33% yield. The earlier failure to add thiophene to benzyne generated by other methods must have been due to intervention of side reactions. Thiophyne also has been similarly trapped to yield benzo[A]thiophene (see Section 3.14.2.2). 

Halogen Derivatives of Thiophenes and Benzo[6]thiophenes 3.15.9.6.1 Fluorine derivatives... 

Fluorination of benzo[6]thiophene in the vapor phase with cobalt trifluoride gives mainly perfluoroethylcyclohexane, formed by fission of the molecule, elimination of sulfur, and fluorination of the hydrocarbon fragment.480... 

A unique acceptor, 5,6-difluoro-2-alkyl-4,7-di(thiophen-2-yl)-2H-benzo-[d][l,2,3]triazole, i.e., FTAZ, structurally similar to the DTflBT, has distinctly different electrochemical properties from those of DTifBT. The alkylation of the central nitrogen in fluorinated benzotriazole is suggested to be carried out in polar aprotic solvents such as DMF to promote the Sn2 reaction. However, typical brominations of the alkylated FTAZ with bromine ended with low yields and a new route was thus developed. The 4 and 7 positions of fluorinated benzotriazole are first deprotonated by a non-nucleophilic base, LDA, and then quenched by trimethylsilyl chloride (TMSCl). The as-formed C Si bonds are more activated than the original C-H bonds so that the alkyl FTAZ benzotriazole can then be successfully brominated (Scheme 15.6). ... 

Brooke GM, Quasem MA (1973) Partially fluorinated heterocyclic compounds. Part XI. The reactions of lithium pentafluorobenzenethiolate with acetylenic compounds giving benzo[fe] thiophen derivatives and/or olefins. 1 Chem Soc Perkin Trans 1 429-432... 

Reaction with Organolithium Reagents. Organolithium derivatives of a variety of heteroaromatics have been fluorinated with NFSi. The direct C-H lithiation at the most reactive position of heteroarene compounds was conducted at low temperature with either t-BuLi, w-BuLi, or LDA in the presence of NFSi to provide regioselective fluorination. This way, oxazoles (eq 34), benzo[i>]thiophene-5,6-dicarbaldehyde, spiro[4,5-dihydrothieno[2,3-c]pyran-7,4 -piperidine, dibenzo-... 

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