2- Fluorobenzo thiophene

Several 3-ai"yl-2-fluorobenzo[/ ]thiophenes have been prepared by fluorination of the 2-lithio derivatives using the electrophilic fluorinating reagent AT-fluorobenzenesulfonimide (Equation 110) <2005SL247>. The yields are fair to excellent. 

The cyclization of the Pummerer rearrangement product 30 derived from o-methylsulfinyl-difluorostyrene 29 leads to 2-fluorobenzo[ ]thiophene 31 (Scheme 7) <1997CC1537>. Treatment of thiol 32 with NaH affords 2-fluoro-4,5-dihydrothiophene 33 by a cyclization <2000CC1887>. 

Very little work has been done on fluoro derivatives of thiophenes. 2-Fluorothiophene was obtained in low yield from treatment of 2-iodothiophene with arsenic trifluoride. The action of fluoroboric acid on thiophenediazonium salts was unsuccessful. It may be useful for the preparation of 4-, 5-, 6- or 7-fluorobenzo[6]thiophenes from the appropriate amines. However, these are more conveniently prepared from fluorine-substituted benzenethiols by ring-closure reactions. For example 4,5,6,7-tetrafluorobenzo[6 Jthiophene was obtained by decarboxylation of the corresponding 2,3-dicarboxylic acid (equation 99) prepared by condensation of pentafluorobenzenethiol with diethyl acetylenedicarboxylate (Section 3.15.3.4.1). 2-Fluorothiophene has been prepared from 2-thienyllithium using perchloryl fluoride, and 2-fluorobenzo[ Jthiophene from the 2-lithio derivative in a similar manner (Section 3.14.3.9.1). 

Chloro-,241,336 404 bromo-,105,112 336,422 iodo-,152- 298,334,330 and fluorobenzo[6]thiophenes 330 may be obtained in high yields from the appropriate diazonium salt by means of the usual replacement reactions. This method is particularly useful for fluoro- and iodo-... 

Carbonation of the lithium derivative of 2-methoxybenzo[6]thio-phene affords the corresponding 3-carboxylic acid.183 2-Methylbenzo-[6]thiophene-3-carboxylic acid has been obtained (45%) by carbonation of 2-benzo[6]thienylmethylmagnesium chloride (Section VI,D, 4).528 re-Butyllithium reacts selectively with the bromine atom in 3-bromo-2-fluorobenzo[b]thiophene to give a product, which on carbonation affords 2-fluorobenzo[6]thiophene-3-carboxylic acid.482 Benzo[6]thiophene-7-carboxylic acid is obtained by reduction of the corresponding thioindoxyl with amalgamated zinc and acetic acid.315 Benzo[6]thiophene-3-carboxylic acid and its 2-ethyl derivative have been prepared in high yield by treatment of the pyridinium salt of the 3-chloroacetyl derivative with alkali.132... 

Difluorobenzonitrile and methylthioglycolate cyclize to give 4-fluorobenzo[fe]thiophene [91JFC(54)104]. The reaction of trifluoromethyl-substituted 2,4-dinitrochloro- and 2,6-dinitrochlorobenzene with alkyl thi-oglycolates and amino acid esters at room temperature in the presence of triethylamine follows the same mechanistic concept to yield trifluoromethyl-substituted benzothiazole and benzimidazole derivatives [88JFC(38)327] (Scheme 25). 

Fluorobenzo[h]thiophen-2(3//)-one has been prepared via diazotization of sodium (2-amino-4-fluorophenyl)acetate followed by reaction with sodium sulphide and ring-closure. The reaction of 3-amino-2-ethoxycarbonyl-benzo [ft] thiophen with 2,5-dimethoxytetrahydrofuran gave 3-(l-pyrrolyl)-2-ethoxycarbonylbenzo [ft] thiophen, which through Curtius reaction was... 

Why was it that only the fluorobenzoic acids and the thiophenes were apparently incorporated In the case of the former, this may reflect the probability that fluorobenzoic acid is structurally the most similar of the analogs to the natural substrate. Fluorine is a fairly inert atom and isosteric with hydrogen. It is not so clear why the thiophenes should have been incorporated. 

The Ichikawa indole synthesis is the base-induced 5-endo-trig cycUzation of nrtfto-amino-p,p-difluorostyrenes 1 to 2-fluoroindoles 2 (Scheme 1, equation 1) [1-3]. The method is applicable to indolines, which can be oxidized to indoles [4, 5]. This nice chemistry exploits the inherent favorable conversion of a difluorinated sp carbon to an sp carbon, which then expels fluoride to give the aromatic indole. Ichikawa also applied this method to the preparation of 2-fluoiobenzo[fc]furans and 2-fluorobenzo[h]thiophenes [1, 2]. 

Methods for the synthesis of fluorobenzothiophenes are rare. A lithiation-fluorination sequence by treatment of benzothiophenes 57 with n-BuLi followed by fluorination with perchloryl fluoride [35], N2F2 [36], or N-fluorodibenzenesulfonimide afforded 2-fluorobenzo[h]thiophenes 58 in good yields [37]. 

Fluorobenzo[h]thiophenes 60 and 62 were synthesized from the lithiated precursors by treatment with perchloryl fluoride [35] or N-fluorodibenzenesulfonimide... 

Fluorobenzo[i ]thiophenes synthesis was also accomplished through a 5-endo-Irig cyclization. Successive reaction of p,p-difluoro-o-methylsulfinylstyrene 63 first with trifluoroacetic anhydride and triethylamine in dichloromethane and then with potassium carbonate provided 2-fluorobenzo[fc]thiophene 64 in 82 % yield [39],... 

Fluorobenzothiophene derivative 68 was prepared in 44 % yield starting from 4-(methylthio)-l-(trifluoromethyl)benzene 65 by double metallation with n-BuLi and subsequent reaction with CO2. The primary intramolecular cycUza-tion of 66 was anchimerically assisted by the carboxylate anion in ortho position and gave rise to a nucleophilic substitution of the fluorine atom by the SCH" anion. The resulting intermediate 67 aromatized after acidification into 3-fluorobenzo[b]thiophene 68 [40]. 

It is interesting to compare the band-edge band gaps of poly(2,3-dihexylthieno[3,4- ]pyrazine) (19, R = C6H13) and poly(5-fluorobenzo[c]thiophenes) (77), both of which are reported to have band gaps of 0.95 eV. The absorption maximum, Amax. is 915 nm for a film of 19, R = C6H13 [55,56], while that for 77 is 720 nm. The difference is clearly due to a long tail in the UV-vis-NIR... 

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