3-fluorothiophene

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). 

Fluorothiophenes 2-Fluorothiophene was prepared first time in low yield by the fluorination of 2-iodothiophene by antimony trifluoride. 

Electrophilic fluorination of the thiophene derivatives was used for preparation of 2-fluorothiophenes but fluorination of thiophene by F2/He mixture leads to a mixture of two isomers, with 2-fluorothiophene being the major product. ° ... 

Fluorothiophene and 2-fluoro-5-methylthiophene were prepared by the exothermic reaction of perchloryl fluoride with the corresponding organolithium heterocyclic compounds in anhydrous ether. 

A -Fluorodibenzensulfonimide was successfully applied for the preparation of 2-fluorothiophenes 112 and 113 ° and A -lluoroquinuclidinium fluoride was used in the synthesis of 2-lluorothiophene. 

The synthetic methods for 2-fluorothiophenes with the usage of acyclic synthones are less studied. For example, 5-fluoro-2,3-dihydrothiophene 114 was prepared by cyclization of 1,1-difluoro-l-butenes. 

Onys ko, Gakh and coworkers have shown that 2-fluorothiophene can be synthesized selectively by heating bis(2-thienyl)iodonium salts with potassium fluoride [78], Specifically, treatment of bis(2-thienyl)iodonium hexafluorophosphate (36) with potassium fiuoride (as a mechanical mixture) at 172-175 °C for 2 h yields 2-fluorothiophene, 2-iodothiophene and thiophene (Scheme 7.12). Bis(2-thienyl)iodonium salts with more nucleophilic anions, such as trifluoroacetate, yielded only trace amounts of the desired 2-fluorothiophene [78]. 

Both acylation (MeCOCl, SnCU-CSj) and lithiation (BuLi-Et 0) of 2-fluorothiophen take place exclusively at the 5-position to give, for example, 2-acetyl-5-fluorothiophen. The and F n.m.r. spectra have been reported for a large number of thiophens substituted by a single fluorine at either the 2- or 3-position. When irradiated in the gas phase, perfluoro-tetramethylthiophen isomerizes to the epithiocyclobutadiene (252), and not to a thioketylcyclopropene, as previously reported. ... 

The first reported method for the preparation of 2-fluorothiophene 2 was the reaction of 2-iodothiophene 38 with SbFs in nitromethane. However, the method was inconvenient since it gave the target 2-fluorothiophene 2 in less than 10 % yield [25]. 

A more useful approach to fluorothiophenes was based on transformations of iodonium salts. 2-Thienyliodoniym salts, for example dithiophen-2-yliodonium hexafluorophosphate 39, afford 2-fluorothiophene 2 (37 %) and thiophene 1 (20 %) after treaunent with potassium fluoride and heating at 172-175 °C [26],... 

Onys ko PP, Kim TV, Kiseleva 01, Rassukana YV, Gakh AA (2009) Cascade iodination-fluorination synthesis of 2-fluorothiophene and 5-fluoro-2-thienyliodonium salts. J Ruor Chem 130 501-504... 

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