2-Fluorothiophene, preparation

Attempts to prepare fluorothiophenes from diazonium salts (the fluoro-borate and hexafluorophosphate salts) have met only variable success. Methyl 3-fluorothiophene-2-carboxylate (32) was obtained in 89% yield by this method (Scheme 12), but the 3-diazonium salt of the corresponding 4-ester could not be isolated. Furthermore, the methyl ester of 2-diazothiophene-3-carboxylic acid coupled before decomposition could be attempted [85H(23) 1431]. 

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). 

A number of fluorothiophenes have been prepared by the action of per-chloryl fluoride on thienyllithium derivatives, which were obtained from the corresponding bromothiophenes by metal-bromine exchange with ethyllithium.60... 

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. 

Chloro-4-fluorothiophene-1,1-dioxide 234, a new synthetically useful fluoro-diene was prepared from commercially available 3-sulfolene. This compound reacts with different types of dienophiles acetylenes, alkenes, furans quinine, and antracene giving the 3-fluoro-4-chloro-substituted arenes or cyclic chlorofluorodienes. " ... 

A seven-step process (13JOC12330) shown below has led to the highly reactive diene and dienophile thiophene dioxide. Interestingly, the dioxo compound, unlike the sufoxide which dimerizes readily at 0°C, survives in solution for many hours at 100°C,thus allowing it to function as a diene or dienophile. In addition, new routes (not shown below) to 3,4-difluoro- and tetrafluorothiophenes was developed, and the previously unknown 2,3,4-tri-fluorothiophene was prepared. 

Thermal stability of thiophene 1,1-dioxides increases with more substituents on the thiophene ring. For example, dimerization of 3-chloro-4-fluorothiophene 1,1-dioxide required heating in refluxing toluene for 20 h to give aromatic product 69 in 57% yield with release of one molecule of SO2 and one molecule of HCI (Scheme 66) [88], Similarly, the dimerization conditions for 3,4-dichlorothiophene 1,1 -dioxide were also very harsh, and a mixture of products 70 and 71 was obtained. It should be noted that 71 could also be prepared from 70, though the conditions were even harsher - reflux at 200-215°C (Scheme 67) [89]. 

In some cases, the direct metallation was also applied for the synthesis of 3-fluorothiophenes. Thus, 3-fluorothiophene-2-carboxylic acid 30 was prepared in two steps from the corresponding thiophene-2-carboxylic acid 22 by treatment with n-butyllithium followed by reaction with N-fluorodibenzenesulfonimide [22]. This approach was applied to the synthesis of monomer 32 for thieno[3,4-fe]thiophene polymers 33 used in organic solar cells [23]. 

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]. 

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