Fiesselmann synthesis

The synthesis of selenophenes uses a modified Fiesselmann synthesis for thiophenes and proceeds as follows ... 

Feist-Benary synthesis (furan) 72 Fiesselmann synthesis... 

The Fiesselmann thiophene synthesis involves the condensation reaction of thioglycolic acid derivatives with a,P-acetylenic esters, which upon treatment with base results in the formation of 3-hydroxy-2-thiophenecarboxyIic acid derivatives. 

The structure of sitaxsentan (2) is also somewhat modular and was divided into three building blocks—namely the phenyl ring, the central thiophene, and the aminoisoxazole. The isoxazole subunit 33 can be prepared by the reaction of hydroxylamine with butynenitrile (31) to form the heterocycle,30 followed by chlorination with NCS.22 The thiophene ring can be formed using a Fiesselmann thiophene synthesis starting from... 

Further investigation of anti-tubulin agents by Romagnoli et al. led to the development of a modified Fiesselmann thiophene synthesis to produce 3-amino-2-(3,4,5-trimethoxybenzoyl)-5-aryl-thiophenes. " The a-mercapto-ketone anion was generated in situ by treating 0-ethyI-5-[2-oxo-2-(3,4,5-trimethoxyphenyl)-ethyl]dithiocarbonate with piperidine. Reaction of the a-mercapto anion with P-chloro-arylcinnamonitriles under thermal conditions afforded the desired thiophene. Much like the 2-amino derivatives, these 3-amino-2-(3,4,5-trimethoxy-benzoyl)-5-aryl-thiophenes were shown to be potent anti-proliferation and anti-tubulin agents as well. 

Benzothiophenes may be accessed by a variety of methods including variations of the Fiesselmann and Gewald thiophenes synthesis. In addition, acid-catalyzed and electrophilic (iodo) cyclizations have been used to create valuable synthetic thiophene and benzothiophene intermediates with varied substitution patterns. 

For the synthesis ofselenophenes [97], for example, a modified Fiesselmann procedure (as established for thiophenes, cf p. 97) can be used ... 

In the earliest examples of this approach, Fiesselmann studied acetylenic esters, including acetylenedicarboxylic acid esters, the former producing 5-substituted 3-hydroxythiophene-2-esters whilst the latter giving rise to 3-hydroxythiophene-2,5-dicarboxylic esters (Scheme 60) [90-92] (Later work used milder conditions for this synthesis [93]). The final ring closing condensation to produce the 3-hydroxythiophene-2-esters is of the Claisen type and one can envisage the first cyclic intermediate as 36 which tautomerises. 

Monocyclic Selenophens.—Ring-closures. The Fiesselmann reaction has been applied to the synthesis of selenophens. The reaction of (500) with sodium selenide and ethyl bromoacetate thus gave (501). ° Also the Gewald reaction is successful cyclohexanone reacts with ethyl cyanoacetate and selenium in the presence of base to give (502). 2,5-Diarylselenophens are obtained, together with small amounts of the 2,4-isomer, on heating 4-aryl-1,2,3-selenadiazoles. Upon pyrolysis of (503) at 250 C the selenophen derivative (504) is formed. "... 

---