Thiophenes Hinsberg synthesis

The Hinsberg synthesis of thiophene derivatives describes the original condensation of diethyl thiodiglycolate and a-diketones under basic conditions which provides 3,4-disubstituted-thiophene-2,5-dicarboxylic acids upon hydrolysis of the crude ester product with aqueous acid. ... 

Finally, the Hinsberg synthesis has been extended to the use of a-aryl-a-carboethoxydimethyl sulfide in conjunction with a series of 1,2-dicarbonyl compounds. Specifically, the 4-nitroaryl substituent provides for sufficient activation of the a-proton to allow condensation and ring closure. These examples appear general and suggest future opportunities for the Hinsberg thiophene protocol. 

Hinsberg synthesis and 1,3-dipolar cycloaddition of thiocarbonyl ylides with dipolatophiles are typical thiophene syntheses in this class (Equation 37). 

Hinsberg synthesis of thiophene derivatives. Formation of thiophene carboxylic acids from a-diketones and dialkyl thiodiacetate. 

Dicarbonyl compounds can be made to cyclize with esters of 3-thiapentanedioic acid 21 under base catalysis (Hinsberg synthesis). This widely applicable and high-yield synthesis leads to substituted thiophene dicarboxylic esters 22 via a double aldol condensation, with the two CH2 groups of 21. Hydrolysis and decarboxylation of the esters yield 3,4-disubstituted thiophenes 23 [23] ... 

The classical Hinsberg synthesis of thiophenes has been applied to the preparation of 2,5-dicarbonylselenophenes (68) <87H(26)909> as shown in Equation (22). 

Mullins, R. J. Williams, D. R. Hinsberg Synthesis of Thiophene Derivatives. InName Reactions in Heterocyclic Chemistry, Li, J. J., Corey, E. J., Eds. Wiley Sons Hoboken, NJ, 2005, pp 199-206. (Review). 

Hinsberg Synthesis of Thiophene Derivatives Hiyama (see Nozaki-Hiyama Coupling Reaction) Hoch-Campbell Aziridine Synthesis Hoesch (see Houben-Hoesch Reaction)... 

Hinsberg thiophene ring synthesis 7, 773 Hofmann degradation... 

Heumann-Pfleger synthesis (indigo) 145 Hinsberg synthesis (thiophene) 98 Hoffmann-Loffler reaction 158 Huisgen synthesis... 

The venerable Hinsberg synthesis (e.g. Scheme 42) [71] involves two consecutive aldol cmidensations between a 1,2-dicarbonyl compound and diethyl 2,2 -thiobisacetate and produces thiophenes carrying ester and carboxylic acid groups at the 2- and 5-positi(Mis, respectively, via a Stobbe-type mechanism [72]. Reactions are often worked up via hydrolysis to afford a diacid as the isolated product. Scheme 43 indicates a reasonable sequence for the condensation and explains the formation of an acid-ester product. 

The Hinsberg thiophene synthesis has seen limited use owing to the potential for regioisomeric mixtures when unsymmetrical 1,2-dicarbonyls are condensed with unsymmetrical thiodiacetates. Thus, symmetrically substituted thiophenes are generally prepared in this manner. 

A notable utilization of the Hinsberg procedure was executed in the synthesis of a thiophene analogue of porphyrin. A previous synthesis of the tetrathioporphyrin dication of 7 found this material to be unsuitable for chemical exploration as a result of its limited accessibility and solubility. Efforts by Vogel et al. were then directed toward... 

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