Hinsberg thiophene synthesis

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The Hinsberg thiophene synthesis , also called Hinsberg condensation , is a name reaction in organic chemistry and was discovered in 1910 by the German chemist Oscar Hinsberg (1857–1939). This is a synthesis reaction for substituted thiophenes.

Overview reaction

In the Hinsberg thiophene synthesis, diketones are reacted with thioglutaric acid diesters in the presence of a base .

Hinsberg thiophene synthesis overview reaction

The overview reaction shows the reaction using diacetyl . Alternatively, further diketones of the form RC (= O) –C (= O) –R can be used, where R is any organyl radical . In order for the reaction to take place, a strong non- nucleophilic base, e.g. B. potassium tert -butanolate can be used.

mechanism

A possible mechanism for the Hinsberg thiophene synthesis was formulated by Zerong Wang in the book Comprehensive Organic Name Reactions and Reagents . This takes place via the formation of a lactone as an intermediate:

Hinsberg thiophene synthesis mechanism

In the first reaction step, a CH-acidic hydrogen atom is split off from one of the two α-carbon atoms by adding a non-nucleophilic base . The carbanion 1 then attacks the carbonyl carbon atom of the diketone. An intramolecular attack by the oxygen atom on a carbonyl carbon causes a ring closure. The lactone 2 is formed by the subsequent elimination of an alcoholate . The split off alcoholate deprotonates the lactone and the ring is broken again. Another proton is split off as a result of the basic reaction conditions. An intramolecular attack on a carbonyl carbon completes the new ring closure. If ethanol is added, the carboxylate 3 is formed with elimination of water and rearomatization . By protonation the final product, a substituted thiophene produced.

application

The reaction is used in the synthesis of various thiophene derivatives. However, other derivatives of various heteroaromatics can also be synthesized. For example, derivatives of furan , pyrrole or selenophene .

Individual evidence

  1. ↑ a b O. Hinsberg: Synthetic experiments with thiodiglycolic acid ester. In: Reports of the German Chemical Society. 43, No. 1, 1910, pp. 901-906, doi : 10.1002 / cber.191004301153 .
  2. ^ A b Hans Wynberg, HJ Kooreman: The Mechanism of the Hinsberg Thiophene Ring Synthesis1,2. In: Journal of the American Chemical Society. 87, No. 8, 1965, pp. 1739-1742, doi : 10.1021 / ja01086a022 .
  3. ↑ a b c d Zerong Wang: Comprehensive Organic Name Reactions and Reagents . John Wiley & Sons, New Jersey 2009, ISBN 978-0-471-70450-8 , pp. 1426-1429 .