Thiazole-aldehyde synthesis

from Wikipedia, the free encyclopedia

The thiazole-aldehyde synthesis is a name reaction in organic chemistry that was developed by Alessandro Dondoni. During the reaction, an aldehyde group (CHO) is added to a molecule , which is why it is also known as Dondoni's homologation . The aldehyde is initially masked as thiazole and can thus be substituted. The Corey-Seebach reaction is also based on the idea of masking a carbonyl group with a heterocycle .

Overview reaction

Dondoni Overview.svg

A C2-substituted thiazole 1 is reacted with a methylating agent such as methyl trifluoromethylsulfonate (CF 3 SO 3 Me) to form a methylthiazolium salt 2 . As an alternative to methyl triflate, methylation reagents such as methyl iodide or trimethyloxonium tetrafluoroborate can also be used. The methylthiazolim salt can be reduced to 3 with sodium borohydride , which is hydrolytically cleaved to aldehyde 4 in the presence of mercury (II) chloride .

Educts

Edukte.svg

Many of the C2-substituted thialzenes can be obtained from 2-bromothiazole. A lithiated thiazole that can be reacted with electrophiles can be obtained via a metal-halogen exchange with butyllithium (BuLi) . Aldehydes can be obtained by reaction with DMF . By reaction with chlorine (trimethyl) silane or trimethyl tin chloride , silyls or stannanes can be obtained. Implementation with esters provides ketones.

Atomic economy

The atom economy of the thiazole-aldehyde synthesis is very unfavorable, since stoichiometric amounts of several waste materials with high molar mass always arise. This synthesis sequence is therefore a purely laboratory process with no potential technical significance, which is also underlined by the use of toxic mercury (II) chloride to release the aldehyde.

See also

Individual evidence

  1. ↑ José Marco-Contelles, Elsa de Opazo: SOME UNEXPECTED RESULTS IN DONDONI'S ONE-CARBON HOMOLOGATION PROCEDURE1 . In: Journal of Carbohydrate Chemistry . tape 20 , no. 7 & 8 , 2001, ISSN  0732-8303 , p. 637-646 , doi : 10.1081 / CAR-100108278 .
  2. ↑ Alessandro Dondoni, Alberto Marra: Thiazole-Mediated Synthetic Methodology . In: Chemical Reviews . tape 104 , no. 5 , May 2004, ISSN  0009-2665 , pp. 2557-2600 , doi : 10.1021 / cr020079l .
  3. ↑ a b c Alessandro Dondoni: The Thiazole Aldehyde Synthesis . In: Synthesis . tape 1998 , no. December 12 , 1998, pp. 1681-1706 , doi : 10.1055 / s-1998-2208 .