An efficient four-component reaction was developed to take advantage of the reactivity of the 2-aminothiophenecarbonitrile functionality. The Gewald reaction is a very useful and versatile method for condensation of aliphatic aldehyde or ketone or β-dicarbonyl compound with active nitrile and. The Gewald reaction is an organic reaction involving the condensation of a ketone (or aldehyde when R2 = H) with a α-cyanoester in the presence of elemental.
|Published (Last):||25 February 2015|
|PDF File Size:||12.24 Mb|
|ePub File Size:||20.10 Mb|
|Price:||Free* [*Free Regsitration Required]|
However, the alternative mechanism for the thiazole formation as described herein has not previously been reported and initially presented some queries. In a second approach the unselective reaction proceeding takes place and the mixture of three compounds 39a, 40 and 41 are created Scheme Ac2O, Mg ClO4 2; b: Please contact mpub-help umich.
The further investigations of such structures are challenging in development of therapeutics of the diabetes mellitus. Data of the utilization of 2aminothiophenes in the synthesis of novel type of fused heterocycles and their application are included. Thiophene and its derivatives.
Pharmazie51, 7. This is presumably due to a subtle balance between the basicity and nucleophilicity of the intermediate gewzld, which could in the case of the more stable electron withdrawing group anion enable a retro-aldol reaction following.
KF-alumina, microwave irradiation, 3. All reactions were assessed for conversion using 1 H NMR analysis of a crude sample followed by work-up and purification via column chromatography to determine the yields. One of the important preparations of 2-aminothieno[2,3-d]pyrimidines was investigated by authors Metals, Illustration of substrates that form thiophenes under Gewald-type conditions. These key intermediates were alkylated with appropriate alkyl halides to furnish the final derivatives 65 Scheme News The updated journal statistics include the impact factor and alternative journal metrics.
She completed her Ph. Five-Membered Heterocycles, Chapter 5, Section 5. This further shows the need for the reactiin and facile formation of 2-substituted thiazole compounds as core building blocks.
Microwave enhanced Gewald egwald in combination with solid-support accelerated method was presented as an easy access to polysubstituted 2-aminothiophenes. Scheme 21 Deazathiamine diphosphate deaza-TDP, Figure 1 is an analogue of thiamine diphosphate TDP, Figure 2the biologically active for of thiamin vitamin B1with a gewalx thiophene replacing positively charged thiazolium ring. In subsequent treatment of 32 with sulfur the 2-aminothiophene core 33 is formed under basic conditions.
The scope of presented work does not include all of the publications on the chemistry of substituted 2-aminothiophenes, but the most interesting studies in the subject areas are considered.
Review of Progress in Coloration11, This allowed access to higher temperatures above the boiling points of the solvents used at atmospheric pressure. M Return to citation in text: The versatility of title compounds as a synthetic entry to fused heterocycles such as thieno[3,4-c]thiolactones, thieno[2,3-b]pyrroles, thieno[2,3-d]pyrimidines and thieno[2,3-b]pyridines is highlighted in following chapters.
The protection of amino group was performed with methyl 2-chloro-2oxoacetate 24 in toluene in the presence of diisopropylethylamine DIPEA again under the microwave irradiation. Sinceshe has been professor of organic chemistry at the Slovak Technical University in Bratislava. SSR5, International Patent No WO TDP is co-enzyme present in a number of enzymes, including pyruvate decarboxylase, transketolase, pyruvate oxidase. Scheme 15 Table 9.
Several protocols have already been described for the synthesis of substituted thiazoles and benzothiazoles . Also, substrate 46lacking an acidic proton, was recovered unchanged from the reaction. Aminothiophenes 62 were converted to isothiocyanato-thiophenes 63 by the thiophosgene method. Substrates which did not react under the optimised conditions. Reactivity of bromoselenophenes in palladium-catalyzed direct arylations. ArkivocXII, Allosteric enhacement of adenosine receptor.
The free amino group allowed the chain elongation and the growth of p-conjugated system to achieve structure with three thiophene units 86 Figure 9 upon its modification via deamination reaction38,39,82, followed by the Gewald reaction.
This resction summarizes the synthetic strategies for substituted 2-aminothiophenes. Tetrahedron57, Because of the inconvenient conditions such as strong base, longer reaction time and difficult purification, the target 5bromo- 2-aminothiophenes 29 were obtained only in moderate yields Table 9. Depending on the type of the used reactants, in some variations of the reaction, the condensation Version 3 or addition of sulfur step Versions 2 and 4 is not required.
Initially, the reaction of several nitriles was screened with aldehyde precursor 10 to determine the selectivity between thiophene and thiazole products.