present-day thiophene research. Since when first report on the Gewald reaction was reported it became a universal method for synthesis of substituted. PDF | Chemistry of 2-aminothiophenes is arguably one of the most extensive and dynamic field of present-day thiophene research. Since when first report. Gewald thiophene synthesis – Method A. Siloxycyclopropanes 53 and 55 were reacted with Et3Nx3HF and Et3N in DMF in order to obtain γ- oxocarboxylates.
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Thiiphene on the used starting substrates and the reaction conditions three basic versions of the Gewald reaction have been developed16, which were lately enriched by a fourth version.
In general, lower concentration was beneficial but at a consequence of longer reaction times in order to obtain a good yield. It was proved, that the parent aminothiophene occurs exclusively in the amino form. 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.
She finished her habilitation in and D. The lack of reactivity of substrate 47 can be attributed to the high degree of steric hindrance inhibiting its enolisation.
Initially, the reaction of several nitriles was screened with aldehyde precursor 10 to determine the selectivity between thiophene and thiazole products. 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.
Aminothiophenes 62 were converted to isothiocyanato-thiophenes 63 by the thiophosgene method. Emphasis is given to the recent studies published, in which the most general approaches to the synthesis of basic 2-aminothiophenes via the Gewald reaction and other target structures were considered.
Tetrahedron54, How to cite this article: Results from his work have been published in about peer-reviewed scientific papers and 62 patents. The synthesis of 3-deazathiamine 61 was effected in ten chemical steps, though it was necessary to prepare and isolate substituted 2-aminothiophene.
As was reported in, the facile one-pot synthesis of polysubstituted thiophenes and thieno[2,3-b]thiophenes was completed through cyclization of a-oxo ketene S,S -acetals. Applications of substituted 2-aminothiophenes in drug design, optoelectronics and dyes 4. Adenosine is an important endogenous tissue-protective compound released during ischemia, hypoxia or inflammation.
Scheme 13 Table 7.
Thiophene and its derivatives. Introduction Highly substituted thiophene tgiophene are important heterocycles found in numerous biologically active and natural compounds.
The most suitable base for the activation with sulfur and the subsequent sulfur addition morpholine has been proved. To date, she has synthesized with her research group more than new organic substances, mainly with heterocyclic structure, and participated on the quantitative studies of aromaticity of p-electronrich newly synthesized furo[b]pyrroles. Experimental and analytical data. We have successfully shown that substitution of the nitrile precursor predetermines the reaction outcome yielding exclusively to a thiophene or thiazole product.
Gewald reaction: synthesis, properties and applications of substituted 2-aminothiophenes
This review summarizes the synthetic strategies for substituted 2-aminothiophenes. Diabetes mellitus is a condition characterized by chronically elevated levels of blood glucose caused by incorrect function of the hormone responsible for the hGCRG activation. Other researchers50 deal that the use acid-base catalyst ammonium salts: Scoping experiments using ethyl phenylcyanoacetate 16 with different solvents and bases.
It was shown that the presence of an alkyl or aryl substituent adjacent to the cyano group leads selectively to the thiazole by blocking the Gewald type mechanism responsible for the formation of the 2-aminothiophene. The free amino group is acylated first and then the methyl group in C-4 position undergoes the radical bromination to create the crucial intermediates 37a-c. As it is presented on Schemesthe substituted 2-aminothiophene ring is formed from the aliphatic starting substrates during the multi step reaction sequence: 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.
Polymer,48, Tetrahedron57, Thieno[2,3-d]pyrimidine-4hydrazide derivatives related to structure 73 Figure 6 were discovered as a moderately potent inhibitors of TGase-2 tissue transglutaminase.
The availability of reagents and the mild reaction conditions all contribute to the versatility of this reaction. TDP is co-enzyme present in a number of enzymes, including pyruvate decarboxylase, transketolase, pyruvate oxidase.
Gewald reaction – Wikipedia
In subsequent treatment of 32 with sulfur the 2-aminothiophene core 33 is gewzld under basic conditions. Tetrahedron60, Reactivity of bromoselenophenes in palladium-catalyzed direct arylations.
The fact that compounds 46 and 47 did not react implies mechanism A is the predominant pathway. Only a small impact upon conversion was observed with changing the ratio of compound 10 and so it was decided to also maintain this at equimolar concentration i.
Recently, the improvements of the Gewald synthesis were announced. The first report on the development and the use of substituted 2-aminothiophenes and the Gewald reaction was published by authors.
Scheme 21 Deazathiamine diphosphate deaza-TDP, Figure 1 is an analogue of thiamine diphosphate TDP, Figure 2the biologically sybthesis for of thiamin vitamin B1with a neutral thiophene replacing positively charged thiazolium ring.
From the data it was concluded that elevated temperatures resulted in lower isolated yields most probably due to decomposition of compound 10 or the resulting aldehyde. Selected examples of biologically active thiazole containing molecules . By the use of improved methods and modified experimental procedures the scope of easily obtainable 2aminothiophenes ultimately spread.