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.

Author: Shaktijinn Gogor
Country: Chile
Language: English (Spanish)
Genre: Environment
Published (Last): 23 July 2016
Pages: 382
PDF File Size: 1.73 Mb
ePub File Size: 16.42 Mb
ISBN: 199-4-69645-268-7
Downloads: 22549
Price: Free* [*Free Regsitration Required]
Uploader: Maurn

Oxford, UK, ; Vol. While in some cases the ylidene dimerization is significant and synthessis by-product is isolated in higher yield than the desired 2-aminothiophene derivative58, on other hand under suitable reaction conditions not only is the straightforward reaction favored, but also the recyclization of dimerized ylidene 14 to appropriate aminothiophene 7 occurs.

The substituted 2-aminothiophenes act as the most suitable synthetic precursors to various thieno[2,3d] pyrimidines. WoldChristopher L.

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. Please gewalc mpub-help umich. Synthesis45, 45— Ac2O, Mg ClO4 2; b: Heterocycles45, Microwave heating is an area of increasing interest in both academic and industrial laboratories because syntheiss can raise the rate of reaction and in many cases improve product yields.

Gewald reaction – Wikipedia

Metals, In this particular version the more stable dimeric forms of an a-sulfanylcarbonyl compound — substituted 1,4-dithiane-2,5-diols 5c undergo condensation and subsequent cyclization with aactivated acetonitrile 6 requiring an amine in stochiometric amount Scheme 6. Mallia 1Lukas Englert 1Gary C. Even though 2-substituted thiazoles are important structures in their own right, further substitution can be easily achieved through published protocols to form 2,4-substituted thiazoles, 2,5-substituted thiazoles and also 2,4,5-substituted thiazoles [30].

Utilization of substituted 2-aminothiophenes and Gewald reaction in the synthesis of condensed heterocycles The substituted 2-aminothiophenes found enormous utility in dye chemistry, modern drug designbiodiagnostics, electronic and optoelectronic devices, conductivity-based sensors, and self-assembled superstructures.

Chemistry16, Using the microwave irradiation reaction was carried out in very short times, but alternatively the reaction proceed well also under conventional heating Table 7. Such derivatives represent a p-heteropentalene system with tetracovalent sulfur nucleus and are investigated from synthetic and theoretical point of view.


However, the alternative mechanism for the thiazole formation as described herein has not previously been reported and initially presented some queries. Conclusions In this review we have extended the problems of synthesis of variety of substituted 2aminothiophenes and their scope and utilization. Reaction starting from 1,4-dithiane-2,5-diol 21 and aactivated acetonitrile 6 was completed after 2 min. Sinceshe has been professor of organic chemistry at the Slovak Technical University in Bratislava.

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. Scheme 18 The same authors have published an improved two step method for the synthesis of Nphenylaminothiophenes 44, which is based on preparation and isolation ketene phenylamino methylthioacetals Tetrahedron29, Please enable Javascript and Cookies to allow this site to work correctly!

Some TGase isoenzymes are involved in diverse pathological conditions like celiac disease, atherosclerosis and neurodegenerative disorders. Conversion of formed ester 58 to final 3-deazathiamine 61 was accomplished in four subsequent steps isolating the crucial intermediates — aldehyde 59 and nitrile 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.

US Patent NoOctober Tetrahedron64, Norris25 and ten years of the last Gewald reaction review26 we felt the time was ripe for a fresh look at this field of heterocyclic chemistry. 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.

This process represents the advancement of the basic version 4 content 2. This allowed access to higher temperatures above the boiling points of the solvents used at atmospheric pressure.

In subsequent treatment of 32 with sulfur the 2-aminothiophene core 33 is formed under basic conditions.

Thiazole formation through a modified Gewald reaction

Additionally, the sulfur atom plays a decisive role by acting as an efficient electron sink as explained by valence band theory.

For that reason, much attention is focused on the inhibition of HLE by low-molecular-weight inhibitors that might serve as therapeutic agents. It was proved, that the parent aminothiophene occurs exclusively in the amino form. Results yhiophene his work have been published in about peer-reviewed scientific papers and 62 patents.


Gewald reaction

In general, lower concentration was beneficial but at a consequence of longer reaction times in order to obtain a good yield. In Purinergic Approaches in Experimental Therapeutics, ed. International Patent No WO The synthesis and pharmacology of this series thiophens derivatives was presented by authors, from ethyl 2-aminomethylthiophenecarboxylate. The strategy presented by authors, is based on the replacement of the benzene ring in gewakd by thiophene one.

In this relatively new synthetic pathway the sulfur, which is electro active, is incorporated in a carbon electrode and used as a sacrificial cathode to yield S3.

How to cite this article: In summary, although our evidence indicates mechanism A is the most likely pathway it should be noted that several benzonitrile derivatives have thhiophene shown to successfully result in thiazole formation when reacted with coupling partners such as 2-mercaptopropionic acid, therefore mechanism B could operate under certain conditions [32].

Synthesis of substituted 2-aminothiophenes via Gewald reaction 2. She has co-authored the publications concerning her research interests in the field of heterocyclic chemistry aminothiophenes and coordination geawld copper complexes.

The reader interested in the latter aspects can find further detailed information in the list of references. However, it is sure, that S8 has to be activated to react with Knoevenagel-Cope product 9.

With regard to solvent selection, trifluroethanol showed thiopheje far the best results, this is probably due to the high polarity and its slightly acidic nature, which assists in solubilising 10and subsequently promotes the formation of the aldehyde monomer. We have collected together detailed descriptions of selected important new reactions and works used Gewald reaction.

Drugs Future27, Only a small impact upon conversion was observed with changing thiopuene ratio of compound 10 and so it was decided to also maintain this at equimolar concentration i.