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.
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Polymer,48, How to cite this article: His main research interests are focused on the design and synthesis of novel pconjugated organic materials in gewalc poly- and oligothiophenes and pyrroles and its fluorine substituted analogs. Norris25 and later reviewed in 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 .
The protection reactlon amino group was ggewald with methyl 2-chloro-2oxoacetate 24 in toluene in the presence of diisopropylethylamine DIPEA again under the microwave irradiation. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: All issues All volumes Interesting articles Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics.
►Gewald reaction –
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.
However, the alternative mechanism for the thiazole formation as described herein has not previously been reported and initially presented some queries.
Sinceshe has been professor of organic chemistry at the Slovak Technical University in Bratislava. Conclusions In this review we have extended the problems of synthesis of variety of substituted 2aminothiophenes and their scope and utilization.
Aminothiophenes 62 were converted to isothiocyanato-thiophenes 63 by the thiophosgene method. Ac2O, Mg ClO4 2; b: Tetrahedron64, Five-Membered Heterocycles, Chapter 5, Section 5. Scoping of the 2-substituted thiazole formation. Thiophene and its derivatives.
Cinnamyl derivatives of thieno[2,3-d]oxazinones 72 Figure 5 inhibits herpes protease processing in HSV-2 infected cells. After the dispersion of reagent 17 in ethanol Gewald reaction was performed in QuestTM synthesizer by mixing with the starting compound – a-methylene carbonyl compounds 18 and substrates – sulfur and morpholine.
Heterogeneous organic reactions using reagents immobilized on porous solid supports have been often proved advantageous over conventional solution phase reactions because of good dispersion of active reagent sites, better selectivity and easier work-up.
Additionally, the sulfur atom plays a decisive role by acting as an efficient electron sink as explained by valence band theory.
Gewald reaction: synthesis, properties and applications of substituted 2-aminothiophenes
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 reactiob Table 9.
Using the microwave irradiation reaction was carried out in very short times, but alternatively the reaction proceed well also under conventional heating Table 7. The fact that compounds 46 and 47 did not react implies mechanism A is the predominant pathway.
The free C-5 position of derivative 33 is substituted with bromine in two following steps — first the free amino gewakd is being Boc protected and then C-5 position brominated with Nbromosuccinimide Scheme Applications of substituted 2-aminothiophenes in drug design, optoelectronics and dyes 4.
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. For more information, read Michigan Publishing’s access and usage policy. The strategy presented by authors, is based on the replacement of the benzene ring in benzoxazinones by thiophene one.
Selected examples of biologically active thiazole containing molecules . The synthetic protocol for thieno[2,3-b]pyrroles, which is based on the reaction of 1,3-dicarbonyl compounds, can be applied also for preparation of thieno[2,3-b]thiophenes.
The versatility of title compounds as a synthetic entry to fused heterocycles gewad 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. In Purinergic Approaches in Experimental Therapeutics, ed. The chemistry of aminothiophenes has been broadly summarized in in the monograph of R.
Jump to Figure 1. Illustration of substrates that form thiophenes under Gewald-type conditions.
The substituted 2-aminothiophenes act as the most suitable synthetic precursors to various thieno[2,3d] pyrimidines. In a second approach the unselective reaction proceeding takes place and the mixture of three compounds deaction, 40 and 41 are created Scheme During a postdoctoral stay in —75 at University of East Anglia, she joined the group of Geawld. Initially, the reaction of several nitriles was screened with aldehyde precursor 10 to determine the selectivity between thiophene and thiazole products.