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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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.
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Screening for the bifurcation conditions Initially, the reaction of several nitriles was screened with aldehyde precursor 10 to determine the selectivity between thiophene and thiazole products. VolumeIssue 1Reviews and Accountspp.
Gewald reaction: synthesis, properties and applications of substituted 2-aminothiophenes
Reactivity of bromoselenophenes in palladium-catalyzed direct arylations. Scheme 15 Table 9. The advantage of this process is in possibility of the prediction of hydrophilic or hydrophobic character of final structures with right choice of starting substrates bearing functional groups. One of the important preparations of 2-aminothieno[2,3-d]pyrimidines was gewad by authors As it is presented on Schemesthe substituted 2-aminothiophene ring is formed gdwald the aliphatic starting substrates during the multi step reaction sequence: However, it is sure, that S8 has to be activated to react with Knoevenagel-Cope product 9.
Scoping of the 2-substituted thiazole formation. In summary, although our evidence indicates mechanism A is the most likely pathway it should be noted that several benzonitrile derivatives have been 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 . 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.
Depending 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. All issues All volumes Interesting articles Isocyanide-based multicomponent reactions towards cyclic constrained hewald. For more information please contact mpub-help umich. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: In addition, a sulfonic acid bound resin QP-SA was also trialled as an additive but showed no conversion allowing full recovery of the starting nitrile see later discussion on mechanism.
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. Finally, in Scammells and co-workers have presented the synthetic pathway to 5-bromo substituted 2-aminothiophenes Oxford, UK, ; Vol.
The authors, have discovered a facile synthesis of substituted azometines by a condensation of diethyl 2,5-diaminothiophene-3,4dicarboxylate 76 with thiophenecarbaldehyde 77 or 5- thiophenyl thiophene-2carbaldehyde 78 the appropriate azomethines were achieved Scheme 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.
Hewald researchers50 deal that the use acid-base catalyst ammonium salts: Drugs Future27, Reactjon review starts with an extensive introduction that discusses the most multidisciplinary areas of 2-aminothiophene research with inputs from medicine, pharmacology, chemistry, biology, biochemistry, materials science and physics.
She has co-authored the publications concerning her research interests in the field of heterocyclic chemistry aminothiophenes and coordination chemistry copper complexes.
Exploiting the reaction conditions with starting substrates tolerating a broad range of functional groups and alkyl, aryl and heteroaryl tewald about 15 new modifications of the Gewald reaction can be found in literature. A high- throughput screening program based on this enzyme from Staphylococcus aureus had identified gewaald 2-ureido-thiophenecarboxylate 74 Figure 7 as a low micromolar inhibitor. The replacement of phenyl isothiocyanate by other commercially available ones decreases dramatically the yields of thiophenes Ac2O, Mg ClO4 2; b: Tetrahedron63, In an attempt to improve the yield of this reaction, a design of experiment analysis DOE was performed initially testing three factors; temperature, concentration of 16 and reaction time, while monitoring the response by measuring the isolated yield of KF-alumina, microwave irradiation, 3.
Heterocycles45, A series of thieno[2,3-d][1,3]oxazinones 65 was synthesized and evaluated in vitro for inhibitory activity toward Human Leukocyte Elastaze HLE. Starting from substituted 2-aminothiophenes 36a-c, the target fused heterocyclic derivatives 39a-c was prepared in a four step reaction sequence. Synthetic strategies and new reactions, structure-property relationships, self- assembling properties and applications in organic electronics, solar cells and fotoionisation of water with visible lights are main highligts of his research.
Synthesis of substituted 2-aminothiophenes via Gewald reaction 2. Introduction Highly substituted thiophene derivatives are important heterocycles found in numerous biologically active and natural compounds.
Walter 2 and Ian R. Adenosine is an important endogenous tissue-protective compound released during ischemia, hypoxia or inflammation. Supporting Information File 1: Diethyl 2-cyanomalonate 45also proved unreactive, this substrate would be expected to form an extensively delocalised anion which would be a poor nucleophile.
The reaction was successful it the R-substituted 2-bromo-1phenylethanones 27 were reacted with 3-oxophenylpropanenitrile 28 and sulfur in the presence of diethylamine as a base in ethanol Scheme The readily available and inexpensive starting materials and reagents, and the lack of protection and de-protection steps make this synthesis very fashionable Scheme M Return to citation in text: Registration is open for this Beilstein Symposium, 9 – 11 April, Scheme 13 Table 7.
Fifty years later, in reaciton, substituted 2-aminothiophenes with electron- withdrawing substituents such as cyano, carbonyl, methoxycarbonyl, aminocarbonyl, etc. 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 neutral thiophene replacing positively charged thiazolium ring. Tetrahedron58,