A green bio-organic catalyst (taurine) promoted one-pot synthesis of (/)-2-thioxo-3,4-dihydropyrimidine(TDHPM)-5-carboxanilides: chiral investigations using circular dichroism and validation by computational approaches

Owing to the massive importance of dihydropyrimidine (DHPMs) scaffolds in the pharmaceutical industry and other areas, we developed an effective and sustainable one-pot reaction protocol for the synthesis of ( R / S )-2-thioxo-DHPM-5-carboxanilides via the Biginelli-type cyclo-condensation reaction...

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Published inRSC advances Vol. 14; no. 13; pp. 93 - 9313
Main Authors Parmar, Mehul P, Vala, Disha P, Bhalodiya, Savan S, Upadhyay, Dipti B, Patel, Chirag D, Patel, Subham G, Gandholi, Srinivasa R, Shaik, Althaf H, Miller, Amy Dunne, Nogales, Joaquina, Banerjee, Sourav, Padrón, José M, Amri, Nasser, Kandukuri, Nagesh Kumar, Patel, Hitendra M
Format Journal Article
LanguageEnglish
Published England Royal Society of Chemistry 14.03.2024
The Royal Society of Chemistry
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Summary:Owing to the massive importance of dihydropyrimidine (DHPMs) scaffolds in the pharmaceutical industry and other areas, we developed an effective and sustainable one-pot reaction protocol for the synthesis of ( R / S )-2-thioxo-DHPM-5-carboxanilides via the Biginelli-type cyclo-condensation reaction of aryl aldehydes, thiourea and various acetoacetanilide derivatives in ethanol at 100 °C. In this protocol, taurine was used as a green and reusable bio-organic catalyst. Twenty-three novel derivatives of ( R / S )-TDHPM-5-carboxanilides and their structures were confirmed by various spectroscopy techniques. The aforementioned compounds were synthesized via the formation of one asymmetric centre, one new C-C bond, and two new C-N bonds in the final product. All the newly synthesized compounds were obtained in their racemic form with up to 99% yield. In addition, the separation of the racemic mixture of all the newly synthesized compounds was carried out by chiral HPLC (Prep LC), which provided up to 99.99% purity. The absolute configuration of all the enantiomerically pure isomers was determined using a circular dichroism study and validated by a computational approach. With up to 99% yield of 4d , this one-pot synthetic approach can also be useful for large-scale industrial production. One of the separated isomers (4 R )-(+)-4 S developed as a single crystal, and it was found that this crystal structure was orthorhombic. Twenty-three new derivatives of ( R / S )-TDHPM-5-carboxanilide have been synthesized with up to 99% yield. All racemates were separated using chiral HPLC (Prep LC) which provided up to 99.99% purity. AC was determined using circular dichroism spectra.
Bibliography:Electronic supplementary information (ESI) available. CCDC
For ESI and crystallographic data in CIF or other electronic format see DOI
2324474
https://doi.org/10.1039/d4ra01391c
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ISSN:2046-2069
2046-2069
DOI:10.1039/d4ra01391c