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 in | RSC advances Vol. 14; no. 13; pp. 93 - 9313 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Royal Society of Chemistry
14.03.2024
The Royal Society of Chemistry |
Subjects | |
Online Access | Get full text |
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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. |
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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 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2046-2069 2046-2069 |
DOI: | 10.1039/d4ra01391c |