Synthesis, Structural, Spectral Studies and Activity Studies of 6-Methyl-4-(3-Nitro-Phenyl)-2-Oxo-1,2,3,4 Tetrahydropyrimidine-5-Carboxylic Acid Ethyl Ester Catalyzed Using BF₃-OEt₂

Abstract

Amide compounds exhibit tautomerism which is an important property in organic synthesis. Evidence for the occurrence of tautomeric forms for amido-imidols is interpreted via mass spectrometry techniques. The tautomeric equilibrium of pyrimidone moiety was rationalized and the existence of amido-imidol tautomerism in 6-methyl-4-(3-nitro-phenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester (6M3NP) was verified. The proton nuclear magnetic resonance splitting pattern shows the intramolecular hydrogen bonding between the keto-enol forms which evidences through a fluctuation in the integration value of C4 proton. Synthesis proceeds through novel BF₃-OEt₂ catalysed one-pot, simple, efficient, minimal catalyst usage, compatible, outstanding yield, and rapid protocol for the Tetrahydropyrimidinones via Biginelli reaction is described. The titled compound 6M3NP was characterized by infrared and nuclear magnetic resonance. The compound was screened for antimicrobial activity against 3 microbes which showed a high zone of inhibition when compared to standard streptomycin. The antioxidant activity using 2,2-diphenyl-1-picryl-hydrazyl-hydrate assay gave a promising IC₅₀ value of 14.11 µM. The more the radical scavenging activity the greater the chance of functioning as an anticancer agent. 6M3NP was tested against breast cancer cells after scrutiny with 60 cell lines. Clonogenicity and soft agar colony formation were significantly reduced in MCF7, MDA-MB-231, and T47D breast cancer cells after treatment with 6M3NP. The in-silico dock score obtained for the title compound was 62.845 which is 40% more than the standard drug Nifedipine. In-vitro cell line analysis results showed that the title compound possesses maximum activity than commercial drug Nifedipine against cardiovascular disease as a calcium channel blocker.

Keywords:

• Lewi’s acid catalyst
• mass spectrum
• antimicrobial study
• anticancer study
• molecular docking

Acknowledgement

Priya Matharasi, one of the authors, expresses gratitude for the SAIF (advanced analytical instruments facility), IIT Madras assistance of FT-IR and NMR experiments.

Disclosure statement

No potential conflict of interest was reported by the authors.