Microwave Assisted Synthesis, Crystal Structure and Hirshfeld Surface Analysis of Some 2-Formimidate-3-carbonitrile Derivatives Bearing 4H-Pyran and Dihydropyridine Moieties

Abstract

Two 4H-pyran- and four dihydropyridine-based 2-formimidate-3-carbonitrile derivatives were synthesized via the conventional solvothermal and microwave radiation methods. The use of the latter technique led to the formation of the desired products in the order of minutes as compared to the former. The formation of the 2-formimidate-3-carbonitrile derivatives was confirmed using spectroscopic techniques whilst the molecular geometry and intermolecular interactions were investigated using single-crystal X-ray diffraction. The formimidate functional group was found to adopt an E configuration in all compounds and this coincides with those of closely related compounds on the Cambridge Structural Database (CSD). Classical but weak intermolecular C—H…O, C—H…N and C—H…π hydrogen bonds were observed in the crystal lattice. According to the Hirshfeld surface analysis, the C—H…π hydrogen bonds contributed the most towards the Hirshfeld surface (14.3–23.9%) than the other two hydrogen bonding types (9.6–12.7%).

The link between relative stability constant of DNA- and BSA-chromenopyrimidine complexes and cytotoxicity towards human breast cancer cells (MCF-7)

“…The implication is that beyond p K a values of ∼5.98, the H pyrimidinyl proton will be the more deshielded relative to the N–H proton. The 13 C NMR spectra of chromenopyrimidines exhibited fewer signals for aliphatic carbons and more signals for the aromatic carbons than compound 1a 50 further supporting the formation of the desired products.…”

“…These included: ethanol, methanol, triethyl orthoformate, acetic acid, aniline, 4-fluoroaniline, 3-chloro-4-fluoroaniline, 4-chloroaniline, 4-methylaniline, 3-chloroaniline, 4-bromoaniline, 4-nitroaniline and DMSO-d 6 . The 2-amino-4-(aryl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4 H -chromene-3-carbonitrile (1a and 1b) 49 and ethyl- N -(3-cyano-4-(2-fluorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4 H -chromen-2-yl)formimidate precursors (2a) 50 including 3-ferrocenylaniline and 4-ferrocenylaniline were prepared according to literature. 74 The microwave syntheses were done using a CEM Discover system.…”

“…The formation of compounds 3a to 3j was conrmed by the absence of the band at around 2210 cm −1 in their IR spectra, which attributed to the stretching vibration mode of the cyano functional group. 50 A band in the IR spectra of 3a to 3j between 3401 and 3450 cm −1 conrmed the presence of the anilinyl moieties in 3a to 3j. In the 1 H-NMR spectra of 3a to 3j, singlets between 8.37 and 9.20 ppm, and between 8.28 and 8.45 ppm attributed to the amino (NH) and pyrimidinyl (H pyrimidinyl ) protons, respectively were observed.…”

“…The 4H-pyran-based 2-amino-3-carbonitriles (1a and 1b) and the uorinated 2-formimidate-3-carbonitrile intermediate (2a), were prepared according to literature. 49,50 The microwaveassisted reactions of 2a with corresponding anilines in an acetic acid medium resulted in the formation of chromenopyrimidines (Scheme 1). The reactions were monitored via TLC and the desired products were precipitated from their mother liquor by the addition of water and were isolated in vacuo in moderate to high yields.…”