Synthesis, bioassay, crystal structure and ab initio studies of Erlenmeyer azlactones

Several 4-arylidene-2-phenyl-5(4H)-azlactones have been synthesized via Erlenmeyer method. The synthesized compounds have been characterized on the basis of systematic spectral studies (IR, 1H NMR, 13C NMR, and MS). The compound (4Z)-4-(3,5-dimethoxybenzylidene)-2-phenyl-1,3-oxazol-5(4H)-one, C18H15NO4, (5), crystallizes in the orthorhombic system, space group P212121, with a = 5.6793(3) Å, b = 15.2038(7) Å, c = 17.6919(10) Å, Mr = 309.31, V = 1527.64(14) Å3, Z = 4 and R = 0.0547. The compound (4Z)-2-phenyl-4-(3,4,5-trimethoxybenzylidene)-1,3-oxazol-5(4H)-one, C19H17NO5, (6) crystallizes in triclinic geometry with space group P-1, having unit cell parameters a = 7.3814(3) Å, b = 8.1446(3) Å, c = 13.9845(5) Å, α = 86.918(3), β = 83.314(2), γ = 82.462(3), Mr = 339.34, V = 827.16(5) Å3, Z = 2 and R = 0.0433. The DFT calculations of compounds (5) and (6) have been carried out to ascertain the stability of Z-conformer. The in vitro antimicrobial activity of all the compounds (1–6) was evaluated by the disk diffusion method against gram +ve and gram −ve microorganism and fungal strains. The MIC of the synthesized compounds was determined by agar well diffusion method in 96-well microtiter plate. All the synthesized compounds were also screened for their free radical scavenging activity by DPPH method.

Graphical abstractA series of 4-arylidene-2-phenyl-5(4H)-azlactones have been synthesized, characterized on the basis of systematic spectral studies and screened for their biological activity. Moreover, the Z-configuration and stability of compounds was ascertained on the basis of spectroscopy techniques, X-ray studies as well as DFT calculations.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► 4-Arylidene-2-phenyl-5(4H)-azlactones were synthesized and fully characterized. ► Antimicrobial and antioxidant activity. ► The structure of 5 & 6 were studied by X-ray study and compared to DFT calculations. ► DFT calculations of two compounds were suggested the stability of the Z-conformer. ► Crystal packing was stabilized by H-bond, weak CH⋯π and π⋯π interactions were observed.