Related Experiment Video
Updated: Jul 25, 2025

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Synthesis, Crystal Structure, DFT, and Anticancer Activity of Some Imine-Type Compounds via Routine Schiff Base
Jamal Lasri1, Naser E Eltayeb1, Saied M Soliman2
1Department of Chemistry, Rabigh College of Science and Arts, King Abdulaziz University, P.O. Box 344, Jeddah 21589, Saudi Arabia.
Abstract:
The synthesis, characterization, and anticancer properties of three imine-type compounds 1-3 and an unexpected oxazine derivative 4 are presented. The reaction of p-dimethylaminobenzaldehyde or m-nitrobenzaldehyde with hydroxylamine hydrochloride afforded the corresponding oximes 1-2 in good yields. Additionally, the treatment of benzil with 4-aminoantipyrine or o-aminophenol was investigated. Routinely, the Schiff base (4E)-4-(2-oxo-1,2-diphenylethylideneamino)-1,2-dihydro-1,5-dimethyl-2-phenylpyrazol-3-one 3 was obtained in the case of 4-aminoantipyrine. Unexpectedly, the reaction of benzil with o-aminophenol proceeded with cyclization to produce the 2,3-diphenyl-2H-benzo[b][1,4]oxazin-2-ol 4. The structures of compounds 3 and 4 were unambiguously determined by single crystal X-ray diffraction. Hirshfeld analysis of molecular packing revealed the importance of the O…H (11.1%), N…H (3.4%), C…H (29.4%), and C…C (1.6) interactions in the crystal stability of 3. In the case of 4, the O…H (8.8%), N…H (5.7%), and C…H (30.3%) interactions are the most important. DFT calculations predicted that both compounds have a polar nature, and 3 (3.4489 Debye) has higher polarity than 4 (2.1554 Debye). Different reactivity descriptors were calculated for both systems based on the HOMO and LUMO energies. The NMR chemical shifts were calculated and were found well correlated with the experimental data. HepG2 growth was suppressed by the four compounds more than MCF-7. The IC50 values of 1 against HepG2 and MCF-7 cell lines were the lowest, and it is considered the most promising candidate as an anticancer agent.
Related Concept Videos
Aldehydes and Ketones with Amines: Imine and Enamine Formation Overview
Aldehydes and Ketones with Amines: Imine Formation Mechanism
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...
Cycloaddition Reactions: Overview
Basicity of Heterocyclic Aromatic Amines
Aryldiazonium Salts to Azo Dyes: Diazo Coupling
Structure and Nomenclature of Epoxides
![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
