X-ray Molecular Structure of ({[(1E)-3-(1&lt;i&gt;H&lt;/i&gt;-Imidazol-1-yl)-1- phenylpropylidene]amino} oxy)(3,4,5-trimethoxyphenyl)- methanone: A Potential Anti-&lt;i&gt;Candida&lt;/i&gt; Agent

Maha S Almutairi,Hoong-Kun Fun,Soraya W Ghoneim,Hazem A Ghabbour,Mohamed I Attia

doi:10.4314/tjpr.v14i11.13

Abstract

Purpose: To elucidate the solid-state conformation as well as the imine double bond configuration of a potential anti-Candida agent ({[(1E)-3-(1H-imidazol-1-yl)-1-phenylpropylidene]amino}oxy)(3,4,5trimethoxyphenyl)methanone. Methods: Acetophenone was used as a starting material to prepare the target oximino ester in a fourstep reaction sequence. Nuclear magnetic resonance ( 1 H-NMR and 13 C-NMR) and mass spectrometry were used to confirm the chemical structure of the synthesized compounds. Thereafter, x-ray crystallography was performed on single crystals of the target compound. The solid-state conformation of the target molecule and the (E)-configuration of its imine double bond were determined via the investigation of its single crystal x-ray molecular structure. Results: The titled compound crystallized in the triclinic space group P-1 with a = 11.0719 (7) A, b = 14.6602 (9) A, c = 14.8530 (9) A, α = 67.205 (4)°, β = 80.388 (5)o, γ = 70.100 (5)°, V = 2088.2 (2) A 3 , and Z = 4. Individual molecules were packed in the crystal by three weak non-classical intermolecular hydrogen interactions, including C9A—H9AA•••O3A, C9B—H9BA•••O3B, C18B—H18C•••O2A and C20B—H20B•••O4B. Conclusion: The results of the single crystal x-ray molecular structure of the titled anti-Candida agent unequivocally confirmed its (E)-configuration.

Highlights

A substantial increase in fungal infections has been observed over the past few decades
Invasive and nosocomial fungal infections are primarily caused by Candida and Aspergillus species, where Candida albicans is responsible for the majority of invasive and superficial Candida infections
Acetophenone was subjected to a Mannich reaction followed by substitution of the resulting Mannich base hydrochloride 1 with imidazole to furnish the pivotal ketone 2

Summary

INTRODUCTION

A substantial increase in fungal infections has been observed over the past few decades. A solution containing compound 1 (3.7 g, 17.4 mmol) and imidazole (2.4 g, 34.8 mmol) in water (10 mL) was refluxed for five hours. Cooling the reaction mixture led to precipitation of the ketone 2 which was filtered off to give 2.7 g (77%) of 2 mp 368370 K [7]. Hydroxylamine hydrochloride (1.39 g, 20 mmol) was added to a solution containing ketone 2 (2.00 g, 10 mmol) and KOH (1.12 g, 20 mmol) in ethanol (10 mL). The assigned chemical structure of oxime 3 was confirmed via 1H and 13C NMR and mass spectral data. The assigned chemical structure of compound 4 was confirmed via 1H and 13C NMR and mass spectral data. The slow evaporation of the isopropanol solution containing pure oximino ester 4 afforded its colorless block single crystals.

RESULTS

OMe OMe

DISCUSSION

CONCLUSION