Synthesis, DFT Study and Antibacterial Activity of some Isoxazoline Derivatives Containing 1,4-benzothiazin-3-one Nucleus Obtained Using 1,3-dipolar Cycloaddition Reaction

Document Type : Research Article

Authors

1 Laboratoire de Chimie Appliquée et Environnement, équipe de Chimie Bioorganique Appliquée, Faculté des Sciences, Université Ibn Zohr, Agadir, MOROCCO

2 Laboratoire de Chimie Organique Hétérocyclique, URAC 21, Pôle de Compétences Pharmacochimie, Centre de Recherche des Sciences des Médicaments, Mohammed V University in Rabat, Faculté des Sciences, Av. Ibn Battouta, BP 10140 Rabat, MOROCCO

3 Laboratoire de Chimie Organique et Etudes Physico-Chimique, ENS Takaddoum, Université Mohammed V, Rabat, MOROCCO

4 Laboratoire National de Contrôle des Médicaments, Direction du Médicament et de la Pharmacie, Ministère de la Santé, Rabat, MOROCCO

5 Laboratoire de Chimie Organique Appliquée, Faculté des Sciences et Techniques, Université Sidi Mohamed Ben Abdallah, Fès, MOROCCO

6 Département de bactériologie, Institut national d’hygiène, avenue Ibn Batouta, B.P. 769, Agdal, Rabat, 11000, MOROCCO

7 Department of Chemistry, Tulane University, New Orleans, LA 70118, USA

10.30492/ijcce.2020.39754

Abstract

Novel series of isoxazoline derivatives containing 1,4-benzothiazin-3-one ring (6a-h) were synthesized via 1,3-dipolar cycloaddition reactions of arylnitrile oxides 5a-d on 4-allyl-2-(substituted)-1,4-benzothiazin-3-ones 3 and 4 led to polyheterocyclic. Systems. During our work,
we mainly focused on the reactivity of nitrile oxides with carbon-carbon extracyclic double bond of the allyl group. The reaction leads exclusively to cycloadducts 6a-h with a good yield. The compounds 
were characterized using s spectral data (1H-NMR, 13C-NMR) and for some structures were also confirmed via single-crystal X-ray diffraction techniques. Density functional theory (DFT) optimized structures at the B3LYP/ 6–311G(d,p) level are compared with the experimentally determined molecular structure in the solid-state. The HOMO—LUMO behavior was elucidated. The results are in agreement with the experimental data. The newly synthesized compounds 1, 2, 3, 4, 6a-g using cycloaddition reactions were evaluated in vitro for their antibacterial activities against some Gram-positive and Gram-negative microbial strains. Several compounds tested showed significant activity.

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Main Subjects


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