An Efficient Synthesis of 3,4-Dihydro-3-substituted-2H-naphtho[2,1-e][1,3]oxazine Derivatives Catalyzed by Zirconyl(IV) Chloride and Evaluation of its Biological Activities

Abstract

An efficient and novel one-pot synthesis of new 3,4-dihydro-3-substituted-2H-naphtho[2,1-e][1,3]oxazine derivatives from 1-naphthol, various anilines and formalin at room temperature grinding is presented. The six-membered N,O-heterocyclic skeleton was constructed via zirconyl(IV) chloride promoted Mannich type reaction. In vitro antimicrobial activities of synthesized compounds have been investigated against Gram-positive Bacillus subtilis, Gram negative Escherichia coli and two fungi Candida albicans and Aspergillus niger in comparison with standard drugs. The results of preliminary bioassay indicate that some of title compounds possess significant antibacterial and antifungal activity.

Mannich bases in medicinal chemistry and drug design

“…Although the majority of the compounds were inactive, the antibacterial activity of few candidates was 2-folde15-fold greater than that of reference drug tetracycline; the enhancement of activity for these candidates has been associated with the presence of a benzimidazole system at the nitrogen atom and at least one halogen in the phenolic starting material. In contradiction to the previously mentioned results, a number of naphtho[2,1-e]-1,3-oxazines 121 obtained from variously substituted arylamines were found to be quite active as antibacterial agents towards E. coli and B. subtilis [148]. These compounds were generally more active against the latter pathogen, and the candidates derived from 4-fluoroaniline, 4-ethoxyaniline and 2,4,6tribromoaniline were even more potent than reference drug streptomycin.…”

Redox-Neutral α-Oxygenation of Amines: Reaction Development and Elucidation of the Mechanism

“… 1 The N,O-acetal moiety can be found in a diverse set of natural products 2 and useful synthetic intermediates. 3 Benzoxazines in particular have been studied as nonsteroidal progesterone receptor agonists, 4 as antibacterial agents 5 and as non-nucleoside reverse transcriptase inhibitors for the treatment of human immunodeficiency virus (HIV) 6 as well as for a wide array of other applications. 7 For example, benzo[ e ][1,3]oxazines such as PD 102 807 ( 2a ) have been identified as potent, selective inhibitors of the m4 muscarinic receptor, which have made such compounds important leads in Parkinson’s disease research.…”

Gum arabic-OPO3H2 as a new natural-based green catalyst for the one-pot pseudo-four-component synthesis of naphtho[1,2-e][1,3]oxazines

“…Some of the catalysts that have previously been used for the synthesis of these products are KAl(SO 4 ) 2 $12H 2 O (alum), 22 ZrOCl 2 , 23 1-benzyl-3-methyl imidazolium hydrogen sulfate [bnmim] [HSO 4 ], 24 polyethylene glycol (PEG), 25 and thiamine hydrochloride (VB 1 ). 26 Despite the remarkable achievements for the synthesis of naphtho [1,2-e] [1,3]oxazine derivatives, some of these catalysts have limitations such as inefficient separation of the catalyst from reaction mixtures, unrecyclable and environmental limitations.…”