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KEYWORDS
Naphth[1,2-e][1,3] oxazines;
Heterocycle;
2-naphthol;
Aromatic aidehydes;
Green catalyst;
Lanthanum chloride.
Abstract. 1-aryl-2,3-dihydro-3-phenyl-1H-naphth[1,2-e][1,3] oxazines are synthesized in good to excellent yields in the presence of LaCl^sub 3^/ClCH^sub 2^COOH as an inexpensive and environmentally benign catalytic system under solvent-free conditions.
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1. Introduction
The N,O-containing heterocycles have received significant attention due to their biochemical activities [1,2]. Additionally, naphthoxazines and their derivatives possess important biological properties, including analgesic, anti-convulsant, anti-tubercular, anti-bacterial and anti-cancer [3-6], and have attracted far more interest due to their therapeutic potential for the treatment of Parkinson's disease [7,8]. The tautomeric character of 1,3-O,N-heterocycles offers a great number of synthetic possibilities [9-11]. Because of the importance of naphthoxazines, the synthesis of new derivatives of these compounds is an important and useful task in organic chemistry.
Multi-Component Reactions (MCRs) are powerful and useful synthetic tools to produce complex organic molecules due to the formation of carboncarbon and carbon-heteroatom bonds in a one-pot process [12-14]. Therefore, the design of novel MCRs has attracted great attention from research groups working in medicinal chemistry and drug discovery.
However, the reported methods for the synthesis of 1,3-diaryl-2,3-dihydro-1H-naphth[1,2-e][1,3]oxazines involve the condensation reaction of 2-naphthol and various substituted aryl and hetero aryl aldehydes in the presence of dry methanolic ammonia, via known two-step reactions [15-17]. In this paper, we report an environmentally benign, solvent-free approach for the synthesis of new naphthoxazine derivatives via multi-component reactions in the presence of LaCl3/ClCH2COOH (Scheme 1).
2. Experimental
2.1. Materials and methods
Chemicals were either prepared in our laboratory or purchased from Merck or Fluka chemical companies, and were used without any further purification. All reactions were monitored by TLC, and petroleum-ether EtOAc, 3:1. Melting points were determined with a hot-plate microscope apparatus. IR spectra were recorded in KBr, using a BRUKER FT-IR spectrophotometer. 1H and 13C NMR spectra were recorded on a Bruker 400-MHz spectrometer using CDCl3 and TMS as the solvent and internal standard, respectively.
2.1.1. Synthesis of phenylmethanimine
A round-bottomed flask (100 ml) was charged with a 6.6 M ammonia solution in methanol (23 ml) and then benzaldehyde (1 g, 9.4 mmol) was added dropwise over time increments of 5 minutes at ambient temperature. After the addition was complete, the reaction mixture...