SYNTHESIS OF 2-AMINO-4 H-PYRAN-3-CARBONITRILES : ITS REACTION TO CHLOROACETYL CHLORIDE

s. Some 2-amino-4-aryl-3-cyano-5-ethoxycarbonyl-6-methyl-4H-pyrans were synthesized by reaction of by using three-component reaction included ethyl acetoacetate, malononitrile and appropriate substituted benzaldehydes. The role of different catalysts was examined, including organic and inorganic substances and ionic liquids. Some 2-amino-4Hpyran-3-carbonitriles were converted by reacting to chloroacetyl chloride. The structures of the obtained compounds were confirmed by the modern spectroscopic methods (IR, H NMR, C NMR).


Introduction
Six-membered heterocyclic compounds containing oxygen such as 4H-pyrans constitute an important class of biologically active natural and synthetic products, playing a fundamental role in bioorganic chemistry and continue to attract interest.Among nitrogen and oxygen containing heterocyclic compounds, pyranopyrimidine and isoxazole pharmacophores are widely used in medicinal chemistry [1,2].Polyfunctionalized 4H-pyran derivative exhibits antibacterial and anti-cancer activity, is an inhibitor of EAAT1 [3] and their fused derivatives, pyranopyrimidines, are important synthetic bioactive compounds.In the recent years the synthesis of pyranopyrimidine derivatives gained renewed interest in the field of medicinal chemistry for their wide range of biological activity including antiplatelet [4], antiviral [5], antimicrobial [6,7], antimalarial [8], antigenic [9], antitumor [10], anti-inflammatory [11], antihistamine [12], ect.properties.We reprted herein the synthesis of 2-amino-4H-pyran-3carbonitriles and its reaction with chloroacetyl chloride.
Strong absorption band in range of 2203-2187 cm -1 belonged to nitrile group.Ester functional group was confirmed by absorption bands in regions at 1728-1695 cm -1 (C=O ester), 1267-1225 and 1065-1057 cm -1 (C-O-C ester).The carbon-carbon double bonds of benzene ring had some absorption bands in regions at 1611-1490 cm -1 .Two alkene bonds of pyran ring had absorption bands in regions at 1684-1674 and 1649-1620 cm -1 .
The 1 H and 13 C NMR spectral data of substituted 2-amino-4-aryl-3-cyano-5ethoxycarbonyl-6-methyl-4H-pyrans (2a-e) shown that protons and carbon-13 atoms in these molecules have proper resonance signals in corresponding spectral regions which are characteristic for each type of atoms (Figs. 1 and 2).Aromatic protons had chemical shifts in region at δ = 8.12-7.26ppm with multiplicities changed in depending on substituted patterns of benzene ring.Resonance signal of amino group on position 6 of pyran ring had signal in range at δ = 7.09-6,91 ppm in singlet.Proton H-4 on pyran ring had chemical shift in region of δ = 5.03-4.30ppm in singlet.2-Amino-3-cyano-4H-pyrans (2a-e) reacted with chloroacetyl chloride.The reaction was carried out in anhydrous DMF at room temperature for 24 hrs.The solution of pyrans 2a-e became dark brown after chloroacetyl chloride was added.The obtained NMR spectral data showed that the ring-closure take place and 4-oxo-3,5-dihydro-4H-pyrano[2,3-d]pyrimidines (3a-e) were formed.Two stretching vibration bands of amino group were absent in its IR spectra.Strong absorption band of nitrile function did not also find at 2203-2187 cm -1 in IR spectra.
Some changes were happened in NMR of these compounds (Figs. 3 and 4).Signal in singlet of amino group of compounds 2a-e that located in range at δ = 7.09-6,91 ppm was disappeared, simultaneously, a new signal in singlet appeared downfield at 13.34-10.70ppm that belonged to amide NH group in pyrimidin-4(3H)-one ring.All above discursions on spectroscopic characteristics asserted the structure of obtained (2a-e and 3a-e).

Experimental Section
Melting points were determined by open capillary method on STUART SMP3 instrument (BIBBY STERILIN, UK) and are uncorrected.IR spectra (KBr disc) were recorded on an Impact 410 FT-IR Spectrometer (Nicolet, USA), 1 H and 13 C NMR spectra were recorded on Avance Spectrometer AV500 (Bruker, Germany) at 500 MHz and 125.8 MHz, respectively, using DMSO-d6 as solvent and TMS as internal standard.Analytical thin-layer chromatography (TLC) was performed on silica gel 60 WF254S (Merck, Germany).

Figure 1 . 1 H
Figure 1. 1 H NMR of pyran 2b.Carboxyl group of ester had chemical shift in range of δ = 165.92-165.31ppm.The following evidences confirmed the presence of propargylic group.Chemical shift that occurred in region of δ = 120.19-119.42belonging to nitrile group on position 5. Methyl group had signal at δ = 2.35-2.27ppm in singlet pattern in 1 H NMR spectra and δ = 18.79-18.59ppm in 13 C NMR spectra.