Fast and convenient synthesis of new symmetric pyrano [ 2 , 3-d : 6 , 5d ' ] dipyrimidinones by an organocatalyzed annulation reaction

Article history: Received August 21, 2016 Received in revised form October 24, 2016 Accepted 7 December 2016 Available online 7 December 2016 A fast and facile one-pot procedure for the preparation of symmetric 5-Aryloyl-1,9-dimethyl5,9-dihydro-2H-pyrano[2,3-d:6,5-d']dipyrimidine-2,4,6,8(1H,3H,7H)-tetraone derivatives by two-component reaction of N-methylbarbituric acid and arylglyoxalmonohydrates catalyzed by DABCO in ethanol at 50 oC is described. This protocol has the advantages of environmental friendless, very simple operation, high regioand chemoselectivity and moderate to excellent yields. © 2017 Growing Science Ltd. All rights reserved.


Introduction
Fused heterocyclic scaffolds have attracted the attention of chemists due to their unique characteristics and wide applications in medicinal chemistry and material science. 1 For example, fusedpyran derivatives are an important class of heterocyclic scaffolds demonstrates a broad range of biological and pharmacological activities (Fig 1). 2 Among different fused-pyran derivatives, pyranopyrimidines are of significant importance in terms of their bioactivities (Fig 2). 3   One-pot multicomponent reactions are highly efficient methods for the synthesis of natural and unnatural products due to their great advantages in environmental friendless. 4  Green chemistry 5 emphasizes on the use of catalysts with specific properties such as high activity, costeffective preparation, high stability and safety and also high selectivity. 6In recent years, organocatalysis 7 has enhanced its importance as a tool for the synthesis of heterocyclic compounds. 8 1,4-diazabicyclo[2.2.2]octane (DABCO) has emerged as an efficient organic base which has been successfully used for various organic transformations like Baylis-Hillman reaction, 9 o-alkylations of phenols, 10 synthesis of glycidic amidester, 11 cross-coupling reactions 12 and heterocyclic compound synthesis. 13  As part of an ongoing investigation on the synthesis of heterocyclic compounds, 14 especially pyrano [2,3-d:6,5-d']dipyrimidine scaffolds, 15 herein we wish to report a fast and convenient one-pot two-component process for the regio-and chemoselective synthesis of 5-aryloyl-1, 9-dimethyl-5,9dihydro-2H-pyrano[2,3-d:6,5-d']dipyrimidine-2,4,6,8(1H,3H,7H)-tetraone derivatives from the reaction between N-methylbarbituric acid and arylglyoxalmonohydrates in ethanol medium at 50 ºC in the presence of DABCO as green base-organocatalyst (Scheme 1).Scheme1.One-pot two-component synthesis of pyrano [2,3-d:6,5-d']dipyrimidinederivatives catalyzed by DABCO
As shown in Table 2, we investigated the reaction with a wide range of arylglyoxalmonohydrates with electron donating and electron withdrawing groups.Both electron rich and electron-deficient arylglyoxalmonohydrates worked well and give moderate to excellent yields of products under the optimization reaction conditions.
The structures of all products were secured on the basis of their spectral data.With surveys conducted on the spectrum data (especially 1 H NMR and FT IR data) determined that no exist any tautomeric forms ( such as lactam-lactim or keto-enol tautomeric forms) in the structure of all the obtained 5-Aryloyl-1, 9-dimethyl-5,9-dihydro-2H-pyrano[2,3-d:6,5-d']dipyrimidine-2,4,6,8(1H,3H,7H)-tetraone derivatives (Scheme 3).For example, in the 1 H NMR spectrum of 3a which is obtained as a sole product, the C5-H proton of the pyran ring appears as a singlet at a δ= 5.92 ppm and also the singlet pick in the region of 9.53 ppm belong to the two NH protons.

General
Melting points were determined on an Electrothermal 9200 apparatus. 1H (300 MHz) and 13 C (75.5 MHz) NMR spectra were recorded on a BRUKER DRX-300 AVANCE spectrometer in DMSO-d6 with tetramethylsilane as internal standard.Infrared spectra were recorded on a Perkin Elmer Spectrum Two FT-infrared spectrophotometer, measured as KBr disks.Microanalyses were performed on a Leco Analyzer 932.
Scheme 2. Possible structures of pyranodipyrimidine derivatives

Table 1 .
Optimization reaction conditions for the synthesis of 9a