A green chemoselective one-pot protocol for expeditious synthesis of symmetric pyranodipyrimidine derivatives using ZrOCl 2 . 8 H 2 O

Article history: Received January 21, 2016 Received in revised form July 10, 2016 Accepted 18 August 2016 Available online 18 August 2016 A convenient, highly efficient and time economic method has been described for the chemoand regioselective synthesis of 5-aryloyl-1,3,7,9-tetraalkyl-2,8-dithioxo-2,3,8,9-tetrahydro1H-pyrano[2,3-d:6,5-dˊ]dipyrimidine-4,6(5H,7H)-diones derivatives by one-pot twocomponent reaction of 1,3-diethyl-2-thiobarbituric acid or 1,3-dimethyl-2-thiobarbituric acid with substituted arylglyoxalmonohydrates using commercially available zirconium (IV) oxydichloride octahydrate (ZrOCl2.8H2O) as green Lewis acid catalyst. This method is associated with some attractive characteristics such as good selectivity, very short reaction time, high yield of products, cleaner reaction profile, no harmful by-product, cheap and environmental benign catalyst, simple experimental and work-up procedure. This procedure does not require solvent separation and purification steps such as column chromatography. © 2016 Growing Science Ltd. All rights reserved.


Introduction
Synthesis of required products in selective and environmentally friendly way is an enduring challenge in chemical sciences.3] Recently, ZrOCl 2 .8H 2 O has emerged as very effective catalyst for various organic reactions such as Knoevenagel condensation, 24 Michael addition, 25 oxidation of alcohols, 26 acylation of alcohols, phenols, amines and thiols, 27 aerobic N-methylation of substituted Anilines, 28 esterification of long chain carboxylic acids, 29 one-pot synthesis of heterocyclic compounds, [30][31][32][33][34] and other organic transformations.
6][37][38][39][40][41][42] The pyranopyrimidines showed a broad range of biological activities, such as antitubercular, 43 antimicrobial, 44 antiplatelet, 45 antifungal 46 and antitumor agents 47 as well as antiviral activities. 48As a result, the development of efficient methods for the synthesis of these compounds is one of the most attractive fields in preparative chemistry.Examples of some substituted pyrimidine marketed drugs.

Table 1. Optimization of the reaction conditions
Finally, the structure of the all compounds were confirmed by means of IR, 1 H-NMR and 13 C-NMR spectroscopies and by comparison with available data for previously reported pyrano[2,3-d:6,5-dˊ]dipyrimidines.In the CDCl 3 solution all pyrano[2,3-d:6,5-dˊ]dipyrimidine derivatives exist as mixture of keto and enol tautomers.In the 1 H-NMR spectra, the sharp singlet at 4.91-5.65 ppm, which belongs to CH of pyran ring, was present.Also broad singlet at 8.21-13.18belongs to the OH group of the enol tautomer.

General
Melting points were measured on an Electrothermal 9200 apparatus after the recrystallization of the products from methanol.IR spectra were recorded on a Nexus-670 FT-IR spectrometer in KBr. 1 H and 13 C NMR spectra were recorded on a Bruker DRX-300 Avance spectrometer at 300 and 75.5 MHz, respectively.
Fig. 1.Examples of some substituted pyrimidine marketed drugs.