Disodium Phosphate: A Highly Efficient Catalyst for One-Pot Synthesis of Substituted 3,4-Dihydropyrano[3,2-C]Chromenes

Disodium phosphate catalyzed one-pot synthesis of 3,4-dihydropyrano[3,2-c]chromenes, from aldehydes, active methylene compounds malononitrile and 4-hydroxycoumarin in ethanol:water (1:1) under reflux temperature. The attractive features of this process are inexpensive, efficient, as well as user friendly.


INTRODUCTION
Multicomponent reactions have emerged as an efficient, powerful tool in modern organic chemistry for the generation of highly diverse, complex products from readily available substrates in a single operation, without isolation of intermediates, in minimal time, with maximum selectivity, high atom-economy, high purity and excellent yields. Multicomponent reactions are widely used in medicinal chemistry and modern organic synthesis because they are one-pot processes for assembling three or more components [1,2]. MCRs have been successful in the synthesis of 3,4dihydropyrano[c]chromenes and their derivatives which considerable interest due to they have pharmaceutical and biological properties [3], like spasmolytic [4], anti-inflammatory [5], anticancer [6], molluscicidal [7], diuretic [8], anti-coagulant [9].
Disodium phosphate is a very inexpensive, nontoxic, and commercially available compound that can be used in the laboratory without special precautions [29]. As part of our ongoing interest in the use of cheap and ecofriendly materials as catalysts for various transformations [30], we herein report a new method for the synthesis of 2-aminochromenes by the one-pot, three-component reaction of an aromatic aldehyde, malononitrile, and 4hydroxycoumarin in the presence of a catalytic amount of disodium phosphate in ethanol water (1:1) under reflux temperature (Scheme 1).

MATERIAL AND METHODS
The chemicals used aldehydes, active

RESULTS AND DISCUSSION
Considered as a standard model reaction as we examined the reaction 4-chlorobenzaldehyde (1 mmol), malononitrile (1 mmol), 4-hydroxycoumarine (1 mmol) and disodium phosphate (10 mol%) as catalyst dissolved in 10 mL of ethanol:water (1:1) at reflux temperature for 25 -40 min (Scheme 1). The corresponding product was obtained in excellent yield. To determine the effect of solvent, various solvents such as water, ethanol:water (1:3,v:v), ethanol:water (1:2,v:v), ethanol:water (1:1,v:v), ethanol and methanol were used for the model reaction. The desired product was obtained in 37, 61, 71, 95, 95 and 82% yields, respectively, after 30 min at reflux condition. Water:ethanol (1:1) stand out as the solvent of choice among the solvents tested. Because of the rapid conversion and excellent yield (95%) of desired product obtained, whereas the product formed in lower yields (37-95%) by using other solvents (Table 1).
To determine the appropriate concentration of the catalyst disodium phosphate, we investigate the model reaction at different concentrations of catalyst like 2.5, 5, 7.5, 10 and 12.5 mol%. The product formed in 42, 65, 72, 95 and 95% yield, respectively. This indicates that 10 mol% of disodium phosphate is sufficient for the best result by considering the reaction time and yield of product (Table 2). To study the generality of this process, variety of examples were illustrated for the synthesis of dihydropyrano [3,2-c] chromenes and results are summarized in Table 3. The reaction is compatible for various substituents such as -CH 3 , -OCH 3 , -OH, -N(CH 3 ) 2 , NO 2 and -Cl. The formation of desired product has been confirmed by 1 H NMR and IR spectroscopic analysis techniques and compared with the corresponding literature data.

CONCLUSION
In conclusion, this paper describes a simple and proficient approach for the synthesis of dihydropyrano [3,2-c]chromenes catalyzed by disodium phosphate in aqueous alcoholic media. Present methodology offers very attractive features such as simple experimental procedure, higher yields and economic viability.

ACKNOWLEDMENTS
We are thankful to the University Grants Commission, New Delhi, for financial support which is gratefully acknowledged and the Sophisticated Analytical Instrument Facility, Punjab University, Chandigarh for providing spectroscopic data.