Nano TiO 2 : An Efficient Catalyst for the Synthesis of Biscoumarins in Aqueous Medium

An easy method for the synthesis of biscoumarins through a one-pot reaction of 4hydroxycoumarin and aryl aldehydes under very mild reaction conditions using nano TiO2 as catalyst in aqueous medium is described. The products were obtained in short reaction times with excellent yields under reflux. This method is of great value because of its environmentally benign character, high yield processing, and easy handling. We believe this applicability of nano-TiO2 with mentioned advantages makes our method superior over all previous reported methods to the synthesis of biscoumarins.

These problems prompted us towards further investigation in search for a new catalyst, which will carry out the synthesis of biscoumarins under simpler experimental set up and environmentally friendly conditions.In this article, we present a onepot reaction for the preparation of biscoumarins derivatives in the presence of nano TiO 2 in aqueous medium(Scheme1).

EXPERIMENTAL
All of the chemical material used in this work purchased from Fluka or Merk and without further purification.Melting points were recorded on an Electrothermal type 9100 melting point apparatus.The IR spectra were obtained on a 4300 Shimadzu spectrophotometer in KBr disks.The 1 H NMR(500 MHz) spectra were recorded on a Bruker-Ac-500 spectrometer.

General procedur for the synthesis of biscoumarins (3a-h)
A solution of 4-hydroxycoumarin 1 (2mmol), an aromatic aldehyde 2a-h (1 mmol) and nano TiO 2 (5 mol% based on aromatic aldehyde) in H 2 O (10 ml) was heated on the oil bath under reflux for the time period as indicated in table 2. Theprogress of the reaction was monitored by TLC.After completion of the reaction, the mixture was cooled to room temperature and the solid product was collected by filtration and washed with cold water.The solid residue was diluted with chloroform (5 ml) and the catalyst was separated.The filtrate was evaporated on rota-evaporator to give a solid which was dried and recrystallized from ethanol to afford pure products 3a-h in high yields.All the products were identified by comparing the analytical data(Melting point, IR, H NMR) with those reported or with authentic samples prepared by the conventional method, in which we used nano TiO 2 as the catalyst.The results are summarized in the table 2.

RESULT AND DISCUSSION
To initiation our study the reaction of4hydroxycoumarin with benzaldehyde were employed as a model reaction to examine the effect of various solvents such as EtOH, MeOH, CHCl 3 and H 2 O and varying amount of nano TiO 2 (5, 10, 15 and 20mol%) as catalyst.In an optimized reaction conditions, 4-hydroxycoumarin (2 mmol) and benzaldehyde (1 mmol) in H 2 O (10 ml) were mixed in the presence of nano TiO 2 (0.05 mmol) for 5 min.The reaction proceeds very cleanly under reflux and was free of side products.After completion of the reaction (monitored by TLC), a simple work up affords the products in high yields (Table 2).Among the solvents tested, the reaction in chloroform using 5 mol% of the catalyst gave a low yield of the desired product.Ethanol and methanol gave moderate to good yields under this conditions.However, the reaction in H 2 O with 5mol% of catalyst afforded product 3a in 96% yields.Using more than 5 mol% of catalyst, has less effect of the yield and time of the reaction.
As shown in table 1, no desirable products could be detected in the absence of catalyst for 120 min, which indicated that the catalyst should be absolutely necessary for this reaction.Only a trace product was obtained in the solvent-free conditions in the presence of 5 mol% of the catalyst even at 110°C.After optimization of the reaction conditions to experimental trials illustrating this method for the synthesis of derivatives were conducted.The results are summarized in table 2.
Benzaldehyde and other aromatic aldehydes containing electron-withdrawing groups (such as halide and nitro groups) or electrondonating groups (such as hydroxyl, methyl and methoxy groups) were employed which were found to react well to give the corresponding biscoumarin derivatives in high yields.

CONCLUSIONS
In conclusion, we have described a highly efficient one-pot synthesis for the preparation of biscoumarin derivatives in the reaction of 4hydroxycoumarin and aryl aldehydes in the presence of nano TiO 2 as catalyst.Easy work up, shor t reaction time, environmentally, ready commercial availability of the catalyst and high yields, make the procedure an attractive alternative to the existing methods for the synthesis of biscoumarin derivatives.

Table 1 : Effect of nano TiO 2 amount and solvent on the model reaction a
b Isolated yields.

Table 2 : Nano TiO 2 catalyzedsynthesis of biscoumarins 3a-h a
b The products were characterized by comparison of their spectroscopic and physical data with authentic samples synthesized by reported procedures.c Isolated yield.