Cobalt ( II ) Chloride Hexahydrate as an Efficient and Inexpensive Catalyst for the Preparation of Biscoumarin Derivatives

Cobalt(II) chloride hexahydrate (CoCl 2 ⋅6H 2 O) has been found to be an efficient catalyst for the one-pot synthesis of biscoumarin derivatives through a combination of aromatic aldehydes and 4-hydroxycoumarin in aqueous media at 70C. Several types of aromatic aldehyde, containing electron-withdrawing groups as well as electron-donating groups, were used in the reaction and in all cases the desired products were synthesized successfully. The present approach offers remarkable advantages such as short reaction times, excellent yields, straightforward procedure, easy purification, environment friendliness, and low catalyst loading.

We hoped to develop a more general protocol for the efficient synthesis of biscoumarin derivatives via CoCl 2 ⋅6H 2 O, which have recently attracted much attention as catalyst to organic synthesis due to their low toxicity and easy availability [16][17][18].
For this study, a reaction between 4-hydroxycoumarin (2 mmol) and 3-nitrobenzaldehyde (1 mmol) was examined as the model reaction.Initial studies showed that better results could be obtained in the presence of ( All reactions were carried out in aqueous ethanol at 70 ∘ C. a Isolated yields. (Table 1, entry 1).When the amount of CoCl 2 ⋅6H 2 O was increased over 10 mol%, neither the yield nor the reaction time was improved (Table 1, entry 3).
To study the effect of temperature on this synthesis, we also performed four experiments in aqueous ethanol at room temperature, 50, and 70 (Celsius degrees) and under reflux condition (Table 2).It was observed that the yield of the product is maximum at 70 ∘ C (Table 2, entry 3).
During the optimization of the reaction condition, various solvents were also screened to test their efficiency and the results are summarized in Table 3.The highest reaction activity was achieved in the system using aqueous ethanol (1 : 1, H 2 O : EtOH) as a solvent in comparison to other solvents under similar reaction conditions (Table 3, entry 5).
With these encouraging results in hand, the generality of this reaction was examined using various aromatic aldehydes containing electron-donating as well as electronwithdrawing groups.In all cases, the reactions gave the corresponding products in good yields and short reaction times without formation of any byproducts (Table 4).Substituents on the aromatic ring had no obvious effect on yield or reaction time under the above optimal conditions.
In order to assess the efficiency of this methodology, the obtained result from the reaction of 3-nitrobenzaldehyde with 4-hydroxycoumarin by this method has been compared with those of the previously reported methods.As demonstrated in Table 5, the use of CoCl 2 ⋅6H 2 O leads to an improved protocol in terms of compatibility with environment, reaction time, yield of the product, and amount of the catalyst when compared with other catalysts.

Experimental
3.1.Materials and Methods.All reagents were purchased from Fluka, Merck, and Aldrich with high-grade quality and used without any purification.The reactions were monitored by TLC.Visualisation of the developed chromatogram was performed by UV light (254 nm).All yields refer to isolated products after purification.Products were characterized by comparison with authentic samples and by spectroscopy data (IR, 1 H NMR spectra).IR spectra were recorded from KBr disk on the FT-IR Bruker Tensor 27. 1 H NMR spectra were recorded on a Bruker Avance 400 MHz spectrometer using TMS as an internal standard (DMSO-d 6 solution).Melting points were measured by using the capillary tube method with IA 9000 series thermal analyser.

General Procedure for the Synthesis of Biscoumarin
Derivatives.A mixture of the 4-hydroxycoumarin (2 mmol), aromatic aldehyde (1 mmol), and CoCl 2 ⋅6H 2 O (10 mol%) was stirred in 5 mL aqueous ethanol (1 : 1, H 2 O : EtOH) 70 ∘ C for the appropriate time.Completion of the reaction was indicated by TLC.After the completion, the reaction mixture was filtered off and washed with n-hexane (2×5 mL) to obtain pure products.As the catalyst is completely soluble in distilled water, it was easily separated from the reaction mixture.All of the products are known compounds and were characterized by IR and 1 H NMR spectroscopic data and their melting points are compared with reported values.

Conclusion
In conclusion, we have developed a green, practical, and facile approach for the preparation of biscoumarin derivatives through the three-component reaction of 4-hydroxycoumarin and aromatic aldehydes using a catalytic amount of CoCl 2 ⋅6H 2 O as an efficient and inexpensive catalyst.The distinguished advantages of this procedure are (i) simple experimental procedure, (ii) mild reaction conditions, (iii) high to excellent yields of products, (iv) short reaction times, (v) and utilization of an inexpensive and readily available catalyst.
a Isolated yields.