Tetrabutylammonium Bromide : An Efficient Catalyst for the Synthesis of Xanthenediones under Solvent-free Conditions

TBAB was found to be an effective catalyst for the synthesis of xanthenediones in good to excellent yields under solvent-free conditions. This method has many advantages such as avoiding the use of harmful solvents and catalysts, highyields and simple work-up.


INTRODUCTION
Xanthene derivatives especially xanthenediones have been attracting great interest becauseof their importance in synthetic organic chemistry.Many products thatcontain the subunit of xanthene exhibit usefuland diverse biological activities such as analgesic 1 , antiviral 2 , antibacterial 3 , and anti-inflammatory activities 4 .Some of them have been used as antagonist for paralyzing the action of zoxazolamine, 5 and in photodynamictherapy. 6 Moreover, they can be use as dyes 7 and are used extensivelyin laser technology 8 and pH sensitive fluorescent materials for visualization of biomolecules. 9Many synthetic procedures for preparing xanthenediones have been reported by the condensation of aromatic aldehydes and 5,5-dimethyl-1,3-cyclohexanedione in the presence of alumina-sulfuric acid, 10 Fe 3 O 4 nanoparticles, 11 Fe 3+ -montmorillonite, 1 2 Z r O C l 2 .8 H 2 O , 1 3 s u c c i n i m i d e -N -s u l f o n i c acid, 14 [Et3NH][HSO4], 15 PMA-SiO 2 , 16 silica sulfuric acid, 17 nano Fe 3 O 4 @SiO 2 -SO 3 H, 18 DSIMHS, 19 and zinc oxide nanoparticles. 20though most of these methods offer distinctadvantages, they suffer from certain drawbacks such as high cost, unsatisfactory yields, the use of volatile organic solvents, stoichiometric amount of catalyst, and also environmentally toxic catalyst.Therefore, the search for green and readily available catalyst is still being activelypursed.

Material and Methods
All chemical compounds have purchased from Fluka, Romill and Merck companies and used without further purifications.The progress of the reaction was monitored by thin layer chromatography (TLC).Melting points were determined using Buchi B-540melting point apparatus.FT-IR were recorded by JACSO FT-IR410 spectrophotometerwith KBr plates and 1 H NMR spectra were recorded by Bruker DRX-500 MHz in CDCl 3 .Chemical shifts were expressed inäppm.

General procedure for the synthesis of xanthenediones under solvent-free conditions
A mixture of aromatic aldehydes (1 mmol), 5,5-dimethyl-1, 3-cyclohexanedione (2.2 mmol) and TBAT(40 mol%) under solvent-free conditions was heated at 120 °C and stirred for the required time (Table 2).After completion of the reaction, monitored by TLC, the reaction mixture was allowed to cool to roomtemperature.The crude product was recrystallized fromhot ethanol to afford pure product.

RESULTS AND DISCUSSION
During initial exploratory reaction, condensation of benzaldehyde and 5,5-dimethyl-1, 3-cyclohexanedione were taken as amodel reactionto establish the feasibility of our strategy and to optimize reaction conditions, the results of which are summarized in Table 1.As expected, the catalytic system is influenced by various reaction parameters such as amounts of the catalyst employed (entries 1-4), effect of temperature (entries 4,5), amount of 5,5-dimethyl-1, 3cyclohexanediones (entries 6) and solvent system (entries 7-11).Through thorough investigation, the best result in 92% yield was obtained by carrying out the reaction with 1:2.2 mol ratios of benzaldehyde and 5,5-dimethyl-1, 3cyclohexanedione at 120°C and the dosage of 40 mol% catalyst for 8h under solvent-free conditions.
Encouraged by the remarkable results obtained with the above reaction conditions and in order to show the generality and scope of this new protocol,we performed the reaction with a variety of aromatic aldehydes with different substituents.The results are shown in Table 2. From the results, we found that all aromatic aldehydes carrying either electron-donating or electron-withdrawing group substituents reacted efficiently to give excellent yields.The high yield wasalso obtained in the case of the heterocyclic aldehyde (Table 2, entry16).The desired products were characterized by 1 H NMR, infrared(IR), melting points andalso, by comparison with authentic samples.

CONCLUSION
In conclusion, we have explained an efficient method for the synthesis of xanthenediones catalyzed by TBAB as an inexpensive and readily available ionic liquid.The methodology has the advantages of high yield, lack of organic solvent, and easy work up for separation of products.

Table 2 : The synthesized of xanthenediones catalyzed by TBAB
a Isolated yield