One-pot green and efficient synthesis of xanthenedione derivativesusing [C₄ (mim) ₂](FeCl₄)₂as a magnetic room temperature dicationic ionic liquid

Introduction

Xanthene derivatives are very important heterocyclic compounds and have been widely used as dyes fluorescent materials for visualization of bio-molecules and laser technologies due to their useful spectroscopic properties.¹They have also been reported for their agricultural bactericide activity, photodynamic therapy, anti-inflammatory effect,and antiviral activity.^2-5Due to their wide range of applications, these compounds have received a great deal of attention in connection with their synthesis.

Magnetic ILs not only have the excellent properties of IL but also exhibit an unexpectedly strong response to an additional magnet. These properties make magnetic ILs have more advantages and potential application prospects than conventional ILs in the fields of catalytic reactions, solvent effects and separation processes.¹¹ [19]. Although several types of magnetic ionic liquids have been created in recent years, there have been only a few reports about their applications as catalyst in chemical transformations.

In continuation of our work on the catalytic properties of magnetic ionic liquids,^12-13 herein, we wish to report a simple, convenient and efficient method for the use of magnetic room temperature dicationicionic liquid (MRTDIL)as catalyst for preparation of 1, 8- dioxo- octahydroxanthenes derivatives.

Experimental

Material and Methods

Melting points were measured on an Electrothermal 9100 apparatus and are uncorrected.¹H &¹³ CNMR spectra were recorded on a Bruker Advanced DPX 400 MHz instrument spectrometer using TMS as the internal standard in CDCl₃. IR spectra were recorded on a BOMEM MB-Series 1988 FT-IR spectrometer. Raman spectroscopy were recorded on a Bruker RFS 100/s Raman spectrometer. Aldehydes, and dimedone were purchased from Merck Company in high purity. Products were characterized by comparison of their physical and spectroscopic data with those of known samples.

Procedure for the preparation of [C₄ (mim)₂]Cl₂(A)

1, 4-Dicholorobutane (1 mmol)was reacted with 1-methylimidazole (2 mmol), respectively, stirred in MeOH, refluxed for 24 h, and then precipitated from ethyl acetate to obtain the required product (white solid 1a, yield 94%).

Procedure for preparation of [Pbmim](FeCl₄)₂ as a magnetic room temperature dicationic ionic liquid

[C₄(mim)₂](FeCl₄)₂, MRTDIL, was prepared by mixing crystal powder of [pbmim]Cl₂(1 mmol) with anhydrous FeCl₃ (2 mmol) at room temperature for 3h, a dark brown liquid was obtained.  The obtained MRTDIL was extracted with small amount of ethyl acetate. The solvent was evaporated and the resulting clear brown liquid was dried in vacuum oven at 60 °C for 24 h. The MRTDIL was obtained in high yield (89%).

General procedure for preparation of 1, 8-dioxo-octahydro-xanthenes (3a-l)

A mixture of dimedone/1, 3-cyclohexanedione (2 mmol), aromatic aldehyde (1 mmol) and MRTDIL (20% mol) was heated at 80 °C for an appropriate time (Table 2). After completion of the reaction (TLC), the mixture was cooled to room temperature and washed with cooled water. The solid product was purified by crystallization from aqueous EtOH to afford products 3a-3m (Scheme 2).

All the products were fully characterized by spectroscopic data and their melting points are compared with reported values.

Spectral data

9-(phenyl)- 3,3,6,6-tetramethyl – 3,4,5,6,7,9- hexahydro-1H-xanthene-1,8-(2H)-dione (3a): ¹H

NMR (CDCl3, 400 MHz) δ: 1.02 (s, 6H), 1.13 (s, 6H), 2.19 (d, (2H, J = 16.2 Hz), 2.26 (d, 2H, J =16.2 Hz), 2.50 (s, 4H), 4.78 (s, 1H), 7.12 (t, 1H, J = 7.2 Hz), 7.24 (t, 2H, J = 7.5 Hz), 7.32 (d, 2H, J= 7.6Hz). ¹³C NMR(CDCl₃, 100 MHz) δ: 27.75, 29.69, 32.26, 32.61, 41.29, 51.18, 116.07, 126.76, 128.45, 128.80, 144.54, 162.70,

Results and Discussion

The supported acidic PEG-MDIL catalyst was prepared according previously reported (Scheme 1).¹³

Scheme1: Synthesis of [C4 (mim) 2] (FeCl4)2 as a magnetic room temperature dicationic ionic liuquid  Click here to View Scheme

 

Figure1: Visible spectrum of [C4(mim)2](FeCl4)2   Click here to View figure

 

Due to the paramagnetic nature of the [C₄(mim)₂](FeCl₄)₂, nuclear magnetic resonance technique could not be used to confirm its structure. Instead, UV spectra was used to characterize the [C₄(mim)₂](FeCl₄)₂ structure. The UV spectrum is shown in Figure 1. [C₄(mim)₂](FeCl₄)₂ spectra exhibited absorption bands in the visible region at 534, 620 and 680 nm which are characteristic for the FeCl₄^– anion.In order to be able to carry out preparation of 1, 8- dioxo- octahydroxanthenes derivatives in a more efficient way minimizing the time, temperature and amount of catalyst, the reaction of benzaldehyde, and dimedone was selected as model system to the effects of the catalyst at different reaction temperatures (25, 60, 80 and 100 °Cand the different amount of catalyst (0, 10, 20, 30, and 40% mol) were investigated. The reaction using 20% mol of MRTDIL at 80 °C proceeded in highest yield.

Further increase in temperature to, 100 °Chad little effect on the rate of reaction. Therefore, we kept the reaction temperature at 80 °C as optimal temperature.

This reaction was carried out without catalyst under solvent free conditions in order to establish the effectiveness of the catalyst. It was found that 1, 8- dioxo- octahydroxanthenes was not made after 1h of heating. The best results were obtained with 1: 2 ratio of benzaldehyde, dimedone, and 20% mol of MRTDIL after 10 min at 80 °C.

After optimizing the conditions, the generality of this process was demonstrated by the wide range of substituted aryl aldehydes to synthesize the corresponding products in excellent yields (Scheme 2, Table 1). As seen from Table 1, aromatic aldehydes having electron-donating as well as electron-withdrawing groups were uniformly transformed into the corresponding products in high yields within 10-15 min. Substituent on the aromatic ring had no obvious effect on yield or reaction time under the above optimal conditions. Unlike some previously reported methods; the present method does not require toxic organic solvents to produce the 1, 8-dioxo-octahydroxanthene derivatives.

The success of the above reactions prompted us to investigate the recyclability of catalyst. We carried out our study by using the reaction benzaldehyde with dimedone and under optimal conditions as a model study. For this aim, after completion of reaction (monitored by TLC), water was added to the reaction mixture and then the solid was isolated by filtration. The aqueous filtrate was then subjected to distillation at 80°C under reduced pressure (10 mmHg) for 4 h to recover the IL almost completely. The IL, thus recovered could bereused five times without loss of activity for the typical reaction (Fig 2).

The efficiency of MRTDIL (time, yield, reaction conditions) was compared with the efficiencies of other catalysts used in synthesis of 1, 8-dioxooctahydroxanthenes, the results are presented in Table 2. It is clear that the presented method is simpler, more efficient and less time consuming compared with other Methods.

Figure2: Recyclability of the catalyst  Click here to View figure

 

Scheme2: Synthesis of 1, 8-dioxo-octahydro-xanthenes Click here to View Scheme

 

Table 1. Synthesis of xanthenes derivatives ^aIsolated yiel

Entry	Ar	Product	R	Time (min)	Yield (%)a	M.P (°C)Found	Reportedref
1	C6H5	3a	CH3	10	92	203-204	204-20514
2	4-Cl-C6H4	3b	CH3	10	90	230-232	230-23114
3	4-Br-C6H4	3c	CH3	10	90	240-241	240-24215
4	2-Cl-C6H4	3d	CH3	10	91	225-227	224-22614
5	3-Cl-C6H4	3e	CH3	10	91	184-186	183-18414
6	4-NO2-C6H4	3f	CH3	10	89	222-223	22214
7	2-NO2-C6H4	3g	CH3	15	87	248-249	246-24814
8	3-NO2-C6H4	3h	CH3	15	89	171-173	170-17214
9	4-OCH3-C6H4	3i	CH3	15	88	241-243	242-24414
10	4-CH3-C6H4	3j	CH3	15	89	215-217	217-21814
11	4-CN-C6H4	3k	CH3	15	90	218-220	23016
12	4-CN-C6H4	3l	H	15	89	268-270	273-27517

 

Table 2. Comparison of results using MDIL catalyst with results obtained by other workers

Catalyst	Conditions	Time (h)	Yield %  Rf
Silica sulfuric acidInCl3  .4H2OFe3+-montmorilloniteNaHSO4 -SiO2Amberlyst-15[C4(mim)2](FeCl4)2	Solvent- free/80°CIonic liquid/80°CEtOH(reflux)CH3CN(reflux)CH3CN(reflux)Solvent-free/80°C	1-2.5  4-10 6 6   5     0.08- 0.25	88-97      [9]76-95      [6]84-96      [10]90-98      [7]90-96      [8]87-91        –

 

Conclusion

In conclusion, we have successfully developed a simple and green catalytic procedure for the efficient synthesis of xanthenes using MRTDIL and under mild reaction conditions. MRTDIL can replace the ILs and other homogeneous catalysts with reasonable recovery and reusability and therefore suitable for industrial applications.

Acknowledgments

We gratefully thank Islamic Azad University, Science and Research Branch Omidiyeh for financial support.

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