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Catalysis Communications 9 (2008) 939942 www.elsevier.com/locate/catcom

1-Methylimidazolium triouroacetate ([Hmim]TFA): An ecient reusable acidic ionic liquid for the synthesis of 1,8-dioxo-octahydroxanthenes and 1,8-dioxo-decahydroacridines
Minoo Dabiri *, Mostafa Baghbanzadeh, Elham Arzroomchilar
Department of Chemistry, Faculty of Science, Shahid Beheshti University, Postal Code 1983963113, Evin, Tehran, Iran Received 20 June 2007; received in revised form 18 September 2007; accepted 19 September 2007 Available online 26 September 2007

Abstract Bronsted acidic ionic liquid, 1-methylimidazolium triouroacetate ([Hmim]TFA) catalyzed synthesis of 1,8-dioxo-octahydroxanth enes and 1,8-dioxo-decahydroacridines in excellent yields and short period of times at 80 C. Anions eects of the ionic liquid on the reaction rate have been investigated. The ionic liquid was easily separated from the reaction mixture by water extraction and was recycled four times without any loss in activity. 2007 Elsevier B.V. All rights reserved.
Keywords: Catalyst; 1,8-Dioxo-octahydroxanthenes; 1,8-Dioxo-decahydroacridines; Ionic liquid; Heterocycle

1. Introduction Ionic liquids (ILs) are now well known as salts with melting points below 100 C, and typically have broad liquid ranges, low vapor pressures, and may be both noncoordinating, but highly polar. They are receiving considerable global attention because they oer a unique environment for chemistry, biocatalysis, separation science, material synthesis, and electrochemistry [1]. The implementation of task specic ionic liquids (TSILs) further enhances the versatility of classical ionic liquids where both reagent and medium are coupled [25]. The union of reagent with medium has been found to be a viable alternative approach toward modern synthetic chemistry especially when considering the growing environmental demands being placed on chemical processes. Xanthene derivatives are parent compounds of a large number of naturally occurring, as well as synthetic deriva-

Corresponding author. Tel.: +98 21 22431661; fax: +98 21 22431663. E-mail address: m-dabiri@sbu.ac.ir (M. Dabiri).

tives, and occupy a prominent position in medicinal chemistry [68]. In particularly, xanthenediones constitute a structural unit in a number of natural products [9], and have been used as versatile synthons because of the inherent reactivity of the inbuilt pyran ring [10]. The synthesis of xanthenediones usually condenses appropriate active methylene carbonyl compounds with aldehydes catalyzed by sulfuric acid or hydrochloric acid [11]. Recently, Van Vranken et al. described two-step synthesis of 9-aryl-6hydroxy-3H-xanthen-3-one uorophores by condensation of aryl aldehydes and uororesorcinol [12]. Singh et al. [13] reported another method for the preparation of xanthenediones through carbon transfer reactions of 1,3-oxazinanes and oxazolidines with carbon nucleophiles. Regarding the availability and the economic viability of starting materials, the rst method is far superior to the second method. Therefore, many alternative catalysts, such as p-toluenesolfonic acid [14], p-dodecylbenzenesulphonic acid [15], InCl3/ionic liquid [16], Fe3+-montmorilonite [17], NaHSO4SiO2 or silica chloride [18], amberlyst-15 [19], and silica sulfuric acid [20] have been reported for the synthesis xanthenedione derivatives. However, some of them often involve the use of expensive reagents, hazard

1566-7367/$ - see front matter 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.catcom.2007.09.023

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M. Dabiri et al. / Catalysis Communications 9 (2008) 939942

organic solvents, and tedious workup. Hence, a more realistic catalyzed condensation between active methylene carbonyl compound and aldehyde is needed for contemporary chemical synthesis with less waste and more facile isolation of products, perhaps with reuse of the catalysts as well.

3. Results and discussion In our continued interest in the development of a highly expedient methodology [2227] for the synthesis of ne chemicals and heterocyclic compounds of biological importance, we report here the synthesis of 1,8-dioxooctahydroxanthenes, and 1,8-dioxo-decahydroacridines in the presence of 1-methylimidazolium triouroacetate ([Hmim]TFA) as an acidic IL. We rst studied a reaction between 5,5-dimethyl-1,3cyclohexanedione (1) and 4-chlorobenzaldehyde by screening the reaction conditions. In order to determine the optimum conditions, we examined the inuence of the reaction temperature, the reaction time, the amounts of IL, and the type IL (Table 1). In all reaction the conditions were optimized for a 100% conversion. It could be seen that the best result was obtain with 0.1 g of [Hmim]TFA at 80 C (Table 1, entry 7). After optimizing the conditions, we next examined the generality of these conditions to other substrates using several aromatic aldehydes (Scheme 1). The results are summarized in Table 2. It could be seen that [Hmim]TFA as environmentally benign acidic IL catalyzed the condensation of dimedone, and a wide range of aromatic aldehydes at 80 C. As indicated in Table 2, in all cases the reaction gives the products in good yields and prevents problems which many associate with solvent use such as cost, handling, safety and pollution.
Table 1 Optimization of the reaction condition Entrya 1 2 3 4 5 6 7 8 9 10 11 12 13
a b c d

2. Experimental 2.1. General Melting points were measured on an Electrothermal 9100 apparatus and are uncorrected. Mass spectra were recorded on a FINNIGAN-MAT 8430 mass spectrometer operating at an ionization potential of 70 eV. 1H and 13C NMR spectra were recorded on a BRUKER DRX-300 AVANCE spectrometer at 300.13 and 75.47 MHz, respectively. IR spectra were recorded on a Bomem MB-Series FT-IR spectrophotometer. 2.2. Synthesis of ionic liquid The synthesis of ionic liquid has been carried out using a similar method reported in the literature [21]. 1-Methylimidazole was placed in a two-necked ask, which was equipped with a magnetic stirrer and cooled in an ice water bath. A small amount of water was added and then the triuoroacetic acid (1 equiv.) was added slowly with stirring. The reaction mixture was stirred for an additional period of 2 h. Then water in the crude product was evaporated with a rotary evaporator at 70 C and thus a colorless liquid product was obtained. The ionic liquid was formed quantitatively and in high purity as assessed by NMR. 2.3. General procedure for the synthesis of 1,8-dioxooctahydroxanthene derivatives To a mixture of an aromatic aldehyde (1 mmol) and 5,5dimethyl-1,3-cyclohexanedione (2 mmol) in a round bottom ask [Hmim]TFA (100 mg) was added. The mixture was heated at 80 C and the reaction was monitored by TLC. After completion of the reaction, water added to the mixture and ltered. The solid residue was recrystallized from ethanol. 2.4. General procedure for the synthesis of 1,8-dioxodecahydroacridine derivatives A primary amine (1.2 mmol) was added to the mixture of an aromatic aldehyde (1 mmol) and 5,5-dimethyl-1, 3-cyclohexanedione (2 mmol) in [Hmim]TFA (100 mg). The reaction was conducted under the conditions as above. After completion of the reaction, water added to the mixture and ltered. The solid residue was recrystallized from ethanol.

ILb [Hmim]TFA [Hmim]TFA [Hmim]TFA [Hmim]TFA [Hmim]TFA [Hmim]TFA [Hmim]TFA [Hmim]TFA [Hmim]TFA [Hmim]HClO4 [Hmim]HSO4 [Hmim]BF4 d

Temperature (C) 25 35 45 50 60 70 80 90 100 80 80 80 80

Yield (%)c Trace Trace 15 40 70 75 90 91 90 50 55 70 40

Time (h) 12 12 12 12 10 6 3 3 2.5 3 3 3 12

In all reaction the conditions were optimized for a 100% conversion. The reactions were run in the presence of 0.1 g of IL. Isolated yield. The reaction was run under neat condition.

O O 2 O + ArCHO [Hmim]TFA (0.1 g) 80C 1 2

Ar

O 3a-3k

Scheme 1.

M. Dabiri et al. / Catalysis Communications 9 (2008) 939942 Table 2 Synthesis of 1,8-dioxo-octahydroxanthenes by the reaction of 5,5dimethyl-1,3-cyclohexanedione and aromatic aldehydes in the presence of [Hmim]TFA at 80 C Product 3a 3b 3c 3d 3e 3f 3g 3h 3i 3j 3k
a b

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Table 3 Synthesis of 1,8-dioxo-decahydroacridines by the reaction of 5,5-dimethyl1,3-cyclohexanedione, aromatic aldehydes and primary amines in the presence of [Hmim]TFA at 80 C Product 5a 5b 5c 5d 5e 5f 5g 5h 5i 5j 5k
a b

Ar C6H5 2-ClC6H4 4-ClC6H4 2,4-(Cl)2C6H3 2-NO2C6H4 4-NO2C6H4 4-BrC6H4 4-FC6H4 4-HOC6H4 4-H3CC6H4 4-H3COC6H4

Yield (%)a 85, 86, 84, 85b 83 93 82 80 82 91 89 90 94 88

Time (h) 3 4 2.5 4 4 3.5 3 3 3 3 3

Referencec [17] [17] [17] [20] [20] [17] [20] [20] [17] [17] [17]

Ar C6H5 2-ClC6H4 4-ClC6H4 4-H3CC6H4 4-HOC6H4 3-NO2C6H4 C6H5 4-H3COC6H4 4-H3COC6H4 4-H3COC6H4 4-H3COC6H4

R 4-H3CC6H4 4-H3CC6H4 4-H3CC6H4 4-H3CC6H4 4-H3CC6H4 4-H3CC6H4 C6H5 C6H5 3-NO2C6H4 C6H5CH2CH2 C6H5CH2

Yield (%)a 85 82 84 86 83 84 86 82 78 82 89

Time (h) 5 6 5 4 5 5 4.5 4.5 7 4 4

Referenceb [19] [19] [19] [19] [19] [19] [19] [19] [19] [19] [19]

Isolated yield. IL was reused for four runs. c All the products are known compounds and were characterized from their spectroscopic (1H NMR and MS) properties.

Isolated yield. All the products are known compounds and were characterized from their spectroscopic (1H NMR and MS) properties.

To make this method more suitable we examine the reusability of the [Hmim]TFA, using 5,5-dimethyl-1,3cyclohexanedione and benzaldehyde, as model substrates. For this aim after completion of the reaction (monitored by TLC), water added to the reaction mixture and then the solid was isolated by ltration. The IL in water could be recovered easily by evaporation at 80 C in vacuum. The recovered IL was washed with diethyl ether. After evaporation at 80 C in vacuum for 1 h, IL was assessed by 1H NMR spectroscopy and no traces of 5,5-dimethyl1,3-cyclohexanedione and benzaldehyde were detected. Investigations proved the successive reuse of the recovered ionic liquid. It could be seen that no considerable change in activity of [Hmim]TFA was observed even after four consecutive runs (Table 2, product 3a). 4-Aryl-1,4-dihydropyridines (1,4-DHPs) have proved to be valuable as drugs for the treatment of cardiovascular disorders [28], and constitute an important class of calcium channel blockers [29,30]. With a 1,4-DHP parent nucleus, 1,8-dioxo-decahydroacridines have been shown to have very high lasing eciencies [31] and used as photoinitiators [34]. Many acridinediones have been synthesized by the reactions of aldehydes with 2 equiv. of 1,3-cyclohexanedione or 5,5-dimethyl-1,3-cyclohexanedione and appropriate amines via various methods [3235]. Encouraged by these results, we carried out reaction of 5,5-dimethyl-1,3-cyclohexanedione (1), aromatic aldehydes, and primary amines in the presence of 0.1 g [Hmim] at 80 C, which aorded 1,8-dioxo-decahydroacridine

derivatives 5a5k in excellent yields within a short period of time (Scheme 2, Table 3). Here also the aromatic aldehydes containing both electron-donating and electronwithdrawing groups aorded the products with high yields. Aromatic as well as aliphatic amines underwent the conversion equally. Work-up procedure was so simple and including addition of water at the end of reaction, ltration, and nally recrystallizing the products from ethanol. 4. Conclusion In conclusion, we have developed a novel and ecient method for the synthesis of 1,8-dioxo-octahydroxanthenes and 1,8-dioxo-decahydroacridines in high yields employing [Hmim]TFA as an acidic IL. The application of an inexpensive, easily available and reusable IL makes this method simple, clean, practical and economically viable. The method is an easy access to functionalized xanthenes and acridines. Acknowledgement Financial support by the Research Council of Shahid Beheshti University is gratefully acknowledged. References
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O O 2 O + ArCHO + RNH2 [Hmim]TFA (0.1 g) 80C 1 2 4

Ar

N R 5a-5k

Scheme 2.

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