A highly efficient green synthesis of 1 , 8-dioxo-octahydroxanthenes

SmCl3 (20 mol%) has been used as an efficient catalyst for reaction between aromatic aldehydes and 5,5-dimethyl1,3-cyclohexanedione at 120°C to give 1,8-dioxo-octahydroxanthene derivatives in high yield. The same reaction in water, at room temperature gave only the open chain analogue of 1,8-dioxo-octahydroxanthene. Use of ecofriendly green Lewis acid, readily available catalyst and easy isolation of the product makes this a convenient method for the synthesis of either of the products. Background 1,8-dioxo-octahydroxanthenes are important class of oxygen heterocycle in which a phenyl substituted pyran ring is fused on either side with two cyclohexenone rings. Presence of conjugated bis-dienone functionality makes these compounds sensitive to attack by nucleophiles and light energy. In the recent past, there is a renewed interest in the synthesis of this class of compounds as number of its applications increased, both in the field of medicinal chemistry and material science. 1,8-dioxo-octahydroxanthenes shows useful biological activities such as anti-inflammatory, antibacterial, antiviral activities [1], finds use in biodegradable agrochemicals [2,3], cosmetics and pigments [4], fluorescent materials [5], photodynamic therapy [6], luminescent sensors [7], and in laser technologies [8]. The formation of intermediate, 2,2’-arylmethylenebis(3-hydroxy-5,5dimethyl-2-cyclohexene-1-one), in the synthesis of 1,8dioxo-octahydroxanthenes can take place even without a catalyst [9]. However, there is always need for a catalyst in the cyclization step to get the cyclized compound [9-12]. A variety of reagents, mainly acids, have been employed to accomplish this transformation [11,13-27]. However many of these reagents has its own disadvantages, such as use of expensive reagents, high catalyst loading and low yield. On exposure to water, conventional Lewis acids such as AlCl3, ZnCl2, BCl3 etc., decomposes whereas lanthanide Lewis acids shows high hydrolytic stability. In fact, several organic reactions catalysed by lanthanide Lewis acids are carried out in water [28]. The catalysts can be recovered and reused without loss of much activity, thus considered to be green Lewis acids. SmCl3 is one of the readily available inexpensive Lewis acids which is ranked as “hard” according to the hard soft acids and bases (HSAB) concept [29]. SmCl3 is an excellent catalyst used in several important organic transformations such as selective removal of acid sensitive protecting groups like Boc, THP and TBDMS in the presence of one another [30], C-acylation of 1, 3-dicarbonyl compounds and malononitrile [31], and in the formation of ether from allylic alcohols [32]. SmCl3 is also used in electro reductive alkylation of ketones [33] and cleavage of allyl ethers [34]. Considering that there is a need for the use of more useful greener acid catalyst we examined SmCl3, a water resistant, reusable, lanthanide Lewis acid for the synthesis of 1,8-dioxo-octahydroxanthenes. Here in we report a highly efficient and clean synthesis of 1,8-dioxo-octahydroxanthenes using SmCl3. Results and Discussion Reaction between 4-NO2-benzaldehyde (1d, 1 mole) and dimedone (2, 2 mole) in presence of SmCl3 was identified as the test reaction and different reaction parameters were studied for the formation of corresponding 1,8-dioxo-octahydroxanthene. Considering the fact that SmCl3 is a water resistant Lewis acid the reaction was carried out in water at room temperature (RT). The reaction was complete in 15 min. However, it was only, the open chain, compound 2,2’-((4-nitrophenyl)methylene)bis(3-hydroxy-5,5-dimethylcyclohex-2-enone) (3d, * Correspondence: ilangovanbdu@yahoo.com School of Chemistry, Bharathidasan University, Tiruchirappalli 620024, India Full list of author information is available at the end of the article Ilangovan et al. Chemistry Central Journal 2011, 5:81 http://journal.chemistrycentral.com/content/5/1/81 © 2011 Ilangovan et al Table 1, Scheme 1, entry 1) obtained as the sole product, in very good yield. Formation of the open chain compound was confirmed from H-NMR spectra of 3d which shows a peak corresponding to phenyl methylene proton at δ 5.54. The reaction mixture when left at RT for 24 h in water (entry 2) or heated at 100°C in water for 24 h (entry 3) gave only the open chain compound 3d. Heating a neat reaction mixture with SmCl3 (10 mol %, entry 4) at 100°C, for 24 h gave cyclised product 4d in 40% yield. However, heating the neat reaction mixture in presence of SmCl3 (20 mol%) at 120°C for 8 h, led to the formation of cyclised product 4d in excellent yield (entry 5, 98%). Based on these results it was concluded that use of SmCl3 (10 mol %) in water, at room temperature and SmCl3 (20 mol %) without solvent at 120°C would be the useful conditions for the formation of open chain compound 3d and the 9-phenyl1,8-dioxo-octahydroxanthane (4d) respectively. A series of examples illustrating versatility of this method was studied using aromatic, hetero aromatic and aliphatic aldehydes (Scheme 2) and the results are summarized in Table 2. In case of formation of open chain compounds 3a to 3o, irrespective of whether it has electron donating or withdrawing substituents on the aromatic ring all the starting materials underwent reaction within 30 min. However, wide difference in reaction rate could be observed, in the formation of xanthenediones 4a to 4m. Among the different nitro benzaldehydes studied, 4nitro-benzaldehyde (1d) underwent reaction faster (8 h) compared to 3-nitro-benzaldehyde (1c, 10 h, entry 3) and 2-nitro-benzaldehyde (1b, 13 h) to give the product 4b, 4c and 4d respectively. Steric hindrance of the 2nitro group may the reason for slow reaction rate. In case of halo substituted benzaldehydes 1e-1g, the mesomerically electron donating character was predominant hence the reaction took place fast (entry 5, 6 and 7) compared to substrates with electron withdrawing substituents. The effect of 4-CH3 substituent was so mild that the 4-CH3-benzaldehyde (1h) did not make any difference in reaction rate (entry 8, 5 h) compared to unsubstituted benzaldehyde (1a). In case of benzaldehydes 1i and 1j (entry 9, and 10), containing just one electron donating substituent, the rate of reaction was fast compared to compounds with electron withdrawing substituents. A significant increase in the rate of the reaction could be observed when more than one electron donating groups (entry 11, 12 and 13) are present. The reaction condition was tolerant to ether, phenolic -OH group. In case of furfuraldehyde (1n) and cinnamaldhyde (1o) the open chain compounds 3n and 3o were obtained in excellent yield where as the corresponding cyclised products 4n and 4o was obtained only in minor quantity along with a mixture of side products. In order to improve the yield of cyclised products 4n and 4o, different reaction conditions were tried by varying the quantity of the catalyst from 20 mol % to 100 mol % and the reaction temperature from ambient to 85°C. None of the reaction conditions gave better result. Polymerisable nature of the furyl ring and cinnamoyl group may be the reason for low yield of the product. Spectral data and melting point observed for all the products were comparable with data reported in the literature (please check additional files 1 and 2). In order to know the efficiency of SmCl3 the data reported in the literature for the synthesis of compound Table 1 Optimisation of condition for reaction between dimedone and 4-NO2-benzaldehyde in the presence of SmCl3 Entry Solvent SmCl3 mol % Time Temp°C Yield b %

On exposure to water, conventional Lewis acids such as AlCl 3 , ZnCl 2 , BCl 3 etc., decomposes whereas lanthanide Lewis acids shows high hydrolytic stability. In fact, several organic reactions catalysed by lanthanide Lewis acids are carried out in water [28]. The catalysts can be recovered and reused without loss of much activity, thus considered to be green Lewis acids. SmCl 3 is one of the readily available inexpensive Lewis acids which is ranked as "hard" according to the hard soft acids and bases (HSAB) concept [29]. SmCl 3 is an excellent catalyst used in several important organic transformations such as selective removal of acid sensitive protecting groups like Boc, THP and TBDMS in the presence of one another [30], C-acylation of 1, 3-dicarbonyl compounds and malononitrile [31], and in the formation of ether from allylic alcohols [32]. SmCl 3 is also used in electro reductive alkylation of ketones [33] and cleavage of allyl ethers [34]. Considering that there is a need for the use of more useful greener acid catalyst we examined SmCl 3 , a water resistant, reusable, lanthanide Lewis acid for the synthesis of 1,8-dioxo-octahydroxanthenes. Here in we report a highly efficient and clean synthesis of 1,8-dioxo-octahydroxanthenes using SmCl 3 .

Results and Discussion
Reaction between 4-NO 2 -benzaldehyde (1d, 1 mole) and dimedone (2, 2 mole) in presence of SmCl 3 was identified as the test reaction and different reaction parameters were studied for the formation of corresponding 1,8-dioxo-octahydroxanthene. Considering the fact that SmCl 3 is a water resistant Lewis acid the reaction was carried out in water at room temperature (RT). The reaction was complete in 15 min. However, it was only, the open chain, compound 2,2'-((4-nitrophenyl)methylene)bis(3-hydroxy-5,5-dimethylcyclohex-2-enone) (3d, * Correspondence: ilangovanbdu@yahoo.com 1 School of Chemistry, Bharathidasan University, Tiruchirappalli -620024, India Full list of author information is available at the end of the article Table 1, Scheme 1, entry 1) obtained as the sole product, in very good yield. Formation of the open chain compound was confirmed from 1 H-NMR spectra of 3d which shows a peak corresponding to phenyl methylene proton at δ 5.54. The reaction mixture when left at RT for 24 h in water (entry 2) or heated at 100°C in water for 24 h (entry 3) gave only the open chain compound 3d. Heating a neat reaction mixture with SmCl 3 (10 mol %, entry 4) at 100°C, for 24 h gave cyclised product 4d in 40% yield. However, heating the neat reaction mixture in presence of SmCl 3 (20 mol%) at 120°C for 8 h, led to the formation of cyclised product 4d in excellent yield (entry 5, 98%).
Based on these results it was concluded that use of SmCl 3 (10 mol %) in water, at room temperature and SmCl 3 (20 mol %) without solvent at 120°C would be the useful conditions for the formation of open chain compound 3d and the 9-phenyl1,8-dioxo-octahydroxanthane (4d) respectively. A series of examples illustrating versatility of this method was studied using aromatic, hetero aromatic and aliphatic aldehydes (Scheme 2) and the results are summarized in Table 2.
In case of formation of open chain compounds 3a to 3o, irrespective of whether it has electron donating or withdrawing substituents on the aromatic ring all the starting materials underwent reaction within 30 min. However, wide difference in reaction rate could be observed, in the formation of xanthenediones 4a to 4m. Among the different nitro benzaldehydes studied, 4nitro-benzaldehyde (1d) underwent reaction faster (8 h) compared to 3-nitro-benzaldehyde (1c, 10 h, entry 3) and 2-nitro-benzaldehyde (1b, 13 h) to give the product 4b, 4c and 4d respectively. Steric hindrance of the 2nitro group may the reason for slow reaction rate. In case of halo substituted benzaldehydes 1e-1g, the mesomerically electron donating character was predominant hence the reaction took place fast (entry 5, 6 and 7) compared to substrates with electron withdrawing substituents.
The effect of 4-CH 3 substituent was so mild that the 4-CH 3 -benzaldehyde (1h) did not make any difference in reaction rate (entry 8, 5 h) compared to unsubstituted benzaldehyde (1a). In case of benzaldehydes 1i and 1j (entry 9, and 10), containing just one electron donating substituent, the rate of reaction was fast compared to compounds with electron withdrawing substituents. A significant increase in the rate of the reaction could be observed when more than one electron donating groups (entry 11, 12 and 13) are present. The reaction condition was tolerant to ether, phenolic -OH group.
In case of furfuraldehyde (1n) and cinnamaldhyde (1o) the open chain compounds 3n and 3o were obtained in excellent yield where as the corresponding cyclised products 4n and 4o was obtained only in minor quantity along with a mixture of side products. In order to improve the yield of cyclised products 4n and 4o, different reaction conditions were tried by varying the quantity of the catalyst from 20 mol % to 100 mol % and the reaction temperature from ambient to 85°C. None of the reaction conditions gave better result. Polymerisable nature of the furyl ring and cinnamoyl group may be the reason for low yield of the product. Spectral data and melting point observed for all the products were comparable with data reported in the literature (please check additional files 1 and 2).
In order to know the efficiency of SmCl 3 the data reported in the literature for the synthesis of compound

Conclusion
In conclusion, SmCl 3 , a water resistant Lewis acid was used for the synthesis of 3,3,6,6-tetramethyl-9-aryl-3,4,5,6,7,9-hexahydro-2H-xanthene-1,8-dione derivatives or its open chain analogue depending upon the reaction condition. Water was used as the green solvent, and the catalyst could be recovered and reused. The reaction work up is very simple, solid separated from the reaction mixture was filtered washed with water to recover the catalyst and dried to get the desired xanthenedione derivatives. This procedure offers several advantages such as use of inexpensive green catalyst, operational simplicity, cleaner reaction and minimal environmental impact, high yield, thus making it one of the attractive and practical protocols for the synthesis of xanthenediones. Further studies on the use of xanthenediones as visible light sensitizers and as better excited state electron donors to TiO 2 for application in dye sensitised solar cells are in progress.