The reaction of 5,5-dimethylcyclohexane-1,3-dione with various heteroarylaldehydes afforded the corresponding heteroaryl substituted xanthene derivatives 1(a–f). The reaction proceeds via the initial Knoevenagel, subsequent Michael, and final heterocyclization reactions using 1,4-diazabicyclo[2.2.2]octane (DABCO) as a catalyst in aqueous media. The synthesized heteroaryl substituted xanthenes 1(a–f) reacted with malononitrile to obtain different alkylidenes 2(a–f). Short reaction time, environmentally friendly procedure, avoiding of cumbersome apparatus, and excellent yields are the main advantages of this procedure which makes it more economic than the other conventional methods. 1. Introduction In the past few decades, the synthesis of new heterocyclic compounds has been a subject of great interest due to their wide applicability. The importance of multicomponent reactions in organic synthesis has been recognized, and considerable efforts have been focused on the design and development of one-pot procedures for the generation of libraries of heterocyclic compounds [1, 2]. Multicomponent reactions (MCRs) have emerged as an important tool for building of diverse and complex organic molecules through carbon-carbon and carbon-heteroatom bond formations taking place in tandem manner [3]. Particularly, in the last three decades a number of three- and four-component reactions have been developed [4–6]. Xanthene derivatives are very important heterocyclic compounds and have been widely used as dyes [7] and fluorescent materials for visualization of biomolecules and in laser technologies [8]. They have also been reported for their agricultural bactericide activity [9] and anti-inflammatory [10] and antiviral activity [11]. These compounds are also utilized as antagonists for paralyzing action of zoxazolamine and in photodynamic therapy [12]. Due to their wide range of applications, these compounds have received a great deal of attention in connection with their synthesis. A wide variety of methods for the preparation of the xanthenes have been reported [13–19]. However, many of these methods are associated with several shortcomings such as long reaction times (16？h to 5 days), expensive reagents, harsh conditions, low product yields, and use of toxic organic solvents. Diazabicyclo[2.2.2]octane (DABCO) is an inexpensive, nontoxic, and commercially available catalyst that can be used in laboratory without special precautions [20–22]. But, it has not been used as a catalyst in xanthene synthesis; only a few reports are therein the literature [23–25]. This
References
[1]
R. V. A. Orru and M. De Greef, “Recent advances in solution-phase multicomponent methodology for the synthesis of heterocyclic compounds,” Synthesis, no. 10, pp. 1471–1499, 2003.
[2]
A. Domling, “Recent developments in isocyanide-based multicomponent reactions in applied chemistry,” Chemical Reviews, vol. 106, no. 1, pp. 17–89, 2006.
[3]
A. Domling and I. Ugi, “Multicomponent reactions with isocyanides,” Angewandte Chemie International Edition, vol. 39, no. 18, pp. 3168–3210, 2000.
[4]
J. Peng, W. Hao, X. Wang, S. Tu, N. Ma, and G. Zhang, “Microwave-assisted synthesis of pyrazolo[4,3-f]quinolin-7-one derivatives via multi-component reactions,” Chinese Journal of Chemistry, vol. 27, no. 9, pp. 1707–1710, 2009.
[5]
L. F. Tietze, H. Evers, and E. T？pken, “A novel concept in combinatorial chemistry in solution with the advantages of solid-phase synthesis: formation of N-betaines by multicomponent domino reactions,” Angewandte Chemie International Edition, vol. 40, no. 5, pp. 903–905, 2001.
[6]
T. Masquelin, H. Bui, B. Brickley, G. Stephenson, J. Schwerkoske, and C. Hulme, “Sequential Ugi/Strecker reactions via microwave assisted organic synthesis: novel 3-center-4-component and 3-center-5-component multi-component reactions,” Tetrahedron Letters, vol. 47, no. 17, pp. 2989–2991, 2006.
[7]
A. Djandé, M. Kiendrébéogo, M. Compaoré et al., “Antioxidant potential of 4-acyl isochroman-1, 3-diones,” Research Journal of Chemical Sciences, vol. 1, no. 5, pp. 88–90, 2011.
[8]
S. M. Menchen, S. C. Benson, J. Y. L. Lam et al., Patent, US, 6583168, 2003.
[9]
C. G. Knight and T. Stephens, “Xanthene-dye-labelled phosphatidylethanolamines as probes of interfacial pH. Studies in phospholipid vesicles,” Biochemical Journal, vol. 258, no. 3, pp. 683–689, 1989.
[10]
A. K. Bhattacharya and K. C. Rana, “Microwave-assisted synthesis of 14-aryl-14H-dibenzo[a.j]xanthenes catalysed by pTSA in solution and solvent-free conditions,” Mendeleev Communications, vol. 17, no. 4, pp. 247–248, 2007.
[11]
G. Mulongo, J. Mbabazi, B. Odongkara, H. Twinomuhwezi, and G. B. Mpango, “New biologically active compounds from 1, 3-diketones,” Research Journal of Chemical Sciences, vol. 1, no. 3, pp. 102–108, 2011.
[12]
Z. Karimi-Jaberi and M. M. Hashemi, “One step synthesis of 14-alkyl- or aryl-14H-dibenzo[a,j]xanthenes using sodium hydrogen sulfate as catalyst,” Monatshefte fur Chemie, vol. 139, no. 6, pp. 605–608, 2008.
[13]
M. Seyyedhamzeh, P. Mirzaei, and A. Bazgir, “Solvent-free synthesis of aryl-14H-dibenzo[a,j]xanthenes and 1,8-dioxo-octahydro-xanthenes using silica sulfuric acid as catalyst,” Dyes and Pigments, vol. 76, no. 3, pp. 836–839, 2008.
[14]
J. Q. Wang and R. G. Harvey, “Synthesis of polycyclic xanthenes and furans via palladium-catalyzed cyclization of polycyclic aryltriflate esters,” Tetrahedron, vol. 58, no. 29, pp. 5927–5931, 2002.
[15]
G. Casiraghi, G. Casnati, M. Catellani, and M. A. A. Corina, “Convenient one-step synthesis of xanthene derivatives,” Synthesis, no. 8, pp. 564–564, 1974.
[16]
S. Gupta, P. Gupta, A. Sachar, and R. L. Sharma, “Synthetic studies of some varied structural systems of biologically potent polynitrogen heteropolycyclics,” Indian Journal of Chemistry B, vol. 49, no. 9, pp. 1243–1256, 2010.
[17]
M. H. Majid, A. Hamideh, B. Khadijeh, S. Mina, A. O. Hossein, and F. B. Fatemeh, “Solvent-free synthesis of xanthenes derivatives by preyssler type heteropolyacid,” Bulletin of Chemical Society of Ethiopia, vol. 25, no. 3, pp. 399–406, 2011.
[18]
K. Muharrem, “Aldol condensation and michael addition of 4, 4-dimethylcyclohexane-1, 3-dione and aromatic aldehydes. Unconventional substituent effects,” Chinese Journal of Chemistry, vol. 29, no. 11, pp. 2355–2360, 2011.
[19]
A. Ilangovan, S. Malayappasamy, S. Muralidharan, and S. Maruthamuthu, “A highly efficient green synthesis of 1, 8-dioxooctahydroxanthenes,” Chemistry Central Journal, vol. 5, pp. 81–86, 2011.
[20]
B. Baghernejad, “4-Diazabicyclo [2,2,2] octane (DABCO) as a useful catalyst in organic synthesis,” European Journal of Chemistry, vol. 1, no. 1, pp. 54–60, 2010.
[21]
H. Yang, R. Tian, and Y. Li, “Organic reactions catalyzed by 1, 4-diazabicyclo [2.2.2] octane (DABCO),” Frontiers of Chemistry in China, vol. 3, no. 3, pp. 279–287, 2008.
[22]
X. Da-Zhen, Y. Liu, S. Shi, and Y. Wang, “A simple, efficient and green procedure for Knoevenagel condensation catalyzed by [C4dabco][BF4] ionic liquid in water,” Green Chemistry, vol. 12, no. 3, pp. 514–517, 2010.
[23]
M. Bigdeli, “Clean synthesis of 1,8-dioxooctahydroxanthenes promoted by DABCO-bromine in aqueous media,” Chinese Chemical Letters, vol. 21, no. 10, pp. 1180–1182, 2010.
[24]
B. Saeed, R. Sorour, B. Morteza, and H. G. Jurgen, “DABCO-catalyzed efficient synthesis of naphthopyran derivatives via one-pot three-component condensation reaction at room temperature,” Synthetic Communications, vol. 38, no. 7, pp. 1078–1089, 2008.
[25]
K. Y. Lee, J. M. Kim, and J. N. Kim, “Synthesis of 2,3,4,4a-tetrahydroxanthen-1-ones and 3,3a-dihydro-2H-cyclopenta[b]chromen-1-ones from the reaction of salicylaldehydes and 2-cyclohexen-1-one and 2-cyclopenten-1-one,” Bulletin of the Korean Chemical Society, vol. 24, no. 1, pp. 17–18, 2003.
[26]
S. Jain, G. N. Babu, S. R. Jetti, S. Harshada, and D. Suryaprakash, “Synthesis, antitubercular and antifungal activities of heteroaryl -substituted oxirance derived from Baylis-Hillman adducts,” Medicinal Chemistry Research, vol. 21, no. 10, pp. 2744–2748, 2012.
[27]
S. Jain, P. Paliwal, and G. N. Babu, “DABCO promoted one-pot synthesis of dihydro pyrano(c) chromene and pyrano[2, 3-d]pyrimidine derivatives and their biological activities,” Journal of Saudi Chemical Society, 2011.
