Article pubs.acs.org/IECR
Chitosan: An Efficient, Reusable, and Biodegradable Catalyst for Green Synthesis of Heterocycles Pramod K. Sahu,†,‡,* Praveen K. Sahu,‡,§,* Sushil K. Gupta,†,‡ and Dau D. Agarwal†,‡,§ †
School of Studies in Chemistry, Jiwaji University, Gwalior 474011, Madhya Pradesh, India Department of Industrial Chemistry, Jiwaji University, Gwalior 474011, Madhya Pradesh, India § Jagdishprasad Jhabarmal Tibrewala University, Jhunjhunu 333001, Rajasthan, India ‡
S Supporting Information *
ABSTRACT: A convenient and rapid method is described for the synthesis of nitrogen heterocyclic derivatives by one-pot three-component reaction of substituted aromatic aldehydes, dicarbonyl- and 2-aminobenzothiazole/3-amino-1,2,4-triazole/ urea/thiourea using commercially available chitosan in 2% acetic acid in aqueous media at 60−65 °C. Chitosan was used as an efficient biodegradable and reusable green catalyst for this multicomponent reaction. The chitosan catalyst can be reused 10 times in fresh reaction. Catalytic activity has been sustained in the first five runs but slightly decreased in subsequent cycles.
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INTRODUCTION Chitosan (CS) is an example of a polysaccharide that is widely distributed in living organisms. Being hydrophilic and possessing basic moieties,1,2 chitosan (Figure 1) is a particularly attractive polysaccharide for application in catalysis.3 Chitosan is actually a heteropolymer containing both glucosamine units and acetylglucosamine units.4 Among various biopolymers, chitosan based materials have attracted great interest as support for catalytic applications.5 Chitosan, due to natural polymer, can be suitable for various homogeneous and heterogeneous catalyst. Chitosan based material has been used as solid catalyst in Suzuki cross-coupling,6 Ullmann reaction,7 Michael addition reaction,8 [3 + 2] Huisgen cycloaddition,9 Heck reaction,10 aldol and Knoevenagel reaction,11 and carbonate and pyridazine synthesis.12 In recent years, the emphasis of science and technology has shifted more toward environmental benign and sustainable resources and progress: in this regard, use of natural catalyst is a good approach. In particular, natural biopolymers are important candidates to explore for catalyst. Multicomponent reactions (MCRs)13 are a powerful tool and have attracted much attention of synthetic organic chemists because of the ability to build of complex molecules with a diverse range of complexity which can easily be achieved from readily available starting materials. Among various carbonyl compounds, 1,3-dicarbonyl derivatives represent important synthetic building blocks, incorporating multiple functionalities.14 Octahydroquinazolinones,15 quinazolines,16 and pyrimidines17 possess interesting pharmacological activities. Shaabani et al.18 have synthesized 4H-pyrimido[2,1-b]benzothiazole derivatives using ionic liquid at 100 °C with poor yields. The drawback of ionic liquids is that they cannot be removed by distillation and their limited solubility in water restricts their use. They have high cost and also acute toxicity for aquatic organisms and humans.19 Rao et al.20 have also synthesized these types of derivatives which suffers from many drawbacks such as hazardous solvent, long reaction time, harsh reaction conditions, and lower yield. According to a literature © 2014 American Chemical Society
survey, methods reported for the synthesis of octahydroquinolinone and octahydroquinoline derivatives also suffer from several drawbacks such as long reaction time, hazardous microwave condition, low yield with byproducts, and usage of heavy and hazardous metal catalysts.21 To the best of our knowledge, chitosan has not been reported as a catalyst in multicomponent synthesis in aqueous media for the synthesis of 4H-pyrimido[2,1-b]benzothiazole (1a−1h), 1,2,4-triazoloquinazolines (2a−2e), octahydroquinazolinones (3a−3h), and fused thiazolo[2,3-b]quinazolinone (4a,4b) derivatives. The present work reports the synthesis of libraries of nitrogen heterocycles using chitosan as a biodegradable green catalyst in water as a green solvent.
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RESULTS AND DISCUSSION Per our knowledge, this is the first time that chitosan was used as a catalyst in aqueous solution of 2% acetic acid for onepot synthesis of compounds 1a−1h, 2a−2e, 3a−3h, and 4a,b (Schemes 1 and 2). To gain optimization of reaction conditions, first of all we studied the effect of different solvents. The target product was obtained in trace amount in all organic solvents. This is due to the insolubility of chitosan catalyst. Chitosan is soluble in minimum 1% aqueous acetic acid solution. With optimized condition in hand, a variety of electron donating and electron withdrawing groups on aromatic aldehydes have been studied (Tables 1 and 2). There was no significant effect of electron donating and electron withdrawing substituents in case of compounds 1a−1h and 4a,b. But in case of compounds 2a−2e and 3a−3h, yield was affected by electron withdrawing and electron releasing groups. All of the electron withdrawing groups showed lower yield with higher reaction time as compared to Received: Revised: Accepted: Published: 2085
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Figure 1. Chemical structure of chitosan.
(10 mL) at 65 °C. The reaction time of 100 min was observed as the optimum time (Figure 2). Further increasing the reaction time does not increase yield. In order to optimize the appropriate loading of catalyst, synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives was carried out using ethyl acetoacetate (5 mmol), benzaldehyde (5 mmol), and 2-aminobenzothiazole (5 mmol) using 0.01, 0.02, 0.05, 0.08, 0.1, and 0.15 g of chitosan (Table 3, entries 1−6) and different amounts of acetic acid (0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4.0%), respectively in 10 mL aqueous medium (Table 3, entries 7−12). The highest yield was obtained with 0.08 g of chitosan in 2% aqueous acetic acid solution. Increasing the amount of chitosan neither improved the yield nor reaction time. At 2.5−4% concentration, a viscous gel was formed and the resultant yield of the target product decreased (Table 3, entries 10−12). No product was formed in the presence of 2% acetic acid (without catalyst; Table 3, entry 14). Acetic acid was used in this reaction only for homogenizing the chitosan catalyst and itself did not work as catalyst which has already been studied in experiment (Table 3, entry 14). We further tested the efficacy of the present catalyst in terms of its reusability in a three-component reaction of ethyl acetoacetate, benzaldehyde, and 2-aminobenzothiazole (Figure 3). After completion of the reactions, solid mass was filtered and the filtrate having chitosan catalyst was reused in the next run as such without any further treatment. Recycled chitosan catalyst was reused for 10 times. No significant yield loss was found in the first five runs, but yield decreased instantly in the subsequent five cycles (Figure 4).
Scheme 1. Preparation of 4H-Pyrimido [2,1-b]benzothiazole Derivatives
donating groups. the meta substituted electron releasing group (Table 2, entry 9) has also shown a lower yield as compared to other electron releasing groups in the series. Results also suggest that reaction proceeds smoothly in the case of 3-amino-1,2,4triazole or urea or thiourea rather than 2-aminobenzothiazole. To optimize the effect of reaction time on the yield of the target product, a model reaction was carried out at different times (20, 40, 60, 80, 100, 120, and 140 min) using ethyl acetoacetate (5 mmol), benzaldehyde (5 mmol), and 2-aminobenzothiazole (5 mmol) in 0.08 g of chitosan in 2% aqueous acetic acid solution
Scheme 2. Synthesis of Octahydroquinazolinones 1,2,4-Triazoloquinazolines and Pyrimidines
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Table 1. Synthesis of 4H-Pyrimido[2,1-b]benzothiazole (1a−1h) Derivativesa
a
Reagents and reaction conditions: Ethyl acetoacetate (5 mmol), aldehydes (5 mmol), 2-aminobenzothiazole (5 mmol), chitosan (0.08 g) in 2% acetic acid in aqueous solution, 80−100 min, at 60−65 °C. bIsolated yield (84−93%). 1
Mechanism. A plausible reaction mechanism for the threecomponent reaction of benzaldehyde, diketone, and amine scaffold catalyzed by chitosan catalyst is shown in Scheme 3. The free amino groups in chitosan distributed on the surface
H NMR spectra of chitosan were the same before and after the reaction do not show any structural changes in chitosan catalyst, which reveals the stability of chitosan catalyst during the consecutive cycles (Figure 5). 2087
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Table 2. Synthesis of 1,2,4-Triazoloquinazoline, Octahydroquinazolinone, and Fused Thiazolo[2,3-b]quinazolinone Derivativesa
a
Reagents and reaction conditions: Dimedone (5 mmol), aromatic aldehydes (5 mmol), 2-aminobenzothiazole or urea or thiourea or 3-amino-1,2,4triazole (5 mmol), chitosan (0.08 g) in 2% acetic acid in aqueous solution, 55−100 min, at 60−65 °C. bIsolated yield (72−96%).
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of chitosan activate the carbonyl group of benzaldehyde through nucleophilic attack to produce the corresponding intermediate. Furthermore, ethyl acetoacetate reacts with this intermediate through Knoevenagel type condensation and produces Knoevenagel condensate by removing water molecules. Knoevenagel intermediate (using benzaldehyde and ethyl acetoacetate) has been characterized using spectroscopic analysis (see the Supporting Information). Chitosan catalyst may be free which again participates in the mechanism. Then the amine moiety is reacted with Knoevenagel condensate through Michael addition to afford the target product.
CONCLUSION
In conclusion, herein is described a new readily recovered biopolymer catalytic system for synthesis of libraries of nitrogen heterocyles using a one-pot three-component reaction of aromatic aldehydes, 1,3-dicarbonyl, and urea/thiourea/ 2-aminobenzothiazole/3-amino-1,2,4-triazole in the presence of aqueous solution of chitosan catalyst in 2% acetic acid. The operational simplicity and availability of starting materials make it a rather forward alternative procedure than traditional multistep methods. The main advantages of this methodology are the ecofriendly catalyst system, recyclability, freedom from organic solvents, and ease of the workup procedure. 2088
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Table 3. Optimization of Chitosan Catalysta
Figure 2. Optimization of reaction time and yield.
entry
chitosan loading, solvent
yieldb
1 2 3 4 5 6 7 8 9 10 11 12 13 14
0.01 g, 2% acetic acid in water 0.02 g, 2% acetic acid in water 0.04 g, 2% acetic acid in water 0.08 g, 2% acetic acid in water 0.1 g, 2% acetic acid in water 0.15 g, 2% acetic acid in water 0.08g, 0.5% acetic acid in water 0.08 g, 1% acetic acid in water 0.08 g, 2% acetic acid in water 0.08 g, 2.5% acetic acid in water 0.08 g, 3% acetic acid in water 0.08 g, 4% acetic acid in waterc water no catalystd
21 46 67 93 93 93 61 77 93 73 65 22
a
Reagents and reaction conditions: Ethyl acetoacetate (5 mmol), benzaldehydes (5 mmol), 2-amino benzothiazole (5 mmol), chitosan (0.08 g) in 2% acetic acid in aqueous solution, at 60−65 °C. bIsolated yield. cNot easy to workup. dIn 2% acetic acid aqueous solution (without chitosan).
In addition, we have isolated and characterized the Knoevenagel intermediate and established a correct mechanistic pathway. Scaled-up Process for Phenyl 4H-Pyrimido[2,1-b]benzothiazole (1a). A 500 mL, three-necked, round-bottom flask equipped with a thermometer and water condenser was charged with 200 mL of an aqueous solution of 2% acetic acid and 1.6 g of chitosan. Benzaldehyde (100 mmol, 10.61 g), 2-aminobenzothiazole (100 mmol, 15.02 g), and ethyl acetoacetate (100 mmol, 13.01) were added into the above solution: the resulting mixture was stirred and refluxed at 65 °C. The reaction was monitored by thin-layer chromatography (TLC) analysis and completed within 2 h. Precipitate was formed which was filtered after completion of the reaction. Phenyl 4H-pyrimido[2,1-b]benzothiazole (1a) was obtained in 91.8% yield and has mp 178−180 °C. The characteristic data for the isolated product were found to be the same as those given in the Supporting Information. Synthesis of Knoevenagel Intermediate. A mixture of ethyl acetoacetate (5 mmol) and benzaldehyde (5 mmol) was heated at 60−65 °C using chitosan (0.08 g) in 2% acetic acid in aqueous solution. After completion of the reaction (judged
Figure 3. Reusability of chitosan catalyst.
Figure 4. Reusability of catalyst.
Figure 5. 1H NMR of chitosan catalyst. 2089
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Scheme 3. Plausible Mechanistic Pathway by Chitosan Catalyst
by TLC analysis), precipitate was formed which was filtered to obtain product. The characteristic data for the Knoevenagel intermediate has been given in the Supporting Information.
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chitosan-silica hybrid microspheres as potential catalyst. Chem. Mater. 2004, 16, 3367. (4) Roberts, G. A. F. Chitin chemistry; MacMillan: London, U.K., 1992. (5) (a) Guibal, E. Heterogeneous catalysis on chitosan-based materials: A review. Prog. Polym. Sci. 2005, 30, 71. (b) Macquarrie, D. J.; Hardy, J. J. E. Applications of functionalized chitosan in catalysis. Ind. Eng. Chem. Res. 2005, 44, 8499. (6) Martina, K.; Leonhardt, S. E. S.; Ondruschka, B.; Curini, M.; Binello, A.; Cravotto, G. In situ cross-linked chitosan Cu(I) or Pd(II) complexes as a versatile, eco-friendly recyclable solid catalyst. J. Mol. Catal. A: Chem. 2011, 334, 60. (7) Zeng, M.; Zhang, X.; Shao, L.; Qi, C.; Zhang, X. M. Highly porous chitosan microspheres supported palladium catalyst for coupling reactions in organic and aqueous solutions. J. Organomet. Chem. 2012, 704, 29. (8) Khalil, K.; Al-Matar, H.; Elnagdi, M. Chitosan as an eco-friendly heterogeneous catalyst for Michael type addition reactions. A simple and efficient route to pyridones and phthalazines. Eur. J. Chem. 2010, 1, 252. (9) Chtchigrovsky, M.; Primo, A.; Gonzalez, P.; Molvinger, K.; Robitzer, M. Functionalized chitosan as a green, recyclable, biopolymer-supported catalyst for the [3 + 2] Huisgen cycloaddition. Angew. Chem., Int. Ed. 2009, 48, 5916. (10) Liu, P.; Wang, L.; Wang, X. Y. Chitosan-immobilized palladium complex: A green and highly active heterogeneous catalyst for Heck reaction. Chin. Chem. Lett. 2004, 15, 475. (11) (a) Reddy, K. R.; Rajgopal, K.; Maheswari, C. M.; Kantam, M. L. Chitosan hydrogel: A green and recyclable biopolymer catalyst for aldol and Knoevenagel reactions. New J. Chem. 2006, 30, 1549. (b) Kuhbeck, D.; Saidulu, G.; Reddy, K. R.; D́ ıaz, D. D. Critical assessment of the efficiency of chitosan biohydrogel beads as recyclable and heterogeneous organocatalyst for C−C bond formation. Green Chem. 2012, 14, 378. (12) (a) Sun, J.; Wang, J.; Cheng, W.; Zhang, J.; Li, X.; Zhang, S.; She, Y. Chitosan functionalized ionic liquid as a recyclable biopolymersupported catalyst for cycloaddition of CO2. Green Chem. 2012, 14, 654. (b) Ghozlan, S. A. S.; Mohamed, M. H.; Abdelmoniem, A. M.; Abdelhamid, I. M. Chitosan as a green catalyst for synthesis of pyridazines and fused pyridazines via [3 + 3] atom combination with arylhydrazones as 3 atom components. ARKIVOC 2009, x, 302.
ASSOCIATED CONTENT
S Supporting Information *
Text describing the general experimental procedure and details of characterization data of the products. This material is available free of charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Authors
*(Pramod K. Sahu) Tel.: +91-9993932425. E-mail: sahu.
[email protected];
[email protected]. *(Praveen K. Sahu) Tel.: +91-8826757921. E-mail:
[email protected]. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We gratefully acknowledge to Dr. Yogesh Sharma, Parabolic Drugs Ltd., Chandigarh, India, and SAIF Punjab University, Chandigarh, India, for spectral analytical data.
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REFERENCES
(1) Niola, F.; Basora, N.; Chornet, E.; Vidal, P. F. A rapid method for the determination of the degree of N-acetylation of chitin-chitosan samples by acid hydrolysis and HPLC. Carbohydr. Res. 1993, 238, 1. (2) Rege, P. R.; Block, L. H. Chitosan processing: Influence of process parameters during acidic and alkaline hydrolysis and effect of the processing sequence on the resultant chitosan’s properties. Carbohydr. Res. 1991, 321, 235. (3) (a) Valentin, R.; Molvinger, K.; Quignard, F.; Brunel, D. Supercritical CO2 dried chitosan: An efficient intrinsic heterogeneous catalyst in fine chemistry. New J. Chem. 2003, 27, 1690. (b) Molvinger, K.; Quignard, F.; Brunel, D.; Boissire, M.; Devoisselle, J. M. Porous 2090
dx.doi.org/10.1021/ie402037d | Ind. Eng. Chem. Res. 2014, 53, 2085−2091
Industrial & Engineering Chemistry Research
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linone derivatives in the presence of H6P2W18O62·18H2O as a green and reusable. Mol. Diversity 2008, 12, 181. (b) Heravi, M. M.; Derikvand, F.; Ranjbar, L. Sulfamic acid-catalyzed, three-component, one-pot synthesis of [1,2,4]triazolo/benzimidazolo quinazolinone derivatives. Synth. Commun. 2010, 40, 677. (c) Kidwai, M.; Saxena, S.; Khan, M. K. R.; Thukral, S. S. Synthesis of 4-aryl-7,7-dimethyl1,2,3,4,5,6,7,8-octahydroquinazoline-2-one/thione-5-one derivatives and evaluation as antibacterials. Eur. J. Med. Chem. 2005, 40, 816. (d) Niralwad, K. S.; Shingate, B. B.; Shingare, M. S. Microwaveassisted one-pot synthesis of octahydroquinazolinone derivatives using ammonium metavanadate under solvent-free condition. Tetrahedron Lett. 2010, 51, 3616. (e) Hassani, Z.; Islami, M. R.; Kalantari, M. An efficient one-pot synthesis of octahydroquinazolinone derivatives using catalytic amount of H2SO4 in water. Bioorg. Med. Chem. Lett. 2006, 16, 4479. (f) Mobinikhaledi, A.; Foroughifar, N.; Khodaei, H. Synthesis of octahydroquinazolinone derivatives using silica sulfuric acid as an efficient catalyst. Eur. J. Chem. 2010, 1, 291. (g) Shaabani, A.; Sarvary, A.; Rahmati, A.; Rezayan, A. H. Ionic liquid/silica sulfuric acid promoted fast synthesis of a Biginelli-like scaffold reaction. Lett. Org. Chem. 2007, 4, 68. (h) Lipson, V. V.; Desenko, S. M.; Borodina, V. V.; Shirovokova, M. G.; Musatov, V. I. Synthesis of partially hydrogenated 1,2,4-triazoloquinazolines by condensation of 3,5-diamino-1,2,4triazole with aromatic aldehydes and dimedone. Russ. J. Org. Chem. 2005, 41, 114. (i) Samantaray, S.; Mishra, B. G. Combustion synthesis, characterization and catalytic application of MoO3−ZrO2 nanocomposite oxide towards one pot synthesis of octahydroquinazolinones. J. Mol. Catal. A: Chem. 2011, 339, 92. (j) Li, J. J.; Sun, J.; Su, W. Diphenylammonium triflate: A novel and efficient catalyst for synthesis of spiro-heterocyclic compounds. Lett. Org. Chem. 2010, 7, 314. (k) El-Gazzar, A. R. B. A.; Hafez, H. N.; Abbas, H. S. S- and Cnucleosidoquinazoline as new nucleoside analogs with potential analgesic and anti-inflammatory activity. Eur. J. Med. Chem. 2009, 44, 4249.
(13) (a) Kappe, C. O. High-speed combinatorial synthesis utilizing microwave irradiation. Curr. Opin. Chem. Biol. 2002, 6, 314. (b) Nair, V.; Rajesh, C.; Vinod, A.; Bindu, U. S.; Streekenth, A. R.; Mathen, S.; Balagopal, L. Strategy for heterocyclic construction via novel multicomponent reactions based on isocyanide and nucleophilic carbenes. Acc. Chem. Res. 2003, 36, 899. (c) Ramon, D. J.; Yus, M. Asymmetric multicomponent (AMCRs): The new frontier. Angew. Chem., Int. Ed. 2005, 44, 1602. (d) Domling, A. A. Recent developments in isocyanide based multicomponent in applied chemistry. Chem. Rev. 2006, 106, 17. (14) (a) Benetti, S.; Romagnoli, R.; De Risi, C.; Spalluto, G.; Zanirato, V. Mastering beta-keto esters. Chem. Rev. 1995, 95, 1065. (b) Langer, P. Regio and diastereoselective cyclization reactions of free and masked 1,3-dicarbonyl dianions with 1,2 dielectrophile. Chem. Eur. J. 2001, 7, 3858. (c) Langer, P. Cyclization reactions of 1,3-silyl enol ethers and related masked. Synthesis 2002, 441. (d) Simone, C.; Constantieux, T.; Rodriguez, J. Utilization of 1,3-dicarbonyl derivatives in multicomponent reactions. Eur. J. Org. Chem. 2004, 4957. (15) Yarim, M.; Sarac, S.; Kilic, F. S.; Erol, K. Synthesis and in vitro calcium antagonist activity of 4-aryl-7,7-dimethyl/1,7,7-trimethyl 1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione derivatives. Farmaco 2003, 58, 17. (16) (a) Alagarsamy, V.; Solomon, V. R.; Murugan, M. Synthesis and pharmacological investigation of novel 4-benzyl-1-substituted-4H[1,2,4]triazolo[4,3-a]quinazolin-5-ones as new class of H1-antihistaminic agents. Bioorg. Med. Chem. 2007, 15, 4009. (b) Alagarsamy, V.; Murugananthan, G.; Venkateshperumal, R. synthesis, analgesic, antiinflammatory and anti-bacterial activity of some novel 2-methyl-3substituted quinazolin-4-(3H)-ones. Biol. Pharm. Bull. 2003, 26, 1711. (c) Hour, M. J.; Huang, L. J.; Kuo, S. C.; Xia, Y.; Bastow, K.; Nakanishi, Y.; Hamel, E.; Lee, K. H. Alkylamino- and 2,3-dihydro-3′methoxy-2-phenyl-4-quinazolinones and related compounds: their synthesis, cytotoxicity and inhibition of tubulin polymerization. J. Med. Chem. 2000, 43, 4479. (d) Alagarsamy, V.; Murugesan, S.; Dhanabal, K.; Muruga, M.; De Clercq, E. AntiHIV, antibacterial and antifungal activities of some novel 2-methyl-3-(substituted methylamino)-(3H)-quinazolin-4-ones. Indian J. Pharm. Sci. 2007, 69, 304. (e) Haridas, V.; Lal, K.; Sharma, Y. K. Design and synthesis of triazolebased peptide dendrimers. Tetrahedron Lett. 2007, 48, 4719. (17) (a) Kozlov, N. G.; Basalaeva, L. I.; Firgang, S. I.; Shashkov, A. S. reaction of methylcyclohexanones with substituted bezaldehydes and 2-napthylamine. Russ. J. Org. Chem. 2004, 40, 518. (b) Martinez, R.; Cortes, E.; Toscano, R. A.; Linzaga, I. Synthesis and spectra of 12-(oand p-R-phenyl)-9,9-dimethyl-7,8,9,10,11,12-hexahydro and 8,9,10,11tetrahydrobenz[a]acridin-11-ones. Structure correction of 1,2,3,4,5,6hexahydro and 1,2,3,4-tetrahydro-2,2-dimethyl-5-aryl-6-aza-9,10-benzophenanthren-4-ones. J. Heterocycl. Chem. 1990, 27, 363. (c) Bahekar, S. S.; Shinde, D. B. Synthesis and anti-inflammatory activity of some [4,6-(4-substituted aryl)-2-thioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]acetic acid derivatives. Bioorg. Med. Chem. Lett. 2004, 14, 1733. (18) Shaabani, A.; Rahmati, A.; Naderi, S. A novel one-pot threecomponent reaction: Synthesis of triheterocyclic 4H-pyrimido[2,1b]benzazoles ring systems. Bioorg. Med. Chem. Lett. 2005, 15, 5553. (19) (a) Matzke, M.; Stolte, S.; Thiele, K.; Juffernholz, T.; Arning, J.; Ranke, J.; Welzbiermann, U.; Jastorff, B. The influence of anion species on the toxicity of 1-alkyl-3-methylimidazolium ionic liquids observed in an (eco)toxicological test battery. Green Chem. 2007, 9, 1198. (b) Kralisch, D.; Stark, A.; Korsten, S.; Kreisel, G.; Ondruschka, B. Energetic, environmental and economic balances: Spice up your ionic liquid research efficiency. Green Chem. 2005, 7, 301. (c) Pham, T.; Cho, C.; Yun, Y. Environmental fate and toxicity of ionic liquids: A review. Water Res. 2010, 44, 352. (20) Rao, G. B. D.; Acharya, B. N.; Verma, S. K.; Kaushik, M. P. N,N′-Dichlorobis(2,4,6-trichlorophenyl)urea (CC-2) as a new reagent for the synthesis of pyrimidone and pyrimidine derivatives via Biginelli reaction. Tetrahedron Lett. 2011, 52, 809. (21) (a) Heravi, M. M.; Ranjbar, L.; Derikvand, F.; Alimadadi, B.; Oskooie, H. A.; Bamoharram, F. F. A three component one-pot procedure for the synthesis of [1,2,4]triazolo/benzimidazolo-quinazo2091
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