A rapid, improved, and ecofriendly synthesis of thiopyrimidines is carried out via one-pot multicomponent reaction of ethylcyanoacetate, substituted benzaldehydes, and thiourea in presence of ethanolic K2CO3 using microwave irradiation heating method. Excellent yields, shorter reaction time, and easy workup are the major advantageous features of this green protocol. So the application of multicomponent reactions involves the combination of multiple starting materials with different functional groups leading to the highly efficient and environmentally friendly construction of multifunctional drug molecules. The structures of the newly synthesized products were assigned on the basis of IR and 1HNMR spectral data. 1. Introduction One-pot multicomponent organic reactions (MCORs) have emerged as an efficient tool for benign synthesis by virtue of their convergence, productivity, facile execution, and generation of highly diverse and complex products from easily available starting materials in a single operation. MCORs are now being tuned for synthesizing various heterocyclic compounds due to their diverse biological activities [1]. The environmental acceptability of the process is improved if the multicomponent strategy is applied under microwave irradiation (MWI) technology [2]. For an organic synthesis, a major adverse effect on the environment is the consumption of energy for heating. To overcome this problem, it is highly desirable to develop suitable methods of heating that use microwave irradiation. So, the synthetic methodologies nowadays should be designed in such a way to use and generate substances that possess little or no toxicity to human health and the environment. Microwave heating provides a valuable tool to perform reactions faster with enhanced product yields with high purity by reducing unwanted formation of byproducts [3]. From an environmental and economic perspective, it is becoming obvious that the traditional methods of performing chemical synthesis are unsustainable and have to be changed. Multicomponent coupling reactions provide a solution since they are more efficient, cost effective, and less wasteful than traditional methods. The achievement of making multiple bonds in a one-pot multicomponent coupling reaction promotes a sustainable synthetic approach to develop new drug molecule in a drug discovery process. Microwave (MW) irradiation facilitates better thermal management of chemical reactions. The rapid MW heat transfer allows reactions to be carried out very much faster compared to conventional heating methods often resulting
References
[1]
M. C. Bagley and M. C. Lubinu, “Microwave-assisted multicomponent reactions for the synthesis of heterocycles,” Journal of Heterocyclic Chemistry, vol. 1, pp. 31–58, 2006.
[2]
S. Ravichandran and E. Karthikeyan, “Microwave synthesis—a potential tool for green chemistry,” International Journal of ChemTech Research, vol. 3, no. 1, pp. 466–470, 2011.
[3]
M. Charde, A. Shukla, V. Bukhariya, J. Mehta, and R. Chakole, “A review on: a significance of microwave assist technique in green chemistry,” International Journal of Phytopharmacy, vol. 2, no. 2, pp. 39–50, 2012.
[4]
B. S. Sekhon, “Microwave-assisted pharmaceutical synthesis: an overview,” International Journal of PharmTech Research, vol. 2, no. 1, pp. 827–833, 2010.
[5]
M. A. Surati, S. Jauhari, and K. R. Desai, “A brief review: microwave assisted organic reaction,” Archives of Applied Science Research, vol. 4, no. 1, pp. 645–661, 2012.
[6]
P. Lidstr？m, J. Tierney, B. Wathey, and J. Westman, “Microwave assisted organic synthesis—a review,” Tetrahedron, vol. 57, no. 45, pp. 9225–9283, 2001.
[7]
A. Loupy, Microwaves in Organic Synthesis, Wiley-VCH, Weinheim, Germany, 2006.
[8]
C. O. Kappe, “Controlled microwave heating in modern organic synthesis,” Angewandte Chemie International Edition, vol. 43, no. 46, pp. 6250–6284, 2004.
[9]
F. R. Alexandre, L. Domon, S. Frère, A. Testard, V. Thiéry, and T. Besson, “Microwaves in drug discovery and multi-step synthesis,” Molecular Diversity, vol. 7, no. 2–4, pp. 273–280, 2003.
[10]
S. Caddick and R. Fitzmaurice, “Microwave enhanced synthesis,” Tetrahedron, vol. 65, no. 17, pp. 3325–3355, 2009.
[11]
A. Madhvi, S. J. Surati, and K. R. Desai, “A brief review: microwave assisted organic reaction,” Archives of Applied Science Research, vol. 4, no. 1, pp. 645–661, 2012.
[12]
H. M. Hügel, “Microwave multicomponent synthesis,” Molecules, vol. 14, no. 12, pp. 4936–4972, 2009.
[13]
J. L. Krstenansky and L. Cotterill, “Recent advances in microwave-assisted organic syntheses,” Current Opinion in Drug Discovery and Development, vol. 3, no. 4, pp. 454–461, 2000.
[14]
M. Borisagar, K. Joshi, H. Ram, K. Vyas, and K. Nimavat, “A one-pot microwave irradiation synthesis of 1,2,4-triazolo[1,5-A]pyrimidines,” Acta Chimica & Pharmaceutica Indica, vol. 2, no. 2, pp. 101–105, 2012.
[15]
A. Kruithof, E. Ruijter, and V. A. Orru, “Microwave-assisted multicomponent synthesis of heterocycles,” Current Organic Chemistry, vol. 15, no. 2, pp. 204–236, 2011.
[16]
S. J. Vaghasia and V. H. Shah, “Microwave assisted synthesis and antimicrobial activity of some novel pyrimidine derivatives,” Journal of the Serbian Chemical Society, vol. 72, no. 2, pp. 109–117, 2007.
[17]
J. M. Gajera and S. N. Tondlekar, “A novel and one-pot synthesis of 6-arylpyrimidin-4-ol,” Research Letters in Organic Chemistry, pp. 1–3, 2008.
[18]
N. Agarwal, P. Srivastava, S. K. Raghuwanshi et al., “Chloropyrimidines as a new class of antimicrobial agents,” Bioorganic and Medicinal Chemistry, vol. 10, no. 4, pp. 869–874, 2002.
[19]
K. Singh, K. Singh, B. Wan, S. Franzblau, K. Chibale, and J. Balzarini, “Facile transformation of Biginelli pyrimidin-2(1H)-ones to pyrimidines. In vitro evaluation as inhibitors of Mycobacterium tuberculosis and modulators of cytostatic activity,” European Journal of Medicinal Chemistry, vol. 46, no. 6, pp. 2290–2294, 2011.
[20]
C. O. Kappe, “A reexamination of the mechanism of the Biginelli dihydropyrimidine synthesis. Support for an N-acyliminium ion intermediate,” Journal of Organic Chemistry, vol. 62, no. 21, pp. 7201–7204, 1997.
[21]
M. Kidwai, K. Singhal, and S. Kukreja, “One-pot green synthesis for pyrimido[4,5-d]pyrimidine derivatives,” Zeitschrift fur Naturforschung, vol. 62, no. 5, pp. 732–736, 2007.
[22]
A. H. Kategaonkar, S. A. Sadaphal, K. F. Shelke, B. B. Shingate, and M. S. Shingare, “Microwave assisted synthesis of pyrimido[4,5-d]pyrimidine derivatives in dry media,” Ukrainica Bioorganica Acta, vol. 1, pp. 3–7, 2009.
