Methyl 6-Methyl-4-(4-iodophenyl)-1,2,3,4-tetrahydro-2-thioxo-5-pyrimidinecarboxylate
Chemical Engineering and Materials Science, Engineering Research Center of Pesticide and Medicine Intermediate Clean Production, Ministry of Education, College of Chemistry, Shandong Normal University, Jinan 250014, China
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Author to whom correspondence should be addressed.
Molbank 2009, 2009(4), M645; https://doi.org/10.3390/M645
Submission received: 23 October 2009
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Accepted: 11 December 2009
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Published: 15 December 2009
Abstract
:Methyl 6-methyl-4-(4-iodophenyl)-1,2,3,4-tetrahydro-2-thioxo-5-pyrimidine-carboxylate has been synthesized via Biginelli reaction of 4-iodobenzaldehyde, methyl acetoacetate and thiourea, promoted by microwave irradiation in the presence of iodine under solvent-free conditions in high yield and good purity.
In recent years, dihydropyrimidinones (DHPMs) and their derivatives have attracted considerable attention in natural and synthetic organic chemistry because of their biological and medicinal properties [1,2]. The venerable Biginelli reaction [3,4], one-pot cyclocondensation of aldehyde, β-ketoester, and urea or thiourea, is inarguably one of the most useful multi-component reactions. Polyfunctionalized dihydropyrimidines represent a heterocyclic system of remarkable pharmacological properties such as antiviral, antitumor, antibacterial, and antiinflammatory properties.
Because of global environmental concern and social sustainable development, green synthesis has received considerable attention [5]. Molecular iodine as an inexpensive, nontoxic, readily available catalyst has been used successfully in the Biginelli reaction [6,7], affording the corresponding products in excellent yields with high selectivity [6,7,8,9]. Microwave-assisted chemistry has also attracted a considerable attention in recent years and has been applied successfully in various fields of synthetic organic chemistry [10,11,12,13], including solvent-free reactions [12,13].
As our continuous investigation on the methodology of green synthesis, we report herein the synthesis of the new DHPM compound, methyl 6-methyl-4-(4-iodophenyl)-1,2,3,4-tetrahydro-2-thioxo-5-pyrimidinecarboxylate via a Biginelli three-component cyclocondensation of 4-iodobenz-aldehyde, methyl acetoacetate and thiourea, catalyzed with iodine and promoted by microwave irradiation (MWI) under solvent-free conditions (Scheme 1). The title compound has been fully characterized by NMR (1H and 13C), IR, MS, and elemental analysis. This protocol is proven to be efficient and environmentally benign.
Experimental Procedure
4-Iodobenzaldehyde (2.5 mmol), methyl acetoacetate (5 mmol), thiourea (5 mmol) and iodine (0.2 mmol) were mixed thoroughly and irradiated in a microwave reactor (600 W) at 60 °C for 15 min and monitored by TLC. After completion of the reaction, the reaction mixture was poured into ethyl acetate, cooled to precipitate out, and filtered off to obtain the crude product in high yield. Recrystallization from ethanol afforded the pure title compound as yellow crystals in a yield of 87.7%, m.p. 187.9–189.2 °C.
Moreover, our investigation showed that the best results were observed when the molar ratio of aldehyde, acetoacetate and thiourea was 1:2:2. In addition, it was found that the yields were not obviously affected by different amount of iodine.
1H NMR (Bruker 300 MHz, DMSO-d6): δH 10.38 (s, 1H, N-H), 9.66 (s, 1H, N-H), 7.71 (d, J = 8.0 Hz, 2H, Ar-H), 7.01 (d, J = 8.1 Hz, 2H, Ar-H), 5.11 (d, J = 3.0 Hz, 1H, C4-H), 3.54 (s, 3H, OCH3), 2.29 (s, 3H, CH3) ppm.
13C NMR (75 MHz, DMSO-d6): δC 174.8, 165.9, 146.0, 143.5, 137.9, 129.1, 100.5, 94.3, 54.0, 51.6, 17.7 ppm.
IR (Bruker Tensor 27, KBr): νmax 3453, 2361, 1662, 1576, 1196, 1118 cm-1.
MS (API 4000, ESI): m/z (%) 389.2 (M+, base peak).
Elemental anal. (Perkin Elmer PE 2400 II HONS): calcd for C13H13IN2O2S: C 40.21, H 3.37, N 7.20; found: C 40.22, H 3.38, N 7.22.
Supplementary materials
Supplementary File 1Supplementary File 2Supplementary File 3Acknowledgements
The authors are grateful to Liu Zhixian and Yu Lixin for determinations of NMR, IR and elemental analysis.
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Scheme 1.
© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
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MDPI and ACS Style
Pan, N.; Zhang, W.; Liu, Q. Methyl 6-Methyl-4-(4-iodophenyl)-1,2,3,4-tetrahydro-2-thioxo-5-pyrimidinecarboxylate. Molbank 2009, 2009, M645. https://doi.org/10.3390/M645
AMA Style
Pan N, Zhang W, Liu Q. Methyl 6-Methyl-4-(4-iodophenyl)-1,2,3,4-tetrahydro-2-thioxo-5-pyrimidinecarboxylate. Molbank. 2009; 2009(4):M645. https://doi.org/10.3390/M645
Chicago/Turabian StylePan, Ning, Wenwen Zhang, and Qingjian Liu. 2009. "Methyl 6-Methyl-4-(4-iodophenyl)-1,2,3,4-tetrahydro-2-thioxo-5-pyrimidinecarboxylate" Molbank 2009, no. 4: M645. https://doi.org/10.3390/M645
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