Issue

Vol. 29 No. 10 (2017): Vol 29 Issue 10

Copyright (c) 2017 AJC

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Critical Modification to Bulk Scale Synthesis of 2-Amino-5-carboethoxy-4-hydroxypyrimidine

https://doi.org/10.14233/ajchem.2017.20608
M. Chandrappa
Bigtec Pvt. Ltd., 59th "C" cross, 4th "M" Block, Rajajinagar, Bangalore-560 010, India; Department of Chemistry, School of Engineering and Technology, CMR University, Bangalore-562 149, India
Girish Kumar
Department of Chemistry, School of Engineering and Technology, CMR University, Bangalore-562 149, India
Phani Kumar Pullela
Bigtec Pvt. Ltd., 59th "C" cross, 4th "M" Block, Rajajinagar, Bangalore-560 010, India; Department of Chemistry, School of Engineering and Technology, CMR University, Bangalore-562 149, India; Department of Chemistry, CMR Institute of Technology, ITPL Main Road, Bangalore-560 037, India

Corresponding Author(s) : Phani Kumar Pullela

phanikumar.p@cmrit.ac.in

Asian Journal of Chemistry, Vol. 29 No. 10 (2017): Vol 29 Issue 10

Abstract

Pyrimidines and pyridines are choice for modern day medicinal chemistry. Pyrimidine synthons are synthesized form guanidine and different substituted malonates. One of such pyrimidine ring synthon is 2-amino-5-carboethoxy-4-hydroxy pyrimidine. The commercially deployed synthesis involved a mixture of KOH and guanidine carbonate and gradual temperature controlled addition of diethylethoxy methylene melonate giving a yellow precipitate. The precipitate is cooled to around 5 °C and recrystallized from ethanol-water mixture. Though purity is never an issue in this popular process, yields are very low (70-75 %). The GC analysis of reaction mixture indicated that almost starting material was left unreacted and the first yellow precipitate formation is the rate determining step. We report silica functionalized magnetic particles as material support for synthesis of 2-amino-5carboethoxy-4-hydroxy pyrimidine. The cyclization reaction yields are reported to be enhanced due to presence of “near-homogeneous” nanomaterial catalyst. The prominent catalyst of interest to us is Fe3O4@SiO2 of 40 nm size. The particles are produced by modified Stober process giving consistent yields and coating of SiO2. The structural characterization is performed with SEM, TEM, IR and the data are consistent across multiple batches. The use of 40 nm size Fe3O4@SiO2 enabled higher yields of cyclization step in synthesis of 2-amino-5-carboethoxy-4-hydroxy pyrimidine. The mechanism of catalysis is stabilization of hetero atoms on the acidic silica surface and hence formation of pyrimidine. The study with different sized nanoparticles has indicated 40 nm size seems to be optimum and ability of catalysis is reduced as the size of nanoparticles has increased. The reaction performed at different batch sizes has indicated that 5 % (w/v) catalyst is optimal in the reaction. This process modification has far reaching applications in medicinal chemistry and bulk drug synthesis.

Keywords

Pyrimidine Magnetite nanoparticles Solid support 2-Amino-5-carboethoxy-4-hydroxypyrimidine
Chandrappa, M., Kumar, G., & Pullela, P. K. (2019). Critical Modification to Bulk Scale Synthesis of 2-Amino-5-carboethoxy-4-hydroxypyrimidine. Asian Journal of Chemistry, 29(10), 2119–2122. https://doi.org/10.14233/ajchem.2017.20608
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. P.P. Kumar, S.C. Stotz, R. Paramashivappa, A.M. Beedle, G.W. Zamponi and A.S. Rao, Mol. Pharmacol., 61, 649 (2002); https://doi.org/10.1124/mol.61.3.649.
  2. P.K. Pullela, P. Rangappa, S.R. Alapati and P.V. Subbarao, Substituted Dihydropyrimidines, Dihydropyrimidones and Dihydropyrimidinethiones as Calcium Channel Blockers, US Patent 7687511 (2010).
  3. V. Ralevic and G. Burnstock, Drug News Perspect., 16, 133 (2003); https://doi.org/10.1358/dnp.2003.16.3.876886.
  4. W. Kobinger, A. Walland and R. Kadatz, Naunyn Schmiedebergs Arch. Pharmacol., 292, 105 (1976); https://doi.org/10.1007/BF00498579.
  5. S. Koyama, J. Pharmacol. Exp. Ther., 233, 480 (1985).
  6. M.S. Mohamed, S.M. Awad and A.I. Sayed, Molecules, 15, 1882 (2010); https://doi.org/10.3390/molecules15031882.
  7. S.G. Newman and K.F. Jensen, Green Chem., 15, 1456 (2013); https://doi.org/10.1039/c3gc40374b.
  8. R. Singh and A. Chouhan, World J. Pharm. Pharm. Sci., 3, 574 (2014).
  9. A. Mathews, M. Joy, S.E. Thomas and J. Mathew, Int. J. Chem. Sci., 13, 1603 (2015).
  10. Y. Rival, G. Grassy and G. Michel, Chem. Pharm. Bull. (Tokyo), 40, 1170 (1992); https://doi.org/10.1248/cpb.40.1170.
  11. C.O. Kappe, Molecules, 3, 1 (1998); https://doi.org/10.3390/30100001.
  12. C.O. Kappe, Acc. Chem. Res., 33, 879 (2000); https://doi.org/10.1021/ar000048h.
  13. S.A. Al-Issa, Molecules, 17, 10902 (2012); https://doi.org/10.3390/molecules170910902.
  14. S.B. Castor and J.B. Hedrick, J. Environ. Radioact., 102, 769 (2001).
  15. R.J. Nevagi, S.N. Dighe and S.N. Dighe, Eur. J. Med. Chem., 97, 561 (2015); https://doi.org/10.1016/j.ejmech.2014.10.085.
  16. Z. Ke, Y.Y. Yeung, G.C. Tsui and S.P. Xiao, Progr. Heterocycl. Chem., 27, 203 (2015); https://doi.org/10.1016/B978-0-08-100024-3.00007-6.
  17. S. Urban, B. Beiring, N. Ortega, D. Paul and F. Glorius, J. Am. Chem. Soc., 134, 15241 (2012); https://doi.org/10.1021/ja306622y.
  18. A.J. Zillich, J. Garg, S. Basu, G.L. Bakris and B.L. Carter, Hypertension, 48, 219 (2006); https://doi.org/10.1161/01.HYP.0000231552.10054.aa.
  19. A.P. Taylor, R.P. Robinson, Y.M. Fobian, D.C. Blakemore, L.H. Jones and O. Fadeyi, Org. Biomol. Chem., 14, 6611 (2016); https://doi.org/10.1039/C6OB00936K.
  20. A. Chaudhary, P.K. Sharma, P. Verma and R. Dudhe, Anal. Univ. Bucuresti Chim., 20, 123 (2011).
  21. A. Dastan, A. Kulkarni and B. Török, Green Chem., 14, 17 (2012); https://doi.org/10.1039/C1GC15837F.
  22. H. Sheibani, M. Seifi and A. Bazgir, Catalyst Synth. Commun., 39, 1055 (2009); https://doi.org/10.1080/00397910802474982.
  23. G.V. Shiva Reddy, M. Chandrappa, F. Rahaman, B.N. Murthy and P.K. Pullela, Asian J. Chem., 29, 124 (2017); https://doi.org/10.14233/ajchem.2017.20155.
  24. R.S. Vardanyan, G.G. Danagulyan, A.D. Mkrtchyan and V.J. Hruby, Heterocycl. Commun., 17, 129 (2011); https://doi.org/10.1515/hc.2011.025.
  25. R.S. Varma, Tetrahedron, 58, 1235 (2002); https://doi.org/10.1016/S0040-4020(01)01216-9.
  26. V. Polshettiwar and R.S. Varma, Green Chem., 12, 743 (2010); https://doi.org/10.1039/b921171c.
  27. G.W. Kabalka and R.M. Pagni, Tetrahedron, 53, 7999 (1997); https://doi.org/10.1016/S0040-4020(97)00264-0.
  28. C.W. Lim and I.S. Lee, Nano Today, 5, 412 (2010); https://doi.org/10.1016/j.nantod.2010.08.008.
  29. R. Abu-Reziq, H. Alper, D. Wang and M.L. Post, J. Am. Chem. Soc., 128, 5279 (2006); https://doi.org/10.1021/ja060140u.
  30. Q. Zhang, H. Su, J. Luo and Y. Wei, Green Chem., 14, 201 (2012); https://doi.org/10.1039/C1GC16031A.
  31. R.K. Sharma, S. Sharma, S. Dutta, R. Zboril and M.B. Gawande, Green Chem., 17, 3207 (2015); https://doi.org/10.1039/C5GC00381D.
  32. D.M. Barnes, A.R. Haight, T. Hameury, M.A. McLaughlin, J. Mei, J.S. Tedrow and J.D. Riva Toma, Tetrahedron, 62, 11311 (2006); https://doi.org/10.1016/j.tet.2006.07.008.
  33. K.C. Majumdar, A. Taher and R.K. Nandi, Tetrahedron, 68, 5693 (2012); https://doi.org/10.1016/j.tet.2012.04.098.
Read More
Author biographies is not available.
Download
PDF
Statistic
Read Counter : 0 Download : 2