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A General Approach to 4-unsubstituted and 4-alkyl-substituted 5-acyl-1,2,3,4-tetrahydropyrimidine-2-thiones(ones) via α-(thio)ureidoalkylation of 1,3-diketones or β-oxoesters

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Chemistry of Heterocyclic Compounds Aims and scope

A new general approach to a large variety of hitherto hardly accessible 4-unsubstituted and 4-alkyl-substituted 5-acyl-1,2,3,4-tetrahydropyrimidine-2-thiones(ones) has been developed. The approach is based on the reaction of enolates of various 1,3-diketones or β-oxoesters with readily available N-[alkyl(tosyl)methyl]thioureas, N-(azidomethyl)thiourea, and N-[alkyl(tosyl)methyl]ureas followed by TsOH-catalyzed dehydration of the intermediate 4-hydroxyhexahydropyrimidine-2-thiones(ones) without or with isolation of the latter.

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References

  1. (a) Singh, K.; Singh, K. In Advances in Heterocyclic Chemistry; Katritzky, A. R., Ed.; Elsevier: Amsterdam, 2012, Vol. 105, p. 223. (b) Kolosov, M. A.; Orlov, V. D.; Beloborodov, D. A.; Dotsenko, V. V. Mol. Diversity 2009, 13, 5. (c) Kappe, C. O. In Multicomponent Reactions; Zhu, J.; Bienaymé, H., Eds.; John Wiley: New York, 2005, p. 95. (d) Kappe, C. O.; Stadler, A. In Organic Reactions; Overman, L. E., Ed.; John Wiley: New York, 2004, Vol. 63, p. 1.

  2. (a) Wan, J.-P.; Pan, Y. Mini-Rev. Med. Chem. 2012, 12, 337. (b) Jadhav, V. B.; Holla, H. V.; Tekale, S. U.; Pawar, R. P. Chem. Sin. 2012, 3, 1213. (c) Kappe, C. O. Eur. J. Med. Chem. 2000, 35, 1043.

  3. (a) Biginelli, P. Gazz. Chim. Ital. 1893, 23, 360. (b) Kürti, L.; Czakó, B. Strategic Applications of Named Reactions in Organic Synthesis; Elsevier: Amsterdam, 2005, p. 58. (c) Comprehensive Organic Name Reactions and Reagents; Wang, Z., Ed.; John Wiley & Sons: Hoboken, 2010, Vol. 1, p. 379.

  4. (a) Nagarajaiah, H.; Mukhopadhyay, A.; Moorthy, J. N. Tetrahedron Lett. 2016, 57, 5135. (b) Suresh; Sandhu, J. S. ARKIVOC 2012, (i), 66. (c) Folkers, K.; Johnson, T. B. J. Am. Chem. Soc. 1933, 55, 3784. (d) Sweet, F. S.; Fissekis, J. D. J. Am. Chem. Soc. 1973, 95, 8741. (e) Kappe, C. O. J. Org. Chem. 1997, 62, 7201. (f) De Souza, R. O. M. A.; Penha, E. T.; Milagre, H. M. S.; Garden, S. J.; Esteves, P. M.; Eberlin, M. N.; Antunes, O. A. C. Chem.–Eur. J. 2009, 15, 9799. (g) Puripat, M.; Ramozzi, R.; Hatanaka, M.; Parasuk, W.; Parasuk, V.; Morokuma, K. J. Org. Chem. 2015, 80, 6959.

  5. Folkers, K.; Harwood, H. J.; Johnson, T. B. J. Am. Chem. Soc. 1932, 54, 3751.

    Article  CAS  Google Scholar 

  6. (a) Damgaard, M.; Al-Khawaja, A.; Nittegaard-Nielsen, M.; Petersen, R. F.; Wellendorph, P.; Frølund, B. Eur. J. Med. Chem. 2017, 138, 300. (b) Sharma, U. K.; Sharma, N.; Kumar, R.; Sinha, A. K. Amino Acids 2012, 44, 1031. (c) Dowarah, J.; Patel, D.; Marak, B. N.; Yadav, U. C. S.; Shah, P. K.; Shukla, P. K.; Singh, V. P. RSC Adv. 2021, 11, 35737. (d) Zhang, Y.-Q.; Wang, C.; Li, G.-S.; Li, J.-C.; Liu, H.-M.; Wu, Q.-H. Chin. J. Org. Chem. 2005, 25, 1265. (e) Safari, J.; Gandomi-Ravandi, S. J. Mol. Catal. A: Chem. 2013, 373, 72.

  7. Shutalev, A. D.; Sivova, N. V. Chem. Heterocycl. Compd. 1998, 34, 848.

    Article  CAS  Google Scholar 

  8. Mobinikhaledi, A.; Forughifar, N.; Safari, J. A.; Amini, E. J. Heterocycl. Chem. 2007, 44, 697.

    Article  CAS  Google Scholar 

  9. Cho, H.; Nishimura, Y.; Yasui, Y.; Kobayashi, S.; Yoshida, S.-i.; Kwon, E.; Yamaguchi, M. Tetrahedron 2011, 67, 2661.

  10. Fu, L.-H.; **e, Z.-B.; Lan, J.; Li, H.-X.; Liu, L.-S.; Le, Z.-G. Heterocycles 2018, 96, 1808.

    Article  CAS  Google Scholar 

  11. (a) Shutalev, A. D.; Kuksa, V. A. Chem. Heterocycl. Compd. 1995, 31, 86. (b) Shutalev, A. D.; Kuksa, V. A. Chem. Heterocycl. Compd. 1997, 33, 91.

  12. Shutalev, A. D.; Kishko, E. A.; Sivova, N. V.; Kuznetsov, A. Yu. Molecules 1998, 3, 100.

    Article  CAS  Google Scholar 

  13. (a) Fesenko, A. A.; Shutalev, A. D. Tetrahedron 2020, 76, 131340. (b) Shutalev, A. D.; Savinkina, E. V.; Albov, D. V.; Zamilatskov, I. A.; Buravlev, E. A. Struct. Chem. 2011, 22, 849.

  14. Staudinger, H.; Wagner, K. Makromol. Chem. 1954, 12, 168.

    Article  CAS  Google Scholar 

  15. Shutalev, A. D.; Zhukhlistova, N. E.; Gurskaya, G. V. Mendeleev Commun. 2004, 14, 31.

    Article  Google Scholar 

  16. Gurskaya, G. V.; Zavodnik, V. E.; Shutalev, A. D. Crystallogr. Rep. 2003, 48, 416.

    Article  CAS  Google Scholar 

  17. Zigeuner, G.; Nischk, W.; Juraszovits, B. Monatsh. Chem. 1966, 97, 1611.

    Article  CAS  Google Scholar 

  18. Liu, J.; Wu, F.; Chen, L.; Hu, J.; Zhao, L.; Chen, C.; Peng, L. Bioorg. Med. Chem. Lett. 2011, 21, 2376.

    Article  CAS  Google Scholar 

  19. Kolosov, M. A.; Kulyk, O. G.; Beloborodov, D. A.; Orlov, V. D. J. Chem. Res. 2013, 37, 115.

    Article  CAS  Google Scholar 

  20. Wang, L.; Zhou, M.; Chen, Q.; He, M.-Y. J. Chem. Res. 2012, 36, 712.

    Article  CAS  Google Scholar 

  21. Tsirelson, V. G.; Stash, A. I.; Potemkin, V. A.; Rykounov, A. A.; Shutalev, A. D.; Zhurova, E. A.; Zhurov, V. V.; Pinkerton, A. A.; Gurskaya, G. V.; Zavodnik, V. E. Acta Crystallogr., Sect. B: Struct. Sci. 2006, B62, 676.

  22. Bozsing, D.; Sohar, P.; Gigler, G.; Kovacs, G. Eur. J. Med. Chem. 1996, 31, 663.

    Article  CAS  Google Scholar 

  23. Li, Y. X.; Bao, W. L. Chin. Chem. Lett. 2003, 14, 993.

    CAS  Google Scholar 

  24. Lim, J.-H.; Yoon, J.-Y.; Song, J.-U.; Sung, L.-T.; Choi, S.-P.; Song, H.-Y.; Kim, J.-Y.; Kim, Y.-Z.; Cho, Y.-G.; Kim, C.-M.; Kim, W.-S.; Kang, S.-W.; Park, J.-H. WO Patent 2004111013; Chem. Abstr. 2004, 142, 74595.

  25. **e, Z.; Fu, L.; Yue, C.; Jiang, G.; Lan, J. Patent CN 108588141; Chem. Abstr. 2018, 169, 461497.

  26. Lei, M.; Ma, L.; Hu, L. Synth. Commun. 2011, 41, 3071.

    Article  CAS  Google Scholar 

  27. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Petersson, G. A.; Nakatsuji, H.; Li, X.; Caricato, M.; Marenich, A. V.; Bloino, J.; Janesko, B. G.; Gomperts, R.; Mennucci, B.; Hratchian, H. P.; Ortiz, J. V.; Izmaylov, A. F.; Sonnenberg, J. L.; Williams-Young, D.; Ding, F.; Lipparini, F.; Egidi, F.; Goings, J.; Peng, B.; Petrone, A.; Henderson, T.; Ranasinghe, D.; Zakrzewski, V. G.; Gao, J.; Rega, N.; Zheng, G.; Liang, W.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Throssell, K.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M. J.; Heyd, J. J.; Brothers, E. N.; Kudin, K. N.; Staroverov, V. N.; Keith, T. A.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A. P.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Millam, J. M.; Klene, M.; Adamo, C.; Cammi, R.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Farkas, O.; Foresman, J. B.; Fox, D. J. Gaussian 16, Revision A.03; Gaussian, Inc.: Wallingford, 2016.

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  1. N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Ave, Moscow, 119991, Russia

    Anatoly D. Shutalev, Anastasia A. Fesenko & Elena D. Strel’tsova

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  1. Anatoly D. Shutalev
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  2. Anastasia A. Fesenko
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Correspondence to Anatoly D. Shutalev.

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Published in Khimiya Geterotsiklicheskikh Soedinenii, 2022, 58(12), 695–711

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Shutalev, A.D., Fesenko, A.A. & Strel’tsova, E.D. A General Approach to 4-unsubstituted and 4-alkyl-substituted 5-acyl-1,2,3,4-tetrahydropyrimidine-2-thiones(ones) via α-(thio)ureidoalkylation of 1,3-diketones or β-oxoesters. Chem Heterocycl Comp 58, 695–711 (2022). https://doi.org/10.1007/s10593-023-03146-6

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