Journal of Chemical Crystallography

, Volume 47, Issue 1–2, pp 30–39 | Cite as

Synthesis and X-ray Crystal Structure of 2 and 4-Trifluoromethyl Substituted Phenyl Semicarbazone and Thiosemicarbazone

  • T. K. Venkatachalam
  • Paul V. Bernhardt
  • Gregory K. Pierens
  • David C. Reutens
Original Paper


NMR and single crystal X-ray structure data for four structurally similar semicarbazones and thiosemicarbazones were compared. In solution, proton NMR showed considerable variation in their chemical shift values especially for the NH2 protons. In the case of the semicarbazones this peak appeared as a broad singlet with an integration ratio of two while for the thiosemicarbazones the amino group showed two distinct singlets with marked chemical shift differences. This is attributed to the differences in the canonical forms of the thiosemicarbazone amino group and the semicarbazone analogue. Additionally, we provide evidence that the 2-trifluoromethyl phenyl substituted semicarbazone (2) formed an intermolecular hydrogen bond with one of the hydrogens of the NH2 group while this was totally absent in the thiosemicarbazone. We explain this by the restricted rotation of the CN bond in the thiosemicarbazone due to its double bond character compared to the less restricted rotation in semicarbazone compound.

Graphical Abstract

NMR and single crystal X-ray structure data for four structurally similar semicarbazones and thiosemicarbazones were compared for their hydrogen bonding characteristics.


Semicarbazones NMR X-ray crystal structure Hydrogen bond 



This research work is partially supported by a Linkage Grant (LP130100703 for DCR) from Australian Research Council Australia.

Supplementary material

10870_2017_677_MOESM1_ESM.pdf (350 kb)
Supplementary material 1 (PDF 349 KB)


  1. 1.
    Klayman DL, Scovill JP, Bartosevich JF, Mason CJ (1979) J Med Chem 22:1367–1373CrossRefGoogle Scholar
  2. 2.
    Easmon J, Heinisch G, Holzer W, Rosenwirth B (1992) J Med Chem 35:3288–3296CrossRefGoogle Scholar
  3. 3.
    Kalinowski DS, Yu Y, Sharpe PC, Islam M, Liao Y-T, Lovejoy DB, Kumar N, Bernhardt PV, Richardson DR (2007) J Med Chem 50:3716–3729CrossRefGoogle Scholar
  4. 4.
    Richardson DR, Sharpe PC, Lovejoy DB, Senaratne D, Kalinowski DS, Islam M, Bernhardt PV (2006) J Med Chem 49:6510–6521CrossRefGoogle Scholar
  5. 5.
    Shipman C Jr, Smith SH, Drach JC, Klayman DL (1981) Antimicrob Agents Chemother 19:682CrossRefGoogle Scholar
  6. 6.
    Aouad F, Florence A, Zhang Y, Collins F, Henry C, Ward RJ, Crichton RR (2002) Inorg Chim Acta 339:470–480CrossRefGoogle Scholar
  7. 7.
    Chaston TB, Lovejoy DB, Watts RN, Richardson DR (2003) Clin Cancer Res 9:402–414Google Scholar
  8. 8.
    Chaston TB, Watts RN, Yuan J, Richardson DR (2004) Clin Cancer Res 10:7365–7374CrossRefGoogle Scholar
  9. 9.
    Le NT, Richardson DR (2004) Blood 104:2967–2975CrossRefGoogle Scholar
  10. 10.
    Nurtjahja-Tjendraputra E, Fu D, Phang JM, Richardson DR (2007) Blood 109:4045–4054CrossRefGoogle Scholar
  11. 11.
    Richardson DR (2005) Curr Med Chem 12:2711–2729CrossRefGoogle Scholar
  12. 12.
    Suvarapu LN, Somala AR, Koduru JR, Baek SO, Ammireddy VR (2012) Asian J Chem 24:1889Google Scholar
  13. 13.
    Yuan J, Lovejoy DB, Richardson DR (2004) Blood 104:1450–1458CrossRefGoogle Scholar
  14. 14.
    Kalinowski DS, Quach P, Richardson DR (2009) Future Med Chem 1:1143–1151CrossRefGoogle Scholar
  15. 15.
    Lobana TS, Sharma R, Bawa G, Khanna S (2009) Coord Chem Rev 253:977–1055CrossRefGoogle Scholar
  16. 16.
    Dearling JL, Blower PJ (1998) Chem Commun 2531–2532Google Scholar
  17. 17.
    Donnelly PS (2011) J Chem Soc Dalton Trans 40:999–1010CrossRefGoogle Scholar
  18. 18.
    Fujibayashi Y, Taniuchi H, Yonekura Y, Ohtani H (1997) J Nucl Med 38:1155Google Scholar
  19. 19.
    Green MA, Mathias CJ, Willis LR, Handa RK, Lacy JL, Miller MA, Hutchins GD (2007) Nucl Med Biol 34:247–255CrossRefGoogle Scholar
  20. 20.
    Oh M, Tanaka T, Kobayashi M, Furukawa T, Mori T, Kudo T, Fujieda S, Fujibayashi Y (2009) Nucl Med Biol 36:419–426CrossRefGoogle Scholar
  21. 21.
    Vāvere AL, Lewis JS (2008) Nucl Med Biol 35:273–279CrossRefGoogle Scholar
  22. 22.
    Zhou J, Liu X, Chen Z-F, Liang H (2006) Chin J Synth Chem 14:471–475Google Scholar
  23. 23.
    Chumakov YM, Tsapkov V, Antosyak BY, Bairac N, Simonov YA, Bocelli G, Pahontu E, Gulea A (2009) Cryst Rep 54:455–463CrossRefGoogle Scholar
  24. 24.
    Garbelini ER, Maria da Graça M, Back DF, Evans DJ, Müller-Santos M, Ribeiro RR, Lang ES, Nunes FS (2012) J Mol Struct 1008:35–41CrossRefGoogle Scholar
  25. 25.
    Garbelini ER, Ribeiro RR, Hörner M, Locatelli A, Nunes FS (2011) Spectrochim Acta Pt A 78:1337–1341CrossRefGoogle Scholar
  26. 26.
    Gulya A, Tsapkov V, Chumakov YM, Roshu T (2006) Russ J Gen Chem 76:1100–1105CrossRefGoogle Scholar
  27. 27.
    Qing Y, Xiaoge B, Ligang Z, Hedong B, Hong L (2006) Chem J Inter 8:49Google Scholar
  28. 28.
    Shaabani B, Khandar AA, Dusek M, Pojarova M, Mahmoudi F, Feher A, Kajňaková M (2013) J Coord Chem 66:748–762CrossRefGoogle Scholar
  29. 29.
    Basu S, Acharyya R, Basuli F, Peng S-M, Lee G-H, Mostafa G, Bhattacharya S (2010) Inorg Chim Acta 363:2848–2856CrossRefGoogle Scholar
  30. 30.
    Tian Y-P, Wu J-Y, Xie F-X, Shanmuga Sundara Raj S, Yang P, Fun H-K (1999) Acta Crystallogr Sect C 55:1641–1644CrossRefGoogle Scholar
  31. 31.
    Venkatachalam T, Pierens GK, Reutens DC (2014) Magn Reson Chem 52:98–105CrossRefGoogle Scholar
  32. 32.
    Rigaku Oxford Diffraction, Version 171.38.43Google Scholar
  33. 33.
    Sheldrick GM (2008) Acta Crystallogr Sect A 64:112–122CrossRefGoogle Scholar
  34. 34.
    Farrugia LJ (2012) J Appl Crystallogr 45:849–854CrossRefGoogle Scholar
  35. 35.
    Spek A (2009) Acta Cryst D 65:148–155CrossRefGoogle Scholar
  36. 36.
    Banks RE, Smart BE, Tatlow J (2013) Organofluorine chemistry: principles and commercial applications. Springer, BerlinGoogle Scholar
  37. 37.
    Müller K, Faeh C, Diederich F (2007) Science 317:1881–1886CrossRefGoogle Scholar
  38. 38.
    Ojima I (2009) Fluorine in medicinal chemistry and chemical biology. Wiley, ChichesterCrossRefGoogle Scholar
  39. 39.
    Attia MI, Ghabbour HA, El-Azzouny AA, Al-Deeb OA, Almutairi MS, Fun H-K (2013) J Chem 2013Google Scholar
  40. 40.
    Bernhardt PV, Caldwell LM, Lovejoy DB, Richardson DR (2003) Acta Crystallogr Sect C 59:o629–o633CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • T. K. Venkatachalam
    • 1
  • Paul V. Bernhardt
    • 2
  • Gregory K. Pierens
    • 1
  • David C. Reutens
    • 1
  1. 1.Centre for Advanced ImagingThe University of QueenslandBrisbaneAustralia
  2. 2.School of Chemistry and Molecular BiosciencesThe University of QueenslandBrisbaneAustralia

Personalised recommendations