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Reactivity of (E)-4-aryl-4-oxo-2-butenoic acid arylamides toward 2-mercaptoethanol. A LFER study

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Abstract

The reactivity of fifteen (E)-4-aryl-4-oxo-2-butenoic (aroylacrylic) acid arylamides toward thiols was studied, measuring the rate constants of the addition of model thiol nucleophile, 2-mercaptoethanol. The influence of the variation of the substituents on the phenyl rings on the rate of reaction was quantified using the Hammett substituent constants and descriptors derived from ab initio or semiempirical calculations (atomic charges, HOMO, and LUMO). Statistically significant linear correlations between second-order rate constants and Hammett substituent constants, as well as energies of LUMO orbitals, were obtained. Substituents on both aroyl and arylamido moieties were shown to influence the reactivity of studied compounds toward thiols. The regioselectivity of reaction was confirmed by NMR spectroscopy. Exclusively β-addition product with respect to the aroyl keto group was obtained. The determined enthalpy and entropy of activation were found to be in agreement with the proposed reaction mechanism, which includes a highly ordered transition state.

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Notes

  1. Estimated value.

References

  1. Singh J, Petter RC, Baillie TA, Whitty A (2011) Nat Rev Drug Discov 10:307

    Article  CAS  Google Scholar 

  2. Vitorović-Todorović MD, Erić-Nikolić A, Kolundžija B, Hamel E, Ristić S, Juranić IO, Drakulić BJ (2013) Eur J Med Chem 62:40

    Article  Google Scholar 

  3. McLemore R, Robb SA, Lee BH, Caplan MR, Vernon BL (2009) Ann Biomed Eng 37:2416

    Article  Google Scholar 

  4. Williams RM, Tomizawa K, Armstrong RW, Dung J-S (1987) J Am Chem Soc 109:4028

    Article  CAS  Google Scholar 

  5. Dimmock JR, Smith LM, Smith PJ (1980) Can J Chem 58:984

    Article  CAS  Google Scholar 

  6. Shi B, Greaney MF (2005) Chem Commun 7:886

    Article  Google Scholar 

  7. Korikov PV, Gerasimova NP, Moskovicev OA, Alov EM, Noznin NA (2001) Izvestiya Vysshikh Uchebnykh Zavedenii. Khimiya i Khimicheskaya Tekhnologiya 44:19

    CAS  Google Scholar 

  8. Avonto C, Taglialatela-Scafati O, Pollastro F, Minassi A, Di Marzo V, De Petrocellis L, Appendino G (2011) Angew Chem Int Ed 50:467

    Article  CAS  Google Scholar 

  9. Carmi C, Cavazzoni A, Vezzosi S, Bordi F, Vacondio F, Silva C, Rivara S, Lodola A, Alfieri RR, La Monica S, Galetti M, Ardizzoni A, Petronini PG, Mor M (2010) J Med Chem 53:2038

    Article  CAS  Google Scholar 

  10. ADMET Predictor 7.0 (2013) Simulations Plus, Inc. http://www.simulations-plus.com

  11. Nising CF, Brase S (2008) Chem Soc Rev 37:1218

    Article  CAS  Google Scholar 

  12. Nising CF, Brase S (2012) Chem Soc Rev 41:988

    Article  CAS  Google Scholar 

  13. Hammett LP (1937) J Am Chem Soc 59:96

    Article  CAS  Google Scholar 

  14. Charton M (1969) J Am Chem Soc 91:6649

    Article  CAS  Google Scholar 

  15. Charton M (1960) Can J Chem 38:2493

    Article  CAS  Google Scholar 

  16. Jackson NE, Savoie BM, Kohlstedt KL, de la Olvera Cruz M, Schatz GC, Chen LX, Ratner MA (2013) J Am Chem Soc 135:10475

    Article  CAS  Google Scholar 

  17. Klamt A, Schürmann GJ (1993) J Chem Soc Perkin Trans 2:799

    Google Scholar 

  18. Miertuš S, Scrocco E, Tomasi J (1981) Chem Phys 55:117

    Article  Google Scholar 

  19. Eyring HJ (1935) Chem Phys 3:107

    CAS  Google Scholar 

  20. Stewart JJP. MOPAC2012, Stewart computational chemistry. Colorado Springs, CO. http://OpenMOPAC.net

  21. Hansch C, Leo A, Hoekman D (1995) Exploring QSAR, hydrophobic, electronic and steric constants. American Chemical Society, Washington, DC

    Google Scholar 

  22. Hansch C, Leo A, Unger SH, Kim KH, Nikaitani D, Lein EJ (1973) J Med Chem 16:1207

    Article  CAS  Google Scholar 

  23. Hawkins PCD, Skillman AG, Warren GL, Ellingson BA, Stahl MT (2010) J Chem Inf Model 50:572. OMEGA v. 2.4.2. http://www.eyesopen.com

  24. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JA Jr, Vreven T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA (2003) Gaussian03, Revision C.02. Gaussian Inc., Pittsburgh

    Google Scholar 

  25. Stewart JJP (2007) J Mol Mod 13:1173

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The work reported makes use of results produced by the High-Performance Computing Infrastructure for South East Europe’s Research Communities (HP-SEE), a project co-funded by the European Commission (under Contract Number 261499) through the Seventh Framework Programme HP-SEE (http://www.hp-see.eu/). The authors gratefully acknowledge M.Sci. Milka Jadranin for HPLC analysis and SimulationsPlus Inc. for estimated pK A value. The Ministry of Education and Science of Serbia supported this work under Grant 172035.

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Authors and Affiliations

  1. Innovation Center of the Faculty of Chemistry, University of Belgrade, Studentski Trg 12–16, Belgrade, Serbia

    Ilija N. Cvijetić

  2. Military-Technical Institute, Ratka Resanovića 1, Belgrade, Serbia

    Maja D. Vitorović-Todorović

  3. Department of Chemistry-IChTM, University of Belgrade, Njegoševa 12, Belgrade, Serbia

    Ivan O. Juranić & Branko J. Drakulić

Authors
  1. Ilija N. Cvijetić
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  2. Maja D. Vitorović-Todorović
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  3. Ivan O. Juranić
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  4. Branko J. Drakulić
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Correspondence to Ilija N. Cvijetić.

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Cvijetić, I.N., Vitorović-Todorović, M.D., Juranić, I.O. et al. Reactivity of (E)-4-aryl-4-oxo-2-butenoic acid arylamides toward 2-mercaptoethanol. A LFER study. Monatsh Chem 144, 1815–1824 (2013). https://doi.org/10.1007/s00706-013-1084-6

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  • DOI: https://doi.org/10.1007/s00706-013-1084-6

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