Skip to main content
SpringerLink
Log in

Mechanistic investigation of the uncatalyzed esterification reaction of acetic acid and acid halides with methanol: a DFT study

  • Original Paper
  • Published:
Journal of Molecular Modeling Aims and scope Submit manuscript

Abstract

Implementation of catalysts to drive reactions from reactants to products remains a burden to synthetic and organic chemists. In spite of investigations into the kinetics and mechanism of catalyzed esterification reactions, less effort has been made to explore the possibility of an uncatalyzed esterification process. Therefore, a comprehensive mechanistic perspective for the uncatalyzed mechanism at the molecular level is presented. Herein, we describe the non-catalyzed esterification reaction of acetic acid and its halide derivatives (XAc, where X= OH, F, Cl, Br, I) with methanol (MeOH) through a concerted process. The reaction in vacuum and methanol was performed using the density functional theory (DFT) method at M06-2X level with def2-TZVP basis set after a careful literature survey and computations. Esterification through cyclic 4- or 6-membered transition state structures in one- or two-step concerted mechanisms were investigated. The present study outlines the possible cyclic geometry conformations that may occur during experiments at simple ratio of reactants. The free energy of activation for acetic acid and acetyl chloride are 36 kcal mol−1 and 21 kcal mol−1, respectively. These are in good agreement with available experimental results from the literature. The selected quantum chemical descriptors proved to be useful tools in chemical reactivity prediction for the reaction mechanism. This quantum mechanics study can serve as a necessary step towards revisiting uncatalyzed reaction mechanisms in some classical organic reactions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Kirby A (1972) Hydrolysis and formation of esters of organic acids. Comprehen Chem Kinet 10:57–207

    Article  CAS  Google Scholar 

  2. Ganapati DY, Pranav HM (1994) Heterogeneous catalysis in esterification reactions: preparation of phenethyl acetate and cyclohexyl acetate by using a variety of solid acidic catalysts. Ind Eng Chem Res 33:2198–2208

    Article  Google Scholar 

  3. Deng Y, Shi F, Beng J, Qiao K (2001) Ionic liquid as a green catalytic reaction medium for esterifications. J Mol Catal A Chem 165:33–36

    Article  CAS  Google Scholar 

  4. Cho CS, Kim DT, Choi H-J, Kim T-J, Shim SC (2002) Catalytic activity of Tin(II) chloride in esterification of carboxylic acids with alcohols. Bull Kor Chem Soc 23:539–540

    Article  CAS  Google Scholar 

  5. Lόpez DE, Suwannakarn K, Goodwin JG Jr, Bruce DA (2008) Reaction kinetics and mechanism for the gas- and liquid-phase esterification of acetic acid with methanol on tungstated zirconia. Ind Eng Chem Res 47:2221–2230

    Article  CAS  Google Scholar 

  6. Otera J, Nishikido J (2010) Esterification : methods, reactions, and applications, 2nd edn. Wiley-VCH, Weinheim

    Google Scholar 

  7. JagadeeshBabu PE, Sandesh K, Saidutta MB (2011) Kinetics of esterification of acetic acid with methanol in the presence of Ion exchange resin catalysts. Ind Eng Chem Res 50:7155–7160

    Article  CAS  Google Scholar 

  8. Zeng Z, Cui L, Xue W, Chen J and Che Y (2012) Recent developments on the mechanism and kinetics of esterification reaction promoted by various catalysts. Chem Kinet 255–282

  9. Smith MB, March J (2007) March’s advanced organic chemistry: reactions, mechanisms, and structure. Wiley, Hoboken

    Google Scholar 

  10. Gooßen LJ, Rodriguez N, Gooßen K (2008) Carboxylic acids as substrates in homogeneous catalysis. Angew Chem Int Ed 47:3100–3120

    Article  CAS  Google Scholar 

  11. Clayden J, Greeves N, Warren S (2012) Organic chemistry. Oxford University Press, New York

    Google Scholar 

  12. Willms T, Anderson HL, Heldt K, Hinz B (2000) Thermokinetics investigation of the reaction of acetly chloride with different alcohols: part II. Thermochim Acta 364:47–58

    Article  CAS  Google Scholar 

  13. Fox JM, Dmitrenko O, Liao L-A, Bach RD (2004) Computational studies of nucleophilic substitution at carbonyl carbon: the SN2 mechanism versus the tetrahedral intermediate in organic synthesis. J Org Chem 69:7317–7328

    Article  CAS  Google Scholar 

  14. Rolfe A, Hinshelwood C (1934) The kinetics of esterification. The reaction between acetic acid and methyl alcohol. Trans Faraday Soc 30:935–944

    Article  CAS  Google Scholar 

  15. Rönnback R, Salmi T, Vuori A, Haario H, Lehtonen J, Sundqvist A, Tirronen E (1997) Development of a kinetic model for the esterification of acetic acid with methanol in the presence of a homogeneous acid catalyst. Chem Eng Sci 52:3369–3381

    Article  Google Scholar 

  16. Mandake MB, Anekar SV, Walke SM (2013) Kinetic study of catalyzed and uncatalyzed esterification reaction of acetic acid with methanol. Am Int J Res Sci Technol Eng Math 3:114–121

    Google Scholar 

  17. Bronsted J (1928) Acid and basic catalysis. Chem Rev 5:231–338

    Article  CAS  Google Scholar 

  18. Williamson A, Hinshelwood C (1934) The kinetics of esterification. The reaction between acetic acid and methyl alcohol catalysed by hydrions. Trans Faraday Soc 30:1145–1149

    Article  CAS  Google Scholar 

  19. Basiuk VA (2002) Reactivity of carboxylic groups on armchair and zigzag carbon nanotube tips: a theoretical study of esterification with methanol. Nano Lett 2:835–839

    Article  CAS  Google Scholar 

  20. Kruger HG (2002) Ab initio mechanistic study of the protection of alcohols and amines with anhydrides. J Mol Struct THEOCHEM 577:281–285

    Article  CAS  Google Scholar 

  21. Gokul V, Kruger HG, Govender T, Fourie L, Power TD (2004) An ab initio mechanistic understanding of the regioselective acetylation of 8,11-dihydroxy-pentacyclo[5.4.0.02,6.03,10.05,9] undecane-8,11-lactam. J Mol Struct THEOCHEM 672:119–125

    Article  CAS  Google Scholar 

  22. Ishikawa SYT (1997) Hydrogen-bond networks for hydrolyses of anhydrides. J Org Chem 62:7049–7053

    Article  Google Scholar 

  23. Birney DM, Wagenseller PE (1994) An ab initio study of the reactivity of formylketene. Pseudopericyclic reactions revisited. J Am Chem Soc 116:6262–6270

    Article  CAS  Google Scholar 

  24. Birney DM, Ham S, Unruh GR (1997) Pericyclic and pseudopericyclic thermal cheletropic decarbonylations: when can a pericyclic reaction have a planar, pseudopericyclic transition state? 1. J Am Chem Soc 119:4509–4517

    Article  CAS  Google Scholar 

  25. Birney DM, Xu X, Ham S (1999) [1, 3],[3, 3], and [3, 5] sigmatropic rearrangements of esters are pseudopericyclic. Angew Chem Int Ed 38:189–193

    Article  CAS  Google Scholar 

  26. Aquino AJ, Tunega D, Haberhauer G, Gerzabek MH, Lischka H (2002) Solvent effects on hydrogen bonds a theoretical study. J Phys Chem A 106:1862–1871

    Article  CAS  Google Scholar 

  27. Abrams ML, Sherrill CD (2003) A comparison of polarized double-zeta basis sets and natural orbitals for full configuration interaction benchmarks. J Chem Phys 118:1604–1609

    Article  CAS  Google Scholar 

  28. Pliego JR, Riveros JM (2004) Free energy profile of the reaction between the hydroxide ion and ethyl acetate in aqueous and dimethyl sulfoxide solutions: a theoretical analysis of the changes induced by the solvent on the different reaction pathways. J Phys Chem A 108:2520–2526

    Article  CAS  Google Scholar 

  29. Takano Y, Houk KN (2004) Benchmarking the conductor-like polarizable continuum model (CPCM) for aqueous solvation free energies of neutral and ionic organic molecules. J Chem Theory Comput 1:70–77

    Article  CAS  Google Scholar 

  30. Yamabe S, Fukuda T, Ishii M (2011) Role of hydrogen bonds in acid-catalyzed hydrolyses of esters. Theor Chem Accounts 130:429–438

    Article  CAS  Google Scholar 

  31. Willms T, Anderson HL, Heldt K, Hinz B (2000) Thermokinetic investigation of the alcoholysis of acetyl chloride — Part I. Thermochim Acta 364:35–45

    Article  CAS  Google Scholar 

  32. Silva PL, Silva CM, Guimarães L, Pliego JR Jr (2015) Acid-catalyzed transesterification and esterification in methanol: a theoretical cluster-continuum investigation of the mechanisms and free energy barriers. Theor Chem Accounts 134:1–13

    Article  CAS  Google Scholar 

  33. Kimura A, Kawauchi S, Yamamoto T, Tezuka Y (2014) SN2 regioselectivity in the esterification of 5- and 7-membered azacycloalkane quaternary salts: a DFT study to reveal the transition state ring conformation prevailing over the ground state ring strain. Org Biomol Chem 12:6717–6724

    Article  CAS  Google Scholar 

  34. Bankole KS, Aurand GA (2014) Kinetic and thermodynamic parameters for uncatalyzed esterification of carboxylic acid. Res J Appl Sci Eng Technol 7:4671–4684

    Google Scholar 

  35. Kruger HG, Mdluli P, Power TD, Raasch T, Singh A (2006) Experimental and computational studies of the regioselective protection of hydantoins using anhydride. J Mol Struct THEOCHEM 771:165–170

    Article  CAS  Google Scholar 

  36. Weigend F, Ahlrichs R (2005) Balanced basis sets of split valence, triple zeta valence and quadruple zeta valence quality for H to Rn: design and assessment of accuracy. Phys Chem Chem Phys 7:3297–3305

    Article  CAS  Google Scholar 

  37. Weigend F (2006) Accurate coulomb-fitting basis sets for H to Rn. Phys Chem Chem Phys 8:1057–1065

    Article  CAS  Google Scholar 

  38. Zhao Y, González-García N, Truhlar DG (2005) Benchmark database of barrier heights for heavy atom transfer, nucleophilic substitution, association, and unimolecular reactions and its use to test theoretical methods. J Phys Chem A 109:2012–2018

    Article  CAS  Google Scholar 

  39. Zhao Y, Truhlar DG (2008) Density functionals with broad applicability in chemistry. Acc Chem Res 41:157–167

    Article  CAS  Google Scholar 

  40. Bryantsev VS, Diallo MS, van Duin AC, Goddard WA III (2009) Evaluation of B3LYP, X3LYP, and M06-class density functionals for predicting the binding energies of neutral, protonated, and deprotonated water clusters. J Chem Theory Comput 5:1016–1026

    Article  CAS  Google Scholar 

  41. Ochterski JW (1999) Vibrational analysis in Gaussian, help@ gaussian. com

  42. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA Jr, Peralta JE, Ogliaro F, Bearpark MJ, Heyd J, Brothers EN, Kudin KN, Staroverov VN, Keith R, Kobayashi R, Normand J, Raghavachari K, Rendell AP, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam NJ, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas Ö, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2013) Gaussian 09. In: Revision D.01, Gaussian, Inc., Wallingford, 2013

  43. Ochterski JW (2000) Thermochemistry in Gaussian. http://www.gaussian.com/g_whitepap/thermo.htm

  44. Foresman JB, Frisch A (1996) Exploring chemistry with electronic structure methods. Gaussian, Inc., Pittsburgh

    Google Scholar 

  45. Pliego JR, Riveros JM (2001) The cluster-continuum model for the calculation of the solvation free energy of ionic species. J Phys Chem A 105:7241–7247

    Article  CAS  Google Scholar 

  46. Ribeiro RF, Marenich AV, Cramer CJ, Truhlar DG (2011) Use of solution-phase vibrational frequencies in continuum models for the free energy of solvation. J Phys Chem B 115:14556–14562

    Article  CAS  Google Scholar 

  47. Marenich AV, Cramer CJ, Truhlar DG (2009) Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions. J Phys Chem B 113:6378–6396

    Article  CAS  Google Scholar 

  48. da Silva PL, Guimaraes L, Pliego JR (2013) Revisiting the mechanism of neutral hydrolysis of esters: water autoionization mechanisms with acid or base initiation pathways. J Phys Chem B 117:6487–6497

    Article  CAS  Google Scholar 

  49. Cances E, Mennucci B, Tomasi J (1997) A new integral equation formalism for the polarizable continuum model: theoretical background and applications to isotropic and anisotropic dielectrics. J Chem Phys 107:3032–3041

    Article  CAS  Google Scholar 

  50. Rega N, Cossi M, Barone V (1999) Improving performance of polarizable continuum model for study of large molecules in solution. J Comput Chem 20:1186–1198

    Article  CAS  Google Scholar 

  51. Tomasi J, Mennucci B, Cances E (1999) The IEF version of the PCM solvation method: an overview of a new method addressed to study molecular solutes at the QM ab initio level. J Mol Struct THEOCHEM 464:211–226

    Article  CAS  Google Scholar 

  52. Cossi M, Rega N, Scalmani G, Barone V (2003) Energies, structures, and electronic properties of molecules in solution with the C‐PCM solvation model. J Comput Chem 24:669–681

    Article  CAS  Google Scholar 

  53. Geerlings P, De Proft F, Langenaeker W (2003) Conceptual density functional theory. Chem Rev 103:1793–1873

    Article  CAS  Google Scholar 

  54. Senet P (1997) Chemical hardnesses of atoms and molecules from frontier orbitals. Chem Phys Lett 275:527–532

    Article  CAS  Google Scholar 

  55. Dennington R, Keith T, Millam J (2009) In GaussView, 5.0.8 ed. Semichem Inc, Shawnee Mission

    Google Scholar 

  56. Aakeröy CB, Seddon KR (1993) The hydrogen bond and crystal engineering. Chem Soc Rev 22:397–407

    Article  Google Scholar 

  57. Arunan E, Desiraju GR, Klein RA, Sadlej J, Scheiner S, Alkorta I, Clary DC, Crabtree RH, Dannenberg JJ, Hobza P (2011) Defining the hydrogen bond: an account (IUPAC technical report). Pure Appl Chem 83:1619–1636

    CAS  Google Scholar 

  58. Wolters LP, Bickelhaupt FM (2012) Halogen bonding versus hydrogen bonding: a molecular orbital perspective. Chem Open 1:96–105

    CAS  Google Scholar 

  59. Shagun V, Voronkov M (2003) Acyl iodides in organic synthesis: III. Quantum-chemical study of the reaction of acyl iodides and acyl chlorides with methanol. Russ J Org Chem 39:331–335

    Article  CAS  Google Scholar 

  60. Gutman M, Nachliel E (1997) Time-resolved dynamics of proton transfer in proteinous systems. Annu Rev Phys Chem 48:329–356

    Article  CAS  Google Scholar 

  61. Gunaydin H, Houk K (2008) Molecular dynamics prediction of the mechanism of ester hydrolysis in water. J Am Chem Soc 130:15232–15233

    Article  CAS  Google Scholar 

  62. Ilieva S, Galabov B, Musaev DG, Morokuma K, Schaefer HF (2003) Computational study of the aminolysis of esters. The reaction of methylformate with ammonia. J Org Chem 68:1496–1502

    Article  CAS  Google Scholar 

  63. Gilkerson W (1956) Kinetics of reaction of ethyl alcohol with p-nitrobenzoyl chloride in nitrobenzene at 7.38. J Phys Chem 60:1142–1144

    Article  CAS  Google Scholar 

  64. Bentley TW, Llewellyn G, McAlister JA (1996) SN2 mechanism for alcoholysis, aminolysis, and hydrolysis of acetyl chloride. J Org Chem 61:7927–7932

    Article  CAS  Google Scholar 

  65. Mittal KL (1991) Acid–base interactions: relevance to adhesion science and technology. Taylor & Francis, Utrecht

    Google Scholar 

  66. Okoli CP, Guo QJ, Adewuyi GO (2014) Application of quantum descriptors for predicting adsorption performance of starch and cyclodextrin adsorbents. Carbohydr Polym 101:40–49

    Article  CAS  Google Scholar 

  67. Arjunan V, Devi L, Subbalakshmi R, Rani T, Mohan S (2014) Synthesis, vibrational, NMR, quantum chemical and structure-activity relation studies of 2-hydroxy-4-methoxyacetophenone. Spectrochim Acta A Mol Biomol Spectrosc 130:164–177

    Article  CAS  Google Scholar 

  68. El-Gammal OA, Rakha TH, Metwally HM, Abu El-Reash GM (2014) Synthesis, characterization, DFT and biological studies of isatinpicolinohydrazone and its Zn(II), Cd(II) and Hg(II) complexes. Spectrochim Acta A Mol Biomol Spectrosc 127:144–156

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors appreciate College of Health Sciences University of KwaZulu-Natal, Asphen Pharmacare, Medical Research Council and National Research Foundation (all in South Africa) for financial support. We are also grateful to the Center for High Performance Computing (http://www.chpc.ac.za) for computational resources.

Author information

Authors and Affiliations

  1. Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, 4041, South Africa

    Monsurat M. Lawal, Thavendran Govender, Glenn E. M. Maguire, Bahareh Honarparvar & Hendrik G. Kruger

  2. School of Chemistry and Physics, University of KwaZulu-Natal, Durban, 4041, South Africa

    Glenn E. M. Maguire

Authors
  1. Monsurat M. Lawal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thavendran Govender
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Glenn E. M. Maguire
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bahareh Honarparvar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hendrik G. Kruger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hendrik G. Kruger.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

Details on the choice of basis sets are presented. Relative thermodynamics and kinetics data of all possible TS structures plus their bond length distances are given. Relative thermodynamics and kinetics values obtained at 373.15 K are also available. (DOCX 131 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lawal, M.M., Govender, T., Maguire, G.E.M. et al. Mechanistic investigation of the uncatalyzed esterification reaction of acetic acid and acid halides with methanol: a DFT study. J Mol Model 22, 235 (2016). https://doi.org/10.1007/s00894-016-3084-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00894-016-3084-z

Keywords

Search

Navigation