Theoretical study of an anti-Markovnikov addition reaction catalyzed by β-cyclodextrin

  • Xiesi Quan
  • Shanfeng Yi
  • Xueye Wang
Original Paper


β-Cyclodextrin (β-CD) has a hydrophilic exterior and a hydrophobic internal cavity, which allows it to form host–guest complexes with a wide range of guests, such as organics, inorganics, and biomolecules. The aforementioned features lead to an extensive range of applications of β-CD, as the properties of β-CD mean that it is environmentally friendly and can be recovered and reused without mass loss. Here, the β-CD-catalyzed anti-Markovnikov addition of styrene to thiophenol in the presence of aerial oxygen and in aqueous solution to give 1-phenyl-2-(phenylsulfanyl)-1-ethanol was studied using density functional theory (DFT) and the Hartree–Fock (HF) method. The optimal configuration of the inclusion complex of styrene and thiophenol within β-CD was obtained, which indicated that styrene and thiophenol enter from the secondary and primary hydroxyl ends of β-CD, respectively. Moreover, hydrogen bonding of β-CD with styrene and thiophenol contributes to the stability of the inclusion complex. An investigation of the charges from electrostatic potentials using a grid-based method (CHELPG) highlighted the distribution of atomic charges upon complexation. The reaction sites of styrene and thiophenol were determined based on electrostatic potentials (ESPs) and condensed dual descriptors. The calculated 1H nuclear magnetic resonance (1H NMR) spectrum of β-CD implied that the chemical shifts of its protons change and H3 and H5 move to higher fields upon complexation, while the calculated 13C nuclear magnetic resonance (13C NMR) spectrum of styrene suggested that this molecule is electrophilic.

Graphical abstract


Anti-Markovnikov addition β-Cyclodextrin Density functional theory (DFT) Inclusion complexes 


  1. 1.
    Zhang J, Ma PX (2013) Cyclodextrin-based supramolecular systems for drug delivery: recent progress and future perspective. Adv Drug Deliv Rev 65:1215–1233Google Scholar
  2. 2.
    Szejtli J (1998) Introduction and general overview of cyclodextrin chemistry. Chem Rev 98:1743–1753Google Scholar
  3. 3.
    Huang M, Li C, Gu Z, Cheng L, Hong Y, Li Z (2014) Mutations in cyclodextrin glycosyltransferase from Bacillus circulans enhance β-cyclization activity and β-cyclodextrin production. J Agric Food Chem 62:11209–11214Google Scholar
  4. 4.
    Yang DS, Stavrides P, Kumar A, Jiang Y, Mohan PS, Ohno M, Dobrenis K, Davidson CD, Saito M, Pawlik M, Huo C, Walkley SU, Nixon RA (2017) Cyclodextrin has conflicting actions on autophagy flux in vivo in brains of normal and Alzheimer model mice. Hum Mol Genet 26:843–859Google Scholar
  5. 5.
    Vilar M, Navarro M (2010) Determination of cyclodextrin inclusion constant for aromatic carbonyl compounds through spectrophotometric and electrochemical methods. Electrochim Acta 56:305–313Google Scholar
  6. 6.
    López CA, De AH, Marrink SJ (2013) Computational microscopy of cyclodextrin mediated cholesterol extraction from lipid model membranes. Sci Rep 3:2071Google Scholar
  7. 7.
    Lu Y, Zou H, Yuan H, Gu S (2017) Triple stimuli-responsive supramolecular assemblies based on host–guest inclusion complexation between β-cyclodextrin and azobenzene. Eur Polym J 91:396–407Google Scholar
  8. 8.
    Saenger W (1980) Cyclodextrin inclusion compounds in research and industry. Angew Chem Int Ed 19:344–362CrossRefGoogle Scholar
  9. 9.
    Li Z, Wang M, Wang F, Gu Z, Du G, Wu J, Chen J (2007) γ-Cyclodextrin: a review on enzymatic production and applications. Appl Microbiol Biotechnol 77:245–255CrossRefGoogle Scholar
  10. 10.
    Valle D, Martin EM (2004) Cyclodextrins and their uses: a review. Process Biochem 39:1033–1046Google Scholar
  11. 11.
    Bensouilah N, Abdaoui M (2012) Inclusion complex of N-nitroso,N-(2-chloroethyl),N′,N′-dibenzylsulfamide with β-cyclodextrin: fluorescence and molecular modeling. C R Chim 15:1022–1036Google Scholar
  12. 12.
    Ohira A, Sakata M, Taniguchi I, Hirayama C, Kunitake M (2003) Comparison of nanotube structures constructed from α-, β-, and γ-cyclodextrins by potential-controlled adsorption. J Am Chem Soc 125:5057–5065Google Scholar
  13. 13.
    Arun KT, Jayaram DT, Avirah RR, Ramaiah D (2011) β-Cyclodextrin as a photosensitizer carrier: effect on photophysical properties and chemical reactivity of squaraine dyes. J Phys Chem B 115:7122–7128Google Scholar
  14. 14.
    Tehri P, Aegurula B, Peddinti RK (2017) Iodine-catalysed regioselective synthesis of β-hydroxysulfides. Tetrahedron Lett 58:2062–2065Google Scholar
  15. 15.
    Fringuelli F, Pizzo F, Tortoioli S, Vaccaro L (2004) One-pot synthesis of benzo[e]1,4-oxathiepin-5-ones under solvent-free condition via self-promoted thiolysis of 1,2-epoxides. J Org Chem 69:8780–8785Google Scholar
  16. 16.
    Chakraborti AK, Rudrawar S, Kondaskar A (2004) An efficient synthesis of 2-amino alcohols by silica gel catalyzed opening of epoxide rings by amines. Org Biomol Chem 35:1277–1280CrossRefGoogle Scholar
  17. 17.
    Movassagh B, Navidi M (2008) One-pot synthesis of β-hydroxysulfides from styrenes and disulfides using the Zn/AlCl3 system. Tetrahedron Lett 49:6712–6714Google Scholar
  18. 18.
    Feng JB, Wu XF (2016) Synthesis of β-hydroxysulfides from thiophenols and disulfides with tert-butyl hydroperoxide as the oxidant and reactant. Chemistry Open 5:315–318Google Scholar
  19. 19.
    Agafontsev AM, Gorshkov NB, Tkachev AV (2011) Efficient synthesis of β-hydroxy sulfides by microwave-promoted ring opening in (+)-3-carene trans-epoxide with sodium thiolates. Mendeleev Commun 21:192–193Google Scholar
  20. 20.
    Guo W, Chen J, Wu D, Ding J, Chen F, Wu H (2009) Rongalite® promoted highly regioselective synthesis of β-hydroxy sulfides by ring opening of epoxides with disulfides. Tetrahedron 65:5240–5243Google Scholar
  21. 21.
    Krishnaveni NS, Surendra K, Rao KR (2004) A simple and highly selective biomimetic oxidation of alcohols and epoxides with n-bromosuccinimide in the presence of β-cyclodextrin in water. Adv Synth Catal 346:346–350Google Scholar
  22. 22.
    Surendra K, Krishnaveni NS, Sridhar R, Rao KR (2006) Synthesis of β-hydroxysulfides from alkenes under supramolecular catalysis in the presence of β-cyclodextrin in water. J Org Chem 71:5819–5821Google Scholar
  23. 23.
    Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery Jr JA, 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, Bakken V, 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) Gaussian 2003W, revision B.05. Gaussian Inc., PittsburghGoogle Scholar
  24. 24.
    Li Z, Couzijn EP, Zhang X (2012) Intrinsic properties of α-cyclodextrin complexes with benzoate derivatives in the gas phase: an experimental and theoretical study. J Phys Chem 116:943–950Google Scholar
  25. 25.
    Entrena A, Jaime C (1997) Cyclodextrin inclusion complexes. Molecular mechanics calculations on the modification of π-face selectivity. J Org Chem 62:5923–5927CrossRefGoogle Scholar
  26. 26.
    Wan Y, Wang X, Liu N (2015) DFT study the interaction of β-cyclodextrin with benzyl azide, and phenyl acetylene in synthesis of 1,2,3-triazoles. J Phys Org Chem. 28:25–30Google Scholar
  27. 27.
    Lu T, Chen F (2012) Multiwfn: a multifunctional wavefunction analyzer. J Comput Chem 33:580–592Google Scholar
  28. 28.
    Yan C, Xiu Z, Li X, Hao C (2007) Molecular modeling study of β-cyclodextrin complexes with (+)-catechin and (−)-epicatechin. J Mol Graph Model 26:420–428CrossRefGoogle Scholar
  29. 29.
    Desiraju GR (2002) Hydrogen bridges in crystal engineering: interactions without borders. Acc Chem Res 35:565–573Google Scholar
  30. 30.
    Desiraju GR (1996) The C–H···O hydrogen bond: structural implications and supramolecular design. Acc Chem Res 29:441–449Google Scholar
  31. 31.
    Chocholoušová J, Špirko V, Hobza P (2004) First local minimum of the formic acid dimer exhibits simultaneously red-shifted O–H···O and improper blue-shifted C–H···O hydrogen bonds. Phys Chem Chem Phys. 6:37–41Google Scholar
  32. 32.
    Uccello-Barretta G, Balzano F, Sicoli G, Fríglola C, Aldana I, Monge A, Paolino D, Guccione S (2004) Combining NMR and molecular modelling in a drug delivery context: investigation of the multi-mode inclusion of a new npy-5 antagonist bromobenzenesulfonamide into β-cyclodextrin. Bioorg Med Chem 12:447–458Google Scholar
  33. 33.
    He Z, Sundström V, Pullerits T (2001) Excited states of carotenoid in LH2: an ab initio study. Chem Phys Lett 334:159–167Google Scholar
  34. 34.
    Maciel GS, Garcia E (2005) Charges derived from electrostatic potentials: exploring dependence on theory and geometry optimization levels for dipole moments. Chem Phys Lett 409:29–33Google Scholar
  35. 35.
    Dimitrova V, Ilieva S, Galabov B (2003) Electrostatic potential at nuclei as a reactivity index in hydrogen bond formation. Complexes of ammonia with C–H, N–H and O–H proton donor molecules. J Mol Struct THEOCHEM 637:73–80Google Scholar
  36. 36.
    Prado MAS, Garcia E, Martins JBL (2006) Theoretical study of cytosine–Mg complex. Chem Phys Lett 418:264–267Google Scholar
  37. 37.
    Umeyama H, Morokuma K (1977) The origin of hydrogen bonding. An energy decomposition study. J Am Chem Soc 99:1316–1332CrossRefGoogle Scholar
  38. 38.
    Fang Y, Hu H (2006) Shape-selectivity in 2,6-dimethylnaphthalene synthesis over ZSM-5: computational analysis using density functional theory. Catal Commun 7:264–267Google Scholar
  39. 39.
    Rong F, Tian L, Feiwu C (2014) Comparing methods for predicting the reactive site of electrophilic substitution. Acta Phys-Chim Sin 30:628–639Google Scholar
  40. 40.
    Cao J, Ren Q, Chen F, Liu T (2015) Comparative study on the methods for predicting the reactive site of nucleophilic reaction. Sci China Chem 58:1845–1852CrossRefGoogle Scholar
  41. 41.
    Murray JS, Politzer P (2011) The electrostatic potential: an overview. WIREs Comp Mol Sci 1:153–163Google Scholar
  42. 42.
    Politzer P, Murray JS (2002) The fundamental nature and role of the electrostatic potential in atoms and molecules. Theor Chem Accounts 108:134–142Google Scholar
  43. 43.
    Sjoberg P, Politzer P (1990) Use of the electrostatic potential at the molecular surface to interpret and predict nucleophilic processes. J Phys Chem 94:3959–3961Google Scholar
  44. 44.
    Politzer P, Murray JS, Concha MC (2002) The complementary roles of molecular surface electrostatic potentials and average local ionization energies with respect to electrophilic processes. Int J Quantum Chem 88:19–27Google Scholar
  45. 45.
    Politzer P, Laurence PR, Jayasuriya K (1985) Molecular electrostatic potentials: an effective tool for the elucidation of biochemical phenomena. Environ Health Perspect 61:191–202CrossRefGoogle Scholar
  46. 46.
    Bader RFW, Carroll MT, Cheeseman JR, Chang C (1987) Properties of atoms in molecules: atomic volumes. J Am Chem Soc 109:7968–7979Google Scholar
  47. 47.
    Murray JS, Paulsen K, Politzer P (1994) Molecular surface electrostatic potentials in the analysis of non-hydrogen-bonding noncovalent interactions. J Chem Sci 106:267–275Google Scholar
  48. 48.
    Lu T, Chen F (2012) Quantitative analysis of molecular surface based on improved marching tetrahedra algorithm. J Mol Graph Model 38:314–323Google Scholar
  49. 49.
    Cheng Y, Wang X, Li W, Chang D (2017) DFT study on the effects of catalysis by β-cyclodextrin in the reaction of p-nitrophenyl acetate. J Mol Model 23:21Google Scholar
  50. 50.
    Wang T, Fang WY, Liang WX (2014) Molecular structure and vibrational bands and 13C chemical shift assignments of both enmein-type diterpenoids by DFT study. Spectrochim Acta A 117:449–458CrossRefGoogle Scholar
  51. 51.
    Zhou J, He B, Chen B, Lu P, Sung HHY, Williams ID, Qin A, Qiu H, Zujin Z, Zhong TB (2013) Deep blue fluorescent 2,5-bis(phenylsilyl)-substituted 3,4-diphenylsiloles: synthesis, structure and aggregation-induced emission. Dyes Pigments 99:520–525Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of ChemistryXiangtan UniversityXiangtanPeople’s Republic of China

Personalised recommendations