Mechanism of the acidic hydrolysis of epichlorohydrin

Research Article Received: 29 March 2010, Revised: 1 October 2010, Accepted: 11 October 2010, Published online in Wiley Online Library: 12 January 2011 (wileyonlinelibrary.com) DOI 10.1002/poc.1825 Mechanism of the acidic hydrolysis of epichlorohydrin Jerzy Gaca a *,Grażyna Wejnerowska a and Piotr Cysewski a The present studies show that the currently accepted scheme for the hydrolysis of epichlorohydrin (ECH) needs to be extended by an additional path which makes allowance for the formation and decomposition of glycidol (GL). It was shown experimentally and through UB3LYP/6-11 RRG(3D,P) calculations that the formation of 3-chloro-1,2-propanediol (MCPD) from ECH should also take into account GL formation as an intermediate product. A modified mechanism for the course of ECH hydrolysis in acidic and neutral medium is proposed. It was shown that ECH hydrolysis in acidic medium in the presence of chloride ions also results in the formation of 1,3-dichloro-2-propanol (DCPD) in addition to GL and MCPD. The possibility of a parallel pathway for water molecule addition to epichlorohydrin was shown which as a consequence led to the parallel appearance of GL and MCPD. It was confirmed by kinetic calculations that the state of equilibrium, reached in the process of ECH chlorination, did not result in GL formation. However, its appearance in the reaction mechanism has been ignored in the literature thus far. Copyright ß 2011 John Wiley & Sons, Ltd. Keywords: 3-chloro-1,2-propanediol; 1,3-dichloro-2-propanol; epichlorohydrin; glycerol; hydrolysis INTRODUCTION Our previous studies on the determination of epichlorohydrin (ECH) [1] and the products of its hydrolysis in acidic (HNO 3 ) and neutral medium showed that 3-chloro-1,2-propanediol (MCPD) was formed in parallel with ECH loss which was expected. However, the concentration of MCPD formed, especially in the initial stage of the reaction, did not make up for the loss of ECH. This fact cannot be explained by the generally accepted scheme, according to which the hydrolysis of epichlorohydrin leads to the formation of MCPD through protonation of the epoxide ring [2 8] (Fig. 1). Such a description of the reaction does not explain the lack of a dependence between the change in the ECH concentration and the amount of MCPD formed, which was observed in our studies. Moreover, it does not explain the pathway for the formation of glycerol (GLC) identified among the reaction products. Due to the discrepancies observed in the description of the course of the reaction, studies were undertaken in order to explain the mechanism of ECH hydrolysis in acidic and neutral medium. These studies take into consideration the formation and decay of GL and account for obtaining only trace amounts of GLC. Preparation of solutions Model water solutions of ECH at the concentration of 1.183 g L 1 and the following ph values: 2.5, 3.5, 4.5 and 7.7 were prepared for testing. The ph of the solutions was adjusted using aqueous solution introducing HNO 3. Then, samples were placed into graduated 25 ml flasks and filled to the top. These samples were kept at temperatures of 10, 20, 30 and 40 8C. Analogous solutions, containing 1.183 and 0.748 g L 1 of NaCl, were used in this study to check the effect of chlorides on the course of ECH hydrolysis. GC analysis Gas chromatograph HP 6890 (Hewlett Packard, CA, USA) fitted with a detector, flame ionization detector (FID), and an on-column injector were applied in our studies. HP-FFAP columns (Crosslinked Polyethylene Glycol) 30 m 0.53 mm, 1.0 mm were used. The volume of the injected solutions was 2 ml. The oven temperature program for water solutions was 100 8C (2min),108Cmin 1 to 240 8C (4 min). Helium was the carrier gas at a constant flow rate of 1.3 ml min 1. Temperatures of the FID detector and the on-column injector were 250 and 103 8C, respectively. EXPERIMENTAL Chemicals Epichlorohydrin (>99%) and glycerol (>96%) were purchased from Sigma-Aldrich (Steinheim, Germany). 3- chloro-1,2- propanediol (98%) and 1,3-dichloro-2-propanol were purchased from Fluka (Chemie, GmbH, Germany). Glycerol (>99%) and water (analytical-reagent grade) were used as solvents purchased from Merck (Darmstadt, Germany). Sodium chloride and nitric (V) acid (analytical-reagent grade) were purchased from POCH S.A. (Gliwice, Poland). Calculation method J. Phys. Org. Chem. 2011, 24 1045 1050 Copyright ß 2011 John Wiley & Sons, Ltd. Calculations were made using a microhydrated environment model. [9,10] It contained two water molecules complexing the * Correspondence to: J. Gaca, Department of Chemistry and Environmental Protection, Faculty of Chemical Technology and Engineering, University of Technology and Life Sciences, Seminaryjna 3 St., 85-326 Bydgoszcz, Poland. E-mail: gaca@utp.edu.pl a J. Gaca, G. Wejnerowska, P. Cysewski Department of Chemistry and Environmental Protection, Faculty of Chemical Technology and Engineering, University of Technology and Life Sciences, Bydgoszcz, Poland 1045

J. GACA, G. WEJNEROWSKA AND P. CYSEWSKI Figure 1. Hydrolysis of ECH 1046 molecule of epichlorohydrin. The calculations were performed by the unrestricted B3LYP method. The size of the functional base was selected on the basis of a series of calculations of Gibbs free energy changes for the reactions ECH! GL and ECH! MCPD. [11] Both polarization and diffusion functions for heavy and hydrogen atoms were used in the calculations. The expansion of the valence basis sets was increased systematically. It was observed that from the basis set 6-311 þ G(3D,P) a further increase in the number of base functions did not have any significant impact on values of DE and DG. This permitted us to assume the 6-311 þþg(3d,p) basis set was already saturated. Thus, the UB3LYP/6-311 þþg(3d,p) method was used for seeking points on the potential energy hypersurface corresponding to the global minimum and the saddle points. All calculations take into consideration zero point energy corrections and the thermal energy. The location of saddle points was confirmed by calculating the reaction paths by the IRC method. The CPCM method was used for taking into account the Gibbs free energies of solvation. All calculations were performed using Gaussian03 program. [12] RESULTS AND DISCUSSION While conducting a preliminary studies on the course of ECH hydrolysis, it was found that especially at the initial stage of reaction, the amount of MCPD formed was considerably smaller that it would result from the loss of ECH. This means that the hydrolysis process described in Fig. 1 does not take into account all the possible paths of conversion. Our study showed that after a long time, amount of the formed MCPD was consistent with the reaction stoichiometry presented in Fig. 1. It means that the substance formed during hydrolysis process is in a later stage converted to MCPD and simultaneously it shows that MCPD is stable under reaction conditions and it does not undergo further conversions. The studies on identification of the reaction products during hydrolysis showed that in parallel with MCPD glicydol was formed, which at a later stage was converted to MCPD. These studies were carried out in acidic and neutral media (ph: 2.5 7.0) within the temperature range of 10 40 8C. The course of the reaction was analogous in all cases. Temperature rise and ph reduction resulted only in faster ECH loss and caused changes in the MCPD:GCL ratio and the reaction rate. Examples of the curves obtained for the reaction occurring at a temperature of 40 8C and ph 3.5 are presented in Fig. 2. It was found that GL was formed in the beginning of the reaction and decayed in time. An important fact is that GL was still identified even after the time that ECH had totally reacted. The decrease in the GL content and its presence after time that ECH had disappeared, allowed us to state that the rate of glycidol decay was slower than the rate of its formation. Figure 2. Hydrolysis of ECH at ph 3.5 and T¼40 8C The facts that GL (whose content decreases in time) was identified among the products of the epichlorohydrin hydrolysis at ph < 7 and that the final product of the reaction was MCPD allowed us to propose a scheme in which the formation of MCPD proceeded or supplemented the formation of GL. The decay of GL during the course of the process can be explained by its reaction with chloride ions (liberated from ECH) resulting in the formation of MCPD (Fig. 3). A similar mechanism can be proposed for the ECH hydrolysis occurring in neutral medium. However, the reaction occurs considerably slower under the conditions used in the current study. In order to confirm the possibility of MCPD formation from GL in acidic medium, further studies on the GL reaction with chlorides or hydrochloric acid in water solutions were carried out. Their results are summarized in Fig. 4. It was shown that the rate of MCDP formation depended significantly on the temperature and the concentration of chloride ions. In order to elimination the less probable alternative of glycerol formation from MCPD, studies on the possibility of glycerol formation from MCPD were performed. It was found that in various Cl concentration and different ph values we did not detected GLC or 1,3-dichloro-propanol (DCP). To explain the absence of GLC among the products of the ECH hydrolysis in acidic medium, studies on MCPD hydrolysis in the absence of chloride ions were carried out. It was found that MCPD was stable under the conditions used, whereas GL in acidic medium was transformed into GLC (Fig. 5). The assumption that GL is one of the products of ECH hydrolysis still did not explain the reason why only a minimal amount of GLC can be identified. Taking into consideration the fact that HCl is released in the process of GL formation, the successive studies on ECH, GL and MCPD hydrolysis in acidic medium in the presence of chloride ions were carried out. Results of such studies for ECH hydrolysis in the presence of chloride ions in acidic medium are presented in Fig. 6. wileyonlinelibrary.com/journal/poc Copyright ß 2011 John Wiley & Sons, Ltd. J. Phys. Org. Chem. 2011, 24 1045 1050

MECHANISM OF THE ACIDIC HYDROLYSIS Figure 3. Proposed scheme of ECH hydrolysis in acidic medium Figure 4. Course of GL reaction with chloride ions Figure 6. Hydrolysis of ECH at ph 3.5 and T ¼ 40 8C in presence of chloride ions Figure 5. Hydrolysis of MCPD and GL in acidic medium Three products, GL, MCPD and DCPD, were simultaneously identified during ECH hydrolysis in the presence of chloride ions. However, after time, the GL formed was converted into MCPD (Fig. 7). It is understandable since GL reacts easily with Cl ions giving MCPD. Apart from temperature and ph, the propanol chloroderivatives (MCPD and DCPD) do not undergo further conversions. Taking into account the fact that in the final product of ECH hydrolysis in acidic medium, the main product of the reaction was MCPD, and that at the beginning of the reaction a subsidiary compound, i.e. glycidol, was identified, it can be concluded that Cl competes with water molecules in the reaction studied (Fig. 3). In order to confirm the experimental observations, both kinetics and thermodynamics modelling were performed. The obtained values (Table 1) show that the equilibrium constant for the reaction of MCPD formation from ECH is by about six orders of magnitude higher than that for GL formation. This confirms our observations that MCPD, but not GL, is the final product of the reaction. On the other hand, our experiments unequivocally suggest that GL appears as an intermediate product at the beginning of the reaction and decays with the progress of ECH chlorination. To clarify our observations, kinetic calculations were made to reveal the actual mechanism on the molecular level. The structures of the transition states and the corresponding values of the activation energies were estimated for processes both in neutral and acidic media. It was found that in both environments, two water molecules played an active role in the mechanism of hydrolysis acting as catalysts forming hydrogen bonds with the oxygen atom of epichlorohydrin. The paths of the reactions occurring in neutral medium are presented in Figs. 8 and 9. As shown in Figs. 8 and 9, the presence of two water molecules is important since one of them plays an active role in the addition reaction, whereas the second one forms strong hydrogen bonds and has an indirect effect on the reaction mechanism reducing by several kcal mol 1 the value of the activation energy. In case of epoxy ring hydrolysis, an accompanying water molecule forms a strong hydrogen bond with the oxygen atom of ECH by the addition of a water molecule to the C 1 or C 2 carbon atom. The substrate is an ECH complex stabilized by two strong hydrogen bonds formed by both water molecules present on opposite sides of the epoxy ring. The product of the reactions is MCPD stabilized by a hydrogen bond formed between a water molecule J. Phys. Org. Chem. 2011, 24 1045 1050 Copyright ß 2011 John Wiley & Sons, Ltd. wileyonlinelibrary.com/journal/poc 1047

J. GACA, G. WEJNEROWSKA AND P. CYSEWSKI Figure 7. Scheme of ECH hydrolysis in acidic medium in the presence of chloride ions Table 1. Results of the theoretical estimation of equilibrium constants based on the thermodynamic cycle presented on Fig. 9 Reaction DE (g) DG (g) DG (s) pk ECH þ H 2 O ¼ MCPD 23.02 6.53 6.57 4.81 MCPD ¼ GL ¼ HCl 26.23 8.40 8.44 6.19 ECH þ HCl ¼ DCPD 25.48 73.65 7.69 5.64 ECH þ H 2 O ¼ GL þ HCl 3.22 1.87 3.02 2.22 and one of the hydroxyl groups. The lattice of hydrogen bonds formed by both water molecules and the oxygen atom of ECH is created in the saddle point. The selected geometrical characteristics of the complexes analysed are presented in Fig. 8. The activation energies of the saddle points TS1 and TS2 are very close which suggests the parallel courses involving both processes. In both cases, the second molecule of water actively supports the process of addition. The value of the Gibbs free energy for the process ECH! MCPD is equal to DG aq ¼ 2.08 kcal mol 1 at room temperature. It is worth emphasizing that an alternative path of ECH hydrolysis exists. The possibility of a direct attack of one water molecule on the C 3 atom with the simultaneous dissociation of hydrogen chloride is shown in Fig. 9. It was found that in the saddle point, two water molecules form hydrogen bonds with the chlorine ion of ECH and with each other. The products of this reaction are glycidol and hydrogen chloride. The value of the Gibbs free energy of the ECH! GL process is higher than for the process of MCPD formation and it is equal to DG aq ¼ 5.59 kcal mol 1 at room temperature. Since the energy value corresponding to the saddle point for this path is almost identical to that leading to MCPD, both products should be formed with similar reaction rates which 1048 Figure 8. Scheme of water molecule addition to the epoxy ring in neutral medium. Energy values are given in kcal mol 1 wileyonlinelibrary.com/journal/poc Copyright ß 2011 John Wiley & Sons, Ltd. J. Phys. Org. Chem. 2011, 24 1045 1050

MECHANISM OF THE ACIDIC HYDROLYSIS Figure 9. Scheme of water molecule addition to the C3 atom of Cl in neutral medium. Energy values are given in kcal mol 1 Figure 10. Scheme of the hydronium ion addition to the epoxy ring in acid medium. Energy values are given in kcal mol 1 was experimentally observed. The decay of GL can be explained by its reaction with HCl formed as a result of ECH hydrolysis. Moreover, calculations including the effect of acidic medium on the mechanism of epichlorohydrin hydrolysis were also performed. The fundamental difference with respect to the above described mechanism in neutral medium is the appearance of spontaneous protonation of the substrate by the hydronium ion. Structural and energetic characteristics are presented in Figs. 10 and 11. The substrate for the first path is the protonated epichlorohydrin ECH þ formed as a result of protonation at the oxygen atom of epichlorohydrin by a hydronium ion. Such a structure corresponds to the global minimum. Addition of one water molecule to the C 1 or C 2 atoms is accompanied by a strong binding effect of the second water molecule. In this case, the reaction path leading to MCPD þ by addition of a water molecule to the C 2 atom is more probable since this pathway is characterized by a lower transition state energy by about Figure 11. Scheme of the hydronium ion addition to the C3 atom in acidic medium. Energy values are given in kcal mol 1 J. Phys. Org. Chem. 2011, 24 1045 1050 Copyright ß 2011 John Wiley & Sons, Ltd. wileyonlinelibrary.com/journal/poc 1049

J. GACA, G. WEJNEROWSKA AND P. CYSEWSKI 6 kcal mol 1. Furthermore, according to our expectations, the process occurs faster in acidic medium because the energies of the corresponding transition states are almost half of the values determined for neutral medium. An alternative pathway of ECH hydrolysis in acidic medium with the addition of a chlorine atom is presented in Fig. 11. There is the possibility of protonated glycidol formation as the result of the epoxy bridge opening by hydrated hydrogen chloride. The value of the activation energy is close to that for the reactions of MCPD þ formation. Thus, GL and MCPD are formed in parallel in acidic medium. Summarizing the considerations described above, it should be emphasized that the equilibrium state achieved in the process of ECH chlorination does not lead to a stable product, i.e. GL. However, its appearance in the reaction mixture is kinetically reasonable, which has not been taken into consideration in literature thus far. CONCLUSIONS As a result of experimental studies on the hydrolysis of epichlorohydrin in acidic medium, we observed the reaction course which has not been described in the literature. The final product of the reaction is 3-chloro-1,2-propanediol and the intermediate products are glycidol and protonated epichlorohydrin ECH þ. The presence of chloride ions in the reaction medium during the hydrolysis of epichlorohydrin in acidic medium results in the formation of the additional product of hydrolysis, i.e. 1,3-dichloro-2-propanediol. The results of experimental studies of the reaction pathway were consistent with calculations. REFERENCES [1] J. Gaca, G. Wejnerowska, Talanta 2006, 70, 1044. [2] M. Moghadam, S. Tangestaninejad, V. Mirkhami, R. Shaibani, Tetrahedron 2004, 60, 6105. [3] V. Mirkhami, S. Tangestaninejad, B. Yadollahi, L. Alipanah, Tetrahedron 2003, 59, 8213. [4] O. Von Piringer, Dtsch. Lebensmittel. Rundsch. 1980, 1, 11. [5] W. S. Shvets, L. W. Aleksanjan, Zh. Prikl. Kvhim. 1994, 70, 2027, [6] N. Iranpoor, H. Adibi, Bull. Chem. Soc. Jpn. 2000, 73, 675. [7] D. L. Whalen, Tetrahedron Lett. 1978, 50, 4973. [8] G. N. Merrill, J. Phys. Org. Chem. 2004, 17, 241. [9] C. Lee, W. Yang, R. G. Parr, Phys. Rev. B 1988, 37, 785. [10] A. D. Becke, Phys. Rev. A 1988, 38, 3098. [11] T. H. Lowry, K. S. Richardson, Mechanism and Theory in Organic Chemistry, Harper Collins Publishers Inc., New York, 1987. [12] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, Jr J. A. Montgomery, Jr T. Vreven, K. N. Kudin,.J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G.A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez, J.A. Pople, Gaussian 03, Revision C.02, Gaussian, Inc., Wallingford, CT, 2004, 1050 wileyonlinelibrary.com/journal/poc Copyright ß 2011 John Wiley & Sons, Ltd. J. Phys. Org. Chem. 2011, 24 1045 1050