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 Gacaa*,Graz˙yna Wejnerowskaa and Piotr Cysewskia

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 Preparation of solutions Model water solutions of ECH at the concentration of 1.183 g L1 Our previous studies on the determination of epichlorohydrin and the following pH values: 2.5, 3.5, 4.5 and 7.7 were prepared (ECH)[1] and the products of its hydrolysis in acidic (HNO ) and 3 for testing. The pH of the solutions was adjusted using aqueous neutral medium showed that 3-chloro-1,2-propanediol (MCPD) solution introducing HNO . Then, samples were placed into was formed in parallel with ECH loss which was expected. 3 graduated 25 ml flasks and filled to the top. These samples were However, the concentration of MCPD formed, especially in the kept at temperatures of 10, 20, 30 and 40 8C. initial stage of the reaction, did not make up for the loss of ECH. Analogous solutions, containing 1.183 and 0.748 g L1 of NaCl, This fact cannot be explained by the generally accepted scheme, were used in this study to check the effect of chlorides on the according to which the hydrolysis of epichlorohydrin leads to the course of ECH hydrolysis. formation of MCPD through protonation of the epoxide ring[2–8] (Fig. 1). GC analysis Such a description of the reaction does not explain the lack of a dependence between the change in the ECH concentration and Gas chromatograph HP 6890 (Hewlett Packard, CA, USA) fitted the amount of MCPD formed, which was observed in our studies. with a detector, flame ionization detector (FID), and an on-column Moreover, it does not explain the pathway for the formation of injector were applied in our studies. HP-FFAP columns (Crosslinked glycerol (GLC) identified among the reaction products. Polyethylene Glycol) 30m 0.53 mm, 1.0 mmwereused.The Due to the discrepancies observed in the description of volume of the injected solutions was 2 ml. The oven temperature 1 the course of the reaction, studies were undertaken in order to program for water solutions was 100 8C(2min),108Cmin to explain the mechanism of ECH hydrolysis in acidic and neutral 240 8C (4 min). Helium was the carrier gas at a constant flow 1 medium. These studies take into consideration the formation and rate of 1.3 ml min . Temperatures of the FID detector and the decay of GL and account for obtaining only trace amounts of GLC. on-column injector were 250 and 103 8C, respectively.

Calculation method EXPERIMENTAL Calculations were made using a microhydrated environment model.[9,10] It contained two water molecules complexing the Chemicals Epichlorohydrin (>99%) and glycerol (>96%) were purchased * Correspondence to: J. Gaca, Department of Chemistry and Environmental from Sigma-Aldrich (Steinheim, Germany). 3- chloro-1,2- Protection, Faculty of Chemical Technology and Engineering, University of propanediol (98%) and 1,3-dichloro-2-propanol were pur- Technology and Life Sciences, Seminaryjna 3 St., 85-326 Bydgoszcz, Poland. chased from Fluka (Chemie, GmbH, Germany). Glycerol (>99%) E-mail: [email protected] and water (analytical-reagent grade) were used as solvents a J. Gaca, G. Wejnerowska, P. Cysewski purchased from Merck (Darmstadt, Germany). Sodium chloride Department of Chemistry and Environmental Protection, Faculty of Chemical and nitric (V) acid (analytical-reagent grade) were purchased Technology and Engineering, University of Technology and Life Sciences, from POCH S.A. (Gliwice, Poland). Bydgoszcz, Poland 1045

J. Phys. Org. Chem. 2011, 24 1045–1050 Copyright ß 2011 John Wiley & Sons, Ltd. J. GACA, G. WEJNEROWSKA AND P. CYSEWSKI

Figure 1. Hydrolysis of ECH

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 Figure 2. Hydrolysis of ECH at pH 3.5 and T¼40 8C energy. The location of saddle points was confirmed by calculating the reaction paths by the IRC method. The CPCM The facts that GL (whose content decreases in time) was method was used for taking into account the Gibbs free energies identified among the products of the epichlorohydrin hydrolysis of solvation. All calculations were performed using Gaussian03 at pH < 7 and that the final product of the reaction was MCPD program.[12] 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 RESULTS AND DISCUSSION reaction with chloride ions (liberated from ECH) resulting in the formation of MCPD (Fig. 3). While conducting a preliminary studies on the course of ECH A similar mechanism can be proposed for the ECH hydrolysis hydrolysis, it was found that especially at the initial stage of occurring in neutral medium. However, the reaction occurs reaction, the amount of MCPD formed was considerably smaller considerably slower under the conditions used in the current that it would result from the loss of ECH. This means that the study. In order to confirm the possibility of MCPD formation from hydrolysis process described in Fig. 1 does not take into account GL in acidic medium, further studies on the GL reaction with all the possible paths of conversion. Our study showed that after chlorides or hydrochloric acid in water solutions were carried out. a long time, amount of the formed MCPD was consistent with Their results are summarized in Fig. 4. It was shown that the rate the reaction stoichiometry presented in Fig. 1. It means that of MCDP formation depended significantly on the temperature the substance formed during hydrolysis process is in a later stage and the concentration of chloride ions. converted to MCPD and simultaneously it shows that MCPD In order to elimination the less probable alternative of glycerol is stable under reaction conditions and it does not undergo formation from MCPD, studies on the possibility of glycerol further conversions. The studies on identification of the reaction formation from MCPD were performed. It was found that in products during hydrolysis showed that in parallel with MCPD various Cl concentration and different pH values we did not glicydol was formed, which at a later stage was converted to detected GLC or 1,3-dichloro-propanol (DCP). MCPD. To explain the absence of GLC among the products of the ECH These studies were carried out in acidic and neutral media hydrolysis in acidic medium, studies on MCPD hydrolysis in the (pH: 2.5–7.0) within the temperature range of 10–40 8C. The absence of chloride ions were carried out. It was found that MCPD course of the reaction was analogous in all cases. Temperature was stable under the conditions used, whereas GL in acidic rise and pH reduction resulted only in faster ECH loss and caused medium was transformed into GLC (Fig. 5). changes in the MCPD:GCL ratio and the reaction rate. Examples of The assumption that GL is one of the products of ECH the curves obtained for the reaction occurring at a temperature hydrolysis still did not explain the reason why only a minimal of 40 8C and pH 3.5 are presented in Fig. 2. amount of GLC can be identified. It was found that GL was formed in the beginning of the Taking into consideration the fact that HCl is released in the reaction and decayed in time. An important fact is that GL was still process of GL formation, the successive studies on ECH, GL and identified even after the time that ECH had totally reacted. The MCPD hydrolysis in acidic medium in the presence of chloride decrease in the GL content and its presence after time that ECH ions were carried out. had disappeared, allowed us to state that the rate of glycidol Results of such studies for ECH hydrolysis in the presence of decay was slower than the rate of its formation. chloride ions in acidic medium are presented in Fig. 6. 1046

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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

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 Figure 5. Hydrolysis of MCPD and GL in acidic medium 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 Three products, GL, MCPD and DCPD, were simultaneously hydrolysis acting as catalysts forming hydrogen bonds with the identified during ECH hydrolysis in the presence of chloride ions. oxygen atom of epichlorohydrin. The paths of the reactions However, after time, the GL formed was converted into MCPD occurring in neutral medium are presented in Figs. 8 and 9. (Fig. 7). It is understandable since GL reacts easily with Cl ions As shown in Figs. 8 and 9, the presence of two water molecules giving MCPD. Apart from temperature and pH, the propanol is important since one of them plays an active role in the addition chloroderivatives (MCPD and DCPD) do not undergo further reaction, whereas the second one forms strong hydrogen bonds conversions. and has an indirect effect on the reaction mechanism reducing by Taking into account the fact that in the final product of ECH several kcal mol1 the value of the activation energy. In case of hydrolysis in acidic medium, the main product of the reaction was epoxy ring hydrolysis, an accompanying water molecule forms a MCPD, and that at the beginning of the reaction a subsidiary strong hydrogen bond with the oxygen atom of ECH by the compound, i.e. glycidol, was identified, it can be concluded that addition of a water molecule to the C1 or C2 carbon atom. The Cl competes with water molecules in the reaction studied substrate is an ECH complex stabilized by two strong hydrogen (Fig. 3). bonds formed by both water molecules present on opposite In order to confirm the experimental observations, both sides of the epoxy ring. The product of the reactions is MCPD kinetics and thermodynamics modelling were performed. The stabilized by a hydrogen bond formed between a water molecule 1047

J. Phys. Org. Chem. 2011, 24 1045–1050 Copyright ß 2011 John Wiley & Sons, Ltd. wileyonlinelibrary.com/journal/poc 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

DE(g) DG(g) DG(s) pK Reaction (kcal mol1) (kcal mol1) (kcal mol1) (kcal mol1)

ECH þ H2O 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 H2O ¼ GL þ HCl 3.22 1.87 3.02 2.22

and one of the hydroxyl groups. The lattice of hydrogen bonds possibility of a direct attack of one water molecule on the C3 atom formed by both water molecules and the oxygen atom of ECH with the simultaneous dissociation of hydrogen chloride is shown is created in the saddle point. The selected geometrical in Fig. 9. It was found that in the saddle point, two water characteristics of the complexes analysed are presented in molecules form hydrogen bonds with the chlorine ion of ECH and Fig. 8. The activation energies of the saddle points TS1 and with each other. The products of this reaction are glycidol TS2 are very close which suggests the parallel courses involving and hydrogen chloride. The value of the Gibbs free energy of both processes. In both cases, the second molecule of water the ECH ! GL process is higher than for the process of MCPD actively supports the process of addition. The value of the formation and it is equal to DGaq ¼ 5.59 kcal mol1 at room Gibbs free energy for the process ECH ! MCPD is equal to temperature. Since the energy value corresponding to the saddle DGaq ¼ 2.08 kcal mol1 at room temperature. It is worth empha- point for this path is almost identical to that leading to MCPD, sizing that an alternative path of ECH hydrolysis exists. The both products should be formed with similar reaction rates which

Figure 8. Scheme of water molecule addition to the epoxy ring in neutral medium. Energy values are given in kcal mol1 1048

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Figure 9. Scheme of water molecule addition to the C3 atom of Cl in neutral medium. Energy values are given in kcal mol1

Figure 10. Scheme of the hydronium ion addition to the epoxy ring in acid medium. Energy values are given in kcal mol1

was experimentally observed. The decay of GL can be explained The substrate for the first path is the protonated epichlor- by its reaction with HCl formed as a result of ECH hydrolysis. ohydrin ECHþ formed as a result of protonation at the oxygen Moreover, calculations including the effect of acidic medium atom of epichlorohydrin by a hydronium ion. Such a structure on the mechanism of epichlorohydrin hydrolysis were also corresponds to the global minimum. Addition of one water performed. The fundamental difference with respect to the above molecule to the C1 or C2 atoms is accompanied by a strong described mechanism in neutral medium is the appearance of binding effect of the second water molecule. In this case, the spontaneous protonation of the substrate by the hydronium ion. reaction path leading to MCPDþ by addition of a water molecule Structural and energetic characteristics are presented in Figs. 10 to the C2 atom is more probable since this pathway is and 11. 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 mol1 1049

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6 kcal mol1. Furthermore, according to our expectations, the REFERENCES process occurs faster in acidic medium because the energies of the corresponding transition states are almost half of the values [1] J. Gaca, G. Wejnerowska, Talanta 2006, 70, 1044. determined for neutral medium. An alternative pathway of ECH [2] M. Moghadam, S. Tangestaninejad, V. Mirkhami, R. Shaibani, Tetra- hydrolysis in acidic medium with the addition of a chlorine atom hedron 2004, 60, 6105. [3] V. Mirkhami, S. Tangestaninejad, B. Yadollahi, L. Alipanah, Tetrahedron is presented in Fig. 11. There is the possibility of protonated 2003, 59, 8213. glycidol formation as the result of the epoxy bridge opening by [4] O. Von Piringer, Dtsch. Lebensmittel. Rundsch. 1980, 1, 11. hydrated hydrogen chloride. The value of the activation energy is [5] W. S. Shvets, L. W. Aleksanjan, Zh. Prikl. Kvhim. 1994, 70, 2027, close to that for the reactions of MCPDþ formation. Thus, GL and [6] N. Iranpoor, H. Adibi, Bull. Chem. Soc. Jpn. 2000, 73, 675. MCPD are formed in parallel in acidic medium. [7] D. L. Whalen, Tetrahedron Lett. 1978, 50, 4973. [8] G. N. Merrill, J. Phys. Org. Chem. 2004, 17, 241. Summarizing the considerations described above, it should be [9] C. Lee, W. Yang, R. G. Parr, Phys. Rev. B 1988, 37, 785. emphasized that the equilibrium state achieved in the process of [10] A. D. Becke, Phys. Rev. A 1988, 38, 3098. ECH chlorination does not lead to a stable product, i.e. GL. However, [11] T. H. Lowry, K. S. Richardson, Mechanism and Theory in its appearance in the reaction mixture is kinetically reasonable, Organic Chemistry, Harper Collins Publishers Inc., New York, 1987. which has not been taken into consideration in literature thus far. [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, CONCLUSIONS B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R Fukuda, J. Hasegawa, As a result of experimental studies on the hydrolysis of M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, epichlorohydrin in acidic medium, we observed the reaction 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, course which has not been described in the literature. The final C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G.A. Voth, product of the reaction is 3-chloro-1,2-propanediol and the P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, intermediate products are glycidol and protonated epichlorohy- A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, drin ECHþ. The presence of chloride ions in the reaction medium 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, during the hydrolysis of epichlorohydrin in acidic medium results I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham C. Y. Peng, in the formation of the additional product of hydrolysis, i.e. A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, 1,3-dichloro-2-propanediol. The results of experimental studies of M. W. Wong, C. Gonzalez, J.A. Pople, Gaussian 03, Revision C.02, the reaction pathway were consistent with calculations. Gaussian, Inc., Wallingford, CT, 2004, 1050

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