Catalysis Science & Technology PAPER Cite this: Catal. Sci. Technol., 2014, 4, 152 Received 9th September 2013, Accepted 16th October 2013 DOI: 10.1039/c3cy00686g www.rsc.org/catalysis Sorbitol dehydration in a ZnCl 2 molten salt hydrate medium: molecular modeling Jianrong Li, a Wim Buijs, a Rob J. Berger, b Jacob A. Moulijn a and Michiel Makkee* a A molecular modelling study, using standard DFT B3LYP/6-31G * , was carried out to develop a better understanding of sorbitol dehydration into isosorbide in ZnCl 2 molten salt hydrate medium. Catalysis of sorbitol dehydration by ZnCl 2 most likely starts with complexation of the sugar alcohol functions to Zn, followed by an internal S N 2 mechanism of a secondary alcohol function attacking a primary alcohol function with the Zn-complex acting as a favourable leaving group. The dehydration reactions to 1,4- and 3,6-anhydrosorbitol show a very similar activation barrier in good accordance with experimental results. The same holds for the formation of isosorbide from 1,4- and 3,6-anhydrosorbitol, albeit with a slightly higher activation barrier. The relative level of the activation barriers reflects the increased strain in the sorbitol skeleton in the corresponding transition states. ZnCl 2 turns the dehydration reaction from an endothermic one to an exothermic one by forming a strong complex with the released water. Finally, the ZnCl 2 –H 2 O system has been compared with HCl–H 2 O, which could have been an alternative; it, however, turned out not to be the case. Introduction Due to the high potential value of isosorbide and the wide interest in sugar chemistry, sorbitol dehydration has been studied and reviewed extensively in the past by Flèche and Huchette 1 and recently by Rose and Palkovits. 2 Several cata- lytic systems have been discovered, such as strong mineral acid catalysts (H 2 SO 4 , 1–3 HCl, 4,5 etc.), solid catalysts, 2,6–12 ionic liquids and molten salt hydrates. 7,8,13,14 Quantitative data on the reaction kinetics, however, are hardly available in the liter- ature. Important conformational aspects of the starting sorbi- tol in the catalytic mechanism using a mineral acid as catalyst have been proposed by Cekovic 5 and by Dosen-Micovic and Cekovic, 6 using molecular mechanics. Basically, the reaction can be described as an S N 2 reaction mechanism beginning with protonation of the primary hydroxyl group of sorbitol to improve its leaving group ability, followed by attack of a secondary alcohol in the sorbitol skeleton. 1,2,5,6 In another study, we described sorbitol dehydration in a molten salt hydrate medium 8 (ZnCl 2 ·xH 2 O, x = 3–4) and developed a simplified overall kinetic model using Athena 9 software. A molecular modeling study was undertaken to elucidate the reaction mechanism and to understand the results of the kinetic modeling study. In this kinetic study, the reaction scheme presented in Fig. 1 was used with the following simplification: 1,4- and 3,6-anhydrosorbitol and, in addition, 1,5-anhydrosorbitol and 2,5-anhydromannitol were each lumped together into one stable pseudo-component as one stable side product, although both components could be separated in the HPLC analysis. In the molecular modeling study presented here, this kinetic model was used, but the lumping was avoided. In this model, the formation of side products has not been taken into account. Under practical conditions, the amounts of side products and unknown products are limited up to 3–5% at full sorbitol and 1,4- and 3,6-anhydrosorbitol conversion. The kinetic model is given in Table 1. The relevant kinetic parameters obtained are shown in Table 2. The main reaction pathway consists of a first dehydration step of sorbitol (A) into a mixture (B) of 1,4-anhydrosorbitol and 3,6-anhydrosorbitol (r 1 ) followed by a second dehydration step into 1,4:3,6-dianhydrosorbitol, called isosorbide (C) (r 3 ). The second sorbitol dehydration step requires a slightly higher activation energy (187.0 ± 11.3 kJ mol -1 ) than that of the first step of sorbitol dehydration (176.76 ± 0.08 kJ mol -1 ). Addition- ally, small amounts of two other monoanhydrohexitols were produced: 1,5-anhydrosorbitol and 2,5-anhydromannitol (D), with a relatively high activation barrier of 206.5 ± 4.6 kJ mol -1 . Because they do not react further to a dianhydrosorbitol, they are referred to as “stable intermediates”. The second step seems slightly endothermic, but it should be noted that the a Catalysis Engineering, Department of Chemical Engineering (ChemE), Delft University of Technology, Julianalaan 136, 2628 BLDelft, The Netherlands. E-mail: m.makkee@tudelft.nl; Fax: +31 15 278 5006; Tel: +31 15 278 1391 b Anaproc c/o Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands 152 | Catal. Sci. Technol., 2014, 4, 152–163 This journal is © The Royal Society of Chemistry 2014