Dehydration of xylose was initially investigated by modeling the reactions of protonated p- D-xylose in vacuum (17,18). The absence of solvent water molecules allows the study of the intrinsic dehydration mechanisms, without the interference ofthe solvent. Furthermore, the quantum mechanical calculations without solvent molecules are more tractable, particularly for static calculations to obtain the energetics of the reactants, intermediates, and products. In addition, the knowledge of the intrinsic reaction in vacuum is often necessary to model solvated systems.

The simulations started when a proton was added to each of the four hydroxyl groups or the ring oxygen on the xylose ring structure. The subsequent reactions in vacuum were followed using ab initio molecular dynamics simulations. The results of these simulations indicate that protonation at O1 and O4 does not lead to any observable xylose degradation during the course of the 2 ps simulations time. Protonation at O5 results in a reversible ring opening and closing reaction. Protonation at O2 results in irreversible dehydration and degradation reac­tion to form furfural. Protonation at O3 leads to the fragmentation of a xylose molecule to a one-carbon (formic acid) and a four-carbon product. Formic acid has been observed exper­imentally. Mechanism 3, which results from the protonation at O1, was not observed during ab initio MD simulations. Static electronic structure calculations confirmed these simula­tion results and determined the likely intermediates in the mechanism of furfural formation. Furthermore, these calculations demonstrated that mechanism (9.4) is the most likely route to furfural formation based upon the calculated activation energies of the reaction steps. Figure 9.1 shows an overview of the reactions of these five isomers of a protonated xylose molecule.

Molecular dynamics simulations starting with protonated xylose provide an indication of the reactivity of that protonated isomer. The results of molecular dynamics simulations for protonation (17) at O2 and O3 are shown in Figures 9.2 and 9.3. The colored pictures at the top of these figures show snap shots of the progress of the reaction as a function of simulation time. Lewis structures of the progress of the reactions are shown at the bottom of the figures to provide clarity. As can be seen in Figure 9.2, xylose protonated at O2 dehydrates and rearranges to a furanyl compound within 700 fs. This mechanism is identical to reaction mechanism (9.4) for the formation of furfural proposed by Shafizadeh (41). As shown in Figure 9.3, xylose protonated at O3 dehydrates and breaks the C1-C2 bond within 250 fs. The resulting ether intermediate readily breaks apart to form formic acid and a 1,4-diol. This mechanism accounts for the formation of formic acid that has been reported in the literature (42). The diol that is formed as a by-product in this reaction is likely reactive and may polymerize to form a resin that is commonly found during acid degradation of

Figure 9.1 Scheme tor reactions of protonated xylose as determined by quantum mechanical modeling (CPMD and Gaussian). Protonation at 02 leads to the formation of furfural while protonation at 03 leads to formic acid. Protonations at 01 and 04 lead to dehydration products that readily recombine with water to reform xylose. Protonation at 05 leads to ring opening, which readily re-closes.

Figure 9.2 Results of CPMD simulation of xylose degradation after protonation of the hydroxyl group on O2. After 125 fs xylose is dehydrated and at approximately 659 fs the remaining carbocation rearranges to form the dehydrated furanyl form of xylose. This product will need to undergo two additional dehydrations to form furfural. (Reproduced in color as Plate 24.) xylose. Early reports (42) suggest that the formation of resin is accompanied by formic acid formation.

Molecular dynamics simulations of xyloses protonated at the other oxygen atoms were run well beyond 1 ps and showed no net reaction. MD simulations of xylose protonated at O1 did not also lead to the formation of the furanyl product as proposed in reaction

Figure 9.3 Results of CPMD simulation of xylose degradation after protonation of the hydroxyl group on O3. After 25 fs xylose is dehydrated and at approximately 250 fs the C1-C2 bond has broken. In this product the C1-O5 will eventually break to yield formic acid as shown in the Lewis structure at the end. (Reproduced in color as Plate 25.)

mechanism (9.2). These simulations showed that protonation at O1 leads to dehydration (see Figure 9.1) to form the oxonium, which did not react further. This ion will most likely react quickly with solvent water molecules to reform xylose. Simulations show that protonation and dehydration of xylose at O4 leads to the formation of the species depicted in Figure 9.1 containing a three-atom ring. This species does not react further, but is likely to recombine with water to reform xylose. Of particular interest is the mechanism for the formation of furfural from the open form of xylose, reaction mechanism (9.2). Molecular dynamics simulations show that protonation of O5 leads to the open form of the sugar, which quickly reverts to the cyclic form.

Static electronic structure calculations (CBS-QB3) were used to determine the energetics of the reaction pathways (18) shown in Figure 9.1. The proton affinities, or the gas phase enthalpies to add a proton, provide an indication of the likelihood of the proton to attack the oxygen atoms on xylose. The proton affinities are found to have the following order: O2 > O5 > O3 > O4 > O1 with values shown in Table 9.1. These values suggest that O2 has the highest proton affinity and is more susceptible to protonation, while O1 is least susceptible to protonation. These results show that the proton has a preference for O2, which leads to the formation of furfural. This is consistent with the experimental obser­vation that acid treatment of xylose leads primarily to furfural. Static electronic structure calculations of the activation energies for the steps shown in Figure 9.1 are also consistent with the observations from the MD simulations. Table 9.1 also lists the calculated acti­vation energies for the steps shown in this figure. Protonation at O1 readily leads to the oxonium ion as confirmed by the low barrier. However, the subsequent reaction to form the furanyl compound shown in Reaction (9.3) has a high-calculated barrier (32.0 kcal mol-1). Protonation at O2 has a low barrier for the first step and all subsequent steps. This is con­sistent with experimental studies that have failed to observe any intermediates. Protonation at O3 has low barriers to form formic acid, consistent with the experimental observation of this product. No reactions were found from the protonation at O4. Protonation at O5 readily leads to ring opening, but subsequent reactions that lead to the formation of fur­fural have high barriers (18) (27-29 kcal mol-1). Thus, the original mechanism proposed for furfural formation, Reaction mechanism (9.2), appears to be less likely than Reaction mechanism (9.4), which has barriers of 10-17 kcal mol-1. These results also suggest that protonation at O2 leads to furfural formation and protonation at O3 leads to formic acid, both of which have been observed experimentally. NMR measurements (18) also confirm these two products and experiments with 13C labeled are consistent with the proposed mechanisms.