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Ind. Eng. Chem. Res. 1999, 38, 3076-3082
Selective Adsorption of Sterically Hindered Phenols through a Single-Point Binding Mechanism Jeffrey A. Koehler,†,§ Kimberlee K. Wallace,§ Paul J. Smith,*,| and Gregory F. Payne*,‡,§ Center for Agricultural Biotechnology, 5115 Plant Sciences Building, University of Maryland, College Park, Maryland 20742-4450, and Departments of Chemical and Biochemical Engineering and Chemistry, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250
There are growing demands for improved selectivity in industrial separations. Although preorganized three-point binding systems can achieve these selectivities, supramolecular systems are seldom economical for the bulk separations of low-valued chemicals. In this study, we examined the potential of a one-point hydrogen-bonding mechanism to confer selectivity to the adsorption of phenolic species encountered in the industrial synthesis of the antioxidant, 2,6di-tert-butyl-p-cresol (butylated hydroxytoluene, BHT). The adsorption of 2,6-di-tert-butyl-p-cresol from hexanes onto an acrylic ester sorbent was observed to have a 270-fold lower affinity and a 2.4 kcal/mol less favorable adsorption enthalpy compared to adsorption of the unbutylated species p-cresol. To provide mechanistic explanations for the observed adsorption behavior, we performed infrared spectroscopic and molecular-modeling studies with a small molecule analogue of the acrylic ester sorbent. These small molecule binding studies indicate that the phenolic hydroxyl of p-cresol forms a strong hydrogen bond with an appropriate accepting site, while the bulky tert-butyl groups sterically hinder hydrogen bonding for 2,6-di-tert-butyl-p-cresol. Introduction Manufacturers are facing greater demands to improve the purity of chemical products and intermediates. In the food, pharmaceutical, and agricultural chemical industries, demands for increased purity are motivated by health and safety concerns. In other industries, increased purity is sought to improve the consistency or performance of chemical intermediates and products. The example in this study is the widely used antioxidant butylated hydroxytoluene (BHT). BHT production involves the sequential alkylation of p-cresol by isobutene using an acid catalyst:1,2
p-cresol + isobutene f 2-tert-butyl-p-cresol (1) 2-tert-butyl-p-cresol + isobutene f 2,6-di-tert-butyl-p-cresol (2) In the past, the BHT product had been used as a mixture of fully alkylated, 2,6-di-tert-butyl-p-cresol (diTBC) and partially alkylated 2-tert-butyl-p-cresol (monoTBC). The desire for more purified ingredientss especially for food applicationssmotivated an increase in the purity of diTBC in BHT formulations. * To whom correspondence should be addressed. P. J. Smith: Phone, 410-455-2519; Fax, 410-455-2608; E-mail:
[email protected]. G. F. Payne: Phone, 301-405-8389; Fax, 301-314-9075; E-mail,
[email protected]. † Current address: Department of Geography and Environmental Sciences and Department of Chemical Engineering, The Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218. ‡ Center for Agricultural Biotechnology, University of Maryland. § Department of Chemical and Biochemical Engineering, University of Maryland Baltimore County. | Department of Chemistry, University of Maryland Baltimore County.
One approach for enriching diTBC in BHT formulations is to alter the reaction conditions or develop new catalysts to enhance the conversion of monoTBC to diTBC. The obvious approach to enhance this conversion is to use excess isobutene to drive reaction 2 to completion. However, the use of excess isobutene has the undesired consequence of increasing the generation of waste oligomeric products resulting from undesired isobutene-isobutene alkylation reactions. Further, it is not obvious how catalysts could be developed to suppress the undesirable oligomerization of isobutene since the accepted mechanism for alkylation involves reaction between the solution-phase (i.e., unbound) phenolic and a catalyst-bound carbonium ion of isobutene.1,2 Unfortunately, this catalyst-bound carbonium ion also undergoes reaction with isobutene to form the undesired byproducts (typically dimers and trimers of isobutene). Thus, the catalyst-bound carbonium ion is the same intermediate in the desired and undesired reactions. An alternative approach for improving the levels of diTBC in BHT formulations is to use a separations operation. Traditional distillation-based separations may be undesirable because the high boiling points of p-cresol (201 °C), monoTBC (237 °C), and diTBC (265 °C) indicate that operation will be energy-intensive and may result in some thermal destruction of the product. Crystallization is currently employed for BHT purification; however, crystallization methods can have difficulties in achieving increasingly stringent purity standards. In this study, we explored the potential of an alternative approach to separate the various phenolic species. Specifically, we examined whether commercially available, inexpensive polymer-based adsorbents offer any selectivity that may be exploited for separating the phenolic species. By inspection of the structures, it seemed that a hydrogen-bonding adsorption mechanism would be most appropriate for conferring selectivitys
10.1021/ie990128t CCC: $18.00 © 1999 American Chemical Society Published on Web 07/03/1999
Ind. Eng. Chem. Res., Vol. 38, No. 8, 1999 3077
especially if the bulky ortho substituents disrupt hydrogen-bond formation between the phenolic hydroxyl and an appropriate hydrogen-bond-accepting site on the adsorbent. In this study, we examined two potential hydrogen-bond-accepting functionalities, π electrons and carbonyl oxygens which are characteristic of the commercially available styrenic and acrylic ester adsorbents. The first goal of our study was to experimentally determine if adsorption can offer selectivities for the separations of these phenolic species. It is well-accepted that three-point binding is necessary to confer stereoselectivity to adsorption.3,4 We studied a system that potentially offers only one-point binding to determine if nonbinding, steric interactions can be exploited to obtain affinity differences between similar compounds. Specifically, we studied adsorbents and conditions in which hydrogen bonding would be expected to provide the major driving force for adsorption.5-10 The limitation of most adsorption experiments is that they yield thermodynamic information (binding affinities and enthalpies) but provide no direct mechanistic information. The second goal of our work was to provide more direct mechanistic information on hydrogen bonding and the role of the bulky ortho substituents in disrupting hydrogen-bond formation. Unfortunately, it is difficult to obtain direct mechanistic information for adsorption because most spectroscopic techniques cannot be applied to the study of solute adsorption from solution onto porous adsorbents. To overcome this limitation, we studied binding between the phenolic compounds and small molecule analogues of the sorbent surfaces. Specifically, we used diethylbenzene and ethylpropionate to mimic the styrenic and acrylic ester sorbent surfaces, respectively. Previous studies with a series of phenolic compounds have shown a reasonable correlation between solution-phase hydrogen bonding to ethylpropionate and adsorption onto the acrylic ester sorbent.11 Materials and Methods Materials. p-Cresol (99%), 2-tert-butyl-4-methylphenol (2-tert-butyl-p-cresol, monoTBC, 99%), 2,6-ditert-butyl-4-methylphenol (2,6-di-tert-butyl-p-cresol, diTBC, 99+%) and diethylbenzene (95%, mixture of isomers) were obtained from Aldrich Chemical Co., Inc. (Milwaukee, WI). Methanol, acetone and hexanes (all Optima grade) were purchased from Fisher Scientific (Pittsburgh, PA). Ethylpropionate (99+%) was obtained from Acros Organics (Pittsburgh, PA). The sorbents, Amberlite XAD-7 (acrylic ester) and Amberlite XAD-16 (styrenic), were obtained from Sigma Chemical Company (St. Louis, MO) and are reported to have surface areas of 450 m2/g and 800 m2/g, respectively. Methods. 1. Adsorption. Prior to use, the sorbents were cleaned by sequentially contacting them with water, methanol, acetone, and hexanes for 24-72 h/solvent. The resins were air-dried between each solvent exchange. Cleaned sorbents were dried under vacuum and heat (about 80 °C) for 2-4 h immediately prior to use. Adsorption studies were conducted by contacting either the acrylic ester or styrenic sorbent with 40 mL of hexanes containing either p-cresol (0.4 mM), monoTBC (0.4 mM), or diTBC (0.27 mM). The sorbent concentrations ranged from 1.5 to 22 g/L for the acrylic ester sorbent and 0.9-12.9 g/L for the styrenic sorbent
with the difference in range being due to differences in specific surface areas for the two sorbents. After equilibriation of the two-phase systems for 1548 h at the appropriate temperature, liquid concentrations were measured using a UV spectrophotometer (Spectronic Genesys 2, Milton Roy Co., Rochester, NY). The solute concentrations were determined by measuring the absorbance at 280, 279, and 284 nm for p-cresol, monoTBC, and diTBC, respectively. The adsorbed-phase amount was determined from the difference in the liquid-phase concentrations before and after equilibration using the equation
q)
(C0 - C)V M
where q is the equilibrium adsorbed-phase concentration (mmol/g of dry sorbent), C0 and C are the initial and final solute concentrations (mmol/L), V is the volume of the hexanes phase (L), and M is the mass of the dry sorbent (g). All adsorption studies were confined to the low solute concentration regime so the adsorbed amount varied linearly with the equilibrium solutionphase concentration (i.e., studies were confined to the linear region of the adsorption isotherm). The adsorption affinity of the solute (q/C) was determined as the ratio of the adsorbed-to-dissolved solute concentrations and is identical to the slopes of the adsorption isotherms in the linear region. 2. Fourier Transform Infrared Spectroscopy. The FTIR spectra were collected using a Perkin-Elmer System 2000 FTIR (Norwalk, CT) with 4 cm-1 resolution using a liquid cell comprised of KBr windows separated by a 0.762 mm spacer. Ethylpropionate and diethylbenzene were chosen as hexane soluble analogues for the acrylic ester and styrenic sorbent, respectively. Spectra were obtained for hexane solutions containing each solute individually and in the presence of either ethylpropionate or diethylbenzene. Spectra were also obtained for each of the polymer analogues (ethylpropionate and diethylbenzene) and were subtracted from the spectra of the solutes in the presence of the hexane soluble analogues in order to isolate the changes in the solute spectra resulting from binding. 3. Molecular Modeling. Molecular modeling was performed using the MacroModel Version 5.012 package and the AMBER*13,14 force field. The binding studies employed the same molecules (ethylpropionate and diethylbenzene) that were used in the FTIR studies to mimic the sorbent surfaces. Each of the phenolic solutes was studied by molecular mechanics (modeling at 0 K) with minimized structures obtained by performing Monte Carlo conformational searches. The studies were performed for ethylpropionate in both air and CHCl3 and with diethylbenzene in CHCl3. Each conformational search was comprised of 1000 structures each of which was minimized for 500 cycles. After each search was completed, the structure with the minimum energy was fully minimized to convergence. The binding energies, which are related to the binding enthalpies, were obtained by first calculating the energy for the minimized structures when the phenolic solute and sorbent analogue (ethylpropionate or diethylbenzene) were separated by more than 100 Å and subtracting this energy from that of the minimized complex. Stochastic dynamics (modeling at 300 K) was performed for the phenolic solutes bound to ethylpropionate
3078 Ind. Eng. Chem. Res., Vol. 38, No. 8, 1999
Figure 1. monoTBC adsorption from hexane onto acrylic ester and styrenic sorbents. The adsorption data is normalized by the specific surface areas. The normalized adsorption affinities (q′/C) are in units of (mmol adsorbed/m2 of sorbent)/(mmol in solution/L of solution). Temperature ) 25 °C.
Figure 2. Adsorption of different phenolic species onto the acrylic ester sorbent. The adsorption affinities (q/C) are in units of (mmol adsorbed/g of sorbent)/(mmole in solution/L of solution). Temperature ) 24 °C.
in a vacuum using the fully minimized structures from the mechanics simulation. The dynamics simulations were comprised of two steps. First, an equilibrium step was used to get the system into thermal equilibrium by performing a molecular dynamics simulation at 300 K lasting 10 ns with a time step of 0.5 fs. The second step provided the data used for calculation of the binding energies and consisted of a dynamics simulation at 300 K lasting 30 ns with a time step of 0.5 fs. It was determined that the average energy had sufficiently converged after this dynamics simulation. The binding energies were once again obtained from the difference in energies of the bound and unbound molecules. Results and Discussion Adsorption. To establish the importance of the sorbent surface chemistry, we studied the adsorption of monoTBC from hexanes onto both the acrylic ester (XAD-7) and the styrenic (XAD-16) sorbents. The adsorbed quantities were normalized by the surface area of the sorbents to allow a direct comparison. Figure 1 shows that monoTBC has an order of magnitude higher adsorption affinity for the acrylic ester sorbent versus the styrenic sorbent. These results are consistent with previous observations5,8-10 and support our contention that adsorption of phenolics from hexane onto these sorbents results from a hydrogen-bonding mechanism. Since the carbonyl group is a better hydrogen-bond acceptor than aromatic π electrons,15,16 the phenolic solute is expected to adsorb (through a hydrogen bond) more effectively to the acrylic ester sorbent. To determine if bulky ortho substituents affect adsorption onto the acrylic ester sorbent, we studied the adsorption of p-cresol, monoTBC and diTBC, individually from hexanes. The adsorption isotherms in Figure 2 show that the adsorption affinities of p-cresol and monoTBC are 270 and 80 times higher, respectively, than that of diTBC. As will be more fully discussed later, the reduced affinity for adsorption of the dibutylated species is likely due to steric hindrance of the hydrogenbonding interaction. It should be noted that the observed adsorption behavior cannot be explained in terms of differences in the phenolics’ solution-phase behavior. p-Cresol, which has the highest adsorption affinity, has
Figure 3. van’t Hoff plot for adsorption of different phenolic species onto the acrylic ester sorbent. The adsorption affinity is the slope of the adsorption isotherms in the linear region and is in units of (mmol adsorbed/g of sorbent)/(mmol in solution/L of solution).
the highest hexane solubility (we did not observe a solubility limit for p-cresol in hexane). monoTBC, which adsorbs with an 80-fold greater affinity than diTBC, is only 10% less soluble in hexane than diTBC (1.76 M for monoTBC and 1.91 M for diTBC). Finally, we measured the enthalpy of adsorption for all of the compounds using the van’t Hoff method. Adsorption isotherms were measured at various temperatures and the adsorption affinities (i.e., the slopes in the linear region of the isotherm) were plotted on a semilogarithmic plot versus 1/T. The positive slopes in Figure 3 indicate that adsorption is exothermic for the three phenolic solutes. Figure 3 shows the adsorption enthalpies for p-cresol and monoTBC were similar (|∆∆H°| ) 0.2 kcal/mol) despite the 3-fold difference in binding affinities (|∆∆G°| ) 0.7 kcal/mol). These thermodynamic calculations indicate significant entropy differences between the adsorption of p-cresol and monoTBC. The enthalpy of adsorption for diTBC is about 2 kcal/mol lower in magnitude (-5.0 kcal/mol) than those for the other compounds. This reduced binding strength is consistent with a hypothesis that steric effects weaken the hydrogen-bonding adsorption mechanism for diTBC.
Ind. Eng. Chem. Res., Vol. 38, No. 8, 1999 3079
a
c
b
d
Figure 4. Infrared spectra of different phenolic species alone and with ethylpropionate or diethylbenzene in hexanes. (a) p-cresol, monoTBC, and diTBC (all at 12.0 mM); (b) p-cresol (p-cresol/ethylpropionate, 12.0/35.0 mM; p-cresol/diethylbenzene, 11.1/513.0 mM); (c) monoTBC (monoTBC/ethylpropionate, 12.0/35.0 mM; monoTBC/diethylbenzene, 11.1/513.0 mM); (d) diTBC (diTBC/ethylpropionate, 11.1/690.0 mM; diTBC/diethylbenzene, 10.8/672.0 mM). The spectra were obtained at 21 °C. Table 1. Comparison of Infrared and Adsorption Enthalpies for Phenolic Speciesa infrared stretching of OH
adsorption enthalpy
DEB binding p-cresol monoTBC diTBC a
EP binding
acrylic ester sorbent
νfree (cm-1)
νbound (cm-1)
∆ν (cm-1)
νbound (cm-1)
∆ν (cm-1)
∆H° (kcal/mol)
3624 3619, 3657 3655
3557 3553 nrc
67 66b nrc
3464 3475 3610
160 144b 45
-7.4 -7.2 -5.0
DEB, diethylbenzene; EP, ethylpropionate. b Based on the most populous free peak (3619 cm-1). c nr, peak not sufficiently resolved.
Fourier Transform Infrared Spectroscopy. 1. Spectra of Phenolic Solutes in Hexanes. The IR spectra of the individual solutes in hexane were measured between 4000 and 3200 cm-1 to determine the location of the unbound hydroxyl stretching peak (Figure 4 and Table 1). When p-cresol or diTBC was dissolved in hexanes, each spectrum has only one symmetric peak in this region (Figure 4a). The absence of additional peaks indicates that each compound has one unique conformation with respect to the hydroxyl group. The peak location for diTBC (3655 cm-1) is shifted by 31 cm-1 to a higher frequency relative to the peak for the p-cresol (3624 cm-1). Since it is energetically favorable for the hydroxyl group to remain coplanar with the aromatic ring,17-19 two possible conformations of the hydroxyl group exist for both p-cresol and diTBC. However, for each solute the two possible conformations are structurally equivalent. Thus, p-cresol has one unique conformation with the hydroxyl group accessible and diTBC has one unique conformation with the hydroxyl group buried. Conversely, Figure 4a shows that the spectrum for monoTBC has two peaks located at 3619 and 3657 cm-1. The two peaks in this spectrum are at the same locations as the single peaks in the p-cresol and diTBC spectra, indicating that monoTBC can exist in two conformations in hexane
Scheme 1
solutions. These conformations are consistent with the hydroxyl group facing toward (buried) and away from (accessible) the tert-butyl group (Scheme 1). Comparison of the peak intensities of the monoTBC spectrum suggests that the molecule’s most favorable conformation in hexane is the one where the hydroxyl group is accessible. 2. Binding of Phenolics to Hexane-Soluble Analogues. To provide insights on the adsorption mechanism, we studied the interactions between the phenolic solutes and hexane soluble analogues of the two sorbents. Figure 4b,c shows that addition of diethylbenzene to the p-cresol and monoTBC solutions resulted in a
3080 Ind. Eng. Chem. Res., Vol. 38, No. 8, 1999 Table 2. Comparison of Calculated Binding Energiesa (kcal/mol) and Adsorption Enthalpies (kcal/mol) for Phenolic Species molecular mechanics (T ) 0 K) DEB in CHCl3 p-cresol monoTBC accessible OH monoTBC buried OH diTBC
molecular dynamics (T ) 300 K)
adsorption enthalpy (from Figure 3)
π stacking
H-bonded
EP in CHCl3
EP in vacuo
EP in vacuo
acrylic ester sorbent
-1.9 -2.7 -2.6 -2.7
-2.1 -2.6 -1.6 -1.9
-5.2 -5.5 -3.3 -3.4
-8.8 -9.2 -6.8 -6.8
-7.5 -7.2 -6.3b -3.7
-7.4 -7.2 -7.2 -5.0
a DEB, diethylbenzene; EP, ethylpropionate. The calculated binding energies calculations are performed with the lowest energy phenolic species which, except where noted, were in the same conformation free and bound. b Upon binding with ethylpropionate, the OH converts from buried to accessible.
decrease in intensities of the original hydroxyl peaks and the formation of new lower frequency peaks near 3555 cm-1, indicating that p-cresol and monoTBC interact similarly with diethylbenzene (∆ν ) 67 and 65 cm-1, respectively). These observations are consistent with the formation of a hydrogen bond between diethylbenzene and either p-cresol or monoTBC. When diethylbenzene is added to hexane solutions of diTBC, Figure 4d shows only a slight broadening of the free hydroxyl stretch peak at 3655 cm-1. This suggests that a small amount of diTBC forms a hydrogen bond with diethylbenzene and that it is a weak interaction (∆ν is smaller than the free hydroxyl peak half-width). Similarly, when ethylpropionate was added to solutions of p-cresol and monoTBC, Figure 4b,c shows that an additional peak appears at a lower frequency (near 3470 cm-1) while the intensities of their unbound hydroxyl peaks decreases. These spectra are consistent with the formation of a hydrogen bond between ethylpropionate and the phenolic molecule. The similarity in frequency for the hydroxyl stretching peaks for the ethylpropionate-bound p-cresol and monoTBC suggests that the hydroxyl for the ethylpropionate-bound monoTBC is in the accessible conformation (i.e., the conformation in which the hydroxyl is facing the tertbutyl group does not appreciably hydrogen bond to ethylpropionate). To observe a hydrogen-bound peak for diTBC, a 20-fold higher concentration of ethylpropionate was required. Figure 4d shows that the observed frequency shift was relatively small (∆ν ) 40 cm-1) compared to the shift observed for p-cresol and monoTBC (∆ν ) 150 cm-1). These observations indicate that diTBC forms a much weaker hydrogen bond with ethylpropionate. There are striking similarities between the results from the solution-phase hydrogen-bonding studies and the adsorption studies. First, for all three solutes, Table 1 shows that the wavenumber shifts of the hydrogenbound peaks with respect to the unbound peaks were much larger for the interaction with ethylpropionate than with diethylbenzene. Also, an order of magnitude higher concentration of diethylbenzene was needed to obtain peak intensities of the hydrogen-bound compounds that were similar to those obtained with ethylpropionate. Both of these observations indicate that ethylpropionate is a much better hydrogen-bond acceptor than diethylbenzene which is consistent with the observation that adsorption affinities are higher for the acrylic ester versus the styrenic sorbent (Figure 1). Second, diTBC showed relatively weak solution-phase interactions with ethylpropionate (Figure 4d) while diTBC was observed to adsorb poorly to the acrylic ester sorbent (Figures 2 and 3). As suggested earlier, this weak interaction with diTBC is possibly due to steric hindrance of the bulky ortho substituents. Third, using the wavenumber shift (∆ν) as an indicator of hydrogen-
bond strength, the IR measurements indicate that the interaction of p-cresol and monoTBC with ethylpropionate are energetically similar (Table 1). This similarity is in agreement with the similar enthalpies measured for p-cresol and monoTBC adsorption onto the acrylic ester sorbent (Figure 3). Further, the similarities for p-cresol and monoTBC binding suggests that monoTBC adsorbs to the sorbent with the hydroxyl group in the accessible conformation. The close agreement between the adsorption and IR results supports our choice of ethylpropionate and diethylbenzene as hexane-soluble sorbent analogues to mimic adsorption. Molecular Modeling. 1. Molecular Mechanics. Molecular modeling was performed to obtain further insight into the mechanism for phenolic-sorbent binding and to indicate the conformations of the bound species. As in the IR studies, ethylpropionate and diethylbenzene were used as analogues of the acrylic ester and styrenic surfaces, respectively. As a first-order approximation, the binding interactions were studied by molecular mechanics to obtain the lowest energy state of the system. Because the MacroModel modeling program does not contain the parameter set for a hexane solvent, interactions were modeled in vacuo and also in chloroform where solvation energies are taken into account. Initial calculations with chloroform indicate that all of the phenolic solutes bind with diethylbenzene in two conformations. One conformation appears to involve hydrogen bonding of the phenolic hydroxyl to the π electrons of diethylbenzene, while the other appears to result from π stacking. The interaction energies listed in Table 2 are similar for both conformations of the three phenolic solutes, indicating they are equally favorable. In contrast, modeled binding to ethylpropionate indicates only one favorable conformation with the solute’s hydroxyl group hydrogen bonding to the carbonyl oxygen of the ester. Table 2 shows that the binding energies for ethylpropionate are considerably more favorable than those for diethylbenzene which agrees with the IR results. By extrapolation, the modeling and IR results suggest that the higher affinity for adsorption onto the acrylic ester sorbent (Figure 1) is due to the formation of a stronger hydrogen bond as compared to that for adsorption onto the styrenic sorbent. Next, we calculated the energy for the binding of phenolic solutes to ethylpropionate in vacuo. Table 2 shows that the ethylpropionate binding energies calculated for each of the phenolic solutes are higher in vacuo than in chloroform, although the trends are the same. For both chloroform and in vacuo, the energy of binding monoTBC with the accessible hydroxyl group was the same as ethylpropionate binding with p-cresol. Similarly, the energy of binding monoTBC with the buried hydroxyl group was the same as the energy of ethylpropionate binding with diTBC. These observations
Ind. Eng. Chem. Res., Vol. 38, No. 8, 1999 3081
Figure 5. Energy-minimized in vacuo structures of different phenolic species bound to ethylpropionate obtained from molecular mechanics using MacroModel 5.0 with the AMBER* force field (see Materials and Methods for details). (a) p-cresol; (b) hydroxyl-accessible monoTBC; (c) hydroxyl-buried monoTBC; (d) diTBC. Table 3. Geometrics Calculated from Molecular Mechanics for Binding of Phenolic Species and Ethylpropionate in vacuo dO‚‚‚H-O bond dO‚‚‚H bond H-O bond angle (deg) length (Å) length (Å) p-cresol monoTBC accessible OH monoTBC buried OH diTBC
164.6 161.7 143.6 140.9
1.687 1.691 1.794 1.821
0.969 0.968 0.968 0.967
support the IR experiments which suggest that monoTBC binds with the hydroxyl group in the accessible conformation. The geometric parameters calculated for ethylpropionate binding to the three phenolic solutes are shown in Table 3 for in vacuo calculations. The energyminimized structures of all three solutes bound to ethylpropionate are shown in Figure 5. It is generally accepted that the strongest hydrogen bonds have angles between the proton donor, the proton, and the proton acceptor which approach 180°.16 On one hand, p-cresol and hydroxyl-accessible monoTBC both have hydrogenbond angles slightly above 160°, indicating the formation of relatively strong hydrogen bonds with ethylpropionate. On the other hand, diTBC and hydroxyl-buried monoTBC both have hydrogen-bond angles considerably lower (around 140°), which are expected to yield weaker hydrogen bonds. The hydrogen-bond length is another
measure of the hydrogen-bond strength and is measured from the carbonyl oxygen to the proton. This length was calculated to be slightly less than 1.7 Å for p-cresol and hydroxyl-accessible monoTBC and about 1.8 Å for diTBC and hydroxyl-buried monoTBC. These calculated lengths are consistent with the weaker hydrogen bonds observed for ethylpropionate binding with diTBC and hydroxyl-buried monoTBC. Table 3 also shows a slight lengthening of the covalent hydroxyl bond calculated for the stronger hydrogen bound species. On the basis of these observations, it appears that the weak hydrogen bonds for diTBC and hydroxyl-buried monoTBC are due to the steric hindrance of the tert-butyl substituents which prevent hydrogen bonding with ethylpropionate in a favorable conformation. By analogy, the lower affinity (Figure 2) and enthalpy (Figure 3) for diTBC adsorption appears to be due to steric hindrance of the bulky ortho substituents. 2. Stochastic Dynamics. To better simulate experiment, stochastic dynamics calculations were performed at 300 K in vacuo. The molecular dynamics calculations were all performed in vacuo since solvation effects in hexanes are likely to be small and the dielectric constant is close to that of hexanes. Table 2 shows that the energy for p-cresol-ethylpropionate binding was calculated to be -7.5 kcal/mol. This value is lower than that calcu-
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lated using molecular mechanics and is in remarkable agreement with the experimentally determined adsorption enthalpy. Starting from either the buried or accessible conformation of unbound monoTBC, dynamics calculations yielded the monoTBC-ethylpropionate complex with monoTBC only in the accessible conformation, indicating that there is enough energy in the system for monoTBC to bind in the more favorable conformation for hydrogen bonding. IR measurements also indicate that the accessible hydroxyl conformation is the most populous form of the unbound monoTBC. This information suggests that the best simulation of experiment would consider a hydroxyl-accessible initial conformation for monoTBC and a hydroxyl-accessible final conformation for ethylpropionate-bound monoTBC. Using these conformations, the monoTBC binding energy was calculated to be -7.2 kcal/mol. Again, this calculated energy is remarkably similar to the observed adsorption enthalpy for monoTBC. Finally, Table 2 shows that ethylpropionate-diTBC binding is least favorable, consistent with the IR measurements. The magnitude of the calculated binding energy was slightly lower than that of the observed adsorption enthalpy. The discrepancy in magnitudes is possibly due to the uncertainties in measuring the adsorption enthalpy for a solute that adsorbs poorly. Conclusions Adsorption is becoming an increasingly popular alternative for separating industrial organics. To fully exploit adsorption, it is necessary to understand and exploit mechanistic interactions responsible for adsorption. In this study, we examined the potential of adsorption to separate the phenolic species encountered during the commercial production of the antioxidant diTBC. Using an acrylic ester sorbent and a nonpolar solvent (hexanes), we observed significant differences in the adsorption affinities for p-cresol, monoTBC, and diTBC (Figures 2 and 3). Also, the observed adsorption enthalpies showed stronger adsorption of p-cresol and monoTBC compared to diTBC. To provide mechanistic explanations for the observed differences in adsorption, we used ethylpropionate as a hexane-soluble analogue of the acrylic ester sorbent and studied solution-phase binding between the analogue and the phenolic species. Experimentally, IR measurements (Figure 4) indicate that p-cresol and monoTBC form relatively strong hydrogen bonds with ethylpropionate while diTBC forms a weak hydrogen bond with ethylpropionate. Computations indicate that the hydrogen bonds are formed between the carbonyl oxygen of ethylpropionate and the hydroxyl groups of the phenolic species (Figure 5). Minimum energy conformations for the complexes indicate a similarity in the geometries and energies for the hydrogen bonds between ethylpropionate and either p-cresol or monoTBC, while the hydrogen bond between ethylpropionate and diTBC is weaker, longer, and less linear (Table 3). These computations support the conclusion that hydrogen bonding of diTBC is suppressed because of steric constraints. There appears to be good agreement between the adsorption of the phenolic species and their solutionphase hydrogen-bonding behavior. This agreement supports the contention that a hydrogen-bonding mechanism is responsible for adsorption of the phenolic species from hexanes onto the acrylic ester sorbent. Further, these studies suggest that the bulky tert-butyl groups of diTBC sterically hinder this hydrogen-bonding adsorption mechanism. Practically, the results suggest
that adsorption through only a single-point hydrogenbonding mechanism can offer an effective means to separate sterically hindered species. Acknowledgment Financial support was provided by the National Science Foundation through Grant CTS-9531812 and REU supplements to this grant. Literature Cited (1) Santacesaria, E.; Silvani, R.; Wilkinson, P.; Carra, S. Alkylation of p-Cresol with Isobutene Catalyzed by CationExchange Resins: A Kinetic Study. Ind. Eng. Chem. Res. 1988, 27, 541. (2) Yadav, G. D.; Thorat, T. S. Kinetics of Alkylation of p-Cresol with Isobutylene Catalyzed by Sulfonated Zirconia. Ind. Eng. Chem. Res. 1996, 35, 721. (3) Pirkle, W. H.; Pochapsky, T. C. Considerations of Chiral Recognition Relevant to the Liquid Chromatographic Separation of Enantiomers. Chem. Rev. 1989, 89, 347. (4) Fornstedt, T.; Sajonz, P.; Guiochon, G. A Closer Study of Chiral Retention Mechanisms. Chirality 1998, 10, 375. (5) Payne, G. F.; Payne, N. N.; Ninomiya, Y.; Shuler, M. L. Adsorption of Nonpolar Solutes onto Neutral Polymeric Sorbents. Sep. Sci. Technol. 1989, 24, 457. (6) Payne, G. F.; Ninomiya, Y. Selective Adsorption of Solutes Based on Hydrogen Bonding. Sep. Sci. Technol. 1990, 25, 1117. (7) Maity, N.; Payne, G. F.; Chipchosky, J. L. Adsorptive Separations Based on the Differences in Solute-Sorbent Hydrogen Bonding Strengths. Ind. Eng. Chem. Res. 1991, 30, 2456. (8) Chaubal, M. V.; Payne, G. F. Use of Acrylic Ester Sorbent for the Selective Adsorption of Avermectins. Biotechnol. Prog. 1995, 11, 468. (9) Brune, B. J.; Payne, G. F.; Chaubal, M. V. Linear Solvation Energy Relationships to Explain Interactions Responsible for Solute Adsorption onto a Polar Polymeric Sorbent. Langmuir 1997, 13, 5766. (10) Glemza, A. J.; Koehler, J. A.; Brune, B. J.; Payne, G. F. Selective Adsoirption of Methoxyphenol Positional Isomers. Ind. Eng. Chem. Res. 1998, 37, 3685. (11) Brune, B. J.; Koehler, J. A.; Smith, P. J.; Payne, G. F. Correlation between Adsorption and Small Molecule Hydrogen Bonding. Langmuir 1999, 15, 3987. (12) Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. MacroModelsAn Integrated Software System for Modeling Organic and Bioorganic Molecules Using Molecular Mechanics. J. Comput. Chem. 1990, 11, 440. (13) Weiner, S. J.; Kollman, P. A.; Case, D. A.; Singh, U. C.; Ghio, C.; Alagona, G.; Profeta, S., Jr.; Weiner, P. A New Force Field for Molecular Mechanical Simulation of Nucelic Acids and Proteins. J. Am. Chem. Soc. 1984, 106, 765. (14) Weiner, S. J.; Kollman, P. A.; Nguyen, D. T.; Case, D. A. An All Atom Force Field for Simulations of Proteins and Nucleic Acids. J. Comput. Chem. 1986, 7, 230. (15) Pimentel, G. C.; McClellan, A. L. The Hydrogen Bond; W. H. Freeman and Co.: San Francisco, 1960. (16) Jeffrey, G. A. Introduction to Hydrogen Bonding; Oxford University Press: New York, 1997. (17) Bellamy, L. J.; Williams, R. L. Solvent Effects on the Infrared Spectra of Hindered Phenols. Proc. Roy. Soc. A 1960, 254, 119. (18) Goddu, R. F. Hydroxyl Spectra of o-tert-Butylphenols. J. Am. Chem. Soc. 1960, 82, 4533. (19) Ingold, K. U. The Infrared Frequencies and Intensities of the Hydroxyl Band of ortho-Alkyl Phenols in the Vapor Phase. Can. J. Chem. 1962, 40, 111.
Received for review February 22, 1999 Revised manuscript received May 4, 1999 Accepted May 27, 1999 IE990128T
