Article pubs.acs.org/IECR
Effect of Solvent Topography and Steric Hindrance on Crystal Morphology Charles Acquah and Matthew Cagnetta Department of Chemical Engineering, University of Connecticut, Storrs, Connecticut 06269, United States
Luke E. K. Achenie Department of Chemical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, United States
Steven L. Suib Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States
Arunprakash T. Karunanithi* Center for Sustainable Infrastructure Systems, University of Colorado Denver, Denver, Colorado 80217, United States S Supporting Information *
ABSTRACT: Effect of steric hindrance resulting from solvent topography on the resultant crystal morphology was examined via cooling crystallization of various carboxylic acids in isomeric butyl and pentyl alcohols. Our experiments show that the magnitude of hindrance is related to the degree of branching at the substituted carbon, with hindrance increasing in the order of 1° < 2° < 3° alcohols. The resulting crystals displayed a trend of low, intermediate, and high aspect ratios, corresponding to 1°, 2°, and 3° alcohols, respectively. In particular, 3° alcohols have a tendency to yield significantly different crystal morphologies, compared to 1° and 2° alcohols. Hence, the position of the hydroxyl functional group plays a major role in enhancing or limiting solute− solvent hydrogen bonding interactions and thereby influencing the resultant crystal morphology. A simple molecular model, with succinic acid as test case, was used to demonstrate the extended hydrogen bonding network and surface chemistry binding at the dominant {100} face. This molecular-level exploration of solvent−carboxyl hydrogen bonding interaction at the crystal interface helped explain observed macroscopic morphological trends.
1. INTRODUCTION Crystallization is an important separation and purification technique that is used in many industries. The ability to engineer crystals to obtain the desired microscopic internal arrangement of molecules and the desired macroscopic external morphology is critical. Crystal structure and morphology can be controlled by manipulating crystallization conditions such as the growth temperature, supersaturation, addition of tailormade auxiliaries and additives, and the choice of solvent being used.1−7 The morphology of a solute recrystallized from a supersaturated solution is largely dependent on the characteristics of the solvent employed; hence, the appropriate choice of solvent plays a crucial role in obtaining the desired crystal morphology. As will be detailed in the following paragraphs, one important consideration involves the properties that inhibit or allow the solvent to form hydrogen bonds with the growth face of the forming crystal. For instance, molecules of pimelic acid and malonic acid pack end-to-end via hydrogen bonding, which implies that crystal growth occurs primarily along a particular axis.8,9 Several works have been reported in the literature detailing effects of solvent polarity on the morphology of crystals.10−16 © XXXX American Chemical Society
The morphology of ibuprofen, which is an important pharmaceutical monocarboxylic acid, has been extensively studied both experimentally and through computational modeling.17−24 The conclusions reached in the above studies describe the influence of solvent polarity on the morphology of organic crystals. The use of highly polar solvents has a tendency to produce crystals with low aspect ratio (ratio between the two major dimensions of each crystal) and nonpolar solvents yielded high-aspect-ratio needlelike morphologies. Hydrogen bonding plays an important role in the observed morphology of solutes crystallized from a solvent.20,21,23 A frequently used indicator of a solvent’s ability to interact with a solute via hydrogen bonding is the Hansen hydrogen bonding solubility parameter (δH). Although δH often provides a sufficient indication of a species’ propensity to interact through hydrogen bonding,24 there are instances where δH inadequately details the attractive interactions that it attempts to describe.25 This is Received: August 6, 2015 Revised: October 8, 2015 Accepted: October 21, 2015
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DOI: 10.1021/acs.iecr.5b02903 Ind. Eng. Chem. Res. XXXX, XXX, XXX−XXX
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Figure 1. Optical microscopy images of succinic acid (SA) crystals grown from butanol isomers.
Figure 2. Optical microscopy images of pimelic acid (PA) crystals grown from butanol isomers.
Figure 3. Optical microscopy images of acetylsalicylic acid (ASA) crystals grown from butanol isomers.
2.2. Experimental Methods. Prior to crystallization of the organic solids, solubility experiments were conducted by dissolving excess amount of each solute in 3 mL of a given solvent placed in a 28 mm × 70 mm vial. The vials were placed in a temperature-regulated water bath shaker and shaken for 3 days until saturation. Solubility studies were carried out at 25, 45, and 65 °C in order to establish a solubility profile. Using these solubilities as baseline, a supersaturation of 1.1 was effected and sample solutions prepared to known concentrations. The supersaturated solution was then heated to 65 °C and allowed to cool to 25 °C over a 4-h time period. The temperature was monitored every 5 min and controlled over the period. All vials were sealed to prevent solvent loss. Samples were cooled at the same time under the same linear cooling profile. The crystals produced were then ready for characterization. 2.3. Crystal Characterization. 2.3.1. Optical Micrographs. Optical photomicrographs were taken on slurry samples using a computer-assisted CCD camera at 120× magnification. Images were analyzed manually with the closest bounding box being drawn around a random selection of crystals and then measured. Aspect ratio was taken as the length-to-width ratio of a crystal, with length being denoted as the longer measured side of the image in a 2D plane. 2.3.2. Powder X-ray Diffraction (PXRD). Powder X-ray diffraction (PXRD) studies were carried out to confirm the solid state of residual solids and also to ensure the internal arrangement of molecules is the same for each crystalline sample within an isomeric solvent series. A normal continuous scan rate of 4.00° per min with a step size of 0.02° from 5° to 90° was used. The PXRD patterns of the original and
particularly important for crystal engineering in industry, because an accurate prediction of crystal morphology can decrease production costs by limiting experimental validations and impact the methodology and procedure devised for production. This paper closely examines the steric demands on the hydrogen-bonding functional group of alcohols and their role in determining crystal morphology. Crystallization of succinic acid, pimelic acid, and acetylsalicylic acid in various isomers of butyl and pentyl alcohols were carried out. A simple molecular model using the Mercury software and succinic acid as test case was used to demonstrate the extended hydrogen bonding network and surface chemistry binding at the dominant {100} face. This molecular-level exploration of solvent−carboxyl hydrogen bonding interaction at the crystal interface has helped to explain observed macroscopic morphological trends.
2. MATERIALS AND METHODS 2.1. Materials. High-grade succinic acid (SA), pimelic acid (PA), and acetylsalicylic acid (ASA) obtained from Sigma− Aldrich with 99.0% purity were used for the experiments. All solvents (1-butanol, 2-butanol, t-butanol, 1-pentanol, 2pentanol, 2-methyl-2-butanol) used for the experimentation were at least 99.0% pure. The two-dimensional (2D) structures of the solvents used are summarized in Table S1 in the Supporting Information). Numerical values26−28 of δH and the Kamlet−Taft parameter (α) for the selected solvents are given in Tables S2 and S3 in the Supporting Information. The chosen solvents can be considered to be similar judging by δH. However, significant differences can be observed if α is used as the criterion for solvent hydrogen-bonding propensity. B
DOI: 10.1021/acs.iecr.5b02903 Ind. Eng. Chem. Res. XXXX, XXX, XXX−XXX
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Figure 4. Optical microscopy images of succinic acid (SA) crystals grown from pentanol isomers.
Figure 5. Optical microscopy images of pimelic acid (PA) crystals grown from pentanol isomers.
Figure 6. Optical microscopy images of acetylsalicylic acid (ASA) crystals grown from pentanol isomers.
and 1° and 3° alcohols of each isomer range were statistically analyzed using Minitab. This provides a useful quantitative check for validating the observed qualitative crystal morphology. Table S5 in the Supporting Information presents the results of the two-sample t-test at a 5% significance level. The results show that, with the exception of PA recrystallized from 1° and 2° pentyl alcohols and SA recrystallized from 1° and 2° butyl alcohols, all other pairwise comparison tests show a significant difference in morphology between the crystals obtained for each compound along each isomer range. More importantly, the t-value for the 1° and 3° pair of each isomer family is notably greater than other examined pairs. Another point worth noting is that, for ASA, the change in aspect ratio between the 1° and 2° pair of isomeric solvents is even much larger than that observed for PA and SA. These trends fortify the findings from the crystallization experiments. 3.3. Powder X-ray Diffraction (PXRD) Patterns. Figure 7 shows a PXRD pattern taken for the original SA and SA crystals obtained from 1-butanol. Peak positions were identical, an indication that the internal crystal structure remains the same before and after crystallization. The sharpness of the peaks also confirms that all samples are fully crystalline and not amorphous. Same observations were made for all solutes (PA and ASA) crystallized from the other isomeric solvents. 3.4. Molecular-Level Explanation of Observed Phenomenon. Primary alcohols (e.g., 1-butanol and 1-pentanol) have linear topography, which allows for the formation of infinite hydrogen-bonded chains and a close association of molecules. Tertiary monoalcohols (e.g., t-butanol and 2-methyl2-butanol), with highly branched topography, generally prefer
recrystallized carboxylic acids were recorded using an X-ray diffractometer (Scintag XDS 2000 X-ray diffractometer equipped with a Cu Kα X-ray source, λ = 1.54 Å) with radiations generated at 30 mA and 40 kV.
3. RESULTS AND DISCUSSION 3.1. Optical Microscopy Images. Figures 1−3 represent OM images of SA, PA, and ASA grown from the respective butanol isomers. Similarly, Figures 4−6 represent SA, PA and ASA grown from the respective pentanol isomers. It can be observed from the optical microscopy images that the same solute crystallized from different solvents display different morphologies. For example, ASA is sheetlike when crystallized from 1butanol or 1-pentanol and in the form of elongated sheets for 2° alcohols, as observed in panels a−c in Figure 3 and panels a−c in Figure 6. The morphology for ASA obtained from 2methyl-2-butanol and t-butanol is needlelike, with high aspect ratios. A novel finding of this work is that the alcohols examined were polar and yet crystals grown from 3° alcohols (t-butanol and 2-methyl-2-butanol) exhibited elongated morphology more akin to crystals grown from nonpolar solvents. This trend is easily recognizable from the OM images for the other carboxylic acids crystallized from each solvent in its respective isomer range. Quantitative analysis of the crystal morphology is provided in section 3.2. 3.2. Statistical Analysis for Differences in Morphology. A summary of mean aspect ratio and corresponding standard deviations calculated from 15 crystals of a given sample are shown in Table S4 in the Supporting Information. For a given solute, the differences between 1° and 2°, 2° and 3°, C
DOI: 10.1021/acs.iecr.5b02903 Ind. Eng. Chem. Res. XXXX, XXX, XXX−XXX
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crystal interface was examined using the molecular modeling software, Mercury. The {100} face is polar, because of the carboxylic oxygen and hydrogen atoms that project normal to this face. Previous work in the literature31−33 have shown that crystals of SA grown from an aqueous solution (polar) develop a steady-state platelike morphology with a large dominant {100} plane. A close examination of the extended crystal structure of SA in Figure 9 reveals that the {100} plane cuts
Figure 7. Powder X-ray diffraction (PXRD) patterns for original SA and SA recrystallized from 1-butanol.
to form isolated or no hydrogen bonds, because of steric factors limiting chain formation. Substituents located at the β-position greatly affected molecular association due to the reliance of packing patterns on steric hindrance.29 Infrared spectroscopic studies of dilute alcohol solutions showed that the telltale “oligomer” band of t-butanol had smaller association correlation values than other alcohols examined.30 Recall from Table S2 that no significant differences in the values for δH are observed for the respective butyl and pentyl isomers. Thus, the use of δH oversimplifies hydrogen bonding and is obviously inadequate to explain the morphological trends observed in this work. The Kamlet−Taft parameter (α) may be more suitable for capturing subtle differences, especially in the case of isomeric solvents. However, α, which is a measure of the proton (hydrogen) donating power of the solvents, is dependent on steric factors. Steric factors, as mentioned in this study, refer to bulky alkyl groups in the neighborhood of a given −OH group of solvent. Previous work by Taylor and Macrae29 has exclusively stated that solvent topography affects the manner in which one solvent molecule hydrogen bonds with another solvent molecule and it is expected that the steric characteristics of a solvent carry over to interactions with solutes and, more specifically, the carboxylic acids examined in the present study. Therefore, it is conceivable that the extent of hydrogen bonding between −OH groups of the solvent and the −COOH groups of the solute will be much more pronounced for 1° alcohols than for 3° alcohols, with 2° alcohols forming intermediate hydrogen bonding. The surface chemistry of SA was explored to help elucidate observed differences in crystal morphology. SA crystallizes in space group P21/c (a = 5.52 Å, b = 8.86 Å, c = 5.10 Å, β = 91.6°). The unit cell of SA with a superimposed {100} plane is shown in Figure 8. The intermolecular hydrogen bonding at the
Figure 9. Extended hydrogen bonding network of SA.
perpendicularly through the direction of molecular packing. Thus, 1° alcohols with highly accessible terminal −OH groups will interact strongly with the {100} face via hydrogen bonding, restricting directional molecular packing and slowing crystal growth. Using a similar argument, it can be reasoned that 2° and 3° alcohols with much less accessible −OH groups due to steric hindrance will bind less effectively to exposed −COOH groups on the {100} face allowing for relatively unhampered growth producing crystals with comparatively higher aspect ratios than 1° alcohols. The results can be more clearly explained through the predictive growth models and analysis proposed by Lovette and Doherty.34 To be more precise in our explanation, the relevant interactions are not directly between the solvent and the faces (i.e., terraces) but are between the solvent and kink sites, which are essentially features present on the faces of the growing crystals. The work of adhesion between crystalline and solution phases is an important parameter that determines the aspect ratio of the crystals being formed. The work of adhesion across an interface includes contributions from dispersive, polar, and hydrogen-bonding interactions, occurring between the crystal and solution.34 Therefore, hydrogen bonding at kink sites causes the solvent-mediated kink energy to increase. This, in turn, causes the density of kink sites to decrease, which causes the step velocity to decrease.34 This decreased step velocity causes the face to grow more slowly in the direction perpendicular to the hydrogen-bond direction, thus influencing the crystal shape, as a result of the solute−solvent interactions.
4. CONCLUSIONS Carboxylic acids recrystallized from isomeric alcohols can have significantly different crystal morphologies, depending on the position of the −OH functional group. This finding is important and it was shown that morphology relies heavily on the solvent’s ability to bind to a given crystal face. The terminal −OH group of 1° alcohols are more accessible than that of 2° alcohols and 3° alcohols, because of hindrance caused by branching at the substituted carbon. 2° alcohols, and
Figure 8. Unit cell of succinic acid with a superimposed {100} plane. D
DOI: 10.1021/acs.iecr.5b02903 Ind. Eng. Chem. Res. XXXX, XXX, XXX−XXX
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especially 3° alcohols with a high degree of branching at the substituted carbon possess a much less-accessible functional group and therefore bind less effectively to the exposed − COOH groups, allowing for relatively unhampered growth, producing elongated crystals with high aspect ratios. In short, 1° alcohols have a higher potential to bind to the polar growth face of the carboxylic acid crystals than 2° alcohols and, in turn, 2° alcohols appear to possess a greater hydrogenbonding potential than 3° alcohols. The stronger the hydrogen bonding between the solute and the solvent, the lower the crystal aspect ratio, because of the solvent’s propensity to bind to the solute at the polar growth face, thereby inhibiting crystal growth along the packing axis. Since the ability of the solvent to retard growth in this manner is related to its topography, the aspect ratios of the crystals parallel an increase in branching at the substituted carbon. Hence, aspect ratio of crystals grown from the solvents increases in the order of valence: 1° < 2° < 3°. Thus, in selecting solvents for use in a particular crystallization application, one must take into account the steric demands of key functional groups responsible for solvent−solute interaction at the crystal interface. Singlecomponent solvent property indices, such as the Kamlet− Taft parameter, could be used to filter out subtle differences, especially in the case of isomeric alcohols. Finally, a simple molecular model using the Mercury software and succinic acid as a test case was used to demonstrate the extended hydrogen bonding network and surface chemistry binding at the dominant {100} face. This molecular-level exploration of solvent-carboxyl hydrogen bonding interaction at the crystal interface helped explain observed macroscopic morphological trends.
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.iecr.5b02903. Structures of selected solvents (Table S1); properties of butyl isomers (Table S2) and pentyl isomers (Table S3); aspect ratios of various solvent−solute systems (Table S4); and statistical analysis for various solvent−solute systems (Table S5) (PDF)
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AUTHOR INFORMATION
Corresponding Author
*Tel.: (303)556-2370. Fax: (303)556-2368. E-mail:
[email protected]. Address: Center for Sustainable Infrastructure Systems, University of Colorado Denver, 1200 Larimer Street, Room 3019 C, Denver, CO 80204, USA. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS Special thanks to Edward Nyutu and Anwar Beshir (Department of Chemistry, University of Connecticut) for their contribution towards acquisition of solubility data. Authors also acknowledge the Cambridge Crystallographic Data Center (CCDC) for use of their free molecular modeling software (Mercury 1.4.2). E
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