Full Terms & Conditions of access and use can be found athttp://www.tandfonline.com/action/journalInformation?journalCode=gpch20

Download by: [ Jordan Univ. of Science & Tech] Date: 17 March 2017, At: 19:58

Physics and Chemistry of LiquidsAn International Journal

ISSN: 0031-9104 (Print) 1029-0451 (Online) Journal homepage: http://www.tandfonline.com/loi/gpch20

Determination of Abraham model solutedescriptors for 2-methyl-3-nitrobenzoic acid frommeasured solubility data in alcohol, alkyl ether,alkyl acetate and 2-alkoxyalcohol mono-solvents

Erin Hart, Ashley M. Ramirez, Sarah Cheeran, Maribel Barrera, Melissa Y.Horton, Anisha Wadawadigi, William E. Acree Jr & Michael H. Abraham

To cite this article: Erin Hart, Ashley M. Ramirez, Sarah Cheeran, Maribel Barrera, Melissa Y.Horton, Anisha Wadawadigi, William E. Acree Jr & Michael H. Abraham (2017): Determination ofAbraham model solute descriptors for 2-methyl-3-nitrobenzoic acid from measured solubility datain alcohol, alkyl ether, alkyl acetate and 2-alkoxyalcohol mono-solvents, Physics and Chemistry ofLiquids, DOI: 10.1080/00319104.2017.1283692

To link to this article: http://dx.doi.org/10.1080/00319104.2017.1283692

Published online: 30 Jan 2017.

Submit your article to this journal

Article views: 20

View related articles

View Crossmark data

Determination of Abraham model solute descriptors for2-methyl-3-nitrobenzoic acid from measured solubility data inalcohol, alkyl ether, alkyl acetate and 2-alkoxyalcoholmono-solventsErin Harta, Ashley M. Ramireza, Sarah Cheerana, Maribel Barreraa, Melissa Y. Hortona,Anisha Wadawadigia, William E. Acree, Jra and Michael H. Abrahamb

aDepartment of Chemistry, University of North Texas, Denton, TX, USA; bDepartment of Chemistry, UniversityCollege London, London, UK

ABSTRACTSpectroscopic methods are employed to measure the solubility of 2-methyl-3-nitrobenzoic acid dissolved in 10 alcohol, 3 alkyl ether, 5 alkylacetate and 3 alkoxyalcohol solvents at 298.2 K. 2-Methyl-3-nitrobenzoicacid is believed to exist in monomeric form in each of the organicsolvents studied. The measured solubilities are used to calculate theAbraham model solute descriptors for the monomeric form of 2-methyl-3-nitrobenzoic acid, which will enable one to predict the solubi-lity of 2-methyl-3-nitrobenzoic acid in additional organic solvents. Thederived solute descriptors back-calculated the observed solubility data towithin 0.06 log units.

ARTICLE HISTORYReceived 13 January 2017Accepted 15 January 2017

KEYWORDS2-Methyl-3-nitrobenzoic acidsolubility; Abraham modelsolute descriptors; alcoholsolvents; alkoxyethanolsolvents; alkyl acetatesolvents; alkyl ether solvents

1. Introduction

Solubility studies can provide valuable information regarding molecular interactions in fluidsolution and regarding both polymorphism and solvate formation in the solid phase. Suchinformation can be used in the design of recrystallisation processes and drug delivery formula-tions. For example, Garg and Sarkar [1] demonstrated that the polymorphism of 4-aminobenzoicacid could be effectively controlled through isothermal anti-solvent recrystallisation with ethanolserving as the solvent and water being the anti-solvent. The authors observed that needle-typecrystals (α-form) were obtained at the larger supersaturation and larger water flow rates studied.Prismatic crystals (β-form) were obtained at the smaller supersaturation ratios and smaller waterflow rates. Several solvent selection methods [2,3] have been proposed in conjunction withpolymorphic screening studies. Brittain and coworkers [4] reviewed the effects that polymorphismand solvate formation have on the solubility and dissolution rate of select pharmaceuticalcompounds. Solubility and dissolution rate are important considerations in drug delivery asthese properties determine the pharmaceutical compound’s bioavailability for its intended ther-apeutic application.

Our solubility studies have been directed towards experimentally determine the solubility ofboth pharmaceutical [5–7] and non-pharmaceutical compounds [8–11] in series of chemicallydiverse mono-solvents and binary solvent mixtures, and then using the measured experimentaldata to develop mathematical expressions for predicting the solute’s solubility in additional mono-solvents or in other binary (ternary and high-higher multicomponent) solvent mixtures. In thisregard, expressions have been derived for predicting solute solubility in ternary solvent mixtures

CONTACT William E. Acree, Jr acree@unt.edu© 2017 Informa UK Limited, trading as Taylor & Francis Group

PHYSICS AND CHEMISTRY OF LIQUIDS, 2017http://dx.doi.org/10.1080/00319104.2017.1283692

from measured solubility data for the solute dissolved in the three contributing binary solventsystems that make up the ternary solvent mixture based on the Combined Nearly Ideal BinarySolvent/Redlich–Kister model. The derived mathematical correlations have proved very useful inpredicting the solubility of anthracene [12–15] and pyrene [16–18] in a wide range of ternarysolvent mixtures.

Abraham model correlations [19–25] have also been derived for predicting the solubility ofcrystalline non-electrolyte pharmaceutical compounds and crystalline non-pharmaceutical organiccompounds in more than 100 chemically diverse organic solvents of varying polarity and hydro-gen-bonding character. Abraham model correlations predict solubilities as the ratio of molarsolubility in the organic solvent, CS,organic, divided by the molar solubility in water, CS,water:

log ðCS;organic=CS;waterÞ ¼ cp þ ep � Eþ sp � Sþ ap � Aþ bp � Bþ vp � V (1)

or as the ratio of the molar solubility in the organic solvent divided by a molar gas phaseconcentration of the solute, CS,gas:

logðCS;organic=CS;gasÞ ¼ ck þ ek � Eþ sk � Sþ ak � Aþ bk � Bþ lk � L (2)

using as input parameters known coefficients for the organic solvents (cp, ep, sp, ap, bp, vp, ck, ek,sk, ak, bk and lk) and known solute descriptors (E, S, A, B, V and L) of the crystalline non-electrolytesolutes whose solubility is being predicted. Solute descriptors are denoted as follows: E and Scorrespond to the excess molar refraction and dipolarity/polarisability descriptors of the solute,respectively, A and B are measures of the solute hydrogen-bond acidity and basicity, V refers to theMcGowan volume of the solute and L is the logarithm of the solute gas phase dimensionless gas tohexadecane partition coefficient at 298 K. The numerical values of the solvent coefficients aredetermined by regression analysis of partition coefficients and solubility ratios for a series of solutesdissolved in the given solvent or two-phase partitioning system. To date we have reported solventcoefficients for more than 100 different organic mono-solvents [19–25], binary aqueous-methanol[26] and binary aqueous-ethanol [27,28] solvent mixtures, and for more than 80 different ionicliquids [29]. Values of log (CS,organic/CS,water) can be transformed into log (CS,organic/CS,gas) used inEquation (1) through log (CS,organic/CS,gas) = log (CS,organic/CS,water) + log Kw, where Kw is the gas-to-water partition coefficient of the solute. We do not know log Kw for 2-methyl-3-nitrobenzoic acidand so we took log Kw as another solute property to be determined.

Terms have been added to Equation (1) to describe the transfer of ions and ionic species fromwater to several organic solvents [26,27,30,31]. The solute transfer properties of substituted-benzoate anions can be obtained from the measured acid-dissociation constants (pKa) of therespective neutral substituted-benzoic acid derivatives. Water-to-organic solvent partition coeffi-cient data or solubility of the parent substituted benzoic acid in the organic solvent is needed inthe calculation of solute transfer properties of substituted-benzoate anions. If the needed experi-mental data is not available, it can be estimated from Equation (2), provided that the solutedescriptors of the substituted benzoic acid derivative are known.

Solute descriptors are available at an online data site [32] for approximately 7,000 differentorganic and inorganic compounds. There are many compounds for which solute descriptorsare not available or for which only preliminary descriptor values are available. Preliminarydescriptor values are of either calculation origin or were determined from very few experi-mental data points. During the past 15 years, we have determined/updated solute descriptorsfor many compounds based on our experimental measurements and measured solubility datataken from the published chemical and engineering literature. 2-Methyl-3-nitrobenzoic acid isone of the organic compounds whose solute descriptors (E = 0.99, S = 1.32, A = 0.73,B = 0.52, V = 1.247, L = 6.239) [32] are considered as preliminary values. In the presentcommunication, we report the experimental solubility data for 2-methyl-3-nitrobenzoic aciddissolved in 10 alcohol (1-propanol, 1-butanol, 1-pentanol, 1-hexanol, 1-heptanol, 1-octanol,

2 E. HART ET AL.

2-propanol, 2-butanol, 2-methyl-1-propanol, 3-methyl-1-butanol), 3 alkyl ether (diisopropylether, methyl tert-butyl ether, 1,4-dioxane), 5 alkyl acetate (methyl acetate, ethyl acetate,propyl acetate, butyl acetate, pentyl acetate) and 3 alkoxyalcohol (2-ethoxyethanol, 2-propy-lethanol, 2-butoxyethanol) solvents. Results of our experimental measurements are used toupdate the solute descriptors of 2-methyl-3-nitrobenzoic acid.

2. Carboxylic acid solute and organic solvents

2-Methyl-3-nitrobenzoic acid (Aldrich Chemical Company, 0.99 mass fraction) was used asreceived. All organic solvents were obtained from commercial sources. The chemical suppliersand mass fraction chemical purities (as supplied by the manufacturers) are given in the second andthird columns of Table 1, respectively. Organic solvents were stored over activated molecular sievesand distilled prior to use. Gas chromatographic analyses (with both a flame ionisation detector andthermal conductivity detector) were used to verify the mass fraction purities stated by the manu-facturers, and showed all solvents to have a mass fraction purity of 0.997 or higher. The purity of 2-methyl-3-nitrobenzoic acid was found to be 0.997 ± 0.004 mass fraction as determined by non-aqueous titration with freshly standardised sodiummethoxide solution to the thymol blue endpointaccording to the method of Fritz and Lisicki [33], except that toluene was substituted for benzene.

3. Experimental methodology

The method of sample equilibration and subsequent analysis of concentration of the dissolved solutein the saturated solutions has been described in detail in earlier publications [5–11]. To conservejournal space, only an abbreviated description of the experimental methodology will be presentedhere. Samples of excess solute and organic solvent in sealed amber glass bottles were allowed toequilibrate periodical shaking in a constant temperature water bath at 298.2 ± 0.1 K for at least 3 days.After equilibrium was established, the saturated samples were allowed to set unagitated for severalhours to allow any dispersed small solid particles to settle to the container bottom.Weighed aliquots ofthe saturated 2-methyl-3-nitrobenzoic acid solutions were transferred through a coarse filter into a

Table 1. Provenances and mass fraction purities of 2-methyl-3-nitrobenzoic acid and organic solvents.

Organic compounds Supplier Purity as specified by supplier

2-Methyl-3-nitrobenzoic acid Aldrich Chemical Co. 0.991-Propanol Aldrich Chemical Co. 0.99+, anhydrous1-Butanol Aldrich Chemical Co. 0.998+, HPLC grade1-Pentanol Aldrich Chemical Co. 0.99+1-Hexanol Alfa Aesar Chemical Co. 0.99+1-Heptanol Alfa Aesar Chemical Co. 0.99+1-Octanol Aldrich Chemical Co. 0.99+, anhydrous2-Propanol Aldrich Chemical Co. 0.99+, anhydrous2-Butanol Aldrich Chemical Co. 0.99+, anhydrous2-Methyl-1-propanol Aldrich Chemical Co. 0.99+, anhydrous3-Methyl-1-butanol Sigma-Aldrich Chemical Co. 0.99+, anhydrousDiisopropyl ether Aldrich Chemical Co. 0.99, anhydrousMethyl tert-butyl ether Aldrich Chemical Co. 0.99+, anhydrous1,4-Dioxane Aldrich Chemical Co. 0.998, anhydrous2-Ethoxyethanol Aldrich Chemical Co. 0.992-Propoxyethanol Sigma-Aldrich Chemical Co. 0.9942-Butoxyethanol Acros Chemical Co. 0.99Methyl acetate Aldrich Chemical Co. 0.995, anhydrousEthyl acetate Aldrich Chemical Co. 0.999, HPLC gradePropyl acetate Aldrich Chemical Co. 0.995Butyl acetate Aldrich Chemical Co. 0.997, HPLC gradePentyl acetate Aldrich Chemical Co. 0.99

HPLC: High Performance Liquid Chromatographic

PHYSICS AND CHEMISTRY OF LIQUIDS 3

volumetric flask and then diluted quantitatively with 2-propanol for spectrophotometric analysis at290 nm on a Milton Roy Spectronic 1000 Plus spectrometer. Molar concentrations of the dilutedsolutions were obtained from a Beer-Lambert law absorbance versus concentrations working curve fornine standard solutions of known concentration (from 3.574 × 10–4 to 1.191 × 10−3 M). The calculatedmolar absorptivity varied slightly with solute concentration, and ranged from approximately ɛ ≈ 1400to ≈ 1320 L mol−1 cm−1. Attainment of equilibrium was verified by repetitive measurementsperformed the following day (or sometimes after 2 days) and by approaching equilibrium fromsuper supersaturation by pre-equilibrating the solutions at a slightly higher temperature.Experimental 2-methyl-3-nitrobenzoic acid mole fraction solubilities, XS, in the 21 different organicsolvents studied are reported in the second and fourth columns of Table 2. Numerical values representthe average of between four and eight independent experimental determinations, and were reprodu-cible to ±2%.

4. Calculation of Abraham model solute descriptors

Computation of Abraham model solute descriptors involves the simultaneous solution of a seriesof log (CS,organic/CS,water) and log (CS,organic/CS,gas) mathematical equations. We have Abrahammodel equation coefficients for 20 of the 21 organic solvents in which solubility measurementswere made. Equation coefficients are given in Table 3 by the type of solute transfer process. Thefirst set of coefficients corresponds to solute transfer into the organic solvent from water, whilethe second set of coefficients describe gas-to-organic solvent transfer processes. All transferprocesses, except for the first process in each set, correspond to the ‘dry’ organic solvent. Thefirst transfer process pertains to the practical water-to-octanol partition coefficient where thesolute is distributed between a water-saturated 1-octanol organic phase and an aqueous phase thatis saturated with 1-octanol. For a practical partitioning process, the two phases are in directcontact with each other. The term ‘wet’ appears after the name of the solvent to indicate that theorganic phase is saturated with water.

To construct the Abraham model log (CS,organic/CS,water) and log (CS,organic/CS,gas) equations,we must convert the experimental mole fraction solubilities, XS

exp, in Table 2 into molarsolubilities. This is accomplished by dividing XS

exp by the ideal molar volume of the saturatedsolution (i.e. CS

exp ≈ XSexp/[XS

exp VSolute + (1 – XSexp) VSolvent]). A value of VSolute = 135.12 cm3

mol−1 was used for the molar volume of the hypothetical subcooled liquid 2-methyl-3-nitro-benzoic acid. The molar volume was estimated as the molar volume of 3-nitrobenzoic acid plusthe molar volume of 2-methylbenzoic acid minus the molar volume of benzoic acid, e.g.Vsolute = V3-nitrobenzoic acid + V2-methylbenzoic acid – Vbenzoic acid. Any errors resulting from ourestimation of the 2-methyl-3-nitrobenzoic acid’s hypothetical subcooled liquid molar volume,

Table 2. Experimental mole fraction solubilities, XSexp, of 2-methyl-3-nitrobenzoic acid at 298.2 K.

Organic solvent XSexp Organic solvent XS

exp

Alcohol solvents Alkyl ether solvents1-Propanol 0.02523 Diisopropyl ether 0.011241-Butanol 0.02522 Methyl tert-butyl ether 0.035071-Pentanol 0.02573 1,4-Dioxane 0.072491-Hexanol 0.02778 Alkyl acetate solvents1-Heptanol 0.02863 Methyl acetate 0.033841-Octanol 0.02672 Ethyl acetate 0.031792-Propanol 0.02498 Propyl acetate 0.031102-Butanol 0.02501 Butyl acetate 0.033292-Methyl-1-propanol 0.01754 Pentyl acetate 0.029103-Methyl-1-butanol 0.022912-Alkoxyethanol solvents2-Ethoxyethanol 0.078632-Propoxyethanol 0.078112-Butoxyethanol 0.07055

4 E. HART ET AL.

VSolute, or the ideal molar volume approximation should have negligible effect of the calculatedCS

exp values.Once the mole fraction solubilities have been converted into molar solubilities, the solubility

ratios (CS,organic/CS,water) are calculated using a value of log CS,water = −2.71 for the molar solubilityof molecular 2-methyl-3-nitrobenzoic acid (determined as part of the present study, corrected forionisation). Calculation of the (CS,organic/CS,gas) solubility ratios is a bit more difficult as we aremissing an experimental value for log CS,gas. The numerical value of log CS,gas will be ‘floated’ anddetermined as part of our solute descriptor computation. This computation has been described indetail in several or our earlier papers [5–11]. Two practical water-to-octanol partition coefficientequations:

Table 3. Coefficients in Equations (1) and (2) for various processesa.

Process/solvent c e s a b v/l

A. Water to solvent: Equation (1)1-Octanol (wet) 0.088 0.562 −1.054 0.034 −3.460 3.8141-Propanol (dry) 0.139 0.405 −1.029 0.247 −3.767 3.9862-Propanol (dry) 0.099 0.344 −1.049 0.406 −3.827 4.0331-Butanol (dry) 0.165 0.401 −1.011 0.056 −3.958 4.0441-Pentanol (dry) 0.150 0.536 −1.229 0.141 −3.864 4.0771-Hexanol (dry) 0.115 0.492 −1.164 0.054 −3.978 4.1311-Heptanol (dry) 0.035 0.398 −1.063 0.002 −4.342 4.3171-Octanol (dry) −0.034 0.489 −1.044 −0.024 −4.235 4.2182-Butanol (dry) 0.127 0.253 −0.976 0.158 −3.882 4.1142-Methyl-1-propanol (dry) 0.188 0.354 −1.127 0.016 −3.568 3.9863-Methyl-1-butanol (dry) 0.073 0.360 −1.273 0.090 −3.770 4.273Diisopropyl ether (dry) 0.181 0.285 −0.954 −0.956 −5.077 4.542Methyl tert-butyl ether (dry) 0.341 0.307 −0.817 −0.618 −5.097 4.4251,4-Dioxane (dry) 0.123 0.347 −0.033 −0.582 −4.810 4.110Methyl acetate (dry) 0.351 0.223 −0.150 −1.035 −4.527 3.972Ethyl acetate (dry) 0.328 0.369 −0.446 −0.700 −4.904 4.150Propyl acetate (dry) 0.288 0.363 −0.474 −0.784 −4.938 4.216Butyl acetate (dry) 0.248 0.356 −0.501 −0.867 −4.973 4.2812-Ethoxyethanol (dry) 0.133 0.392 −0.419 0.125 −4.200 3.8882-Propoxyethanol (dry) 0.053 0.419 −0.569 0.000 −4.327 4.0952-Butoxyethanol (dry) −0.055 0.377 −0.607 −0.080 −4.371 4.234(Gas to water) −0.994 0.577 2.549 3.813 4.841 −0.869B. Gas to solvent: Equation (2)1-Octanol (wet) −0.198 0.002 0.709 3.519 1.429 0.8581-Propanol (dry) −0.042 −0.246 0.749 3.888 1.076 0.8742-Propanol (dry) −0.048 −0.324 0.713 4.036 1.055 0.8841-Butanol (dry) −0.004 −0.285 0.768 3.705 0.879 0.8901-Pentanol (dry) −0.002 −0.161 0.535 3.778 0.960 0.9001-Hexanol (dry) −0.014 −0.205 0.583 3.621 0.891 0.9131-Heptanol (dry) −0.056 −0.216 0.554 3.596 0.803 0.9331-Octanol (dry) −0.147 −0.214 0.561 3.507 0.749 0.9432-Butanol (dry) −0.034 −0.387 0.719 3.736 1.088 0.9052-Methyl-1-propanol (dry) −0.003 −0.357 0.699 3.595 1.247 0.8813-Methyl-1-butanol (dry) −0.052 −0.430 0.628 3.661 0.932 0.937Diisopropyl ether (dry) 0.139 −0.473 0.610 2.568 0.000 1.016Methyl tert-butyl ether (dry) 0.231 −0.536 0.890 2.623 0.000 0.9991,4-Dioxane (dry) −0.034 −0.389 1.724 2.989 0.000 0.922Methyl acetate (dry) 0.134 −0.477 1.749 2.678 0.000 0.876Ethyl acetate (dry) 0.182 −0.352 1.316 2.891 0.000 0.916Propyl acetate (dry) 0.165 −0.383 1.264 2.757 0.000 0.985Butyl acetate (dry) 0.147 −0.414 1.212 2.623 0.000 0.9542-Ethoxyethanol (dry) −0.064 −0.257 1.452 3.672 0.662 0.8432-Propoxyethanol (dry) −0.091 −0.288 1.265 3.566 0.390 0.9022-Butoxyethanol (dry) −0.109 −0.304 1.126 3.407 0.660 0.914(Gas to water) −1.271 0.822 2.743 3.904 4.814 −0.213

aThe dependent variable is log (CSsat/CW

sat) and log (CSsat/CG) for all of the correlations, except for the one water-to-octanol

partition coefficient.

PHYSICS AND CHEMISTRY OF LIQUIDS 5

logP wet octanolð Þ ¼ 0:088þ 0:562E� 1:054Sþ 0:034A� 3:460Bþ 3:814V (3)

logK wet octanolð Þ ¼ � 0:198þ 0:002Eþ 0:709Sþ 3:519Aþ 1:429Bþ 0:858L (4)

where log P(wet octanol) = 2.160 [34] and log K(wet octanol) = log P(wet octanol) + log CS,water –log CS,gas, and two equations describing the logarithm of the gas-to-water partition coefficient(log Kw):

logKw ¼ � 0:994þ 0:577Eþ 2:549Sþ 3:813Aþ 4:841B� 0:869V (5)

logKw ¼ � 1:271þ 0:822Eþ 2:743Sþ 3:904Aþ 4:814B� 0:213L (6)

give us a total of 44 mathematical equations that must be solved, counting the 20 log (CS,organic/CS,water) and 20 log (CS,organic/CS,gas) constructed from the measured solubility data and equationcoefficients in Table 3. As noted earlier, 2-methyl-3-nitrobenzoic acid is expected to existpredominantly in monomeric form in each of the organic solvents studied here. Solvents wheredimerisation occurs must be excluded from the present calculation as the numerical values of thesolute descriptors of a monomeric and dimeric carboxylic acid are quite different. Determinationof solute descriptors of carboxylic acid dimers are based on solubility data in non-polar alkane,chloroalkane and alkylbenzene solvents as described elsewhere [35].

The present computation is further simplified by noting that two of the six solute descrip-tors can be calculated from molecular structure considerations. The McGowan characteristicvolume, V, can be computed from the molecular structure, atomic sizes and number of bonds[36]. The E solute descriptor can be obtained using the Absolv ACD software [37], which isbased on molecular structure considerations using fragment group values [38,39], or estimatedusing a measured value (liquid solute) or an estimated value (solid solute) for the solute’srefractive index. The refractive index of solid solutes can be estimated using the (free) ACDsoftware [40]. The values of V and E that we calculate for 2-methyl-3-nitrobenzoic acid areV = 1.2468 and E = 1.040.

The 44 mathematical equations were solved simultaneously using Microsoft Solver software toyield numerical values of the following: E = 1.040; S = 1.396; A = 0.541; B = 0.532; V = 1.2468;L = 6.332; log Kw = 6.737 and log CS,gas = −9.447 with the overall standard error being SE = 0.061log units. Individual standard errors are SE = 0.058 and SE = 0.065 for the 22 calculated andobserved log (P or CS,organic/CS,water) values and the 22 calculated and observed log (K or CS,organic/CS,gas) values, respectively. Statistically there is no difference between the set of 22 log (P or CS,

organic/CS,water) values and the total set of 44 log (P or CS,organic/CS,water) and log (K or CS,organic/CS,

gas) values, thus suggesting that log CS,gas = −9.447 is a feasible value for 2-methyl-3-nitrobenzoicacid. Table 4 provides a summarised comparison of the experimental molar solubility data andback-calculated values using the solute descriptors that we have determined. As an informationalnote, the solute descriptors that we have calculated are not too different from the values ofE = 0.99, S = 1.32, A = 0.73, B = 0.52, V = 1.247 and L = 6.239 for 2-methyl-3-nitrobenzoic listedin the UFZ-LSER database v 3.1 [32]. The most noticeable difference concerns the reduction inthe H-bond acidity solute descriptor, e.g. A = 0.541 (our value) versus A = 0.73 (UFZ-LSERdatabase). The solute descriptors in the UFZ-LSER database are preliminary only, as there isalmost no partition coefficient or solubility data for 2-methyl-3-nitrobenzoic acid in the chemicalliterature. 2-Methyl-3-nitrobenzoic acid and 3-methyl-4-nitrobenzoic acid (E = 1.04, S = 1.336,A = 0.525, B = 0.500, V = 1.2468 and L = 6.266) [9] have very similar solute descriptors. Thebenzoic acid derivatives differ only in the placement of the methyl and nitro functional groupsrelative to the -COOH group in the benzene ring.

6 E. HART ET AL.

Table4.

Comparison

betweenob

served

andback-calculatedmolar

solubilitiesof

2-methyl-3-nitrob

enzoicacid

basedup

onEquatio

n(1)andEquatio

n(2)andcalculated

values

formolecular

solute

descrip

tors.

Equatio

n(1)

Equatio

n(2)

Solvent

logC S

exp

log(C

S/C W

)exp

log(C

S/C W

)calc,a

logC S

calc

log(C

S/C G)exp

log(C

S/C G)calc,a

logC S

calc

1-Octanol

(wet)

2.160b

2.136b

8.897

8.889

1-Prop

anol

(dry)

−0.482

2.228

2.225

−0.485

8.965

8.956

−0.491

2-Prop

anol

(dry)

−0.496

2.214

2.206

−0.504

8.951

8.951

−0.496

1-Bu

tano

l(dry)

−0.567

2.143

2.139

−0.571

8.880

8.878

−0.569

1-Pentanol

(dry)

−0.628

2.082

2.098

−0.612

8.819

8.829

−0.618

1-Hexanol

(dry)

−0.655

2.055

2.067

−0.643

8.792

8.799

−0.648

1-Heptano

l(dry)

−0.695

2.015

2.041

−0.669

8.752

8.772

−0.675

1-Octanol

(dry)

−0.771

1.939

2.012

−0.698

8.676

8.672

−0.775

2-Bu

tano

l(dry)

−0.573

2.137

2.179

−0.531

8.874

8.896

−0.551

2-Methyl-1-propano

l(dry)

−0.727

1.983

2.065

−0.645

8.720

8.787

−0.660

3-Methyl-1-butanol

(dry)

−0.683

2.027

2.043

−0.667

8.764

8.786

−0.661

Diisop

ropyle

ther

(dry)

−1.105

1.605

1.593

−1.117

8.342

8.321

−1.126

Methyltert-bu

tyle

ther

(dry)

−0.536

2.174

1.994

−0.716

8.911

8.660

−0.787

1,4-Dioxane

(dry)

−0.091

2.619

2.691

−0.019

9.356

9.422

−0.025

Methylacetate

(dry)

−0.383

2.327

2.360

−0.350

9.064

9.074

−0.373

Ethylacetate

(dry)

−0.496

2.214

2.278

−0.432

8.951

9.016

−0.431

Prop

ylacetate(dry)

−0.572

2.138

2.212

−0.498

8.875

8.942

−0.505

Butylacetate

(dry)

−0.600

2.110

2.144

−0.566

8.847

8.867

−0.580

2-Etho

xyethano

l(dry)

−0.106

2.604

2.639

−0.071

9.341

9.371

−0.076

2-Prop

oxyethanol

(dry)

−0.174

2.536

2.500

−0.210

9.273

9.222

−0.225

2-Bu

toxyethano

l(dry)

−0.273

2.437

2.402

−0.308

9.174

9.127

−0.320

Gas-to-Water

6.737

6.715

6.737

6.734

a Num

ericalvalues

ofthedescrip

torsused

inthesecalculations

areas

follows:E=1.040,

S=1.396,

A=0.541,

B=0.532,

V=1.2468

andL=6.332.

bValueisthelogarithm

ofawater-to-1-octano

lpartitioncoefficient.

PHYSICS AND CHEMISTRY OF LIQUIDS 7

5. Conclusion

The Abraham solvation parameter model has been found to provide a reasonably accuratemathematical description of the observed solubility behavior of 2-methyl-3-nitrobenzoic aciddissolved in 10 alcohol (1-propanol, 1-butanol, 1-pentanol, 1-hexanol, 1-heptanol, 1-octanol, 2-propanol, 2-butanol, 2-methyl-1-propanol, 3-methyl-1-butanol), 3 alkyl ether (diisopropyl ether,methyl tert-butyl ether, 1,4-dioxane), 5 alkyl acetate (methyl acetate, ethyl acetate, propyl acetate,butyl acetate, pentyl acetate) and 3 alkoxyalcohol (2-ethoxyethanol, 2-propylethanol, 2-butox-yethanol) solvents. Abraham model solute descriptors determined as part of the present studyback-calculated the observed solubility data to within 0.06 log units. The very small differencebetween the measured solubility data and back-calculated values suggests that the derived solutedescriptors will enable one to predict the solubility of 2-methyl-3-nitrobenzoic acid in additionalorganic solvents in which the extent of dimerisation of the carboxylic acid solute is minimal.

Acknowledgements

Maribel Barrera thanks the University of North Texas and the U.S. Department of Education for support providedunder the Ronald E. McNair Postbaccalaureate Achievement Program.

Disclosure statement

No potential conflict of interest was reported by the authors.

References

[1] Garg RK, Sarkar D. Polymorphism control of p-aminobenzoic acid by isothermal anti-solvent crystallization. JCryst Growth. 2016;454:180–185.

[2] Alleso M, van den Berg F, Cornett C, et al. Solvent diversity in polymorph screening. J Pharm Sci.2008;97:2145–2159.

[3] Gu CH, Li H, Gandhi RB, et al. Grouping solvents by statistical analysis of solvent property parameters:implication to polymorph screening. Int J Pharm. 2004;283:117–125.

[4] Brittain HG, Grant DJR, Myrdal PB. Effects of polymorphism and solid-state solvation on solubility anddissolution rate. In: Brittain HG, Ed. Drugs and the pharmaceutical sciences. Vol. 192. New York (NY):Informa Healthcare; 2009. p. 436–480.

[5] Charlton AK, Daniels CR, Acree WE Jr, et al. Solubility of crystalline nonelectrolyte solutes in organicsolvents: mathematical correlation of acetylsalicylic acid solubilities with the Abraham general solvationmodel. J Solut Chem. 2003;32:1087–1102.

[6] Daniels CR, Charlton AK, Wold RM, et al. Mathematical correlation of naproxen solubilities in organicsolvents with the Abraham solvation parameter model. Phys Chem Liq. 2004;42:481–491.

[7] Blake-Taylor BH, Deleon VH, Acree WE Jr, et al. Mathematical correlation of salicylamide solubilities inorganic solvents with the Abraham solvation parameter model. Phys Chem Liq. 2007;45:389–398.

[8] Abraham MH, Acree WE Jr, Brumfield M, et al. Deduction of physicochemical properties from solubilities:2,4-dihydroxybenzophenone, biotin, and caprolactam as examples. J Chem Eng Data. 2015;60:1440–1446.

[9] Acree WE Jr, Bowen KR, Horton MY, et al. Computation of Abraham model solute descriptors for 3-methyl-4-nitrobenzoic acid from measured solubility data. Phys Chem Liq. 2016:1–10. Ahead of Print. DOI:10.1080/00319104.2016.1227813

[10] Schmidt A, Grover D, Zettl H, et al. Determination of Abraham model solute descriptors for isophthalic acidfrom experimental solubility data in organic solvents at 298 K. Phys Chem Liq. 2016;54:747–757.DOI:10.1080/00319104.2016.1149178

[11] Brumfield M, Wadawadigi A, Kuprasertkul N, et al. Determination of Abraham model solute descriptors forthree dichloronitrobenzenes from measured solubilities in organic solvents. Phys Chem Liq. 2015;53:163–173.

[12] Deng T, Acree WE Jr. Solubility of anthracene in ternary propanol + butanol + cyclohexane solvent mixtures.J Chem Eng Data. 1998;43:1062–1064.

[13] Pribyla KJ, Spurgin MA, Chuca I, et al. Solubility of anthracene in ternary 1,4-dioxane + alcohol + heptanesolvent mixtures at 298.15 K. J Chem Eng Data. 2000;45:965–967.

[14] Pribyla KJ, Spurgin MA, Chuca I, et al. Solubility of anthracene in ternary dibutyl ether + alcohol + 2,2,4-trimethylpentane solvent mixtures. J Chem Eng Data. 1999;44:1265–1268.

8 E. HART ET AL.

[15] Pribyla KJ, Ezell C, van TT, et al. Solubility of anthracene in ternary methyl tert-butyl ether + alcohol + 2,2,4-trimethylpentane solvent mixtures at 298.15 K. J Chem Eng Data. 2000;45:974–976.

[16] Debase EM, Acree WE Jr. Solubility of pyrene in ternary alcohol + cyclohexane + heptane solvent mixtures at299.15 K. J Chem Eng Data. 2001;46:1297–1299.

[17] Fishback S, Duenas S, Kuehn N, et al. Solubility of pyrene in ternary propanol + butanol + heptane solventmixtures at 299.15 K. J Chem Eng Data. 2002;47:62–64.

[18] Debase EM, Acree WE Jr. Solubility of pyrene in ternary propanol + butanol + cyclohexane solvent mixturesat 299.15 K. J Chem Eng Data. 2001;46:991–993.

[19] Abraham MH, Smith RE, Luchtefeld R, et al. Prediction of solubility of drugs and other compounds inorganic solvents. J Pharm Sci. 2010;99:1500–1515.

[20] Brumfield M, Acree WE Jr, Abraham MH. Abraham model correlations for describing solute transfer intodiisopropyl ether. Phys Chem Liq. 2015;53:25–37.

[21] Brumfield M, Wadawadigi A, Kuprasertkul N, et al. Abraham model correlations for solute transfer intotributyl phosphate from both water and the gas phase. Phys Chem Liq. 2015;53:10–24.

[22] Sedov IA, Khaibrakhmanova D, Hart E, et al. Development of Abraham model correlations for solute transferinto both 2-propoxyethanol and 2-isopropoxyethanol at 298.15 K. J Mol Liq. 2015;212:833–840.

[23] Stovall DM, Dai C, Zhang S, et al. Abraham model correlations for describing solute transfer into anhydrous1,2-propylene glycol for neutral and ionic species. Phys Chem Liq. 2016;54:1–13.

[24] E Cheeran SLittle GE, et al. Abraham model expressions for describing water-to-organic solvent and gas-to-organic solvent partition coefficients for solute transfer into anhydrous poly(ethylene glycol) dialkyl ethersolvents at 298.15 K. Phys Chem Liq. 2017;55:347–357. DOI: doi:10.1080/00319104.2016.1218008

[25] Sedov IA, Salikov T, Hart E, et al. Abraham model linear free energy relationships for describing thepartitioning and solubility behavior of nonelectrolyte organic solutes dissolved in pyridine at 298.15 K.Fluid Phase Equilib. 2017;431:66–74.

[26] Abraham MH, Acree WE Jr. Equations for the partition of neutral molecules, ions and ionic species fromwater to water-methanol mixtures. J Solut Chem. 2016;45:861–874.

[27] Abraham MH, Acree WE Jr. Equations for the partition of neutral molecules, ions and ionic species fromwater to water-ethanol mixtures. J Solut Chem. 2012;41:730–740.

[28] Abraham MH, Acree WE Jr. Partition coefficients and solubilities of compounds in the water-ethanol solventsystem. J Solut Chem. 2011;40:1279–1290.

[29] Jiang B, Horton MY, Acree WE Jr, et al. Ion-specific equation coefficient version of the Abraham model forionic liquid solvents: determination of coefficients for tributylethylphosphonium, 1-butyl-1-methylmorpho-linium, 1-allyl-3-methylimidazolium and octyltriethylammonium cations. Phys Chem Liq. 2016:1–28. inpress. DOI:10.1080/00319104.2016.1218009

[30] Abraham MH, Acree WE Jr. Equations for the transfer of neutral molecules and ionic species from water toorganic phases. J Org Chem. 2010;75:1006–1015.

[31] Abraham MH, Acree WE Jr. Solute descriptors for phenoxide anions and their use to establish correlations ofrates of reaction of anions with iodomethane. J Org Chem. 2010;75:3021–3026.

[32] Endo S, Brown TN, Watanabe N, et al. UFZ-LSER database v 3.1 [Internet], Leipzig, Germany, HelmholtzCentre for Environmental Research-UFZ. 2015 [cited 2016 Nov 08; cited 2017 Jan 8]. Available from http://www.ufz.de/lserd

[33] Fritz JS, Lisicki NM. Titration of acids in nonaqueous solvents. Anal Chem. 1951;23:589–591.[34] BioLoom. BioByte Corp. USA. 201W. 4th Street, #204 Claremont, CA 91711–4707.[35] Bradley J-C, Abraham MH, Acree WE Jr, et al. Determination of Abraham model solute descriptors for the

monomeric and dimeric forms of trans-cinnamic acid using measured solubilities from the open notebookscience challenge. Chem Central J. 2015;9:11/1-11/6.

[36] Abraham MH, McGowan JC. The use of characteristic volumes to measure cavity terms in reversed phaseliquid chromatography. Chromatographia. 1987;23:243–246.

[37] Absolv. ADME suite 5.0, Advanced Chemistry Development. Canada. 110 Yonge Street, 14th Floor, Toronto,Ontario, M5C 1T4,.

[38] Platts JA, Butina D, Abraham MH, et al. Estimation of molecular linear free energy relation descriptors usinga group contribution approach. J Chem Inf Comp Sci. 1999;39:835–845.

[39] Platts JA, Abraham MH, Butina D, et al. Estimation of molecular linear free energy relationship descriptors bya group contribution approach. 2. Prediction of partition coefficients. J Chem Inf Comp Sci. 2000;40:71–80.

[40] Advanced Chemistry Development, 110 Yonge St., 14th Floor, Toronto, Ontario M5C 1T4, Canada. The ACDFreeware Available from: http://www.acdlabs.com/

PHYSICS AND CHEMISTRY OF LIQUIDS 9

本文献由“学霸图书馆-文献云下载”收集自网络，仅供学习交流使用。

学霸图书馆（www.xuebalib.com）是一个“整合众多图书馆数据库资源，

提供一站式文献检索和下载服务”的24 小时在线不限IP

图书馆。

图书馆致力于便利、促进学习与科研，提供最强文献下载服务。

图书馆导航：

图书馆首页 文献云下载 图书馆入口 外文数据库大全 疑难文献辅助工具