(Cyclopentanone, Cyclohexanone): Alcohol (methanol, ethanol)

Supporting Information: Solvent

Polarity

of

Cyclic

Ketone

(Cyclopentanone,

Cyclohexanone): Alcohol (methanol, ethanol) Renewable MixedSolvent Systems for Applications in Pharmaceutical and Chemical Processing Alif Duereh,† Haixin Guo, ‡ Tetsuo Honma,§ Yuya Hiraga‡, Yoshiyuki Sato,† Richard Lee Smith Jr.*†, ‡ and Hiroshi Inomata† †

Graduate School of Engineering, Research Center of Supercritical Fluid Technology, Tohoku University, Aramaki Aza Aoba 6-6-11, Aoba-ku, Sendai 980-8579, Japan ‡ Graduate School of Environmental Studies, Research Center of Supercritical Fluid Technology, Tohoku University, Aramaki Aza Aoba 6-6-11, Aoba-ku, Sendai 980-8579, Japan § Material and Biological Engineering Course, Department of Industrial System Engineering, National Institute of Technology, Hachinohe College, 16-1 Uwanotai, Tamonoki-Aza, Hachinohe, 039-1192, Japan.

*Corresponding Author Tel (Fax): +81-22-795-5863, e-mail: [email protected]

Numbers of Pages: 39 Numbers of Figures: 13 Numbers of Tables: 17

S1

Table of contents

Section A Table S1 Table S2 Table S3 Table S4 Table S5 Table S6 Table S7 Figure S1 Figure S2 Figure S3 Figure S4

Section B Table S8 Table S9 Table S10 Table S11 Table S12 Table S13 Table S14 Figure S5 Figure S6 Figure S7

Section C Table S15 Table S16 Table S17 Figure S8 Figure S9 Figure S10 Figure S11 Figure S12 Figure S13

Page S3 Kamlet-Taft parameters Experimental Kamlet-Taft solvatochromic parameters of pure solvents S5 Experimental wavenumber of indicators and Kamlet-Taft solvatochromic S6 parameters for the methanol and cyclohexanone mixed-solvent system Experimental wavenumber of indicators and Kamlet-Taft solvatochromic S7 parameters for the methanol and cyclopentanone mixed-solvent system Experimental wavenumber of indicators and Kamlet-Taft solvatochromic S8 parameters for the ethanol and cyclohexanone mixed-solvent system Experimental wavenumber of indicators and Kamlet-Taft solvatochromic S9 parameters for the ethanol and cyclopentanone mixed-solvent system Preferential solvation parameters of hydrogen bond (HBD) donor solvents S10 and hydrogen bond (HBA) acceptor solvent mixtures Sensitivity of preferential solvation parameters S11 Comparison of KT values calculated from original and modified methods S12 Sensitivity of preferential solvation parameters from dipolarity data S13 Sensitivity of preferential solvation parameters from basicity data S14 Sensitivity of preferential solvation parameters from acidity data S15 S16 Density and viscosity Effect of water on densities and dynamic viscosities of pure methanol S18 Actual calibration values used for density and viscosity calibrations S19 Densities and dynamic viscosities of pure solvents S20 Densities and dynamic viscosities of methanol –cyclohexanone mixtures S21 Densities and dynamic viscosities of methanol-cyclopentanone mixtures S22 Densities and dynamic viscosities of ethanol-cyclohexanone mixtures S23 Densities and dynamic viscosities of ethanol - cyclopentanone mixtures S24 Deviation plot in density data for pure solvents S25 Relative deviation plot s in viscosity data for pure solvents S26 Deviation plot in density data for solvent mixtures S27 S28 IR spectra and working compositions IR spectral shift of C=O stretching and fraction of H-bond S29 Dielectric relaxation time and reorientation activation free energy of S30 methanol along with Kamlet-Taft parameters Kamlet-Taft windows for API dissolution ideal working compositions (of S31 hydrogen bond donor and hydrogen bond acceptor mixed solvent systems IR spectra for methanol-cyclohexanon mixed-solvent system S32 IR spectra for methanol-cyclopentanone mixed-solvent system S33 IR spectra for ethanol-cyclohexanon mixed-solvent system S34 IR spectra for ethanol-cyclopentanone mixed-solvent system S35 Mixed-solvent systems of cyclohexanone -methanol and -ethanol S36 Plots of C=O spectral shift and fraction of H-bond for propanol - methyl S37 ethyl ketone mixture and methanol-cyclohexanone mixture

S2

Section A Kamlet-Taft parameters Kamlet-Taft parameters (π*, β, α) were determined by measuring the maximum absorption wavenumbers ( vmax ) of indicators in a solvent and using the original method of Kamlet and Taft [1-4] with following empirical equations: Indicator 1-

   (28.10  vmax1 ) / 3.52

(S1)

Indicator 2-

  (0.984vmax1  3.49  vmax 2 ) / 2.759

(S2)

Indicator 3-

  (1.318vmax1  47.7  vmax3 ) / 5.47

(S3)

where vmax is the wavenumber in units of kiloKaiser (1kK=1,000 cm-1=10,000/λmax (nm)) obtained from the UV-Vis spectrophotometer. Indicators for the π*-scale (e.g. dimethyl-4-nitroaniline and 4-nitroanisole) respond to solvent dipolarity/polarizability with no specific hydrogen bond with the solvent. The π*scale was normalized to have a value of zero for cyclohexane and a value of one for dimethyl sulfoxide [1]. Both original and modified methods provide similar results for the π*-scale. Indicators for the β-scale (e.g. 4-nitroaniline and 4-nitrophenol) respond to both solvent dipolarity/polarizability and solvent basicity (hydrogen-bond acceptor). Thus, to obtain only basicity, pair of indicators (e.g. dimethyl-4-nitroaniline with 4-nitroaniline and 4-nitroanisole with 4-nitrophenol) with analogues molecular structures are used to subtract the effect of dipolarity/polarizability as proposed in original method (eqs. (S1)-(S3)). Although a pair of indicators is required to calculate basicity from the modified method (eqs. (1)-(4), main text), the pair of indicators do not need to have analogous molecular structures because basicity is calculated from averaging the π* values. The β-scale was normalized to have a value of one for hexamethylphosphoramide [3]. Indicators for the α-scale (e.g. 2,6-diphenyl-4-(2,4,6-triphenylpyridinio) phenolate) respond to both solvent dipolarity/polarizability and solvent acidity (hydrogen-bond donor) S3

and thus a pair of indicators were used to subtract the effects of dipolarity/polarizability, which is similar to the β-scale. The α-scale was normalized to have a value of one for methanol [4]. Figure S1 show comparisons of β and α values of the HBD-HBA solvent mixtures calculated from original and modified methods. The β and α values from modified method (Fig. S1) were slightly higher than those from original method within the uncertainties. In general, β values obtained from modified method with multiple indicators are higher 1.16 time than those from original methods reported from literature [5]. In this work, modified method was used to calculate KT parameters for estimating working composition. The preferential solvation model (eqs. (6)-(8)) could correlate the experimental KT data with R2 > 0.99 (Table S6, Supporting Information). The preferential solvation parameters obtaining by fitting the KT data are tabulated in Table S6 and interpretation of these parameters (Table S6) is accordance with discussion of Table 1 (main text). KT parameters of methanol-cyclohexanone mixtures were used to discuss sensitivity of preferential solvation parameters (f2/1 and f12/1) and complex KT parameters (  12 , β12, α12) *

with number of data and composition ranges as shown in Table S7 and Figures S2-S4. With sufficient data fitted (n > 7), the preferential solvation parameters and complex KT parameters reached constant values (Table S7 and Figs. S2-S4). Although complex KT parameters (  12 , β12, α12) seemed to insensitive with number of data (Table S7), they greatly *

affected quality fit of preferential solvation model (eqs. (6)-(8), main text) for KT parameters.

S4

Table S1. Experimental (Exp.) Kamlet-Taft solvatochromic parameters of pure methanol (MeOH), ethanol (EtOH), cyclohexanone (CHN), cyclopentanone (CPN) at 25 °C with comparisons with literature values. Solventa MeOH

EtOH

CHN CPN

Dipolarity/polarizability (*) Exp. Ref. 0.71a, b 0.60 [6] 0.60 [7] 0.77 [8] 0.73 [9] 0.65a, b 0.54 [6] 0.54 [7] 0.65 [10] 0.72 [9] a, b 0.76 0.68 [6] 0.76 [7] a, b 0.76 0.71 [6] 0.76 [7]

Basicity (β) Exp. Ref. 0.66a 0.66 [6] 0.69b 0.62 [7] 0.58 [8] 0.63 [9] 0.77a 0.75b [6] 0.79b 0.77 [7] 0.76 [10] 0.72 [9] a 0.52 0.53 [6] 0.56b 0.53 [7] a 0.53 0.52 [6] b 0.56 0.52 [7]

Acidity (α) Exp. Ref. 0.99 a 0.98 [6] 1.04b 0.93 [7] 1.03 [8] 1.05 [9] 0.83a 0.86 [6] b 0.86 0.83 [7] 0.82 [10] 0.87 [9] a, b 0.00 0.00 [6] a, b 0.00 0.00 [6] -

Uncertainties: u (π*) = ±0.03, u (β) = ±0.05 and u (α) = ±0.07 a

calculated from original method (eqs. (S1)-(S3), Section A, Supporting Information).

b

calculated from modified method (eqs. (1)-(4), main text).

S5

Table S2. Experimental wavenumber ( vmix ) of indicators and calculated Kamlet-Taft solvatochromic parameters for the methanol (MeOH, component 1) and cyclohexanone (CHN, component 2) mixed-solvent system at 25 °C calculated from original and modified methods. Indicator 1 for dipolarity/polarizability (*) was N, N-dimethyl-4-nitroaniline; indicator 2 for basicity (β) was 4-nitroaniline; indicator 3 for acidity (α) was 2, 6-diphenyl-4-(2,4,6-triphenyl-1-pyridinio) phenolate. x2

0.00 0.04 0.08 0.12 0.18 0.25 0.33 0.43 0.57 0.75 1.00

vmix (kK) of indicator Ind. 1 Ind. 2 Ind. 3 25.68 26.95 19.29 25.63 26.90 19.07 25.60 26.89 18.95 25.58 26.89 18.84 25.55 26.89 18.75 25.52 26.89 18.59 25.50 26.91 18.42 25.47 26.92 18.20 25.46 26.94 17.86 25.49 27.06 17.22 25.51 27.15 14.01

Dipolarity/polarizability (*) Original Modified 0.71 0.71 0.72 0.72 0.73 0.73 0.74 0.74 0.75 0.75 0.76 0.76 0.76 0.76 0.77 0.77 0.77 0.77 0.76 0.76 0.76 0.76

Basicity (β) Original Modified 0.66 0.69 0.66 0.69 0.65 0.68 0.64 0.67 0.63 0.67 0.62 0.66 0.61 0.64 0.59 0.63 0.58 0.62 0.55 0.59 0.52 0.56

Uncertainties: u (x2) = ±1.010-4, u ( vmix ) = ±0.05, u (π*) = ±0.03, u (β) = ±0.05 and u (α) = ±0.07.

S6

Acidity (α) Original 0.99 0.94 0.91 0.89 0.86 0.83 0.79 0.75 0.68 0.57 0.00

Modified 1.04 0.99 0.96 0.93 0.91 0.88 0.84 0.79 0.73 0.62 0.00

Table S3. Experimental wavenumber ( vmix ) of indicators and calculated Kamlet-Taft solvatochromic parameters for the methanol (MeOH, component 1) and cyclopentanone (CPN, component 2) mixed-solvent system at 25 °C calculated from original and modified methods. Indicator 1 for dipolarity/polarizability (*) was N, N-dimethyl-4-nitroaniline; indicator 2 for basicity (β) was 4-nitroaniline; indicator 3 for acidity (α) was 2, 6-diphenyl-4-(2,4,6-triphenyl-1-pyridinio) phenolate.

x2

0.00 0.04 0.09 0.14 0.20 0.28 0.36 0.47 0.60 0.77 1.00

vmix (kK) of indicator Ind. 1 Ind. 2 Ind. 3 25.68 26.95 19.29 25.66 26.91 19.06 25.62 26.88 19.01 25.58 26.88 18.86 25.54 26.88 18.71 25.51 26.89 18.44 25.48 26.91 18.33 25.46 26.93 18.24 25.44 26.98 17.88 25.44 27.04 17.22 25.49 27.12 13.99

Dipolarity/polarizability (*) Original Modified 0.71 0.71 0.72 0.72 0.73 0.73 0.74 0.74 0.75 0.75 0.76 0.76 0.77 0.77 0.77 0.77 0.78 0.78 0.78 0.78 0.76 0.76

Basicity (β) Original Modified 0.66 0.69 0.66 0.70 0.66 0.69 0.65 0.68 0.63 0.67 0.62 0.65 0.60 0.64 0.59 0.62 0.56 0.60 0.54 0.58 0.53 0.56

Uncertainties: u (x2) = ±1.010-4, u ( vmix ) = ±0.05, u (π*) = ±0.03, u (β) = ±0.05 and u (α) = ±0.07.

S7

Acidity (α) Original 0.99 0.95 0.93 0.89 0.86 0.80 0.77 0.75 0.68 0.56 0.00

Modified 1.04 0.99 0.97 0.94 0.90 0.84 0.82 0.80 0.73 0.61 0.00

Table S4. Experimental wavenumber ( vmix ) of indicators and calculated Kamlet-Taft solvatochromic parameters for the ethanol (EtOH, component 1) and cyclohexanone (CHN, component 2) mixed-solvent system at 25 °C calculated from original and modified methods. Indicator 1 for dipolarity/polarizability (*) was N, N-dimethyl-4-nitroaniline; indicator 2 for basicity (β) was 4-nitroaniline; indicator 3 for acidity (α) was 2, 6-diphenyl-4-(2,4,6-triphenyl-1-pyridinio) phenolate. x2 0.00 0.05 0.11 0.17 0.24 0.32 0.41 0.52 0.65 0.81 1

vmix (kK) of indicator Ind. 1 Ind. 2 Ind. 3 25.90 26.85 18.08 25.85 26.82 17.99 25.75 26.81 17.94 25.70 26.83 17.89 25.65 26.84 17.84 25.61 26.86 17.76 25.57 26.88 17.59 25.53 26.91 17.38 25.50 26.95 17.05 25.51 27.01 16.24 25.51 27.15 14.01

Dipolarity/polarizability (*) Original Modified 0.65 0.65 0.66 0.66 0.69 0.69 0.71 0.71 0.72 0.72 0.73 0.73 0.74 0.74 0.75 0.75 0.76 0.76 0.76 0.76 0.76 0.76

Basicity (β) Original Modified 0.77 0.79 0.76 0.79 0.73 0.76 0.71 0.74 0.69 0.72 0.66 0.70 0.64 0.68 0.62 0.65 0.59 0.63 0.57 0.61 0.52 0.56

Uncertainties: u (x2) = ±1.010-4, u ( vmix ) = ±0.05, u (π*) = ±0.03, u (β) = ±0.05 and u (α) = ±0.07.

S8

Acidity (α) Original 0.83 0.80 0.76 0.74 0.72 0.70 0.66 0.61 0.54 0.39 0.00

Modified 0.86 0.83 0.80 0.78 0.76 0.74 0.70 0.65 0.58 0.44 0.00

Table S5. Experimental wavenumber ( vmix ) of indicators and calculated Kamlet-Taft solvatochromic parameters for the ethanol (EtOH, component 1) and cyclopentanone (CPN, component 2) mixed-solvent system at 25 °C calculated from original and modified methods. Indicator 1 for dipolarity/polarizability (*) was N, N-dimethyl-4-nitroaniline; indicator 2 for basicity (β) was 4-nitroaniline; indicator 3 for acidity (α) was 2, 6-diphenyl-4-(2,4,6-triphenyl-1-pyridinio) phenolate. x2 0.00 0.06 0.12 0.19 0.27 0.35 0.45 0.56 0.69 0.83 1.00

vmix (kK) of indicator Ind. 1 Ind. 2 Ind. 3 25.90 26.85 18.08 25.84 26.85 18.10 25.74 26.84 18.05 25.68 26.86 17.98 25.63 26.87 17.90 25.59 26.88 17.78 25.56 26.93 17.64 25.53 26.95 17.40 25.50 26.99 17.04 25.49 27.05 16.30 25.49 27.12 13.99

Dipolarity/polarizability (*) Original Modified 0.65 0.65 0.66 0.66 0.69 0.69 0.71 0.71 0.72 0.72 0.74 0.74 0.75 0.75 0.75 0.75 0.76 0.76 0.77 0.77 0.76 0.76

Basicity (β) Original Modified 0.77 0.79 0.75 0.77 0.72 0.74 0.69 0.72 0.67 0.70 0.65 0.68 0.62 0.65 0.60 0.64 0.58 0.61 0.55 0.59 0.53 0.56

Uncertainties: u (x2) = ±1.010-4, u ( vmix ) = ±0.05, u (π*) = ±0.03, u (β) = ±0.05 and u (α) = ±0.07.

S9

Acidity (α) Original 0.83 0.81 0.78 0.75 0.73 0.70 0.66 0.61 0.54 0.40 0.00

Modified 0.86 0.85 0.82 0.80 0.77 0.74 0.71 0.66 0.58 0.44 0.00

Table S6. Preferential solvation parameters (f2/1, f12/1) from the preferential solvation model (eqs. (6)-(8), main text) with solvent mixtures of hydrogen bond (HBD) donor solvents and hydrogen bond (HBA) acceptor solvent (component 2) using experimental Kamlet-Taft data in Tables S2-S5, at 25 °C. HBD solvents (component 2) are methanol (MeOH) and ethanol (EtOH). HBA solvents (component 1) are cyclopentanone (CPN) and cyclohexanone (CHN).

MeOH-CHN MeOH-CPN EtOH-CHN EtOH-CPN

 2*

 12*

f2/1

f12/1

0.71 0.71 0.65 0.65 β1

0.76 0.76 0.76 0.76 β2

0.79 0.81 0.78 0.78 β12

3.59 1.14 2.79 1.90 f2/1

4.35 0.209 2.28 0.194 3.15 0.278 3.27 0.286 f12/1 %AAD

0.984 0.992 0.993 0.992 R2

Original Modified Original Modified Original Modified Original Modified

0.66 0.69 0.66 0.69 0.77 0.79 0.77 0.79 α1

0.52 0.56 0.53 0.56 0.52 0.56 0.53 0.56 α2

0.64 0.69 0.69 0.71 0.62 0.76 0.59 0.66 α12

11.19 45.46 21.31 33.93 1.23 18.49 1.17 2.23 f2/1

10.22 0.407 41.28 0.316 8.08 0.384 18.81 0.347 3.00 0.572 16.56 0.666 2.73 0.401 3.54 0.372 f12/1 %AAD

0.993 0.993 0.994 0.996 0.993 0.989 0.997 0.997 R2

Original Modified Original Modified Original Modified Original Modified

0.99 1.04 0.99 1.04 0.83 0.86 0.83 0.86

0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00

0.81 0.83 0.72 0.79 0.68 0.75 0.65 0.67

Acidity (α) MeOH-CHN MeOH-CPN EtOH-CHN EtOH-CPN

%AAD =

1 N



R2

 1*

Kamlet-Taft Method (HBD(1)-HBA(2)) Dipolarity/polarizability (π*) MeOH-CHN Both MeOH-CPN Both EtOH-CHN Both EtOH -CPN Both Basicity (β)

KTCal  KTExp KTExp

 100

S10

1.89 11.75 0.87 6.52 0.38 3.71 0.41 4.19 0.84 4.63 0.97 5.62 0.34 2.38 0.21 1.74

%AAD

0.999 0.507 0.811 0.804 0.501 0.374 0.319 0.232

0.999 0.999 0.999 0.999 0.999 0.999 0.999 0.999

Table S7. Sensitivity of preferential solvation parameters (f2/1, f12/1) from the preferential solvation model (eqs. (6)-(8), main text) for methanol (1)-cyclohexanone (2) with number of data fitted at 25 °C (see Figs. S2-S4). Data point

x2

(n)

range

f2/1

f12/1

 12*

1*

 2*

%AAD

R2

Dipolarity/polarizability (π*) 3

0-0.04

3.01

1.99

0.90

0.71

0.76

0.001

0.993

5

0-0.13

3.59

12.38

0.76

0.71

0.76

0.053

0.993

7

0-0.25

2.80

6.48

0.78

0.71

0.76

0.127

0.988

9

0-0.43

1.60

4.94

0.78

0.71

0.76

0.134

0.990

11

0-1.00

3.59

4.35

0.79

0.71

0.76

0.209

0.984

f2/1

f12/1

β12

β1

β2

%AAD

R2

Basicity (β) 3

0-0.04

45.48

40.88

0.70

0.69

0.56

0.001

0.997

5

0-0.13

42.50

31.35

0.69

0.69

0.56

0.095

0.997

7

0-0.25

44.52

35.83

0.69

0.69

0.56

0.063

0.998

9

0-0.43

48.90

40.51

0.69

0.69

0.56

0.147

0.997

11

0-1.00

45.46

41.28

0.69

0.69

0.56

0.316

0.993

f2/1

f12/1

α12

α1

α2

%AAD

R2

Acidity (α) 3

0-0.04

0.39

5.21

0.85

1.04

0.00

0.001

0.999

5

0-0.13

0.39

5.21

0.85

1.04

0.00

0.095

1.000

7

0-0.25

0.79

8.57

0.85

1.04

0.00

0.350

1.000

9

0-0.43

0.85

6.92

0.84

1.04

0.00

0.510

0.999

11

0-1.00

0.87

6.52

0.83

1.04

0.00

0.507

0.999

S11

0.8

1.0

(a)

(e)

0.8





0.7

0.6 0.4

0.6

0.2 0.5

0.0 0.8

1.0

(b)





0.7

(f)

0.8 0.6 0.4

0.6

0.2 0.5

0.0 1.0

(c)

0.8

(g)

0.8





0.7

0.6 0.4

0.6

0.2 0.5

0.0 1.0

(d)

0.8

(h)

0.8





0.7

0.6 0.4

0.6

0.2 0.5

0.0 0.0

0.2

0.4

0.6

0.8

1.0

0.0

x2bulk

0.2

0.4

0.6

0.8

1.0

x2bulk

Figure S1. Comparison of basicity (β) and acidity (α) calculated from original (open symbols) and modified (filled symbols) methods for methanol-cyclohexanone ( CHN), methanol-cyclopentanone ( ethanol-cyclopentanone (

MeOH-

MeOH-CPN), ethanol-cyclohexanone ( EtOH-CHN),

EtOH-CPN) mixed-solvent systems at 25 °C as a function of

bulk mole fraction of component 2 ( x2bulk , CHN or CPN).

S12

0.8

n=5

n =3

f2/1

0.9 0.7 0.8 0.6

n=7 2.5

n=9 1.5 12

9

n=7

0.6 0.8 0.9

6

3

n=9

0.5 0.7

0.9

π*12

0.8 0.6

π*

n = 11

n=3

2.0

n=5

0.9 0.7 0.5 0.8 0.6 0.7 0.9 0.5

π*

3.0

f12/1

π*

π*

π*

3.5

0.5

0.8 0.7

0.7

n = 11 0.0

0.2

0.4

0.6

0.8

1.0

x2bulk

0.6

0.0

0.2

0.4

0.6

0.8

1.0

x2bulk

Figure S2. Sensitivity of preferential solvation parameters (f2/1, f12/1,

 12* ) from

dipolarity/polarizability (π*) data (eq. (6), main text) for methanol (1)-cyclohexanone (2) with number of data (n) fitted at 25 °C (see Table S7).

S13

50

n =3

0.7

n=9

f2/1



48

0.9 0.6



0.8

f12/1

n=7

0.6 0.8

40

35

0.9 0.5 0.7

30

n=9

0.8

0.8 0.6 0.7 0.5

n = 11

β12



n=5

45

0.5 0.7 0.9



n=7

44

40

0.6 0.8



n = 11

n=3

42

n=5

0.5 0.7 0.9

46

0.7

0.6

0.6

0.5 0.0

0.2

0.4

0.6

0.8

1.0

x2bulk

0.5

0.0

0.2

0.4

0.6

0.8

1.0

x2bulk

Figure S3. Sensitivity of preferential solvation parameters (f2/1, f12/1, β12) from basicity data (β) (eq. (7), main text) for methanol (1)-cyclohexanone (2) with number of data (n) fitted at 25 °C (see Table S7).

S14

n =3

0.9

0.6

α

1.0 0.4

0.5

0.6 0.0

0.4

n=3 n=5

9

n=7

8

0.8 0.2

f12/1

α

n=7

0.7

0.8 0.2

0.6 0.0

7 6

0.4 1.0

α

n = 11

0.6

n=5

1.0 0.4

n=9

0.2 0.8

5

0.0 0.6

4

1.0 0.4

1.0

n = 11

0.9

α12

0.8 0.2

α

n=9

0.8

0.8

f2/1

α

1.0

0.6 0.0

0.8

0.4 0.7

0.2 0.6

0.0 0.0

0.2

0.4

0.6 bulk 2

0.8

1.0

0.0

0.2

0.4

0.6

0.8

1.0

bulk 2

x

x

Figure S4. Sensitivity of preferential solvation parameters (f2/1, f12/1, α12) from acidity data (α) (eq. (8), main text) for methanol (1)-cyclohexanone (2) with number of data (n) fitted at 25 °C (see Table S7).

S15

Section B Density and viscosity Experimental ρ and η data for pure solvents and HBD-HBA mixed-solvent systems used in this work are tabulated in Tables S8-S14 (Supporting Information). Cyclohexanone (reagent plus, 99.8%) and cyclopentanone (reagent plus, 99.8%) were purchased from SigmaAldrich Co. Methanol (100.0%) and ethanol (100.0%) were purchased from Wako Pure Chemical Industries, Ltd. Mass fraction basis water contents of the solvents ( 10  wH2O ) were 6

measured by Karl Fischer titration.

Those value before (after) the measurements were

determined as 644 (679), 760 (751),