Oldenburg Progress Report 06/08/2009 1

Activity of Complex Multifunctional Organic

Compounds in Common Solvents

Bruce Moller

Juergen Rarey

Deresh Ramjugernath

Oldenburg Progress Report 06/08/2009 2

Overview

� Motivation

� Current Methods

� Plan of Action

� Applications

� Future Work

Oldenburg Progress Report 06/08/2009 3

Project Motivation

� Solute activity required for:

� Design of separation equipment

� Partitioning between compartments

� Dispensing of drugs

� …

Oldenburg Progress Report 06/08/2009 4

Some Current Methods

� Group contribution methods

� UNIFAC, Mod. UNIFAC (Do)

� Quantum chemical methods

� COSMO-RS/SAC

� Molecular simulation

� Problems …

Oldenburg Progress Report 06/08/2009 5

Proposed Plan of Action

� Reference solvents

Dispersive e.g.

Hexane

H-bonding e.g.

Water

Dispersive &

H-bonding

e.g. Alcohols

Oldenburg Progress Report 06/08/2009 6

Simplify the Problem

� Solvent

� Reference solvents

� Concentration

� Solid solubility data mainly of interest

� Infinite dilution (x < 0.01)

� Pressure

� Small at low to moderate pressures

� Temperature

� Non-trivial

� 298 K

( , , , , )f x T P solvent soluteγ =

Oldenburg Progress Report 06/08/2009 7

Simplify the Problem

� Pure component property

� Trained to data for a single solvent

solute in solvent

1ln

2 ( )

i j

i ii i j

GIv C

n mγ

−∞= +∑ ∑∑

Group Contributions Group Interactions

298 , ( )K solvent f soluteγ ∞ =

vi – group frequency

Ci - group contribution

GI – interaction

contribution

n – number of non-H

atoms

m – number of

interaction groups

Oldenburg Progress Report 06/08/2009 8

Available Data

� Most frequent solvents in the γ∞ DDB

� Water

� Others ??? Solvent No. Solutes

Water 585

Squalane 207

Hexadecane 198

Sulfolane 137

1-Octanol 128

Phthalic acid dinonyl ester 126

Heptane 116

N-Methyl-2-pyrrolidone 115

Octadecane 103

19,24-Dioctadecyldotetracontane 99

alkane

water

Oldenburg Progress Report 06/08/2009 9

Results for Infinite Dilution Activity

Coefficients in Water @ 298 K

30.0 29523.4 29514.9 39623.7 4427.3 630All compounds

COSMO-

SAC**

COSMO-

RS(OL)**

Mod.

UNIFAC*UNIFAC*

This

WorkName

Typically 2nd best, far

superior to the other

literature methods

Significantly lower

relative mean

deviation (%) in lnγ∞More generally applicable

(greater number of

compounds) * Consortium version 2008

** Based on B3LYP-6-311G(d,p)

Oldenburg Progress Report 06/08/2009 10

Available Data

� Most frequent solvents in the γ∞ DDB

� Water

� Others ??? Solvent No. Solutes

Water 585

Squalane 207

Hexadecane 198

Sulfolane 137

1-Octanol 128

Phthalic acid dinonyl ester 126

Heptane 116

N-Methyl-2-pyrrolidone 115

Octadecane 103

19,24-Dioctadecyldotetracontane 99

alkane

water

Oldenburg Progress Report 06/08/2009 11

Reduction to a Common Solvent - Hexane

� Combinatorial and residual contribution

� Solution of groups concept

1 1 1

, ,

, , ,

R C

hexane hexane hexaneγ γ γ∞ ∞ ∞= ×

1 1 1

, ,

, , ,

R C

squalane squalane squalaneγ γ γ∞ ∞ ∞= ×

Oldenburg Progress Report 06/08/2009 12

Reduction to a Common Solvent - Hexane

� Combinatorial and residual contribution

� Solution of groups concept

1 1 1

, ,

, , ,

R C

hexane hexane hexaneγ γ γ∞ ∞ ∞= ×

1 1 1

, ,

, , ,

R C

squalane squalane squalaneγ γ γ∞ ∞ ∞= ×

Oldenburg Progress Report 06/08/2009 13

Reduction to a Common Solvent - Hexane

� Combinatorial and residual contribution

� Solution of groups concept

1 1 1

, ,

, , ,

R C

hexane hexane hexaneγ γ γ∞ ∞ ∞= ×

1 1 1

, ,

, , ,

R C

squalane squalane referenceγ γ γ∞ ∞ ∞= ×

1,hexaneγ ∞

1,referenceγ ∞

Oldenburg Progress Report 06/08/2009 14

Performance of Combinatorial Expressions

� Ethanol (2) in alkanes (1) …

15

30

45

60

75

90

2 4 6 8 10 12 14 16 18

q1

γγ γγ2∞

Exp. Data

UNIFAC

Mod. UNIFAC

FV

squalane (ref.)

hexane

hexadecane

Oldenburg Progress Report 06/08/2009 15

Performance of Combinatorial

Expressions

� Ethylcyclohexane (2) in alkanes (1) …

0.4

0.7

1

1.3

1.6

2 4 6 8 10 12 14 16 18

q1

γγ γγ2∞

Exp. Data

UNIFAC

Mod. UNIFAC

FV

squalane (ref.)

pentane

hexadecane

q1=q2

decane

Error starts

to become

noticeable

when q1/q2

< 0.8

Oldenburg Progress Report 06/08/2009 16

Performance of Combinatorial

Expressions

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

20000

<0.5 0.5-0.8 0.8-1.2 1.2-1.5 >1.5

[q-solvent]/[q-solute]

Data

po

ints

11.9%

14.1%

18.5%

9.0%

46.4%

Infinite dilution activity

coefficient data

Big solutes in

small solvents

Oldenburg Progress Report 06/08/2009 17

New Combinatorial Expression

� Modified the FV expression as follows:

, 'exp ln ln

'

FV FVC

FV FV

r rV V r r

qq qV Vq q

γ ∞

= − + − − +

2 2

2 2 1 12 2

2 21 1

1 1

1 5 1

( ) ( )*'FVi i i

V V V= −22

33

Vi – Molar volume (cm3/mol)

Vi* - van der Waals Volume (cm3/mol)

qi – UNIQUAC surface area

ri – UNIQUAC volume

Oldenburg Progress Report 06/08/2009 18

Performance of the New Combinatorial

Expression

� Ethylcyclohexane (2) in alkanes (1) …

0.4

0.7

1

1.3

1.6

2 4 6 8 10 12 14 16 18

q1

γγ γγ2∞

Exp. Data

UNIFAC

Mod. UNIFAC

FV

New Expression

squalane (ref.)

pentane

hexadecane

q1=q2

decane

Oldenburg Progress Report 06/08/2009 19

Performance of the New Combinatorial

Expression

400

500

600

700

800

3 4 5 6 7 8 9 10

q1

γγ γγ2∞

Exp. Data

UNIFAC

Mod. UNIFAC

FV

New Expression

hexadecane (ref.)

hexane

N

O

HN Cl

N'-(4-Chlorophenyl)-N,N-dimethyl-urea

Oldenburg Progress Report 06/08/2009 20

Results for Infinite Dilution Activity

Coefficients in Hexane

54.5 15648.1 15637.7 17047.6 17625.9 202All compounds

COSMO-

SAC**

COSMO-

RS(OL)**

Mod.

UNIFAC*UNIFAC*

This

WorkName

Lowest relative mean

deviation (%) in lnγ∞

Typically 2nd bestMore generally

applicable (greater

number of compounds)

* Consortium version 2008

** Based on B3LYP-6-311G(d,p)

Oldenburg Progress Report 06/08/2009 21

Interpolation between Water and

Hexane

( ) ( ), ,22, ,i CH i OHa a

CH OH

i i iγ γ γ∞∞ ∞=

H3C CH2

CH2

CH2

OH

, 2i CHa ,i OHa

( )0.5, ,2CH hexane

i iγ γ∞ ∞

= ( )1

, 1.8, 2H OOHi iγ γ

∞∞ =

Oldenburg Progress Report 06/08/2009 22

Applications

Solute

O

NH

OH

Paracetamol

Solvent aOH aCH3 γγγγ∞ exp. γγγγ

∞ pred.

Water 1.8 0 13

Ethanol 0.296 0.704 16.53 15.8

Hexane 0 2 764

4.5%

RMD

Oldenburg Progress Report 06/08/2009 23

Applications

0.0

10.0

20.0

30.0

40.0

50.0

60.0

0.0 10.0 20.0 30.0 40.0 50.0 60.0

γγγγ∞∞∞∞ experimental

γγ γγ∞∞ ∞∞

pre

dic

tio

n This w ork

UNIFAC

Mod. UNIFAC

Ideal f it line

tert-pentanol

methanol

ethanol

9H-Fluorene

Oldenburg Progress Report 06/08/2009 24

Future Work

� Add a polar solvent?

� Other approaches?

Polar

Dispersive

H-bonding

All

Solvents

Oldenburg Progress Report 06/08/2009 25

Conclusion

Initial problem

Pure component

property Water / Hexane

Interpolate to

alcohols

Solvent

Extrapolation

Oldenburg Progress Report 06/08/2009 26

Acknowledgements

� Supervisor:� Prof. J. Rarey

� Project Leaders:� Prof. J. Gmehling

� Prof. D. Ramjugernath

� Software:� DDBST GmbH

Thanks to:

BMBF (WTZ-Project)and

NRF (International Science Liaison and

Thuthuka

Programmes) for financial support