Octanol/Water Partition

Coefficients and Aqueous

Solubilities of Organic Compounds

U S. DEPARTMENT OF COMMERCE

National Bureau of Standards

Center for Chemical Physics

Chemical Thermodynamics Division

Washington, DC 20234

December 1981

-QC'

prepared for

...j-p. )ffice of Toxic Substances

invironmental Protection Agency

.1)56 Vashington, DC 20460

81-2^106

1981

c. 2
I
NATIONAL BURBAV

or 8TANDAAU8

librart

NBSIR 81-2406

r f OCTANOL/WATER PARTITION

COEFFICIENTS AND AQUEOUS

SOLUBILITIES OF ORGANIC COMPOUNDS

JAN 8 1982

/lot

Qc.100

no.

Stanley P. Wasik, Yadu B. Tewari, Michele M. Miller,

and Daniel E. Martire

U.S. DEPARTMENT OF COMMERCE

National Bureau of Standards

Center for Chemical Physics

Chemical Thermodynamics Division

Washington, DC 20234

December 1981

Prepared for Office of Toxic Substances

Environmental Protection Agency

Washington, DC 20460

U.S. DEPARTMENT OF COMMERCE, Malcolm Baldrige, Secretary

NATIONAL BUREAU OF STANDARDS, Ernest Ambler, Director

OCTANOL/WATER PARTITION

COEFFICIENTS AND AQUEOUS

SOLUBILITIES OF ORGANIC

COMPOUNDS

Stanley P. Wasik, Yadu B. Tewari, and

Michele M. Miller

Chemical Thermodynamics Division

Center for Chemical Physics

National Bureau of Standards

Washington, D.C. 20234

and

Daniel E. Martire

Chemistry Department

Georgetown University

Washington, D.C. 20057

Under

Interagency Agreement EPA-80--X0985

ABSTRACT

A generator column method for measuring the octanol /water partition

coefficient, and the aqueous solubility, C^, is described. When water

is pumped through a generator column packed with solid support coated with

an organic stationary phase, an aqueous solution is generated that is in

equilibrium with the stationary phase. The solute concentration in the

eluted aqueous phase was measured either by high pressure liquid

chromatography or by solvent extraction followed by gas chromatographic

analysis.

Aqueous solubilities and octanol /water partition coefficients of organic

solutes, falling into 7 general chemical classes, have been systematically

determined using the modified generator column method. From thermodynamics

an equation is derived relating to the volume-fraction-based solute

activity coefficient in water (y^» the latter being determinable from C^.

For each class of compounds, excellent linear correlations are found between

log and log y^, with slopes close to the theoretical value of unity.

i
ACKNOWLEDGMENT

The authors gratefully acknowledge the financial support of thei

work by the Environmental Protection Agency.
TABLE OF CONTENTS

Page

ABSTRACT i

ACKNOWELDGMENT ii

TABLE OF CONTENTS iii

LIST OF TABLES v

LIST OF FIGURES vi

DISCLAIMER vii

I. SUMMARY 1

II. INTRODUCTION 2

III. COMPARISON OF EXPERIMENTAL METHODS 6

IV. EXPERIMENTAL

A. Aqueous Solubility and Partition Coefficients 8

B. Solute Activity Coefficient in Octanol 15

V. VALIDATION

A. Stir-Flask Equilibrations 17

B. Solubility 18

C. Partition Coefficient 18

D. Activity Coefficients 21

VI. RESULTS AND DISCUSSION 24

VII. RECOMMENDATIONS FOR FUTURE RESEARCH

A. Salinity Dependence 40

B. Temperature Dependence 40

C. Head-Space Measurements 41

D. Tests for Other Classes 41

E. Predictive Schemes 42

VIII. REFERENCES 43
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LIST OF TABLES

Page

1 Aqueous Solubility of n-Propyl benzene 19

2 Octanol/Water Partition Coefficient, of n-Propyl benzene . 20

3 Activity Coefficients and Octanol/Water Partition Coefficients

of Organic Compounds at 25.0°C 23

4 Aqueous Solubility and Octanol/Water Partition Coefficients

of Organic Compounds: Aromatic Hydrocarbons 25

4-A Aqueous Solubilities and Octanol/Water Partition Coefficients

of Organic Compounds: Miscellaneous Aromatic Compounds .... 26

5 Aqueous Solubilities and Octanol/Water Partition Coefficients

of Organic Compounds: Unsaturated Hydrocarbons 27

6 Aqueous Solubilities and Octanol/Water Partition Coefficients

of Organic Compounds: Halogenated Hydrocarbons 28

7 Aqueous Solubilities and Octanol/Water Partition Coefficients

of Organic Compounds: Normal Hydrocarbons 29

8 Aqueous Solubilities and Octanol/Water Partition Coefficients

of Organic Compounds: Aldehydes and Ketones 30

9 Aqueous Solubilities and Octanol/Water Partition Coefficients

of Organic Compounds: Esters 31

10 Aqueous Solubilities and Octanol/Water Partition Coefficients

of Organic Compounds: Alcohols 32

11 Coefficients of the Regression Equation and the Correlation

Coefficient of the Solutes 33

V
LIST OF FIGURES

Figure

1

2

3

4

5

6

7

Generator Column

Schematic of HPLC System

Generator Column and Collecting Vessel

Experimental Log Versus Literature Log .

Experimental Log C^ Versus Literature Log C^ . . .

Log Versus Log for the Literature Values .

1 ^ Log K^, Versus Log for the Experimental Values

Page

9

11

14

35

36

38

39

VI
DISCLAIMER

Certain commercial equipment, instruments, and materials are identified

in this paper in order to specify adequately the experimental procedure.

In no case does such identification imply recommendation or endorsement by

the National Bureau of Standards, nor does it imply that the material,

instruments, or equipment identified are necessarily the best available

for the purpose.
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I . SUMMARY

A chromatographic method for measuring the octanol /water partition

coefficient, and the aqueous solubility, C^, of hydrophobic substances

is described. When water is pumped through generator columns containing

a solid support coated with an organic stationary phase, an aqueous solution

is generated which is in equilibrium with the stationary phase. When the

organic phase is pure solute, the concentration of the solute in the eluted

aqueous phase is the solute solubility. When the organic phase is octanol

containing a solute of concentration C° and the concentration of the solute

in the aqueous phase is determined to be C^, then the octanol /water

parti ton coefficient is given as = C°/C^. Validation of the generator

column method was made by comparing and values of n-propyl benzene

carefully measured by the conventional shake-flask method with those

measured by the generator column method. Additional validation of the w method was made by analyzing and data measured by the generator

column method in terms of the thermodynamically derived equation.

log Vw ° <

- log Y°

where Yc Is the solute activity coefficient, on a volume fraction basis, in

octanol as measured by the GC method and is the solute volume fraction in

water which is determined from data.

s Thermodynamic theory predicts that plots of log K , versus log ^w

O/W (j)^ should have slopes of unity if the data are accurate while the coefficient

of determination gives precision of the measurements. Analysis of the data

for 62 compounds representing seven chemical classes gave slopes in the

range 0.93 to 1.08 with an average coefficient of determination 0.994.

Our studies indicate that the and data obtained by using the

generator column method agree very well with the shake-flask literature data

obtained experimentally. Thus these results establish that the data are

accurate and the generator column method is a valid method for measuri ng

c'^ and K , . s o/w

1
II. INTRODUCTION

Measurement of the aqueous solubility, C^, and the octanol/water

partition coefficient, important for determining the fate

and transport of organic chemicals in the environment. may be

considered as a quantitative measure of the hydrophobicity of the compound.

In this respect, it has been used to predict bioconcentration of

organic pollutants in trout muscle [Neely et ^. , 1974] and for making

other chemical and biological correlations [Leo et ^. , 1971]. The aqueous

solubility gives an insight into environmental movement and distribution and

the potential for biodegradation by microorganisms in soil surfaces, water,

and sewage treatment plants as well as other degradation pathways such as

photolysis, hydrolysis, and oxidation.

Octanol/water partition coefficients and aqueous solubilities are

often measured by a shake-flask method. Solubilities are determined

by shaking the solute with water, allowing the two phases to separate,

and then determining the solute concentration in the aqueous phase by

an appropriate analytical technique. Octanol/water partition coefficients

are determined by shaking a known volume of octanol containing a small

amount of solute with water, allowing the two phases to separate,

and measuring the solute concentration in the aqueous phase, C^, and

in the octanol phase, is determined as the ratio C°/C^

In any shake-flask experiment with a hydrophobic substance,

the solute concentration in the aqueous phase is low. Consequently

the measurement of this concentration can be seriously affected by

the presence of colloidal dispersions (emulsions), adsorption of

the solute onto surfaces of transfer vessels, and loss of a volatile

solute into the atmosphere. These errors can be reduced, but only

at a cost of inconvenience and increased time, by centrifuging or

2
replacing the shaking by gentle stirring, by prerinsing the glassware

with the aqueous phase, and by avoiding exposure of the aqueous phase to

the atmosphere. A rapid, convenient method for preparing equilibrated

aqueous phases without significant errors from such effects would be

desirable.

For this purpose we have adapted the generator column method

described by May et [1978]. A generator column has a solid support

coated with a solid or liquid stationary phase. When water is pumped

through the column, an aqueous solution is generated which is equilibrated

with the stationary phase. May ^ [1978] used their generator

columns, packed with glass beads, mainly to measure solubilities

of solid polycyclic aromatic hydrocarbons; the only liquid stationary

phase used by them was benzene [May ^ , 1978]. We have redesigned

the generator column, changed the support to silanized silica in order

to increase the coverage, and extended the stationary phase to hydrocarbon-octanol

mixtures

In this report we discuss the work done under Interagency Agreement

EPA-80-2095 in the period October 1, 1980 to September 30, 1981. The objective

of this work was to develop and validate a chromatographic method to measure

w

Cs and and to make measurements on selected classes of organic compounds

in order to obtain accurate and precise and values.

In the third section of this report, "Comparison of the Experimental

Methods," the shake-flask method is compared with the generator column

method. The advantages and limitations of both methods are discussed.

The fourth section includes experimental details of the generator

column method and the gas-liquid chromatographic method for determination of

activity coefficients and c^tanol/water parti ton coefficients of organic

compounds

3
In the fifth section, "Direct Experimental Validation of the Generator

Column Method," the work done to establish a bench-mark and measurement

for n-propyl benzene is discussed. A detailed error analysis investigating

every experimental parameter was made in order to arrive at the best

and values. These values were then compared with the values measured

by the shake-flask method.

In the sixth section, "Results and Discussion," and values are

given for over 90 compounds representing seven types of organic

compounds. Further validation of the generator column method is made by

analyzing the data using linear regression analysis to the thermodynamical ly

derived equation log = c log d, where c and d are series constants

and is the activity coefficient of solutes in water saturated with octanol

The accuracy and precision of the data is discussed in terms of the value of

2

the slope, c, and the coefficient of determination, r , for the regression

analysis of the data to the different chemical classes.

In the seventh section, "Recommendations for Future Work," we

recommend that additional and measurements be made in aqueous NaCl

solutions and simulated sea water in order to establish the salinity dependence

of these properties. We also recommend that measurements be made at different

temperatures in order to establish the temperature dependence of solubility

and that solute activity coefficients be measured by a head-space method

to further validate the generator column method. There is also a need

for and measurement on classes of compounds not studied in this report.

In Appendix I, the thermodynamic derivation is given for the correlating

equation

' - log - log Y° w where is the volume fraction of solute in water saturated with octanol

and is the activity coefficient, on a volume fraction basis, of the

4
solute in octanol saturated with water.

Appendix II includes the proposed test method for determination

of the aqueous solubility of organic compounds.

5
III. COMPARISON OF EXPERIMENTAL METHODS

Generator columns have several advantages over shake-flask methods

for equilibrating water with a liquid organic phase. The flow rate of water

through the column can be made slow enough to avoid colloidal dispersions,

while the large interfacial area between the organic and aqueous phases allows

rapid equilibration. When the column is part of a continuous and closed flow

system, the system walls become equilibrated with the aqueous solution and

errors from adsorption are avoided; also there is no exposure of the solution

to the atmosphere, thus loss of volatile solutes is avoided. Only about 1 mL

of the organic phase is sufficient to load the column, and the column will

generate samples of the aqueous solution of whatever volume is needed for

analysis until the organic phase has been stripped. Once a column has been

loaded with a given organic phase, it is a simple matter to vary other

parameters such as pH or salinity of the aqueous phase to determine these

effects on the aqueous solubilities of organic compounds.

For compounds having relatively large aqueous solubilities (>1.0 M)

and low values (<100), there is no particular advantage in the

generator columm method over the shake-flask method, since colloidal

dispersion and surface adsorption are no longer an experimental problem.

However, the generator column method is still preferred because it is more

convenient to thermostat a generator column than a flask that must be shaken.

The generator column method requires no special skill of the operator.

The generator column is easy and inexpensive to construct and generally

yields reproducible and accurate data at desired temperatures ; whereas,

one will require a thermostated centrifuge to obtain accurate results

using the shake-flask method.

6
In summary, the generator column method is much better than the shake-flask

method in that the measurement time is much less than the shake-flask method.

Although equipment is required to measure the solute concentration in the

two phases (HPLC or GLC) the generator column method with its

closed flow system makes the measurements more convenient and avoids the

intrinsic errors associated with the shake-flask method.

7
IV. EXPERIMENTAL

A. Aqueous solubility and partition coefficients

Reagents

The compounds (solutes) for which aqueous solubilities and

octanol/water partition coefficients were measured were

obtained from various commercial sources with purities >98%. The octanol

was purified by washing successively with 0.1 M H2S0^, 0.1 M NaOH, and

distilled water. It was then dried with CaCl2, filtered and distilled

at atmospheric pressure. HPLC grade methanol and water were used to

prepare the mobile phases for liquid chromatography. Ordinary distilled

water was used for the aqueous phase solutions. Octanol saturated with

water (w-octanol) was used for making up the solute in octanol solution.

This solution was made up by stirring 10 mL of water with 250 mL of octanol for

several hours. The lower excess water layer was removed by a siphon. For the

Ko/w measurements, a 1% (by weight) solute in w-octanol was used for coating

the solid support in the generator column.

The design of the generator column and the method used to determine the

solute concentration, C^, in the aqueous phase depended on whether the

solute absorbed the U.V. For compounds which absorbed in the U.V., high

pressure liquid chromatography, HPLC, was used to determine C^; for compounds

which did not absorb in the U.V., solvent extraction followed by gas

chromatographic analysis was used to determine C^.

Generator Col urn

The design of the generator column is shown in Figure 1. The column

consists of a 6 mm (outside diameter) Pyrex tube joined to a short enlarged

section of 9 mm Pyrex tubing. To pack the column a plug of silanized glass

wool was inserted at one end of the 6 mm tube. Silanized diatomaceous silica

support (about 0.5g 100-120 mesh Chromosorb W cleaned by Soxhlet extraction

with ethanol and dried) was poured into the tube with tapping and retained

with a second plug of silanized glass wool.

8
[niet

Figure 1

T

u

20 cm

Glass Woc^l

Support (100-120 mesh

Chromsorb W)

I

Outlet

Generator column used to generate the aqueous phase. The column is 20

cm. long and packed with 100-120 mesh ehromosorb W for the solid support.

9
The column was coated with a liquid solute by pulling approximate ly

1 ml of the liquid through the clean dry support with gentle suction. The

column was coated with a solid solute by dissolving the solute in a volatile

solvent (10% v/v) and then pouring the mixture into the column until all

the solid support was saturated as evident by the appearance of the volatile

solution at the base of the column. The solvent was then distilled off

under reduced pressure.

HPLC Method

The HPLC analytical system is shown schematically in Figure 2. Two

reciprocating piston pumps delivered the mobile phase (water or a methanol

water mixture) through two 6-port high pressure rotary valves and a

30 X 0.6 cm C-18 analytical column to an ultraviolet absorption detector

operating at 254 nm. Chromatogram peaks were recorded and integrated with

a recording integrator.

One of the 6-port valves was sample injection valve used for injecting

samples of either the octanol phase for analysis, or standard solutions

of the solute in methanol for determining response factors. The sample loop

volume was determined by a spectrophotometric method using basic chromate

solution which are known to be suitable as absorption standards [Edisbury,

1967J. The method consisted of measuring the absorbance at 373 nm of three

loopfuls of an aqueous stock solution of K2CrO^ (1.3% by weight) diluted to 50 mL

with 0.2 percent KOH, and measuring the absorbance of the same stock

solution after diluting 1:500 with 0.2 percent KOH. From these absorbances

the loop volume was calculated to be (35.7 +0.1) mL.

The other 6-port valve in the system served as a switching valve for

the extractor column which was used to remove solute from the aqueous

solutions. The extractor column was a 6.6 X 0.6 cm stainless steel tube

10
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11

and

into

the

analytical

column.

The

syringe

injection

is

use

detector.
with stainless steel end fittings containing 5-iam frits, filled with

a superficially porous reverse phase packing (Bondapak C-jg/Corasi 1

Waters Associates). Aqueous solution from a generator column entered

the switching valve through the 1/16 in (1.6 mm) stainless steel tubing

labelled "A" in Figure 2. A water bath was used to thermostat

to + 0.05°C the generator column, the switching valve, the extractor

column, and the interconnecting stainless steel tubing.

The procedure for analyzing the aqueous phase was first to flow

the aqueous solution to waste with the switching valve in the inject

position in order to equilibrate internal surfaces with the solution, thus

insuring that the analyzed sample would not be depleted by solute

adsorption on surfaces upstream from the valve. At the same time, water

was pumped from the HPLC pumps in order to displace methanol from the

extractor column. The switching valve was next changed to the load position

to divert a sample of the solution through the extractor column, and the

liquid leaving this column was collected in a weighing bottle. During

this extraction step, the mobile phase was changed to a methanol -water

mixture to condition the analytical column. After the desired volume

of sample had been extracted, the switching valve was returned to the

inject position for elution and analysis. Provided that there was no

breakthrough of solute from the extractor column during the extraction

step, the chromatographic peak represented all of the solute in the

sample. The solute concentration in the aqueous phase was calculated

from the peak area and the weight of the extracted liquid collected in

the weighing bottle.

12
The octanol/water partition coefficient was calculated from the solute

concentration in the octanol and aqueous phases by dividing the concentration

in the octanol phase by the concentration in the aqueous phase. The water

flow through the generator column was 2 mL/min. Further experiments

with a generator column at 25°C show that within experimental error

(standard deviation 3% or less) the measured aqueous concentration was

independent of flow rate (in the range 0.5-2 mL/min).

GC Method

In the GC method aqueous solutions from the generator column entered

a collecting vessel (Figure 3) containing a known weight of extracting solvent

which was immiscible in water. The outlet of the generator column was positioned

such that the aqueous phase always entered below the extracting solvent.

After the aqueous phase was collected, the collecting vessel was stoppered

with a 3/8" Teflon Swagelok cap, and the quantity of aqueous phase was determined

by weighing. The solvent and the aqueous phase were equilibrated by either

stirring with a glass enclosed magnet or by rotating the collecting vessel

at the rate of two revolutions per minute for five minutes. It was found

that rotating the collecting vessel for longer than five minutes did not

increase the amount of solute extracted into the extracting solvent. A small

amount of the solvent was then injected into a gas chromatograph equipped

with flame ionization detector, and the solvent concentration in aqueous

phase was determined from a calibration ^urve constructed using known

concentrations of the solute. In order to determine the partition coefficient,

ko/w> samples of the 1% (by weight) solute in n-octanol solution were injected

into the GC, and concentration of the solute in the octanol phase was

similarly calculated from a calibration curve. As for the HPLC method, our

experimental error in the GC method was less than 3%.

13
Figure 3

Bath ^ Return

Generator

Column

Inlet

Generator

Column

To Constant

Temperature

Bath

-a— Extracting

Solvent

Generator column and collecting vessel used for analysis of the

aqueous phase by the GC-solvent extraction method.

14
B. Solute activity coefficient in octanol

The stationary phase in octanol, was coated onto the support material,

Chromosorb W-HP, 100/120 mesh, and the weight percent of coating was

determined by an ashing method. A stainless steel column (1/8" OD) was then

packed with a known amount of the coated support and was connected to a

Hewlett-Packard 5830A gas chromatograph equipped with a flame ionization

detector (FID) for the determination of the solute retention time. The

temperature of the column was controlled by circulating water through a

copper tubing jacket around the column and by a Haake Model FK temperature

regulator which regulated the water temperature to 25.0 + 0.05 °C.

The column inlet pressure, measured with a precalibrated pressure

gauge (range 0-15 PSI), was kept constant during a run by regulating with

a precision valve. In order to measure the carrier gas flow rate the column

was disconnected from the FID, just before and after the experiment, and

a soap bubble flowmeter was connected to the column outlet. The carrier

gas was presaturated with n-octanol in order to reduce bleeding of the

stationary phase.

Since the retention times decreased as the experiment progressed due

to column loss of the n-octanol, toluene was used as a reference retention

time standard and injected with each solute. The measured retention times

were then corrected for bleeding using the reference solute retention time.

15
The solute specific retention volumes (V^) were calculated by using

the following equation p Vw 273.2 3

V_ = —• -p j w

2

^

(Pi/P,) -1

where tj^ is the retention time (minutes), F is the carrier gas flow

rate (ml/min), P. and P are the column inlet and atmospheric pressure

1 a (in Torr), P is the saturated water vapor pressure (in Torr) at room w temperature T (°K), and W is the weight (in gram) of stationary phase

a packed in the column. The solute activity coefficients at infinite

dilution (y°) were determined from the following equation

^ PR

T 0 273. 2Rd ^s“^s

In = In

s g s RT

where d is the density of n-octanol at 25.0°C, P^ and are, respectively,

the vapor pressure and the gas phase second virial coefficient of the pure

solute at temeperature T(°K), R is the gas constant, and is the molar

volume of the solute at temperature T. Calculation of these quantities has

been described in detail in our recent publication [Tewari ^ , in press].

The estimated uncertainty in the activity coefficients is about 2%. However,

we emphasize that the applicability of this technique is limited to only

a few compounds due to the volatility of n-octanol. This technique can not

be applied to those compounds which have 1mm or lower vapor pressure at 25.0°C.

16
V. VALIDATION

Because of the general lack of agreement in reported and

values, the first steps toward validation of the generator column method

was to compare generator column data with data measured in this laboratory

by the shake-flask method. Propyl benzene was chosen as the compound

to establish a bench mark measurement because it is very stable, absorbs

in the U.V., has a typical log and log value, and can be

obtained pure (>99.9 %) from commercial sources.

A. Shake-Flask Equilibrations

For each equilibration about 10 mL of water and about 4 mL of the

organic phase were placed in a closed Pyrex vessel and stirred with a glass

enclosed stirring bar. For the solubility measurements the organic phase

was the pure solute. For the measurements the organic phase was

a V/o (by weight) octanol solution. All precautions were taken to eliminate

systematic error. All transfer vessels and tubing were prerinsed with

the aqueous phase to avoid solute adsorption on the walls. The equilibration

flask was stoppered at all times to avoid exposing the aqueous phase to the

atmosphere. To prevent emulsion formation in the aqueous phase vigorous

stirring was avoided. Most of the organic layer was confined to a narrow

neck at the top of the vessel. Above the neck was a 3/8-inch tube septum

for sampling the organic layer. The equilibrated aqueous phase was

transferred to the HPLC system for analysis with the aid of nitrogen pressure.

17
B. Solubility

Table 1 lists our solubility results for propyl benzene. The aqueous

samples were 2-6 ml in volume. The shake-flask and generator column results

for comparable temperatures agree within experimental uncertainty. Our

-4

value at 25°C, 4.3 X 10 M, is similar to the values for this temperature

reported by Andrews and Keefer [1950] (4.6 X

10""^ M) and by Hermann [1972]

(5.0 X 10"^ M). The temperature dependence of the solubility suggests

that there is a minimum in the neighborhood of 20°C. Solubility minima

near 18°C have been observed for benzene and its methyl, dimethyl, and

ethyl derivatives [Bohon and Claussen, 1951]. In the case of propylbenzene.

Gill ^ [1976] predict from the temperature dependence of the heat

of solution that there is a solubility minimum at (18.6 +0.2) °C which is

consistent with our results.

C. Partition Coefficient

The octanol -water partition coefficient, was calculated from the

measured propylbenzene concentrations in the equilibrated octanol and

aqueous phases by dividing the concentration in the octanol phase by the

concentration in the aqueous phase.

The volumes of the aqueous phase samples used to obtain the partition

coefficient values listed in Table 2 were in the range 1-4 mL for the

shake-flask results and 10-24 ml for the generator column results. The

water flow rate through the generator columns was 2 mL/min. Further

experiments with a generator column at 25°C showed that within experimental

uncertainty (standard deviation 3% or less) the measured aqueous

concentration was independent of the water flow rate (in the range 0.5-2

mL/min) and was independent of the volume of sample passed through the

extractor column (in the range 2-24 mL). These experiments show that

under our experimentc;! conditions the equilibration was complete in the

18
Table 1

Aqueous Solubility of n-Propyl benzene

t/°C^ c". 10

stir-flask , stirred 16 h

ambient 4 4.27 + 0.06

Generator column

15.0 3 4.26 + 0.05

20.0 2 4.25 + 0.12

25.0 3 4.32 + 0.02

30.0 3 4.45 + 0.05

^Equilibration temperature. Ambient is (23 + 1)°C.

^Number of aqueous solution samples analyzed.

^Aqueous concentration; the mean value and the confidence limits

at a 95% confidence level are listed.

19
Octanol/Water

Partition

Coefficient, K,,

of

nPropyl

benzene

CM 1 r— t f— r— r— 0 0 0 0 0 0 0 0 0 0 0 s 0 0 0 0 0 0 0 0 0 0 0 0 + 1 + 1 + 1 + 1 + 1 + 1 + 1 + 1 + 1 + 

+

oo OsJ (T» 0 CVJ CM <OJ 00

CD r>^ VO 0- <0 0 • _J CO CO CO CO CO CO CO CO CO CO CO

t/5 OJ

MQ.-0 E OJ 0 03 N

CO 00 >,

S- 3

<u 0 <U 03 Jd 0) to C E 3 03 cC 3 cr JZ

z: < OM030) p-"Q.-0 E OJ 0 1— 03 N 0 to >5

SC 1—

(U 03 OJ 03 -P to C E 0 03 C 3 0

Q_ oO)

Ss- M- •- O 4-> oo

s_

O) (/) i- E 3 3 O

2: n: ^ I

OJ I E <U 3 S-

•I- 3

S- -»-> JD 03

•I- S_ I— <u

•r- Q. 3 E

cr 0) Lu 1— oo + 1 + 1 + 1 0 0 0 0 0 0 0 0

CO CO CO IT) un to <3 tn 0 0 uo

CN CVJ CVJ CVJ CVJ CVJ 1— CVJ CO CO

O I e I— fO >>+-> Q. 0 0 0

i_Q.

C

S-0)

4-> CVJ CO 0 00 to CO CO CO CO CO CO • r* CVJ CVJ CVJ CO 00 CVJ CVJ CVJ CVJ CVJ CVJ

vj- CVJ CVJ CVJ 0 0 CVJ CVJ CVJ CVJ CVJ CVJ 0 O)C to 0 0 0 0 0 0 0 0 0 0 0 • O) O) ON I—

c: c o o O) s: o JD —

T3

cu

(/) ao

+-> cu cE30u

(/) s-

(T3 0p

M- 03 I s. s- cu

•r-* c

4-> (U 00 CO

20
generator column, and that there was no significant breakthrough of

propyl benzene from the extractor column.

Three shake-flask equilibrations with different stirring times were

carried out (Table 2). With increased stirring time, there was a decrease

in the partition coefficient values of about the same size as the experimental

uncertainty. There is good agreement between these values and the generator

column results.

The partition coefficient is seen to vary with temperature (Table

2) having a maximum in the vicinity of 20°C. However, further studies are

required to generalize this phenomenon. It is interesting to note that while

the solubility and the partition coefficient of propylbenzene both vary

with temperature, their product over the temperature range in which both

quantities were measured (15-30°C) is essentially constant (2.26 + 0.05 M).

This suggests that the heat of solution of propylbenzene in octanol is small.

The partition coefficient measurements at 25°C (Table 2) show a small

but systematic decrease of log with decreasing concentration in the

octanol phase. Extrapolation to infinite dilution gives log = 3.69 +0.01

at 25°C. Iwasa ^ [1965] report log = 3.68 + 0.01 from shake-flask

measurements at ambient temperature, in excellent agreement with our

results.

Activity Coefficients

In Appendix I an expression is derived showing the relationship of

log with the aqueous solubility in term of solute volume fraction

^s

'^0/w

" ' s '°9

's

where (})^ is the solute volume fraction in water saturated with octanol

21
and Y is the solute activity coefficient, on a volume fraction basis.

5 in octanol saturated with water. This equation provides an indirect method

to determine from the solute activity coefficient in octanol and its

aqueous solubility.

The solute activity coefficient in octanol, Yg » can be determined from the

retention volume [Conder and Young, 1979] of the solute eluting from a G.C.

column containing octanol saturated with water as the stationary phase.

This method for determination of has been documented in our recent

publication [Tewari ^ , in press]. Since is measured at infinite

dilution and cj)^ is also at infinite dilution, the determined using

the above equation is also at infinite dilution.

The value for log y° determined by the G.C. method for a number of

solutes are listed in Table 3. Using y° and determined from

the aqueous solubility and solute molar volume, octanol/water partition

coefficients for the solutes were calculated and compared with the

experimental These two quantities are listed in the last two

columns of table 3. An examination of these two columns shows an excellent

agreement between the experimental and the calculated Based

on our measurements, there is a complete consistency in the above

equation. Thus these results suggest that our data are precise and

accurate and that the generator column is a valid method for determination

of the aqueous solubility and octanol/water partition coefficient of organic

compounds

In conclusion, we have demonstrated in this section that the

generator column method for determining and is a valid and an

accurate method for measuring these quantities.
Table 3

Activity Coefficients and Octanol/Water Partition

Coefficients of Organic Compounds at 25.0°C

Solutes log Y° log Ys '-°9 ^0/w

(GLC) Calculated Experimental

Benzene 0.565 2.59 2.03 2.13

Toluene 0.509 3.17 2.66 2.65

Ethylbenzene 0.506 3.66 3.15 3.13

o-Xylene 0.494 3.60 3.11 3.13

m-Xylene 0.477 3.73 3.25 3.20

Chlorobenzene 0.533 3.36 2.83 2.81

n-Propylbenzene 0.494 4.22 3.73 3.69

n-Pentane 0.555 4.19 3.64 3.62

n-Hexane 0.530 4.73 4.20 4.11

n-Heptane 0.517 5.28 4.76 4.66

n-Octane 0.513 5.80 5.29 5.18

Ethyl acetate 0.621 1.15 0.53 0.68

n-Propyl acetate 0.534 1.64 1.11 1.24

n-Butyl acetate 0.425 2.12 1.69 1.82

3-Pentanone 0.496 1.25 0.75 0.99

2-Heptanone 0.222 2.30 2.08 1.98

1 -Hexene 0.504 3.98 3.47 3.47

1-Octene 0.479 5.24 4.76 4.88

1-Nonene 0.469 5.81 5.34 5.35

n-Butyl bromide 0.372 3.16 2.79 2.75

1 -Butanol 0.336 1.10 0.76 0.79

23
VI. RESULTS AND DISCUSSION

The experimentally determined values of ^nd and the calculated

values of are listed in Tables 4 through 10 for several classes of compounds.

The notations a and b refer, respectively, to the HPLC and GC methods of analysis.

The average experimental uncertainties in and are around 1.0%. An

asterisk is used to indicate that the literature data are calculated values

according to Hansch ^

aj^. (1968). Our results are generally in good agreement

with available experimental literature data obtained by the conventional

shake-flask method.

The present data were subjected to a linear regression of log =

c log + d for each class of compound and for all compounds taken together.

The results of these analyses are shown in Table 11.

The present equations are inadequate to explain and data of

aromatic solids listed in Table 4A. Analysis of these data is, therefore,

not included in Table 11.

According to equation 9 of Appendix I the slope for each class should be

unity and the negative of the intercept is log (assumed to be relatively

constant). Examination of Table 11 shows that the slopes are indeed close to

unity, ranging between 0.91 and 1.08. These small deviations are most likely

caused by slight variations in log y° within each class (Tewari ^ , in

press). For example, the average of the difference between log y^ and log

for the aromatic compounds is 0.55 for those with aliphatic substituents and 0.68

for those with halogen substituents, whereas the least-squares value of log

y° is 0.77 when all the aromatic compounds are included. Therefore, the intercepts

represent only approximate (averaged) values of log y° for each class.

These findings show that the octanol/water partition coefficient of a

solute may be estimated with reasonable accuracy from knowledge of its aqueous

24
Table 4

AQUEOUS SOLUBILITIES AND OCTANOL/WATER PARTITION

COEFFICIENTS OF ORGANIC COMPOUNDS

Aromatic Hydrocarbons

Aqueous Concentration ^/w

Solute

This Study

(M) Literature Value

(M) ,

This Study

3 ) Literature

Toluene 6.28 X 10"^ 5.80 X lO'"* 3.17 2.65^®^ 2.69^^^

Ethylbenzene 1.76 X lo'-^ 1.52 X 10'^^^^ 3.66 3.13^^^ 3.15^^^

o-Xylene 2.08 X 10'^ 1.61 X lO'^^'^^ 3.60 3.13^^^ 3.12^^^

m-Xylene 1.51 X 10-3(a) 1.38 X lO"^^'^^ 3.73 3.20^®^ 3.20^^^

p-Xylene 2.02 X 1.47 X lO'^^'^^ 3.60 3.18^®’^^ 3.15^^^

n-Propyl benzene 4.34 X 1 0”^^^ 4.99 X 10"^^^^ 4.22 3.69^^’^^ 3.68^^^

n-Butyl benzene 1.03 X 8.79 X 10"^^^^ 4.79 4.28^®’*^^ 4.26^^^

m-Pentyl benzene 2.59 X 10-5(a) — 5.35 4.90^^^ ...

n-Hexyl benzene 6.27 X 10-6(a) — 5.92 5.52^^^ ...

1 ,2,3-Trimethyl benzene

5.45 X 10-4(a)

4.01 X 10"^^^^ 4.13 3.55^®^ ...

1 -Ethyl -2- methyl benzene

6.21 X lO-^(a) — 4.07 3.53^^^ ...

Chlorobenzene 2.62 X 10-3(a) 2.84 X 10'^^®^ 3.56 2.98^®^ 2.84^^^

Bromobenzene 2.62 X 10-3(e)

4.41 X 10'^^®^ 3.56 2.98^^^ 2 , 99

(f)

lodobenzene 9.84 X 10“4(a) — 3.96 3.28^®^ 3.25^^^

o-Fluorobenzyl

chloride

2.88 X lQ-3(a) — 3.47 2.67^®^ ...

m-Fluorobenzyl

chloride

2.86 X 10'3(a) — 3.46 2.77^^^ ...

m-Cresol 2.59 X 10

‘ 2 (a) — 2.52 1.96^^) ...

Nitrobenzene 3.11 X 10

" 2 {a) ... 2.50 1.85^®^ ...

Indicates that the literature data are calculated values according to Hansch ^ al_. , 1968. HPLC method of analysis.

GC method of analysis. Sutton and Calder, 1975. McAuliffe, 1966. Hansch ^ , 1968. Hansch and Leo, 1979. MacKay et , 1980. Reddick and Burger, 1955. Average standard deviation of log measurements is 0.04.

(j) Average standard deviation of log measurements is 0.04.

25
AQUEOUS SOLUBILITIES, AND OCTANOL/WATER PARTITION COEFFICIENTS.

OF ORGANIC COMPOUNDS

Miscellaneous Aromatic Compounds

Aqueous Concentration log Solute This study

(M) Literature

(M) This Study^'^^ Literature

n-Heptyl benzene 2.54 X 10"®^®^ 6.28 ... ...

n-Uctylbenzene 3.48 X 10'^^®^ 7.11 ... ...

Hexamethy 1 benzene 1.45 X 10'®^®^ ... 4.61^®* ...

1 ,2,3,5-Tetramethylbenzene

... ... 4.04^®^ ...

Naphthalene 2.39 X 10"^^®^ 2.36 X 10'^*9^ — 3.35<®> 3.37*^)

1 -Methyl naphthalene 2.23 X lO"'*^®^ 2.11 X lO"'^*^^ — — ...

1-Ethylnaphthalene 7.41 X 10"^^®* 6.40 X 10*^*^* — ... —

1-Fluoronaphthalene 3.53 X 10'^^®^ ... ... ...

1 -Chi oronaphthal ene 1.07 X 10"^^®^ ... ... ...

1 -Bromonaphthalene 6.72 X 10'^^®^ ... ... ...

p-Fluorobenzyl chloride

... ... 2.73^®* ...

o-Dichlorobenzene ... ... 3.38*®^ 3.38*^)

m-Di chlorobenzene ... 3.48^®^ 3.38*^)

p-Dichlorobenzene ... 3.37<®) 3.38*^)

1 ,2,3-Trichlorobenzene ... 4.04*®^ ...

1 ,2,4-Trimethylbenzene ... 3.63*®^ ...

1 ,2,3,4-Tetramethyl benzene

... 3.98^®^ ...

Phenol 0.813^®) ... 1.45'®) ...

2,5-Dimethylphenol 6.61 X 10'^^®^ 2.35*®^ ...

2, 4-Dimethyl phenol 6.40 X 10'^^®^ 2.34^®^ ...

2, 6-Di methyl phenol 7.90 X 10"^*®) 2.31<®) ...

2,3,6-Trimethyl

phenol

1 .16 X 10'^^®) 2.67*®) ...

2,4,6-Trimethyl

phenol

... 2.73*®) ...

o-Cresol 2.52 X 10'^^®^ 1.96*®) ...

Indicates that the literature data are calculated values according to Hansch et £l_. , 1968. HPLC method of analysis.

GC method of analysis. Sutton and Calder, 1975. McAuliffe, 1966.

(e

Hansch et aj_. , 1968. Hansch and Leo, 1979. MacKay et , 198D. Reddick and Burger. 1955.

(j) standard deviation of log measurements is 0.05. Average standard deviation of log measurements is 0.04.

26
AQUEOUS

SOLUBILITIES

AND

OCTANOL/WATER

PARTITION

00

v£)

CT>

I/O OOO-SOoocooo

C/i oI—

oo

•JC 03

S- 03 03 o 1 +-> 03 O 1 O 1 1 1 03 O 1 tx 1 1 1 S- I— • • 1 1 1 03 03 CNJ CO

-P > S _J o

O)o

P-"

CO , c JD JO JO JO JO o >3 '—

" ' ' " JO •i-j "O 1^ 03 00 uo CM CO

S- 3 <T> 00 CO r— Px

03 CO -P • • • • • • O •I- cn OO CO cn CM CM O j=

&- h- T3>»

JZ , •a •r— <u

+-> S CO CO 00 cd" r^— r—

03 >-

C3 U3 OJ 00 CO o S- • • • • • • 3 03 ro LO cn CM CO

+->

O

03 r—

COC

ra

03

S- ^ CO 3 ,—

-o c -P 03 T3 o 03 3 ' LO

•r“ S- 1— 2! 1 4-> 03 03 O o 1 1 1 03 -P > r« r— 1 1 1 S- • r— 1 1 1 1 -P _J X 1 X c 1 03 03 o O 00 c • • o >, Lf> CM o T33

CO -P ^—

.»

—

^ — ^ 

o CO '

JO JO JO JH JO JO o s: ^ ' ' ^ ^ ^ - V ^ 03 CO '

cn CO CM CO o •r“ 1 1 1 1 1 1 a- o o o o O o <c 1— '

r*

''

'

XXX

XXX

00 LOU3 U3 IX

OJ 00 CO 00 LO CO • • • • • • 00 ' CO 00 ' 00

03 03

03 c 03 03 SZ 03 3 03 c 3 >> 3

03 03 4-> 03 03

p >>

+->

X CL +J sz 3 X Z3 03 03 L> o 03 03 or az O z O. 00 O 1 1 1 1 1 1 C/3 r~ r— r— r-~ r—

n3|

‘-‘I a>| u

CO

fO rco4-> cnc

-o

s-oao

ra

CO

O)

•St" • o cno o O CO

fO>

T3

(U

+-> «3

Z3U

nsu0) sfO

fO

-l-» (O -O

CO CO P CO C p 03 3 E

03 03 E S- 03 3

S- CO 3 <T3 CO 03

fO E

03E 5 S CO o

?*-

C7> C7) O O

<u

s_3

+J

03S0)

+->

<u s:

+->

-i-> 03 JZ

+->

CO

<U

-!-> 03O

-ac

CO Lf)

•p— • IX

CO CO <T> >> •r" p— • CO CO

(T3 >)

p LO 3 S- cy> <a na 03 • r— 3 o LO p (T3 n— LO ct o fd CT> • p o r— 1—

-o o rd| o -o p -o 3 03 +^l p o fd P 03 

03 J3 E p 3 •r“ x:

03O p—

a

O E P 3 CO P C 3

Q. o 3 CJ (d oz C3 C/0 S 31 P p O o 3 3 • O O

LO •r- •r— CO P P

CT» fd fd • 1— •p“ •rcr^ • > > X O 03 03

CT> 00 s. o -o

r— C3^ 0303 •c -o

pv s- s- s- o r\ 3 fd fd

03 • CQ -o -a P 1— 1 3 3

<d| -o fd fd -o 3 p P 3 +^1 fd CO LO

(d 03|

p 03 03 JZ >» a 03 03

CJ fd •r“ fd fd CO iii X3 s- s- 3 CJ -o 03 03

fd fd 03 > >

3Z S DC =a: c£

03 o -a QJ O) -C T27
Table 6

AQUEOUS SOLUBILITIES AND OCTANOL/WATER PARTITION

COEFFICIENTS OF ORGANIC COMPOUNDS

Halogenated Hydrocarbons

Aqueous Concentration Log ,“«> log ^/w

Solute This Study

(M)

Literature

Value

(M)

This^'^^ StudyLiterature

Value

1 -Chlorobutane 9.43 X 10'^^*^^ 7.19 X 10"^^®^ 3.00 2.55^*^^ 2 . 39

(e)

1 -Chloroheptane 1.01 X lO"^^*^^ — 4.81 4,15<'=> —

1 -Bromobutane 6.34 X lO"^^'^^ 4.13 X 10'^^®^ 3.16 2.75^*^^ 2.60^®^*

1 -Bromopentane 8.38 X 10‘^^^^ —- 3.98 3.49^^^^ —

1 -Bromohexane 1.56 X lO'^^*^^ — 4.65 3.80^*^^ —

1-Bromoheptane 3.71 X 10'^^^^ — 5.23 4.36^*^^ —

1-Bromooctane 8.65 X 10'^^^^^ — 5.82 4.89^*^^ —

Bromochl oromethane 0.129^*^^ — 2.06 —-

l-Bromo-2-chloropropane1.42 X lO'^^*^^ —- 2.82 2.18^*^^ —

1 -lodoheptane 1 .55 X 10"^^^^ —- 5.60 4.70^^^^ —

Trichloroethylene 1.04 X 10'^ 0.80 X 10'^^®^ 3.03 2.53^^^ —

4-Bromo-l -butene 5.66 X 10’^ — 3.24 2.53^^^ —

Allyl bromide 3.17 X 10'^ — 2.56 1.79^^^ —

* Indicates that the literature data are calculated values according

HPLC method of analyis.

GC method of analysis.

( c ) ' ' Sutton and Calder, 1975. McAuliffe, 1966.

(g' )

' Hansch et al . , 1968. Hansch and Leo, 1979. MacKay^al., 1980. Reddick and Burger, 1955. Average standard deviation of log y. measurements is 0.03.

(i) ^ Average standard deviation of log measurements is 0.03.

to Hansch et al .

1968.

28
<L)

(T3

cu

S-3

-P CU Jc fO 3 Cp ^ ^ S- r— '—

0) cu cu CU CO CO 3 4-> > oo o o o •r“ • o to

CO • • • ro CO 'O' COo

J3 jQ JTJ JD '

VSmC* •o CM r— cjO 00

to ^ >> to r— to r— o c to -o • • • • 1—

o •I- 3 CO to i

JO J= -P

S- C/1 y— fO Od o < c/^ o

Q. o s_ •r" 3 -o — Od o >0 3 to

LlI or >- 1

O- oi CO CX) o

<X s: f— C3 r— CM CX) 3 o (t5 O • • • • o E r— Lf) tn 1 S- O o o

1—

3

t— < C_) to o ct; o Q u. ^ s .

< o -o TJ »—

-o - ^ -o —

c/> c/1C CU > p to

UJ h- o p 1 1 1 1 t—

•P“ 3 o O o o H- +-> +J CU-

r— p— r—

t—

»—

fO CO 3 s:

_J o &- ^ n" ^ X

XXX t—

1—

4-> CU (O CO u. E +-> r> OI ro to IX

ro U- CU •p— CO r~ o CD

_! LU o _j • • • • o o E to r—

CO to

00 o oo oo . < « ro to JD J3 JT) o 3 >> N ^ '—

LU o -o uo to

zo cu 3 1 1 1 1 Of P '

o O o o < cr C/1 s: 1 < —

to

X

XXX • r* SZ to ro tx to 1— to to to

to - CO CD

CU p3 cu cu t— E CD E CU o CO C CO E

oo P fO P ca E X Cl p

CU CD CUu

Q-1 IC zr1 o 1 E c E E

00

<X) o\

fO I

cul JZo

(/) s=o+JCD

-a

s-ooo

ft3

to

(U

fO>

*o

(U

+-> fO3o

rOa

cu

sfO

(T3

4-> (Q -o

O)

5-3

4-> fO

i. . . CU to to p • p— • X •r— to to CD • r— •r" r— • CD • to CXD X o CU CO >> r\ to CD 00 JE E s- CD p— CD P CO CO cu . r— E o to r\ P P CO 1— to o

CO

O CO CD • . ^ • JZ P o r— (

p r“ p XJ O CO CO 1 O •o p , -a p jE -o E CU P E -P|

cu P o COp CU 1 cul

p CU

p

(O E p E •1— x: >1 o cu O p— o CJ CO

•r" t_) E P 3 1/1 (/) -o p P < E E o E Q_ c_> 3 CJ (O CO CO 1—

in CO CO 2: rc rc ,—

,—,—

. - CO JZt o -o cu p O) . V—-- V '—

-—

''

—

p ^—-p

—

p >

tn

un

CTi

S-O)CO

S-3

CQ

(T3 U

•r“ o

"O

cu Cd

c\j • o to • o o o to

•r— to

•r— to P

t/J E P CU E f= QJ CU E E

CU 3 E to 3 CO

(/) CU

CO E

CUE 3 W s o

CD CD o O '

'

p P o o E E o o • r~ • r~ p P

CO CO

>r— • r— > >

CU CU O O

"O "O E E

CO CO o "O E E

CO CO P P

to to

CU CU CD CD

CO CO E E

CU CU > > < <c

29
Table 8

AQUEOUS SOLUBILITIES AND OCTANOL/WATER PARTITION

COEFFICIENTS OF ORGANIC COMPOUNDS

Aldehydes and Ketones

Solute Aqueous Concentrations log

This Study

(M)

Literature

Value

(M)

This^J^

Study

Literature

Value

2-Butanone <Ti 00 1 — 0.77 0.69^^^ 0.29^®^

3-Pentanone 0.53^^^ 0.48^®^ 1.25 0.99^^^ 0.79^®^*

2-Heptanone

p(a)

3.57 X lO""^ 3.79 X 10“^^®^ 2.30 1.98^^^ 1.79^®^*

2-Octanone 8.85 X lO"-^ — 2.86 2.76^®^ —

2-Nonanone

JaT

2.61 X 10" — 3.35 3.18^®^ —

2-Decanone

. 4

( 9 ) 5.03 X 10

^ — 4.02 3.81 —

Acetal 0.75^*^^ 0.42^*^^ 0.97 0.52^®^ —

2-Furaldehyde 0.81 0.85^®^ 1.17 .52^^^ —

Indicates that the literature data are calculated values according to Hansch ejt , 1968.

HPLC method of analysis.

GC method of analysis.

Sutton and Calder, 1975.

McAuliffe, 1966.

(el ^ ' Hansch ^ , 1968.

Hansch and Leo, 1979.

MacKay ^ , 1980.

Reddick and Burger, 1955.

Average standard deviation of log measurements is 0.05.

(il

^

^ Average standard deviation of log K

^ measurements is 0.03.

30
Table 9

AQUEOUS SOLUBILITIES AND OCTANOL/WATER PARTITION

COEFFICIENTS OF ORGANIC COMPOUNDS

Esters

Aqueous Concentrations L09y"‘'> Log

*^o/w

Solute

This Study

(M)

Literature

Value

(M)

This^J^

Study

Literature

Value

Methyl nonanoate

7^)

1.33 X 10

’ — 4.58 4.32^^^^ —

Methyl decanoate

_s(b)

2.05 X 10

^ 5.36 4.41

Ethyl acetate 0.726^^^ 0.912^®^ 1.15 0.68^^^ 0.73^®^*

n-Propyl acetate 0.200^^^ 0.185^®^

1.64 1.24^^^ 1.23^®^*

n-Butyl acetate

^TbT

5.77 X 10'“^ 0.203^®^ 2.12 1.82^^^ 1.73^®^*

Ethyl propionate 0.148 0.187^*^^ 1.77 1.43^^^ —

2-Bromoethyl

acetate

0.212^®^ — 1.63 i.ii‘^> —

Indicates that the literature data are calculated values according to Hansch ^ , 1968.

HPLC method of analysis.

GC method of analysis.

Sutton and Calder, 1975.

McAuliffe, 1966.

Hansch e^ , 1968.

Hansch and Leo, 1979.

MacKay ^ , 1980.

Reddick and Burger, 1955.

Average standard deviation of log measurements is 0.04.

Average standard deviation of log measurements is 0.02.

31

L
Table 10

AQUEOUS SOLUBILITIES AND OCTANOL/WATER PARTITION

COEFFICIENTS OF ORGANIC COMPOUNDS

Alcohols

Aqueous Concentration Log '-“9 l<o/w

Solute This Study

(M)

Literature

Value

(M)

This^-^^

Study

Literature

Value

1 -Butanol 0.854^^^ — 1.0 0.785^^^ 0.84^®^*

1 -Pentanol 0.133^*^^ 0.249^*^^ 1.84 1.53^*^^ 1.34^^^*

1-Hexanol

p(b)

4.14 X 10“^ — 2.28 2.03^^^ 1.84^®^*

1 -Heptanol 1.13 X 10"^ — 2.80 2.57^^^ 2.34^®^*

1 -Nonanol 7.35 X 10

’ — 3.89 3.77^*^^ —

2 Ethyl -1,3-hexanediol 1.56 X 10 — 3.61 3.22^^^

ic Indicates that the literature data are calculated values according to Hansch et aj[. » 1968.

HPLC method of analysis.

6C method of analysis.

Sutton and Calder, 1975.

McAuliffe, 1966.

Hansch ^ , 1968.

Hansch and Leo, 1979.

MacKay ^ al^. , 1980.

Reddick and Burger, 1955.

Average standard deviation of log y!^ measurements is 0.03.

( i ) ^

' Average standard deviation of log K

^ measurements is 0.03.

32
I

cu

03

CM

S- ^ 

M-O

CO

4-> *1- C 4-> o CO CO C73 00 CM

03 fO CTi 00 00 C33 00 C33 •r- C CT> CT« 03 C33 C33 C33 C33 O -r- . . . . . . . ‘f— E

4- S- 4- 03

03 +-> O 03

(_3

Q

O o o o 0 0 0

in , ^ 03 T3 o oo 1 LO P^ CM

+-> o CO CO 03 LO CO 1— 3 +-> 1

CM rTMO 1— 1

1—

r— CL . . . • • T3 o 03 o o o o 0 0 0 C CO U

fO s- + 

+ + + 

+ 1 + + 1 03 03 c jC +J CO lO CO 00 LO LO 00 o +-> c CD 00 CM CO CO 00

•r" 1—LO CO •d" CM CO

-(-> i. • • • • . . . 03 o o o o o 0 0 0 13 >+- 1 1 1 1 1 1 1 O'

LU co CD 1 CO CD LO LO r— C •r“ CM CO CO r— CO LO r— o 4-> (J O o o o 0 0 0 •r" fO • . . . • . . «/l c O o o o 0 0 0 (/) •r- 03 03 E Q. + 1 1- 

+ 1 + 

+ 1 + 1 + 1 S_ S- O

cn 03 r— CO p>. CM C33 CM 0 03 4-> CO LO CM o P>. CO CO

q; 03 o O CT> C33 0 C33 0 Q . . . . . . . 03 (

(

o O 1— 0 1—

jc: M4-> O

M- +-> O C

03

(/J •r“

4->

O in

C •r“ 4- T3

03 MO

C

•r— M- 3 00 CD CO 'd- CO CD U 03 S- o r— p—

•r—

O 03 Q.

<+-

O E 4- E O

03 03 13

O

O JC O +->

in in in tn c c c c T3 o o o o C

4- JO -a JD -o JD JD fd o in i- 03 S- 03 S- i- T3 fO 03 +-> 03 03 in in

03C o a fd (_) 03OO 03 03 in Cl 3 •r- o s- o C O O "O C ,

>> o +J s- 13 S- 03 S- r- S_ >> 0 in 0

1— Q. 03 "O +-> "O 03 T3 (d -o 0: 4-> s- E E >> fO >> o >, E >1 03 03 03 0 o O IC in r— ZC S- DZ -0 +-> 0

C_3 c 03

O r— l/) r—

«=c CD zc 2: <=c LU <c

33

All

compounds

62

0.944+0.018

-0.311

+0.066

0.980
solubility, its molar volume and the regression equation for compounds

of its class. Also, this study establishes that the generator column

method coupled with either HPLC or GC modes of analysis provides an accurate

and rapid method for systematic determination of K^^^and for organic

compounds.

Equation 9 of Appendix I was rigorously derived from thermodynamic

principles. Plots of log versus log having slopes of unity are a

strong indication of the accuracy of the data. The scatter or precision of

the data should be reflected in the coefficient of determination obtained from

a linear regression analysis of the data. A coefficient near unity indicates

good precision in the measurements.

The fact that the slopes of the log versus log plots for the

seven different classes of compounds are near unity (Table 11) is a strong

argument in favor of the generator column method giving accurate and

values and is a further validation of the method.

It is interesting to analyze literature values of and in the same

manner and compare these results with those obtained by the generator column

method. In Figure 4 are plotted log values measured by the generator

column against literature log values measured by the shake-flask method.

The points that are obviously off in the literature log range of 2 to 4

are alkanes that have been calculated by the group additivity method and are

not experimental values.

In Figure 5 are plotted log values measured by the generator column

method against literature log values measured by the shake-flask method.

Th‘ agreement is much better than that in Figure 5 because all the literature

values are experimental values.

34
Figure

4.

Experimental

Log

Versus

Literature

Log
CO lO ^

CO CM

CD

If)

CO

CM

O

3 CO

(lVlN3Wiy3dX3) lo 901 -

36

-

LOG r

(LITERATURE)

Figure

5.

Experimental

Log

Versus

Literature

Log

C
In Figure 6 are plotted literature log values versus literature

log 1/C^ values. The large scatter in the points indicates the accuracy

and/or the precision of the measurements is not very good. In Figure 7 are

plotted log versus log 1/C^ where both and were measured by the

generator column method. The error bars indicate the precision of the

measurements. A linear regression analysis of the data gives a slope of

0.994 with a coefficient of determination of 0.998 indicating that the

measurements are accurate and precise.

In conclusion we feel that the Figures 4 through 7 and the regression

analysis of the data on the seven different groups of compounds show that the

slopes of the log versus log plots and the coefficients of

determination of these plots are all approximately equal to unity. This is

further validation of the generator column method.

37
38

-

Log q

Figures.

Log

Versos

-Log

for

the

Literature

Values
39

-

Log

c;

Figure

7,

Log

K

,

Versus

-Log

for

tne

experimental

Values.
VII. RECOMMENDATIONS FOR FUTURE RESEARCH

In any research endeavor it is frequently the case that more new

questions are asked than old ones answered. This is the case for this

work. Two studies were initiated that are incomplete: (1) salinity

dependence of and C,, and (2) the temperature dependence of and w o/w

C^. Information obtainted from these studies is important for determining

the rate and transport of organic substances in the environment.

Salinity Dependence

It can be shown from thermodynamics that the octanol/salt water

partition coefficient is related to the concentration of the aqueous

salt solution, C^, by equation 1:

^ o/sw ^ o/w s s

( 1 )

where k^ is the salting out coefficient which is characteristic of the solute.

Thermodynamics also shows that for compounds of similar chemical

structure k^ is related to the solute molar volume V by equation 2:

k^ = kn + k^ V

s 1 2

( 2 )

where k-j and k^ are series constants. Combining equations 1 and 2

^0/sw = ^/w " ‘h " 4

(3)

To date we have data on two different classes of compounds, the

n-alcohols and the al kyl benzenes. These data were taken in order to

test equation 3. It would be desirable to have data on other types of

compounds in order to generalize equation 3.

Temperature Dependence

The temperature dependence of aqueous solubility may be expressed as

.w d log C”/d(l/T) = -

AH is the heat of solution, and R is gas constant. Very little is known

40
about the heats of solution of hydrophobic substances. Since water temperature

varies from -40°C (in the artic) to 40°C (near the equator), it is desirable

to study temperature dependence in order to make accurate predictions of the

aqueous solubility of organic compounds.

Head-Space Measurements

During the course of this work it was realized that it would be

desirable to have another method (other than shake-flask) for measuring

Ko/w for volatile polar compounds. The shake-flask method gives unreliable

results because of the relative large solubility of water in these compounds.

The head-space method for determining [Brinckman and Bel lama, 1978]

avoids these experimental errors because there is no solute-water interface

in these measurements. These results should be very helpful in the development

of a reliable predictive scheme.

Tests for Other Classes

Additional reliable data on monofunctional groups should be generated to

develop a sound prediction scheme. Compounds containing multifunctional

groups should be studied and the results analyzed using additivity rules for

functional groups to assess the effects of steric hindrance. Also, the aqueous

solubility of organic mixtures should be studied in order to develop a sound

predictive scheme for mixtures.

MacKay et [1980] have developed an equation which may be used

to predict the aqueous solubility and octanol/water partition coefficient

of rigid (solid) molecules. However, predictions are generally poor.

Here our study will generate data for rigid and flexible molecules in the solid

state and will develop suitable expressions to explain their aqueous solubilities.

In the study just completed, there was an attempt to choose

compounds to represent a wide selection of chemical types which would be

of environmental interest. Unfortunately one important group of chemicals

41
was left out, the organometals [Brinckman and Bellama, 1978]. The occurrence

of these compounds in water is known to cause sickness and deaths. It is, therefore,

desirable to determine the aqueous solubility and octanol/water partition

coefficient for this class of compounds.

This study will, of course, include other classes of compounds

of immediate interest to ERA.

Predictive Schemes

Success of a predictive scheme depends crucially on the accuracy

of the limited experimental data on which the calculations must rest.

Hansch et al

[1968] have developed a predictive scheme based on group

contributions. However, there has been some concern on their reported it

values. Here our goal will be to develop a more comprehensive predictive

scheme. This is based on the experimental results obtained in this

laboratory and should also include data on compounds containing multifunctional

groups that have not been measured to date. and measurements should

be made on compounds containing multifunctional groups that have obvious

steric hinderence. measurements should be taken on compounds of

increasing complexity in order to determine where the group additivity breaks

down.

Using thermodynamics and a simple model, log and log will be

related to some simple physical properties (such as, solute molar volumes,

boiling points, and carbon numbers). Our preliminary study suggests

that log 3nd log may be correlated to the solute molar volumes.

Organic pollutants are often multicomponent mixtures. It is,

therefore, desirable to develop thermodynamic relations which can predict

the aqueous solubility of each component in the mixture. These will be

modeled on hydrocarbon-hydrocarbon systems but may be used to predict

the solubility of complex mixtures such as DDT-kerosene systems.

42
VIII. REFERENCES

Andrews, L. and R. Keefer. 1950. Cation Complexes of Compounds Containing

Carbon-Carbon Bonds. VIII. Further Studies on the Argentation of

Substituted Benzenes. J. Am. Chem. Soc. 7^: 5034-5037.

Bohon, R. and W. Claussen. 1951. The Solubility of Aromatic Hydrocarbons

in Water. J. Am. Chem. Soc. 7^: 1571-1578.

Brinckman, F. and J. Bellama, eds. 1978. Organometals and Organometalloids.

ACS Symposium Series, Washington, D.C. 314-326.

Conder, J. and C. Young. 1979. Solution Thermodynamics, Chapter 5 in Physicochemical Measurements by Gas Chromatography. John Wiley and Sons,

New York. 154-221

DeVoe, H. , M. Miller, and S. Wasik. 1981. Generator Columns and High Pressure

Liquid Chromatography for Determining Aqueous Solubilities and

Octanol-Water Partition Coefficients of Hydrophic Substances. N.B.S.

J. Res. 86: 361-366.

Edisbury, J. 1967. Practical Hints of Absorption Spectrometry (Ultraviolet

and Visible). Plenum Press, New York.

Gill, S. , Nichols, and I. Wadso. 1976. Calorimetric Determination of

Enthalpies of Solution of Slightly Soluble Liquids. J. Chem. Thermo.

8: 445-452.

Hansch, C. and A. Leo. 1979. Substituent Constants for Correlation

Analysis in Chemistry and Biology. John Wiley and Sons, New York.

Hansch, C. and W. Dunn, III. 1972. Linear Relationships Between

Liphophilic Character and Biological Activity of Drugs. J. Pharm.

Sci. §±: 1-19.

Hansch, C., J. Quinlan, and G. Lawrence. 1968. The Linear Free-Energy

Relationship Between Partition Coefficients and the Aqueous Solubility

of Organic Liquids. J. Org. Chem. 33: 347-350.

43
Hermann, R. 1972. Theory of Hydrophobic Bonding. II. The Correlation

of Hydrocarbon Solubility in Water with Solvent Cavity Surface

Area. J. Phys. Chem. 76: 2754-2759.

Iwasa, J., T. Fujita, and C. Hansch. 1965. Substituent Constants for

Aliphatic Functions Obtained from Partion Coefficients. J. Med.

Chem. 8: 150-153.

Leo, A., C. Hansch, and D. Elkins. 1971. Partition Coefficients and Their

Uses. Chem. Rev. IV. 525-616.

MacKay, D. , A. Bobra, W. Shiu, S. Yalkowsky. 1980. Relationships Between

Aqueous Solubility and Octanol -Water Partition Coefficients. Chemosphere.

2: 701-711.

May, W. , S. Wasik, and D. Freeman. 1978. Determination of the Aqueous

Solubility of Polynuclear Aromatic Hydrocarbons by a Coupled Coluntn

Liquid Chromatographic Technique. Anal. Chem. 50: 175-179.

May, W. , S. Wasik, and D. Freeman. 1978. Determination of the Solubility

Behavior of Some Polycyclic Aromatic Hydrocarbons in Water. Anal.

Chem. 997-1000.

McAuliffe, C. 1966. Solubility in Water of Paraffin, Cycloparaffin, Olefin,

Acetylene, Cycloolefin, and Aromatic Hydrocarbons. J. Phys. Chem.

70: 1267-1275.

Neely, W. , D. Branson, and G. Blau. 1974. Partition Coefficient to Measure

Bioconcentration Potential of Organic Chemicals in Fish. Environ.

Sci. Technol. 8: 1113-1115.

Reddick, J. and W. Burger. 1955. Techniques of Organic Chemistry vol . 2.

Wiley Interscience Inc., New York.

Sutton, C., and J.A. Calder. 1975. Solubility of Alkylbenzenes in Distilled

and Seawater at 25.0°C. J. Chem. Eng. Data. 20: 320-322.

Tewari , Y. M. Miller, and S. Wasik. Calculation of Aqueous Solubility of

Organic Compounds. In press.

44
APPENDIX I

The octanol /water parti on coefficient, is defined as the

ratio of molar concentration of solute s in octanol saturated with water.

C°, to its concentration in water saturated with octanol, c'^, under

s s equilibrium condition in an octanol/water system:

^/w = C«

Furthermore, the chemical potential of the solute in water, y

y°, may be expressed by the following equations:

+ RT In

w

(

1 )

and in octanol,

( 2 )

y° = y;

+ RT In ( 3 )

where y^ is the chemical potential of pure solute, R is the gas constant,

T is the temperature of the system in Kelvin, (j)^ and (j)® are, respectively,

the volume fraction of solute in water and in octanol, and and y° are the

solute activity coefficients on a volume fraction basis, where y^ approaches

unity as (j)^ approaches unity, in water and in octanol, respectively.

Under equilibrium condition, y^ = y°, hence

w ^w 0 ^0

Ts = ^S '*>S ( 4 )

Similarly for a solute in equilibrium with its aqueous solution (y^ = yp

the activity coefficient may also be expressed as w ^w s ^s

Ys fs - Ys *5 ( 5 )

s s where y^ and (j)^ are, respectively, the solute activity coefficient and

volume fraction in solute. For a solute of low aqueous solubility

45
approaches unity as approaches unity, hence

w _ T Y (p - I 'S ^S

or w( 6 )

At infinite dilution solute concentration in aqueous phase

(c'^) and in octanol phase (C°) may be expressed by the following

s s equations

and C° =

where and are, respectively, the solute partial molar

volume in water and in octanol.

Combining equations 1, 4, and 7 we get

(7)

1 / _ ^

o/w

^w

0

iW

,0

w ^w

s = log T3 - log Y3 + log - ( 8 )

But for all practical purposes ^3

= = V^, the molar volume of

pure solute. Hence equation (8) reduces to

log = log - log (9)

46
APPENDIX II

Proposed Method for Determining

Aqueous Solubility of Organic Compounds

Scope - This method covers the determination of aqueous solubility of

both liquid and solid compounds. There are no restrictions on the type of

compounds.

Summary of Method - Generator columns packed with a solid support and

loaded with an organic substance make it possible to rapidly and conveniently

equilibrate water with the organic phase by coupling the generator column

to an extractor column for high pressure liquid chromatographic analysis

of the aqueous solution. Errors from surface adsorption and loss to the

atmosphere are avoided. Another method for determining the solute

concentration in the aqueous phase is by solvent extraction of the aqueous

phase followed by gas chromatographic analysis of the solvent extract.

Apparatus

1. Generator column - Two different designs were used depending on whether

the eluted aqueous phase was analyzed by HPLC (Procedure A) or by solvent

extraction followed by GC analysis of solvent extract (Procedure B).

The design of the generator column for procedure A is shown in Figure

II-l. The column consists of a 1/4-inch O.D. Pyrex tube joined to a short

enlarged section of 9mm Pyrex tubing which in turn is connected to another section

of 1/4-inch O.D. Pyrex tubing. Connections to inlet Teflon tubing

(1/8-inch O.D.) and to outlet stainless steel tubing (1/16-inch O.D.) are by

means of stainless steel fittings with Teflon ferrules.

2. Constant temperature bath with circulation pump-bath should be

capable of controlling temperature to + 0.05°C.

47
i L Glass Wool

20 cm

Inlet

Support (100-120 mesh

Chromsorb W)

1

'

I

Outlet

Figure II-l Generator column.

48
3. High pressure liquid chromatograph equipped with a UV detector.

4. Extractor column - 6.6 X 0.6 cm stainless steel tube with end fittings

containing 5 ym frits filled with a superficially porous phase packing

(Bondapack C-jg/corasil Waters Associates).

5. Two 6-port high pressure rotary valves.

6. The design of the generator column for procedure B is shown in

Figure II-2. The column consists of a 1/4-inch Pyrex tube jointed to a short enlarged

enlarged section of 9mm O.D. Pyrex tubing. The outlet end of the 9mm O.D.

tubing is connected to a long section of 3mm O.D. stainless steel tubing.

The column is enclosed in a water jacket for temperature control.

7. Collecting tube for procedure B (Figure II-2) - 8X3/4 inch

section of Pyrex tubing with a flat bottom is connected to a short section of

3/8-inch O.D. Pyrex tubing. The collecting tube is sealed with a 3/8-inch

Teflon cap fitting.

8. Gas chromatograph with hydrogen flame detector.

Procedure A - HPLC Method

Procedure A covers the determination of the aqueous solubility of

compounds which absorb in the U.V. The HPLC analytical system is shown schematically

in Figure 1 1-3. Two reciprocating piston pumps deliver the mobile phase (water or methanol -water mixture) through two 6-port high pressure rotary valves and a 30 X 0.6 cm C-18 analytical column to an ultraviolet adsorption detector operating

at 254 nm. Chromatogram peaks are recorded and integrated with a recording

integrator.

1. Determination of response factor

a. Prepare known concentrations (mole/L (M)) solute in methanol

(standard solution).

b. Inject samples of standard solution into HPLC system using a calibrated sample loop.

49
Bath

^

Return

Generator

Cc [umn

Inlet

/

/

//

/

/

/

/

/

/

//

/

/

/

/

/

/ A

Generator

Column

V

Collecting

Vessel

To Constant

Temperature

Bath

Extracting

Solvent

V/ater Containing Solute

Figure II-2 Design of generator column for GC method.

50
T3 O

TO o O

—II u i u c0)

X.o o X- CO ^0) ^CT > ^ ^ rii 0) o ^ 0) CL S Q o

COTO

to

O Q.

_J E

CL 3 X D. oCM

Xo

O)

<u +J

to>>

tooEE3

"oo

S-04-> fOE

<uc

QJ

C7^ 1 O

_J

D.<4-O

+J

toE

cu -Cu

00

ro

cu

S-

(30

51
c. Adjust organic solvent (methanol )/water ratio to obtain a reasonable

retention time for solute peak.

d. Obtain an average peak area for several injections of standard

sample at a set absorbance unit full scale (AUFS).

e. Calculate response factor from following equation:

RF = (conc.(M)) (average area)(AUFS)

2. Loading of Generator Column

a. The design of the generator column is shown in Figure II-l. The

column consists of a 6mm of Pyrex tube jointed to a short enlarged

section of 9mm Pyrex tubing.

b. To pack the column a plug of silanized glass wool is inserted into

one end of the 6mm Pyrex tubing. Silanized diatomaceous silica

support (about 0.5g 100-120 mesh chromosorb W cleaned by Soxhlet

extraction with ethanol and dried) is poured into the tube with tapping

and retained with a second plug of silanized glass wool.

c. If the solute is a liquid, the column is loaded by pulling the

liquid solute through the dry support with gentle section. If the

solute is a solid, a 1% solution of the solid in a volatile solvent

is added to the dry packing. The solvent is then distilled off the

column under reduced pressure.

3. Analysis of Solute

a. Pump water to the generator column by means of a minioumo.

b. With the switching valve (Figure II-3) in the inject position, pump

water through the generator column at a flow rate of 1 ml /min for

approximately 5 minutes.

c. Switch HPLC pump to 100% water.

d. Weigh a 25 mL weighing bottle.

52
e. Once the water reaches the HPLC detector which is indicated by a negative

reading on the detector, simultaneously place the weighing bottle at

the waste position and turn the switching valve to the load position.

f. Switch HPLC pump back to organic (methanol )/water mixture.

g. After collecting approximately 10 mL of water in weighing bottle

turn the switching valve back to inject position.

h. Replace the weighing bottle with the waste container.

i. Turn on the integrator.

j. Weigh the weighing bottle containing water sample.

k. Determine average area/g. of water collected at a selected AUFS

setting from several collections.

l. Calculate the solute concentration in water by the following

equation:

solute concentration (M) = (RF) (average area/g) (AUFS) (997g/L)

(volume of sample loop in L)

Procedure B - GC Method

1. Determination of Calibration Curve

a. Prepare solute standard solutions of varying concentrations

b. Select a column and optimum GC operating conditions for suitable

resolution between the solute and solvent and the solute and

extracting solvent.

c. Inject a known volume of each standard solution into injecton

part of GC.

d. Determine average area/yl for each standard solution.

e. Determine linear regression equation of concentration vs area/yl

for in the following form

conc(M) = a + b

53
2, Loading of Generator Column

a. Generator column is packed and loaded with solute in the same manner

as for the HPLC method.

b. Approximately 20 cm of straight stainless steel tubing is connected

to the bottom of the generator column and a beaker is placed beneath

the tubing to collect the water.

c. The top of the generator column is connected to a water reservoir

(Figure II-4) using Teflon tubing.

d. Air or nitrogen pressure (5 P.S.I.) from an air or nitrogen cylinder

is applied to the water reservoir thus forcing water from the reservoir

through the column to the beaker.

e. Water is collected in the beaker for approximately 10 min. while

the solute concentration in water equilibrates.

3. Collection and Extraction of the Solute

a. During the equilibration time, a known weight of extracting solvent

is added to a collection vessel which contains a glass-enclosed

stirring rod and can be capped. The extracting solvent should completely

cover the bottom of the collection vessel.

b. Record the weight of collection vessel with cap and extracting

solvent.

c. Remove the cap from the collection vessel and place it under the

generator column so that water from the generator column enters below

the level of the extracting solvent (Figure II-2).

d. When the collection vessel is filled, remove it from under the

generator column, replace the cap, and weigh the filled vessel.

e. Determine the weight of water collected.

54
Column Inlet

Figure 1 1-4 Water reservoir for GC method.
4.

f. Place the collection vessel on a magnetic stirrer and stir the

contents for approximately 30 min. controlling the rate of stirring

so as not to break the meniscus between the extracting solvent

and water layers.

Analysis of the solute

a. After stirring remove a known volume of extracting solvent from

the vessel using a microliter syringe and inject into the G.C.

Record the peak area/yL injected and from the regression equation

of the calibration line, determine the concentration of solute

in extracting solvent.

The concentration of solute in water (M), , is determined from

the following equation

,w ^ «es

b.

es

where C” is the concentration of solute in extracting solvent

dn ^ and are the densities of water and extracting solvent,

respectively, and g^^ and g^ q are the grams of extracting solvent

and water, respectively, contained in the collection vessel.

d. Replicate injections are made from each collection vessel to determine

an average concentration in water for the vessel.

e. At least one additional collection vessel is prepared in a similar

manner for each generator column.

56
NBS-114A (REV. 2 - 80 ) U.S. DEPT. OF COMM. 1. PUBLICATION OR 2. Performing Organ. Report No. 3. Publication Date BIBLIOGRAPHIC DATA

SHEET (See instructions)

REPORT NO.

NBSIR-81-2406 December 1981

4. TITLE AND SUBTITLE ^ „ "Octanol /Water Partition Coefficients and Aqueous Solubilities of Organic

Compounds"

5. AUTHOR(S) Stanley P. Wasik, Yadu B. Tewari , Michele M. Miller,

and Daniel E. Marti re

6. PERFORMING ORGANIZATION (If joint or other than NBS, see instructions) 7 . Contract/Grant No. NATIONAL BUREAU OF STANDARDS

DEPARTMENT OF COMMERCE «. Type of Report & Period Covered

WASHINGTON, D.C. 20234

9.

SPONSORING ORGANIZATION NAME AND COMPLETE ADDRESS (Street, City, State, ZIP)

Office of Toxic Substances

Environmental Protection Agency

Washington, DC 20460

10.

SUPPLEMENTARY NOTES

I I Document describes a computer program; SF-185, FIPS Software Summary, is attached.

11.

ABSTRACT (A 200-word or less factual summary of most significant information. If document includes a significant

bibliography or literature survey, mention it here)

A generator column method for measuring the octanol /water partition

coefficient, and the aqueous solubility, C^, is described. When water

is pumped through a generator column packed with solid support coated with

an organic stationary phase, an aqueous solution is generated that is in

equilibrium with the stationary phase. The solute concentration in the

elutea aqueous phase was measured either by high pressure liquid

chromatography or by solvent extraction followed by gas chromatographic

analysis.

Aqueous solubilities and octanol/water partition coefficients of organic

solutes, falling into 7 general chemical classes, have been systematically

determined using the modified generator column method. From thermodynamics

an equation is derived relating to the volume-fraction-based solute

activity coefficient in water (y^)* The latter being determinable from C^.

For each class of compounds, excellent linear correlations are found between

log and log y^, with slopes close to the theoretical value of unity.

12. KEY WORDS (Six to twelve entries; alphabetical order; capitalize only proper names; and separate key words by semicolons)

Activity coefficients; aqueous solubility; gas chromatography; generator

column; high pressure liquid chromatography; and octanol/water partition

coefficients

13. AVAILABILITY

pc j Uni imited

1 I For Official Distribution. Do Not Release to NTIS

Order From Superintendent of Documents, U.S. Government Printing Office, Washington, D.C.

20402.

Order From National Technical Information Service (NTIS), Springfield, VA, 22161

14. NO. OF

PRINTED PAGES

66

15. Price

$ 8.00

USCOMM-DC 6 143-pi-
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