REPORT

Study Title:

CALCULATION OF THE DISSOCIATION CONSTANT

OF TKA 40278 (CGI 827)

Study Director:

Mrs. Alessandra Tognucci

Study Completion Date:

May 23, 2003

Test Facility:

RCC Ltd

Environmental Chemistry & Pharmanatytics

CH-4452 ItlngerdSwitzerland

S~onsor,’

CIBA SPECIALTY CHEMICALS INC.

CH - 4002 Basel/Switzerland

RCC Study Number:

845430

Page 1 of 10

59
RCC Study Number 845430 REPORT Page 2 TKA 40278 (CGI 827)

SIGNATURES

Study Director: Mrs. Aleesandra Tognucci

Management: Dr. JSrn Schreitm(Jller

60
RCC Study Number 845430 REPORT Paga 3

TKA 40278 (CGI 827)

CONTENTS

SIGNATURES ................................................................................................................. 2

CONTENTS .................................................................................................................... 3

PREFACE ....................................................................................................................... 4

1 PURPOSE .............................................................................................................. 5

2 MATERIALS AND METHODS ................................................................................ 5

2.1 TEST ITEM ........................................................................ ~ ..........................5

2.2 DISSOCIATION CONSTANT ........................................................................ 6

2.3 ESTIMATION METHODS .............................................................................. 7

2.3.1 Taft and Hammett Correlations ........................................................ 7

2.3.2 Ranking According to Strength ........................................................ 8

2.3.3 Zwitterion ......................................................................................... 8

2.3.4 Uncertainty in Estimated Values ...................................................... 8

3 RESULTS AND DISCUSSION ............................................................................... 9

4 CONCLUSION ....................................................................................................... 9

5 REFERENCE ....................................................................................... i ...............10

61
RCC Study Number 845430 REPORT Page 4

TKA 40278 (CG1827)

PREFACE

GENERAL

Title:

Sponsor:

Monitoring Scientist:

Test Facility:

Calculation of the Dissociation Constant of TKA 40278

(CGI 827)

ClBA SPECIALTY CHEMICALS INC.

CH-4002 Basel/Switzerland

Dr. Moung Sook Lee

RCC Ltd

Environmental Chemistry & Pharmanalytics

Zelgliweg 1

CH-4452 Itingen/Switzerland

RESPONSIBILITIES

Study Director:

Deputy Study Director:

Mrs. Alessandra Tognucci

Dr. Wolfgang VSIkel

SCHEDULE

Study completion date: May 23, 2003/toa

ARCHIVING

RCC Ltd, CH-4452 Itingen]Switzerland will retain the study plan, raw data, a sample of test

item and the final report of the present study for at least ten years.

No data will be discarded without the sponsor’s consent.

62
RCC Study Number 845430 REPORT Page 5 TKA 40278 (CGI 827)

1 PURPOSE

The purpose of this study was to estimate the dissociation constants (pK~-values) of TKA

40278 (CGI 827).

The dissociation of a chemical in water is of importance in assessing its impact upon the

environment. It governs the form of the test item, which in turn determines its behaviour and

transport. It may affect the adsorption of the chemical on soils and adsorption into biological

ceils.

2 MATERIALS AND METHODS

2.1 TEST ITEM

The test item and the information concerning the test item were provided by the sponsor.

Identity: TKA 40278

Product Name: CGI 827

Appearance: Solid, slightly yellow

63
RCO Study Number 845430 REPORT TKA 40278 (CGI 827) Page 6

2.2 DISSOCIATION CONSTANT

Dissociation is the reversible splitting into two or more chemical species, which are ionic. The

process is indicated generally by

RX = R÷ + X" (1)

and the concentration equilibrium constant governing the reaction is

K _

[R*].[X-]

[RX] (brackets indicate the concentration of the species) (2)

For example, In the particular case where R is hydrogen (the substance is an acid), the

constant is

K. = fH+l’ [X-] [H+]

" " [HX] (3)

or

pK=

= pH - log !,X,.-.]"

(4)

where

= Acid dissociation ionisation constant

Equation 4 expresses the strength of the conjugate acidic form of a basic compound. The

greater the pKa value the weaker the acid or, conversely, the stronger is its conjugate basic

form.

In aqueous media, however, the range of interest is restricted to acids with pK=’s of 0-14.

Acids with pK~ < 0 will be completely dissociated to the corresponding conjugate base, while

those with pK= > 14 completely associated. If the focus is further narrowed to aqueous media

within the normal environmental pH range of pH 5-8, the range of acidities that are of concern

is even more restricted.

Equation 4 implies that the acidity range of principal interest corresponds to a pKa range from

pK~ 3 to pKa 10. If an organic species has a pK~ outside these limits, it is expected to be

either completely (> 99%) dissociated (pKa of organic acid pH < 3) or completely undissociated (pK~ of conjugated acid pH > 10) in an aqueous environment.

64
RCC Study Number 845430 REPORT TKA 40278 (CGI 827) Page 7

2.3 ESTIMATION METHODS

The estimation methods as described in the literature make pK= predictions based on the

molecular structures of compounds [1-6].

The dissociation constant of an organic acid (or conjugated acid of an organic base) can be

estimated by applying a linear free energy relation ship. At a constant temperature the pKa of

a molecule is linear related to the free energy change for the reaction of ionisation of a

proton:

 ̄~Go = 2.303  ̄ R. T. pK~

The insertion of a substituent leads to a corresponding change in AGo and therefore in pKa. If

these changes are not very big, the effects can be added together, This observation is the

basis of the Hammett and Taft equations. The Hammett relationship for aromatic systems

end the Taft relationship for aliphatics are the most generally applicable linear free energy

relationships for estimating acid dissociation constants. These correlations should provide

estimates of acid dissociation constants that are adequately accurate for evaluation of

probable environmental partitioning behaviour.

2.3.1 Taft and Hammett Correlations

The Taft correlation is used for aliphatic and alicyciic species most commonly written as

follows:

pK = PK°- p*" (~; o*) (6)

where

pKo = Ionisation constant of the parent compound

= Constant for the particular reaction

= Characteristic constant of a given substituent

The Hammett equation is used for the prediction of pKa values for aromatic substances:

pKa = PKa°" p’ (Z (~) (7)

where

P

= pK~ of the unsubstituted acid or base

= Constant for a particular equilibrium

= Constant assigned to a particular substituent

65
RCC Study Number 845430 REPORT TKA 40278 (CGI 827) Page 8

2.3.2 Ranking According to Strength

When a polybaslc acid (or base) has chemically different centres (for example three phenol

groups as in pyrogallol), the centres loose protons one after the other. The order of protons

less depends on the strength of the apparent pK~ of the centres (apparent pK~ is the pKa,

which the centre has if it is the only reaction centre in the molecule). The reaction centre

having the strongest apparent pK~ will be iontsed and so on. When the second (third, etc.)

centre looses a proton, the first is (theoretically) totally ionised, so its modifying effect on the

second centre is changed in comparison with the non-ionised form. The second (third, etc.)

pK~ must be recalculated with the modified sigma valued of the ionised centre(s).

2,3.3 Zwitterlon

If a neutral molecule carries both a positive and negative charge, it is known as a zwittedon.

Zwitterions are formed from amphoteric compounds if the pK~ of the protonated basic is close

to or higher than the pK,, of the acidic group (for example: o~-amino acids). In this case both

pl~ values must be recalculated with the o-values of ionlsed groups.

2,3.4 Uncertainty in Estimated Values

Fundamental sources of error in predicated values include deviations from the basic linear

free energy relationship assumption of separability of substituent constants (G-values) and

reaction constants (p-values). These deviations, and hence the errors in the predicated

values, are likely to be largest for strongly interacting substituents (large absolute value of

G). It seems obvious that errors are smallest for aromatic species with a single acid

functionality. Errors are larger for aliphatic species and for compounds containing more than

one acid functional group.

The greater uncertainty is associated with difficulties in selecting an appropriate parent

compound as well as in extending the correlations beyond the range of substituents used in

defining p for the parent.

A further source of uncertainty in estimated values results from the fact that the substituent

and reaclion constants given in the literature are obtained from a variety of sources, rather

than from one consistent set of measurements.

Although the reliability of the estimated pKa’s cannot be determined quantitatively, values

estimated according to the procedures as described above can confidently be regarded as

reliable to within an order of magnitude. Most estimates are probably good within ± 0.5 in pkg.

66
RCC Study Number 845430 REPORT Page 9 TKA 40278 (CGI 827)

3 RESULTS AND DISCUSSION

The molecular structure of TKA 40278 (CGI 827) was used for the estimation of the

dissociation behaviour. The compound has several sites, which can be protonated or

dissociated.

Acid/Base pK= Method

Alkohol (R’R’CH(OH)) (2 x) 12.8 Taft

The test item was evaluated as an alcohol. The calculation of the dissociation constant was

performed using the respective substituents.

4 CONCLUSION

TKA 40278 (CGI 827) does not dissociate or protonate in the environmentally relevant pH

range (pH 5 to pH 8).

67
RCC Study Number 845430 REPORT TKA 40278 (CGI 827) Page 10

5 REFERENCE

[2]

[4]

[6]

[7]

Perrin, D.D., Boyd Dempsey and E.P. Serjeant

pKa Prediction for Organic Acids and Bases, Chapman and Hall, Ltd., London

(1981).

A. Streitwieser, Jr., C.H. Heathcock

Organische Chemie, Verlag Chemie, Weinheim (1980).

Lyman W.J., W.F. Reehl, D.M. Rosenblatt

Handbook of Chemical Property Estimation Methods; Environmental Behaviour of

Organic Compounds. McGraw-Hill, New York (1982).

Serjeant, E.P. and B. Dempsey

"lonisation Constants of Organic Acids in Aqueous Solutions", Pergamon Press,

New York (1979).

Kort0m, G., W. Vogel, K. Andrussow

"Dissociation Constants of Organic Acids in Aqueous Solutions", Butterworth,

London (1961).

Perrin, D.D.

"Dissociation constants of organic bases in aqueous solutions", Butterworths,

London (1972).

March, J.

Advanced Organic Chemistry, 2nd edition, McGraw-Hill, Tokyo (1984).