## 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



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TKA 40278 (CGI 827) 

## SIGNATURES

Study Director: Mrs. Aleesandra Tognucci

Management: Dr. JSrn Schreitm(Jller



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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



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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.



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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



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



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### 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



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### 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.



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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).



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## 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).