cyproconazole (ISO); (2RS,3RS;2RS,3SR)-2-(4-chlorophenyl)-3-cyclopropyl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol

Dissociation constant

Link to relevant study record(s)

Reference

Endpoint:

dissociation constant

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 Jan 1989 to 30 Jan 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 112 (Dissociation Constants in Water)

Version / remarks:

May 1981

GLP compliance:

yes

Dissociating properties:

no

Remarks on result:

other: the test substance has no dissociation within the range pH 3 to pH 10

RESULTS AND DISCUSSION

The graphical representation of the 6 titrations shows that the 6 titrations yield practically the same results and that there are no significant differences between titrations with or without test substance present. The pH-mL points follow exactly the pattern to be expected for the titration of a strong acid with a strong base: At the beginning

of the titration the pH increases approximately linearly with the volume of base. Near the equivalence point (where 2.0 mL 0.01 M NaOH have been added to 2.0 mL 0.01 M HCl) a sharp rise of the pH occurs. At the end of the titration the pH increases only smoothly as determined by the activity of OH- and the pK of water. The only significant differences between the 6 titrations occur near the equivalence point. This of course is due to the fact that in this zone small differences in the total amount of added base have a large influence on the pH.

From this qualitative inspection of the titration data it is evident that between pH 3.5 and 10 test substance in water has neither acid nor base character, i.e., under ambient conditions (de)protonation of test substance does not occur.

A quantitative evaluation of the titration data was done by means of the program "TITFIT", which performs a non-linear least-squares fit according to the Newton-Gauss-Marquardt technique. The selection of the proper chemical model was straightforward since each of the six data sets is as expected for the titration of a strong acid. In our case all the concentrations are known and therefore, there are only two parameters for each set of titration data to be adjusted: 1. the proton activity coefficient (in TITFIT its; inverse value, 1/α, is used) which determines the low-pH part· o the titration and 2. the pK of water (in TITFIT its negative decadic logarithm, pKw, is used) which determines the high-pH region.

Fitting each set of titration data separately showed that the assumed model indeed gave a good fit of the data. The standard deviation between experimental and calculated points was 0.05 mL throughout, the values for 1/α were 2.6 - 2.7, and for pKw 13.6 - 13.7 was calculated. The fact that the calculated parameters for the six titrations closely agreed clearly shows the absence of an influence of test substance on the titration curve.

Table 1 Titration data

Titration	Control	Control	Control	Substance	Substance	Substance
Exp. pH for buffer pH 4.00	4.07	4.06	4.08	4.04	4.08	4.08
Exp. pH for buffer pH 7.00	6.99	6.99	6.99	6.96	7.00	7.00
Volume of NaOH (mL)	pH (corrected values)
0.00	3.52	3.53	3.52	3.54	3.53	3.53
0.20	3.57	3.58	3.57	3.59	3.58	3.58
0.40	3.63	3.63	3.62	3.65	3.64	3.63
0.60	3.69	3.70	3.69	3.71	3.70	3.69
0.80	3.76	3.78	3.76	3.78	3.77	3.77
1.00	3.86	3.87	3.84	3.87	3.86	3.86
1.20	3.97	3.97	3.97	3.99	3.98	3.97
1.40	4.11	4.12	4.12	4.14	4.13	4.12
1.60	4.35	4.35	4.35	4.38	4.36	4.36
1.80	4.85	4.83	4.85	4.90	4.82	4.85
2.00	8.88	8.94	8.78	8.93	7.76	8.19
2.20	9.63	9.59	9.59	9.61	9.46	9.44
2.40	9.89	9.86	9.86	9.87	9.79	9.78

Conclusions:

The test substance has no dissociation within the range pH 3 to pH 10.

Executive summary:

The study was performed to evaluate the dissociation constant of the test substance in water according to OECD TG 112 in compliance with GLP. Potentiometric titrations of the test substance were conducted in water at 20 °C at constant ionic strength (I= 0.1 M; KCl) under nitrogen. The results show that the test substance does not have acid/base properties in the pH range between 3 and 10.In other words: the identity of the compound remains unchanged when it is dissolved in water under field conditions.

Description of key information

No dissociation within the range of pH 3 - 10, OECD TG 112, potentiometric titration, Gampp 1998