1,4-Diazabicyclo[2.2.2]octane-2-methanol

Dissociation constant

Link to relevant study record(s)

Reference

Endpoint:

dissociation constant

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 Mar 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 112 (Dissociation Constants in Water)

GLP compliance:

no

Dissociating properties:

yes

No.:

#1

pKa:

8.37

Temp.:

20 °C

SPARC predictions

8.38 and 8.78 (two respective tertiary amine reaction sites)

15.24 (hydroxyl group as reaction site)

Experimental results

Neutralization by hydrochloric acid:

Test substance solution was titrated by 0.1 N hydrochloric acid three times. 10 points before equivalence points were selected and pKa was calculated.

pKa = pH + log[BH+]/[B]

[BH+]: (Normal acid titration solution) * (factor of titration solution) * (added volume of titration solution (mL))/(volume of test solution (mL))

[B]: Concentration of test solution (M) – [BH+]

1st titration:

No.	Volume [mL]	pH	[BH+]	[B]	log ([BH+]/[B])	pKa
1	2.00	8.58	0.003846	0.006154	- 0.20	8.38
2	2.05	8.57	0.003939	0.006061	- 0.19	8.38
3	2.10	8.55	0.004031	0.005969	- 0.17	8.38
4	2.15	8.53	0.004123	0.005877	- 0.15	8.38
5	2.20	8.51	0.004215	0.005785	- 0.14	8.37
6	2.25	8.49	0.004306	0.005694	- 0.12	8.37
7	2.30	8.47	0.004398	0.005602	- 0.11	8.36
8	2.35	8.46	0.004489	0.005511	- 0.09	8.37
9	2.40	8.45	0.004580	0.005420	- 0.07	8.38
10	2.45	8.46	0.004671	0.005329	- 0.06	8.36

Mean pKa: 8.37, standard deviation: 0.01

2nd titration:

No.	Volume [mL]	pH	[BH+]	[B]	log ([BH+]/[B])	pKa
1	2.00	8.60	0.003846	0.006154	- 0.20	8.40
2	2.05	8.58	0.003939	0.006061	- 0.19	8.39
3	2.10	8.56	0.004031	0.005969	- 0.17	8.39
4	2.15	8.52	0.004123	0.005877	- 0.15	8.37
5	2.20	8.52	0.004215	0.005785	- 0.14	8.38
6	2.25	8.49	0.004306	0.005694	- 0.12	8.37
7	2.30	8.48	0.004398	0.005602	- 0.11	8.37
8	2.35	8.46	0.004489	0.005511	- 0.09	8.37
9	2.40	8.44	0.004580	0.005420	- 0.07	8.37
10	2.45	8.42	0.004671	0.005329	- 0.06	8.36

Mean pKa: 8.38; standard deviation: 0.01

3rd titration:

No.	Volume [mL]	pH	[BH+]	[B]	log ([BH+]/[B])	pKa
1	2.00	8.59	0.003846	0.006154	- 0.20	8.39
2	2.05	8.56	0.003939	0.006061	- 0.19	8.37
3	2.10	8.55	0.004031	0.005969	- 0.17	8.38
4	2.15	8.54	0.004123	0.005877	- 0.15	8.39
5	2.20	8.51	0.004215	0.005785	- 0.14	8.37
6	2.25	8.49	0.004306	0.005694	- 0.12	8.37
7	2.30	8.47	0.004398	0.005602	- 0.11	8.36
8	2.35	8.46	0.004489	0.005511	- 0.09	8.37
9	2.40	8.44	0.004580	0.005420	- 0.07	8.37
10	2.45	8.42	0.004671	0.005329	- 0.06	8.36

Mean pKa: 8.37; standard deviation: 0.01.

Neutralization by sodium hydroxide:

Test substance solution was titrated by 0.1 N sodium hydroxide once. No significant change in pH was observed around equivalence points (approx. 5 mL of added volume).

Interpretation

pKa was 8.37 as a result of the dissociation constant measurement of the test substance (tertiary amine) using neutralization titration with hydrochloric acid. This value was similar to the predicted pKa at tertiary amine sites: 8.38 and 8.75. Because the literature pKa value of a similar substance DABCO (1,4-diazacyclo[2.2.2]octane) is 2.97 and 8.82, pKa = 8.37 is considered as the first step of dissociation.

Since the measurement of pKa by sodium hydroxide resulted in no pH change around the equivalence points, pKa was not able to be measured. The predicted values of hydroxyl group of the test substance, and methanol used as analogue, are 15.24 and 15.50, respectively. This is the reason why the titration method is not an appropriate method in this case.

Description of key information

8.37 at 20 °C (OECD 112, titration method)

Key value for chemical safety assessment

pKa at 20°C:

8.37

Additional information

Obtained pKa value results from the measurement of the test substance (tertiary amine) using neutralization titration with hydrochloric acid. This value is similar to the with SPARC predicted pKa at tertiary amine sites: 8.38 and 8.75. Because the literature pKa value of a similar substance DABCO (1,4-diazacyclo[2.2.2]octane) is 2.97 and 8.82, pKa = 8.37 is considered as the first step of dissociation.

Since the measurement of pKa by sodium hydroxide resulted in no pH change around the equivalence points, pKa was not able to be measured. The predicted values of hydroxyl group of the test substance, and methanol used as analogue, are 15.24 and 15.50, respectively. This is a reason why the titration method is not an appropriate method in this case.