Table 4. Predicted pKa values for the secondary and tertiary amines shown in Fig. 2, using di- and tri-ethylamine as a reference, respectively.
In the case or piperazine and DABCO the pKa value corresponds to the singly protonated species.
| Exp | PM6-D3H+/SMD | PM6-D3H+/SMD* | PM6/SMD* | PM6/COSMO* | |
|---|---|---|---|---|---|
| Secondary amines | |||||
| Diethylamine | 11.1 | ||||
| Morpholine | 8.4 | 7.3 | 7.8 | 7.2 | 7.9 |
| Piperidine | 11.2 | 10.9 | 11.3 | 10.8 | 10.9 |
| Piperazine | 9.8 | 8.8 | 9.0 | 8.4 | 9.1 |
| Pyrrolidine | 11.3 | 11.3 | 11.1 | 10.6 | 11.3 |
| Diallylamine | 9.3 | 8.0 | 8.7 | 7.9 | 8.3 |
| Diisopropylamine | 11.0 | 12.6 | 12.4 | 11.7 | 11.4 |
| MAD | 0.9 | 0.6 | 1.0 | 0.5 | |
| Max AD | 1.6 | 1.4 | 1.4 | 1.0 | |
| Tertiary amines | |||||
| Tri-ethylamine | 10.7 | ||||
| N-methyl morpholine | 7.4 | 4.9 | 5.8 | 4.6 | 7.4 |
| Quinuclidine | 11.0 | 8.1 | 8.7 | 7.5 | 9.4 |
| DABCO | 8.8 | 5.1 | 5.6 | 4.3 | 6.7 |
| N-Ethylpyrrolidine | 10.4 | 9.0 | 9.5 | 8.6 | 10.4 |
| Triallylamine | 8.3 | 4.8 | 6.9 | 5.2 | 6.9 |
| Diisopropylmethylamine | 10.5 | 11.8 | 12.4 | 11.3 | 11.5 |
| MAD | 2.5 | 1.9 | 2.7 | 1.0 | |
| Max AD | 3.7 | 3.2 | 4.5 | 2.1 | |
Note:
*
Indicates that the rigid rotor, harmonic oscillator free energy term is neglected.