Some of my colleagues have challenged the pKa values Marvin calculates for ephedrine, N-methylephedrine and norephedrine stating that the basicity should follow the general trend of tertiary > secondary > primary. Marvin shows the reverse trend. Is there an explaination for this behavior?
With the improved pKa calculator I obtained the next values:
ephedrine: 9.52 (9.60)
N-methyl ephedrine 9.06 (9.30)
norephedrine 9.37 (smaller than 9.44)
Literature values are given in parenthesis.
Any ideas as to why the basicity of the tertiary is lower than the primary and secondary? The secondary is the most basic. Is there some special circumstance/structure in this molecule to explain this?
Where did you get your pKa values (reference)?
When will this improved calculator be available?
I still get anomolous pKa values for nucleobases (adenine, etc.).
Is there a beta available?
Józsi is on holiday until the end of next week. He will send a detailed response when he is back. Some comments until then:
I think this is usually the case: secondary amines are stronger than tertiary amines because of steric effects. (Józsi will correct me if I am wrong)
|Any ideas as to why the basicity of the tertiary is lower than the primary and secondary? The secondary is the most basic. Is there some special circumstance/structure in this molecule to explain this? |
We will release Marvin after fixing a few bugs (not related to pKa calculation). Hopefully very soon.
|When will this improved calculator be available? |
The latest test release is at http://www.chemaxon.com/shared/alpha/marvin/, but this doesn't look like to produce the same numbers that Józsi posted, so please wait for the release.
|Is there a beta available? |
I obtained our pKa data from our "in house" database.
If you calculates solvent accesible surface area increments of atoms of ephedrine derivatives you will obtain the next values:
prim. amin: 7.01 [Angstrom]
sec. amin: 8.71 [Angstrom]
tert. amin : 5.48 [Angstrom]
These values are in good agreement with calculated pKa order.