Sodium salt of naproxen is levorotatory (-11 degree), but the free acid of naproxen is dextrorotatory...?

Question

...(+66 degree), This shows a striking example of the lack of obvious relationship between structure and optical rotation, since both the acid and salt have the same configuration about the chiral centre, unlike enantiomers that are non-superimposable to each other.

The question is: how can this be? I thought with same configuration around the chiral centre, the same rotation should be obtained.

Answer 1

You are correct in your statement. This is one of those compounds that show no relationship between the optical rotation and the chemical structure. I am not sure why, but this is one of the exceptions to the rule of salts vs. free acids. I am not advanced enough in this area to give a better answer as I also find this to be an interesting phenomenon. A good pharmacist might be able to put you in touch with a university that is studying this in depth and maybe they have the answers. I am a chemist who mainly deals with agricultural chemicals, and almost all of those behave as expected.