[mrsmith]

Hello, I have a few questions pertaining to my prelab assignment. The first part deals with synthesizing N Acetyl D L phenylalanine from D L phenylalanine.

THe first question asks why acetylation occurs at the amino site rather than the COOH site, and I think it is because the amino group is a better nucleophile, and the fact that the lone pairs on the COOH are delocalized doesnt help things either.

The second question is the one I cant get. It asks why it is necessary to dissolve the D L phenylalanine in NaOH before reacting it with acetic anhydride. I *think* it has to do with the fact that the NaOH will deprotonate the amino group...making it more reactive?? Not sure but thats my guess.

Any additional help would be greatly appreciated, thank you.

[Kryolith]

Welcome to the forum 

THe first question asks why acetylation occurs at the amino site rather than the COOH site, and I think it is because the amino group is a better nucleophile, and the fact that the lone pairs on the COOH are delocalized doesnt help things either.

Thats' right.

The second question is the one I cant get. It asks why it is necessary to dissolve the D L phenylalanine in NaOH before reacting it with acetic anhydride. I *think* it has to do with the fact that the NaOH will deprotonate the amino group...making it more reactive?? Not sure but thats my guess.

What does the structure of an amino acid (in dependency of the pH) look like?

[mrsmith]

+NH3 - C - COO-

A zwitterion, strong bases take protons, so the NH3 would become NH2, lowering steric hindrance, allowing for easier acetylation?

I cant see it

[Kryolith]

There is a certain pH where the amino acid is 100 % a zwitterion (in aqueous solution). It is called isoelectric point (IEP). At higher pH values the NH₃⁺ group will be deptrotonated, at lower pH values the COO^- group will be protonated.

Your acetylation agent is electrophilic, so it prefers the reaction with a nucleophilic center. The question is: Which form of the amino group (protonated or not) is the better nucleophile?

[mrsmith]

The deprotonated form of the amino group is the better Nu, thats why we need to add the base because that will give us the better Nu for the electrophilic agent.

I see now, thanks alot. +1

[Kryolith]

You're welcome.