[anilin]

Hi,
I need to know in acid-catalysed hydrolysis of a dipeptide, whether Oxygen or Nitrogen in the peptide bond will be protonated first. and why?
thanks

[Dolphinsiu]

Hard to hard, soft to soft

N is soft species. O is hard species

H+ is also hard species.....Hence, this question is simple. O will be protonated first.

[lutesium]

What do you mean by hard and soft?


Lutesium...

[Dolphinsiu]

Yes...actually I just predict from Hard and soft acid and base principle (HSAB)

Also, I think that the best choice of two mechanisms that you send to my email is the first one.

[anilin]

Yes...actually I just predict from Hard and soft acid and base principle (HSAB)

Also, I think that the best choice of two mechanisms that you send to my email is the first one.

you mean my second mechanism (protanation of N in peptide bond) happens as well?

[Dolphinsiu]

Yes. second mechanism also occurs since the carbocation formed may be stabilized by methyl group (electron donating group). However, in most acid catalyzed reaction of carbonyl compound, H+ will prefer to react on carbonyl O because it is more electron rich (more nucleophilic) when compared to N. (more lone pair electrons)

[macman104]

The nucleophilicity of the nitrogen is decreased because it's lone pair participates in a resonance structure with the carbonyl group.  This not only decreases the electron-rich character of the nitrogen, but increases the electron-rich character of the oxygen.  Oxygen is also more electronegative.  Oxygen is protonated.

Here's is a mechanism for the hydrolysis of an amide.

http://www.chem.ucalgary.ca/courses/350/Carey5th/Ch20/ch20-3-4-1.html