Comments on: Nucleophilic Acyl Substitution (With Negatively Charged Nucleophiles)

By: James Ashenhurst

James Ashenhurst — Tue, 19 Mar 2024 19:29:08 +0000

In reply to failinguoftstudent. Glad to hear you find it useful - if the username is accurate, hope you're getting help! James

By: failinguoftstudent

failinguoftstudent — Tue, 19 Mar 2024 03:59:08 +0000

The fact that all of this is free… you’re doing the service of god my friend.

By: Misagh

Misagh — Tue, 18 Apr 2023 16:13:57 +0000

thank you james very much. It was helpful indeed.
I wish more progress for you in particular in your researc

By: Rubén

Rubén — Fri, 31 Mar 2023 07:45:16 +0000

Hi James, thanks for your web. I noticed that DIBAL-H has one more C-atom in your drawing.
Regards,
Rubén

By: James Ashenhurst

James Ashenhurst — Wed, 11 Jan 2023 18:40:42 +0000

In reply to Anna. Good question. It's likely due to the inductive effect of the sp2-hybridized carbon atoms of the aromatic ring attached to the carbonyl. You can think of them as having a greater effective electronegativity, since they have 33% s-character (vs 25% for sp3) and the electrons are held more tightly to the nucleus.

By: Anna

Anna — Sun, 16 Oct 2022 04:55:27 +0000

Why does the acidity of the corresponding carboxylic acid increase due to attachment of phenyl or vinyl group , contrary to the decrease expected due to resonance effect ?

By: James Ashenhurst

James Ashenhurst — Wed, 21 Sep 2022 15:39:43 +0000

In reply to L L.

Great question. The product of nucleophilic acyl substitution is a carboxylic acid.

Now you have a carboxylic acid (pKa = 4) in the presence of an alkoxide (conjugate base of an alcohol, pKa about 16).

It is then deprotonated to give a carboxylate.

Now what happens?

If you add RO(-) to the carboxylate, in order for nucleophilic acyl substitution to occur, your leaving group would have to be O(2-). That’s impossible, basically.

By: L L

L L — Wed, 21 Sep 2022 15:28:42 +0000

For the nucleophilic acyl substitution of an ester with OH-, why is the OR- group the leaving group?
In the graph showing the pKa of leaving groups, it appears that OH- is a slightly better leaving group than OR-. If so, why does the reaction still occur? The graph states that this is a special case, but I’m not really sure why.

By: James Ashenhurst

James Ashenhurst — Fri, 16 Sep 2022 20:45:42 +0000

In reply to Aaryan. thank you

By: Aaryan

Aaryan — Fri, 16 Sep 2022 17:43:18 +0000

Beautifully crafted! Such a gem for the avid learners :)