[lutesium]

Dear Sir/Ma'am

Can Ethyl Acetate be used to acylate Aniline??? Or this RXN is impossible without the usage of Acetic Anhydride???

Thank You Very Much


Lutesium

[sjb]

I don't think ethoxide would be good enough of a leaving group to do this reaction as planned.

I've run columns for a variety of anilines in EtOAc / hexane mixtures, and don't recall seeing any (relevant) amide by products in the fractions.

You would need acetic anhydride, or perhaps the acyl halide to form the amide (with possible surrogate base to mop up the acid by product).

S

[lutesium]

I remember myself acetylating an amide with Ac-Cl lots of HCl gas formed and a crystalline mass at the bottom of the flask... Does anyone know if the amine or its HCl salt would be important for acylation??? I mean can the HCl salt of the amine be acylated like his freebase situation??? If yes why do we waste so much time to make the acetic anhydride???

[AWK]

Try Schotten-Baumann conditions

[lutesium]

Thank you very much AWK but so from right on can we say that there's no need to make Acetic Anhydride???


Lutesium...

[agrobert]

wiki balls

[lutesium]

What does it mean???


Lutesium...

[sjb]

Does anyone know if the amine or its HCl salt would be important for acylation??? I mean can the HCl salt of the amine be acylated like his freebase situation??? If yes why do we waste so much time to make the acetic anhydride???

A simple consideration of a mechanism of acylation (lone pair on the nitrogen attacking a carbonyl) suggests that the acid salt would be less successful at acylating. (There are also some conditions in which it's thought there's an formally substituted carbon monoxide RC(triple bond)O⁺ in operation I think)

S

[lutesium]

So you say that we have to make the anhydride huh???


Lutesium...

[sjb]

So you say that we have to make the anhydride huh???

Assuming that's in answer to me, no. All I'm saying is that acidic conditions will probably protonate the amine to the detriment of your desired reaction. Acetyl chloride will work just as well

[lutesium]

So why were we wasting so much time making him (Acetic anhydride) guys???

[AWK]

So why were we wasting so much time making him (Acetic anhydride) guys???

The original question cocerned using ethyl acetate for acylation of aniline. Aniline is a wery weak amine, and acylation with ethyl acetate is rather difficult (sealed ampoule and temperature over 100 C).

There are many other methods of acylating amines. For aniline - acetic anhydride and acetyl chloride will work (for sure).
Acetyl chloride can work in water solution where acetic anhydride work only in anhydrous solutions. Ib both cases there are different side products. Moreover sometimes selectivity of reaction is needed. Then we use even much more complex, much more expensive reagents, eq active esters (see methods of peptide synthesis)

[RBF]

AWK-I would think that acetyl chloride is more reactive with water than is acetic anhydride, with both hydrolyzing to acetic acid.  Is it your experience that the reaction with amines and acetyl chloride is so fast that water can be present in the reaction medium?
(Thank the forum moderators for the modify button)
Let me take that back and rephrase the question, since the Schotten-Baumann reaction obviously works.  In view of the reactivity of  acyl halides, why doesn't the halide undergo significant hydrolysis under these conditions?  Standard texts list acid halides as the most reactive acid derivatives toward reactions with nucleophiles.

[lutesium]

Yes I also do think the same way as RBF that Ac-Cl is more reactive with water than Ac-O-Ac cuz it fumes from the bottle! And what do you mean by a strong amine???


Lutesium...

[lutesium]

Please can someone who has access to a lab try the Schotten-Baumann RXN on Aniline and report the results??? And if you have an otoclave can you please try acetylating Aniline w/ Et-O-Ac!!!


Lutesium...