[Marcus]

I performed an aminolyzation of an acid halide a few days ago in lab, and I have a few questions about the process.

Now, as I understand it, you need two equivalents of ammonia: one to form the amide, and one to neutralize the hydrogen halide.

We used a solution of aqueous ammonia: NH₃/H₂O, so what would happen if I added this aqueous ammonia dropwise into my solution of acid halide, instead of adding the acid halide to the ammonia?

This is my prediction:

There would be an excess of acid halide, all of which would react with all of the ammonia. Effectively, there is only 1 equivalent of ammonia in this reaction.

So, formation of the amide would occur, but there would also be HX in the solution, along with the H₂O. Normally, the second equivalent would neutralize the HX, producing a rather exothermic reaction and eliminating the NH₄⁺X^-

It seems the final result of using just one equivalent of ammonia will be the amide and hydrogen halide.

Will any subsequent reactions occur? I wonder if an acid-catalyzed hydrolysis of the amide might follow, reforming the carboxylic acid and producing an ammonium ion?

Basically, what's the difference between adding the acid halide to the aqueous ammonia versus adding the aqueous ammonia to the acid halide?

[nj_bartel]

Hint: Does water react with acyl halides?

[Marcus]

Yes!

The carboxylic acid is more stable than both the acid halide and amide, so would reformation of the carboxylic acid be favored?

I'm having a little trouble understanding exactly what's going on.

I understand the reaction like this:


This would not occur with two equivalents because the second equivalent of ammonia would form the ammonium chloride leaving water and the amide.

[nj_bartel]

Sorry, I misread the conditions to start with.  I think you have it

[Marcus]

So, reformation of the carboxylic acid would occur in a one equivalent setup?

[nj_bartel]

I believe so, because acidic conditions speed amide hydrolysis

[tmartin]

I think there is also another product that could be considered, especially if you add the ammonia in water to the acid chloride.

[408]

I have hydrolysed amides before and it is not exactly a mild procedure.  I doubt amide hydrolysis would occur significantly.  What I would worry about more is you have a pile of acyl halide, and are slowly adding a water containing and water producing reagent...

After each drop of ammonia solution is added, amide is formed.  The water in your solution is now floating around in an acyl halide...Carboxylic acid will form, but not from the hydrolysis of your amide.  I would guess <50% of acyl chloride would end up amide, the rest being carboxylic acid

[tmartin]

Just to play devil's advocate and keep this going, there is still theoretically another product that can form.  Let's just say for argument's sake when you add one drop you somehow add exactly one equivalent of NH4OH (obviously you don't but still), the Ar-C(O)Cl will react with the amine (and water) to give you HCl, an amide and an acid.  If you're thinking about all the reactivities, something can still go on.

[nj_bartel]

I have hydrolysed amides before and it is not exactly a mild procedure.  I doubt amide hydrolysis would occur significantly.  What I would worry about more is you have a pile of acyl halide, and are slowly adding a water containing and water producing reagent...

After each drop of ammonia solution is added, amide is formed.  The water in your solution is now floating around in an acyl halide...Carboxylic acid will form, but not from the hydrolysis of your amide.  I would guess <50% of acyl chloride would end up amide, the rest being carboxylic acid

Ok, this is where I was going with my first reply, but something made me change my mind about it.  I can't see why now though.

[Marcus]

So I've been thinking....

In the dropwise addition of ammonium hydroxide to the acyl chloride, the amide (a nucleophile) is going to be surrounded by electrophiles, so wouldn't it want to form a bond with the acyl halides?

R'-C(O)-NH2 + R-C(O)-Cl ----> R'-C(O)-NH-C(O)-R + HCl

[tmartin]

That is the other outcome I was trying to hint at oh so vaguely earlier.   

[Marcus]

Cool!

What sort of compound is that called?

Diester amide? I don't even know where to start with it's nomenclature.