[Doom91]

Does anyone know the condition to hydrolyse a nitrile such that it just stop at an amide and not go all the way to form a carboxylic acid

[Vidya]

if acids are desired use base like NaOH to create basic conditions
If amide is desired use acidic conditions like H2SO4,formic acid ,HCl or HBr

[russellm72]

Hi,

Dont know how easy this would be. Usually I use 6N HCl at ~100 oC to hydrolise a aromatic nitrile to a carboxylic acid and it usually goes quantitavely. I used ethanolic KOH recently and you could see the intermediate amide (TLC) but it was never something I wanted to isolate and in the mixture was SM, Pdt and amide. I wanted the acid again so it was just a case of a longer reaction time. I think you may struggle to do this effectively under these conditions.

Why not just make the acid then a simple transformation into the amide.....


R.

[Doom91]

Dear Russellm72
If it is an aliphatic nitriles,what condition and reagents must be added to obtain the aliphatic amide intermediate, instead of the carboxylic acid

[alphahydroxy]

IIRC, isolating the amide from an acidic nitrile hydroylsis is rather difficult because the second step of the reaction (giving the acid) occurs at a faster rate. Therefore, in practice, you are likely to get a mixture of acid and amide...

Again, google is your friend...

[Doom91]

how do you sepereate amide from carboxylic acid

[aldoxime_amine]

If you want to kill the amide, you can probably react the mixture with excess of conc. NaHO  solution, followed by an acid work up to retrieve the acid.

If you want to get rid of the acid, maybe you can use ammonia and then evaporate the solvent, and heat the dry powder (of the ammonium salt of the acid), but I'm not sure if this is nice..

If you want to simultaneously separate both, then I'm not so sure...

[reactormart]

warm in 96%-100% sulfuric acid to 70°C and hold, moniter by tlc.
Quench onto excess ice/water- filter or extract product
Certainly works fine for aromatic nitriles to amides.

[orgopete]

warm in 96%-100% sulfuric acid to 70°C and hold, moniter by tlc.
Quench onto excess ice/water- filter or extract product
Certainly works fine for aromatic nitriles to amides.

This is one of many ways to do it. We calculated the amount of water present in the sulfuric acid to add to the (protonated) nitrile. (I kind of doubt that was actually true, but that was how we did them.)

The difficulty of hydrolyzing nitriles under acidic conditions is because the amide is more basic than the starting nitrile. Once water adds to the nitrile, the amide is protonated more easily and results in its hydrolysis. I believe the success of the sulfuric acid hydrolysis is its ability to limit the amount of water available.

If you do the hydrolysis under basic conditions, you are more likely to have an incomplete hydrolysis. Success requires formation of the dianion of the hydroxide addition product in order to expel the anion of ammonia. This would be an uphill reaction otherwise. However, from the dianion, the weakest base is now the amide anion (the anion of ammonia). Since the carboxamide is the intermediate, if the hydrolysis conditions are not too harsh, it will be the major product. If you do the hydrolysis aggressively (large excess of concentrated base, and heat), it will go all the way to the carboxylate. 

There is a simple variation of the base catalyzed hydrolysis that is perhaps simpler, use base (carbonate?) and peroxide. The peroxide anion adds to the nitrile to give a per-imidate. This can decompose to oxygen and an amide. The perimidate can also be a mild peracid equivalent. If I recall correctly, this is a Payne oxidation (or something like that).

[g-bones]

check out this article in which a platinum catalyst is used to reduce the nitrile ( to the primary amide (26) in scheme 5.

Org. Lett., Vol. 12, No. 7, 2010