Sciencemadness Discussion Board

Acetamide Synthesis

Dr.Q - 25-2-2013 at 10:23

So i tried to make acetamide from the reaction of Ethyl acetate and NH3 .
I poured both of them in to the flask waited 3 days for mixng them. After that , i made a reflux and than distilled it.
First thing come from disttilation was amonnia . Than ethyl acetate came. It was still smells like amonnia too. After that water came it was also smeell like amonnia. And in the there in the flask there was a Yellow colored chemical which i cant recognize. It was liquid so it is not acetamide. It was more viscose than water and smells like acetic acid but not pungent as acetic acid.

Here is a picture from that yellow liquid.

From what i read , this reaction should reveal acetamide and ethanol. But thing i get was something different.

The thing that weird for me is , i tried different method to make acetamide , from heating amonnium acetate , i still get the same weird liquid .

What am i doing wrong ? Is that liquid a solution of acetamide with amonnia and water ???

[Edited on 25-2-2013 by Myeou]

asd.png - 123kB

bananaman - 25-2-2013 at 18:34

Acetic acid is one of the products from the reaction between ethyl acetate and ammonia.

CH3COOC2H5 + NH3 ---> CH3CONH2 + C2H5COOH

Try removing the acetic acid with a base + liquid-liquid extraction with a suitable organic solvent.

Collect the organic layer and dry down.

Dr.Q - 26-2-2013 at 07:11

Quote: Originally posted by bananaman  
Acetic acid is one of the products from the reaction between ethyl acetate and ammonia.

CH3COOC2H5 + NH3 ---> CH3CONH2 + C2H5COOH

Try removing the acetic acid with a base + liquid-liquid extraction with a suitable organic solvent.

Collect the organic layer and dry down.


wow that is suprising for me because i thought that the raction mechanism goes same as NaOH and CH3COOC2H5 .

Could you explain the mechanism to me ?

ScienceSquirrel - 26-2-2013 at 07:31

Quote: Originally posted by bananaman  
Acetic acid is one of the products from the reaction between ethyl acetate and ammonia.

CH3COOC2H5 + NH3 ---> CH3CONH2 + C2H5COOH

Try removing the acetic acid with a base + liquid-liquid extraction with a suitable organic solvent.

Collect the organic layer and dry down.


No it is not.
You have just magicked up an extra carbon and two oxygen atoms.

Dr.Q - 26-2-2013 at 07:39

Quote: Originally posted by ScienceSquirrel  
Quote: Originally posted by bananaman  
Acetic acid is one of the products from the reaction between ethyl acetate and ammonia.

CH3COOC2H5 + NH3 ---> CH3CONH2 + C2H5COOH

Try removing the acetic acid with a base + liquid-liquid extraction with a suitable organic solvent.

Collect the organic layer and dry down.


No it is not.
You have just magicked up an extra carbon and two oxygen atoms.



Could we be clear that reaction between ethyl acetate and amonnia yields acetamide and ethanol..

If this is true why is the yellow solution smells like acetic acid ?

ScienceSquirrel - 26-2-2013 at 08:15

A competing reaction is hydrolysis of the ethyl acetate to yield ethanol and acetic acid. The acetamide will also hydrolyse.
What you have is an aqueous solution of acetamide with traces of acetic acid. Acetamide is extremely soluble in water, 2000g per litre, so even small amounts of water will make it into a solution.

Nicodem - 26-2-2013 at 09:04

Quote: Originally posted by Myeou  
It was liquid so it is not acetamide.

It should be liquid. I can't see it possible to obtain pure and thus solid acetamide without a redistillation with a distillation column. Keep in mind that water will form from the thermolysis of the ammonium acetate side product during the first distillation and it is thus not possible to obtain an anhydrous acetamide this way. Also, ammonium acetate decomposes also to ammonia and acetic acid which is unlikely to condense in a 1:1 ratio, thus causing contamination with acetic acid and ammonium acetate.

What is the reference of this procedure and how do the authors isolate acetamide? Are you sure they did not fractionate the crude product?

bananaman - 26-2-2013 at 17:33

Sorry for the mistakes previously. Attached is a relevant paper regarding the preparation of acetamide from ethyl acetate and ammonia.

Attachment: Preparation of Acetamide by the Action of Ammonium Hydroxide and Ethyl Aetate.pdf (738kB)
This file has been downloaded 3359 times


Polesch - 6-5-2013 at 13:03

So I did a very quick synthesis of acetamide this week following this discussion, by simply mixing aqueous ammonia (household grade, 9%) with what is supposedly 99% ethyl acetate (dubious source). I simple mixed stoichiometric amounts, about 9.1 grams ethyl acetate with 20 mL 9% ammonia. Approximately 100 mmol of both reagents. The solution initially forms two separate layers as the ethyl acetate has a low solubility in water (8.3 g/dL).

I left the solution on the magnetic stirrer for 24 hours, at about 700 rpm. At this point there were no longer two separate layers, so it's safe to assume that a reaction had taken place. I simple poured the resulting solution into an evaporating dish and left it at room temperature for 3 days, when crystals finally started forming. The crystals were collected and placed in a desiccator with phosphorus pentoxide for another 24 hours. A simple melting-point test did give confirmation that the product is relatively pure acetamide with a melting point at ~80 C, all of the product melted to a clear liquid not exceeding 90 C.

This procedure clearly seems like a success. I forgot to weigh my final product, so I don't know any yields at this moment, but I could do that if anybody is interested.


Adas - 6-5-2013 at 13:54

Very nice results, Polesch! Taking into consideration that you used just 9% ammonia... Nice :)

Polesch - 7-5-2013 at 00:54

Quote: Originally posted by Adas  
Very nice results, Polesch! Taking into consideration that you used just 9% ammonia... Nice :)


When I used what is 'most likely' a saturated solution of ammonia in ice-cold water, I did get a much higher yield, as I used about the same volume of solution - but obtained much more crystals:


Nitro-esteban - 18-9-2013 at 18:18

I tried making acetamide with 30% ammonia and 98.5% ethyl acetate. After evaporating the solution at about 60C. The solution started turning yellow and it smelled like acetic acid so I let it cool to room temperature and crystals started forming. I didn't weigh the crystals so I don't know the yield but it certainly was very low.

AndersHoveland - 18-9-2013 at 19:15

Usually the anhydrous ammonia gas is first dissolved in pure ethanol, and this is then reacted with the ethyl acetate. Otherwise, ammonia is not very soluble in ethyl acetate.

Another method is to heat ammonium acetate in a sealed tube under flame.

Adas - 6-11-2013 at 07:02

Would this also work with primary amines or their salts? Could anybody try this with ammonium chloride?

HgDinis25 - 11-4-2015 at 11:45

Acetamide is an interesting compound and making it from something so common as Ethyl Acetate would be excellent. However, I have serious doubts about this procedure.

Polesch, how do you know that you don't simply have Ammonium Acetate crystals? Acetamide melts at 79ºC, Ammonium Acetate melts at 110ºC, I believe, while starting to slowly decompose. How accurate was your melting point measurement?

We all know that Ethyl Acetate hydrolyzes readily in water, as follows:
Ethyl Acetate(l) + Water(l) --> Acetic Acid(aq) + Ethanol(aq)

Ammonia readily forms Ammonium Hydroxide in water:
NH3(aq) + H2O(l) <--> NH4+(aq) + OH-(aq)

Ammonium Hydroxide and Acetic Acid react to form Ammonium Acetate. The equilibrium of the hydrolysis of Ethyl Acetate shifts to the right and proceeds to completion. We should be left with Ammonium Acetate, Water and Ethanol.

I can't thing of a way this process could actually work.

gdflp - 11-4-2015 at 11:58

There is a procedure in Vogel, 3rd edition page 403. Ethyl acetate will not hydrolyze simply by placing it into water, it either needs refluxing with an acid catalyst or the addition of a stoichiometric amount of base(typically hydroxide). The base acts by nucleophilically attacking the carbonyl in ethyl acetate with the ethoxide then acting as a leaving group and being protonated by the now acidic hydrogen originally present on the hydroxide. In ammonia, I doubt that the hydroxide concentration is high enough for this to happen at any appreciable rate. The free ammonia in solution can instead act as a nucleophile itself, this still results in ethoxide as the leaving group, but it leaves acetamide rather than acetate as the final product.

HgDinis25 - 11-4-2015 at 12:48

@gdflp,

Quote:

Ethyl acetate will not hydrolyze simply by placing it into water, it either needs refluxing with an acid catalyst or the addition of a stoichiometric amount of base(typically hydroxide).


The equilibrium constant for the hydrolysis of Ethyl Acetate is around 0,25. So yes, Ethyl Acetate hydrolyzes just by coming in contact with water (of course, only a part of it gets hydrolyzed).

Adding a stoichiometric amount of base will, as you said, make the equilibrium go into completion.


Quote:

The base acts by nucleophilically attacking the carbonyl in ethyl acetate with the ethoxide then acting as a leaving group and being protonated by the now acidic hydrogen originally present on the hydroxide. In ammonia, I doubt that the hydroxide concentration is high enough for this to happen at any appreciable rate



The hydroxide concentration in ammonia is probably low, as you said:
NH3(aq) + H2O(l) <--> NH4+(aq) + OH-(aq)

However, the neutralization reaction between Acetic Acid and Ammonium Hydroxide (an acid/base reaction) happens much much much more easily than the reaction between free ammonia and Ethyl Acetate.

As both Ammonium Hydroxide and Acetic Acid disappear, the ammonia equilibrium will shift to the right making more Ammonium Hydroxide and the equilibrium of the hydrolysis of Ethyl Acetate will also shift to the right, producing more Acetic Acid.


gdflp - 11-4-2015 at 13:18

Quote: Originally posted by HgDinis25  

Quote: Originally posted by gdflp  

Ethyl acetate will not hydrolyze simply by placing it into water, it either needs refluxing with an acid catalyst or the addition of a stoichiometric amount of base(typically hydroxide).


The equilibrium constant for the hydrolysis of Ethyl Acetate is around 0,25. So yes, Ethyl Acetate hydrolyzes just by coming in contact with water (of course, only a part of it gets hydrolyzed).

Adding a stoichiometric amount of base will, as you said, make the equilibrium go into completion.

Where did you get this number? Also this gives no information about the rate of this uncatalyzed hydrolysis reaction, I would expect it to be extremely slow.
Quote: Originally posted by HgDinis25  

Quote: Originally posted by gdflp  

The base acts by nucleophilically attacking the carbonyl in ethyl acetate with the ethoxide then acting as a leaving group and being protonated by the now acidic hydrogen originally present on the hydroxide. In ammonia, I doubt that the hydroxide concentration is high enough for this to happen at any appreciable rate



The hydroxide concentration in ammonia is probably low, as you said:
NH3(aq) + H2O(l) <--> NH4+(aq) + OH-(aq)

However, the neutralization reaction between Acetic Acid and Ammonium Hydroxide (an acid/base reaction) happens much much much more easily than the reaction between free ammonia and Ethyl Acetate.

As both Ammonium Hydroxide and Acetic Acid disappear, the ammonia equilibrium will shift to the right making more Ammonium Hydroxide and the equilibrium of the hydrolysis of Ethyl Acetate will also shift to the right, producing more Acetic Acid.


The issue is that, as I explained above, not much free acetic acid will be present in the solution at any given time. In addition, the equilibrium between acetic acid and ammonia, a weak acid and a weak base, is not overly favorable to begin with and ammonia acetate will decompose to acetic acid and ammonia on prolonged standing, this is the reason that ammonium acetate can not simply be made by mixing ammonia and vinegar. No doubt, some ammonium acetate will be formed but this is not a significant problem for the reaction as most of it will dehydrate to acetamide when the mixture is distilled during workup.

[Edited on 4-11-2015 by gdflp]

Nicodem - 11-4-2015 at 13:26

Quote: Originally posted by HgDinis25  
The equilibrium constant for the hydrolysis of Ethyl Acetate is around 0,25. So yes, Ethyl Acetate hydrolyzes just by coming in contact with water (of course, only a part of it gets hydrolyzed).

The equilibrium constant for the reaction of ethyl acetate with water is totally irrelevant for the ammonolysis of ethyl acetate. You are confusing the kinetics with thermodynamics.
Quote:
Adding a stoichiometric amount of base will, as you said, make the equilibrium go into completion.

Only if the base as such is non-nucleophilic in water, thus making only the hydroxide ions as the only relevant nucleophilic species present. Otherwise, other reaction pathways could prevail. And the reaction rate would still be determined by the kinetics and not thermodynamics.
Quote:
The hydroxide concentration in ammonia is probably low, as you said:NH3(aq) + H2O(l) <--> NH4+(aq) + OH-(aq)

It is not just about the hydroxide concentration being low, it is about it being very low in relation to the concentration of ammonia.
Quote:
However, the neutralization reaction between Acetic Acid and Ammonium Hydroxide (an acid/base reaction) happens much much much more easily than the reaction between free ammonia and Ethyl Acetate.

It takes acetic acid for deprotonating acetic acid. Since there is no acetic acid, the reaction cannot give a solution of ammonium acetate as the main product. The acetate can only form by the hydrolysis of ethyl acetate, a reaction that is of minor importance considering the wast majority of the nucleophiles in the system is ammonia molecules.

Consider it this way. You have plenty of ammonia and only very little of hydroxide. Both are comparably nucleophilic. So why would you expect the acetate as the main product? It makes more logic for the acetamide to be the main product. (And experimentally acetamide is the main product!)

Essentially, you are using a faulty logic. Instead of looking at the entire system, you look just at one tiny component of the system (the hydroxide) and misuse thermodynamic data by ignoring the kinetic aspects. In chemistry you need to evaluate every problem holistically, like evaluating the entire system, not just parts of it.

Furthermore, reacting acyl chlorides by adding them to aqueous ammonia gives the corresponding carboxamides as main product in addition to ammonium chloride byproduct. So why would you expect the way less reactive ethyl acetate undergoing the hydrolysis pathway rather than the ammonolysis? So even without using any logical thinking, merely using deduction makes your conclusion that ammonium acetate should be the main product appear quite unusual.

gdflp - 11-4-2015 at 13:39

Quote: Originally posted by Nicodem  

Consider it this way. You have plenty of ammonia and only very little of hydroxide. Both are comparably nucleophilic.

Are they? I was under the impression that since hydroxide was a negatively charged nucleophile, it was better nucleophile than neutral nucleophiles such as ammonia, even though the nitrogen equivalent, amide, is a better nucleophile than hydroxide.

[Edited on 4-11-2015 by gdflp]

Nicodem - 11-4-2015 at 14:04

Quote: Originally posted by gdflp  
Are they? I was under the impression that since hydroxide was a negatively charged nucleophile, it was better nucleophile than neutral nucleophiles such as ammonia, even though the nitrogen equivalent, amide, is a better nucleophile than hydroxide.

Just because a nucleophile is charged, it does not mean that it is stronger that any neutral nucleophile. A negative charge here is merely a lone electron pair. A charge on a poorly polarizable ion can even reduce the nucleophilicity in protic solvents. For example, the hydroxide ion is very strongly solvated in water due to its excellent H-bonding ability. For this reason its nucleophilicity in water is not particularly high.

According to Meyr et al. measurements (see his database), hydroxide in water is just slightly more nucleophilic than ammonia in water:

ammonia in water
N Parameter: 9.48
SN Parameter: 0.59

OH- in water
N Parameter: 10.47
SN Parameter: 0.61

In addition, ammonia can react with ethyl acetate in both phases while hydroxide can only react with ethyl acetate in the aqueous phase. It would be interesting to measure the kinetics of the ammonolysis in each phase.

HgDinis25 - 11-4-2015 at 14:24

@Nicodem,


Quote:
The equilibrium constant for the reaction of ethyl acetate with water is totally irrelevant for the ammonolysis of ethyl acetate. You are confusing the kinetics with thermodynamics.


I was merely stating that Ethyl Acetate can hydrolyze just by coming in contact with water because of gdflp's claim "Ethyl acetate will not hydrolyze simply by placing it into water"

Careful with your conclusions. Before saying I'm confusing kinetics with thermodynamics (I don't even know why you brought them up on such an easy argument to understand):
Person 1 - Ethyl Acetate needs more than just water to hydrolyze.
Person 2 - Actually, the equilibrium constant is 0,25 (not 0,000001 for instance). Therefore the reaction happens. The rate may be slow but it is there.

Everything else you said does make sense. However, I would expect the rate of reaction to form acetamide would be much slower than the acid/base reaction between Acetic Acid and Ammonium Hydroxide.


Quote:

Essentially, you are using a faulty logic. Instead of looking at the entire system, you look just at one tiny component of the system (the hydroxide) and misuse thermodynamic data by ignoring the kinetic aspects. In chemistry you need to evaluate every problem holistically, like evaluating the entire system, not just parts of it.


I was focusing on the hydroxide part, as you said, because I thought the rate of the acid/base reaction to be much greater than the rate of Acetamide formation. I may be wrong, though. Anyway, let's elaborate on this:
misuse thermodynamic data by ignoring the kinetic aspects

Where did I misuse thermodynamic data, as you claim? And ignored kinteic aspects?

DraconicAcid - 11-4-2015 at 14:33

Quote: Originally posted by HgDinis25  

Careful with your conclusions. Before saying I'm confusing kinetics with thermodynamics (I don't even know why you brought them up on such an easy argument to understand):
Person 1 - Ethyl Acetate needs more than just water to hydrolyze.
Person 2 - Actually, the equilibrium constant is 0,25 (not 0,000001 for instance). Therefore the reaction happens. The rate may be slow but it is there.
...
Where did I misuse thermodynamic data, as you claim? And ignored kinteic aspects?


The equilibrium constant is thermodynamic data. Whether or not the reaction will occur at *any* rate in the absence of a catalyst is a kinetics question.

There are many, many reactions that are thermodynamically favourable, but do not occur under standard conditions, even on the geological time scale. Diamond converting to graphite has a favourable Gibb's Free Energy change (it has no eq'm constant), but it does not occur. Hydrogen mixed with oxygen will not react in the absence of a spark or catalyst, despite its sky-high eq'm constant.

The reaction 2 Ag+(aq) + 2 I-(aq) = 2 Ag(s) + I2(s) has a very high eq'm constant, but that reaction also simply doesn't happen upon mixing the two reactants, for obvious reasons, and no catalyst in the world will make it happen.

gdflp - 11-4-2015 at 14:40

Quote: Originally posted by HgDinis25  

I was merely stating that Ethyl Acetate can hydrolyze just by coming in contact with water because of gdflp's claim "Ethyl acetate will not hydrolyze simply by placing it into water"

Careful with your conclusions. Before saying I'm confusing kinetics with thermodynamics (I don't even know why you brought them up on such an easy argument to understand):
Person 1 - Ethyl Acetate needs more than just water to hydrolyze.
Person 2 - Actually, the equilibrium constant is 0,25 (not 0,000001 for instance). Therefore the reaction happens. The rate may be slow but it is there.

Everything else you said does make sense. However, I would expect the rate of reaction to form acetamide would be much slower than the acid/base reaction between Acetic Acid and Ammonium Hydroxide.

I was talking about this instance, the ethyl acetate hydrolysis will not occur at a rate fast enough to introduce acetic acid and interfere with the reaction. Again, the aminolysis in this case will be preferred because the ammonia is present in such a large concentration as compared to the hydroxide, both of which have reasonably comparable nucleophilicity in water as shown by the data Nicodem provided.

Quote: Originally posted by HgDinis25  

I was focusing on the hydroxide part, as you said, because I thought the rate of the acid/base reaction to be much greater than the rate of Acetamide formation. I may be wrong, though. Anyway, let's elaborate on this:
misuse thermodynamic data by ignoring the kinetic aspects

Where did I misuse thermodynamic data, as you claim? And ignored kinteic aspects?

By quoting equilibriums, you are using thermodynamic data which is less relevant in this case. When determining the favored product when dealing with a mixture with competing reactions, kinetic data is often far more important, of which you provided none.

@Nicodem
Thank you for that data, my post wasn't intended to disagree with you, I was merely curious as I have always been taught that negatively charged nucleophiles were better nucleophiles than neutral nucleophiles.

Etaoin Shrdlu - 11-4-2015 at 14:40

Quote: Originally posted by HgDinis25  
Acetamide is an interesting compound and making it from something so common as Ethyl Acetate would be excellent. However, I have serious doubts about this procedure.

Here's a reference from 1907. They find only traces of ammonium salt.

HgDinis25 - 11-4-2015 at 14:54

@ Etaoin Shrdlu
http://www.google.pt/url?sa=t&rct=j&q=&esrc=s&am...



Ammonia is present in large excess over hydroxide ions. Acetic acid is also present in very small quantities (let's say trace amounts). The aminolysis of Ethyl Acetate should have a much lower rate than the acid/base reaction between Ammonium Hydroxide and Acetic Acid. Because the acid/base reaction is faster than the aminolysis reaction, the equilibriums I mentioned in my previous posts should shift to the right. Of course, the aminolysis would shift it to the left. However, the reaction that makes them shift to the right is faster.

At least, I would expect large contamination of Ammonium Acetate. Or is my assumption that the acid/base reaction is faster wrong?

Etaoin Shrdlu - 11-4-2015 at 16:17

Did you read the article? There is data on the contamination. I don't know exactly where your predictions went wrong.

EDIT: Oops, I missed that bananaman had posted the same document. Still relevant, though.

[Edited on 4-12-2015 by Etaoin Shrdlu]

gdflp - 11-4-2015 at 16:23

Quote: Originally posted by HgDinis25  

Ammonia is present in large excess over hydroxide ions. Acetic acid is also present in very small quantities (let's say trace amounts). The aminolysis of Ethyl Acetate should have a much lower rate than the acid/base reaction between Ammonium Hydroxide and Acetic Acid. Because the acid/base reaction is faster than the aminolysis reaction, the equilibriums I mentioned in my previous posts should shift to the right. Of course, the aminolysis would shift it to the left. However, the reaction that makes them shift to the right is faster.

At least, I would expect large contamination of Ammonium Acetate. Or is my assumption that the acid/base reaction is faster wrong?

That's where you are getting confused. It isn't the difference in rate between the acid-base reaction, and the aminolysis of ethyl acetate. It is the difference in rate between the hydrolysis of the ethyl acetate(EXTREMELY SLOW, it doesn't matter if the equilibrium is shifted because the concentration of hydroxide ions is only 0.01M in 6M ammonia whereas the concentration of free ammonia 5.99M) and the acid-base reaction, and the aminolysis of ethyl acetate.

[Edited on 4-12-2015 by gdflp]

HgDinis25 - 11-4-2015 at 17:32

Quote: Originally posted by gdflp  
Quote: Originally posted by HgDinis25  

Ammonia is present in large excess over hydroxide ions. Acetic acid is also present in very small quantities (let's say trace amounts). The aminolysis of Ethyl Acetate should have a much lower rate than the acid/base reaction between Ammonium Hydroxide and Acetic Acid. Because the acid/base reaction is faster than the aminolysis reaction, the equilibriums I mentioned in my previous posts should shift to the right. Of course, the aminolysis would shift it to the left. However, the reaction that makes them shift to the right is faster.

At least, I would expect large contamination of Ammonium Acetate. Or is my assumption that the acid/base reaction is faster wrong?

That's where you are getting confused. It isn't the difference in rate between the acid-base reaction, and the aminolysis of ethyl acetate. It is the difference in rate between the hydrolysis of the ethyl acetate(EXTREMELY SLOW, it doesn't matter if the equilibrium is shifted) and the acid-base reaction, and the aminolysis of ethyl acetate.


Of course it matters if the equilibrium is shifted! That's why you can easily hydrolyze Ethyl Acetate using, for instance, Sodium Hydroxide.

Now, what you could argue is that there is never enough Hydroxide ions in solution to actually accelerate the hydrolysis equilibrium enough to cause problems.

From what I can see, this is more complex than simply stating "it happens because reaction 1 is faster than 2". Kinetics of all the equilibriums should be taken into account. However, Nicodem's explanation makes sense.

I was planing a synthesis of this compound using dried Ammonia gas and dried Ethyl Acetate. I may resort to the much more simple method of adding the two reagents together, though.


DraconicAcid - 11-4-2015 at 17:45

Quote:
Quote: Originally posted by HgDinis25  
Of course it matters if the equilibrium is shifted! That's why you can easily hydrolyze Ethyl Acetate using, for instance, Sodium Hydroxide.


No, it doesn't, because it's NOT at equilibrium!


gdflp - 11-4-2015 at 17:58

Quote: Originally posted by HgDinis25  

Of course it matters if the equilibrium is shifted! That's why you can easily hydrolyze Ethyl Acetate using, for instance, Sodium Hydroxide.

No, the shifted equilibrium ensures that the ethyl acetate will be fully hydrolyzed. The high concentration of hydroxide ions increases the rate of reaction so that it can occur at an appreciable rate in a laboratory experiment. These are two entirely different concepts!

HgDinis25 - 11-4-2015 at 18:49

@gdflp

Quote:

No, the shifted equilibrium ensures that the ethyl acetate will be fully hydrolyzed.


At which point did I state otherwise?

Quote:

The high concentration of hydroxide ions increases the rate of reaction so that it can occur at an appreciable rate in a laboratory experiment.


Yes, that's why I stated:
Now, what you could argue is that there is never enough Hydroxide ions in solution to actually accelerate the hydrolysis equilibrium enough to cause problems.

And that quote of yours gets in contradiction with a previous one you made:
Quote:

(EXTREMELY SLOW, it doesn't matter if the equilibrium is shifted)



@DraconicAcid

I respect you and you are probably a very good chemist. But please don't do that. Don't just throw stuff into the air like you're adding fuel to the fire. Don't state things like
No, it doesn't, because it's NOT at equilibrium!
without explaining better.

What exactly isn't at equilibrium? And why doesn't it matter if the equilibrium is shifted? I can't decode your comment into useful information. Could you elaborate a little bit more, please?

What isn't at equilibrium?


[Edited on 12-4-2015 by HgDinis25]

Etaoin Shrdlu - 11-4-2015 at 19:16

The reaction doesn't ever reach equilibrium, because it's so slow.

gdflp - 11-4-2015 at 19:23

Quote: Originally posted by HgDinis25  
@gdflp

Quote:

No, the shifted equilibrium ensures that the ethyl acetate will be fully hydrolyzed.


At which point did I state otherwise?

Quote:

The high concentration of hydroxide ions increases the rate of reaction so that it can occur at an appreciable rate in a laboratory experiment.


Yes, that's why I stated:
Now, what you could argue is that there is never enough Hydroxide ions in solution to actually accelerate the hydrolysis equilibrium enough to cause problems.

And that quote of yours gets in contradiction with a previous one you made:
Quote:

(EXTREMELY SLOW, it doesn't matter if the equilibrium is shifted)


No, you're talking about accelerating the equilibrium and such, that's not what happens. And I am not contradicting myself, as those two quotes are saying entirely different things. The equilibrium of a reaction and the rate of a reaction are two entirely different concepts. A hydrolysis reaction could have an extraordinarily high equilibrium constant which favors entirely products, but that irrelevant if the kinetics of the reaction show that it would take a century to reach equilibrium(extreme case obviously). An equilibrium determines what the concentration of the reactants will be after a mixture has had ample time to react, but most equilibrium's don't occur instantly. Thus, the time it takes for a reaction to reach equilibrium is determined by the kinetics of the reaction which are separate from the equilibrium of the reaction. There may be a change in the rate of the reaction due to the kinetics being based off of the concentration of some reactants, but it is quite possible for the reaction rate to be unaffected regardless of the concentration of any of the reactants and thus be a slow reaction even if there is a high or low equilibrium constant. This is why a reaction can be extremely slow(unfavorable kinetics), but have a favorable equilibrium and will eventually reach equilibrium if no other faster reactions are competing. This is the case here, the hydrolysis of ethyl acetate will eventually occur, but since the concentration of free ammonia is so much higher than hydroxide in the reaction mixture, the aminolysis has much more favorable kinetics and will thus be the predominant reaction.

The equation for the equilibrium of A + B <--> C + D is k = ([C]*[D])/([A]*[B]) whereas the equation for the kinetics of that reaction is Rate = k[A]^n*[B]^m*[C]^p*[D]^q, but n m p and q could all be 0 and thus the concentration of any of them would not affect the rate of reaction.(Note that the two k's are different)

HgDinis25 - 11-4-2015 at 19:52

@gdflp

The presence of Hydroxide ions increases the hydrolysis rate. It also shifts the equilibrium to the right (product gets consumed). I don't understand your persistence in trying to textbook me with kinetics.

This all comes down to:
Reaction A - Hydrolysis of Ethyl Acetate
Reaction B - Ionization of Ammonia
Reaction C - Aminolysis of Ethyl Acetate
Reaction D - NH4OH and Acetic Acid to form Ammonium Acetate

If Reaction C is faster than reaction A then Acetamide will be the major product. If reaction A is faster than reaction C then reaction D prevails and Ammonium Acetate will be the major product.

Now, in the absence of Hydroxide ions, reaction A is very slow. However, in the presence of said ions, the rate of reaction A increases. Thus, if OH ions are being consumed (reaction D), reaction B will ionize more ammonia. What you're all trying to sell is that reaction C still prevails. Some actual data could help, though.

About your contradiction:
The high concentration of hydroxide ions increases the rate of reaction so that it can occur at an appreciable rate in a laboratory experiment.

and

(EXTREMELY SLOW, it doesn't matter if the equilibrium is shifted)

Hydroxide ions increase the rate of reaction and shift the equilibrium to the right (by consuming one of the products).

In these conditions, if the rate is increased it is because of the Hydroxide ions. So, we can conclude that there must be hydroxide ions to increase reaction rate. Then you said that reaction is extremely slow, not mattering if the equilibrium is shifted. For the equilibrium to be shifted there must be hydroxide ions. And therefore, if there are hydroxide ions reaction rate increases. Now, what you might be saying is that the increase in rate, with such small amount of hydroxide is negligible. I stated that a few posts ago:
Now, what you could argue is that there is never enough Hydroxide ions in solution to actually accelerate the hydrolysis equilibrium enough to cause problems.



@Etaoin Shrdlu
Is reaction A that slow even in the presence of the Hydroxide ions? If so it must have a very low rate to allow acetamide formation free from Ammonium Acetate.



gdflp - 11-4-2015 at 20:13

Yes, that is true. The reason that I didn't contradict myself is that in the two statements of mine, I was talking about a different equilibrium. It was a poor choice of words, but my point was that it doesn't matter if the equilibrium concerning the ionization of ammonia is shifted, the concentration of hydroxide ions will be miniscule and thus the reaction will be extremely slow. What it boils down to is that the aminolysis and hydrolysis(in basic conditions) of ethyl acetate have similar reaction rates if the concentration of the nucleophile(NH3 and OH- respectively) is the same. Even though the hydroxide is being constantly regenerated by the ionization of more ammonia molecules, it's concentration at any one point is never very high, as I stated a few posts back the concentration in 6M ammonia is 0.01M OH-, whereas the concentration of the other nucleophile, NH3 is very high throughout the entire reaction, thus it is the faster reaction. Some ammonium acetate will be formed, but as I stated previously, this isn't much of an issue anyway since most of it should decompose to acetamide during the workup. In addition, in basic conditions, reactions A and D occur simultaneously as different parts of the same mechanism.

[Edited on 4-12-2015 by gdflp]

DraconicAcid - 12-4-2015 at 07:04

Quote:
@gdflp
The presence of Hydroxide ions increases the hydrolysis rate. It also shifts the equilibrium to the right (product gets consumed). I don't understand your persistence in trying to textbook me with kinetics.


Because kinetics are what's important in this particular case. You can't shift the equilibrium to the right or the the left unless the system has reached equilibrium, and because the hydrolysis reaction with water is so slow, it doesn't get there over any reasonable time span.

Look- a wise man once said that there is no need to argue if an experiment can be done. Do you have any ethyl acetate? Take a mL of that, and a mL of water, put them in a test tube, shake it up. Once equilibrium is reached for the hydrolysis reaction, there should be enough ethanol and acetic acid present to give you a homogeneous mixture instead of a two-phase one. Shake it twice a day, and let us know when it stops separating. Do the same thing with ethyl acetate and aqueous sodium carbonate solution (carbonate isn't very nucleophilic, unlike ammonia). See if the hydrolysis reaches equilibrium any faster.

Quote:

This all comes down to:
Reaction A - Hydrolysis of Ethyl Acetate
Reaction B - Ionization of Ammonia
Reaction C - Aminolysis of Ethyl Acetate
Reaction D - NH4OH and Acetic Acid to form Ammonium Acetate

If Reaction C is faster than reaction A then Acetamide will be the major product. If reaction A is faster than reaction C then reaction D prevails and Ammonium Acetate will be the major product.

Now, in the absence of Hydroxide ions, reaction A is very slow. However, in the presence of said ions, the rate of reaction A increases. Thus, if OH ions are being consumed (reaction D), reaction B will ionize more ammonia. What you're all trying to sell is that reaction C still prevails.


This is correct. Even in the presence of a low concentration of hydroxide ions, reaction A is extremely slow, so we basically don't have to worry about it. If you were to use 1 M sodium hydroxide, you'd probably have appreciable hydrolysis quite quickly, but not in aqueous ammonia.

ETA: It seems that even a lower concentration of sodium hydroxide will hydrolyze ethyl acetate, at least according to several undergraduate experiments that measure the rate, such as http://www.uni-ulm.de/physchem-praktikum/media/literatur/Kin...


[Edited on 12-4-2015 by DraconicAcid]

HgDinis25 - 13-4-2015 at 11:51

Well, this has been an interesting discussion so far. I'll make sure to attempt a synthesis on Acetamide from Ammonia and Ethyl Acetate

@gdflp
Again, this all comes down to both reaction rates. Some actual values would be good, though. Anyway, your arguments make sense. If we consider the hydrolysis of Ethyl Acetate too slow in the presence of minimum amounts of Hydroxide ions then the most logical outcome would be the aminolysis of Ethyl Acetate.

@DraconicAcid

Quote:

Because kinetics are what's important in this particular case. You can't shift the equilibrium to the right or the the left unless the system has reached equilibrium, and because the hydrolysis reaction with water is so slow, it doesn't get there over any reasonable time span.


You can't shift the equilibrium, that's correct. But you can dramatically increase the reaction rate by adding small amounts of hydroxide ions. That would allow the system to reach equilibrium and then would allow it to be shifted.


Quote:

Look- a wise man once said that there is no need to argue if an experiment can be done. Do you have any ethyl acetate? Take a mL of that, and a mL of water, put them in a test tube, shake it up. Once equilibrium is reached for the hydrolysis reaction, there should be enough ethanol and acetic acid present to give you a homogeneous mixture instead of a two-phase one. Shake it twice a day, and let us know when it stops separating. Do the same thing with ethyl acetate and aqueous sodium carbonate solution (carbonate isn't very nucleophilic, unlike ammonia). See if the hydrolysis reaches equilibrium any faster.


I couldn't disagree more. Of course there is a need to argue! The reaction you just mentioned can occur exactly like you said. However, it can be for completely different reasons than the ones you stated. That's just like saying you can evaporate gold at ordinary temperatures. Just add it to mercury and it will disappear! It evaporated! This is ridiculous. I can also think of he good old story about the earlier tests for benzene. The substance wasn't actually testing for benzene.


xfusion44 - 24-11-2015 at 02:23

Hi!

I've tried the Polesch's method of acetamide synthesis, but after 24h of stirring, when I turned off stirrer, there were still two separate layers. Currently I'm waiting if some crystals will appear after some days. I used 25% NH4OH and probably pure enough EtOAc. Does someone know why this doesn't work for me?

Thanks!

xfusion44 - 1-12-2015 at 00:15

I'm back again, to tell you that the polesch's method worked! After a few days I did get some crystals (as on his pictures), even though solutions still separated after 24h of mixing :D

Best regards, xfusion44

Hegi - 25-4-2016 at 10:46

After 48 hours of stirring there were no more separate layers. BUT there was a small amount of white solid! After filtrating and reducing the volume nothing came out. I will let the solution to evaporate freely and I´ll see. 7 mL of 27% ammonium solution was used.

Magpie - 25-4-2016 at 17:52

Quote: Originally posted by Hegi  
... After filtrating and reducing the volume nothing came out.


I hope that DraconicAcid does not see this. :o

[Edited on 26-4-2016 by Magpie]

xfusion44 - 26-4-2016 at 11:12

Quote: Originally posted by Hegi  
After 48 hours of stirring there were no more separate layers. BUT there was a small amount of white solid! After filtrating and reducing the volume nothing came out. I will let the solution to evaporate freely and I´ll see. 7 mL of 27% ammonium solution was used.


It looks like it takes a few days for crystals to start forming, just leave it to sit a few more days and I'm sure you'll see crystals soon ;)



IMG_20151203_225949.jpg - 1.4MB IMG_20151203_225847.jpg - 1.6MB IMG_20160426_205915.jpg - 1.3MB

[Edited on 26-4-2016 by xfusion44]

Hegi - 27-4-2016 at 10:22

Quote: Originally posted by xfusion44  
Quote: Originally posted by Hegi  
After 48 hours of stirring there were no more separate layers. BUT there was a small amount of white solid! After filtrating and reducing the volume nothing came out. I will let the solution to evaporate freely and I´ll see. 7 mL of 27% ammonium solution was used.


It looks like it takes a few days for crystals to start forming, just leave it to sit a few more days and I'm sure you'll see crystals soon ;)





[Edited on 26-4-2016 by xfusion44]



I´m not so sure. There is absolutely minimum amount of the solution. I would say max 2-3 mL.


[Edited on 27-4-2016 by Hegi]

xfusion44 - 27-4-2016 at 17:30

Quote: Originally posted by Hegi  
Quote: Originally posted by xfusion44  
Quote: Originally posted by Hegi  
After 48 hours of stirring there were no more separate layers. BUT there was a small amount of white solid! After filtrating and reducing the volume nothing came out. I will let the solution to evaporate freely and I´ll see. 7 mL of 27% ammonium solution was used.


It looks like it takes a few days for crystals to start forming, just leave it to sit a few more days and I'm sure you'll see crystals soon ;)





[Edited on 26-4-2016 by xfusion44]



I´m not so sure. There is absolutely minimum amount of the solution. I would say max 2-3 mL.


[Edited on 27-4-2016 by Hegi]


How much of ethyl acetate did you use? 2-3ml doesn't make sense to me, if you started with total of about 20ml (EtOAc + NH4OH) What about filtered part of solution? You said that volume of solution was reduced significantly after filtering - maybe you filtered off your acetamide, since you also mentioned that you could see some white stuff forming in solution (perhaps that was it). Although it's theoretically impossible to filter acetamide, due to its very high solubility in water, you probably succeded with that, since crystals already started to form and if you didn't mix the solution before filtering it, the crystals had no time to dissolve so they were probably stopped by the filter. Although, I could be wrong... How about the purity of EtOAc? And are you sure your ammonia solution is 27%? If its old or if it was stored in warm place, it could be much less concentrated.

I'd suggest you to try again, but this time don't filter the solution, just leave it in wide container, at room temperature for 3-4 days and you should see the crystals.

Hegi - 13-4-2018 at 01:08

I got back to the synthesis. I mixed 10 ml of p.a. ethyl acetate in a baker with 7 ml of 25-26% ammonia solution and stirred at 1000 rpms the mixture for over 24 hours. The layers are still present. Can somebody explain this? Should I use excess of ammonia solution?

Thanks in advance.

Hegi - 17-4-2018 at 04:25

Quote: Originally posted by Hegi  
I got back to the synthesis. I mixed 10 ml of p.a. ethyl acetate in a baker with 7 ml of 25-26% ammonia solution and stirred at 1000 rpms the mixture for over 24 hours. The layers are still present. Can somebody explain this? Should I use excess of ammonia solution?

Thanks in advance.


I used more ammonia and layers separated. Then I got wrong by heating the solution and hydrolyzed my product... now I have acetic acid... I should have left the solution freely to crystalize...

Hegi - 20-4-2018 at 00:51

Quote: Originally posted by Hegi  
Quote: Originally posted by Hegi  
I got back to the synthesis. I mixed 10 ml of p.a. ethyl acetate in a baker with 7 ml of 25-26% ammonia solution and stirred at 1000 rpms the mixture for over 24 hours. The layers are still present. Can somebody explain this? Should I use excess of ammonia solution?

Thanks in advance.


I used more ammonia and layers separated. Then I got wrong by heating the solution and hydrolyzed my product... now I have acetic acid... I should have left the solution freely to crystalize...


I repeated the procedure... After homogenization of solution I got final solution that was pretty basic (pH over 12). I poured this into Petri´s dish and left freely to crystalllize. Next day I came to the lab the smell of ammonia was gone and replaced by the smell of acetic acid. However, small crystals are on the surface of the liquid. I will wait till monday what is going to happen.