Sciencemadness Discussion Board

Ester hydrolysis of ASA to salicylic acid.

nb198 - 8-4-2014 at 18:26

I changed the original title. I was originally asking how to get the ASA out of the acetone without evaporating. I wanted to try and crash it out. I ended up rotovapping it.

I crushed up 500 325mg tablets of acetylsalicylic acid and added them to 1L of acetone.

I then rotovapped off the acetone and let the ASA dry in an oven at 110C overnight

I would like to hydrolyze the ester now to make salicylic acid. I am going to go with base hydrolysis because it is not an equilibrium like the acid hydrolysis. I am going to use NaOH.

How much NaOH should I use? The base is going to be consumed in the reaction, so I would be foolish to use stoichiometric amounts.

My theoretical yield of ASA is ~162g. This is 0.9 mol, so at 1:1 ASA:NaOH, i would need a minimum of about 36g of NaOH.

I was thinking that I could add my product to 400mL of 6M NaOH (about 108g, severe excess) to speed up the reaction. I would then just stir it at room temperature for a few days.

Is the amount of NaOH I plan to use complete overkill? It is almost 3x what is required.

[Edited on 9-4-2014 by nb198]

thesmug - 8-4-2014 at 18:57

If you have a rotovap, the obvious answer is to use that.

Bert - 8-4-2014 at 19:20

Could you edit this to provide links or at least an attribution & an exact quote of the source material you're working from? "According to a website I found" isn't really sufficient.

nb198 - 8-4-2014 at 19:43

Quote: Originally posted by Bert  
Could you edit this to provide links or at least an attribution & an exact quote of the source material you're working from? "According to a website I found" isn't really sufficient.


Sorry about that, no problem. Here is the link

nb198 - 8-4-2014 at 19:46

Quote: Originally posted by thesmug  
If you have a rotovap, the obvious answer is to use that.


True. I was looking to find a way to do it without the rotovap though. I wanted to figure out a more "home friendly" method. That is why I used acetone in the first place. I should definitely edit my post

confused - 8-4-2014 at 20:46

i don't see why evaporating it shouldn't work, it may take a long time though, depending on amount of solvent

Chemosynthesis - 8-4-2014 at 20:59

Quote: Originally posted by nb198  
True. I was looking to find a way to do it without the rotovap though. I wanted to figure out a more "home friendly" method.

If you don't have a vacuum with a solvent trap, use very mild heat with a small stream of air across your solvent or, less preferably, hosed into the solution from above. This will speed up evaporation.

Zephyr - 8-4-2014 at 21:20

IIRC, when I performed this purification, I dissolved the acetylsalicylic acid in boiling ethanol, then filtered and cooled in an ice bath. The acetylsalicylic acid crystallized out nicely. I am unsure of the solubility of ASA in acetone at varying temperatures, however it couldn't hurt to put it in an ice bath and see if anything crystallizes out?

nb198 - 9-4-2014 at 04:56

Quote: Originally posted by Pinkhippo11  
IIRC, when I performed this purification, I dissolved the acetylsalicylic acid in boiling ethanol, then filtered and cooled in an ice bath. The acetylsalicylic acid crystallized out nicely. I am unsure of the solubility of ASA in acetone at varying temperatures, however it couldn't hurt to put it in an ice bath and see if anything crystallizes out?


I will definitely try this. How much ASA did you attempt to extract and with how much solvent?

nb198 - 9-4-2014 at 04:58

Quote: Originally posted by confused  
i don't see why evaporating it shouldn't work, it may take a long time though, depending on amount of solvent


It is 1L, so it is quite a bit in my opinion to just evaporate off. I am going to try cooling it and seeing if anything precipitates. If not, I will just rotovap it.

I was really hoping that there would be a nifty way to crash it out of the acetone. That way I could reuse the acetone.

HeYBrO - 9-4-2014 at 23:57

Don't bother with the NaOH just use HCl to directly yield Salicylic acid. Check my Blog if you want to know more.

hyfalcon - 10-4-2014 at 05:03

ASA is definitely less soluble in acetone then it is in ethanol.

nb198 - 10-4-2014 at 06:22

Quote: Originally posted by hyfalcon  
ASA is definitely less soluble in acetone then it is in ethanol.


According to this paper, it is most soluble in acetone.

http://pubs.acs.org/doi/pdf/10.1021/je7005693

"The solubility of acetylsalicylic acid is highest in acetone in all studied temperature ranges..."

nb198 - 10-4-2014 at 06:23

Quote: Originally posted by HeYBrO  
Don't bother with the NaOH just use HCl to directly yield Salicylic acid. Check my Blog if you want to know more.


I was going to go with NaOH because it isn't an equilibrium. However, I think you are right. It is just not worth the time to prepare an NaOH solution and then add HCl to crash out the crystals. Using HCl saves time and materials.

EDIT: I am actually going to go with the NaOH method in the end because I don't like the equilibrium

[Edited on 10-4-2014 by nb198]

nb198 - 10-4-2014 at 07:36

I went ahead with 325mL of 6M NaOH. I am refluxing it for 1h.

[Edited on 10-4-2014 by nb198]

HeYBrO - 10-4-2014 at 23:15

If you want more work go for it. Just as loss of water during esterification pushes the equilibrium to the product side, the opposite is true for for excess water and the hydrolysis. The hydrolysis is nearly quantitative in this case. I got a 95% yield with 45 min reflux. "because I don't like equilibrium" doesn't sit right, every reaction is in equilibrium to an extent. In reality, the amount of extra work you have to put in with the sodium hydroxide loses more yield than the nearly quantitative equilibrium. Have a look at the mechanism
http://www.chemguide.co.uk/physical/catalysis/hydrolyse.html
http://web.uvic.ca/~pmarrs/chem463/463e35aspirinhydrolysis.p...
Any way I'm done flogging this dead horse, so to speak. Next time try the acid catalysed hydrolysis :)

EDIT: Sorry if this sounds passive aggressive ( i think it does but i'm not trying to be)

[Edited on 11-4-2014 by HeYBrO]

nb198 - 11-4-2014 at 04:59

Quote: Originally posted by HeYBrO  
If you want more work go for it. Just as loss of water during esterification pushes the equilibrium to the product side, the opposite is true for for excess water and the hydrolysis. The hydrolysis is nearly quantitative in this case. I got a 95% yield with 45 min reflux. "because I don't like equilibrium" doesn't sit right, every reaction is in equilibrium to an extent. In reality, the amount of extra work you have to put in with the sodium hydroxide loses more yield than the nearly quantitative equilibrium. Have a look at the mechanism
http://www.chemguide.co.uk/physical/catalysis/hydrolyse.html
http://web.uvic.ca/~pmarrs/chem463/463e35aspirinhydrolysis.p...
Any way I'm done flogging this dead horse, so to speak. Next time try the acid catalysed hydrolysis :)

EDIT: Sorry if this sounds passive aggressive ( i think it does but i'm not trying to be)

[Edited on 11-4-2014 by HeYBrO]


Ha no problem. I know that every reaction is an equilibrium to some extent but some are mor than others. I think the reason I chose base hydrolysis was because since you didn't take a melting point, it is hard to tell how pure your SA is, I.e. how much ASA remains. Also I just wanted to try the base hydrolysis and see what the results were. I letthe crude SA dry in an oven overnight. I'll see what the crude yield and mp is before recryst.

HeYBrO - 11-4-2014 at 16:38

Quote: Originally posted by nb198  

I think the reason I chose base hydrolysis was because since you didn't take a melting point, it is hard to tell how pure your SA is, I.e. how much ASA remains.


Because I didn't take a melting point?! :o:P
Many people have done this experiment with the acid;
Quote: Originally posted by UnintentionalChaos  

Conversion of Aspirin to Salicylic Acid

A 1L RBF is charged with a stirbar, 45.04g of acetylsalicylic acid (250mmol), 600ml of distilled water, and 10ml of 31.45% hydrochloric acid. A vertical condenser is attached and the reaction mixture heated to reflux. After 30 minutes (This may be excessive, but I know it works), heating is stopped and stirring turned off. The solution, which should be a clear, colorless liquid, is very nearly saturated with salicylic acid and after cooling for a few minutes should be agitated to induce crystallization or seeded with a small quantity of salicylic acid crystals. The flask is left to stand undisturbed for several hours while crystallization occurs. Solubility at 20oC is nearly negligible (~2g/L), and cooling in an ice bath is unnecessary. The product is a mass of small, white needle-like crystals that fill the solution. The solution is agitated to break up the fragile crystal mass and vacuum filtered. A clean stopper is used to press the "fluffy" mass of crystals to aid in removal of the mother liquor. This cake is washed with two 50ml portions of distilled water. The product can be dried in a dessicator, at room temp, or at mildly elevated temperatures. The yield of salicylic acid is roughly 95% of the theoretical as glittering white needles melting at 156-157.5oC (uncorr, lit m.p. 158.6oC)




Maybe do a test to see which gives better yield and purity? I would love to see.

Ps. good job on your videos, they are excellent.

nb198 - 11-4-2014 at 17:21

Quote: Originally posted by HeYBrO  
Quote: Originally posted by nb198  

I think the reason I chose base hydrolysis was because since you didn't take a melting point, it is hard to tell how pure your SA is, I.e. how much ASA remains.


Because I didn't take a melting point?! :o:P
Many people have done this experiment with the acid;
Quote: Originally posted by UnintentionalChaos  

Conversion of Aspirin to Salicylic Acid

A 1L RBF is charged with a stirbar, 45.04g of acetylsalicylic acid (250mmol), 600ml of distilled water, and 10ml of 31.45% hydrochloric acid. A vertical condenser is attached and the reaction mixture heated to reflux. After 30 minutes (This may be excessive, but I know it works), heating is stopped and stirring turned off. The solution, which should be a clear, colorless liquid, is very nearly saturated with salicylic acid and after cooling for a few minutes should be agitated to induce crystallization or seeded with a small quantity of salicylic acid crystals. The flask is left to stand undisturbed for several hours while crystallization occurs. Solubility at 20oC is nearly negligible (~2g/L), and cooling in an ice bath is unnecessary. The product is a mass of small, white needle-like crystals that fill the solution. The solution is agitated to break up the fragile crystal mass and vacuum filtered. A clean stopper is used to press the "fluffy" mass of crystals to aid in removal of the mother liquor. This cake is washed with two 50ml portions of distilled water. The product can be dried in a dessicator, at room temp, or at mildly elevated temperatures. The yield of salicylic acid is roughly 95% of the theoretical as glittering white needles melting at 156-157.5oC (uncorr, lit m.p. 158.6oC)




Maybe do a test to see which gives better yield and purity? I would love to see.

Ps. good job on your videos, they are excellent.


Yeah I'm thinking base hydrolysis is a waste. I got 92% crude yield and mp of 156-159C. It had a slight hint of acetic acid smell so I am recrystallizing. I am going to see on Monday what the purity is after drying it. I probably could have just washed it more when filtering though to get rid of the remaining acetic acid. It is seeming to me that base hydrolysis just isn't worth the extra effort.

nb198 - 15-4-2014 at 19:53

Recrystalization resulted in a 10% loss and a new M.P. of 157-159C. It was not worth the time at all.

Also, acid hydrolysis is almost definitely better. I think though, that it is possible to do the base hydrolysis without reflux. Adding the NaOH quickly dissolved the normally water insoluble ASA to form the water soluble Na-salt. It also heat up quite a bit. I think that stirring for 20 minutes without reflux could have worked just as well. That would have to be verified though. Skipping a reflux would be about the only benefit I would see of base hydrolysis over acid in this case.