Acid-Catalyzed Ester Hydrolysis

Concept: General Reaction

2m
Video Transcript

Let's talk about a reaction called acid-catalyzed ester hydrolysis. Acid-catalyzed ester hydrolysis is literally just the reverse of Fischer esterification. It's literally just the reverse reaction of producing an ester. You could then hydrolyze that ester back to a carboxylic acid. The general reaction would be that you have your ester but you react your ester in an aqueous solution with acid. You’re going to hydrolyze that ester to a carboxylic acid. Also if you recall, the three rules of NAS. This would be rule number three. The carboxylic acid conversion that says that pretty much carboxylic acid derivative in combination with water or acid or base could turn into a carboxylic acid. Now what I want to do is go through the mechanism for this. By the way, I already told you it’s the exact opposite of Fischer esterification. If you literally wanted to go to the Fisher esterification video and draw out every arrow backwards, every nucleophile backwards, you would get the mechanism. But I know that you guys are going to complain if I don't draw the reverse reaction. Let's go ahead and do that now. I’m going to show you guys exactly how to draw the reverse of Fisher esterification. 

Concept: General Mechanism

3m
Video Transcript

Alright, so let's start off with our ester, okay? And, I'm going to go ahead and use H3O plus as my acid, okay? So, what can be the first step? okay it going to be protonation, you got it, that's going to give me a compound that looks like this, positive charge, what's my next step? resonate. So, it's resonate, that's going to give me a positive here, draw my resonance structure and this is a great time to nucleophilically attack. So, I'm going to get water and my water is going to attack and I'm going to form some molecule, wait, let me draw my equilibrium arrows, I'm going to form a molecule, it looks like this OH at the top, OR on the side and water at the bottom, can you guess what the next step is going to be? So guys, what are we trying to get rid of? we're trying to get rid of the OR, which means that I want to do a proton transfer specifically to the OR this time, okay? if you say, Well, Johnny, how do you know that it doesn't go to the OH? Well, because then that would be the forward mechanism, okay? So, I'm just trying to go backwards here. So, I'm trying to get rid of the OR. So, this OR grabs that H and turns into OH R positive, okay? Now, what happens is I eliminate, I use the electrons from my O to kick out the OR we, that's not going to work, and I now have a structure that looks like this OH positive ROH and now I use what to deprotonate? water, to regenerate my acid, okay guys? So, if anything this serves as extra practice for you for the Fischer esterification mechanism because it is that mechanism, okay? Plus my H3O plus and plus my alcohol, right? Because I generated one equivalent of alcohol that I lost, okay? So guys, that's really it, let's move on to the next video.

Acid-Catalyzed Ester Hydrolysis Additional Practice Problems

The mechanism for the acid-catalyzed hydrolysis of ester involves the breaking of which of the following bonds?

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(a) The Key Mechanism for Fischer esterification omitted some important resonance forms of the intermediates shown in brackets. Complete the mechanism by drawing all the resonance forms of these two intermediates. 

(b) Propose a mechanism for the acid-catalyzed reaction of acetic acid with ethanol to give ethyl acetate.

(c) The principle of microscopic reversibility states that a forward reaction and a reverse reaction taking place under the same conditions (as in an equilibrium) must follow the same reaction pathway in microscopic detail. The reverse of the Fischer esterification is the acid-catalyzed hydrolysis of an ester. Propose a mechanism for the acid-catalyzed hydrolysis of ethyl benzoate, PhCOOCH2CH3.

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a. What species other than an acid can be used to increase the rate of the transesterification reaction that converts methyl acetate to propyl acetate?

b. Explain why the rate of aminolysis of an ester cannot be increased by H+, HO–, or RO–.

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Write the mechanism for the acid-catalyzed reaction of tert-butyl acetate with methanol.

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Write the mechanism for the acid-catalyzed transesterification of ethyl acetate with methanol.

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In the mechanism for the acid-catalyzed hydrolysis of an ester,

a. what species could be represented by HB+?

b. what species could be represented by :B?

c. what species is HB+ most likely to be in the hydrolysis reaction?

d. what species is HB+ most likely to be in the reverse reaction?

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Using the mechanism for the acid-catalyzed hydrolysis of an ester as your guide, write the mechanism—showing all the curved arrows—for the acid-catalyzed reaction of acetic acid and methanol to form methyl acetate. Use HB+ and :B to represent the proton-donating and protonremoving species, respectively.

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What products would be formed from the acid-catalyzed hydrolysis of the following esters?

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a. State three factors cause the uncatalyzed hydrolysis of an ester to be a slow reaction.

b. Which is faster, the hydrolysis of an ester or the aminolysis of the same ester? Explain your answer.

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Provide the reagents necessary and the mechanism to complete this transformation.

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Complete the mechanism for the following acid catalyzed ester hydrolysis reaction. Be sure to show arrows to indicate movement of all electrons, write all lone pairs, all formal charges, and all the products for each step. IF A NEW CHIRAL CENTER IS CREATED IN AN INTERMEDIATE OR THE PRODUCTS, MARK IT WITH AN ASTERISK AND LABEL AS "RACEMIC" IF RELEVANT. IN THE BOX BY EACH SET OF ARROWS, WRITE WHICH OF THE 4 MECHANISTIC ELEMENTS IS INDICATED IN EACH STEP OF YOUR MECHANISM (For example, "Add a proton").

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Complete the mechanism for the following ester hydrolysis reaction. In the boxes provided, write which of the 4 mechanistic elements describes each step (make a bond, break a bond, etc.).

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Which structure is a reasonable intermediate in the acid-catalyzed hydrolysis of ethyl acetate in dilute aqueous acid?

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Draw a reasonable mechanism for the reaction below.

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