Fischer Esterification Acid vs Base catalyzed

[betterfuture]

So my understanding is that protonation of the carbonyl carbon of a carboxylic acid makes the C more susceptible to nucleophilic attack, since the protonated O pulls electron density towards itself, thus leaving a more partial positive charge on the C (increasing electrophilicty)

But for a base catalyzed reaction, the base, OH-, would remove a proton from the carboxylic acid, thus leaving it as a carboxylate anion (negative charge) making it highly unlikely for nucleophilic attack.

So my question is, how does the base not remove a proton from the alcohol group aka the nucleophile? Wouldn't that increase its nucleophilicity, making it attack the carbonyl carbon faster? Or does it not work out that way in the lab hence the reason for base catalyzed not being favored in fisher esterification?

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[GiantPanda1]

Carboxylic acid hydrogen is far more acidic than an alcohol group. Even if you made the alcohol group a better nucleophile, the carboxylic acid still doesn't want to accept it.

 

[betterfuture]

I am sorry, can you clarify what you mean by," ...the carboxylic acid still doesn't want to accept it."

 

[GiantPanda1]

I am sorry, can you clarify what you mean by," ...the carboxylic acid still doesn't want to accept it."

Sure, so let's actually run through the base reaction and see what you end up with. The carboxylic acid acts as the electrophile. The alcohol acts as the nucleophile. You do the attack on the carboxylic carbon. You end up with two negative oxygens. That's a no-no for a million reasons. How do we try and stabilize that? One of the negative O tries to kick down an electron to form a double bond and has to kick off the other negative oxygen. Have you ever seen a negative oxygen ion all by itself? Noooope. So if for whatever reason we're at the kicking off step (very high energy already), it'll probably just kick off the alcohol to restabilize itself leaving you back at where you started.

 

[theonlytycrane]

mix the R-O-H group with a strong base first -> H2O + R-O- (nucleophile).

Then take the nucleophile and mix it with the carboxylic acid -> ester.

Mixing the carboxylic acid, strong base, and R-O-H group together all at once will result in an acid-base reaction between the carboxylic acid and strong base.

 

[Necr0sis713]

But for a base catalyzed reaction, the base, OH-, would remove a proton from the carboxylic acid, thus leaving it as a carboxylate anion (negative charge) making it highly unlikely for nucleophilic attack.

So my question is, how does the base not remove a proton from the alcohol group aka the nucleophile? Wouldn't that increase its nucleophilicity, making it attack the carbonyl carbon faster? Or does it not work out that way in the lab hence the reason for base catalyzed not being favored in fisher esterification?

You don't mix OH- as a base with your alcohol. Otherwise, you would just hydrolyze (add the OH) on the carboxylic acid, which is redundant.

let's say you want to do base catalyzed esterification to add an OEt on the carboxylic acid. You would add HOEt with -OEt (as your base). You wouldn't add OH- to remove the H from the HOEt. In fact, OH- is way too weak of a base to deprotonate an alcohol.

You basically choose the combo of base/alcohol based on what group you want to add to the Carboxylic acid. So if you want to add an OEt, you use -OEt (Or NaOEt; same thing) and HOEt. If you want to add OMe, then you add HOMe and -OMe.

Also, to me, it sounds like you're thinking of this as there is just ONE base in the mixture. You have to keep in mind that your substrate is essentially floating around with a ton of base and alcohol. So yeah, even you're gonna deprotonate the OH on the caboxyl, there's still plenty of other base to attack to carbonyl.

 

[betterfuture]

mix the R-O-H group with a strong base first -> H2O + R-O- (nucleophile).

Then take the nucleophile and mix it with the carboxylic acid -> ester.

Mixing the carboxylic acid, strong base, and R-O-H group together all at once will result in an acid-base reaction between the carboxylic acid and strong base.

So you are saying its possible?

 

[betterfuture]

You don't mix OH- as a base with your alcohol. Otherwise, you would just hydrolyze (add the OH) on the carboxylic acid, which is redundant.

let's say you want to do base catalyzed esterification to add an OEt on the carboxylic acid. You would add HOEt with -OEt (as your base). You wouldn't add OH- to remove the H from the HOEt. In fact, OH- is way too weak of a base to deprotonate an alcohol.

You basically choose the combo of base/alcohol based on what group you want to add to the Carboxylic acid. So if you want to add an OEt, you use -OEt (Or NaOEt; same thing) and HOEt. If you want to add OMe, then you add HOMe and -OMe.

Also, to me, it sounds like you're thinking of this as there is just ONE base in the mixture. You have to keep in mind that your substrate is essentially floating around with a ton of base and alcohol. So yeah, even you're gonna deprotonate the OH on the caboxyl, there's still plenty of other base to attack to carbonyl.

So there are specific base/alcohol pairings for fischer esterification to take place? Meaning, it is possible?

 

[Necr0sis713]

So there are specific base/alcohol pairings for fischer esterification to take place? Meaning, it is possible?

What do you mean? What are you asking is possible.

There are specific base pairings for what you want. It's really easy (which is why I love esterfication) It's as easy as this:

You have a carboxylic acid. Let's say you want to make a metyl ester. You just add the carboxylic acid, Methoxide/Methanol combo, and bam, you have the methyl ester. The METHYL in the ester comes from the METHoxide.

You want to make an ETHYL ester? Just add ETHoxide and ETHanol

In regards to OH-. Any ester will get hydrolyzed by OH- to make a carboxylic acid. So it kind of defeats the purpose to adding OH- in a mixture of the alcohol you want to add.