Ch. 20 - Carboxylic Acid Derivatives: NAS WorksheetSee all chapters
All Chapters
Ch. 1 - A Review of General Chemistry
Ch. 2 - Molecular Representations
Ch. 3 - Acids and Bases
Ch. 4 - Alkanes and Cycloalkanes
Ch. 5 - Chirality
Ch. 6 - Thermodynamics and Kinetics
Ch. 7 - Substitution Reactions
Ch. 8 - Elimination Reactions
Ch. 9 - Alkenes and Alkynes
Ch. 10 - Addition Reactions
Ch. 11 - Radical Reactions
Ch. 12 - Alcohols, Ethers, Epoxides and Thiols
Ch. 13 - Alcohols and Carbonyl Compounds
Ch. 14 - Synthetic Techniques
Ch. 15 - Analytical Techniques: IR, NMR, Mass Spect
Ch. 16 - Conjugated Systems
Ch. 17 - Aromaticity
Ch. 18 - Reactions of Aromatics: EAS and Beyond
Ch. 19 - Aldehydes and Ketones: Nucleophilic Addition
Ch. 20 - Carboxylic Acid Derivatives: NAS
Ch. 21 - Enolate Chemistry: Reactions at the Alpha-Carbon
Ch. 22 - Condensation Chemistry
Ch. 23 - Amines
Ch. 24 - Carbohydrates
Ch. 25 - Phenols
Ch. 26 - Amino Acids, Peptides, and Proteins

Fischer Esterification is also known as acid-catalyzed esterification. Why is it so important? Because we convert an OH group to an OR group. 

Concept #1: General Reaction


Hey guys! Now we’re going to talk about one of the more important mechanisms in this course. That is mechanism of Fischer Esterification. Fischer Esterification is just another name for acid-catalyzed esterification. When we think about what that is, that would just mean that I’m taking a carboxylic acid and reacting it with alcohol in the presence of acid and I’m getting an ester. I'm getting an ester product hence the term esterification. According to our three rules, this is a totally fine reaction because we said that carboxylic acid and esters have about the same reactivity. It’s pretty easy to switch between the two. According to my three rules, I know this is a favored reaction that this can work. Then why do I have this video? Because it turns out that professors just love to ask about this mechanism because it’s one of the fundamental mechanisms of nucleophilic acyl substitution. That’s why I’m going to go into depth and we're going to draw the whole mechanism for this from scratch. Let's go ahead and do that now.

Concept #2: General Mechanism


So, if you've been following clutch for a while or if you're just naturally good at Orgo it shouldn't be so hard because we're going to see these recurring themes of these acid catalyzed reactions that just keep happening over and over with just minor adjustments, okay? So, one thing before begin, I hope you guys are okay with me using a protonated version of alcohol as my acid because I don't want to have two different things hanging around. So, I'm just going to let you guys know that alcohol plus H plus, my acid, is going to give me ROH2 plus, which is what I'm going to use my acid, okay? So, if you couldn't see that I'll move it up a little bit. Okay cool. So, I'm going to say H-ORH positive, my first step is going to be, you got it, protonation, because it's acid catalyzed. So, it's going to give me something looks like this OH, OH positive, we know this is going to open up the opportunity for a resonance structure. So, let's draw that, okay? Again guys, if you look in your textbook or if you watch your professor drawing this, they may not include this resonance structure but it's okay, because it's still valid, all the arrows are going in to the same place, I'm just splitting it up a little bit better, okay? So, Now this is a perfect environment for a nucleophilic addition, right? So, I'm going to take my alcohol, I'm sorry, a nucleophilic attack, I'm going to take my alcohol and I'm going to make this intermediate, what do we have? we have OH, OH, OHR and then our R group and this has a positive, okay? So, at this point look, what we've done so far, we've done protonation, we have done a nucleophilic attack and now what are we going to do? Well, guys, we're trying to get rid of one of the OH's to replace it with OR. So, we're going to do a proton transfer so we can get rid of one of those ovations so this is going to be proton transfer, after I do that I get a molecule, looks like this, where now I have OH2 positive, OR and my R group.

Now, guys I can do an elimination reaction where the lone pair from my O comes down and kicks out my water, what that gives me is now a compound looks like this, and what's my last step? my last step is deprotonation with the original alcohol to regenerate my catalytic acid. So, at the end I'm going to get an ester and guess what guys, this is a completely reversible reaction. So, if we wanted to take every step backwards we could. Alright, make sense? Guys, so I'm not sure if you guys have seen these mechanisms already or not but if you look at the mechanisms of acetals or if you look at the mechanisms of amines, these our carbonyl reactions that are, I have videos for in other parts of your clutch textbook, right? And, if you look at those mechanisms you're going to see so many similarities, these mechanisms just keep kind of like replicating themselves, okay? By the way, I forgot to say this was elimination and this was deprotonation. Awesome guys, are you getting a little better at mechanisms? hopefully, I hope so, I hope I'm making a little easier for you, let's move on to the next reaction.


BTW if you notice that when drawing the first resonance structure in red there is an arrow that looks off, don't be alarmed! The arrow should go the opposite direction [from the double bond to the +OH group]