Ch. 12 - Alcohols, Ethers, Epoxides and ThiolsWorksheetSee 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

Alcohols are highly reactive. This can be a problem if we want to react on some other part of the molecule. How can we guarantee that a reaction won’t take place at the alcohol? 

Concept #1: General features of Alcohol Protecting Groups. 


Hey guys, so now let's talk about protecting groups. Protecting groups are reactions that are used to shield certain types of functional groups. In this case, I'm using the word moieties just means some kind of reaction region of the molecule from a reaction that's going to happen on another part of the molecule.
I know that sounds complicated, but basically what we're going to try to do is we're going to try to shield vulnerable functional groups from certain types of strong reagents. By definition, this has to be a completely reversible, easily reversible reaction. The reason for that is that you're supposed to be able to take the molecule off after the reaction is complete. So if you're not able to regenerate that vulnerable functional group at the end, that's not really a great protecting group.
Let me give you an example of why I might need something like this. Let's go ahead and look at this reaction. We've got an alcohol and an alkyl halide on the same molecule. First of all, that brings up our first point. You're only going to use a protecting group if you have more than one functional group on a molecule. If you only have one functional group, we don't care, you don't need to protect anything. But if you have more than one, then there may be some instances where you want to react with one and not the other and that's when you use a protecting group.
Let's look at this reagent. Our reagent is an alkynide. As you guys might remember, alkynides are good nucleophiles, but they're also strong bases. Is there anything – oh, that's supposed to be erasing. Is there anything that the alkynide could do to those functional groups? Well, in this case, what I'm trying to do is as you can see, my end product, I'm trying to make this alkynide perform a substitution reaction on the alkyl halide. In this case, this would be an SN2 reaction. So that's what I'm trying to make happen.
But notice that there's that other functional group of the molecule, the alcohol. Can alcohols react with alkynides? Actually, yes and they react through a different mechanism. They react through an acid-base mechanism because we know that alcohols have an acidic proton and alkynides are very strong bases. It turns out that this reaction will not proceed to completion. In fact, the alkynide will almost exclusively react with the OH and it will pretty much not react at all with the alkyl halide.
So if I do want this reaction to happen, is there any way to make it only react with the alkyl halide and not the alcohol? Well, scientists determined, you know what, alcohols are messing up a lot of different reactions, so if we can figure out a way to get rid of the alcohol for a few minutes, then run the rest of the reaction and then regenerate the alcohol, that would be really helpful. That's exactly what we're going to do with our protecting group. 

For example, the following substitution reaction has a major problem as drawn. Can you spot the issue?

Protecting groups are reversible reactions that temporarily block groups from reacting, so that we can transform other parts of the molecule.