Alcohol Synthesis - Online Tutor, Practice Problems & Exam Prep

Alcohols can be synthesized through four primary methods: oxymercuration, which adds a hydroxyl group at the Markovnikov position without carbocation rearrangement; hydroboration, yielding anti-Markovnikov alcohols at the least substituted position; acid-catalyzed hydration, producing alcohols at tertiary positions via carbocation intermediates; and SN2 reactions, which invert stereochemistry when converting alkyl halides to alcohols. Understanding these mechanisms is crucial for mastering organic synthesis and reaction pathways.

Forming alcohols through Oxymercuration-Reduction.

In this section, we're going to talk a lot about alcohols. So it's important for us to take a minute to remember all the different ways that we can make alcohols from prior chapters. So let's go ahead and get started. It turns out that there are 4 different ways that we've already learned to make alcohols. And I'm going to go ahead and remind you of what those are now. So let's say that I have a double bond and I'm trying to add a hydroxyl group to it. And I want to add it specifically in this position, what addition reaction could I use to put a hydroxyl right on that secondary position? The answer is that there's only one reaction that could yield this kind of alcohol and that would be oxymercuration or what we just called oxymerc. Why is that? Because if you remember, oxymercuration is an addition reaction that adds Markovnikov alcohol, which is good because you can tell that that is the Markovnikov or more substituted location. But there's another thing about oxymerc, which is that there's no carbocation in the intermediate. Okay? And remember that carbocations have a tendency to do what? They shift. So in this case, this is an example of where I can add Markovnikov alcohol without worrying about a rearrangement. So now all we have to do is fill in the reagents for oxymerc. Does anyone remember them? Well, basically what we would have is some kind of mercury molecule, so it would be HgOAC₂. And then what we would put with that is water. Why is that? Because we want to show specifically that we're using water to add the alcohol. On the bottom of the arrow, then we did the reduction step. Remember that the full name of this reaction is oxymercuration reduction. The reduction is completed by NaBH₄, which later on we will learn as a reducing agent and a base, so NaOH. Okay? Those are the reagents. I know it looks like a lot, but we have been over this before and this is one of the ways that you can add alcohol to a double bond. All right? So we've been over one of the 4 ways, but let's keep going because it turns out that there's a lot more that we can do to a double bond.

Forming alcohols through Hydroboration-Oxidation.

So what if we take that same double bond, but we want to add the alcohol here instead? Notice that in this molecule, I have the alcohol on the least substituted position. Does anyone remember what kind of reaction that would be? Well, it's going to be another addition reaction but has a completely different name. This is hydroboration. Remember hydroboration is really unique because it's going to be the only anti Markovnikov way we have to add alcohol to the least substituted position. Okay? So let's just go ahead and remember what the reagents were. Does anyone remember? It was really hydroboration means that you need boron in there. And it was really going to be any boron source, most commonly BH₃, but your professor, your textbook may use a different source of boron. There are all kinds of different sources that we can use. And BH₃ and many times that will be complexed to THF. But sometimes you won't see that step, but sometimes THF is a solvent, so it's not absolutely required that you write that. But sometimes you'll see it. And that's it for the top. The top is just adding boron. The bottom is the oxidation step because remember that it's hydroboration oxidation. Let's fill those reagents in. That was hydrogen peroxide and once again a base. Okay? So those are the reagents that could generate an anti Markovnikov alcohol from a double bond.

Forming alcohols through Acid-Catalyzed Hydration.

Cool. So we've gone over 2 ways. Now let's go on to the next one. Notice that let's say I start off with that double bond, but now what I end up getting is an alcohol not in the secondary position, but in the tertiary position. That's kind of odd. Notice that the double bond used to be here, but now my alcohol isn't even attached where the double bond was before. Okay? Any clue what this might be? This is also going to be a Markovnikov addition, but it's a Markovnikov addition that also has a carbocation in the intermediate in the reaction. So what this means is that this is going to have to be an acid-catalyzed hydration. Sorry. Acid-catalyzed hydration. There we go. And the reagents for this one were much easier. It was really just any strong acid. So I'm just going to put here over water. But most commonly, the acid that we would use is sulfuric acid. So most commonly what you're going to see is, like H2O over H2SO4 or the other way around too. Both are fine. Okay? So that's usually what you would see. And remember what that's going to do is it's going to add water, but it's going to add it to the most stable location, which is the one that is created. The tertiary position is created after it shifts. So those are the 3 different ways that we have to make alcohol from an addition reaction. And this is just meant to be an overview of the reactions that we've already learned. If you need to brush up on your addition reactions, I would recommend to go to the addition reactions chapter and I always teach all these 3 in a row as well, so you'll be able to really learn the full mechanisms and catch up on some of the stuff that you might be rusty on.

Here’s what students ask on this topic:

What are the reagents and conditions for oxymercuration-demercuration in alcohol synthesis?

Oxymercuration-demercuration is a method to synthesize alcohols by adding a hydroxyl group to the Markovnikov position of an alkene without carbocation rearrangement. The reagents for this reaction are mercuric acetate (Hg(OAc)₂) and water (H₂O) for the oxymercuration step. The demercuration step is carried out using sodium borohydride (NaBH₄) and a base, typically sodium hydroxide (NaOH). The overall reaction can be summarized as:

${R=R}_1+{\mathrm{Hg}\left(\mathrm{OAc}\right)2}_2+{H2O}_2\to {R-\mathrm{OH}}_1+{\mathrm{NaBH}4}_2+{\mathrm{NaOH}}_2$

How does hydroboration-oxidation differ from oxymercuration-demercuration in alcohol synthesis?

Hydroboration-oxidation and oxymercuration-demercuration are both methods to synthesize alcohols from alkenes, but they differ in regioselectivity and mechanism. Hydroboration-oxidation adds the hydroxyl group to the anti-Markovnikov position (least substituted carbon), while oxymercuration-demercuration adds it to the Markovnikov position (most substituted carbon). Hydroboration-oxidation involves two steps: the addition of borane (BH₃) or a boron source to the alkene, followed by oxidation with hydrogen peroxide (H₂O₂) and a base (usually NaOH). The overall reaction can be summarized as:

${R=R}_1+{\mathrm{BH}3}_2+{H2O2}_2\to {R-\mathrm{OH}}_1+{\mathrm{NaOH}}_2$

What is the role of sulfuric acid in acid-catalyzed hydration of alkenes?

In acid-catalyzed hydration of alkenes, sulfuric acid (H₂SO₄) acts as a catalyst to facilitate the addition of water (H₂O) across the double bond. The reaction proceeds via the formation of a carbocation intermediate, which follows Markovnikov's rule, adding the hydroxyl group to the more substituted carbon. The steps are as follows: protonation of the alkene to form a carbocation, nucleophilic attack by water, and deprotonation to yield the alcohol. The overall reaction can be summarized as:

${R=R}_1+{H2O}_2+{H2\mathrm{SO}4}_2\to {R-\mathrm{OH}}_1+{H2\mathrm{SO}4}_2$

How does the SN2 mechanism lead to the formation of alcohols from alkyl halides?

The SN2 (bimolecular nucleophilic substitution) mechanism involves a single-step reaction where a nucleophile attacks the electrophilic carbon of an alkyl halide from the opposite side, leading to the inversion of stereochemistry. In the context of alcohol synthesis, the nucleophile is typically hydroxide ion (OH⁻), which attacks the carbon bonded to the halogen (X). This results in the displacement of the halogen and formation of an alcohol. The reaction is most efficient with primary and secondary alkyl halides due to less steric hindrance. The overall reaction can be summarized as:

${R-X}_1+{\mathrm{NaOH}}_2\to {R-\mathrm{OH}}_1+{\mathrm{NaX}}_2$

What are the four primary methods to synthesize alcohols from alkenes?

The four primary methods to synthesize alcohols from alkenes are:

1. Oxymercuration-Demercuration: Adds a hydroxyl group to the Markovnikov position without carbocation rearrangement using Hg(OAc)₂, H₂O, and NaBH₄.

2. Hydroboration-Oxidation: Adds a hydroxyl group to the anti-Markovnikov position using BH₃ and H₂O₂ with NaOH.

3. Acid-Catalyzed Hydration: Adds a hydroxyl group to the Markovnikov position via a carbocation intermediate using H₂SO₄ and H₂O.

4. SN2 Reaction: Converts alkyl halides to alcohols with inversion of stereochemistry using NaOH.