Alcohols Can Act As Acids Or Bases (And Why It Matters)

Alcohols: The Conjugate Acid Is A Better Leaving Group, and The Conjugate Base Is A Better Nucleophile

In the last post we explored some of the properties and nomenclature of alcohols. We said that alcohols tend to have high boiling points due to hydrogen bonding, and that  we commonly divide alcohols into the categories  “primary”, “secondary”,  and “tertiary” (with a nod to the unique, “methanol”) according to how many carbons are attached to the C bearing the hydroxyl group.

Now that we’ve dipped our toe in the a little bit, we’re going to start looking at the key reactions of alcohols. We’re going to begin in this post by discussing acid base reactions of alcohols. As we’ll see, these reactions really “set up” a lot of the reactions we’ll later see in this section.

Table of Contents

1. Reviewing Two Earlier Reactions of Alcohols
2. Neutral Alcohols Only Tend To Undergo Reactions With Very Reactive Electrophiles
3. The Conjugate Acid of An Alcohol Is A Better Electrophile
4. The Conjugate Base of An Alcohol Is A Better Nucleophile
5. Summary: Making Alcohols More Reactive
6. Notes

1. Reviewing Two Earlier Reactions Of Alcohols: Addition To Carbocations And To Halonium Ions

Before going there, however, let’s just review the reactions of alcohols we’ve already seen that aren’t explicitly acid base reactions. There are really only two. 

• First, we’ve seen that alcohols will react with carbocations to give ethers. The carbocation can either come from protonation of an alkene (path 1) or from “ionization” (that is, loss of a good leaving group) of an alkyl halide or similar starting material. This latter reaction falls into the category of S_N1 reactions.

• Secondly, we’ve also seen that reactive, positively charged, 3-membered ring intermediates such as halonium ions and mercurinium ions can also be attacked by alcohols at the most substituted carbon  (“Markovnikov” addition) to give “halo ethers” (for halonium ions) and ethers ( if we use Hg(OAc)₂ and then add  NaBH₄). Note that alcohol is the solvent here.

2. Neutral Alcohols Only Tend To Undergo Reactions With Extremely Reactive Electrophiles

Do you notice something that both of these reactants [carbocations and “3 membered ring” intermediates] have in common? They’re both extremely reactive electrophiles.

Getting alcohols to act as nucleophiles is a little like trying to get pandas to mate in a zoo. It only happens if the female (electrophile) is incredibly horny. That’s not too often, apparently. Note 1. 

As for hydroxyl groups as leaving groups, forget it. We’ve seen that in order for a leaving group to leave in S_N2 and E2 reactions, it has to be a fairly weak base. (See post: What Makes A Good Leaving Group). The hydroxy (HO-)  and alkoxy (RO -) groups are both fairly strong bases, and therefore poor leaving groups.

The bottom line here is that the hydroxyl groups of R–OH are not particularly reactive nucleophiles or electrophiles, as themselves.

But, like frustrated zookeepers must have wondered at some point: can’t we find some kind of aphrodisiac that can speed up the process?

While I am currently unaware of progress on the panda aphrodisiac front, I can tell you that it is actually quite straightforward to make alcohols more reactive.

Think about  two concepts we’ve explored previously. Leaving group ability and nucleophilicity. 

3. The Conjugate Acid Of An Alcohol Has A Better Leaving Group (and is therefore a better electrophile)

Hydroxyl groups (HO-)  are poor leaving groups because they’re strong bases.

However, if we protonate them (add acid), then we get an oxonium ion (R-OH₂+). The leaving group is now H₂O – a weak base and a great leaving group. The oxonium ion is much better set up to participate in reactions such as the S_N1 and E1, as well as (more rarely) the S_N2 and E2.

So a simple reaction with an acid converts a relatively boring alcohol R–OH into a species with a much better leaving group, R–OH₂(+).

Since a protonated alcohol has a better leaving group, this also makes it a much better electrophile as well.

The conjugate acid is a better leaving group!

4. The Conjugate Base Of An Alcohol Is A Better Nucleophile

Hydroxyl groups in R–OH are poor nucleophiles because they’re neutral and the electron pair is held tightly to the oxygen.

However, if we remove a proton (by adding a base) we then get an alkoxide ion (RO-)  which has much higher electron density, and is a much better nucleophile (as well as being a strong base). Alkoxide ions are far more reactive in substitution reactions (S_N2) than neutral alcohols, and because they are far more basic than neutral alcohols, more reactive in the E2 reaction as well.

So simple treatment with base converts a relatively boring alcohol into the excellent nucleophile (and strong base) RO(–).

The conjugate base is a better nucleophile!

5. Summary: Making Alcohols More Reactive

Adding or removing a proton can have a drastic effect on the reactivity of an alcohol.

Here’s a summary image:

So the bottom line for this post is that converting an alcohol into its conjugate acid makes it a better leaving group (setting up S_N1 and E1 reactions, mostly) while converting an alcohol into its conjugate base makes it a better nucleophile (setting up the S_N2) and a better base (setting up the E2).

This is old news – “the conjugate acid is always a better leaving group”, and “the conjugate base is always a better nucleophile” – but worth drawing attention to again, because we’ll see these patterns again and again in reactions of alcohols.

In the next post, we’re going to go into these acid-base reactions of alcohols in slightly more detail, and use what we learn to figure out the limits of how we can apply these concepts to substitution and elimination reactions.

Next Post: Alcohols (3) – Acidity And Basicity

Notes

Note 1.  Rare but it apparently does happen. NSFW (especially if you are a panda) link to a happy couple at the Washington Zoo