Alcohols, Epoxides and Ethers
By James Ashenhurst
How To Make Alcohols More Reactive
Last updated: March 26th, 2019
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.
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 SN1 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.
Do you notice something that both of these reactants [carbocations and “3 membered ring” intermediates] have in common? They’re both extremely reactive.
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.
As for hydroxyl groups as leaving groups, forget it. We’ve seen that in order for a leaving group to leave in SN2 and E2 reactions, it has to be a fairly weak base. The hydroxy (HO-) and alkoxy (RO – groups are both fairly strong bases, and therefore poor leaving groups.
The bottom line here is that hydroxyl groups 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.
Adjusting The “Personality” of Alcohols
Think about those two concepts we’ve explored previously. Leaving group ability and nucleophilicity.
Hydroxyl groups (HO-) are poor leaving groups because they’re strong bases. BUT if we protonate them (add acid), then we get an oxonium ion (R-OH2+). The leaving group is now water – a weak base and a great leaving group. The oxonium ion is much better set up to participate in reactions such as the SN1 and E1, as well as (more rarely) the SN2 and E2.
Hydroxyl groups 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 (SN2) than neutral alcohols, and because they are far more basic than neutral alcohols, more reactive in the E2 reaction as well.
The bottom line
So the bottom line for this post is that converting an alcohol into its conjugate acid makes it a better leaving group (setting up SN1 and E1 reactions, mostly) while converting an alcohol into its conjugate base makes it a better nucleophile (setting up the SN2) 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
PS Rare but it apparently does happen. NSFW (especially if you are a panda) link to a happy couple at the Washington Zoo