Alcohols, Epoxides and Ethers
Alcohols To Ethers via Acid Catalysis
Last updated: February 1st, 2023 |
How To Make Ethers With Alcohols And Acid
- Symmetrical ethers can be made from the acid-catalyzed dehydration of primary alcohols.
- A classic example is the heating of ethanol at 130-140 °C to give diethyl ether.
- The reaction proceeds through protonation of a hydroxyl group to give the conjugate acid followed by an SN2 reaction to give the symmetrical ether.
- The process works best for making symmetrical ethers of primary alcohols.
Table of Contents
- Synthesis of Symmetrical Ethers Via Acid-Catalyzed Dehydration of Alcohols
- The Mechanism: Acid-Catalyzed Dehydration of Alcohols
- Summary: Symmetrical Ether Synthesis via Alcohol Dehydration
- (Advanced) References and Further Reading
1. Synthesis Of Symmetrical Ethers Via Acid-Catalyzed Dehydration of Alcohols
Last post I got a little ahead of myself. I was all excited about getting into the reactions of ethers, and forgot that there’s one last method for ether synthesis that we haven’t covered. It’s actually not that general so you can likely skip ahead. But for the sake of completeness, here it is.
Remember when we said that alcohols often need a “kick in the pants” in order to participate in reactions? That is, we either add acid to protonate them (forming their conjugate acid, which has a better leaving group) or add base to deprotonate them (forming their conjugate base, which is a better nucleophile).
Today’s post is a perfect example. Here’s the summary.
Here’s the deal. If we take a simple alcohol – ethanol is a perfect example – and heat it in the presence of strong acid, an ether can form.
How does this work?
2. Mechanism: Synthesis Of Symmetrical Ethers via Acid-Catalyzed Dehydration of Alcohols
There are three key steps.
First of all, one equivalent of alcohol is protonated to its conjugate acid – which has the good leaving group, OH2 (water, a weak base). (Remember that the conjugate acid is a better leaving group – see What Makes a Good Leaving Group).
Next, another equivalent of the alcohol can now perform nucleophilic attack at carbon (SN2), leading to displacement of OH2 (water) and formation of a new C-O bond. This is an SN2 reaction. (See The SN2 Mechanism)
The final step is deprotonation of the product by another equivalent of solvent (or other weak base), resulting in our ether product.
Here’s a drawing of the mechanism:
3. Summary: Formation of Symmetrical Ethers From Alcohols
So how important is this process, really?
Industrially, it’s very important process for the synthesis of diethyl ether, which is a commodity chemical and useful solvent for organic chemistry. Ethanol is cheap. Sulfuric acid is cheap. Heat, distill, and Bob’s your uncle. Over 10 million tons of the stuff is made annually via this process.
Practically – and I say this to you, undergraduate student of chemistry – from a synthetic perspective –it’s not a very general synthesis of ethers.
First of all, it’s limited to symmetrical ethers. If we try to make unsymmetrical ethers using this process, we will end up with mixtures that will need to be separated, giving us low yields of each individual component.
Secondly, the temperature has to be carefully optimized, because there are lots of side reactions possible. For example the optimal temperature for the formation of diethyl ether is about 130-140 degrees C. Once the temperature gets to 150 degrees and above, elimination starts to compete, leading to the formation of ethylene gas.
[And this is for primary alcohols, which don’t form carbocations very easily. Once you get into the category of using this process for secondary and tertiary alcohols, carbocations are much easier to form and elimination becomes an even more significant destructive pathway.]
You should know what the correct answer for the quesion below. And be able to draw the mechanism. That’s it.
Beyond that, unless you’re Sigma-Aldrich and are planning to make several metric tons of an ether, you can comfortably omit this method of ether synthesis from your synthetic toolbox. The Williamson ether synthesis will do the job just as well, and can also be used to make unsymmetrical ethers to boot.
Okay . Finally, next post we get to write all about the different reactions of ethers. We’ve learned five (5) – count ’em – ways of making ethers, and now that we’re armed with all this knowledge, we’ll go out and talk about all the different things we can do!
Next Post – Cleavage Of Ethers With Acid
Note 1. This synthesis of ethers is so practically straightforward that it lends itself to “How-To” videos. Don’t do this unless you know what you’re doing – ether is extremely flammable.
(Advanced) References and Further Reading
- Catalysts for forming Diethyl Ether
Inventors: Cheng Zhang, Victor J. Johnson
Assignee: Celanese International Corp.
Publication Date: 18, 2014
Pub. No.: US 20140275636A1
This describes an industrial process for diethyl ether synthesis, which is done using a heterogeneous catalyst.
- Single stage synthesis of diisopropyl ether – an alternative octane enhancer for lead-free petrol
Frank P. Heese, Mark E. Dry, Klaus P. Möller
Catalysis Today 1999, 49 (1-3), 327-335
This paper shows that the mechanism for formation of symmetrical ethers from secondary alcohols (e.g. isopropanol) is more complex, as bimolecular dehydration can compete with other pathways (e.g. SN1 or elimination-addition). Diisopropyl ether is sometimes used as a solvent but requires even more care with handling and storage compared to other ethers, as it is even more prone to formation of explosive peroxides.
- Process for Preparing Diisopropyl Ether
Inventor: Hanbury John Woods
Assignee: Gulf Oil Canada Limited
Publication Date: 16, 1977
Pub. No.: US 4,042,633
A patent on an industrial process for preparing diisopropyl ether from isopropanol. This is also done with a heterogeneous catalyst (Montmorillonite clay in this case).
- Reactions of phenols and alcohols over thoria: Mechanism of ether formation
Karuppannasamy, K. Narayanan, C. N. Pillai
J. Catalysis 1980, 66 (2), 281-289
Under forcing conditions, phenol can dehydrate to diphenyl ether, but this proceeds through an unusual mechanism.
24 thoughts on “Alcohols To Ethers via Acid Catalysis”
Would an Sn2 mechanism be possible if we heated a secondary alcohol?
Possible, yes, it wouldn’t be a very clean reaction due to competition with other pathways. One would obtain a lot of elimination and rearrangement through E1 pathways.
Why wouldn’t the second alcohol’s oxygen attack the protonated oxygen? That oxygen has a full positive charge, and the carbon atom only has a partial positive charge.
It has a full “formal charge”, but formal charge is not always a helpful gauge of electron density. Compare the electronegativities of O and H, and that will tell you where the electron density is. See this post: Watch Out, Formal Charge Can Mislead: https://www.masterorganicchemistry.com/2012/02/22/common-mistakes-formal-charges-can-mislead/
Instead of alkyl halides what else can be used ? Thank you.
? This post doesn’t address alkyl halides. It addresses formation of ethers from alcohols. Can you be more specific?
An alcohol like water is a bad nucleophile, so why does SN2 occur? Is it the high temperature or because water is an exceptionally good leaving group?
The reaction here is one where there are very few possible side reactions. A single reactant, and the electrophile only differs from the nucleophile in being its conjugate acid. A primary electrophile, with no chance of ionizing to a carbocation, no chance of rearrangement, and the only side-product is elimination. So it’s kind of a special case.
What would be the result if 3° alcohol or some hindered alcohol is taken as substrate?would it follow sn2 mechanism or go for sn1
For a tertiary alcohol? SN1.
If I want to prepare a symmetric ether from solid primary alcohol, what is the best solvent can be used and Can I use H2SO4 as catalyst at 140C
Is DMF suitable or DMSO as solvent, or they well decompose?
I actually suggest you don’t use this method, unless you are trying to make diethyl ether on industrial scale. Use anything else. You can thank me later.
if you heated an alcohol with conc H2SO4 wouldnt you form an alkene? what changes are made to ensure its an ether that is formed
I mentioned that the temperature has to be carefully optimized to avoid side reactions. In the case of diethyl ether formation, this temperature is 140 degrees C. It is likely very different for other alcohols.
if you heated an alcohol with conc acid wouldn’t you get an alkene instead?
Yes, it can happen, but the rate will depend on the structure of the alcohol.
How would you know the ratio of products for this reaction when two different alcohols are mixed?
You wouldn’t be able to know it without actually getting your hands dirty and doing the experiment.
umm…Why does this follow Sn2 mechanism?
Shouldnt it follow Sn1 mechanism as the nucleophile is neutral?
does the fact that it is primary trump everything else?
Formation of a primary carbocation is unlikely, and attack on a primary carbon via SN2 is relatively favorable.
Why this reaction isn’t feasible for unsymmetrical ethers?
The problem is that you get mixtures. If you tried to mix methanol and ethanol in acid, hoping for methyl ethyl ether, you’d also end up with dimethyl ether and diethyl ether. Not very efficient.
Perhaps a dumb question : What is the Wilkinson ether synthesis? Is this another name for the williamson ether synthesis?
Oh dear. There’s a Wilkinson’s catalyst but no Wilkinson’s ether synthesis. It should have been Williamson. Fixed. Thanks Kaina!