Alcohols To Ethers via Acid Catalysis

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

1. Synthesis of Symmetrical Ethers Via Acid-Catalyzed Dehydration of Alcohols
2. The Mechanism: Acid-Catalyzed Dehydration of Alcohols
3. Summary: Symmetrical Ether Synthesis via Alcohol Dehydration
4. Notes
5. (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 (S_N2), leading to displacement of OH₂ (water) and formation of a new C-O bond.  This is an S_N2 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.

Click to Flip

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

Notes

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

1. 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.
2. 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
   DOI: 10.1016/S0920-5861(98)00440-4
   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. S_N1 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.
3. 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).
4. Reactions of phenols and alcohols over thoria: Mechanism of ether formation
   Karuppannasamy, K. Narayanan, C. N. Pillai
   J. Catalysis 1980, 66 (2), 281-289
   DOI: 10.1016/0021-9517(80)90032-9
   Under forcing conditions, phenol can dehydrate to diphenyl ether, but this proceeds through an unusual mechanism.