Elimination Reactions of Alcohols

All About Elimination Reactions of Alcohols (With Acid)

• The hydroxyl group of alcohols is normally a poor leaving group.
• However, when treated with strong acid, R-OH is converted into R-OH₂(+) and H₂O is a much better leaving group.
• With tertiary alcohols, H₂O can then leave, resulting in a carbocation.
• If a strong acid such as H₂SO₄ or p-TsOH is used, the most likely result is elimination, since the conjugate bases of these acids (HSO₄ ^– and TsO^– ) are poor nucleophiles and unlikely to add to the carbocation.

Table of Contents

1. Hydrohalic Acids (HX) Plus Alcohols Give Substitution Products…
2. …But H₂SO₄, H3PO4, and TsOH Give Elimination Products!
3. Elimination of Tertiary Alcohols Proceeds Through an E1 Mechanism
4. Why Do H2SO4, H3PO4 and TsOH Give Elimination Products? 
5. What About Secondary Alcohols?
6. Elimination Reactions With Carbocation Rearrangements
7. Ring Expansion Followed By Elimination
8. Primary Alcohols and H2SO4 Can Form Alkenes (via E2)
9. Summary: Elimination Reactions of Alcohols
10. (Advanced) References and Further Reading

1. Hydrohalic acids (HX)  plus alcohols give substitution products…

Previously (See post: Making Alkyl Halides from Alcohols) we saw that treating an alcohol with a strong hydrohalic acid – think HCl, HBr, or HI – resulted in the formation of alkyl halides. With a tertiary alcohol like the one drawn below, this proceeds through an S_N1 mechanism. [Protonation of alcohol, then loss of H₂O to form a carbocation, then attack of nucleophile on carbocation].

2. …But H₂SO₄, H₃PO₄, and TsOH Give Elimination Products!

You’d be forgiven for thinking that if we treated an alcohol with H₂SO₄ (sulfuric acid) the same type of thing would occur, and the carbocation would be attacked by the (-)OSO₃H anion to make the product below. Very reasonable to propose. In practice, however, it doesn’t work that way!

So what happened here?

First, look at what bonds formed and broke. We formed C-C (π) and broke C-OH and C-H. (We also formed H-O , in that molecule of water that forms as a byproduct). This is the pattern of an elimination reaction.

Now let’s ask: How could this have formed? If you look closely, note that we’ve broken a C-H bond on the carbon adjacent to the carbocation and formed a new C-C π bond at that spot. It’s reasonable to propose that instead of attacking the carbocation to form a new substitution product, a  base removed a proton adjacent to the carbocation and formed the alkene. [That carbon adjacent to the carbocation is often referred to as the “β (beta) carbon”. The carbocation itself is the “α (alpha) carbon”].

3. Elimination of Tertiary Alcohols Proceeds Through an E1 Mechanism

We’ve seen this type of process before actually! This is an E1 process [elimination (E) , unimolecular (1) rate determining step]. You might also remember that elimination reactions tend to follow “Zaitsev’s rule” – we always form the most substituted alkene [or to put it another way, we remove a proton from the carbon with the fewest attached hydrogens] because alkene stability increases as we increase the number of attached carbons.

[By the way, you might ask – why “heat” ? Heat generally tends to favour elimination reactions.]

By no means is H₂SO₄ the only acid that does this. Phosphoric acid (H₃PO₄) as well as “tosic acid” (p-toluenesulfonic acid) also tend to form elimination products.

4. Why Does H₂SO₄ (Or H₃PO₄ or TsOH) Give Elimination Products But HCl, HBr, HI give Substitution Products?

So why do we get elimination reactions with H₂SO₄ as acid (or H₃PO₄, or TsOH) whereas we get substitution reactions with HCl, HBr, and HI?

The answer is that the HSO₄–  anion is a very poor nucleophile , being quite stabilized by resonance. In the diagram below, note how that negative charge is delocalized over three different oxygens [the same is true for the TsO^– and H₂PO₄^– anions].  

Compare that to halide anions, where the negative charge cannot be spread over more than one atom. The upshot is that delocalization of charge results in a slower reaction of HSO₄– as a nucleophile compared to deprotonation of C-H by a base, and the alkene product dominates.

So the bottom line here is that heating tertiary alcohols with these acids will result in loss of water [“dehydration”] and formation of an alkene [elimination].

5. What About Elimination Reactions Of Secondary Alcohols?

Heating a secondary alcohol with sulfuric acid or phosphoric acid? Same deal as with tertiary alcohols: expect an alkene to form. As with all elimination reactions, there are two things to watch out for: first, the “most substituted” alkene (Zaitsev) will be the dominant product, and also, don’t forget that trans alkenes will be favoured (more stable) than cis alkenes due to less steric strain.

There is one last thing to watch out for with secondary alcohols, though… like a bad nightmare, they keep coming back.

6. Elimination  Reactions With Carbocation Rearrangements

As we saw with the reactions of HCl, HBr, and HI with secondary alcohols, we have to watch out for carbocation rearrangement reactions. If a more stable carbocation can be formed through migration of an adjacent hydride (H- )  or an alkyl group, then that migration will occur.

For example, treatment of the alcohol below with H₂SO₄ leads to formation of a secondary carbocation, followed by a hydride shift to give a tertiary carbocation, followed by deprotonation at whichever β carbon leads to the most substituted alkene.

7. Ring Expansion Followed By Elimination

It’s also possible for alkyl shifts to occur to give a more stable carbocation. A classic example of this are expansions of strained rings (like cyclobutanes) to give less strained rings (like cyclopentanes).

For example in the case below the key step is where the C3-C4 bond breaks to form the C2-C4 bond, resulting in a new (tertiary) carbocation on C-3 as well as a less strained ring. Since there isn’t a good nucleophile around, elimination occurs in such a way that the most substituted alkene is formed.

8. Primary  Alcohols And H₂SO₄ Can Form Alkenes (E2)

The final class of alcohols to be concerned about is primary alcohols. You might ask: if we treat a primary alcohol (say, 1-butanol) with a strong acid like H₂SO₄, will also get elimination to an alkene?

Yes, alkenes can be formed this way (along with some formation of symmetrical ethers [see this previous post]). Here’s an example.

There is a catch however:  the E1 pathway (formation of a primary carbocation) is not the most likely pathway here. Primary carbocations tend to be extremely unstable, and it’s more likely that the reaction passes through an E2 mechanism where the transition state will be lower in energy. Notice what happens here: first we protonate the alcohol to give the good leaving group OH₂+ , and then a weak base (which I’m leaving vague, but could be H₂O, (-)OSO₃H, or another molecule of the alcohol) could then break C-H, leading to formation of the alkene.

9. Summary: Elimination Reactions of Alcohols (E1)

If you see a tertiary or secondary alcohol with H₂SO₄, TsOH, or H₃PO₄ (and especially if you see “heat”) think: carbocation formation followed by elimination reaction (E1).

And if you see that a more stable carbocation could be formed through migration of an adjacent H or alkyl group, expect that to happen.

If you see a primary alcohol with H₂SO₄, TsOH, or H₃PO₄, expect symmetrical ether formation accompanied by elimination to form the alkene.

Next Time…

So far we’ve learned two ways to convert alcohols to alkenes:

• convert them to a good leaving group, and then add base (2 steps)
• add strong acid with heat (one step)

Ideally, we’d like to just use one step. But strong acid can lead to complications (carbocation rearrangements, cough cough) and we might ask: “isn’t there an easier way”?
There is! That’s what we’ll cover in the next post.

Next Post: Elimination Of Alcohols To Alkenes With POCl₃

Notes

(Advanced) References and Further Reading

A variety of conditions are possible for this transformation (alcohol -> alkene), all of which involve converting the -OH into a better leaving group. The use of acid is the simplest method to achieve this, as protonation of -OH gives -OH₂⁺, an excellent leaving group (water).

Elimination with POCl₃:

1. The Effect of Structure on the Course of Phosphoryl Chloride-Pyridine Dehydration of Tertiary Alcohols
   Ronald R. Sauers
   Journal of the American Chemical Society 1959 81 (18), 4873-4876
   DOI: 1021/ja01527a028
2. Stereospecificity and regiospecificity of the phosphorus oxychloride dehydration of sterol side chain alcohols
   Jose Luis Giner, Christian Margot, and Carl Djerassi
   The Journal of Organic Chemistry 1989 54 (2), 369-373
   DOI: 1021/jo00263a020
   This article by the legendary chemist Carl Djerassi (who developed norethindrone, the first female contraceptive) describes the selectivity of POCl₃-pyridine dehydration conditions in steroid synthesis. It also has a general procedure for POCl₃-pyridine dehydration in the experimental section.
3. A general approach to linearly fused triquinane natural products. Total syntheses of (.+-.)-hirsutene, (.+-.)-coriolin, and (.+-.)-capnellene
   Goverdhan Mehta, A. Narayana. Murthy, D. Sivakumar. Reddy, and A. Veera. Reddy
   Journal of the American Chemical Society 1986 108 (12), 3443-3452
   DOI: 1021/ja00272a046
   This paper by Prof. Goverdhan Mehta (considered the ‘Indian E. J. Corey’) demonstrates the applicability of the POCl₃-pyridine dehydration in natural product total synthesis.
4. The 3-methylcholestanols and their derivatives
   D. H. R. Barton, A. da S. Campos-Neves and R. C. Cookson
   J. Chem. Soc., 1956, 3500-3506
   DOI: 10.1039/JR9560003500
   This paper by Nobel Laureate Prof. Derek H. R. Barton has a POCl3-pyridine dehydration (see p. 3504-3505 in the experimental section).Using a Brønsted acid:
5. THE COMPOSITION OF BUTENE MIXTURES RESULTING FROM THE CATALYTIC DECOMPOSITION OF THE NORMAL BUTYL ALCOHOLS
   William G. Young and Howard J. Lucas
   Journal of the American Chemical Society 1930, 52 (5), 1964-1970
   DOI: 1021/ja01368a030
   While this would seem to be an easy thing to study today, with NMR and GC-MS, in the early days this was not so easy. The butenes were converted to dibromides, distilled, and then the three-component dibromide mixture analyzed by density, refractive index, and determination of the second-order rate constants with potassium iodide in acetone. Both Bill Young and H. J. Lucas contributed greatly to the development of chemistry in Southern California – H. J. Lucas was a professor of chemistry at Caltech, and Bill Young later became a professor of chemistry at UCLA, and was the advisor for Prof. Saul Winstein’s M.S. in chemistry (Prof. Winstein ended up joining Bill Young at UCLA after his PhD!).
6. The Dehydration of Secondary and Tertiary Alcohols
   Albert L. Henne and Alfred H. Matuszak
   Journal of the American Chemical Society 1944, 66 (10), 1649-1652
   DOI: 1021/ja01238a012
   An early paper that demonstrates the E1 nature of this reaction, by demonstrating that dehydration of various secondary and tertiary alcohols give products obtained through rearrangement.
7. Tracer studies on alcohols. Part II. The exchange of oxygen-18 between sec.-butyl alcohol and water
   C. A. Bunton and D. R. Llewellyn
   J. Chem. Soc., 1957, 3402-3407
   DOI: 10.1039/JR9570003402
   This paper provides experimental evidence that stronger acids favor elimination over substitution. As the Hammett acidity (-H₀) of the medium increases, carbocation formation is increasingly favorable, which promotes elimination over substitution. Sulfuric acid and perchloric acid are much stronger acids than the hydrogen acids (HCl, HBr, HI), which explains why sulfuric acid is commonly used to make olefins from alcohols.
8. Reactions of n-butene and butan-2-ol in dilute acid. The elucidation of the mechanism and the intermediate in elimination from secondary alcohols and in the hydration of olefins
   Joost Manassen and Fritz S. Klein
   J. Chem. Soc., 1960, 4203-4213
   DOI: 10.1039/JR9600004203
   The authors use radiolabeling to study both the forward and reverse reactions (hydration of alkene and elimination of alcohol), to prove that they both go through a common carbocation intermediate.
9. The mechanism of the acid-catalyzed dehydration of 1,2-diphenylethanol
   Donald S. Noyce, Donald R. Hartter, and Ralph M. Pollack
   Journal of the American Chemical Society 1968, 90 (14), 3791-3794
   DOI: 1021/ja01016a034
   Interestingly, in the reaction of 1,2-diphenylethanol in acid, formation of the intermediate carbocation is fast and reversible, and proton loss to the olefin is rate-determining.
10. The effect of substituents on the rate of the acid-catalyzed dehydration of 1,2-diarylethanols
    Donald S. Noyce, Donald R. Hartter, and Frank B. Miles
    Journal of the American Chemical Society 1968, 90 (14), 3794-3796
    DOI: 1021/ja01016a035
    In this reaction, the effect of substitution on the phenyl ring a to the -OH is greater than that of substitution on the other ring.
11. Catalytic, Tunable, One-Step Bismuth(III) Triflate Reaction with Alcohols: Dehydration Versus Dimerization
    Laura E. Kolsi, Jari Yli-Kauhaluoma, and Vânia M. Moreira
    ACS Omega 2018, 3 (8), 8836-8842
    DOI: 1021/acsomega.8b01401
    A modern variant of this reaction using Lewis Acids. The authors also show that these conditions can be used for forming dimers vs. simple elimination products. The dimer is formed by the carbocation reacting with the alkene.