Acidic cleavage of ethers (SN2)
Description: When ethers are treated with strong acid in the presence of a nucleophile, they can be cleaved to give alcohols and alkyl halides. If the ether is on a primary carbon this may occur through an SN2 pathway.
Notes: Common acids for this purpose are HI and other hydrogen halides, as well as H2SO4 in the presence of H2O.
In the case where the ether being cleaved is secondary and has a stereocenter, there will be inversion of configuration.
Notes: The third example could also be written “H3O+” . Note that excess HI will convert primary alcohols to alkyl halides via SN2, but not phenol (C6H5OH) since sp2 hybridized carbons do not undergo SN1 or SN2 reactions.
Mechanism: Strong acid (HI) protonates the ether oxygen, which turns it into a better leaving group (Step 1, arrows A and B). Next, the iodide ion attacks the carbon in an SN2 reaction (Step 2, arrows C and D) to give the alcohol and methyl iodide.
Notes: In cases where the ether being cleaved is secondary and has a stereocenter, there will be inversion of configuration.
Another example: Opening of tetrahydrofuran (THF) with aqueous acid:
(Advanced) References and Further Reading
Ethers are widely inert to a lot of conditions, and thus find common use as solvents (e.g. diethyl ether, THF (tetrahydrofuran), dioxane, glyme, and others). Ether cleavage generally requires strong acid and heat, which are forcing conditions. Alternatively, silane reagents can be used, which are reactive at room temperature.
- A NEW METHOD FOR THE PREPARATION OF ORGANIC IODIDES
HERMAN STONE and HAROLD SHECHTER
The Journal of Organic Chemistry 1950, 15 (3), 491-495
Instead of using HI, which is expensive (and an inconvenient gas, to boot), one can use the combination of phosphoric acid + KI for ether cleavage, which generates HI in situ.
Herman Stone and Harold Shechter
Org. Synth. 1950, 30, 33
This procedure from Organic Syntheses, a reliable source of independently tested synthetic organic laboratory procedures, demonstrates the cleavage of THF with refluxing strong acid.Below are a variety of papers using silane-based reagents for ether cleavage. The Nobel Laureate late Prof. George Olah did a lot of work in this area in the middle of his career.
- Cleavage of Esters and Ethers with Iodotrimethylsilane
Tse‐Lok Ho Prof. Dr. George A. Olah
Angew. Chem. Int. Ed. 1976, 15 (12), 774-775
- Mild cleavage of methoxymethyl (MOM) ethers with trimethylsilyl bromide
Stephen Hanessian, Daniel Delorme, Yves Dufresne
Lett. 1984, 25 (24), 2515-2518
MOM ethers are commonly used as protecting groups for -OH in organic synthesis, and so strategies for selective deprotection of MOM ethers under mild cleavage are invaluable.
Org. Synth. 1943, 23, 67
DOI Link: 10.15227/orgsyn.023.0067
Org. Synth. 1950, 30, 33
DOI Link: 10.15227/orgsyn.030.0033
Org. Synth. 1951, 31, 31
DOI Link: 10.15227/orgsyn.031.0031
Org. Synth. 1969, 49, 50
DOI Link: 10.15227/orgsyn.049.0050