Demethylation is the chemical process resulting in the removal of a methyl group (CH3) from a molecule. A common way of demethylation is the replacement of a methyl group by a hydrogen atom, resulting in a net loss of one carbon and two hydrogen atoms.
- R2N-CH3 + O → R2N-H + CH2O
In organic chemistry
In organic chemistry, demethylation typically refers to the cleavage of ethers, especially aryl ethers, which are pervasive in lignin-derived compounds. The reaction typically requires harsh conditions or harsh reagents. For example, the methyl ether in vanillin can be removed by heating near 250 °C with strong base. Stronger nucleophiles such as diorganophosphides (LiPPh2) also cleave aryl ethers under milder conditions.
Boron tribromide is a classical reagent for the dealkylation of methyl arylethers. The mechanism of ether dealkylation proceeds via the formation of a complex between the boron center and the ether oxygen followed by the elimination of an alkyl bromide to yield a dibromo(organo)borane. The dibromo(organo)borane can then undergo hydrolysis to give the alcohol or phenol, boric acid, and hydrogen bromide as products.
- ROR + BBr3 → RO+(-BBr3)R
- RO+(-BBr3)R → ROBBr2 + RBr
- ROBBr2 + 3 H2O → ROH + B(OH)3 + 2 HBr
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- Irwin A. Pearl (1949), "Protocatechulic Acid", Org. Synth. 29: 85; Coll. Vol. 3: 745
- Robert E. Ireland and David M. Walba (1977), "Demethylation of Methyl Aryl Ethers: 4-Ethoxy-3-hydroxybenzaldehyde", Org. Synth. 56: 44; Coll. Vol. 3: 745
- J. F. W. McOmie, D. E. West (1969), "3,3'-Dihydroxybiphenyl", Org. Synth. 49: 13; Coll. Vol. 5: 412