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Demethylation
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.
The counterpart of demethylation is methylation.
Demethylation is relevant to epigenetics. Demethylation of DNA is catalyzed by demethylases. These enzymes oxidize N-methyl groups, which occur in histones, in lysine derivatives, and in some forms of DNA.
One family of such oxidative enzymes is the cytochrome P450. Alpha-ketoglutarate-dependent hydroxylases are also active for demethylation of DNA, operating by a similar stoichiometry. These reactions, which proceed via hydroxylation, exploit the slightly weakened C-H bonds of methylamines and methyl ethers.
Demethylation of some sterols are steps in the biosynthesis of testosterone and cholesterol. Methyl groups are lost as formate.
Methoxy groups heavily decorate the biopolymer lignin. Much interest has been shown in converting this abundant form of biomass into useful chemicals (aside from fuel). One step in such processing is demethylation. The demethylation of vanillin, a derivative of lignin, requires 250 °C (482 °F) and strong base. Pulp and paper industry digests lignin using aqueous sodium sulfide, which partially depolymerizes the lignin. Delignification is accompanied by extensive O-demethylation, yielding methanethiol, which is emitted by paper mills as an air pollutant.
Demethylation often refers to cleavage of ethers, especially aryl ethers.
Historically, aryl methyl ethers, including natural products such as codeine (O-methylmorphine), have been demethylated by heating the substance in molten pyridine hydrochloride (melting point 144 °C (291 °F)) at 180 to 220 °C (356 to 428 °F), sometimes with excess hydrogen chloride, in a process known as the Zeisel–Prey ether cleavage. Quantitative analysis for aromatic methyl ethers can be performed by argentometric determination of the N-methylpyridinium chloride formed. The mechanism of this reaction starts with proton transfer from pyridinium ion to the aryl methyl ether, a highly unfavorable step (K < 10−11) that accounts for the harsh conditions required, given the much weaker acidity of pyridinium (pKa = 5.2) compared to the protonated aryl methyl ether (an arylmethyloxonium ion, pKa = –6.7 for aryl = Ph). This is followed by SN2 attack of the arylmethyloxonium ion at the methyl group by either pyridine or chloride ion (depending on the substrate) to give the free phenol and, ultimately, N-methylpyridinium chloride, either directly or by subsequent methyl transfer from methyl chloride to pyridine.
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Demethylation AI simulator
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Demethylation
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.
The counterpart of demethylation is methylation.
Demethylation is relevant to epigenetics. Demethylation of DNA is catalyzed by demethylases. These enzymes oxidize N-methyl groups, which occur in histones, in lysine derivatives, and in some forms of DNA.
One family of such oxidative enzymes is the cytochrome P450. Alpha-ketoglutarate-dependent hydroxylases are also active for demethylation of DNA, operating by a similar stoichiometry. These reactions, which proceed via hydroxylation, exploit the slightly weakened C-H bonds of methylamines and methyl ethers.
Demethylation of some sterols are steps in the biosynthesis of testosterone and cholesterol. Methyl groups are lost as formate.
Methoxy groups heavily decorate the biopolymer lignin. Much interest has been shown in converting this abundant form of biomass into useful chemicals (aside from fuel). One step in such processing is demethylation. The demethylation of vanillin, a derivative of lignin, requires 250 °C (482 °F) and strong base. Pulp and paper industry digests lignin using aqueous sodium sulfide, which partially depolymerizes the lignin. Delignification is accompanied by extensive O-demethylation, yielding methanethiol, which is emitted by paper mills as an air pollutant.
Demethylation often refers to cleavage of ethers, especially aryl ethers.
Historically, aryl methyl ethers, including natural products such as codeine (O-methylmorphine), have been demethylated by heating the substance in molten pyridine hydrochloride (melting point 144 °C (291 °F)) at 180 to 220 °C (356 to 428 °F), sometimes with excess hydrogen chloride, in a process known as the Zeisel–Prey ether cleavage. Quantitative analysis for aromatic methyl ethers can be performed by argentometric determination of the N-methylpyridinium chloride formed. The mechanism of this reaction starts with proton transfer from pyridinium ion to the aryl methyl ether, a highly unfavorable step (K < 10−11) that accounts for the harsh conditions required, given the much weaker acidity of pyridinium (pKa = 5.2) compared to the protonated aryl methyl ether (an arylmethyloxonium ion, pKa = –6.7 for aryl = Ph). This is followed by SN2 attack of the arylmethyloxonium ion at the methyl group by either pyridine or chloride ion (depending on the substrate) to give the free phenol and, ultimately, N-methylpyridinium chloride, either directly or by subsequent methyl transfer from methyl chloride to pyridine.