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Phase II Reactions: Methylation Reactions

Phase II Reactions: Methylation Reactions

Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...

Aldehydes and Ketones with HCN: Cyanohydrin Formation Overview

Aldehydes and Ketones with HCN: Cyanohydrin Formation Overview

Cyanohydrins are compounds that contain –CN and –OH groups on the same carbon atom. They are formed by the nucleophilic addition of the cyanide ions to the carbonyl group. Cyanide ions are highly basic and nucleophilic and can be generated from HCN under aqueous conditions. However, since HCN is a weak acid, the number of cyanide ions generated is very small. Hence, a small amount of base or KCN/NaCN is added to HCN to increase the concentration of the cyanide ions in the reaction...

Carboxylic Acids to Methylesters: Alkylation using Diazomethane

Carboxylic Acids to Methylesters: Alkylation using Diazomethane

Carboxylic acids react with diazomethane in an ether solvent via alkylation at the carboxylate oxygen atom to give methyl esters of the corresponding acid with excellent yields.

Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction

Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction

α-Substituted ketones or aldehydes can be synthesized from enamines by the Stork enamine reaction, named after its pioneer Gilbert Stork. Enamines are useful synthetic intermediates where the lone pair on nitrogen is in conjugation with the C=C bond. They resemble enolate ions, as the resonance forms of both species have a nucleophilic α carbon.

Preparation of Alkynes: Alkylation Reaction

Preparation of Alkynes: Alkylation Reaction

Introduction
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.

Aldehydes and Ketones with HCN: Cyanohydrin Formation Mechanism

Aldehydes and Ketones with HCN: Cyanohydrin Formation Mechanism

Cyanohydrins are formed when cyanide nucleophiles and carbonyl compounds like aldehydes and ketones react. A strong base, the cyanide ion, catalyzes cyanohydrin formation. The ions are generated from HCN under aqueous conditions. Once the cyanide ions are generated, the first step involves the nucleophilic attack of the cyanide ions on the electrophilic carbonyl carbon. This attack shifts the π electrons from the C=O to the oxygen atom forming the alkoxide ion intermediate. The alkoxide anion...

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Related Experiment Video

Updated: Nov 14, 2025

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues

Published on: November 22, 2014

Installing the "magic methyl"- C-H methylation in synthesis.

Daniya Aynetdinova¹, Mia C Callens, Harry B Hicks

¹Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford, OX1 3TA, UK. j.leitch@ucl.ac.uk darren.dixon@chem.ox.ac.uk.

Chemical Society Reviews

|March 10, 2021

Summary

Selective C-H methylation enables efficient synthesis of complex molecules. This powerful transformation installs a "Magic Methyl" group, crucial for altering drug properties in discovery and development programs.

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Methodology for Accurate Detection of Mitochondrial DNA Methylation

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Last Updated: Nov 14, 2025

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues

Published on: November 22, 2014

Enhanced Reduced Representation Bisulfite Sequencing for Assessment of DNA Methylation at Base Pair Resolution

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Methodology for Accurate Detection of Mitochondrial DNA Methylation

Methodology for Accurate Detection of Mitochondrial DNA Methylation

Published on: May 20, 2018

Area of Science:

Organic Chemistry
Synthetic Chemistry
Medicinal Chemistry

Background:

Selective C-H methylation is a key synthetic transformation.
The
Magic Methyl
group can significantly alter physicochemical properties of lead compounds.
This is highly desirable in drug discovery and synthesis.

Purpose of the Study:

To review diverse techniques for selective C-H methylation.
To cover methods for installing the C-Me bond across various chemical structures.

Main Methods:

Review of literature on C-H methylation techniques.
Categorization of methods based on substrate type (sp2 and sp3 carbons).

Main Results:

Diverse techniques exist for selective C-H methylation of sp2 and sp3 carbons.
These methods are applicable to a wide range of structures, from simple building blocks to complex drug-like molecules.

Conclusions:

C-H methylation is a powerful and versatile synthetic tool.
Its application is crucial for modern drug discovery and synthesis programs aiming to optimize lead compounds.