Hydroxymethylation is a chemical reaction that installs the CH2OH group. The transformation can be implemented in many ways and applies to both industrial and biochemical processes.
A common method for hydroxymethylation involves the reaction of formaldehyde with active C-H and N-H bonds:
A typical active C-H bond is provided by a terminal acetylene [1] or the alpha protons of an aldehyde. [2] In industry, hydroxymethylation of acetaldehyde with formaldehyde is used in the production of pentaerythritol:
P-H bonds are also prone to reaction with formaldehyde. Tetrakis(hydroxymethyl)phosphonium chloride ([P(CH2OH)4]Cl) is produced in this way from phosphine (PH3). [3]
5-Methylcytosine is a common epigenetic marker. The methyl group is modified by oxidation of the methyl group in a process called hydroxymethylation: [4]
This oxidation is thought to be a prelude to removal, regenerating cytosine.
A two-step hydroxymethylation of aldehydes involves methylenation followed by hydroboration-oxidation: [5]
Silylmethyl Grignard reagents are nucleophilic reagents for hydroxymethylation of ketones: [6]
A common reaction of hydroxymethylated compounds is further reaction with a second equivalent of an active X-H bond:
This pattern is illustrated by the use of formaldehyde in the production various polymers and resins from phenol-formaldehyde condensations ( Bakelite, Novolak, and calixarenes). Similar crosslinking occurs in urea-formaldehyde resins.
The hydroxymethylation of N-H and P-H bonds can often be reversed by base. This reaction is illustrated by the preparation of tris(hydroxymethyl)phosphine: [7]
When conducted in the presence of chlorinating agents, hydroxymethylation leads to chloromethylation as illustrated by the Blanc chloromethylation.
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cite book}}
: CS1 maint: multiple names: authors list (
link)
Hydroxymethylation is a chemical reaction that installs the CH2OH group. The transformation can be implemented in many ways and applies to both industrial and biochemical processes.
A common method for hydroxymethylation involves the reaction of formaldehyde with active C-H and N-H bonds:
A typical active C-H bond is provided by a terminal acetylene [1] or the alpha protons of an aldehyde. [2] In industry, hydroxymethylation of acetaldehyde with formaldehyde is used in the production of pentaerythritol:
P-H bonds are also prone to reaction with formaldehyde. Tetrakis(hydroxymethyl)phosphonium chloride ([P(CH2OH)4]Cl) is produced in this way from phosphine (PH3). [3]
5-Methylcytosine is a common epigenetic marker. The methyl group is modified by oxidation of the methyl group in a process called hydroxymethylation: [4]
This oxidation is thought to be a prelude to removal, regenerating cytosine.
A two-step hydroxymethylation of aldehydes involves methylenation followed by hydroboration-oxidation: [5]
Silylmethyl Grignard reagents are nucleophilic reagents for hydroxymethylation of ketones: [6]
A common reaction of hydroxymethylated compounds is further reaction with a second equivalent of an active X-H bond:
This pattern is illustrated by the use of formaldehyde in the production various polymers and resins from phenol-formaldehyde condensations ( Bakelite, Novolak, and calixarenes). Similar crosslinking occurs in urea-formaldehyde resins.
The hydroxymethylation of N-H and P-H bonds can often be reversed by base. This reaction is illustrated by the preparation of tris(hydroxymethyl)phosphine: [7]
When conducted in the presence of chlorinating agents, hydroxymethylation leads to chloromethylation as illustrated by the Blanc chloromethylation.
{{
cite book}}
: CS1 maint: multiple names: authors list (
link)