Hydroxymethylation

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.

Tetrakis(hydroxymethyl)phosphonium chloride ([P(CH2OH)4]Cl) is produced in this way from phosphine (PH3).

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).

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.