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:
R3C-H + CH2O → R3C-CH2OH
R2N-H + CH2O → R2N-CH2OH
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:
5-Methylcytosine is a common epigenetic marker. The methyl group is modified by oxidation of the methyl group in a process called hydroxymethylation:[4]
RCH3 + O → RCH2OH
This oxidation is thought to be a prelude to removal, regenerating cytosine.
A common reaction of hydroxymethylated compounds is further reaction with a second equivalent of an active X-H bond:
hydroxymethylation: X-H + CH2O → X-CH2OH
crosslinking: X-H + X-CH2OH → X-CH2-X + H2O
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]
^Eric J. Leopold (1986). "Selective Hydroboration of a 1,3,7-Triene: Homogeraniol". Organic Syntheses. 64: 164. doi:10.15227/orgsyn.064.0164.
^Kohei Tamao; Neyoshi Ishida; Yoshihiko Ito; Makoto Kumada (1990). "Nucleophilic Hydroxymethylation by the (Isopropoxydimethylsilyl)Methyl Grignard Reagent: 1-(Hydroxymethyl)Cyclohexanol from Cyclohexanone". Organic Syntheses. 69: 96. doi:10.15227/orgsyn.069.0096.
^M. Caporali, L. Gonsalvi, F. Zanobini, M. Peruzzini (2011). Synthesis of the Water-Soluble Bidentate (P,N) Ligand PTN(Me). Inorganic Syntheses. Vol. 35. pp. 92–108. doi:10.1002/9780470651568.ch5.{{cite book}}: CS1 maint: multiple names: authors list (link)
^Gaudry, Michel; Jasor, Yves; Khac, Trung Bui (1979). "Regioselective Mannich Condensation with Dimethyl(Methylene)Ammonium Trifluoroacetate: 1-(Dimethylamino)-4-Methyl-3-Pentanone". Organic Syntheses. 59: 153. doi:10.15227/orgsyn.059.0153.
