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Hydroxymethylation is a
P-H bonds are also prone to reaction with formaldehyde.
chemical reaction
A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...
that installs the CH2OH group. The transformation can be implemented in many ways and applies to both industrial and biochemical processes.
Hydroxymethylation with formaldehyde
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 or the alpha protons of an aldehyde. In industry, hydroxymethylation of acetaldehyde with formaldehyde is used in the production ofpentaerythritol
Pentaerythritol is an organic compound with the formula C(CH2OH)4. Classified as a polyol, it is a white solid. Pentaerythritol is a building block for the synthesis and production of explosives, plastics, paints, appliances, cosmetics, and many o ...
:
P-H bonds are also prone to reaction with formaldehyde. Tetrakis(hydroxymethyl)phosphonium chloride
Tetrakis(hydroxymethyl)phosphonium chloride (THPC) is an organophosphorus compound with the chemical formula (CH2OH)4l. The cation P(CH2OH)4+ is four-coordinate, as is typical for phosphonium salts. THPC has applications as a precursor to fire-re ...
( (CH2OH)4l) is produced in this way from phosphine (PH3).
Hydroxymethylation in demethylation
5-Methylcytosine is a common epigenetic marker. The methyl group is modified by oxidation of the methyl group in a process called hydroxymethylation: :RCH3 + O → RCH2OH This oxidation is thought to be a prelude to removal, regenerating cytosine.Representative reactions
A two-step hydroxymethylation of aldehydes involvesmethylenation
In organic chemistry, methylenation is a chemical reaction that inserts a methylene () group into a chemical compound:
:\ce + \longrightarrow \ce\ce
Typically, the reaction is used to prepare terminal alkenes from aldehydes and, less frequentl ...
followed by hydroboration-oxidation:
:RCHO + Ph3P=CH2 → RCH=CH2 + Ph3PO
:RCH=CH2 + R2BH → RCH2-CH2BR2
:RCH2-CH2BR2 + H2O2 → RCH2-CH2OH + "HOBR2"
Silylmethyl Grignard reagents
A Grignard reagent or Grignard compound is a chemical compound with the general formula , where X is a halogen and R is an organic group, normally an alkyl or aryl. Two typical examples are methylmagnesium chloride and phenylmagnesium bromide . ...
are nucleophilic reagents for hydroxymethylation of ketones:
:R2C=O + ClMgCH2SiR'3 → R2C(OMgCl)CH2SiR'3
:R2C(OMgCl)CH2SiR'3 + H2O + H2O2 → R2C(OH)CH2OH + "HOSiR'3"
Reactions of hydroxymethylated compounds
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
Polyoxybenzylmethylenglycolanhydride, better known as Bakelite ( ), is a thermosetting phenol formaldehyde resin, formed from a condensation reaction of phenol with formaldehyde. The first plastic made from synthetic components, it was developed ...
, Novolak
Novolaks (sometimes: novolacs) are low molecular weight polymers derived from phenols and formaldehyde. They are related to Bakelite, which is more highly crosslinked. The term comes from Swedish "lack" for lacquer and Latin "novo" for new, sin ...
, and calixarene
A calixarene is a macrocycle or cyclic oligomer based on a methylene-linked phenols. With hydrophobic cavities that can hold smaller molecules or ions, calixarenes belong to the class of cavitands known in host–guest chemistry.
Nomenclature
Cal ...
s). Similar crosslinking occurs in urea-formaldehyde
Urea-formaldehyde (UF), also known as urea-methanal, so named for its common synthesis pathway and overall structure, is a nontransparent thermosetting resin or polymer. It is produced from urea and formaldehyde. These resins are used in adhesiv ...
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:
: (CH2OH)4l + NaOH → P(CH2OH)3 + H2O + H2C=O + NaCl
When conducted in the presence of chlorinating agents, hydroxymethylation leads to chloromethylation as illustrated by thee Blanc chloromethylation
The Blanc chloromethylation (also called the Blanc reaction) is the chemical reaction of aromatic rings with formaldehyde and hydrogen chloride to form chloromethyl arenes. The reaction is catalyzed by Lewis acids such as zinc chloride. The rea ...
.
Related
*Hydroxyethylation involves the installation of the CH2CH2OH group, as practiced inethoxylation
Ethoxylation is a chemical reaction in which ethylene oxide adds to a substrate. It is the most widely practiced alkoxylation, which involves the addition of epoxides to substrates.
In the usual application, alcohols and phenols are converted in ...
.
*Aminomethylation is often effected with Eschenmoser's salt, CH3)2NCH2Tf{{cite journal , doi=10.15227/orgsyn.059.0153, title=Regioselective Mannich Condensation with Dimethyl(Methylene)Ammonium Trifluoroacetate: 1-(Dimethylamino)-4-Methyl-3-Pentanone, journal=Organic Syntheses, year=1979, volume=59, page=153, first1=Michel, last1=Gaudry, first2=Yves, last2=Jasor, first3=Trung Bui, last3=Khac
References