Editing Formaldehyde (section)

==Organic chemistry==
Formaldehyde is a building block in the synthesis of many other compounds of specialised and industrial significance. It exhibits most of the chemical properties of other aldehydes but is more reactive.<ref>{{Cite book |last1=Cheng |first1=Chan |title=Formaldehyde: Chemistry, Applications and Role in Polymerization (Pollution Science, Technology and Abatement) |last2=Lu |first2=Feng |year=2012 |language=English}}</ref>

===Polymerization and hydration===
Monomeric CH<sub>2</sub>O is a gas and is rarely encountered in the laboratory.  Aqueous formaldehyde, unlike some other small aldehydes (which need specific conditions to oligomerize through [[aldol condensation]]) oligomerizes spontaneously at a common state. The trimer 1,3,5-trioxane, {{chem2|(CH2O)3}}, is a typical oligomer. Many cyclic [[oligomer]]s of other sizes have been isolated. Similarly, formaldehyde hydrates to give the geminal diol [[methanediol]], which condenses further to form hydroxy-terminated oligomers HO(CH<sub>2</sub>O)<sub>''n''</sub>H. The polymer is called [[paraformaldehyde]]. The higher concentration of formaldehyde—the more equilibrium shifts towards polymerization. Diluting with water or increasing the solution temperature, as well as adding alcohols (such as methanol or ethanol) lowers that tendency.

Gaseous formaldehyde polymerizes at active sites on vessel walls, but the mechanism of the reaction is unknown.<ref>{{Cite journal |last1=Boyles |first1=James G. |last2=Toby |first2=Sidney |date=June 1966 |title=The mechanism of the polymerization of gaseous formaldehyde |url=https://onlinelibrary.wiley.com/doi/10.1002/pol.1966.110040608 |journal=Journal of Polymer Science Part B: Polymer Letters |volume=4 |issue=6 |pages=411–415 |doi=10.1002/pol.1966.110040608 |bibcode=1966JPoSL...4..411B |access-date=2023-04-20 |archive-date=2023-04-20 |archive-url=https://web.archive.org/web/20230420083849/https://onlinelibrary.wiley.com/doi/10.1002/pol.1966.110040608 |url-status=live|url-access=subscription }}</ref> Small amounts of [[hydrogen chloride]], [[boron trifluoride]], or [[stannic chloride]] present in gaseous formaldehyde provide the catalytic effect and make the polymerization rapid.<ref>{{Cite journal |date=1951-03-07 |title=The catalyzed polymerization of gaseous formaldehyde |url=https://royalsocietypublishing.org/doi/10.1098/rspa.1951.0046 |journal=Proceedings of the Royal Society of London. Series A. Mathematical and Physical Sciences |language=en |volume=205 |issue=1083 |pages=516–529 |doi=10.1098/rspa.1951.0046 |bibcode=1951RSPSA.205..516B |issn=0080-4630 |last1=Bevington |first1=J. C. |last2=Norrish |first2=R. G. W. |s2cid=95395629 |access-date=2023-04-20 |archive-date=2019-10-25 |archive-url=https://web.archive.org/web/20191025013353/https://royalsocietypublishing.org/doi/10.1098/rspa.1951.0046 |url-status=live|url-access=subscription }}</ref>

===[[Cross-link]]ing reactions===
Formaldehyde forms cross-links by first combining with a protein to form [[methylol]], which loses a water molecule to form a [[Schiff base]].<ref name="pmid26354429">{{cite journal | vauthors = Hoffman EA, Frey BL, Smith LM, Auble DT | title = Formaldehyde crosslinking: a tool for the study of chromatin complexes | journal = [[Journal of Biological Chemistry]] | volume = 290 | issue = 44 | pages = 26404–26411 | date = 2015 | pmid = 26354429 | pmc = 4646298  | doi = 10.1074/jbc.R115.651679 | doi-access = free }}</ref> The Schiff base can then react with DNA or protein to create a cross-linked product.<ref name="pmid26354429" /> This reaction is the basis for the most common process of [[Fixation (histology)#Chemical fixation|chemical fixation]].

===Oxidation and reduction===
Formaldehyde is readily [[oxidation|oxidized]] by atmospheric oxygen into [[formic acid]]. For this reason, commercial formaldehyde is typically contaminated with formic acid. Formaldehyde can be hydrogenated into [[methanol]].

In the [[Cannizzaro reaction]], formaldehyde and [[base (chemistry)|base]] react to produce [[formic acid]] and methanol, a [[disproportionation reaction]].

===Hydroxymethylation and chloromethylation===
Formaldehyde reacts with many compounds, resulting in [[hydroxymethylation]]:
:X-H + CH<sub>2</sub>O → X-CH<sub>2</sub>OH{{nbsp|5}}(X = R<sub>2</sub>N, RC(O)NR', SH).

The resulting hydroxymethyl derivatives typically react further. Thus, amines give [[hexahydro-1,3,5-triazine]]s:
:3{{nbsp}}RNH<sub>2</sub> + 3{{nbsp}}CH<sub>2</sub>O → (RNCH<sub>2</sub>)<sub>3</sub> + 3{{nbsp}}H<sub>2</sub>O

Similarly, when combined with [[hydrogen sulfide]], it forms [[trithiane]]:<ref>{{OrgSynth|last1=Bost|first1=R. W.|last2=Constable|first2=E. W.|title=''sym''-Trithiane|prep=cv2p0610|volume=16|pages=81|year=1936|collvol=2|collvolpages=610}}</ref>
:3{{nbsp}}CH<sub>2</sub>O + 3{{nbsp}}H<sub>2</sub>S → (CH<sub>2</sub>S)<sub>3</sub> + 3{{nbsp}}H<sub>2</sub>O

In the presence of acids, it participates in [[electrophilic aromatic substitution]] reactions with [[aromatic compound]]s resulting in hydroxymethylated derivatives:
:ArH + CH<sub>2</sub>O → ArCH<sub>2</sub>OH
When conducted in the presence of hydrogen chloride, the product is the chloromethyl compound, as described in the [[Blanc chloromethylation]]. If the arene is electron-rich, as in phenols, elaborate condensations ensue. With 4-substituted phenols one obtains [[calixarenes]].<ref>{{OrgSynth|authorlink1=C. David Gutsche|last1=Gutsche|first1=C. D.|last2=Iqbal|first2=M.|title=''p-tert''-Butylcalix&#91;4&#93;arene|prep=cv8p0075|year=1993|collvol=8|collvolpages=75}}</ref> Phenol results in polymers.

===Other reactions===
Many amino acids react with formaldehyde.<ref name= Kamps>{{cite journal |doi=10.1038/s42004-019-0224-2 |title=How formaldehyde reacts with amino acids |date=2019 |last1=Kamps |first1=Jos J. A. G. |last2=Hopkinson |first2=Richard J. |last3=Schofield |first3=Christopher J. |last4=Claridge |first4=Timothy D. W. |journal=Communications Chemistry |volume=2 |issue=1 |page=126 |s2cid=207913561 |doi-access=free|bibcode=2019CmChe...2..126K }}</ref> Cysteine converts to [[thioproline]].