In organic chemistry, phenols, sometimes called phenolics, are a class of chemical compounds consisting of one or more hydroxyl Functional group (−Oxygen Hydrogen) Chemical bond directly to an aromatic hydrocarbon group.
Phenols are both synthesized industrially and produced by plants and microorganisms.
Properties
Acidity
Phenols are more
than typical alcohols. The acidity of the hydroxyl group in phenols is commonly intermediate between that of
aliphatic alcohols and
(their pK
a is usually between 10 and 12). Deprotonation of a phenol forms a corresponding negative phenolate ion or phenoxide ion, and the corresponding salts are called phenolates or phenoxides (aryloxides, according to the IUPAC Gold Book).
Condensation with aldehydes and ketones
Phenols are susceptible to electrophilic aromatic substitutions. Condensation with
formaldehyde gives resinous materials, famously
Bakelite.
Another industrial-scale electrophilic aromatic substitution is the production of bisphenol A, which is produced by the condensation with acetone.
C-Alkylation with alkenes
Phenol is readily alkylated at the ortho positions using alkenes in the presence of a Lewis acid such as aluminium phenoxide:
- CH2=CR2 + C6H5OH → R2CHCH2-2-C6H4OH
More than 100,000 tons of
tert-butyl phenols are produced annually (year: 2000) in this way, using
isobutylene (CH
2=CMe
2) as the alkylating agent. Especially important is 2,6-ditert-butylphenol, a versatile
antioxidant.
Other reactions
Phenols undergo
esterification. Phenol esters are
, being prone to
hydrolysis. Phenols are reactive species toward
oxidation. Oxidative cleavage, for instance cleavage of 1,2-dihydroxybenzene to the monomethylester of 2,4-hexadienedioic acid with oxygen,
copper chloride in
pyridine.
[2,4-Hexadienedioic acid, monomethyl ester, (Z,Z)- Organic Syntheses, Coll. Vol. 8, p. 490 (1993); Vol. 66, p. 180 (1988) Article.] Oxidative de-aromatization to
also known as the
Teuber reaction. Oxidizing reagents are Fremy's salt
and
oxone.
In reaction depicted below 3,4,5-trimethylphenol reacts with
singlet oxygen generated from
oxone/
sodium carbonate in an
acetonitrile/water mixture to a para-peroxyquinole. This
hydroperoxide is reduced to the quinole with sodium thiosulfate.
Phenols are oxidized to
in the Elbs persulfate oxidation.
Reaction of naphtols and hydrazines and sodium bisulfite in the Bucherer carbazole synthesis.
Synthesis
Many phenols of commercial interest are prepared by elaboration of
phenol or
. They are typically produced by the alkylation of
benzene/
toluene with
propylene to form
cumene then is added with to form phenol (
Hock process). In addition to the reactions above, many other more specialized reactions produce phenols:
-
rearrangement of esters in the Fries rearrangement
-
rearrangement of N-phenylhydroxylamines in the Bamberger rearrangement
-
dealkylation of phenolic ethers
-
reduction of
-
replacement of an aromatic amine by an hydroxyl group with water and sodium bisulfide in the Bucherer reaction
-
thermal decomposition of aryl diazonium salts, the salts are converted to phenol
-
by the oxidation of aryl silanes—an aromatic variation of the Fleming-Tamao oxidation
-
catalytic synthesis from aryl bromides and iodides using nitrous oxide
Classification
There are various classification schemes.
[Wilfred Vermerris and Ralph Nicholson. Phenolic Compound Biochemistry Springer, 2008.] A commonly used scheme is based on the number of carbons and was devised by
Jeffrey Harborne and Simmonds in 1964 and published in 1980:
| the parent compound, used as a disinfectant and for chemical synthesis |
| and other bisphenols produced from ketones and phenol / cresol |
| (butylated hydroxytoluene) - a fat-soluble antioxidant and food additive |
| a breakdown product of detergents and nonoxynol-9 |
| a fungicide used for waxing |
| (trinitrophenol) - an explosive material |
| pH indicator |
| used in antiseptics & disinfectants |
Drugs and bioactive natural products
More than 371 drugs approved by the FDA between the years of 1951 and 2020 contain either a phenol or a phenolic ether (a phenol with an alkyl), with nearly every class of small molecule drugs being represented, and natural products making up a large portion of this list.| one of the 20 standard amino acids |
| dopamine prodrug used to treat Parkinson's disease |
| short-acting intravenous Anesthesia agent |
| blood-clotting agent that converts |
| Top-selling drug to treat thyroid hormone deficiency. |
| Top-selling antibiotic |
| the major female sex hormone |
Analysis
In chemical analysis, phenols can be detected using 2,6‑dibromoquinonechlorimide.
