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CHAPTER-11
Phenols
The word phenol is also used to refer to any compound which contains a sixmembered aromatic ring, bonded directly to a hydroxyl group (-OH). In effect,
phenols are a class of organic compounds of which the phenol discussed in this
article is the simplest member.
Production Phenol can be made from the partial oxidation of benzene or
benzoic acid, by the cumene process, or by the Raschig process.
Reactions of phenols
Phenols react in a wide variety of ways.

Esterfication reactions and ether formation

Electrophilic aromatic substitutions as the hydroxyl group is activating, for
example synthesis of calixarenes [3]

Reaction of naphtols and hydrazines and sodium bisulfite in the Bucherer
carbazole synthesis

Oxidative cleavage, for instance cleavage of 1,2-dihydroxybenzene to the
monomethylester of 2,4 hexadienedioic acid with oxygen, copper chloride
in pyridine [4]

Oxidative de-aromatization to quinones also known as the Teuber
reaction. Oxidizing reagents are Fremy's salt [5] and oxone [6]. In reaction
depicted below 3,4,5-trimethylphenol reacts with singlet oxygen generated
from oxone/sodium carbonate in an acetonitrile/water mixture to a paraperoxyquinole. This hydroperoxide is reduced to the quinole with sodium
thiosulfate.

Phenols are oxidized to phediols in the Elbs persulfate oxidation
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
Phenolate anions (deriving from phenols by the loss of H+) can act as
ligands towards metal cations
Properties
1. Phenol has a limited solubility in water (8.3 g/100 ml).
2. It is slightly acidic: the phenol molecule has weak tendencies to lose the
H+ ion from the hydroxyl group, resulting in the highly water-soluble
phenolate anion C6H5O−, also called phenoxide anion.
3. Compared to aliphatic alcohols, phenol shows much higher acidity; it even
reacts with aqueous NaOH to lose H+, whereas many long chain aliphatic
alcohols do not. However, many carboxylic acids are more acidic than
phenol.
4. One explanation for the increased acidity over alcohols is resonance
stabilization of the phenoxide anion by the aromatic ring. In this way, the
negative charge on oxygen is shared by the ortho and para carbon atoms.
5. In another explanation, increased acidity is the result of orbital overlap
between the oxygen's lone pairs and the aromatic system.
Uses
Phenol has antiseptic properties, and was used by Sir Joseph Lister (1827–1912)
in his pioneering technique of antiseptic surgery, though the skin irritation caused
by continual exposure to phenol eventually led to the substitution of aseptic
(germ-free) techniques in surgery. Lister decided that the wounds themselves
had to be thoroughly cleaned. He then covered the wounds with a piece of rag or
lint covered in carbolic acid. It is also the active ingredient in some oral
analgesics such as Chloraseptic spray. Phenol was also the main ingredient of
the Carbolic Smoke Ball, a device marketed in London in the 19th century as
protecting the user against influenza and other ailments.
It is also used in the production of drugs (it is the starting material in the industrial
production of aspirin), herbicides, and synthetic resins (Bakelite, one of the first
synthetic resins to be manufactured, is a polymer of phenol with formaldehyde).
Phenol is the preferred chemical in use of embalming bodies for anatomical use
and study because of its ability to preserve tissues for extended periods of time.
However, formaldehyde is usually preferred over phenol for embalming with
intent of public viewing because of phenol's tendency to turn tissues an
unpleasant bleach-white color.
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Phenol is also used in the preparation of cosmetics including sunscreens,[11] hair
dyes, and skin lightening preparations. Compounds containing phenol moieties
can be used to prevent ultraviolet light-induced damage to hair and skin due to
the UV-absorbing properties of the aromatic ring of the phenol.
It is also used in cosmetic surgery as an exfoliant, to remove layers of dead skin.
It is also used in phenolization, a surgical procedure used to treat an ingrown
nail, in which it is applied to the nail bed to prevent regrowth of nails. 5% Phenol
is sometimes injected near a sensory nerve in order to temporarily (up to a year)
stop it from transmitting impulses in some intractable cases of chronic
neuropathic pain.
Toxicity
Phenol and its vapor are corrosive to the eyes, the skin and the respiratory
tract.[14] Repeated or prolonged skin contact with phenol may cause dermatitis, or
even second and third-degree burns due to phenol's caustic and defatting
properties.[15] Inhalation of phenol vapor may cause lung edema. The substance
may cause harmful effects on the central nervous system and heart, resulting in
dysrhythmia, seizures, and coma. The kidneys may be affected as well.
Exposure may result in death and the effects may be delayed. Long-term or
repeated exposure of the substance may have harmful effects on the liver and
kidneys. The substance is a suspected carcinogen. Besides its hydrophobic
effects, another mechanism for the toxicity of phenol may be the formation of
phenoxyl radicals.
Chemical burns from skin exposures can be decontaminated by washing with
polyethylene glycol, isopropyl alcohol, or perhaps even copious amounts of
water.[21] Removal of contaminated clothing is required, as well as immediate
hospital treatment for large splashes. This is particularly important if the phenol is
mixed with chloroform (a commonly-used mixture in molecular biology for DNA &
RNA purification from proteins).
Biosynthesis of Phenolics
Phenolic compounds are aromatic structures bearing one or more
hydroxyl groups. Most are polyphenols, having several hydroxyl group
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substituents, one or more of which may be substituted by methyl or glycosyl
groups. Phenolics share a common biosynthetic origin from phenylalanine (Fig.
3.9), one of the three protein amino acids formed from sedoheptulose via the
shikimate pathway.
Different Phenolic classes and their relationship
PHENOLIC COMPOUNDS
Consist of a large number of molecules of heterogeneous structure. Their
common feature is the presence of at least one hydroxyl-substituted aromatic
ring system.
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Most phenolic compounds belong to the flavonoids. Lignin, the primary
substance of wood, is the most common member of this group. The following
table outlines the most important groups of plant phenolic compounds.
The starting product of the biosynthesis of most phenolic compounds is
shikimate. Phenols are acidic due to the dissociability of their -OH group. They
are rather reactive compounds and as long as no steric inhibition due to
additional side chains occurs, they form hydrogen bonds. Consequently, many
flavonoids have intramolecular bonds. Another important feature is their ability to
form chelate complexes with metals. Also, they are easily oxidized and, if so,
form polymers (dark aggregates). The darkening of cut or dying plant parts is
caused by this reaction. They have usually an inhibiting effect on plant growth.
Among the phenylpropanol derivatives of lower molecular weight are a number of
scents like the coumarins, cinnamic acid, sinapinic acid, the coniferyl alcohols
and others. These substances and their derivatives are at the same time
intermediates of the biosynthesis of lignin.
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The Most Important Classes of Phenolic Compounds in Plants
number of Cbasic skeleton
atoms
class
6
C6
simple phenols, benzoquinones
7
C6 - C1
phenolic acids
8
C6 - C2
acetophenone, phenylacetic acid
9
C6 - C3
hydroxycinnamic acid, polypropene,
coumarin, isocoumarin
10
C6 - C4
naphtoquinone
13
C6 - C1 - C6
xanthone
14
C6 - C2 - C6
stilbene, anthrachinone
15
C6 - C3 - C6
flavonoids, isoflavonoids
18
(C6 - C3)2
lignans, neolignans
30
(C6 - C3 - C6)2
biflavonoids
n
(C6 - C3)n
(C6)n
(C6 - C3 - C6)n
lignins
catecholmelanine
(condensed tannins)
The Ecological Meaning of Some Phenolic Compounds for Plants
function
group
example(s) and plant species
where the effect was studied
flower
pigments
anthocyanes
chalcons
aurones
yellow flavonoids
flavones
cyanidin-3,5-diglucosid in Rosa
coreopsin in Coreopsis tinstoria
aureusin in Anthirrhinum majus
gossypetine-7-glucoside in Gossypium
apigenin-7-glucoside in Bellis perennis
fruit
pigments
anthocyanines
isoflavones
chalcons
petunidin glucoside in Atropa belladonna
osajin in Maclura pomifera
ocanin in Kyllingi brevifolia
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allelopathic
substances
quinones
phenols
phenolcarboxylic
acids
hydrocinnamic acid
juglon in Juglans regia
hydroquinone in Arctostaphylos
sialic acid in Quercus falcata
ferulic acid in Adenostoma
protection
against pests
quinones
tannines
flavonols
juglon in Carya ovata
gallotannine in Quercus robur
quercitine-glycosids in Gossypium
fungicide
isoflavones
phenolcarboxylic
acids
dihydrochalones
luteon in Lupinus
protocatechunic acid in Allium
phloridcine in Malus pumila
phytoalexines
stilbens
phenylanthrenes
isoflavanes
pterocarpanes
phenylpropanoids
fucocoumarins
reservatrol in Arachis hypogaea
orchinol in Orchis militaris
vestitiol in Lotus corniculatus
pisatin in Pisum sativum
coniferyl alcohol in Linum usitiltissimum
psoralen in Petroselinum crispum
Phenolics in Plants
Phenolic acids are plant metabolites widely spread throughout the plant kingdom.
Recent interest in phenolic acids stems from their potential protective role,
through ingestion of fruits and vegetables, against oxidative damage diseases
(coronary heart disease, stroke, and cancers). Phenolic compounds are essential
for the growth and reproduction of plants, and are produced as a response for
defending injured plants against pathogens. The importance of antioxidant
activities of phenolic compounds and their possible usage in processed foods as
a natural antioxidant have reached a new high in recent years.
Phenolic acid compounds seem to be universally distributed in plants. They have
been the subject of a great number of chemical, biological, agricultural, and
medical studies. Phenolic acids form a diverse group that includes the widely
distributed
hydroxybenzoic
and
hydroxycinnamic
acids.
Hydroxycinnamic acid compounds occur most frequently as simple esters with
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hydroxy
carboxylic
acids
or
glucose
Hydroxybenzoic acid compounds are present mainly in the form of glucosides.
Content
of
Phenolic compounds in
Tea,
Coffee,
Berries
and
Fruits:
The content of total phenolic acids range from 0 (pear cider) to 103 mg/100 g
fresh weight (rowanberry). Besides rowanberry, the best phenolic acid sources
among berries are chokeberry (96 mg/100 g), blueberry (85 mg/100 g), sweet
rowanberry (75 mg/100 g), and saskatoon berry (59 mg/100 g). Among fruits, the
highest contents (28 mg/100 g) ared in dark plum, cherry, and one apple variety
(Valkea Kuulas). Coffee (97 mg/100 g) as well as green and black teas (30-36
mg/100 g) are the best sources among beverages. Caffeic acid dominates in all
of these samples except in tea brews.
Phenolic acids and cholesterol
Drinking a cup of coffee induces an increase in the resistance of
LDL cholesterol to oxidative changes, probably as a result of the
incorporation of phenolic acids found in coffee into LDL
cholesterol.
Chemistry of Phenolics
Plant phenolic compounds are diverse in structure but are characterised by
hydroxylated aromatic rings (e.g. flavan-3-ols). They are categorised as
secondary metabolites, and their function in plants is often poorly understood.
Many plant phenolic compounds are polymerised into larger molecules such as
the
proanthocyanidins
(PA;
condensed
tannins)
and
lignins.
Furthermore, phenolic acids may occur in food plants as esters or glycosides
conjugated with other natural compounds such as flavonoids, alcohols,
hydroxyfatty acids, sterols, and glucosides.
Phenols
Phenols, sometimes called phenolics, are a class of chemical compounds
consisting of a hydroxyl functional group (-OH) attached to an aromatic
hydrocarbon group. The simplest of the class is phenol (C6H5OH). Some
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phenols are germicidal and are used in formulating disinfectants. Others possess
estrogenic
or
endocrine
disrupting
activity.
Phenolic compounds
Phenol, the parent compound, used as an disinfectant and for chemical
synthesis.
Polyphenols like the flavonoids and tannins.
Capsaicin, the pungent compound of chilli peppers.
Tyrosine, an amino acid.
The neurotransmitters serotonin, dopamine, adrenaline, and noradrenaline.
L-DOPA, a drug to treat Parkinson's disease.
Eugenol, the main constituent of the essential oil of clove.
Chavibetol from betel.
Salicylic acid is a phenolic compound
Gallic acid, found in gallnuts.
Ellagic acid
Thymol (2-Isopropyl-5-methyl phenol), an antiseptic that is used in mouthwashes.
BHT (butylated hydroxytoluene), a fat-soluble antioxidant and food additive.
... and many more.
Natural Substances with Phenolic acids:
Propolis is one of the few natural remedies that has maintained its popularity over
a long period of time. The pharmacologically active molecules in the propolis are
flavonoids and phenolic acids and their esters. These components have multiple
effects on bacteria, fungi and viruses. In addition, propolis and its components
have anti-inflammatory and immunomodulatory activities. Moreover, propolis has
been shown to lower blood pressure and cholesterol levels. However, clinical
studies to substantiate these claims are required.
Coffee is particularly rich in bound phenolic acids, such as
caffeic acid, ferulic acid, and p-coumaric acid.
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Purple corn maize
Quince has phenolic acids
Aloe ferox has phenolic acids
Phenolic Acids in Berries
The composition of phenolic acids in several small berries grown in Northeastern
Poland, namely, low-bush blueberries, black mulberries, European juneberries,
black currants, fruits of blue-berried honeysuckle, and blackberries. The total
content of phenolic acids ranged from 2845 (black mulberries) to 5418 (blueberried honeysuckle). Twenty phenolic acids were identified in the berries. Of
these, hydroxycaffeic, m- and p-coumaric, and 3,4-dimethoxycinnamic acids
were the major phenolic acids in blackberries and blueberries, m-coumaric acid
was the major phenolic acid in blue-berried honeysuckle and black currant fruits,
while salicylic, caffeic, and m- and p-coumaric acids were the predominant
phenolic acids in European juneberries. Syringic and veratric acids were
detected only in blueberries, while p-hydroxybenzoic and sinapic acids were
present only in black currants and o-coumaric acid was present in blueberries
and black mulberries.
Phenolics in Spices
Spices are known to significantly contribute to the flavor, taste,
and medicinal properties of food because of phenolics. Most
spices contain phenolic acids such as tannic, gallic, caffeic,
cinnamic, chlorogenic, ferulic and vanillic acids. A high amount
of tannic and gallic acids are found in black mustard and clove.
Caffeic, chlorogenic and ferulic acids are found in a good
amount in cumin. Vanillic and cinnamic acids are found in onion
seeds.
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Other Phenolic compounds
Cannabinoids, the active constituents of Cannabis.
Cresols from coal tar and creosote.
Guaiacol (2-methoxyphenol) from roasted coffee, whisky, and smoke that
has a smoky flavor.
Salicylic acid, a plant hormone and analgesic, antipyretic, and antiinflammatory drug, precursor compound to Aspirin. Aspirin (acetylsalicylic
acid) is still the most commonly used salicylate. After oral administration as an
aqueous solution aspirin is rapidly absorbed at the low pH of the stomach millieu.
Less rapid absorption is observed with other formulations due to the rate limiting
step of tablet disintegration - this latter factor being maximal in alkaline pH. The
rate of aspirin absorption is dependent not only on the formulation but also on the
rate of gastric emptying. Aspirin absorption follows first-order kinetics with an
absorption half-life ranging from 5 to 16 minutes. Hydrolysis of aspirin to salicylic
acid by nonspecific esterases occurs in the liver and, to a lesser extent, the
stomach so that only 68% of the dose reaches the systemic circulation as aspirin.
Both aspirin and salicylic acid are bound to serum albumin (aspirin being capable
of irreversibly acetylating many proteins), and both are distributed in the synovial
cavity, central nervous system, and saliva. The serum half-life of aspirin is
approximately 20 minutes. The fall in aspirin concentration is associated with a
rapid rise in salicylic acid concentration. Salicylic acid is renally excreted in part
unchanged and the rate of elimination is influenced by urinary pH, the presence
of organic acids, and the urinary flow rate. Metabolism of salicylic acid occurs
through glucuronide formation (to produce salicyluric acid), and salicyl phenolic
glucoronide), conjugation with glycine (to produce salicyluric acid), and oxidation
to gentisic acid.
Orthophenyl phenol , a fungicide used for waxing citrus fruits.
The pH indicators phenolphthalein, phenol red, bromothymol blue,
thymolphthalein, and bromophenol blue.
Psilocin, a hallucinogenic alkaloid of Psilocybe mushrooms.
Phenolic Compounds in Herbs
There are countless herbs that have phenolic compounds, here is one example:
Phenolic components and antioxidant activity of Fernblock, an aqueous extract of
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the aerial parts of the fern Polypodium leucotomos.
Methods Find Exp Clin Pharmacol. 2006 Apr;28(3):157-60. Industrial
Farmaceutica Cantabria, Arequipa 1, Madrid, Spain
Fernblock, an aqueous extract of the aerial parts of the fern Polypodium
leucotomos is used as raw material for topical and oral photoprotective
formulations. Phenolic compounds were identified as 3,4-dihydroxybenzoic acid,
4-hydroxybenzoic acid, vanillic acid, caffeic acid, 4-hydroxycinnamic acid, 4hydroxycinnamoyl-quinic acid, ferulic acid, and five chlorogenic acid isomers.
QUESTION/answer
Ecological Meaning of Some Phenolic Compounds for Plants
flower pigments :- anthocyanes, chalcons, aurones, yellow flavonoids
flavones fruit pigments:- anthocyanines,isoflavones,chalcons
fungicide isoflavones:- phenolcarboxylic acids,dihydrochalones
Coffee is particularly rich in bound phenolic acids, such as caffeic acid,
ferulic acid, and p-coumaric acid.
Polyphenols like the flavonoids and tannins.
Capsaicin, the pungent compound of chilli peppers.
L-DOPA, a drug to treat Parkinson's disease.
Eugenol, the main constituent of the essential oil of clove.
Gallic acid, found in gallnuts.
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