1a UNITII Phenols

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UNIT-II: Phenols: Acidity of phenols, effect of substituents on acidity,

qualitative tests, Structure and uses of phenol, cresols, resorcinol, naphthols
Dr. Sumanta Mondal _ Lectur...
Presentation · June 2018

DOI: 10.13140/RG.2.2.24895.41120
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UNIT- II: Phenols: Acidity of phenols, effect of substituents on acidity, qualitative tests, Structure and
uses of phenol, cresols, resorcinol, naphthols
PHENOL
 Introduction
- Phenols are molecules that have a hydroxyl group attached to the carbon atom of an aromatic ring.
- In phenol, hydroxy functional group is directly attached to the sp2 hybridized carbon atom of the benzene ring.
The interaction of six unhybridized 2pz orbitals of carbon atoms of the benzene ring leads to the formation of
delocalized pi-electron clouds.
- The C-O-H bond angle in phenol is 1090. The carbon-oxygen bond length (136pm)
- In phenol carbon-oxygen bond length is slightly less than that in methanol (142 pm). This is due to partial double
bond character on account of the conjugation of unshared electron pair of oxygen with the aromatic ring.
- Similarly, In ethers, the four electron pairs, ie; the two bond pairs and two lone pairs of electrons around oxygen
are arranged approximately in a tetrahedral arrangement. The C-O-C bond angle (111.70 in methoxy methane) is
slightly greater than the tetrahedral angle (109028) due to the repulsive C-O bond length (141 pm) in ethers is
almost the same as in alcohols (142 pm in methanol).
Preferred IUPAC name Phenol

Systematic IUPAC name Benzenol
Other names Carbolic acid; Phenylic acid; Hydroxybenzene; Phenic acid
Chemical formula C6H6O
Molar mass 94.11 g·mol−1
Appearance Transparent crystalline solid
Odor Sweet and tarry
Density 1.07 g/cm3
Melting point 40.5 °C
Boiling point 181.7 °C
Solubility in water 8.3 g/100 mL (20 °C)
Note by: If the pKa value is increased what happens to the acidic strength and basic strength?
Answer: If the pKa value increased, the value of Ka decreased by the formula pKa= - logKa. And if Ka value is decreased, the
number of H+ ions in the solution will also be decreased as Ka is directly proportional to [H+] so acidity will decrease. So, if the
Pka value is increased, acidic strength decreases and vice versa for basic strength.
Dr. Sumanta Mondal _ Lecture Notes _Pharmaceutical Organic Chemistry-II (BP 301T)_B.Pharm-III Sem Page | 1
GITAM (Deemed to be University) E-mail: logonchemistry@gmail.com
 Acidity of Phenols
- Compare to alcohols, phenols are stronger acid as the pKa value for phenol is 10 while for alcohols it’s close to
16. Because of acidic nature, phenols can turn blue litmus red and react with aqueous alkali to form phenate. Both
reactions are not shown by alcohols. Compare to carboxylic acids, phenols are weaker acid.
- Hence hydroxy group bonded to benzene ring is much more acidic than hydroxy group to alcohol. This is because
of the resonance in phenol. Because of the resonance in phenol, the oxygen atom acquires a positive charge which
weakens the oxygen-hydrogen bond and facilitates the release of a proton.
- The deprotonation of phenol forms phenoxide ion or phenate which also exists as a resonance.
- Hence both phenol and phenoxide ion are stabilized by resonance. Compare to phenol, phenoxide ion is more
stable as the negative charge gets delocalized over benzene ring. But the resonating structure of phenol involves the
separation of negative and positive charges. Therefore phenol has greater tendency to form phenate by releasing
the proton. The deprotonation of alcohol forms alkoxide ion which is not stable due to negative inductive effect of
alkyl group and alcohols become less acidic than phenol.
- In Ethoxide, the resonance is not possible and The + I effect of the hydrocarbon chain increases the electron
density between O and H and decreases the chances of H+ to leave the alcohol. The more the chain is long and
branched the greater the effect, the less will the alcohol be acidic.
 What is the reasoning behind the increasing pKa for organic compounds?
- Cyclohexanol is an alcohol. An alcohol contains an OH group connected to a tetrahedral carbon. Phenol is

slightly different; it contains an OH group connected to a trigonal planar carbon that is part of an aromatic ring.
Cyclohexane carboxylic acid contains a very different functional group, carboxylic acid.
- Cyclohexanol has a pKa of about 16. It is less acidic than water. It can give up a proton, but the proton is much
more likely to be bound to the oxygen than dissociated. Phenol has a pKa of about 10 and is considered mildly
acidic. Cyclohexane carboxylic acid has a pKa of about 4.9; its acidity is similar to hydrofluoric acid.
- Compare stability of the conjugate bases of Cyclohexanol, Phenol and Cyclohexane carboxylic acid:
o In cyclohexanol, the anion formed by loss of a proton is localized on the oxygen. There is no resonance
stabilization.
o In phenol, the anion formed by loss of a proton is delocalized. Resonance structures show the negative
charge can be shared between the oxygen atom and three of the carbons in the benzene ring.
o In cyclohexane carboxylic acid, the anion is also delocalized. This time the negative charge is shared
between two different oxygen atoms.
- Resonance delocalization plays a clear role in stabilizing the conjugate base formed after loss of a proton. Despite
the similar bond polarity in cyclohexanol and phenol, the proton is much more tightly bound in cyclohexanol. The
greater stability of the phenolate anion compared to the cyclohexanoxide anion makes it easier to remove a
proton from phenol than cyclohexanol.
- The atom onto which the charge is delocalized still plays a major role in determining stability. Delocalization onto
an additional oxygen atom may be more stabilizing than delocalization onto several carbons.
 Effect of Substituent on Acidity of Phenol

- As the acidic nature of phenol is due to the resonance stabilization of phenate compare to phenol. Therefore the
presence of any substituent on aromatic ring which can stabilized the phenoxide ion will tend to increases the
acidity of phenol. While any substituent which destabilized the phenate ion by increasing the negative charge will
decrease the acidic nature of phenol.
- In other words; the presence of electron withdrawing group on benzene ring in phenol increase the acidity of
phenol and electron releasing group will decrease the acidity. For example; if there is a nitro group substituted
on phenol, it will increase the acidic nature of phenol. Hence nitrophenol will be more acidic than phenol as nitro
group imparts negative mesomeric effect and negative inductive effect, hence acts as electron withdrawing
group.
- The position of nitro group on phenol will affect the acidity of phenol. A nitro group at -ortho and para-position
withdraws electrons from hydroxy group of phenol by stronger –M effect while nitro group at -meta position
withdraws electrons by weaker –I effect only, as meta position cannot involve in resonance with hydroxy group.
Hence o- and p-nitrophenols are more acidic than m-nitrophenol. Similarly as the number of nitro groups
increases on phenol, the acidic nature of phenol increases. The decreasing order of acidity of nitrophenols is as
given below.
2,4,6-trinitrophenol > 2,4-dinitrophenol > 4-Nitrophenol > 2-Nitrophenol > Phenol
- Electron donating groups like amino (-NH2), alkyl (-R) decreases the acidity of phenol. For example, cresol or
methylphenols are less acidic compare to phenol due to positive inductive effect as well as hyperconjugation of
methyl group. As both of these effects increases the electron density on hydroxy group and results in low acidity of
phenols. Hyperconjugation can operate only at ortho and para position while inductive effect operates at all the
three positions. Therefore o-cresol is least acidic. The decreasing order of acidity is as follow.
Phenol > m-cresol > p-Cresol > o-Cresol
- Some of the substituted phenols with their pKa values are as follow.
Compound pKa Substituent Effect of substituent

Phenol 10.0 - -
o-Methoxyphenol 10.0 -OCH3 +M and -I
o-Methylphenol 10.3 -CH3 +I and hyperconjucation
o-Chlorophenol 8.6 -Cl -I and +M
o-Nitrophenol 7.2 -NO2 -M and -I
m-nitrophenol 8.4 -NO2 -M and -I
p-Methoxyphenol 10.2 -OCH3 +M and -I
p-Methylphenol 10.3 -CH3 +I and hyperconjugation
p-Chlorophenol 9.4 -Cl -I and +M
p-Nitrophenol 7.2 -NO2 -M and -I
 Resonating structures of ortho Cresol
 Resonating structures of o-nitrophenoxide ions (o-nitro phenol)
 Resonating structures of p-nitrophenoxide ions (p-nitro phenol)
 Resonating structures of 2,4 dinitro phenol
 Resonance forms of 2,4,6-trinitrophenol or picric acid

o Resonance around the nitro groups (-NO2), around the ring, and you can also have one with the hydroxyl
group (-OH) making giving it a + charge.
 Why is meta-nitrophenol less acidic than para-nitrophenol?

- The acidity of nitrophenols (or any acid for that matter) is determined by the stability of the conjugate base. In the
case of m-nitrophenol and p-nitrophenol, the relative stability can be determined by looking at the resonance
structures.
- Whereas p-nitrophenol has an additional resonance structure where the negative charge is delocalised onto the
oxygen’s of the nitro group, which is highly electronegative and therefore stabilise the charge effectively. This
stabilisation is not possible in the case of m-nitrophenol because there is no opportunity via resonance for
delocalisation onto the nitro group.
- Resonance forms of m-nitrophenol
- Resonance forms of p-nitrophenol
 pKa values of various phenol derivatives
 Why is picric acid more acidic than benzoic acid?

- Picric acid is more acidic than benzoic acid because picric acid contains three NO2 groups which is electron
withdrawing group. Presence of electron withdrawing group on ring increases acidic character on the other hand
presence of electron donating group on ring decreases the acidic character.
 Qualitative tests for Phenol

 Identification of Phenols – Ferric Chloride Test
- Compounds with a phenol group will form a blue, violet, purple, green, or red-brown color upon addition of
aqueous ferric chloride. This reaction can be used as a test for phenol groups.
(a) Iron (III) Chloride Test for Water-Soluble Phenols
- Reaction:
- Procedure: The iron (III) chloride test for phenols is not completely reliable for acidic phenols, but can be
administered by dissolving 15 mg of the unknown compound in 0.5 mL of water or water-alcohol mixture and add
1 to 2 drops of 1% aqueous iron (III) chloride solution.
- Observation: A red, blue, green, or purple color observed.
(b) Iron(III) Chloride - Pyridine Test for Water-Insoluble Phenols
- Procedure (for water-insoluble phenols or less reactive phenols): A more sensitive test for phenols consists of
dissolving or suspending 15 mg of the unknown in 0.5 mL of methylene chloride and adding 3-5 drops of a 1%
solution ferric chloride in methylene chloride. Add a drop of pyridine and stir.
- Observation: Addition of pyridine and stirring will produce a color if phenols or enols are present.
 Uses of Phenol
- Approximately two-third of the total phenol produced worldwide is used to prepare reagents used in plastic
manufacturing industries.
- The polymerization reaction of phenol with formaldehyde is used to commercially prepare phenolic resins.
- Phenol is also used in the study and extraction of bio-molecules. Molecular biology finds application of phenol in
the extraction of nucleic acids from tissue samples for further investigations.
- Phenol is also used in cosmetic industry in the manufacturing of sunscreens, skin lightening creams and hair
coloring solutions.
- Phenol is also a versatile precursor to a large collection of drugs, most notably aspirin but also many herbicides and
pharmaceutical drugs.
"Diamonds are a girl's best friend" is a well-known saying. Diamonds are created from carbon under extreme
pressurize and over time, so carbon will eventually become "a girl's best friend" - hence her "future best friend."
CRESOLS
- Cresols (also hydroxytoluene) are organic compounds which are methylphenols. They are a widely occurring
natural and manufactured group of aromatic organic compounds, which are categorized as phenols (sometimes
called phenolics).
- Cresols have a disinfectant and corrosive effect due to the degradation of proteins.
Isomers of Cresol
Structural formula
General
Common name o-cresol m-cresol p-cresol
Systematic name 2-methylphenol 3-methylphenol 4-methylphenol
Other names ortho-cresol meta-cresol para-cresol
Molecular formula C7H8O
Molar mass 108.14 g/mol
Appearance at room
colorless crystals thicker liquid greasy-looking solid
temperature and pressure
Properties
Density and phase 1.05 g/cm3, solid 1.03 g/cm3, liquid 1.02 g/cm3, liquid
Solubility in water at 20−25 °C 2.5 g/100 ml 2.4 g/100 ml 1.9 g/100 ml
Soluble in strongly alkaline water
Melting point 29.8 °C 11.8 °C 35.5 °C
Boiling point 191.0 °C (464.2 K) 202.0 °C (475.2 K) 201.9 °C (475.1 K)
Acidity (pKa) 10.28 10.09 10.26
Toxicity (LD50 in Rats) 1.35 g/kg, oral 2.02 g/kg, oral 1.8 g/kg, oral
 Uses of Cresols
- Mixed cresols are used as disinfectants, preservatives, and wood preservatives.
- o-Cresol is used as a solvent, disinfectant, and chemical intermediate.
- m-Cresol is used to produce certain herbicides, as a precursor to the pyrethroid insecticides, to produce
antioxidants and to manufacture the explosive, 2,4,6-nitro-m-cresol.
- p-Cresol is used largely in the formulation of antioxidants and in the fragrance and dye industries.
- Uses for various Drugs Synthesis:
o o-Cresol used for synthesis of Carvacrol.
o m-Cresol used for synthesis of Toliprolol, Tolamolol etc.
o p-Cresol is consumed mainly in the production of antioxidants, e.g., Butylated HydroxyToluene (BHT)
Note By: Pyrethroid insecticides are a special chemical class of active ingredients found in many of the modern
insecticides found on store shelves and used by pest management professionals. The name pyrethroid means
“pyrethrum-like” and refers to the origin of this class of pesticides.
 Health Hazard Information

 Acute Effects:
- Acute inhalation exposure by humans to mixed cresols results in respiratory tract irritation, with symptoms such as
dryness, nasal constriction, and throat irritation. Mixed cresols are also strong dermal irritants.
 Chronic Effects (Noncancerous):

- No information is available on the chronic effects of mixed cresols in humans.
- Animal studies have reported effects on the blood, liver, kidney, and CNS, as well as reduced body weight, from
oral and inhalation exposure to mixed cresols.
RESORCINOL
- Resorcinol (or resorcin) is a benzenediol (m-dihydroxybenzene).
Preferred IUPAC name Benzene-1,3-diol

Resorcinol, Resorcin, m-Dihydroxybenzene, 1,3-Benzenediol, 1,3-Dihydroxybenzene,
Other names
3-Hydroxyphenol, m-Hydroquinone, m-Benzenediol
Chemical formula C6H6O2
Molar mass 110.1 g/mol
Appearance White solid, turns pink on exposure to air, light, and iron
Odor Faint
Density 1.28 g/cm3, solid
Melting point 110 °C (230 °F; 383 K)
Boiling point 277 °C (531 °F; 550 K)
Solubility in water 110 g/100 mL at 20 °C
Acidity (pKa) 9.15
 Uses of Cresols
 Medicinal Uses
- It is an antiseptic and disinfectant, and is used 5 to 10% in ointments in the treatment of chronic skin diseases such
as psoriasis, hidradenitis suppurativa, and eczema.
- It has also been employed in the treatment of gastric ulcers in doses of 125 to 250 mg in pills, and is said to be
analgesic and hemostatic (stops bleeding) in its action.
- A 2% solution used to treat external vaginal itching and irritation.
- Resorcinol is a skin protectant and topical analgesic.
 Chemical Uses
- It is used in the production of diazo dyes and plasticizers and as a UV absorber in resins.
- Resorcinol is an analytical reagent for the qualitative determination of ketoses (Seliwanoff's test).
- Resorcinol reacts with formaldehyde to form a thermoset resin which can form the basis of an aerogel (frozen
smoke).
Naphthol
- Naphthol is a fluorescent colorless (or occasionally yellow) crystalline solid with the formula C10H7OH. It has two
isomer of 1-naphthol and 2-naphthol, differing by the location of the hydroxyl group on the naphthalene ring. The
naphthols are naphthalene homologues of phenol, but more reactive.
Isomers of Napthol
Structural formula
IUPAC name Naphthalen-1-ol Naphthalen-2-ol

1-Hydroxynaphthalene; 1-Naphthalenol; 2-Hydroxynaphthalene; 2-Naphthalenol;
Other names
alpha-Naphthol beta-Naphthol; Naphth-2-ol
Molecular formula C10H8O C10H8O
Molar mass 144.17 g/mol 144.17 g/mol
Appearance at room Colorless or white solid; commercial
Colorless crystalline solid
temperature and pressure material is often strongly colored
Density 1.10 g/cm3 1.280 g/cm3
Solubility Both isomers are soluble in simple alcohols, ethers, and chloroform.
Melting point 95 to 96 °C 121 to 123 °C
 Polarity of naphthols
- Since naphthols contain a hydroxyl group, it's a highly polar molecule, with the oxygen atom attracting electron
density through the bonds toward itself. For a molecule to be polar, there has to be a difference in electronegativity
(the ability of an atom to attract electrons to itself) between one or more atoms, and in the case of naphthol, oxygen
is more electronegative than both carbon and hydrogen.
- For this reason, it can 'hog' more of the electron density in the form of the bonds, making it polar.
 Solubility
- In terms of the solvents that naphthol is soluble in (things it will form solutions with), it's very versatile. Because of
the presence of the hydroxyl group, it can hydrogen bond with other alcohol-based (polar) solvents like ethanol,
methanol, and isopropanol. The ability to form these hydrogen bonds makes it readily soluble in these kinds of
solvents. For example, consider the case of 2-naphthol forming hydrogen bonds with methanol molecules
Polarity of naphthol
Naphthol forming hydrogen bonds with methanol molecules
 Uses of Napthols
- Naphthols (both 1 and 2 isomers) are used as biomarkers for livestock and humans exposed to polycyclic aromatic
hydrocarbons
- 1-Naphthol is a precursor to a variety of insecticides including carbaryl and pharmaceuticals including nadolol. It
undergoes azo coupling to give various azo dyes, but these are generally less useful than those derived from
2-naphthol.
- In Molisch's test, 1-naphthol dissolved in ethanol, known as Molisch's reagent, is used as reagent for detecting the
presence of carbohydrates.
- The Sakaguchi test uses 1-naphthol with sodium hypobromite to detect the presence of arginine in proteins.
- The Voges–Proskauer Test uses 1-naphthol in potassium hydroxide (KOH) solution to detect the breakdown of
glucose into acetoin which is used by bacteria for external energy storage. A positive test will be indicated by the
appearance of a red color of the original yellow solution.
 What is the order of acidic strength among phenol, catechol, resorcinol

and hydroquinone?
- Resorcinol is more acidic that catechol, followed by phenol. Because
o Hydroquinone: strong +M effect and weak -I effect
o Phenol: the normal resonance in all phenols
o Resorcinol: -I effect
o Catechol: +M effect, stronger -I effect and hydrogen bonding
- Taking these factors into account, it is easy to see why hydroquinone is least acidic. Hydrogen bonding and the
vicinity of the −OH to the anion (for the stronger -I effect) make catechol more acidic than the phenol despite its
+M contribution. Resorcinol has only -I effect and no counteracting electron-donating effects, which makes it the
most acidic.
Hydroquinone < Phenol < Catechol < Resorcinol
(pKa 10.85) (pKa 10) (pKa 9.45) (pKa 9.26)
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UNIT-II: Phenols: Acidity of phenols, effect of substituents on acidity,

Presentation · June 2018

The user has requested enhancement of the downloaded file.

Preferred IUPAC name Phenol

- Cyclohexanol is an alcohol. An alcohol contains an OH group connected to a tetrahedral carbon. Phenol is

 Effect of Substituent on Acidity of Phenol

Compound pKa Substituent Effect of substituent

 Resonating structures of ortho Cresol

 Resonating structures of o-nitrophenoxide ions (o-nitro phenol)

 Resonating structures of p-nitrophenoxide ions (p-nitro phenol)

 Resonating structures of 2,4 dinitro phenol

 Resonance forms of 2,4,6-trinitrophenol or picric acid

 Why is meta-nitrophenol less acidic than para-nitrophenol?

- Resonance forms of p-nitrophenol

 pKa values of various phenol derivatives

 Why is picric acid more acidic than benzoic acid?

 Qualitative tests for Phenol

 Health Hazard Information

 Chronic Effects (Noncancerous):

Preferred IUPAC name Benzene-1,3-diol

IUPAC name Naphthalen-1-ol Naphthalen-2-ol

 What is the order of acidic strength among phenol, catechol, resorcinol

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