Phenols - Methods of preparation of phenol molecules (Industrial method)

• Phenols are important organic compounds that are widely used in many industries.
• They can be synthesized through various methods, including the industrial method.
• In this lecture, we will discuss the industrial method for the preparation of phenol molecules.
• The industrial method involves the conversion of benzene to phenol using a series of chemical reactions.
• Here are the steps involved in the industrial preparation of phenol:

1. Step 1: Nitration of Benzene
   • Benzene is treated with a mixture of concentrated nitric acid and sulfuric acid.
   • The reaction takes place at a low temperature to control the formation of unwanted by-products.
   • Nitric acid acts as the nitronium ion (NO2+) donor, which replaces one of the hydrogen atoms in the benzene ring.

2. Step 2: Reduction of Nitrobenzene
   • The nitrobenzene obtained from the nitration step is then reduced to give phenylamine.
   • A reducing agent, such as iron filings and hydrochloric acid, is used for this purpose.
   • The reduction reaction involves the replacement of the nitro group (-NO2) with an amino group (-NH2).

3. Step 3: Diazotization of Phenylamine
   • Phenylamine is then treated with a solution of sodium nitrite (NaNO2) and hydrochloric acid (HCl).
   • This reaction leads to the formation of a diazonium salt, which is an intermediate compound in the synthesis of phenols.
   • Diazotization involves the replacement of the amino group (-NH2) with a diazonium group (-N2+).

4. Step 4: Hydrolysis of Diazonium Salt
   • The diazonium salt is then hydrolyzed using dilute sulfuric acid (H2SO4) or water.
   • Hydrolysis of the diazonium salt leads to the formation of phenol and other by-products.
   • Phenol is separated from the reaction mixture by various separation techniques, such as distillation or extraction.

5. Example: Preparation of Phenol from Benzene
   • Benzene is first nitrated by reacting it with a mixture of concentrated nitric acid and sulfuric acid.
   • The nitrobenzene obtained is then reduced using iron filings and hydrochloric acid to give phenylamine.
   • Phenylamine is diazotized by treating it with sodium nitrite and hydrochloric acid.
   • Finally, the resulting diazonium salt is hydrolyzed to obtain phenol.

Phenols - Acidic nature and reactions

• Phenols exhibit acidic properties due to the presence of an -OH group attached to an aromatic ring.
• The acidity of phenols can be attributed to the stability of the phenoxide ion formed after deprotonation.
• Here are some important reactions and properties of phenols:

1. Acidic Nature of Phenols
   • Phenols are weak acids with a pKa ranging from 9 to 11.
   • In water, phenols undergo partial ionization to form phenoxide ions (C6H5O-).
   • The presence of a resonance-stabilized phenoxide ion contributes to the acidic nature of phenols.

2. Reactions with Metal Bases
   • Phenols react with strong bases, such as sodium hydroxide (NaOH), to form phenoxide salts.
   • The hydrogen atom bonded to the oxygen in the -OH group is replaced by a metal cation (e.g., Na+).
   • The reaction can be represented as: Phenol + NaOH → Sodium Phenoxide + Water

3. Reactions with Strong Acids
   • Phenols react with strong mineral acids, such as hydrochloric acid (HCl), to regenerate phenol.
   • The acidic proton from the mineral acid replaces the proton in the -OH group of phenol.
   • The reaction can be represented as: Phenol + HCl → Chlorobenzene + Water

4. Halogenation Reactions
   • Phenols readily undergo halogenation reactions due to the presence of an aromatic ring.
   • Halogens, such as chlorine or bromine, can be added to the phenol molecule.
   • The reaction can be represented as: Phenol + Br2 → 2-Bromophenol + HBr

5. Substitution Reactions
   • Phenols undergo substitution reactions, similar to other aromatic compounds.
   • Substituents can be added to the phenol ring, either through electrophilic or nucleophilic substitution reactions.
   • Examples include nitration, sulfonation, and Friedel-Crafts reactions.

Phenols - Oxidation reactions

• Phenols undergo various oxidation reactions, leading to the formation of different products.
• The oxidation reactions of phenols are useful in organic synthesis and contribute to their biological activities.
• Here are some common oxidation reactions of phenols:

1. Oxidation to Quinones
   • Phenols can be oxidized to form quinones through the loss of two hydrogen atoms.
   • Quinones are important intermediates in many biochemical processes.
   • The oxidation reaction can be represented as: Phenol → Quinone + 2H+ + 2e-

2. Reaction with Mild Oxidizing Agents
   • Phenols react with mild oxidizing agents, such as potassium dichromate (K2Cr2O7) or potassium permanganate (KMnO4), to form quinones.
   • The reaction involves the loss of two hydrogen atoms from the phenol molecule.
   • The reaction can be represented as: Phenol + [O] → Quinone + H2O

3. Oxidation to Benzoquinone
   • Phenols can be oxidized to benzoquinone by strong oxidizing agents, such as lead tetraacetate.
   • Benzoquinone is an important intermediate in the synthesis of many aromatic compounds.
   • The reaction can be represented as: Phenol + 2[O] → Benzoquinone + H2O

4. Oxidation to Carboxylic Acids
   • Phenols undergo oxidation in the presence of alkaline KMnO4 or acidic KMnO4 to form carboxylic acids.
   • The oxidation involves the loss of not only hydrogen atoms but also carbon atoms.
   • The reaction can be represented as: Phenol + 4[O] → Benzoic Acid + H2O

5. Example: Oxidation of Phenol to Benzoquinone
   • Phenol can be oxidized to benzoquinone by treating it with lead tetraacetate.
   • The reaction involves the loss of two hydrogen atoms from the phenol molecule.
   • The resulting product is benzoquinone, which has several applications in the chemical industry.

Phenols - Reactions with Nitrous Acid (Diazotization)

• Phenols react with nitrous acid (HNO2) in the presence of hydrochloric acid (HCl) to form diazonium salts.
• Diazotization is an important reaction involving the replacement of the -OH group in phenols with a diazonium group (-N2+).
• The diazonium salts formed in this reaction are versatile intermediates in the synthesis of various aromatic compounds.
• Here are the steps involved in the reaction of phenols with nitrous acid (diazotization):

1. Preparation of Nitrous Acid
   • Nitrous acid (HNO2) is prepared by the reaction of sodium nitrite (NaNO2) with a strong acid, such as hydrochloric acid (HCl).

2. Reaction with Phenol
   • Phenol is treated with a solution of nitrous acid in the presence of hydrochloric acid.
   • The -OH group of phenol is replaced by the diazonium group (-N2+) to form a diazonium salt.
   • The reaction can be represented as: Phenol + HNO2 + HCl → Diazonium Salt + Water

3. Importance of Diazonium Salts
   • Diazonium salts formed from the reaction of phenols with nitrous acid are versatile intermediates in organic synthesis.
   • They can be used for various substitution (electrophilic and nucleophilic) reactions to introduce different functional groups.
   • Diazonium salts are particularly important in the synthesis of azo compounds, which find applications in dyes and pigments.

4. Example: Diazotization of Phenol to Diazonium Salt
   • Phenol is diazotized by treating it with a solution of nitrous acid and hydrochloric acid.
   • The -OH group of phenol is replaced by the diazonium group (-N2+), leading to the formation of a diazonium salt.
   • The resulting diazonium salt can be further utilized in various organic synthesis reactions.

Phenols - Reactions with Halogens

• Phenols readily undergo halogenation reactions due to the presence of an aromatic ring.
• Halogenation reactions involve the addition of halogen atoms (e.g., chlorine or bromine) to the phenol molecule.
• The reaction can take place under different conditions, leading to the formation of halogenated phenols.
• Here are some important reactions of phenols with halogens:

1. Halogenation with Chlorine or Bromine
   • Phenols can be halogenated by treating them with chlorine or bromine.
   • The reaction can be carried out in the presence of a Lewis acid catalyst, such as iron(III) chloride (FeCl3).
   • The halogen atom adds to the aromatic ring, replacing one of the hydrogen atoms in the phenol molecule.
   • The reaction can be represented as: Phenol + X2 → Halogenated Phenol + HX

2. Formation of 2,4,6-Tribromophenol
   • Phenols react with excess bromine in the presence of a catalyst, such as iron(III) chloride (FeCl3), to form 2,4,6-tribromophenol.
   • The reaction involves the substitution of all three hydrogen atoms in the phenol molecule with bromine atoms.
   • The reaction can be represented as: Phenol + 3Br2 → 2,4,6-Tribromophenol + 3HBr

3. Competition between Electrophilic Substitution and Oxidation
   • When phenols react with halogens, there is a competition between electrophilic substitution and oxidation reactions.
   • Depending on the reaction conditions and the nature of the phenol, either substitution or oxidation can be favored.
   • For example, phenols with electron-donating groups are more prone to undergo electrophilic substitution reactions, whereas phenols with electron-withdrawing groups may undergo oxidation.

4. Example: Halogenation of Phenols
   • Phenols can be halogenated by treating them with halogens, such as chlorine or bromine, in the presence of a Lewis acid catalyst.
   • Depending on the conditions and the presence of substituents on the phenol ring, various halogenated phenols can be obtained.

Phenols - Reactions with Alkalis (Metal Bases)

• Phenols react with alkalis, such as sodium hydroxide (NaOH), to form phenoxide salts.
• The reaction involves the replacement of the hydrogen atom bonded to the oxygen in the -OH group with a metal cation.
• Phenoxide salts are highly soluble in water and have applications in various fields.
• Here are some important reactions of phenols with alkalis:

1. Reaction with Sodium Hydroxide
   • Phenols react with sodium hydroxide (NaOH) to form sodium phenoxide salts.
   • The reaction can be represented as: Phenol + NaOH → Sodium Phenoxide + Water

2. Solubility of Phenoxide Salts
   • Phenoxide salts formed from the reaction of phenols with alkalis are highly soluble in water.
   • This solubility is due to the negative charge on the oxygen atom in the phenoxide ion (C6H5O-).

3. Acidification of Phenoxide Salts
   • Phenoxide salts can be converted back to phenols by acidification with a strong acid, such as hydrochloric acid (HCl).
   • The acidic proton from the strong acid replaces the metal cation in the phenoxide salt.
   • The reaction can be represented as: Sodium Phenoxide + HCl → Phenol + NaCl

4. Applications of Phenoxide Salts
   • Phenoxide salts find applications in various fields, including pharmaceuticals, dyes, and organic synthesis.
   • They can be used as nucleophiles in substitution reactions to introduce different functional groups.
   • Phenoxide salts are also utilized in the synthesis of polymers and coordination compounds.

5. Example: Reaction of Phenol with Sodium Hydroxide
   • Phenol reacts with sodium hydroxide to form sodium phenoxide.
   • The -OH group in phenol is replaced by the sodium cation, resulting in the formation of a soluble salt.
   • Sodium phenoxide can further react with acid to regenerate phenol.

Phenols - Electrophilic Substitution Reactions

• Phenols undergo electrophilic substitution reactions, similar to other aromatic compounds.
• The presence of the -OH group in phenols influences the reactivity and regioselectivity of the substitution reactions.
• Here are some important electrophilic substitution reactions of phenols:

1. Nitration of Phenols
   • Phenols can undergo nitration reactions in the presence of nitric acid and sulfuric acid.
   • The -OH group in phenols activates the aromatic ring towards electrophilic attack, leading to the substitution of a hydrogen atom by a nitro group (-NO2).
   • The reaction can be represented as: Phenol + HNO3 → Nitrophenol + H2O

2. Sulfonation of Phenols
   • Phenols can be sulfonated by treating them with concentrated sulfuric acid (H2SO4).
   • The -OH group in phenols activates the aromatic ring towards electrophilic attack, leading to the substitution of a hydrogen atom by a sulfonic acid group (-SO3H).
   • The reaction can be represented as: Phenol + H2SO4 → Benzenesulfonic Acid + H2O

3. Friedel-Crafts Acylation of Phenols
   • Phenols can undergo Friedel-Crafts acylation reactions, similar to other aromatic compounds.
   • The -OH group in phenols activates the aromatic ring towards electrophilic attack by an acylating agent, such as an acyl chloride or an acid anhydride.
   • The reaction can be represented as: Phenol + RCOCl → Phenyl Esters + HCl

4. Esterification of Phenols
   • Phenols can undergo esterification reactions with carboxylic acids to form esters.
   • The -OH group in phenols acts as a nucleophile and reacts with the carboxylic acid, resulting in the formation of an ester.
   • The reaction can be represented as: Phenol + RCOOH → Phenyl Esters + H2O

5. Example: Nitration of Phenol
   • Phenol can undergo nitration reactions in the presence of nitric acid and sulfuric acid.
   • The -OH group in phenol activates the aromatic ring, making it susceptible to electrophilic attack by the nitronium ion (NO2+).
   • The resulting product is a nitrophenol, which can have different positional isomers depending on the substitution of the -OH group in the phenol.

Phenols - Separation Techniques

• Phenols can be separated from reaction mixtures by employing various separation techniques.
• These techniques aim to isolate and purify phenols for further use in the chemical industry and medicinal applications.
• Here are some important separation techniques used for phenols:

1. Distillation
   • Distillation is a commonly used technique for the separation and purification of phenols from reaction mixtures.
   • Distillation relies on the differences in boiling points between phenols and other compounds present in the mixture.
   • The reaction mixture is heated, and the volatile phenol compounds are vaporized and condensed to obtain pure phenols.

2. Extraction
   • Extraction techniques, such as liquid-liquid extraction or solid-phase extraction, can be used to separate phenols from reaction mixtures.
   • In liquid-liquid extraction, the reaction mixture is mixed with a suitable solvent that selectively extracts phenols.
   • The solvent is then separated from the mixture, and phenols are recovered by evaporating the solvent.
   • Solid-phase extraction involves the use of a solid adsorbent to selectively adsorb phenols from the reaction mixture.

3. Crystallization
   • Crystallization is another useful technique for the separation and purification of phenols.
   • By applying appropriate temperature and solvents, phenols can be converted into their solid crystal form.
   • The crystal can then be separated from the mixture by filtration or centrifugation to obtain pure phenols.

4. Chromatography
   • Chromatographic techniques, such as column chromatography or high-performance liquid chromatography (HPLC), can be used for the separation of phenols.
   • These techniques rely on the differential migration of compounds in a stationary phase and a mobile phase.
   • The phenols can be separated based on their different interactions with the stationary phase, allowing for their isolation.

5. Example: Distillation of Phenol
   • Distillation is a commonly used technique for the separation and purification of phenols.
   • The reaction mixture containing phenols is heated, and the volatile phenol compounds are vaporized.
   • The vapor is then condensed to obtain pure phenols, which can be further analyzed or used in various applications.

Phenols - Industrial Applications

• Phenols have wide-ranging industrial applications due to their unique properties and reactivity.
• They are utilized in various industries, including pharmaceuticals, plastics, dyes, and personal care products.
• Here are some important industrial applications of phenols:

1. Pharmaceuticals
   • Phenols are used as active ingredients in pharmaceuticals due to their antimicrobial and antiseptic properties.
   • They are used in the production of disinfectants, antiseptics, and analgesics.
   • Examples include phenol itself, which is used as a disinfectant and antiseptic, and aspirin, which is derived from salicylic acid (a phen