Unit 4: Alcohols and Phenols: Preparation and Reactions

Alcohols

Preparation of Primary (1°), Secondary (2°), and Tertiary (3°) Alcohols

Grignard reagents (R-MgX) are organometallic compounds used to synthesize alcohols by reacting with carbonyl compounds. The type of alcohol (1°, 2°, or 3°) depends on the carbonyl compound used.

Formation of Primary (1°) Alcohols

When a Grignard reagent reacts with formaldehyde (HCHO), followed by hydrolysis, a primary alcohol is formed.

R-MgX + HCHO → R-CH₂-OMgX

R-CH₂-OMgX + H₂O → R-CH₂-OH (1° alcohol) + Mg(OH)X

Formation of Secondary (2°) Alcohols

When a Grignard reagent reacts with an aldehyde (R'-CHO) other than formaldehyde, followed by hydrolysis, a secondary alcohol is formed.

R-MgX + R'-CHO → R-CH(R')-OMgX

R-CH(R')-OMgX + H₂O → R-CH(R')-OH (2° alcohol) + Mg(OH)X

Formation of Tertiary (3°) Alcohols

When a Grignard reagent reacts with a ketone (R'-CO-R''), followed by hydrolysis, a tertiary alcohol is formed.

R-MgX + R'-CO-R'' → RR'R''C-OMgX

RR'R''C-OMgX + H₂O → RR'R''C-OH (3° alcohol) + Mg(OH)X

Observation: Tertiary alcohols can also be formed by reaction of a Grignard reagent with esters, but this is often considered a less direct or more complex route when compared to ketones for 3° alcohol synthesis.

Ester Hydrolysis

Esters can be hydrolyzed in acidic or basic conditions to yield a carboxylic acid and an alcohol.

In acidic hydrolysis, the ester reacts with water in the presence of an acid catalyst.

R-COOR' + H₂O (H⁺) → R-COOH + R'-OH

In basic hydrolysis (saponification), the ester reacts with a base (e.g., NaOH) to form a carboxylate salt and an alcohol.

R-COOR' + NaOH → R-COONa + R'-OH

Reduction of Aldehydes, Ketones, Carboxylic Acids, and Esters

Carbonyl compounds can be reduced to alcohols using various reducing agents like lithium aluminum hydride (LiAlH₄) or sodium borohydride (NaBH₄).

Reduction of Aldehydes

Aldehydes reduce to primary (1°) alcohols.

R-CHO (reducing agent, e.g., LiAlH₄ or NaBH₄) → R-CH₂-OH

Reduction of Ketones

Ketones reduce to secondary (2°) alcohols.

R-CO-R' (reducing agent, e.g., LiAlH₄ or NaBH₄) → R-CH(OH)-R'

Reduction of Carboxylic Acids

Carboxylic acids reduce to primary (1°) alcohols. Stronger reducing agents like LiAlH₄ are typically required as NaBH₄ is not effective for carboxylic acids.

R-COOH (1. LiAlH₄ / 2. H₂O) → R-CH₂-OH

Reduction of Esters

Esters reduce to two alcohols: the alcohol moiety from the ester and a primary alcohol from the carbonyl part. Strong reducing agents like LiAlH₄ are used.

R-COOR' (1. LiAlH₄ / 2. H₂O) → R-CH₂-OH + R'-OH

Reactions of Alcohols

Reaction with Sodium

Alcohols react with active metals like sodium to form alkoxides and liberate hydrogen gas. This reaction demonstrates the acidic nature of the hydrogen atom attached to the oxygen in the hydroxyl group.

2R-OH + 2Na → 2R-ONa + H₂

Reaction with HX (Hydrogen Halides - Lucas Test)

Alcohols react with hydrogen halides (HCl, HBr, HI) to form alkyl halides. The reactivity order of HX is HI > HBr > HCl. The reactivity order of alcohols is 3° > 2° > 1°.

R-OH + HX → R-X + H₂O

The Lucas test uses a solution of anhydrous zinc chloride (ZnCl₂) in concentrated hydrochloric acid (HCl) as the Lucas reagent. It is used to distinguish between primary, secondary, and tertiary alcohols. The test is based on the difference in reactivity of these alcohols with HX.

• Tertiary (3°) Alcohols: React immediately at room temperature, producing turbidity (cloudiness) due to the rapid formation of an insoluble alkyl chloride.
• Secondary (2°) Alcohols: React within 5-10 minutes at room temperature, producing turbidity.
• Primary (1°) Alcohols: Do not react at room temperature, and the solution remains clear. Reaction may occur upon heating.

Esterification

Alcohols react with carboxylic acids (or acid derivatives like acid anhydrides or acid chlorides) in the presence of an acid catalyst to form esters and water. This is a condensation reaction.

R-OH + R'-COOH (H⁺) ⇌ R'-COOR + H₂O

Oxidation of Alcohols

Oxidation of alcohols involves the removal of hydrogen atoms and/or addition of oxygen atoms, leading to the formation of aldehydes, ketones, or carboxylic acids depending on the type of alcohol and the oxidizing agent used.

With PCC (Pyridinium Chlorochromate)

PCC is a mild oxidizing agent. It oxidizes primary alcohols to aldehydes and secondary alcohols to ketones, stopping at the aldehyde stage for primary alcohols and preventing further oxidation to carboxylic acids.

R-CH₂-OH (1°) (PCC) → R-CHO (Aldehyde)

R-CH(OH)-R' (2°) (PCC) → R-CO-R' (Ketone)

With Alk. KMnO₄ (Alkaline Potassium Permanganate)

Alkaline KMnO₄ is a strong oxidizing agent. It oxidizes primary alcohols directly to carboxylic acids. Secondary alcohols are oxidized to ketones. Tertiary alcohols are generally resistant to oxidation under mild conditions but can undergo C-C bond cleavage under harsh conditions.

R-CH₂-OH (1°) (Alk. KMnO₄) → R-COOH (Carboxylic acid)

R-CH(OH)-R' (2°) (Alk. KMnO₄) → R-CO-R' (Ketone)

With Acidic Dichromate (K₂Cr₂O₇/H₂SO₄)

Acidic dichromate (e.g., K₂Cr₂O₇/H₂SO₄) is also a strong oxidizing agent, similar in effect to alkaline KMnO₄. Primary alcohols are oxidized to carboxylic acids, and secondary alcohols are oxidized to ketones.

R-CH₂-OH (1°) (Acidic K₂Cr₂O₇) → R-COOH (Carboxylic acid)

R-CH(OH)-R' (2°) (Acidic K₂Cr₂O₇) → R-CO-R' (Ketone)

With Conc. HNO₃ (Concentrated Nitric Acid)

Concentrated nitric acid is another strong oxidizing agent. It oxidizes primary alcohols to carboxylic acids and secondary alcohols to ketones. Under harsh conditions, it can also cause C-C bond cleavage.

R-CH₂-OH (1°) (Conc. HNO₃) → R-COOH (Carboxylic acid)

R-CH(OH)-R' (2°) (Conc. HNO₃) → R-CO-R' (Ketone)

Diols (Up to 6 Carbons)

Oxidation of Diols

Diols, compounds with two hydroxyl groups, undergo oxidation reactions similar to monohydric alcohols. The outcome depends on the position of the hydroxyl groups and the strength of the oxidizing agent.

• Vicinal diols (1,2-diols): Can undergo oxidative cleavage (C-C bond breaking) with reagents like periodic acid (HIO₄) or lead tetraacetate (Pb(OAc)₄) to form aldehydes or ketones.
• Other diols: Each hydroxyl group can be oxidized independently or sequentially depending on its type (primary or secondary) and the oxidizing agent. For example, a primary hydroxyl group can be oxidized to an aldehyde or carboxylic acid, and a secondary hydroxyl group to a ketone.

Pinacol-Pinacolone Rearrangement

The Pinacol-Pinacolone rearrangement is an acid-catalyzed rearrangement of a 1,2-diol (vicinal diol), specifically pinacol (2,3-dimethylbutane-2,3-diol), to a ketone (pinacolone). It involves dehydration and a 1,2-methyl shift.

Mechanism Steps:

1. Protonation of one hydroxyl group.
2. Loss of water to form a tertiary carbocation.
3. 1,2-Methyl shift (rearrangement) to form a more stable carbocation where the positive charge is stabilized by the oxygen lone pair (forming a protonated ketone).
4. Deprotonation to yield the pinacolone (ketone).

Example:

(CH₃)₂C(OH)-C(OH)(CH₃)₂ (H⁺, heat) → (CH₃)₃C-CO-CH₃

Pinacol (1,2-diol) → Pinacolone (ketone)

Phenols (Phenol Case)

Preparation of Phenol

Cumene Hydroperoxide Method

The cumene hydroperoxide method is a major industrial process for the synthesis of phenol and acetone. It starts with the alkylation of benzene with propene to form cumene (isopropylbenzene), which is then oxidized with air to cumene hydroperoxide, and finally cleaved in acidic medium to phenol and acetone.

1. Benzene + Propene (H₃PO₄ catalyst) → Cumene (Isopropylbenzene)
2. Cumene + O₂ (Air) → Cumene Hydroperoxide
3. Cumene Hydroperoxide (H⁺, H₂O) → Phenol + Acetone

From Diazonium Salts

Phenol can be prepared by the hydrolysis of benzenediazonium chloride (a diazonium salt). Benzenediazonium chloride is formed by the diazotization of aniline with sodium nitrite (NaNO₂) and hydrochloric acid (HCl) at low temperatures (0-5 °C).

C₆H₅-NH₂ (NaNO₂/HCl, 0-5 °C) → C₆H₅-N₂⁺Cl^- (Benzenediazonium chloride)

C₆H₅-N₂⁺Cl^- + H₂O (warm) → C₆H₅-OH (Phenol) + N₂ + HCl

Reactions of Phenol

Phenol is an aromatic compound with a hydroxyl group directly attached to the benzene ring. The hydroxyl group is an activating group and an ortho/para director, making the benzene ring highly susceptible to electrophilic aromatic substitution.

Electrophilic Substitution

Nitration

Phenol undergoes nitration with dilute nitric acid at room temperature to form a mixture of ortho-nitrophenol and para-nitrophenol. With concentrated nitric acid, picric acid (2,4,6-trinitrophenol) can be formed under more vigorous conditions.

C₆H₅-OH + dil. HNO₃ (room temp) → o-nitrophenol + p-nitrophenol

Halogenation

Phenol reacts readily with halogens. For example, with bromine water (Br₂/H₂O), phenol forms a white precipitate of 2,4,6-tribromophenol, indicating the strong activating nature of the -OH group.

C₆H₅-OH + 3Br₂ (aq) → 2,4,6-tribromophenol + 3HBr

If a less reactive solvent like CS₂ or CCl₄ is used, monobromination (o-bromophenol and p-bromophenol) can be achieved.

Sulphonation

Phenol reacts with concentrated sulfuric acid (H₂SO₄) to form sulphonic acids. The product depends on the temperature:

• At low temperature (25 °C): Ortho-phenolsulfonic acid is the major product (kinetic control).
• At high temperature (100 °C): Para-phenolsulfonic acid is the major product (thermodynamic control).

C₆H₅-OH + H₂SO₄ (conc.) (low temp) → o-phenolsulfonic acid

C₆H₅-OH + H₂SO₄ (conc.) (high temp) → p-phenolsulfonic acid

Reimer-Tiemann Reaction

The Reimer-Tiemann reaction is a chemical reaction used for the ortho-formylation of phenols. It involves the reaction of phenol with chloroform (CHCl₃) in the presence of a strong base (e.g., NaOH) to produce salicylaldehyde (o-hydroxybenzaldehyde) as the major product. The electrophile is dichlorocarbene (:CCl₂).

C₆H₅-OH + CHCl₃ + NaOH → o-hydroxybenzaldehyde (Salicylaldehyde) + H₂O + NaCl

Schotten-Baumann Reaction

The Schotten-Baumann reaction is a method for the acylation of alcohols or amines. For phenols, it refers to the benzoylation of phenol using benzoyl chloride (C₆H₅COCl) in the presence of an aqueous base (e.g., NaOH or pyridine) to form phenyl benzoate. This is a type of esterification.

C₆H₅-OH + C₆H₅-COCl (NaOH/H₂O) → C₆H₅-COO-C₆H₅ (Phenyl Benzoate) + HCl