FAD1018 W7 — Alcohol and Phenol

Week 7 lecture (62 slides) on alcohols and phenols. Lecturer: Dr Ahmad Danial Azzahari (CHEMISTRY DIVISION, PASUM, Universiti Malaya). Source files: W7 (1).pdf from lecture notes folders.

Learning Objectives

Describe structural and optical isomerism in hydroxy compounds.
State the physical properties of hydroxy compounds.
Classify alcohols into primary, secondary and tertiary alcohol.
Describe the preparation of alcohols (e.g. ethanol from fermentation, hydration of ethene).
Understand reactions of alcohols: oxidation, dehydration, reaction with Na, formation of haloalkanes, iodoform reaction, esterification and acylation.
Explain tests to determine class and type of alcohols: Lucas test.
State uses of alcohols as antiseptic, solvent and fuel.
Explain relative acidity of water, phenol and alcohol with reference to inductive and resonance effects.
Describe preparation of phenols from Cumene process.
Understand reactions of phenols with Na, NaOH, acyl chloride and electrophilic substitution in benzene ring.
Describe use of bromine water and aqueous iron(III) chloride as tests for phenol.
Explain use of phenol in manufacture of cyclohexanol, and hence nylon-6,6.

Structure & Classification

Alcohol vs Phenol

Alcohol: $-\text{OH}$ attached directly to an $\text{sp}^3$ hybridized carbon atom (general formula: $\text{C}n\text{H}{2n+2}\text{O}$ for saturated monohydric alcohols).
Phenol: $-\text{OH}$ attached directly to a benzene ring.
Phenol is NOT an alcohol and NOT an aromatic alcohol.
Alcohols are functional isomers of ethers ($\text{R-O-R}$).
- Example: ethanol ($\text{CH}_3\text{CH}_2\text{-OH}$) and dimethyl ether ($\text{CH}_3\text{-O-CH}_3$).
- ```
ethanol: CCO
dimethyl ether: COC
```

Determine the longest chain containing the hydroxyl group. Substituted phenols are named as derivatives of phenol. butan-2-ol: CCC(C)O When comparing boiling points across a series, consider (in order of dominance):

acetic acid: CC(=O)O
phenol: c1ccccc1O
2,2,2-trichloroethanol: ClC(Cl)(Cl)CO
water: O
2-chloroethanol: ClCCO
methanol: CO
ethanol: CCO
isopropyl alcohol: CC(C)O
tert-butyl alcohol: CC(C)(C)O
cyclohexanol: C1CCCCC1O

Basicity of Alcohols

In the presence of strong acids, alcohol serves as a weak base (lone pairs on oxygen accept a proton).

Protonation is the first important step in several reactions of alcohols.

Acidity of Phenols

Phenols are weak acids, but much stronger acids than alcohols.

Most alcohols: $pK_a \approx 18$.
Most phenols: $pK_a \approx 10$.
Phenol is nearly 100 million times more acidic than cyclohexanol.

Resonance Stabilization of Phenoxide

The phenoxide ion is more stable than a typical alkoxide because the negative charge is delocalized over the oxygen and three carbon atoms of the ring.

$$\text{PhOH (aq)} \rightleftharpoons \text{PhO}^- \text{(aq)} + \text{H}^+ \text{(aq)}$$

Reactions with Bases

Phenol reacts with Na metal and NaOH (more acidic than water and alcohols).
Phenol does NOT give $\text{CO}_2$ with $\text{Na}_2\text{CO}_3$ or $\text{NaHCO}_3$ — not acidic enough.
- Useful diagnostic test: phenol dissolves in NaOH but does not evolve $\text{CO}_2$ with carbonate.

Effect of Ring Substituents on Phenol Acidity

Electron-Withdrawing Groups (EWG)

Remove electron density from the ring → weaken electron density on O atom → stabilize phenoxide → increase acidity (lower $pK_a$).
Ortho and para positions are most effective (resonance can place +ve charge on carbon adjacent to $-\text{OH}$).
Example: 2-nitrophenol ($pK_a = 7.20$), 4-nitrophenol ($pK_a = 7.20$) vs phenol ($pK_a = 10.00$).
3-nitrophenol ($pK_a = 8.40$): meta position cannot place +ve charge adjacent to $-\text{OH}$ in resonance, so weaker effect.

Electron-Donating Groups (EDG)

Enhance electron density onto ring → strengthen electron density on O atom → destabilize phenoxide → decrease acidity (higher $pK_a$).
Ortho and para positions are most effective (resonance can place −ve charge on carbon adjacent to $-\text{OH}$).
Example: 4-aminophenol ($pK_a = 10.30$) vs phenol ($pK_a = 10.00$).
3-aminophenol ($pK_a = 9.82$): slightly more acidic than phenol because meta position does not enhance O electron density via resonance; the $-\text{NH}_2$ basicity can actually facilitate intramolecular proton abstraction.

2-nitrophenol: Oc1ccccc1[N+](=O)[O-]
3-nitrophenol: Oc1cccc(c1)[N+](=O)[O-]
4-nitrophenol: Oc1ccc(cc1)[N+](=O)[O-]
4-aminophenol: Nc1ccc(O)cc1
3-aminophenol: Nc1cccc(O)c1

[!tip] Explaining o-/m-/p- effects Always draw resonance structures showing electron density on the carbon adjacent to the phenolic $-\text{OH}$. If that carbon carries +ve charge (EWG), acidity increases. If it carries −ve charge (EDG), acidity decreases.

Preparation of Alcohols

1. Fermentation of Carbohydrate

Yeast converts sugars to ethanol.
Yields only 12–15% alcohol (yeast survival limit).
Distillation increases concentration to 40–50% (hard liquor).
Example: glucose → ethanol + $\text{CO}_2$.

2. Hydration of Alkene

Alkene + dilute aqueous acid ($\text{H}_2\text{SO}_4$ or $\text{H}_3\text{PO}_4$).
Water adds according to Markovnikov's rule.
Dilute acid (excess water) favors alcohol (Le Châtelier).
Concentrated acid (little water) favors alkene.
Industrial ethanol: high-temperature, high-pressure gas-phase hydration of ethylene with catalysts ($\text{P}_2\text{O}_5$, tungsten oxide, treated clays).

3. Nucleophilic Substitution of Haloalkane

$\text{R-X} + \text{NaOH}/\text{KOH}$ (strong base) in aqueous solution/acetone → $\text{R-OH} + \text{X}^-$.
1° R-X → 1° alcohol (SN2)
2° R-X → 2° alcohol (SN2, may compete with E2)
3° R-X → alkene (E2 dominates, too hindered for SN2)

4. Grignard Reagent

Formation: $\text{R-X} + \text{Mg} \xrightarrow{\text{dry ether}} \text{RMgX}$

Reaction with carbonyl compounds:

Formaldehyde → 1° alcohol
Aldehydes → 2° alcohol
Ketones → 3° alcohol

Workup: protonate alkoxide with $\text{H}_2\text{O}$ or dilute acid in a separate step.

[!warning] Grignard reagents react with water Water destroys Grignard reagent: $\text{RMgX} + \text{H}_2\text{O} \rightarrow \text{R-H} + \text{Mg(OH)X}$ Must use anhydrous conditions.

5. Other Methods

Reduction of carbonyl compounds (covered later in Sem 2).

Preparation of Phenols

1. Cumene Process (Industrial)

Three steps:

Alkylation: benzene + propene → cumene (isopropylbenzene)
Oxidation: cumene → cumene hydroperoxide
Decomposition/rearrangement: cumene hydroperoxide → phenol + acetone

Most worldwide phenol production uses this method. Requires demand for both phenol and acetone by-product.

2. Laboratory Preparation

Primary aromatic amine + $\text{HNO}_2$ (nitrous acid) → arenediazonium salt.
Diazonium salt + $\text{H}_2\text{O}$ → phenol + $\text{N}_2$.

Chemical Reactions of Alcohols

1. Reaction with Reactive Metals

$$2,\text{ROH} + 2,\text{Na} \rightarrow 2,\text{RONa} + \text{H}_2 \uparrow$$

Redox reaction: metal oxidized, $\text{H}^+$ reduced.
More acidic alcohols (methanol, ethanol) react rapidly.
Less acidic (2°) react more slowly; 3° react very slowly (use K or NaH in THF).

2. Conversion to Haloalkane

With Hydrohalic Acids (HX)

General: $\text{R-OH} + \text{HX} \rightarrow \text{R-X} + \text{H}_2\text{O}$
Reactivity for same HX: phenol (no reaction) < 1° < 2° < 3° < benzyl alcohol
Reactivity for same alcohol: $\text{HCl} < \text{HBr} < \text{HI}$
For HCl with 1°/2° alcohols: $\text{ZnCl}_2$ catalyst needed (Lucas reagent principle).
Mechanism: SN1 generally (carbocation), but SN2 if carbocation would be unstable.

With Phosphorus Halides ($\text{PX}_3$, $\text{PX}_5$)

General: $3,\text{R-OH} + \text{PX}_3 \rightarrow 3,\text{R-X} + \text{H}_3\text{PO}_3$
Advantages: good yields for 1° and 2°; no carbocation; no rearrangement.
Disadvantage: does not work well with 3° alcohols.
$\text{PI}_3$ generated in situ from $\text{P} + \text{I}_2$.

With Thionyl Chloride ($\text{SOCl}_2$)

Usually in presence of pyridine.
General: $\text{R-OH} + \text{SOCl}_2 \xrightarrow{\text{pyridine}} \text{R-Cl} + \text{SO}_2 \uparrow + \text{HCl} \uparrow$
Advantages: by-products are gases (no reverse reaction); often allows retention of configuration.

Lucas Test (Experiment 2.5, FAD1019)

Differentiates 1°, 2°, and 3° alcohols.
Reagent: concentrated HCl + $\text{ZnCl}_2$.
$\text{Zn}^{2+}$ complexes with lone pairs on oxygen, weakening C–O bond.
Alcohol dissolves in reagent; alkyl halide product is insoluble → cloudy/turbid solution.
Limited to alcohols with <6 carbons (requires complete solubility).
Reactivity: 3° > 2° > 1°.

3. Dehydration to Alkene

Elimination reaction, usually E1 mechanism.
Rearrangements may occur to form more stable carbocations.
Eliminates one $\text{H}_2\text{O}$ from adjacent carbons.

Dehydrating agents:

Conc. $\text{H}_2\text{SO}_4$, $\Delta$, 180 °C
85% $\text{H}_3\text{PO}_4$, $\Delta$, 350 °C
Alumina ($\text{Al}_2\text{O}_3$), $\Delta$, 350 °C
Lower temperature (~140 °C) gives symmetrical ethers.
Follows Zaitsev's rule: most substituted alkene predominates.
Ease of dehydration: 3° > 2° > 1° (ease of carbocation formation).
Primary alcohols: poor yields, rearrangements common.

4. Oxidation

Definition: conversion of C–H bonds to C–O bonds.

Alcohol Class	Product	Notes
1°	Aldehyde → Carboxylic acid	With strong oxidants; stops at aldehyde with mild oxidant
2°	Ketone	—
3°	Resistant	No H on carbinol carbon; requires C–C cleavage

Common oxidizing agents:

Chromic acid ($\text{K}_2\text{Cr}_2\text{O}_7/\text{H}^+$): orange → green/blue (viridian). Strong; oxidizes 1° all the way to carboxylic acid.
Acidified $\text{KMnO}_4$: purple. Strong; oxidizes 1° to carboxylic acid.
PCC (pyridinium chlorochromate): mild. Oxidizes 1° alcohols to aldehydes in excellent yields. Soluble in nonpolar solvents (e.g. $\text{CH}_2\text{Cl}_2$). Also oxidizes 2° to ketones.

[!tip] Chromic acid test Add orange chromic acid to unknown. 1° or 2° alcohol → green/blue color. 3° alcohol, ketone, alkane → no immediate color change.

5. Esterification

Alcohol + carboxylic acid $\xrightarrow{\text{H}^+}$ ester + water.
Equilibrium reaction; use excess reagent or dehydrating agent to drive forward.
Acylation with acyl chloride: alcohol + acyl chloride → ester + HCl. Exothermic; no equilibrium problem.

6. Iodoform Test

Positive for compounds with $\text{-CH}_3$ bonded directly to $\text{-C=O}$ or oxidizable to that state.

Positive results:

Ethanal ($\text{CH}_3\text{CHO}$)
Methyl ketones ($\text{CH}_3\text{COR}$)
Ethanol (only 1° alcohol that gives positive result)
2° alcohols that can be oxidized to methyl ketones

Negative results:

Methanol (oxidizes to $\text{HCOOH}$, no $\text{-CH}_3$ on carbonyl)
3° alcohols (cannot be oxidized to carbonyl)

Product: yellow precipitate of triiodomethane ($\text{CHI}_3$) + carboxylate salt.

Chemical Reactions of Phenols

Breaking O–H vs C–O Bonds

Phenols react by breaking the O–H bond (like alcohols).
Breaking the C–O bond is very difficult — phenols do NOT undergo acid-catalyzed elimination or SN2 back-side attack.
Phenols are not easily oxidized (no H on the carbon bearing $-\text{OH}$).

Formation of Phenoxide

Phenols are more acidic than water → aqueous NaOH deprotonates phenols to phenoxide ions.
Phenol is a weaker nucleophile than alcohol (lone pairs delocalized into ring).
Phenoxide ion is a better nucleophile than phenol → reacts with acyl chlorides or anhydrides to form esters.

Electrophilic Aromatic Substitution (EAS)

$-\text{OH}$ is strongly activating and ortho-para directing.
Benzene ring in phenol is more reactive than benzene itself.
Reactions occur without Lewis acid catalyst.

Halogenation:

Non-polar solvent, low temperature: mixture of o- and p-halophenol.
Aqueous solution, higher temperature: 2,4,6-trihalophenol.
2,4,6-tribromophenol: white precipitate — used as test for phenol.

2,4,6-tribromophenol: Brc1cc(Br)c(O)c(Br)c1
2,4,6-trinitrophenol: [O-][N+](=O)c1cc(c(O)c(c1)[N+](=O)[O-])[N+](=O)[O-]

Nitration:

Dilute $\text{HNO}_3$ at room temperature: o-nitrophenol + p-nitrophenol (no catalyst needed).
Conc. $\text{HNO}_3$: 2,4,6-trinitrophenol (picric acid).

Identification Tests for Phenol

Bromine water: decolorizes rapidly; white precipitate of 2,4,6-tribromophenol.
Iron(III) chloride ($\text{FeCl}_3$): forms a light purple complex. Also positive for any compound with $-\text{OH}$ bonded to an unsaturated system (e.g. enols).

Commercial & Industrial Applications

Ethanol

Fermentation of grains (corn, wheat, rye, barley) → 12–15% ethanol.
Distillation cannot exceed 95% (minimum-boiling azeotrope at 78.15 °C).
Absolute ethanol (100%) requires dehydrating agent (e.g. anhydrous CaO).
Uses: solvent, motor fuel (Indianapolis 500 since 2006), gasohol (~10% ethanol in gasoline), antiseptic, mouthwash.
Denatured alcohol: ethanol with impurities (methanol, MIBK, aviation gasoline) to make it undrinkable and untaxed.

Methanol

Originally from destructive distillation of wood (wood alcohol).
Now synthesized from CO + $\text{H}_2$ (high T, P, catalyst).
Uses: industrial solvent, starting material for methyl ethers/esters, motor fuel (Indianapolis 500, 1965–2006).
Less flammable than gasoline; water effective against methanol fires.
Toxic: ~100 mL fatal dose (vs ~200 mL for ethanol).

Propan-2-ol (Isopropyl Alcohol)

Catalytic hydration of propylene.
Rubbing alcohol (less drying than ethanol on skin).
Effective topical antiseptic (kills microorganisms but not skin cells).

Phenol

Hydrogenation to cyclohexanol/cyclohexanone.
Key intermediate in production of nylon-6 and nylon-6,6.
Uses: textiles, plastics, airbags, carpet fibres.
Reaction: $\text{C}_6\text{H}_5\text{OH} + 3,\text{H}_2 \rightarrow (\text{CH}_2)_5\text{CHOH}$ ($\Delta G = -55.31\ \text{kJ/mol}$ at 100 °C).

Key Equations & Reagents Summary

Reaction	Reagent/Condition	Product
1° alcohol → aldehyde	PCC, $\text{CH}_2\text{Cl}_2$	Aldehyde
1° alcohol → carboxylic acid	$\text{K}_2\text{Cr}_2\text{O}_7/\text{H}^+$ or $\text{KMnO}_4/\text{H}^+$	Carboxylic acid
2° alcohol → ketone	PCC, $\text{K}_2\text{Cr}_2\text{O}_7/\text{H}^+$, $\text{KMnO}_4/\text{H}^+$	Ketone
Alcohol → alkyl chloride	$\text{SOCl}_2$, pyridine	Alkyl chloride
Alcohol → alkyl bromide	$\text{PBr}_3$	Alkyl bromide
Alcohol → alkyl iodide	$\text{P} + \text{I}_2$ (in situ)	Alkyl iodide
Alcohol → alkene	Conc. $\text{H}_2\text{SO}_4$, 180 °C	Alkene (Zaitsev)
Alcohol → ether	Conc. $\text{H}_2\text{SO}_4$, 140 °C	Symmetrical ether
Lucas test	Conc. HCl + $\text{ZnCl}_2$	Cloudy if 1°/2°/3° (rate varies)
Iodoform test	$\text{I}_2$ + NaOH	Yellow $\text{CHI}_3$ precipitate
Phenol test	$\text{Br}_2$ (aq)	White precipitate
Phenol test	$\text{FeCl}_3$ (aq)	Light purple complex

References

Lecture notes credited to Dr. Nurshafiza Shahabudin and En. Mohd Hilmi Jaafar
Prof Madya Dr. Norbani Abdullah, Dr. Hazar Bebe Mohd Ismail. (2015). Comprehensive College Chemistry (Upgraded). SAP Publications.
Wade, L. G. (2012). Organic Chemistry (8th Ed). Pearson Education.
William H. Brown et al. (2018). Organic Chemistry (8th Ed). Cengage Learning.
Favre, H. A., & Powell, W. H. (2014). Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013. Royal Society of Chemistry.