§1 · Preparation from Alkenes
Most important industrial and laboratory routes — alkenes are cheap, abundant starting materials
🟠 Acid-Catalysed Hydration (H₂SO₄ / H₂O)
R–CH=CH₂ + H₂O ──conc. H₂SO₄, Δ──→ R–CHOH–CH₃
Markovnikov addition: OH goes to more substituted C
Mechanism: H⁺ protonates alkene → 2°/3° carbocation → H₂O attacks
Rearrangements possible via carbocation
Gives Markovnikov alcohol
🔵 Oxymercuration-Demercuration
Step 1: R–CH=CH₂ + Hg(OAc)₂ / H₂O → Markovnikov addition
Step 2: NaBH₄ / NaOH → R–CHOH–CH₃
Markovnikov alcohol; NO rearrangement
Bridged mercurinium ion intermediate (like halonium)
Anti addition to alkene; stereospecific
🟢 Hydroboration-Oxidation
Step 1: R–CH=CH₂ + BH₃·THF → R–CH₂–CH₂–BH₂ (syn addition)
Step 2: H₂O₂ / NaOH → R–CH₂–CH₂OH
Anti-Markovnikov alcohol; syn addition; NO rearrangement
B goes to less hindered C; retention of configuration
9-BBN for bulky/selective hydroboration
🟣 Hydroxylation (cis-diol)
R–CH=CH₂ + OsO₄ (cat.) / NMO or KMnO₄ (cold, dil.) → cis-1,2-diol
Syn addition of two –OH groups (both on same face)
OsO₄/NMO: Upjohn oxidation; better yield and control
Cold, dil. KMnO₄: older method; gives syn diol (Baeyer's reagent turns colourless)
🔴 Wacker Oxidation (Alkene → Ketone / Aldehyde)
Terminal alkene + O₂ ──PdCl₂/CuCl₂, H₂O──→ methyl ketone (Markovnikov)
CH₂=CH₂ → CH₃CHO (acetaldehyde) — industrial production of acetaldehyde
R–CH=CH₂ → R–CO–CH₃ (methyl ketone) — useful for 2° alcohol synthesis after reduction
Acid hydration:
CH₃CH=CH₂ + H₂O ──H₂SO₄──→ CH₃CHOHCH₃ (propan-2-ol, Markovnikov)
Hydroboration-oxidation:
CH₃CH=CH₂ + BH₃·THF → CH₃CH₂CH₂–B ──H₂O₂/NaOH──→ CH₃CH₂CH₂OH (propan-1-ol, anti-Markovnikov)
Oxymercuration:
CH₃CH=CH₂ + Hg(OAc)₂/H₂O → adduct ──NaBH₄──→ CH₃CHOHCH₃ (propan-2-ol, no rearrangement)
§8 · All Reactions of Alcohols
8.1 · Reaction with Active Metals (Acidic Nature) → Alkoxide + H₂
2 R–OH + 2Na → 2 R–ONa (sodium alkoxide) + H₂↑
2 R–OH + 2K → 2 R–OK + H₂↑
Rate with Na: CH₃OH > 1° > 2° > 3° (higher s-character / less electron density)
Reaction vigour: K > Na (K reacts more vigorously with lower alcohols)
Alkoxides (RO⁻Na⁺) are strong bases used in Williamson ether synthesis
2 C₂H₅OH + 2Na → 2 C₂H₅ONa + H₂↑ (sodium ethoxide)
2 (CH₃)₃COH + 2K → 2 (CH₃)₃COK + H₂↑ (potassium t-butoxide)
8.2 · Esterification — Reaction with Acids
Fischer Esterification: R–OH + R'COOH ⇌ R'COOR + H₂O (H₂SO₄ cat., Δ, reversible)
Mechanism: nucleophilic acyl substitution; OH of acid leaves, not alcohol
Equilibrium driven right by: excess alcohol, remove water (Dean-Stark trap), or excess acid
With Acid Chloride: R–OH + R'COCl → R'COOR + HCl (fast, irreversible)
With Anhydride: R–OH + (R'CO)₂O → R'COOR + R'COOH (acetylation of –OH)
Fischer:
C₂H₅OH + CH₃COOH ──H₂SO₄, Δ──→ CH₃COOC₂H₅ + H₂O (ethyl acetate)
Acid chloride:
C₂H₅OH + CH₃COCl ──pyridine──→ CH₃COOC₂H₅ + HCl (fast, no catalyst)
Anhydride:
C₂H₅OH + (CH₃CO)₂O → CH₃COOC₂H₅ + CH₃COOH (acetic anhydride)
8.3 · Dehydration — Reaction with Conc. H₂SO₄
At 170°C (excess acid, single alcohol): R–OH → alkene (E1/E2; Zaitsev product)
At 140°C (two molecules alcohol): 2 R–OH → R–O–R + H₂O (ether; SN₂)
Order of dehydration ease: 3° > 2° > 1° (carbocation stability)
Rearrangements possible with 2° carbocations → skeletal rearrangement
Al₂O₃ at 350°C also dehydrates to alkene (heterogeneous, no rearrangement)
Dehydration to alkene (170°C):
C₂H₅OH + H₂SO₄ ──170°C──→ CH₂=CH₂ + H₂O (ethylene)
(CH₃)₂CHOH ──H₂SO₄, Δ──→ CH₃CH=CH₂ (propene, Zaitsev)
Ether formation (140°C):
2 C₂H₅OH ──H₂SO₄, 140°C──→ C₂H₅–O–C₂H₅ + H₂O (diethyl ether)
8.4 · Conversion to Alkyl Halides
HX (Lucas test): R–OH + HX → R–X + H₂O | 3° immediate; 2° slow; 1° no reaction without Δ
SOCl₂: R–OH + SOCl₂ ──pyridine──→ R–Cl + SO₂ + HCl (inversion)
PBr₃: 3R–OH + PBr₃ → 3R–Br + H₃PO₃ (inversion)
PCl₅: R–OH + PCl₅ → R–Cl + POCl₃ + HCl
(CH₃)₃COH + HCl ──ZnCl₂──→ (CH₃)₃CCl + H₂O (3°, instant)
CH₃CH₂OH + SOCl₂ ──pyridine──→ CH₃CH₂Cl + SO₂ + HCl
3 (CH₃)₂CHOH + PBr₃ → 3 (CH₃)₂CHBr + H₃PO₃
8.5 · Oxidation — Most Tested Reaction
1° Alcohol: → Aldehyde (with PCC, PDC, Swern, MnO₂) OR → Carboxylic acid (with KMnO₄, K₂Cr₂O₇/H⁺, Jones, CrO₃)
2° Alcohol: → Ketone only (all oxidants give same product)
3° Alcohol: NOT oxidised under normal conditions (no α-H); only by very harsh conditions (conc. HNO₃ with C–C cleavage)
| Oxidant | 1° Alcohol Gives | 2° Alcohol Gives | Notes |
|---|
| PCC (pyridinium chlorochromate) | Aldehyde (stops here) | Ketone | CH₂Cl₂; mild; no over-oxidation |
| PDC (pyridinium dichromate) | Aldehyde (mild) | Ketone | Less acidic than PCC; sensitive substrates |
| Swern Oxidation (DMSO/oxalyl chloride) | Aldehyde | Ketone | –78°C; no over-oxidation; sulfur odour |
| MnO₂ (activated) | Aldehyde | Ketone | Selective: allylic/benzylic alcohols only |
| K₂Cr₂O₇ / H₂SO₄ (Jones) | Carboxylic acid | Ketone | Acidic; harsh; also oxidises aldehydes |
| KMnO₄ (hot, conc.) | Carboxylic acid | Ketone | Alkaline: gives carboxylate salt |
| CrO₃ / H₂SO₄ (Jones reagent) | Carboxylic acid | Ketone | Standard for lab-scale oxidation |
| Tollens' / Fehling's | Carboxylic acid (aldehyde detected) | No reaction | Used to distinguish 1° from 2°/3° |
PCC:
CH₃CH₂CH₂OH ──PCC/CH₂Cl₂──→ CH₃CH₂CHO (propanal, aldehyde — stopped)
KMnO₄ (hot):
CH₃CH₂CH₂OH ──KMnO₄/H⁺──→ CH₃CH₂COOH (propanoic acid)
2° oxidation:
(CH₃)₂CHOH ──K₂Cr₂O₇/H₂SO₄──→ (CH₃)₂CO (acetone, ketone)
8.6 · Williamson Ether Synthesis
R–OH + NaH → R–ONa (alkoxide) + H₂ (NaH deprotonates alcohol)
R–ONa + R'–X → R–O–R' + NaX (SN₂)
R'–X must be 1° (or methyl) — 2° and 3° give elimination with alkoxide base
Unsymmetrical ethers: choose which R gets Na (less hindered) and which R' gets X (1°)
CH₃OH + NaH → CH₃ONa + H₂
CH₃ONa + C₂H₅Br → CH₃–O–C₂H₅ + NaBr (methyl ethyl ether)
For (CH₃)₃C–O–CH₃:
Use CH₃ONa + (CH₃)₃CBr → WRONG (3°, gives elimination)
Use (CH₃)₃CONa + CH₃Br → CORRECT (CH₃Br is 1°)
8.7 · Reaction with Phosphorus Compounds → Esters of Phosphoric Acid
R–OH + PCl₅ → R–Cl + POCl₃ + HCl (halide)
3 R–OH + POCl₃ → (RO)₃P=O (trialkyl phosphate) + 3HCl
Phosphate esters biologically important (DNA, ATP backbone)
Dialkyl phosphates: nerve agent precursors — handle with care
8.8 · Reaction with HNO₃ / HNO₂ → Nitrate / Nitrite Esters
R–OH + HONO₂ (HNO₃) ──H₂SO₄──→ R–O–NO₂ (nitrate ester) + H₂O
R–OH + HONO (HNO₂) → R–O–NO (nitrite ester)
Glycerol + 3 HNO₃ → glyceryl trinitrate (nitroglycerin, explosive)
Cellulose + HNO₃ → nitrocellulose (guncotton)
Amyl nitrite (R–ONO): vasodilator, used in angina
C₃H₅(OH)₃ + 3HNO₃ ──H₂SO₄──→ C₃H₅(ONO₂)₃ + 3H₂O (nitroglycerin)
8.9 · Tosylation (Activation of –OH) → Tosylate (R–OTs)
R–OH + TsCl (tosyl chloride) ──pyridine──→ R–OTs + HCl
R–OTs is an excellent leaving group (TsO⁻ is weak base, stable anion)
Configuration at C is retained during tosylation (O–H broken, C–O intact)
R–OTs then undergoes SN₂ (inversion) or SN₁ (racemisation)
Overall: R–OH → R–OTs → R–Nu with net inversion (via two steps)
(R)-butan-2-ol ──TsCl/pyridine──→ (R)-butan-2-yl tosylate [O–H broken, retention at C]
(R)-OTs + NaBr ──DMSO──→ (S)-2-bromobutane [SN₂, inversion]
8.10 · Periodic Acid Cleavage of Vicinal Diols
1,2-diol (vicinal) + HIO₄ → 2 carbonyl compounds + HIO₃ + H₂O
Each carbon of the diol becomes a separate carbonyl (aldehyde or ketone)
1° C of diol → RCHO (aldehyde); 2° C of diol → R₂CO (ketone); 3° C → CO₂
Pb(OAc)₄ (lead tetraacetate): same cleavage, used in non-aqueous conditions
Each C–C bond between the two OH groups is cleaved
CH₂OH–CHOH–CH₂OH + 2HIO₄ → 2HCHO + OHC–CHO + 2HIO₃ + 2H₂O
(glycerol gives 2 formaldehyde + glyoxal)
(CH₃)₂C(OH)–CH(OH)–CH₃ + HIO₄ → (CH₃)₂CO + CH₃CHO (acetone + acetaldehyde)
8.11 · Victor Meyer Test (Distinguishes 1°, 2°, 3°)
Step 1: R–OH + P (red) + I₂ → R–I (convert to iodide in situ)
Step 2: R–I + AgNO₂ → R–NO₂ (nitroalkane)
Step 3: R–NO₂ + HNO₂ ──then NaOH──→ colour
1°: blood-red colour (nitrolic acid formed)
2°: blue / indigo colour (pseudo-nitrole)
3°: no colour (no α-H; cannot form coloured product)
8.12 · Iodoform Test (CH₃CO– or CH₃CHOH– group)
R–CHOH–CH₃ or CH₃CHO or CH₃COCH₃ + I₂ + NaOH → CHI₃↓ (iodoform, yellow ppt)
Alcohols that give iodoform: ethanol (CH₃CH₂OH), secondary methyl carbinols (R–CHOH–CH₃)
Methanol does NOT give iodoform
Positive test: yellow precipitate of CHI₃ with antiseptic smell
Also detects the CH₃CO– group (acetaldehyde, acetone, methyl ketones)
CH₃CH₂OH + I₂ + NaOH → CHI₃↓ + HCOONa + NaI + H₂O (iodoform, positive)
CH₃OH (methanol): NO iodoform (does NOT have CH₃–CHOH group)
CH₃CHOH–C₂H₅ (butan-2-ol): positive (has CH₃–CHOH)
8.13 · Lucas Test (ZnCl₂ + conc. HCl — Distinguishes 1°, 2°, 3°)
R–OH + HCl ──ZnCl₂──→ R–Cl (turbidity due to insoluble R–Cl in HCl layer)
3°: immediate turbidity (SN₁, carbocation formed instantly)
2°: turbidity in 5 min (SN₁, slower)
1°: no turbidity at room temperature (SN₂ too slow; needs heating)
Test valid only for C₄–C₆ alcohols (soluble in Lucas reagent; higher are insoluble)
8.14 · Reaction with Na₂CO₃ / NaHCO₃
Alcohols do NOT react with Na₂CO₃ or NaHCO₃ (pKa too high; too weak as acid)
Phenol reacts with Na₂CO₃ (Na₂CO₃ strong enough) but NOT with NaHCO₃
Carboxylic acids react with BOTH Na₂CO₃ AND NaHCO₃ (with effervescence of CO₂)
This is used to distinguish: acid vs phenol vs alcohol
8.15 · Catalytic Dehydrogenation
1° R–CH₂OH ──Cu, 300°C──→ RCHO + H₂ (aldehyde)
2° R₂CHOH ──Cu, 300°C──→ R₂CO + H₂ (ketone)
Industrial: ethanol → acetaldehyde (dehydrogenation by Cu)
3° alcohol: no α-H → dehydration to alkene instead
CH₃CH₂OH ──Cu, 300°C──→ CH₃CHO + H₂ (acetaldehyde, industrial)
(CH₃)₂CHOH ──Cu, Δ──→ (CH₃)₂CO + H₂ (acetone)