Difficulty: Intermediate | Prerequisites: Chapter 7 (SN1, SN2, E1, E2 mechanisms), Part 1 of these notes (nomenclature, properties, acidity)
Big picture: Alcohols are poor leaving groups on their own. The entire theme of this section is how to convert the -OH into something that can leave, whether by protonation with acid, reaction with PBr₃ or SOCl₂, or conversion to a sulfonate ester. Once you have a good leaving group, substitution and elimination follow the same rules from Chapter 7. The section ends with oxidation, which converts alcohols to aldehydes, ketones, or carboxylic acids depending on the reagent and the alcohol class.
Alcohols are poor leaving groups, so to make them react via substitution or elimination you first need to convert -OH into something better. You can protonate it with HX, swap it using PBr₃ or SOCl₂, or turn it into a sulfonate ester (tosylate, mesylate). Dehydration with acid and heat gives alkenes (watch for carbocation rearrangements). Oxidation with chromic acid gives the "full" oxidation product; PCC stops at the aldehyde for primary alcohols.
Leaving group
The group that departs with the bonding electrons during a substitution or elimination. -OH is a poor leaving group; -OH₂⁺ (water), -OTs, and -OMs are good leaving groups.
SN1 (unimolecular nucleophilic substitution)
A two-step mechanism: the leaving group departs first to form a carbocation, then a nucleophile attacks. Favoured by tertiary substrates.
SN2 (bimolecular nucleophilic substitution)
A one-step mechanism: the nucleophile attacks while the leaving group departs simultaneously, in a backside attack. Favoured by primary (and some secondary) substrates. Produces inversion of stereochemistry.
E1 (unimolecular elimination)
A two-step mechanism: leaving group departs to form a carbocation, then a base removes a proton from an adjacent carbon to form the alkene. Favoured by tertiary and secondary substrates under acidic conditions with heat.
E2 (bimolecular elimination)
A one-step mechanism: a strong base removes a proton while the leaving group departs simultaneously, forming an alkene. Requires anti-periplanar geometry of the H and leaving group.
Tosylate (OTs)
A sulfonate ester leaving group derived from p-toluenesulfonyl chloride. Stabilised by resonance across three oxygens and sulfur. pKa of the conjugate acid is about -2.6.
Mesylate (OMs)
A sulfonate ester leaving group derived from methanesulfonyl chloride. Similar stability and reactivity to tosylate.
Carbocation rearrangement
A 1,2-hydride shift or 1,2-alkyl shift that converts a less stable carbocation (2°) to a more stable one (3°). Common in E1 and SN1 reactions.
Pinacol rearrangement
Acid-catalysed rearrangement of a vicinal diol (1,2-diol) to a ketone, involving a 1,2-alkyl shift to a carbocation stabilised by an adjacent oxygen.
PCC (pyridinium chlorochromate)
A mild chromium-based oxidising agent (CrO₃, HCl, pyridine). Oxidises primary alcohols to aldehydes and secondary alcohols to ketones. Does not over-oxidise primary alcohols to carboxylic acids.
Jones oxidation (chromic acid, H₂CrO₄)
A strong chromium-based oxidation using CrO₃, H₂SO₄, H₂O. Oxidises primary alcohols all the way to carboxylic acids and secondary alcohols to ketones.
Oxidation (in organic chemistry)
Either a loss of H₂ or a gain of oxygen (or both). In simple terms, adding bonds to oxygen or removing bonds to hydrogen at the carbon of interest.
The central problem: -OH is a poor leaving group. Every method below solves this by converting it into something better.
The mechanism depends on the alcohol's class:
Tertiary alcohols follow SN1. Step 1: the alcohol (acting as base) is protonated by HX, converting -OH to -OH₂⁺ (water, a good leaving group). Step 2: water leaves, forming a tertiary carbocation. Step 3: the halide ion (nucleophile) attacks the carbocation.
Primary alcohols follow SN2. Step 1: protonation of -OH to -OH₂⁺. Step 2: the halide ion attacks the carbon bearing -OH₂⁺ in a concerted backside attack, displacing water.
Secondary alcohols can go by either SN1 or SN2, depending on the specific substrate and conditions.
The key insight: protonation converts -OH (poor leaving group) into -OH₂⁺ (good leaving group, since water is stable and neutral).
Converts alcohols to alkyl bromides via an SN2-type mechanism. Works best on primary and secondary alcohols.
Step 1: The alcohol oxygen (nucleophile) attacks the electrophilic phosphorus of PBr₃, displacing Br⁻. This creates a good leaving group (an -O-PBr₂ species).
Step 2: Br⁻ (nucleophile) attacks the carbon in a backside SN2, displacing the phosphorus-containing leaving group.
Because the mechanism is SN2, expect inversion of configuration at the carbon.
Converts alcohols to alkyl chlorides via an SN2-type mechanism. Requires a base (typically Et₃N, triethylamine).
Step 1: The alcohol oxygen (nucleophile) attacks the electrophilic sulfur of SOCl₂, displacing Cl⁻. This creates a chlorosulfite intermediate with a good leaving group.
Step 2: Et₃N (base) deprotonates the intermediate.
Step 3: Cl⁻ (nucleophile) attacks the carbon in an SN2, displacing the chlorosulfite leaving group along with SO₂ and Cl⁻.
The departure of SO₂ gas helps drive the reaction forward.
Electrons flow from nucleophile to electrophile in every step. When drawing mechanisms, always show the curved arrows moving from the electron-rich species toward the electron-poor one.
Sulfonate esters (tosylates and mesylates) are excellent leaving groups, stabilised by resonance across three oxygen atoms and the sulfur. The conjugate acid of a sulfonate has a pKa of about -2.6, which tells you these anions are extremely stable and therefore very willing to leave.
React the alcohol with a sulfonyl chloride (TsCl for tosylates, MsCl for mesylates) in the presence of a base such as Et₃N:
Step 1: The alcohol oxygen (nucleophile) attacks the electrophilic sulfur of the sulfonyl chloride, displacing Cl⁻.
Step 2: Et₃N deprotonates the intermediate to give the sulfonate ester product.
The carbon-oxygen bond is not broken during this step. The stereochemistry at carbon is retained because no bond to carbon is made or broken.
Once the sulfonate is in place, the molecule behaves like any good SN2 substrate (for primary and secondary). A nucleophile attacks the carbon bearing the -OTs or -OMs group, displacing the sulfonate in a backside attack.
This means the overall two-step sequence (alcohol to sulfonate, then sulfonate displaced by nucleophile) produces inversion at carbon:
Alcohol to sulfonate: retention (no bond to carbon broken).
Sulfonate displaced by nucleophile: inversion (SN2 backside attack).
Net result: inversion of configuration at that carbon.
Converting -OH to -OTs or -OMs lets you do substitutions and eliminations without needing acid, which means you can use strong bases (such as alkoxides) to promote E2 elimination. This avoids the carbocation rearrangements that plague acid-catalysed methods.
Heating an alcohol with a strong acid (typically H₂SO₄) removes water to form an alkene. The product follows Zaitsev's rule: the more substituted double bond is favoured because it is more stable.
Step 1: Protonation. The alcohol oxygen (base) picks up a proton from H₃O⁺ or H₂SO₄ (acid), converting -OH into -OH₂⁺, a good leaving group.
Step 2: Loss of water. The -OH₂⁺ departs, generating a carbocation.
Step 3: Deprotonation. A base (often water or another alcohol molecule) removes a proton from a carbon adjacent to the carbocation, forming the C=C double bond.
The most substituted alkene is the major product.
Primary alcohols undergo dehydration slowly because a primary carbocation is too unstable to form. Instead, after protonation of -OH to -OH₂⁺, a base removes an adjacent proton in a concerted step with the departure of water (E2). This is slower than the E1 path available to tertiary and secondary alcohols.
Whenever a carbocation forms (E1 pathway), it can rearrange if a more stable carbocation is accessible:
1,2-hydride shift: A hydrogen with its bonding electrons migrates from an adjacent carbon to the carbocation centre, converting a 2° carbocation to a 3° one.
1,2-alkyl shift: An entire alkyl group with its bonding electrons migrates, again to form a more stable carbocation.
The rearranged carbocation then loses a proton to give a product whose carbon skeleton has changed. This is a common source of "unexpected" products on exams.
A special case involving vicinal diols (1,2-diols). Under acid conditions:
Step 1: One -OH is protonated and water leaves, forming a 3° carbocation stabilised by the adjacent -OH.
Step 2: A 1,2-alkyl shift moves an adjacent group to the carbocation centre.
Step 3: The oxygen lone pair donates into the positive centre, forming an oxocarbenium ion (stabilised by resonance). Oxygen fulfils its octet this way.
Step 4: Deprotonation gives a ketone product.
The classic example is pinacol (2,3-dimethylbutane-2,3-diol) rearranging to pinacolone (3,3-dimethylbutan-2-one).
If you want to dehydrate an alcohol without risking carbocation rearrangements, first convert the -OH to a good leaving group (such as -OMs) under non-acidic conditions, then treat the sulfonate with a strong base (such as t-BuO⁻). The E2 mechanism proceeds in one concerted step with no carbocation intermediate, so no rearrangement can occur.
Oxidation in organic chemistry means either gaining bonds to oxygen or losing bonds to hydrogen (loss of H₂). What an alcohol oxidises to depends on its class and the reagent used.
Alcohol class | Reagent | Product |
|---|---|---|
Primary (1°) | H₂CrO₄ (Jones) | Carboxylic acid |
Primary (1°) | PCC | Aldehyde |
Secondary (2°) | H₂CrO₄ (Jones) | Ketone |
Secondary (2°) | PCC | Ketone |
Tertiary (3°) | Any oxidant | No reaction |
Chromic acid is made from CrO₃ + H₂SO₄ + H₂O. It is a strong oxidant:
Primary alcohols are oxidised first to an aldehyde, then further to a carboxylic acid. The aqueous acidic conditions drive the second oxidation.
Secondary alcohols are oxidised to ketones. No further oxidation is possible because the ketone carbon has no remaining C-H bond to lose.
PCC is a milder, selective oxidant (CrO₃ + HCl + pyridine). The pyridinium counterion and the anhydrous conditions prevent over-oxidation:
Primary alcohols are oxidised to aldehydes and stop there.
Secondary alcohols are oxidised to ketones.
This selectivity makes PCC the reagent of choice when you want an aldehyde from a primary alcohol.
Tertiary alcohols cannot be oxidised under standard conditions. There is no hydrogen on the carbon bearing the -OH, so no C-H bond is available to be lost. If you see a tertiary alcohol with an oxidant, the answer is "no reaction."
Oxidation of alcohols is one of the most important transformations in both laboratory and industrial chemistry. Ethanol is oxidised to acetaldehyde and then acetic acid in vinegar production. In biochemistry, alcohol dehydrogenase enzymes catalyse similar oxidations in metabolism, which is how your body processes ethanol.
Students often think -OH can leave directly in substitution reactions. It cannot. -OH must be converted to a better leaving group (protonated, turned into a sulfonate, etc.) before substitution or elimination can proceed.
Students frequently confuse PCC and Jones oxidation outcomes for primary alcohols. PCC stops at the aldehyde. Jones (chromic acid) goes all the way to the carboxylic acid. For secondary alcohols, both give the same product (ketone).
When drawing E1 dehydration mechanisms, students forget to look for possible 1,2-shifts. If the initial carbocation can rearrange to a more stable one, it will. Always check.
Students assume that converting an alcohol to a tosylate or mesylate breaks the C-O bond. It does not. The C-O bond stays intact during sulfonate formation; only the O-H bond is replaced by the O-S bond. The C-O bond is broken later, when a nucleophile displaces the sulfonate.
⚠️ You will be asked to convert an alcohol to a specific alkyl halide and choose the correct reagent (HX vs PBr₃ vs SOCl₂). Know which mechanism each uses and which alcohol classes each works best on.
⚠️ Stereochemistry questions are very common: SN2 with PBr₃, SOCl₂, or sulfonate displacement gives inversion. SN1 with HX on a tertiary alcohol gives racemisation.
⚠️ Dehydration problems will test whether you can predict the major product (Zaitsev's rule) and whether a rearrangement occurs. Draw the full mechanism, including any 1,2-shift.
⚠️ Expect a question asking you to choose between PCC and Jones oxidation. "Give me the aldehyde" means PCC. "Give me the carboxylic acid" means Jones.
⚠️ The pinacol rearrangement is a favourite exam question because it combines protonation, leaving group departure, 1,2-alkyl shift, and resonance stabilisation in one problem.
True or false: PBr₃ converts a primary alcohol to an alkyl bromide via an SN1 mechanism. (False. PBr₃ uses an SN2 mechanism.)
Fill in the blank: Acid-catalysed dehydration of a tertiary alcohol follows an ___ mechanism. (E1)
True or false: PCC oxidises a primary alcohol to a carboxylic acid. (False. PCC stops at the aldehyde.)
Fill in the blank: Converting an alcohol to a tosylate and then displacing the tosylate with a nucleophile gives overall ___ of configuration. (inversion)
True or false: Tertiary alcohols can be oxidised to ketones under standard conditions. (False. No reaction occurs.)
Q: A secondary alcohol is treated with SOCl₂ and Et₃N. What is the product, and what is the mechanism?
A: The product is the corresponding secondary alkyl chloride. The mechanism is SN2-type: the alcohol attacks SOCl₂ to form a chlorosulfite intermediate, Et₃N deprotonates, and then Cl⁻ displaces the chlorosulfite leaving group in a backside attack, giving inversion of configuration.
Q: 2-methylbutan-2-ol is treated with H₂SO₄ and heated. Draw the major product.
A: The major product is 2-methylbut-2-ene. The tertiary alcohol undergoes E1 dehydration: protonation, loss of water to form a 3° carbocation, then loss of a proton to give the most substituted alkene (Zaitsev product). No rearrangement is needed because the carbocation is already tertiary.
Q: 3,3-dimethylbutan-2-ol is treated with H₂SO₄ and heated. The major product has a different carbon skeleton from the starting material. Explain.
A: After protonation and loss of water, a 2° carbocation forms. A 1,2-methyl shift converts it to a more stable 3° carbocation (the methyl migrates from the adjacent quaternary carbon). Deprotonation then gives 2,3-dimethylbut-2-ene as the major product, which has a rearranged skeleton.
Q: You need to convert 1-butanol to butanal (an aldehyde). Which reagent do you choose, and why?
A: PCC. It oxidises primary alcohols to aldehydes without over-oxidising to the carboxylic acid. Jones oxidation (H₂CrO₄) would give butanoic acid instead.
Q: An (S)-configured secondary alcohol is converted to the mesylate with MsCl/Et₃N, then treated with NaCN. What is the configuration of the product?
A: (R). The mesylate formation retains configuration at carbon (no C-O bond broken). The subsequent SN2 displacement by CN⁻ gives inversion. Retention followed by inversion gives overall inversion: S becomes R.
This connects directly to Chapter 7's SN1, SN2, E1, and E2 mechanisms. The same rules apply (substrate class, nucleophile/base strength, solvent), the difference being that alcohols need an extra activation step. It also connects forward to carbonyl chemistry (Chapters 18-21), where the aldehydes, ketones, and carboxylic acids produced by oxidation become the starting materials for a huge range of further transformations.
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