Reactions of Alcohols – Oxidation, Substitution, and Related Transformations

Reactions of Alcohols

Types of Alcohol Reactions

Alcohols are versatile organic compounds due to the reactivity of the hydroxy group, which can be transformed into a wide variety of functional groups. The main types of reactions alcohols undergo include:

• Dehydration to form alkenes

• Oxidation to aldehydes, ketones, or carboxylic acids

• Substitution to form alkyl halides

• Reduction to alkanes

• Esterification to form esters

• Tosylation to form tosylates

• Williamson synthesis to form ethers

Type of Reaction	Alcohol (R–OH)	Product
Dehydration	R–OH	Alkene (R=R)
Oxidation	R–OH	Aldehyde, ketone, acid
Substitution	R–OH	R–X (alkyl halide)
Reduction	R–OH	R–H (alkane)
Esterification	R–OH	R–O–C=O (ester)
Tosylation	R–OH	R–OTs (tosylate)
Williamson Synthesis	R–OH	R–O–R' (ether)

Oxidation States of Alcohols and Related Functional Groups

Definitions and Principles

• Oxidation (inorganic): Loss of electrons

• Reduction (inorganic): Gain of electrons

• Oxidation (organic): Gain of O, O2, X2 or loss of H2

• Reduction (organic): Gain of H2 (or H−), loss of O or O2, or loss of X2

• Gain or loss of H+, H2O, OH−, HX, etc. is neither oxidation nor reduction

Alcohols are more oxidized than alkanes but less oxidized than carbonyl compounds (ketones, aldehydes, acids).

Oxidation of Alcohols

General Overview

• Alcohol oxidations commonly form aldehydes, ketones, and carboxylic acids.

• 1° alcohol → aldehyde → carboxylic acid

• 2° alcohol → ketone

• 3° alcohols are generally not oxidizable under standard conditions

• Common oxidants: Chromium(VI) compounds (e.g., Na2Cr2O7, CrO3), potassium permanganate, nitric acid, sodium hypochlorite (NaOCl)

Mechanism Example: Oxidation of Secondary Alcohol by Bleach (NaOCl)

• Protonation of hypochlorite forms a reactive intermediate

• Formation of an alkyl hypochlorite derivative

• Elimination of HCl oxidizes the carbon and reduces Cl

Selective Oxidation with TEMPO

• NaOCl with TEMPO (a stable free radical) selectively oxidizes primary alcohols to aldehydes

• Excess NaOCl with TEMPO oxidizes primary alcohols to carboxylic acids

Oxidation of Secondary Alcohols

• Secondary alcohols are easily oxidized to ketones

• Traditional oxidants: CrO3, Na2Cr2O7 in H2SO4 (chromic acid)

• Chromium-based reagents are toxic; NaOCl/acetic acid is a safer alternative

Chromic Acid Oxidation Mechanism

• Formation of chromate ester intermediate

• Elimination yields oxidized product and reduced chromium(III)

• Color change (orange to green/blue) indicates oxidation progress

Oxidation of Primary Alcohols

• Primary alcohols oxidize to aldehydes, then to carboxylic acids

• Chromic acid is too strong to stop at the aldehyde stage

Pyridinium Chlorochromate (PCC)

• PCC is used for selective oxidation of primary alcohols to aldehydes and secondary alcohols to ketones

• Does not over-oxidize to carboxylic acids

Oxidation of Tertiary Alcohols

• Tertiary alcohols lack a hydrogen on the carbon bearing the OH group, making oxidation difficult

• Chromic acid test distinguishes between primary/secondary (positive) and tertiary (negative) alcohols

Additional Oxidizing Methods

• Collins reagent: Selectively oxidizes primary alcohols to aldehydes

• Jones reagent: Oxidizes primary alcohols to acids, secondary to ketones

• Potassium permanganate and nitric acid: Strong oxidants for secondary alcohols (to ketones) and primary alcohols (to acids)

Swern Oxidation

• Uses DMSO and oxalyl chloride at low temperature, followed by a base (e.g., triethylamine)

• Converts alcohols to aldehydes or ketones under mild conditions

Dess–Martin Periodinane (DMP)

• Oxidizes primary alcohols to aldehydes and secondary alcohols to ketones

• Operates under mild, neutral conditions with high yields

To Oxidize	Product	Chromium-Free Reagent	Chromium Reagent
2° alcohol	ketone	NaOCl/HOAc, Swern, DMP	chromic acid (or PCC)
1° alcohol	aldehyde	NaOCl-TEMPO, Swern, DMP	PCC
1° alcohol	carboxylic acid	NaOCl (excess)-TEMPO	chromic acid

Alcohols as Nucleophiles and Electrophiles

Alcohols as Nucleophiles

• Alcohols can be deprotonated to form alkoxide ions, which are strong nucleophiles

• Alkoxide ions attack weaker electrophiles in substitution reactions

Alcohols as Electrophiles

• Alcohols are weak electrophiles due to poor leaving ability of the OH group

• Protonation of the OH group (to form H2O) makes it a good leaving group

• HBr reacts with primary alcohols via SN2, with secondary/tertiary via SN1

Conversion to Tosylates

• Alcohols can be converted to tosylate esters (ROTs) using p-toluenesulfonic acid (TsOH)

• Tosylates are excellent leaving groups, allowing for substitution and elimination reactions

Reaction	Product
R–OTs + OH−	R–OH + OTs−
R–OTs + CN−	R–CN + OTs−
R–OTs + Br−	R–Br + OTs−
R–OTs + R'O−	R–O–R' + OTs−
R–OTs + NH3	R–NH2 + OTs−
R–OTs + LiAlH4	R–H + OTs−

Reduction of Alcohols

• Alcohols can be reduced by dehydration to alkenes (acid-catalyzed), then hydrogenation to alkanes

• Alternatively, convert to tosylate, then reduce with LiAlH4

Reactions of Alcohols with Acids

• Protonation of the hydroxyl group by acid converts it into a good leaving group (H2O)

• Allows for substitution (to alkyl halide) or elimination (to alkene)

Reaction with HBr

• OH is protonated, becomes a good leaving group

• 3° and 2° alcohols react via SN1; 1° alcohols via SN2

SN1 and SN2 Mechanisms

• SN1: Protonation → carbocation formation → nucleophilic attack

• SN2: Protonation → direct nucleophilic attack with inversion of configuration

Reaction with HCl (Lucas Reagent)

• HCl and ZnCl2 (Lucas reagent) convert alcohols to alkyl chlorides

• 1° alcohols react slowly (SN2), 2° in 1–5 min, 3° in less than 1 min (SN1)

Limitations of HX Reactions

• Poor yields with 1° and 2° alcohols

• Elimination competes with substitution

• Carbocation rearrangements possible

Reactions with Phosphorus Halides

• Phosphorus tribromide (PBr3), trichloride (PCl3), and pentachloride (PCl5) convert alcohols to alkyl halides

• Good yields with 1° and 2° alcohols

• PBr3 forms alkyl bromides, PCl3/PCl5 form alkyl chlorides, PI3 forms alkyl iodides (unstable)

Mechanism with PBr3

• Step 1: Oxygen attacks phosphorus, displacing a bromide ion

• Step 2: Bromide attacks the alkyl group (SN2)

Summary Table: Alcohol to Alkyl Halide Conversion

Alcohol	Reagent	Product
1° or 2°	PBr3	R–Br
1° or 2°	PCl3, PCl5	R–Cl
1° or 2°	PI3	R–I

Additional info:

• These notes cover the core content of "Reactions of Alcohols" as found in a standard Organic Chemistry II course, including mechanisms, reagents, and synthetic applications.