By Puan Azduwin Khasri 6th NOVEMBER 2012 ALCOHOL By Puan Azduwin Khasri 6th NOVEMBER 2012

INTRODUCTION

Reaction of Alcohol Others OXIDATION SUBSTITUTION ELIMINATION (DEHYDRATION) OXIDATION SUBSTITUTION Others ALKYL HALIDE SULFONATE ESTER KETONE ALDEHIDE CARBOXILIC ACID ALKENE

Nucleophilic substitution of Alcohol An alcohol has a strongly base leaving group (HO-) therefore alcohol cannot undergo a nucleophilic substitution reaction Convert the strongly basic leaving group (OH–) into the good leaving group, H2O (a weaker base):

Primary, secondary, and tertiary alcohols all undergo nucleophilic substitution reactions with HI, HBr, and HCl:

SN1 REACTION OF ALCOHOL Secondary and tertiary alcohols undergo SN1 reactions with hydrogen halides:

Look out for rearrangement product in the SN1 reaction of the secondary or tertiary alcohol:

SN2 REACTION OF ALCOHOL Primary alcohols undergo SN2 reactions with hydrogen halides:

When HCl is used; SN2 reaction is slower, but the rate can be increased using ZnCl2 as catalyst . ZnCl2 functions as a Lewis acid that complexes strongly with the lone-pair electrons on oxygen:

CLASS EXERCISE 1 Give the major product of each of the following reactions:

Other Methods for Converting Alcohols into Alkyl Halides Utilization of phosphorus tribromide: PYRIDINE Other phosphorus reagents can be used: PBr3, phosphorus tribromide PCl3, phosphorus trichloride PCl5, phosphorus pentachloride POCl3, phosphorus oxychloride

Activation by SOCl2 Pyridine is generally used as a solvent and also acts as a base:

Summary: Converting of Alcohols to Alkyl Halides Recommended procedures:

Converting Alcohols into Sulfonate Esters

Several sulfonyl chlorides are available to activate OH groups:

ELIMINATION REACTION OF ALCOHOL (DEHYDRATION) Dehydration of alcohol requires acid catalyst and heat Dehydration of Secondary and Tertiary Alcohols by an E1 Pathway 17

Mechanism of E1 Dehydration of an Alcohol

The major product is the most stable alkene product: The most stable alkene product has the most stable transition state

The rate of dehydration reflects the ease with which the carbocation is formed:

Look out for carbocation rearrangement:

Pinicol Rearrangement Protonate alcohol: Eliminate water: Rearrange carbocation: Deprotonate: Resonance-stabilized oxocarbocation

Ring Expansion and Contraction Mechanism for this reaction: Protonate the alcohol. Eliminate water. Rearrange carbocation to afford the more stable cyclohexane ring. Deprotonate.

Primary Alcohols Undergo Dehydration by an E2 Pathway

A Milder Way to Dehydrate an Alcohol

Oxidation of Alcohols Oxidation by chromic acid: Secondary alcohols are oxidized to ketones

Primary alcohols are oxidized to aldehydes and eventually carboxylic acids: Mechanism:

The oxidation of aldehydes to acids requires the presence of water: In the absence of water, the oxidation stops at the aldehyde: PCC, a methylene chloride–soluble reagent: No water present

A tertiary alcohol cannot be oxidized and is converted to a stable chromate ester instead: No hydrogen on this carbon Di-tert-Butyl Chromate

ETHER

Nucleophilic substitution reaction of Ether Ethers, like alcohols, can be activated by protonation: Ether can undergo nucleophilic substitution with HBr and HI only (HCl cannot be used because Cl- too poor nucleophile

Ether cleavage: an SN1 reaction:

Reagents such as SOCl2 and PCl3 can activate alcohols but not ethers Ethers are frequently used as solvents because only they react with hydrogen halides

Nucleophilic Substitution Reactions of Epoxides Acidic condition; HBr: Aqueous acid:

Reaction of an epoxide in different substituent Regioselectivity: Mechanism:

Neutral or Basic condition: When a nucleophile attacks an unprotonated epoxide, the reaction is a pure SN2 reaction: Therefore:

Epoxides Are Synthetically Useful Reagents Enantiomers

CLASS EXERCISE 2 Give the major product of the following reactions:

THE END