Chapter 07

Alcohols and Ethers

 IUPAC Substitutive Nomenclature
 An IUPAC name may have up to 4 features: locants, prefixes,
parent compound and suffixes
 Numbering generally starts from the end of the chain which is
closest to the group named in the suffix

 IUPAC Nomenclature of Alcohols

 Select the longest chain containing the hydroxyl and change the
suffix name of the corresponding parent alkane from -ane to -ol
 Number the parent to give the hydroxyl the lowest possible
number
 The other substituents take their locations accordingly

Chapter 7 2
 Examples

 Common Names of simple alcohols are still often used and are
approved by IUPAC

Chapter 7 3
 Alcohols with two hydroxyls are called diols in IUPAC
nomenclature and glycols in common nomenclature

Chapter 7 4
 Nomenclature of Ethers
 Common Names
 The groups attached to the oxygen are listed in alphabetical order

 IUPAC
 Ethers are named as having an alkoxyl substituent on the main chain

Chapter 7 5
 Physical Properties of Alcohols and Ethers
 Ether boiling points are roughly comparable to hydrocarbons of
the same molecular weight
 Molecules of ethers cannot hydrogen bond to each other
 Alcohols have considerably higher boiling points
 Molecules of alcohols hydrogen bond to each other

 Both alcohols and ethers can hydrogen bond to water and have
similar solubilities in water
 Diethyl ether and 1-butanol have solubilites of about 8 g per 100 mL in water

Chapter 7 6
 Synthesis of Alcohols from Alkenes
 Acid-Catalyzed Hydration of Alkenes
 This is a reversible reaction with Markovnikov regioselectivity

 Oxymercuration-demercuration
 This is a Markovnikov addition which occurs without
rearrangement

Chapter 7 7
 Hydroboration-Oxidation
 This addition reaction occurs with anti-Markovnikov
regiochemistry and syn stereochemistry

Chapter 7 8
 Alcohols as Acids
 Alcohols have acidities similar to water
 Sterically hindered alcohols such as tert-butyl alcohol are less
acidic (have higher pKa values)
 Why?: The conjugate base is not well solvated and so is not as stable

 Alcohols are stronger acids than terminal alkynes and primary or

secondary amines

 An alkoxide can be prepared by the reaction of an alcohol with

sodium or potassium metal

Chapter 7 9
 Conversion of Alcohols into Alkyl Halides
 Hydroxyl groups are poor leaving groups, and as such, are often
converted to alkyl halides when a good leaving group is needed
 Three general methods exist for conversion of alcohols to alkyl
halides, depending on the classification of the alcohol and the
halogen desired
 Reaction can occur with phosphorus tribromide, thionyl chloride or hydrogen
halides

Chapter 7 10
 Alkyl Halides from the Reaction of Alcohols with
Hydrogen Halides
 The order of reactivity is as follows
 Hydrogen halide HI > HBr > HCl > HF
 Type of alcohol 3o > 2o > 1o < methyl

 Mechanism of the Reaction of Alcohols with HX

 SN1 mechanism for 3o, 2o, allylic and benzylic alcohols
 These reactions are prone to carbocation rearrangements
 In step 1 the hydroxyl is converted to a good leaving group

 In step 2 the leaving group departs as a water molecule, leaving behind a

carbocation

Chapter 7 11
  In step 3 the halide, a good nucleophile, reacts with the carbocation

 Primary and methyl alcohols undergo substitution by an S N2

mechanism

 Primary and secondary chlorides can only be made with the

assistance of a Lewis acid such as zinc chloride

Chapter 7 12
 Synthesis of Ethers
 Ethers by Intermolecular Dehydration of Alcohol
 Primary alcohols can dehydrate to ethers
 This reaction occurs at lower temperature than the competing dehydration to an
alkene
 This method generally does not work with secondary or tertiary alcohols because
elimination competes strongly

 The mechanism is an SN2 reaction

Chapter 7 13
 Williamson Ether Synthesis
 This is a good route for synthesis of unsymmetrical ethers

 The alkyl halide (or alkyl sulfonate) should be primary to avoid E 2

reaction
 Substitution is favored over elimination at lower temperatures

Chapter 7 14
 Reactions of Ethers
 Acyclic ethers are generally unreactive, except for cleavage by
very strong acids to form the corresponding alkyl halides
 Dialkyl ethers undergo SN2 reaction to form 2 equivalents of the alkyl bromide

Chapter 7 15
 Epoxides
 Epoxides are three-membered ring cyclic ethers
 These groups are also called oxiranes

 Epoxides are usually formed by reaction of alkenes with peroxy

acids
 This process is called epoxidation and involves syn addition of oxygen

Chapter 7 16
 Reaction of Epoxides
 Epoxides are considerably more reactive than regular ethers
 The three-membered ring is highly strained and therefore very reactive
 Acid-catalyzed opening of an epoxide occurs by initial protonation
of the epoxide oxygen, making the epoxide even more reactive
 Acid-catalyzed hydrolysis of an epoxide leads to a 1,2-diol

Chapter 7 17
 Anti 1,2-Dihydroxylation of Alkenes via Epoxides
 Opening of the following epoxide with water under acid catalyzed
conditions gives the trans diol

Chapter 7 18
 Chapter 04.2
Alcohols from Carbonyl Compounds:
Oxidation-Reduction and
Organometallic Compounds
 Reactions of Carbonyl Compounds with Nucleophiles
 Carbonyl groups can undergo nucleophilic addition
 The nucleophile adds to the + carbon
 The  electrons shift to the oxygen
 The carbon becomes sp 3 hybridized and therefore tetrahedral
 Hydride ions and carbanions are two examples of nucleophiles that react with the
carbonyl carbon

 Carbonyl groups and alcohols can be interconverted by oxidation

and reduction reactions
 Alcohols can be oxidized to aldehydes; aldehydes can be reduced to alcohols

Chapter 7 20
 Oxidation-Reduction Reactions in Organic
Chemistry
 Reduction: increasing the hydrogen content or decreasing the
oxygen content of an organic molecule
 A general symbol for reduction is [H]

 Oxidation: increasing the oxygen content or decreasing the

hydrogen content of an organic molecule
 A general symbol for oxidation is [O]
 Oxidation can also be defined as a reaction that increases the content of any
element more electronegative than carbon

Chapter 7 21
 Alcohols by Reduction of Carbonyl Compounds
 A variety of carbonyl compounds can be reduced to alcohols

 Carboxylic acids can be reduced to primary alcohols

 These are difficult reductions and require the use of powerful reducing agents
such as lithium aluminum hydride (LiAlH 4 also abbreviated LAH)

Chapter 7 22
 Esters are also reduced to primary alcohols
 LAH or high pressure hydrogenation can accomplish this transformation

 Aldehydes and ketones are reduced to 1o and 2o alcohols

respectively
 Aldehydes and ketones are reduced relatively easily; the mild reducing agent
sodium borohydride (NaBH4) is typically used
 LAH and hydrogenation with a metal catalyst can also be used

Chapter 7 23
 The key step in the reduction is reaction of hydride with the carbonyl
carbon

 Carboxylic acids and esters are considerably less reactive to

reduction than aldehydes and ketones and require the use of LAH

 Lithium aluminium hydride is very reactive with water and must be

used in an anhydrous solvent such as ether
 Sodium borohydride is considerably less reactive and can be used in solvents such as
water or an alcohol

Chapter 7 24
 Oxidation of Alcohols
 Oxidation of Primary Alcohols to Aldehydes
 A primary alcohol can be oxidized to an aldehyde or a carboxylic
acid
 The oxidation is difficult to stop at the aldehyde stage and usually proceeds to the
carboxylic acid

 A reagent which stops the oxidation at the aldehyde stage is

pyridinium chlorochromate (PCC)
 PCC is made from chromium trioxide under acidic conditions
 It is used in organic solvents such as methylene chloride (CH 2Cl2)

Chapter 7 25
 Oxidation of Primary Alcohols to Carboxylic Acids
 Potassium permanganate (KMnO4) is a typical reagent used for
oxidation of a primary alcohol to a carboxylic acid
 The reaction is generally carried out in aqueous solution; a brown precipitate of
MnO2 indicates that oxidation has taken place

 Oxidation of Secondary Alcohols to Ketones

 Oxidation of a secondary alcohol stops at the ketone
 Many oxidizing agents can be used, including chromic acid (H 2CrO4) and Jones
reagent (CrO3 in acetone)

Chapter 7 26
 Organometallic Compounds
 Carbon-metal bonds vary widely in character from mostly covalent
to mostly ionic depending on the metal

 The greater the ionic character of the bond, the more reactive the
compound
 Organopotassium compounds react explosively with water and burst into flame
when exposed to air

Chapter 7 27
 Preparation of Organo-magnesium Compounds -
Grignard Reagents
 Grignard reagents are prepared by the reaction of organic halides
with magnesium turnings
 An ether solvent is used because it forms a complex with the Grignard reagent
which stabilizes it

Chapter 7 28
 Reactions of Grignard Reagents with Oxiranes
(Epoxides)
 Grignard reagents are very powerful nucleophiles and can react
with the + carbons of oxiranes
 The reaction results in ring opening and formation of an alcohol product
 Reaction occurs at the least-substituted ring carbon of the oxirane
 The net result is carbon-carbon bond formation two carbons away from the
alcohol

Chapter 7 29
 Alcohols from Grignard Reagents
 Aldehydes and ketones react with Grignard reagents to yield
different classes of alcohols depending on the starting carbonyl
compound

Chapter 7 30
 Esters react with two molar equivalents of a Grignard reagent to
yield a tertiary alcohol
 A ketone is formed by the first molar equivalent of Grignard reagent and this
immediately reacts with a second equivalent to produce the alcohol
 The final product contains two identical groups at the alcohol carbon that are both
derived from the Grignard reagent

Chapter 7 31
Chapter 7 32