Chapter 5Alcohols Thiols

Ethers

Chapter 10 2

Structure of Water and Methanol

• Oxygen is sp3 hybridized and tetrahedral.• The H—O—H angle in water is 104.5°. • The C—O—H angle in methyl alcohol is 108.9°.

Chapter 10 3

Classification of Alcohols

• Primary: carbon with —OH is bonded to one other carbon.

• Secondary: carbon with —OH is bonded to two other carbons.

• Tertiary: carbon with —OH is bonded to three other carbons.

• Aromatic (phenol): —OH is bonded to a benzene ring.

Chapter 10 4

Examples of Classifications

CH3 C

CH3

CH3

OH*

CH3 CH

OH

CH2CH3*

CH3 CH

CH3

CH2OH*

Chapter 10 5

Examples of Classifications

CH3 C

CH3

CH3

OH*

CH3 CH

OH

CH2CH3*

CH3 CH

CH3

CH2OH*

Primary alcohol

Chapter 10 6

Examples of Classifications

CH3 C

CH3

CH3

OH*

CH3 CH

OH

CH2CH3*

CH3 CH

CH3

CH2OH*

Primary alcohol Secondary alcohol

Chapter 10 7

Examples of Classifications

CH3 C

CH3

CH3

OH*

CH3 CH

OH

CH2CH3*

CH3 CH

CH3

CH2OH*

Primary alcohol Secondary alcohol

Tertiary alcohol

Chapter 10 8

IUPAC Nomenclature

• Find the longest carbon chain containing the carbon with the —OH group.

• Drop the -e from the alkane name, add -ol.• Number the chain giving the —OH group the lowest

number possible.• Number and name all substituents and write them in

alphabetical order.

Chapter 10 9

Examples of Nomenclature

2-methyl-1-propanol2-methylpropan-1-ol

2-methyl-2-propanol2-methylpropan-2-ol

2-butanolbutan-2-ol

CH3 C

CH3

CH3

OH

CH3 CH

CH3

CH2OH CH3 CH

OH

CH2CH33 2 1 1 2 3 4

2 1

Chapter 10 10

Alkenols (Enols)

• Hydroxyl group takes precedence. Assign the carbon with the —OH the lowest number.

• End the name in –ol, but also specify that there is a double bond by using the ending –ene before -ol

4-penten-2-ol pent-4-ene-2-ol

CH2 CHCH2CHCH3

OH

5 4 3 2 1

Chapter 10 11

Naming Priority

1. Acids2. Esters3. Aldehydes4. Ketones5. Alcohols6. Amines 7. Alkenes8. Alkynes9. Alkanes10. Ethers11. Halides

Highest ranking

Lowest ranking

Chapter 10 12

Hydroxy Substituent

• When —OH is part of a higher priority class of compound, it is named as hydroxy.

4-hydroxybutanoic acidalso known as -hydroxybutyric acid (GHB)

CH2CH2CH2COOH

OHcarboxylic acid

4 3 2 1

Chapter 10 13

Common Names

• Alcohol can be named as alkyl alcohol.• Useful only for small alkyl groups.

isobutyl alcohol sec-butyl alcohol

CH3 CH

CH3

CH2OH CH3 CH

OH

CH2CH3

Chapter 10 14

Naming Diols

• Two numbers are needed to locate the two —OH groups.

• Use -diol as suffix instead of -ol.

hexane-1,6- diol

1 2 3 4 5 6

OHOH

Chapter 10 15

Glycols• 1, 2-diols (vicinal diols) are called glycols.• Common names for glycols use the name of the alkene

from which they were made.

OHOH

ethane-1,2- diolethylene glycol

propane-1,2- diolpropylene glycol

OHOH

Chapter 10 16

Phenol Nomenclature• —OH group is assumed to be on carbon 1.• For common names of disubstituted phenols, use

ortho- for 1,2; meta- for 1,3; and para- for 1,4.• Methyl phenols are cresols.

3-chlorophenol(meta-chlorophenol)

4-methylphenol(para-cresol)

OH

Cl

OH

H3C

Chapter 10 17

Give the systematic (IUPAC) name for the following alcohol.

The longest chain contains six carbon atoms, but it does not contain the carbon bonded to the hydroxyl group. The longest chain containing the carbon bonded to the —OH group is the one outlined by the green box, containing five carbon atoms. This chain is numbered from right to left in order to give the hydroxyl-bearing carbon atom the lowest possible number.

The correct name for this compound is 3-(iodomethyl)-2-isopropylpentan-1-ol.

Solved Problem 1

Solution

Chapter 10 18

Physical Properties

• Alcohols have high boiling points due to hydrogen bonding between molecules.

• Small alcohols are miscible in water, but solubility decreases as the size of the alkyl group increases.

Chapter 10 19

Boiling Points of alcohols

• Alcohols have higher boiling points than ethers and alkanes because alcohols can form hydrogen bonds.

• The stronger interaction between alcohol molecules will require more energy to break them resulting in a higher boiling point.

Chapter 10 20

Solubility in Water

Small alcohols are miscible in water, but solubility decreases as the size of the alkyl group increases.

Chapter 10 21

Methanol• “Wood alcohol”• Industrial production from synthesis gas• Common industrial solvent• Toxic Dose: 100 mL methanol• Used as fuel at Indianapolis 500

– Fire can be extinguished with water– High octane rating– Low emissions– Lower energy content– Invisible flame

Chapter 10 22

Ethanol

• Fermentation of sugar and starches in grains• 12–15% alcohol, then yeast cells die• Distillation produces “hard” liquors• Azeotrope: 95% ethanol, constant boiling• Denatured alcohol used as solvent• Gasahol: 10% ethanol in gasoline• Toxic dose: 200 mL

Chapter 10 23

Acidity of Alcohols

• pKa range: 15.5–18.0 (water: 15.7)

• Acidity decreases as the number of carbons increase.

• Halogens and other electron withdrawing groups increase the acidity.

• Phenol is 100 million times more acidic than cyclohexanol!

Chapter 10 24

Table of Ka Values

Chapter 10 25

Formation of Alkoxide Ions

• Ethanol reacts with sodium metal to form sodium ethoxide (NaOCH2CH3), a strong base commonly used for elimination reactions.

• More hindered alcohols like 2-propanol or tert-butanol react faster with potassium than with sodium.

Chapter 10 26

Formation of Phenoxide Ion

The aromatic alcohol phenol is more acidic than aliphatic alcohols due to the ability of aromatic rings to delocalize the negative charge of the oxygen within the carbons of the ring.

Chapter 10 27

Charge Delocalization on the Phenoxide Ion

• The negative charge of the oxygen can be delocalized over four atoms of the phenoxide ion.

• There are three other resonance structures that can localize the charge in three different carbons of the ring.

• The true structure is a hybrid between the four resonance forms.

Chapter 10 28

Synthesis of Alcohols (Review)

• Alcohols can be synthesized by nucleophilic substitution of alkyl halide.

• Hydration of alkenes also produce alcohols:

Chapter 10 29

Synthesis of Vicinal Diols

Vicinal diols can be synthesized by two different methods:

• Syn hydroxylation of alkenes– Cold, dilute, basic potassium permanganate

Chapter 10 30

Reduction of Carbonyl

• Reduction of aldehyde yields 1º alcohol.• Reduction of ketone yields 2º alcohol.• Reagents:

– Sodium borohydride, NaBH4

– Lithium aluminum hydride, LiAlH4

– Raney nickel

Chapter 10 31

Sodium Borohydride

• NaBH4 is a source of hydrides (H-)• Hydride attacks the carbonyl carbon,

forming an alkoxide ion.• Then the alkoxide ion is protonated by

dilute acid.• Only reacts with carbonyl of aldehyde or

ketone, not with carbonyls of esters or carboxylic acids.

Chapter 10 32

Lithium Aluminum Hydride

• LiAlH4 is source of hydrides (H-)• Stronger reducing agent than sodium

borohydride, but dangerous to work with.• Reduces ketones and aldehydes into the

corresponding alcohol.• Converts esters and carboxylic acids to 1º

alcohols.

Chapter 10 33

Reduction with LiAlH4

O

OCH3 OH1. LAH2. H3O+

H H

• The LiAlH4 (or LAH) will add two hydrides to the ester to form the primary alkyl halide.

• The mechanism is similar to the attack of Grignards on esters.

Chapter 10 34

Reducing Agents• NaBH4 can reduce

aldehydes and ketones but not esters and carboxylic acids.

• LiAlH4 is a stronger reducing agent and will reduce all carbonyls.

Chapter 10 35

Catalytic Hydrogenation

• Raney nickel is a hydrogen rich nickel powder that is more reactive than Pd or Pt catalysts.

• This reaction is not commonly used because it will also reduce double and triple bonds that may be present in the molecule.

• Hydride reagents are more selective so they are used more frequently for carbonyl reductions.

Chapter 10 36

Thiols (Mercaptans)

• Sulfur analogues of alcohols are called thiols.• The —SH group is called a mercapto group.• Named by adding the suffix -thiol to the

alkane name.• They are commonly made by a substitution. • Primary alkyl halides work better.

Chapter 10 37

Synthesis of Thiols

• The thiolate will attack the carbon displacing the halide.

• This is a substitution reaction• methyl halides will react faster than primary alkyl

halides.• To prevent dialylation use a large excess of sodium

hydrosulfide with the alkyl halide.

Chapter 11 38

Alcohol Reactions

• Dehydration to alkene• Oxidation to aldehyde, ketone• Substitution to form alkyl halide• Reduction to alkane• Esterification• Williamson synthesis of ether

Chapter 11 39

Summary Table

Chapter 11 40

Oxidation States

• Easy for inorganic salts (reduced, organic oxidized)– CrO4

2- reduced to Cr2O3

– KMnO4 reduced to MnO2

• Oxidation: loss of H2, gain of O, O2, or X2

• Reduction: gain of H2 or H-, loss of O, O2, or X2

• Neither: gain or loss of H+, H2O, HX

Chapter 11 41

Oxidation States

• Easy for inorganic salts (reduced, organic oxidized)– CrO4

2- reduced to Cr2O3

– KMnO4 reduced to MnO2

• Oxidation: loss of H2, gain of O, O2, or X2

• Reduction: gain of H2 or H-, loss of O, O2, or X2

• Neither: gain or loss of H+, H2O, HX

Chapter 11 42

1º, 2º, 3º Carbons

Chapter 11 43

Oxidation of 2° Alcohols• 2° alcohol becomes a ketone• Reagent is Na2Cr2O7/H2SO4 = H2CrO4

• Active reagent probably H2CrO4

• Color change: orange to greenish-blue

CH3CHCH2CH3

OHNa2Cr2O7 / H2SO4

CH3CCH2CH3

O

=>

Chapter 11 44

Oxidation of 1° Alcohols• 1° alcohol to aldehyde to carboxylic acid• Difficult to stop at aldehyde• Use pyridinium chlorochromate (PCC) to

limit the oxidation.• PCC can also be used to oxidize 2° alcohols

to ketones.

CH3CH2CH2CH2

OH N H CrO3Cl

CH3CH2CH2CH

O

Chapter 11 45

3° Alcohols Don’t Oxidize• Cannot lose 2 H’s• Basis for chromic acid test

Chapter 11 46

Alcohol as a Nucleophile

• ROH is weak nucleophile• RO- is strong nucleophile• New O-C bond forms, O-H bond breaks.

CO

H

R X

Chapter 11 47

Alcohol as an Electrophile• OH- is not a good leaving group

unless it is protonated, but most nucleophiles are strong bases which would remove H+.

• Convert to tosylate (good leaving group) to react with strong nucleophile (base).

CO

H

+

C-Nuc bond forms, C-O bond breaks

Chapter 11 48

Reduction of Alcohols

• Dehydrate with conc. H2SO4, then add H2

CH3CHCH3

OHH2SO4

CH2 CHCH3H2

PtCH3CH2CH3

alcohol alkene alkane

Chapter 11 49

Reaction with HBr• -OH of alcohol is protonated• -OH2

+ is good leaving group

• 3° and 2° alcohols react with Br- via SN1

• 1° alcohols react via SN2

H3O+

Br-

R O H R O H

H

R Br

Chapter 11 50

Reaction with HCl• Chloride is a weaker nucleophile than

bromide.• Add ZnCl2, which bonds strongly with

-OH, to promote the reaction.• The chloride product is insoluble.• Lucas test: ZnCl2 in conc. HCl

– 1° alcohols react slowly or not at all.– 2 alcohols react in 1-5 minutes.– 3 alcohols react in less than 1 minute.

Chapter 11 51

Limitations of HX Reactions

• Poor yields of 1° and 2° chlorides• May get alkene instead of alkyl halide

Chapter 11 52

Reactions with Phosphorus Halides• Good yields with 1° and 2° alcohols• PCl3 for alkyl chloride (but SOCl2 better)• PBr3 for alkyl bromide

Chapter 11 53

Dehydration Reactions• Conc. H2SO4 (or H3PO4) produces alkene

• Carbocation intermediate• Zaitsev product• Bimolecular dehydration produces ether• Low temp, 140°C and below, favors ether• High temp, 180°C and above, favors alkene

Ethers

O

H H

O

H R

O

R R

Hydrogen OxideAka Water

Alcohol Ether

• Ethers contain an sp3 hybridized oxygen atom

• Ethers do not hydrogen bond between each other, but will hydrogen bond with water and alcohols.

• Ethers are polar and water soluble

Ether NomenclatureCommon System

Give alkyl names to the carbon groups (alkyl groups) bonded to the oxygen, followed by ether.

Examples

O

H3C CH3

O

H3C CH2CH3

O O

Ether NomenclatureCommon System

Give alkyl names to the carbon groups (alkyl groups) bonded to the oxygen, followed by ether.

Examples

O

H3C CH3

O

H3C CH2CH3

O O

Dimethyl ether

Ether NomenclatureCommon System

Give alkyl names to the carbon groups (alkyl groups) bonded to the oxygen, followed by ether.

Examples

O

H3C CH3

O

H3C CH2CH3

O O

Dimethyl ether Ethylmethyl ether

Ether NomenclatureCommon System

Give alkyl names to the carbon groups (alkyl groups) bonded to the oxygen, followed by ether.

Examples

O

H3C CH3

O

H3C CH2CH3

O O

Dimethyl ether Ethylmethyl ether

Isopropylmethyl ether

Ether NomenclatureCommon System

Give alkyl names to the carbon groups (alkyl groups) bonded to the oxygen, followed by ether.

Examples

O

H3C CH3

O

H3C CH2CH3

O O

Dimethyl ether Ethylmethyl ether

Isopropylmethyl ether Sec-butylcyclopropyl ether

Ether Nomenclature

IUPAC System

Name the longest chain of carbons in the normal fashion. The oxygen containing group is named by giving the carbon portion the Latin root followed by oxy.

Examples

O

H3C CH3

O

H3C CH2CH3

O O

Methoxymethane

Ether Nomenclature

IUPAC System

Name the longest chain of carbons in the normal fashion. The oxygen containing group is named by giving the carbon portion the Latin root followed by oxy.

Examples

O

H3C CH3

O

H3C CH2CH3

O O

Methoxymethane Methoxyethane

Ether Nomenclature

IUPAC System

Name the longest chain of carbons in the normal fashion. The oxygen containing group is named by giving the carbon portion the Latin root followed by oxy.

Examples

O

H3C CH3

O

H3C CH2CH3

O O

Methoxymethane Methoxyethane2-Methoxypropane

Ether Nomenclature

IUPAC System

Name the longest chain of carbons in the normal fashion. The oxygen containing group is named by giving the carbon portion the Latin root followed by oxy.

Examples

O

H3C CH3

O

H3C CH2CH3

O O

Methoxymethane Methoxyethane2-Methoxypropane 2-Cyclopropoxybutane

Ether Formation• 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 stronglyThe mechanism is an SN2 reaction:

Williamson Ether Synthesis• Good for unsymmetrical ethers

Chapter 11 66

Dehydration Mechanisms

CH3CHCH3

OHH2SO4

alcoholCH3CHCH3

OH

H

CH3CHCH3

CH2 CHCH3H2O

CH3OH

H3O+

CH3OH CH3 OH2 CH3 O

H

CH3

H2OCH3OCH3

Chapter 11 67

Esterification• Fischer: alcohol + carboxylic acid• Nitrate esters• Phosphate esters

Chapter 11 68

Fischer Esterification

• Acid + Alcohol yields Ester + Water• Sulfuric acid is a catalyst.• Each step is reversible.

CH3 C OH

O

+ CH2CH2CHCH3

CH3

OHH

+

CH3C

O

OCH2CH2CHCH3

CH3

+ HOH

Chapter 11 69

Sulfate EstersAlcohol + Sulfuric Acid

+HO S

O

O

OH H O CH2CH3H

+

OCH2CH3

O

O

SHO

CH3CH2O H + OCH2CH3

O

O

SHOH

+

CH3CH2O S

O

O

OCH2CH3

=>

Chapter 11 70

Nitrate Esters

+ H O CH2CH3H

+

N OH

O

OOCH2CH3N

O

O

Chapter 11 71

Phosphate Esters

=>

Chapter 11 72

Phosphate Esters in DNA

=>

OCH2

HH

H

base

OP

O

O O

OCH2

HH

H

base

OP

O

O O

OCH2

HH

H

base

OP

O

O O

O

OCH2

HH

H

base

OP

O

O O

Chapter 11 73

End of Chapter 5