8 8-1 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Introduction to Organic Chemistry 2 ed William H. Brown

88

8-1Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.

Introduction to Introduction to Organic Organic

ChemistryChemistry2 ed2 ed

William H. BrownWilliam H. Brown

88


Alcohols, Alcohols, Ethers, and Ethers, and ThiolsThiols

Chapter 8Chapter 8

88


Structure - AlcoholsStructure - Alcohols• The functional group of an alcohol

is an -OH group bonded to an sp3 hybridized carbon• bond angles about the hydroxyl

oxygen atom are approximately 109.5°

• Oxygen is also sp3 hybridized• two sp3 hybrid orbitals form sigma

bonds to carbon and hydrogen• the remaining two sp3 hybrid orbitals

each contain an unshared pair of electrons

88


Structure - EthersStructure - Ethers• The functional group of an ether is an oxygen

atom bonded to two carbon atoms• Oxygen is sp3 hybridized with bond angles of

approximately 109.5°. In dimethyl ether, the C-O-C bond angle is 110.3°

H

H O

H

C H

H

H

C••

••

88


Structure - ThiolsStructure - Thiols• The functional group of a thiol is an

-SH (sulfhydryl) group bonded to an sp3 hybridized carbon

• The bond angle about sulfur in methanethiol is 100.3°, which indicates that there is considerably more p character to the bonding orbitals of divalent sulfur than there is to oxygen

88


Nomenclature-AlcoholsNomenclature-Alcohols• IUPAC names

• the longest chain that contains the -OH group is taken as the parent.

• the parent chain is numbered to give the -OH group the lowest possible number

• the suffix -ee is changed to -olol

• Common names • the alkyl group bonded to oxygen is named followed

by the word alcoholalcohol

88


Nomenclature - AlcoholsNomenclature - Alcohols

1-Propanol

(Propyl alcohol)

C H 3 C H 2 C H 2 O H

2-Propanol

(Isopropyl alcohol)

O H

C H 3 C H C H 3

1-Butanol

(Butyl alcohol)

C H 3 C H 2 C H 2 C H 2 O H

2-Butanol

(sec-Butyl alcohol)

O H

C H 3 C H 2 C H C H 3

2-Methyl-1-propanol

(Isobutyl alcohol)

2-Methyl-2-propanol

(tert-Butyl alcohol)

C H 3

C H3

C H3

C H 3 C H C H 2 O H

C H3

C O H

88


Nomenclature - AlcoholsNomenclature - Alcohols• Problem: write IUPAC names for these alcohols

(a) (b)

(c)

C H3

O H

C H3

C H 3 C H C H 2 C H C H 3

O H

(d) C

C H2

O H

H3

C

H

C H2

C H3

C H3

( C H2

)6

C H2

O H

88


Nomenclature - AlcoholsNomenclature - Alcohols• Compounds containing more than one -OH group

are named diols, triols, etc.

1,2-Ethanediol

(Ethylene glycol)

1,2-Propanediol

(Propylene glycol)

1,2,3-Propanetriol

(Glycerol, Glycerin)

H O O H

H O O H H O H O O H

C H3

C H C H2

C H2

C H2

C H2

C H C H2

88


Nomenclature - AlcoholsNomenclature - Alcohols• Unsaturated alcohols

• the double bond is shown by the infix -enen-• the hydroxyl group is shown by the suffix -olol• number the chain to give OH the lower number

H O C H2

C H2

C C

C H2

C H3

H H

4

5 6

trans -3-Hexen-1-ol

3

21

88


Nomenclature - EthersNomenclature - Ethers• IUPAC: the longest carbon chain is the parent. Name the

OR group as an alkoxy substituent• Common names: name the groups attached to oxygen

followed by the word etherether

Ethoxyethane

(Diethyl ether)

2-Methoxy-2-methylpropane

(methyl tert -butyl ether, MTBE)

C H3

C H3

C H 3 C H 2 O C H 2 C H 3

C H 3 O C C H 3

trans -2-Ethoxycyclohexanol

O C H2

C H3

O H

88


Nomenclature - EthersNomenclature - Ethers• Although cyclic ethers have IUPAC names, their

common names are more widely used

Ethylene

oxide

Tetrahydro-

furan, THF

Tetrahydro-

pyran

1,4-Dioxane

O O

O

O

O

88


Nomenclature - ThiolsNomenclature - Thiols• IUPAC names:

• the parent is the longest chain that contains the -SH group

• change the suffix -ee to -thiolthiol

• Common names:• name the alkyl group bonded to sulfur followed by the

word mercaptanmercaptan

1-Butanethiol

(Butyl mercaptan)

C H3

C H2

C H2

C H2

S H

2-Butanethiol

(sec-Butyl mercaptan)

S H

C H3

C H2

C H C H3

88


Physical Prop - AlcoholsPhysical Prop - Alcohols• Alcohols are polar compounds

• Alcohols are associated in the liquid state by hydrogen bonding

δ -

δ +

δ +

O

H

H

H

C

H

88


Physical Prop - AlcoholsPhysical Prop - Alcohols• Hydrogen bondingHydrogen bonding: the attractive force between a

partial positive charge on hydrogen and a partial negative charge on a nearby oxygen, nitrogen, or fluorine atom

• the strength of hydrogen bonding in water is approximately 5 kcal/mol• hydrogen bonds are considerably weaker than

covalent bonds• nonetheless, they can have a significant effect on

physical properties

88


Physical Prop - AlcoholsPhysical Prop - Alcohols• Ethanol and dimethyl ether are constitutional

isomers. • Their boiling points are dramatically different

• ethanol forms intermolecular hydrogen bonds which increases attractive forces between its molecules, which results in a higher boiling point

bp -24°C

Ethanol

bp 78° C

Dimethyl ether

CH3

CH2

OH CH3

OCH3

88


Physical Prop. - AlcoholsPhysical Prop. - Alcohols• In relation to alkanes of comparable size and

molecular weight, alcohols• have higher boiling points• are more soluble in water

• The presence of additional -OH groups in a molecule further increases boiling points and solubility in water

88


Physical Prop. - AlcoholsPhysical Prop. - AlcoholsFormula Name MW

bp

(°C)

Solubility

in Water

methanol 32 65 infinite

ethane 30 -89 insoluble

ethanol 46 78 infinite

propane 44 -42 insoluble

1-propanol 60 97 infinite

butane 58 0 insoluble

1-pentanol 88 138 2.3 g/100 g

1,4-butanediol 90 230 infinite

hexane 86 69 insoluble

CH3

CH2

CH2

OH

CH 3 CH 2 CH 2 CH 3

CH3

OH

CH 3 CH 3

CH3

CH2

OH

CH3

CH2

CH3

CH 3 ( CH 2 ) 4 OH

HO ( CH2

)4

OH

CH3

( CH2

)4

CH3

88


Physical Prop. - EthersPhysical Prop. - Ethers• Ethers are polar molecules;

• the difference in electronegativity between oxygen (3.5) and carbon (2.5) is 1.0

• each C-O bond is polar covalent• oxygen bears a partial negative

charge and each carbon a partial positive charge

88


Physical Prop. - EthersPhysical Prop. - Ethers• Ethers are polar molecules, but because of steric

hindrance, only weak attractive forces exist between their molecules in the pure liquid state

• Boiling points of ethers are • lower than alcohols of comparable MW and • close to those of hydrocarbons of comparable MW

• Ethers hydrogen bond with H2O and are more soluble in H2O than are hydrocarbons

88


Physical Prop. - ThiolsPhysical Prop. - Thiols• Low-molecular-weight thiols have a STENCHSTENCH

• the scent of skunks is due primarily to these two thiols

2-Butene-1-thiol3-Methyl-1-butanethiol

C H3

C H = C H C H2

S HC H3

C H C H2

C H2

S H

C H3

88


Physical Prop. - ThiolsPhysical Prop. - Thiols• The difference in electronegativity between S

(2.5) and H (2.1) is 0.4. Because of the low polarity of the S-H bond, thiols• show little association by hydrogen bonding• have lower boiling points and are less soluble in water

than alcohols of comparable MW

117

78

65

1-butanol

ethanol

methanol

98

35

6

1-butanethiol

ethanethiol

methanethiol

bp (° C)Alcoholbp (° C)Thiol

88


Acidity of AlcoholsAcidity of Alcohols• In dilute aqueous solution, alcohols are weakly

acidic

H

H

OH

[CH3

O-] [H

3O

+]

[CH3

OH]

CH3

O-H O H

H

CH3

O -

+

Ka

=

+ +

= 15.5

88


Acidity of AlcoholsAcidity of AlcoholsCompound pK a

-7

15.5

15.7

15.9

17

18

4.8

CH 3 OH

H2

O

CH3

CH2

OH

(CH 3 ) 2 CHOH

(CH3

)3

COH

CH3

CO2

H

HClhydrogen chloride

acetic acid

methanol

water

ethanol

2-propanol

2-methyl-2-propanol

Formula

Stronger

acid

Weaker

acid

88


Basicity of AlcoholsBasicity of Alcohols• In the presence of strong acids, the oxygen atom

of an alcohol behaves as a weak base • proton transfer from the strong acid forms an oxonium

ion

••

••

••A n acidA base

A n oxonium ion

+

+

+••

••

+

H

HCH3

H

HCH3

H

H

H

H

OO

O

H2

SO4

O

88


Reaction with MetalsReaction with Metals• Alcohols react with Li, Na, K, and other active

metals to liberate hydrogen gas and form metal alkoxides

2 C H3

O H + 2 N a 2 C H3

O-

N a+

H2

Sodium

methoxide

+

Methanol

88


Conversion of ROH to RXConversion of ROH to RX• Conversion of an alcohol to an alkyl halide

involves substitution of halogen for -OH at a saturated carbon • the most common reagents for this purpose are the

halogen acids, HX, and thionyl chloride, SOCl2

88


Reaction with HXReaction with HX• Water-soluble 3° alcohols react very rapidly with

HCl, HBr, and HI. Low-molecular-weight 1° and 2° alcohols are unreactive under these conditions

C H3

C O H25°C

2-Methyl-2-

propanol

2-Chloro-2-

methylpropane

+ H C l C H3

C C l + H2

OC H3

C O H25°C

2-Methyl-2-

propanol

2-Chloro-2-

methylpropane

+ H C l + H2

O

C H3

C H3

C H3

C H3

88


Reaction with HXReaction with HX• Water-insoluble 3° alcohols react by bubbling

gaseous HX through a solution of the alcohol dissolved in diethyl ether or THF

CH3

OH

HCl

CH3

Cl

H2

O

1 -Chloro-1-methyl-

cyclohexane

1-Methylcyclo-

hexanol

0o

C

ether+ +

88


Reaction with HXReaction with HX• 1° and 2° alcohols require concentrated HBr and

HI to form alkyl bromides and iodides

C H3

C H2

C H2

C H2

O H H B r

C H3

C H2

C H2

C H2

B r H2

O

H 2 O

reflux

1-Bromobutane

1-Butanol

+

+

88


Mechanism: 3° ROH + HClMechanism: 3° ROH + HCl• An SN1 reaction

• Step 1: rapid, reversible acid-base reaction that transfers a proton to the OH group

2-Methyl-2-propanol

(tert-Butyl alcohol)

••

••

An oxonium ion

+

rapid and

reversible

+

••

••

+

+

C H3

C H 3

O - H

C H3

C H3

O

H

H

H

H

H

H HC H3

- C

C H3

- C O

O

88


Mechanism: 3° ROH + HClMechanism: 3° ROH + HCl• Step 2: loss of H2O to give a carbocation intermediate

An oxonium ion

+

rate-limiting

step

+••

CH3

CH3

O

H

H

H

H

CH3

-C O

CH3

CH3

CH3

-C+

A 3° carbocation

intermediate

88


Mechanism: 3° ROH + HClMechanism: 3° ROH + HCl• Step 3: reaction of the carbocation intermediate (a

Lewis acid) with halide ion (a Lewis base)

2-Chloro-2-methylpropane

(tert-Butyl chloride)

••

••

••

••rapid

Cl+

C H3

C H 3

C H3

C H 3

C H3

- C - C lC H3

- C +

88


Mechanism: 1°ROH + HBrMechanism: 1°ROH + HBr• An SN2 reaction

• Step 1: rapid and reversible proton transfer

••••

rapid and

reversible

+

H

H

CH3

CH2

CH2

CH2

-

CH3

CH2

CH2

CH2

- O-H

O

An oxonium ion

H O H

H

+••

+

••

O H

H

+

88


Mechanism: 1° ROH + HXMechanism: 1° ROH + HX• Step 2: displacement of HOH by halide ion

••

••

••

••

rate-limiting

step

Br

Br +

+

H

H

C H3

C H2

C H2

C H2

- O

C H3

C H2

C H2

C H2

- +

H

H

O

SN

2

88


Mechanisms: SMechanisms: SNN1 vs S1 vs SNN22• Reactivities of alcohols for SN1 and SN2 are in

opposite directions

3° alcohol 2° alcohol 1° alcohol

Increasing stability of cation intermediate

Increasing ease of access to the reaction site

SN

1

SN

2

88


Reaction with SOClReaction with SOCl22• Thionyl chloride is the most widely used reagent

for the conversion of 1° and 2° alcohols to alkyl chlorides• a base, most commonly pyridine or triethylamine, is

added to neutralize the HCl

Thionyl

chloride

1-Heptanol

1-Chloroheptane

CH3

(CH2

)5

CH2

Cl + SO2

+ HCl

CH3

(CH2

)5

CH2

OH + SOCl2

pyridine

88


Dehydration of ROHDehydration of ROH• An alcohol can be converted to an alkene by

elimination of H and OH from adjacent carbons (a -elimination)• 1° alcohols must be heated at high temperature in the

presence of an acid catalyst, such as H2SO4 or H3PO4

• 2° alcohols undergo dehydration at somewhat lower temperatures

• 3° alcohols often require temperatures only at or slightly above room temperature

88


Dehydration of ROHDehydration of ROH

140o

C

Cyclohexanol Cyclohexene

OH

+ H2

OH

2SO

4

180o

C

CH3

CH2

OH

H2

SO4

CH2

=CH2

+ H2

O

+ H2

OC H3

C O H

C H3

C H3

50o

C

H2

S O4

C H3

C = C H2

C H 3

2-Methylpropene

(Isobutylene)

88


Dehydration of ROHDehydration of ROH• Where isomeric alkenes are possible, the alkene

having the greater number of substituents on the double bond generally predominates (Zaitsev rule)

1-Butene

(20%)

2-Butene

(80%)

2-Butanol

+

heat

O H

8 5 % H3

P O4

C H3

C H = C H C H3

C H3

C H2

C H C H3

C H3

C H2

C H = C H2

88


Dehydration of ROHDehydration of ROH• A three-step mechanism

• Step 1: proton transfer from H3O+ to the -OH group to form an oxonium ion

+••

A n oxonium ion

rapid and

reversible

+

••

••

••+

+

H O

O

H H

H H

H

C H3

C H C H2

C H3 O

C H3

C H C H2

C H3 O

H

H

88


Dehydration of ROHDehydration of ROH• Step 2: the C-O bond is broken and water is lost,

giving a carbocation intermediate

+

A 2o

carbocation

+

slow and

rate limiting

+••

••

O

HH

C H3

C H C H2

C H3

C H3

C H C H2

C H3 H

2O

88


Dehydration of ROHDehydration of ROH• Step 3: proton transfer of H+ from a carbon adjacent to

the positively charged carbon to water. The sigma electrons of the C-H bond become the pi electrons of the carbon-carbon double bond

rapid+

+

••

+••

H

H

HH

H

C H3

- C H - C H - C H3

C H3

- C H = C H - C H3

O

O

H

+

88


Dehydration of ROHDehydration of ROH• Acid-catalyzed alcohol dehydration and alkene

hydration are competing processes

• large amounts of water favor alcohol formation• scarcity of water or experimental conditions where

water is removed favor alkene formation

An alkene A n alcohol

C C C C

H O H

+ H2

O

acid

catalyst

88


Oxidation: 1° ROHOxidation: 1° ROH• A primary alcohol can be oxidized to an aldehyde

or a carboxylic acid, depending on the oxidizing agent and experimental conditions

O H

[O]

C H 3 - C H 2 C H 3 - C - H C H3

- C - O H

O O

[O]

A primary

alcohol

An aldehyde A carboxylic

acid

88


Oxidation: chromic acidOxidation: chromic acid• Chromic acid is prepared by dissolving

chromium(VI) oxide or potassium dichromate in aqueous sulfuric acid

Potassium

dichromate

Chromic acid

K2

Cr2

O7

H2

SO4

H2

Cr2

O7

H2

O

2 H2

CrO4

+

Chromic acidChromium(VI)

oxide

CrO3

H2

O H2

CrO4

H2

SO4

88


Oxidation: 1° ROHOxidation: 1° ROH• Oxidation of 1-octanol by chromic acid gives

octanoic acid• the aldehyde intermediate is not isolated

Octanal

(not isolated)

Octanoic acid

1-Octanol

O O

C H3

( C H2

)6

C H2

O HC r O

3

H2

S O4

, H2

O

C H3

( C H2

)6

C H C H 3 ( C H 2 ) 6 C O H

88


PCCPCC• Pyridinium chlorochromate (PCC)Pyridinium chlorochromate (PCC): a form of

Cr(VI) prepared by dissolving CrO3 in aqueous HCl and adding pyridine to precipitate PCC

• PCC is selective for the oxidation of 1° alcohols to aldehydes; it does not oxidize aldehydes further to carboxylic acids

N

H

+

CrO3

Cl-

88


Oxidation: 1° ROHOxidation: 1° ROH• PCC oxidation of a 1° alcohol to an aldehyde

CH2

OH CH

O

PCC

Geraniol Geranial

88


Oxidation: 2° ROHOxidation: 2° ROH• 2° alcohols are oxidized to ketones by both

chromic acid and and PCC

2-Isopropyl-5-methyl-

cyclohexanone

(Menthone)

2-Isopropyl-5-methyl-

cyclohexanol

(Menthol)

acetone

CH3

CH(CH3

)2

OH O

CH(CH3

)2

CH3

H2

CrO4

88


Reactions of ethersReactions of ethers• Ethers, R-O-R, resemble hydrocarbons in their

resistance to chemical reaction• they do not react with strong oxidizing agents such as

chromic acid, H2CrO4

• they are not affected by most acids and bases at moderate temperatures

• Because of their good solvent properties and general inertness to chemical reaction, ethers are excellent solvents in which to carry out organic reactions

88


EpoxidesEpoxides• EpoxideEpoxide: a cyclic ether in which oxygen is one

atom of a three-membered ring• Common names are derived from the name of the

alkene from which the epoxide is formally derived

Ethylene oxide

CH2

CH2

O

CHCH3

CH2

O

Propylene oxide

88


Synthesis of Epoxides-1Synthesis of Epoxides-1• Ethylene oxide, one of the few epoxides

manufactured on an industrial scale, is prepared by air oxidation of ethylene

Oxirane

(Ethylene oxide)

CH2

CH2

O

2 CH2

=CH2

+ O2

Ag2

88


Synthesis of Epoxides-2Synthesis of Epoxides-2• The most common laboratory method for the

synthesis of epoxides is oxidation of an alkene using a peroxycarboxylic acid (a peracid) such as peroxyacetic acid

C H3

C O O H

Peroxyacetic acid

(Peracetic acid)

O

88


Synthesis of Epoxides-2Synthesis of Epoxides-2• Epoxidation of cyclohexene

A carboxylic

acid

1,2-Epoxycyclohexane

(C yclohexene oxide)

A p eroxy-

carboxylic

acid

C yclohexene

+

+

OH

H

O

O

R C O H

C H2

C l2

R C O O H

88


Hydrolysis of EpoxidesHydrolysis of Epoxides• In the presence of an acid catalyst, an epoxide is

hydrolyzed to a glycol

+

Ethylene oxide

1,2-Ethanediol

(Ethylene glycol)

C H2

O

C H2

H O C H2

C H2

O HH2

OH

+

88


Hydrolysis of EpoxidesHydrolysis of Epoxides• Step 1: proton transfer to the epoxide to form a

bridged oxonium ion intermediate

H2

C C H2

O

OH H

H

H2

C C H2

O

H

++

88


Hydrolysis of EpoxidesHydrolysis of Epoxides• Step 2: attack of H2O from the side opposite the

oxonium ion bridge

O

H H

H2

C CH2

O

H

+

O

H H

H2

C CH2

O

H

+

88


Hydrolysis of EpoxidesHydrolysis of Epoxides• Step 3: proton transfer to solvent to complete the

hydrolysis

O

H H

H2

C CH2

O

H

+

O

H H

O

H

H2

C CH2

O

H

+ OH H

H

+

88


Hydrolysis of EpoxidesHydrolysis of Epoxides• Attack of the nucleophile on the protonated

epoxide shows anti stereoselectivity• hydrolysis of an epoxycycloalkane gives a trans-diol

H

H

O + H 2 OH

+

O H

O H

1,2-Epoxycyclopentane

(Cyclopentene oxide)

trans -1,2-Cyclopentanediol

88


Hydrolysis of EpoxidesHydrolysis of Epoxides• Compare the stereochemistry of the glycols

formed by these two methods

trans -1,2-Cyclopentanediol

cis- 1,2-Cyclopentanediol

O

H

H

O H

O H

O H

O H

H2

O

H+

R C O3

H

O s O4

R O O H

88


ThiolsThiols• Thiols are stronger acids than alcohols

pKa

= 8.5

CH3

CH2

SH CH3

CH2

S-

+ H3

O+

+ H2

O

pKa

= 15.9

CH3

CH2

OH CH3

CH2

O-

+ H3

O+

+ H2

O

88


ThiolsThiols• When dissolved an aqueous NaOH, they are

converted completely to alkylsulfide salts+

+

Stronger

acid

Stronger

base

Weaker base Weaker

acid

pKa

= 8.5

pKa

= 15.7

CH3

CH2

SH Na+

OH-

CH3

CH2

S-

Na+

H2

O

88


ThiolsThiols• Thiols are oxidized to disulfides by a variety of

oxidizing agents, including O2. • they are so susceptible to this oxidation that they must

be protected from air during storage

• The most common reaction of thiols in biological systems in interconversion between thiols and disulfides, -S-S-

A thiol A disulfide2

+1

+2 RSH O2

RSSR H2

O

88


Alcohols,Alcohols,

Ethers, andEthers, and

ThiolsThiols

End of Chapter 8End of Chapter 8

Documents

8 8-1 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Introduction to Organic Chemistry 2 ed William H. Brown