99-1 Organic Chemistry William H. Brown & Christopher S. Foote.

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Organic Organic Chemistry Chemistry

William H. Brown &William H. Brown &

Christopher S. FooteChristopher S. Foote

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AlcoholsAlcoholsand and

ThiolsThiolsChapter 9Chapter 9

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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 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

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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 -e-e is changed to -ol-ol

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

by the word alcoholalcohol

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Nomenclature-AlcoholsNomenclature-Alcohols

1-Propanol(Propyl alcohol)

CH3CH2 CH2OH

2-Propanol(Isopropyl alcohol)

OH

CH3CHCH3

1-Butanol(Butyl alcohol)

CH3CH2CH2CH2 OH

CH3CH2CHCH3

OH

CH3CHCH2OH

CH3

CH3COH

CH3

CH3

2-Butanol(sec-Butyl alcohol)

2-Methyl-1-propanol(Isobutyl alcohol)

2-Methyl-2-propanol(tert-Butyl alcohol)

cis-3-Methylcyclohexanol

OH

OH

Bicyclo[4.4.0]decan-3-ol

14

58

10

9 12 2

33

456 7

6

Numbering of thebicyclic ring takes precedence overthe location of -OH

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Nomenclature of AlcoholsNomenclature of AlcoholsProblem: Write the IUPAC name for each alcohol.

(a) (b)

(c)

OH

HO

OH

(d) HO

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

are named diols, triols, etc.

CH3CHCH2

HO OHCH2CH2

OH OH

CH2CHCH2

HO HO OH1,2-Ethanediol

(Ethylene glycol) 1,2-Propanediol

(Propylene glycol)1,2,3-Propanetriol

(Glycerol, Glycerine)

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Nomenclature of AlcoholsNomenclature of Alcohols Unsaturated alcohols

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

12 3

4 56

(E)-2-Hexene-1-ol(trans-2-Hexen-1-ol)

HO

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Physical PropertiesPhysical Properties Alcohols are polar compounds

They interact with themselves and with other polar compounds by dipole-dipole interactions

Dipole-dipole interaction:Dipole-dipole interaction: the attraction between the positive end of one dipole and the negative end of another

δ-

δ+

δ+O

HH

H

C

H

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Physical PropertiesPhysical Properties Hydrogen bondingHydrogen bonding: when the positive end of one

dipole is an H bonded to F, O, or N (atoms of high electronegativity) and the other end is F, O, or N• the strength of hydrogen bonding in water is

approximately 21 kJ (5 kcal)/mol• hydrogen bonds are considerably weaker than

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

physical properties

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Hydrogen BondingHydrogen Bonding

QuickTime™ and aPhoto - JPEG decompressor

are needed to see this picture.

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Physical PropertiesPhysical Properties Ethanol and dimethyl ether are constitutional

isomers. Their boiling points are dramatically different

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

bp -24°CEthanolbp 78°C

Dimethyl ether

CH3CH2 OH CH3OCH3

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Physical PropertiesPhysical Properties 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 solubility in water and boiling point

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Physical PropertiesPhysical PropertiesStructural FormulaName

bp(°C)

Solubilityin Water

Methanol 32 65 InfiniteEthane 30 -89 Insoluble

Ethanol 46 78 InfinitePropane 44 -42 Insoluble

1-Propanol 60 97 InfiniteButane 58 0 Insoluble

1-Pentanol 88 138 2.3 g/100 g1,4-Butanediol90 230 Infinite

Hexane 86 69 Insoluble

8 g/100 g117741-ButanolPentane 72 36 Insoluble

CH3CH2 CH2OH

CH3CH2 CH2CH3

CH3OH

CH3CH3

CH3CH2 OH

CH3CH2 CH3

CH3(CH2)3CH2 OH

HOCH2(CH2)2CH2 OH

CH3(CH2)4CH3

CH3(CH2)2 CH2OH

CH3(CH2)3CH3

MW

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

acidic

CH3O H O HH

CH3O:– OH

H

H

[CH3 OH]

[CH3 O-][H3O+]

+

Ka =

+ +

= 10-15.5

pKa = 15.5

:

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Acidity of AlcoholsAcidity of Alcohols

(CH3)3COH

(CH3)2CHOH

CH3CH2OH

H2O

CH3OH

CH3COOH

HClHydrogen chloride

Acetic acid

Methanol

Water

Ethanol

2-Propanol

2-Methyl-2-propanol

Structural Formula

Stronger acid

Weaker acid

*Also given for comparison are pKa values for water, acetic acid, and hydrogen chloride.

Compound pKa

-7

15.5

15.7

15.9

17

18

4.8

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Acidity of AlcoholsAcidity of Alcohols Acidity depends primarily on the degree of

stabilization and solvation of the alkoxide ion• the negatively charged oxygens of methanol and

ethanol are about as accessible as hydroxide ion for solvation; these alcohol are about as acidic as water.

• as the bulk of the alkyl group increases, the ability of water to solvate the alkoxide decreases, the acidity of the alcohol decreases, and the basicity of the alkoxide ion increases.

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

metals to liberate hydrogen gas and form metal alkoxides

Sodium methoxide(MeO-Na+)

+2CH3OH + 2Na 2CH3O- Na+ H2

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Reaction with NaHReaction with NaH Alcohols are also converted to metal salts by

reaction with bases stronger than the alkoxide ion• one such base is sodium hydride

Ethanol Sodiumhydride

Sodium ethoxideCH3CH2 OH CH3CH2 O- Na++ + H2Na+ H-

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Reaction with HXReaction with HX• 3° alcohols react very rapidly with HCl, HBr, and HI• low-molecular-weight 1° and 2° alcohols are unreactive

under these conditions

• 1° and 2° alcohols require concentrated HBr and HI to form alkyl bromides and iodides

2-Chloro-2-methylpropane2-Methyl-2-

propanol

25°CCH3COH

CH3

CH3

+ HCl CH3CCl

CH3

CH3+ H2O

reflux1-Bromobutane1-Butanol

++ HBr H2OH2O

OH Br

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Reaction with HXReaction with HX• with HBr and HI, 2° alcohols generally give some

rearrangement

• 1° alcohols with extensive -branching give large amounts of rearranged product

2-Bromopentane3-Bromopentane(major product)

3-Pentanolheat

+ +HBr + H2OOH Br

Br

a product ofrearrangement

α 2-Bromo-2-methylbutane(a product of rearrangement)

2,2-Dimethyl-1-propanol

+ +HBr H2OOHBr

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Reaction with HXReaction with HX Based on

• the relative ease of reaction of alcohols with HX (3° > 2° > 1°) and

• the occurrence of rearrangements,

Chemists propose that reaction of 2° and 3° alcohols with HX • occurs by an SN1 mechanism, and

• involves a carbocation intermediate

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Reaction with HX - SReaction with HX - SNN11Step 1: proton transfer to the OH group gives an

oxonium ion

Step 2: loss of H2O gives a carbocation intermediate

:O

H

HCH3-C

CH3

CH3+

CH3

CH3

CH3-C-OH + :H

H

H O H

HO

rapid andreversible+

+

O

H

HCH3-C

CH3

CH3 CH3

CH3

CH3-C+

H

H

O+

A 3° carbocation intermediate

slow, ratedetermining

SN1+:

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Reaction with HX - SReaction with HX - SNN11Step 3: reaction of the carbocation intermediate (a Lewis

acid) with halide ion (a Lewis base) gives the product

CH3

CH3

CH3-C+ CH3-C-Cl

CH3

CH3

2-Chloro-2-methylpropane (tert-Butyl chloride)

fast+ :Cl-

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Reaction with HX - SReaction with HX - SNN22 1° alcohols react with HX by an SN2 mechanism

Step 1: rapid and reversible proton transfer

Step 2: displacement of HOH by halide ion

:+ :H

H

H O HHO

rapid andreversible+ +

RCH2-O

H

HRCH2-OH +

:+

RCH2-OH

HBr:- RCH2-Br

H

HO+

SN2+


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Reaction with HXReaction with HX For 1° alcohols with extensive -branching

• SN1 not possible because this pathway would require a 1° carbocation

• SN2 not possible because of steric hindrance created by the -branching

These alcohols react by a concerted loss of HOH and migration of an alkyl group

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• Step 1: proton transfer gives an oxonium ion

• Step 2: concerted elimination of HOH and migration of a methyl group gives a 3° carbocation

Reaction with HXReaction with HX

:CH3-C-CH2-O-H O

H

HH OH

HCH3

CH3

CH3-C-CH2 O H

H

+

rapid and reversible+

+

2,2-Dimethyl-1-propanol

An oxonium ion

+:

CH3

CH3

:OH

HCH3-C-CH2 CH3-C-CH2-CH3

CH3

O

H

H

slow andrate determining (concerted)

A 3° carbocation intermediate

+CH3

CH3

++

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Reaction with HXReaction with HXStep 3: reaction of the carbocation intermediate (a Lewis

acid) with halide ion (a Lewis base) gives the product

CH3

CH3-C-CH2-CH3 Cl-Cl

CH3

CH3-C-CH2-CH3fast+

+

2-Chloro-2-methylbutane

:

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Reaction with PBrReaction with PBr33 An alternative method for the synthesis of 1° and

2° alkyl bromides is reaction of an alcohol with phosphorus tribromide• this method gives less rearrangement than with HBr

PBr3 H3PO30°

Phosphorousacid

+ +

2-Methyl-1-propanol

(Isobutyl alcohol)

Phosphorus tribromide

1-Bromo-2-methyl-propane

(Isobutyl bromide)

OH Br

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Reaction with PBrReaction with PBr33Step 1: formation of a protonated dibromophosphite,

which converts H2O, a poor leaving group, to a good leaving group

Step 2: displacement by bromide ion

:Br-

H

O PBr2R-CH2P BrBr

Br

R-CH2-O-H + +

a good leaving group

+:

Br - O PBr2R-CH2

H

R-CH2-Br HO-PBr2++

+SN2 :

:

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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 catalyze the reaction and to neutralize the HCl

OH SOCl2

Cl SO2 HCl

Thionylchloride

1-Heptanol

1-Chloroheptane

pyridine+

+ +

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Reaction with SOClReaction with SOCl22 Reaction of an alcohol with SOCl2 in the presence

of a 3° amine is stereoselective; proceeds with inversion of configuration

Thionylchloride

+ 3° amine +

(R)-2-Chlorooctane

SOCl2 SO2 + HClC OH

CH3(CH2)5

H3CH

(S)-2-Octanol

CCl

(CH2)5CH3

CH3

H

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Reaction with SOClReaction with SOCl22Step 1: nucleophilic displacement of chlorine

Step 2: proton transfer to the 3° amine gives an alkyl chlorosulfite

C

R1

HR2

OS

Cl

O

H+ NR3 HNR3

A 3° amine

++

An alkyl chlorosulfite

+: C

R1

HR2

OS

Cl

O

:

C

R1

HR2

O H Cl S Cl+

Thionylchloride

C

R1

HR2

O Cl-+S

Cl

O

H+: :

O

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Reaction with SOClReaction with SOCl22Step 3: backside displacement by chloride ion and

decomposition of the chlorosulfite ester gives the alkyl chloride

+C

R1

HR2

OS

O

Cl

OS

OSN2 C

R1

HR2

Cl +Cl:- :Cl-+

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Alkyl SulfonatesAlkyl Sulfonates Sulfonyl chlorides are derived from sulfonic

acids • sulfonic acids are strong acids like sulfuric acid

A sulfonylchloride

A sulfonate anion(a very weak base and

stable anion; a verygood leaving group

A sulfonic acid(a very strong acid)

R-S-OH R-S-O-R-S-ClO

O

O

O

O

O

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Alkyl SulfonatesAlkyl Sulfonates A commonly used sulfonyl chloride is p-

toluenesulfonyl chloride (Ts-Cl)

+

p-Toluenesulfonylchloride

pyridine

Ethyl p-toluenesulfonate(Ethyl tosylate)

+

Ethanol

O

OCl-S CH3CH3CH2 OH

HClCH3CH2 O-SO

OCH3

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Alkyl SulfonatesAlkyl Sulfonates Another commonly used sulfonyl chloride is

methanesulfonyl chloride (Ms-Cl)

Methanesulfonylchloride

+pyridine

+

Cyclohexyl methanesulfonate

(Cyclohexyl mesylate)

Cyclohexanol

OH Cl-S-CH3

O-S-CH3 HCl

O

O

O

O

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Alkyl SulfonatesAlkyl Sulfonates Sulfonate anions are very weak bases (the

conjugate base of a strong acid) and are very good leaving groups for SN2 reactions

Conversion of an alcohol to a sulfonate ester converts HOH, a very poor leaving group, into a sulfonic ester, a very good leaving group

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Alkyl SulfonatesAlkyl Sulfonates This two-step procedure converts (S)-2-octanol

to (R)-2-octyl acetateStep 1: formation of a p-toluenesulfonate (Ts) ester

(S)-2-Octanol

+ pyridine

(S)-2-Octyl tosylate

+C OH

CH3 (CH2)5

CH3

H

C

HCH3

CH3 (CH2)5

OTsCl-Ts HCl

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Alkyl SulfonatesAlkyl SulfonatesStep 2: nucleophilic displacement of tosylate

(S)-2-Octyl tosylate

+

(R)-2-Octyl acetate

ethanol

+

C OTs

CH3 (CH2)5

CH3

H

CH

CH3

(CH2 )5CH3

CH3CO Na+OTs-

CH3CO- Na+ SN2O

O

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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 at or slightly above room temperature

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Dehydration of ROHDehydration of ROH

180°CCH3CH2 OH

H2 SO4CH2=CH2 + H2O

140°CCyclohexanol Cyclohexene

OH+ H2 O

H2 SO4

CH3COH

CH3

CH3

H2 SO4CH3C=CH2

CH3

+ H2 O50°C

2-Methyl-2-propanol(tert-Butyl alcohol)

2-Methylpropene(Isobutylene)

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

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

1-Butene (20%)

2-Butene (80%)

2-Butanol

+

heat85% H3PO4

CH3CH=CHCH3

CH3CH2 CHCH3

CH3CH2 CH=CH2 + H2O

OH

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Dehydration of ROHDehydration of ROH Dehydration of 1° and 2° alcohols is often

accompanied by rearrangement

• acid-catalyzed dehydration of 1-butanol gives a mixture of three alkenes

OH

H2SO4

140 - 170°C+

3,3-Dimethyl-2-butanol

2,3-Dimethyl-2-butene

(80%)


(20%)

H2SO4

140 - 170°C1-Butanol

+

trans-2-butene(56%)

cis-2-butene(32%)

+

1-Butene(12%)

OH

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Dehydration of ROHDehydration of ROH Based on evidence of

• ease of dehydration (3° > 2° > 1°)• prevalence of rearrangements

Chemists propose a three-step mechanism for the dehydration of 2° and 3° alcohols• because this mechanism involves formation of a

carbocation intermediate in the rate-determining step, it is classified as E1

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Dehydration of ROHDehydration of ROHStep 1: proton transfer to the -OH group gives an

oxonium ion

Step 2: loss of H2O gives a carbocation intermediate

:HO

CH3CHCH2CH3 H O

H

H

OH H

CH3CHCH2CH3 :O

H

H+

An oxonium ion

rapid andreversible

+

++

CH3CHCH2CH3 H2O+

A 2° carbocationintermediate

+slow, rate

determining OH H

CH3CHCH2CH3

+

:

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Dehydration of ROHDehydration of ROHStep 3: proton transfer 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

CH3-CH-CH-CH3 HHO

CH3-CH=CH-CH3 HH

H

O

rapid andreversible+

+

++

H

:

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•Dehydration of ROHDehydration of ROH 1° alcohols with little -branching give terminal

alkenes and rearranged alkenes• Step 1: proton transfer to OH gives an oxonium ion

• Step 2: loss of H from the -carbon and H2O from the α-carbon gives the terminal alkene

:O-H H O H

H

O-H

H

O-HH

++

++

rapid andreversible

1-Butanol

:

O-H+

H

O

H

HHH

++

H O HH

+1-Butene

E2:

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Dehydration of ROHDehydration of ROHStep 3: shift of a hydride ion from -carbon and loss of

H2O from the α-carbon gives a carbocation

Step 4: proton transfer to solvent gives the alkene

:O-H

H

O-H

HHH H

+++

1,2-shift of ahydride ion

A 2° carbocation

H

H2O H3O++ E1+ + +

trans-2-butene

cis-2-butene

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Dehydration of ROHDehydration of ROH Dehydration with rearrangement occurs by a

carbocation rearrangement



H2O

H2O



+ H3O+

+ H3O+

3,3-Dimethyl-2-butanol

-H2O

H+

+

+

OH

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

hydration are competing processes

Principle of microscopic reversibility:Principle of microscopic reversibility: the sequence of transition states and reactive intermediates in the mechanism of a reversible reaction must be the same, but in reverse order, for the backward reaction as for the forward reaction

An alkene An alcohol

C C C C

H OH

+ H2O

acidcatalyst

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Pinacol RearrangementPinacol Rearrangement The products of acid-catalyzed dehydration of a

glycol are different from those of alcohols

2,3-Dimethyl-2,3-butanediol(Pinacol)

3,3-Dimethyl-2-butanone(Pinacolone)

H2SO4CH3-C-C-CH3

HO

H3C CH3

OH

CH3-C-C-CH3

CH3

CH3

+ H2O

O

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Pinacol RearrangementPinacol RearrangementStep 1: proton transfer to OH gives an oxonium ion

Step 2: loss of water gives a carbocation intermediate

: rapid andreversible

An oxonium ion

++

H

H H H

HO OCH3-C-C-CH3

HO

H3C CH3

O-HCH3-C-C-CH3

HO

H3C CH3

O-H

H+

+ :

+CH3-C-C-CH3

HO

H3C CH3

O-H

H+

CH3-C-C-CH3

HO

H3C CH3

+ H2O:

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Pinacol RearrangementPinacol RearrangementStep 3: a 1,2- shift of methyl gives a more stable

carbocation

Step 4: proton transfer to solvent completes the reaction

+CH3-C-C-CH3

O

H3C

CH3H

+CH3-C-C-CH3

O CH3H

CH3

+

CH3-C-C-CH3

O CH3H

CH3

:

+

CH3-C-C-CH3

O CH3

H

CH3

H2O: + CH3-C-C-CH3

O CH3

CH3

H3O++

:

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

or a carboxylic acid, depending on the experimental conditions

• to an aldehyde is a two-electron oxidation• to a carboxylic acid is a four-electron oxidation

[O] [O]OH

H

HCH3-C

A primary alcohol

An aldehyde A carboxylic acid

CH3-C-H

O

CH3-C-OH

O

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Oxidation: 1° ROHOxidation: 1° ROH A common oxidizing agent for this purpose is

chromic acid, prepared by dissolving chromium(VI) oxide or potassium dichromate in aqueous sulfuric acid

Potassiumdichromate

Chromic acid

K2Cr2O7H2 SO4 H2 Cr2O7

H2 O2H2 CrO4

+Chromic acidChromium(VI)

oxide

CrO3 H2 O H2 CrO4H2 SO4

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Oxidation: 1° ROHOxidation: 1° ROH Oxidation of 1-octanol gives octanoic acid

• the aldehyde intermediate is not isolated

CH3(CH2)6CH2OHCrO3

H2SO4, H2O

CH3(CH2)6CHO

CH3(CH2)6COHO

Octanal(not isolated)

Octanoic acid

1-Octanol

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Oxidation: 1° ROHOxidation: 1° ROH 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+

CrO3Cl-

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

PCC

Geraniol GeranialOH H

O

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

and chromic acid

2-Isopropyl-5-methyl-cyclohexanone(Menthone)

2-Isopropyl-5-methyl-cyclohexanol(Menthol)

acetone

OH O+ H2 CrO4 + Cr

3 +

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Oxidation: 1° & 2° ROHOxidation: 1° & 2° ROH The mechanism of chromic acid oxidation of an

alcohol involves two stepsStep 1: formation of an alkyl chromate ester

H

OH+ HO-Cr-OH

O

O

H

O-Cr-OH+

O

OH2O

An alkyl chromate

Cyclohexanol

fast and reversible

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Oxidation: 1° & 2° ROHOxidation: 1° & 2° ROHStep 2: proton transfer to solvent and decomposition of

the alkyl chromate ester gives the product

:H

O Cr-OH

O

O

OHH

O

O

O-

Cr-OH+ +

Cyclohexanone

chromium(IV)


H3O+

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Oxidation: 1° & 2° ROHOxidation: 1° & 2° ROH In chromic acid oxidation of a CHO group, it is

the hydrated form that is oxidized fast andreversible

R-C-H + H2O R-C-OH

OH

HAn aldehyde An aldehyde

hydrate

R-C-OH

OH

H

R-C-OHH2CrO4

An alkylchromate ester

R-C-OH

O-CrO3H

HH2OA carboxylic acid

O

:

O

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Oxidation of GlycolsOxidation of Glycols Glycols are cleaved by oxidation with periodic

acid, H5IO6 (or, alternatively HIO4•2H2O)

OH

OH+ HIO4 CHO

CHO+ HIO3

cis-1,2-Cyclo-hexanediol

HexanedialPeriodicacid

Iodicacid

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Oxidation of GlycolsOxidation of Glycols• the glycol undergoes a two-election oxidation

• periodic acid undergoes a two-electron reduction

C

C

OH

OH C O

C O+ 2H

+ + 2e

-

Iodic acidPeriodic acid

+ 2H+

+ 2e-

HIO4 HIO3 + H2O

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Oxidation of GlycolsOxidation of Glycols The mechanism of periodic acid oxidation of a

glycol is divided into two stepsStep 1: formation of a cyclic periodic ester

Step 2: redistribution of electrons within the five-membered ring

A cyclic periodic ester

+C

C

OH

OHIO

OOC

CO

OO

O

IOH OH + H2O

C O

C OI

O

O

C

C O

OOH + HIO3

99

9-9-6767

Thiols: StructureThiols: Structure The functional group of a thiol is an -

SHSH (sulfhydrylsulfhydryl) 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

99

9-9-6868

NomenclatureNomenclature IUPAC names:

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

• change the suffix -e-e to -thiol-thiol• as a substituent, it is a sulfanyl group

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

word mercaptanmercaptan

CH3CH2 SH

CH3

CH3CHCH2SH HSCH2CH2OH

Ethanethiol(Ethyl mercaptan)

2-Methyl-1-propanethiol(Isobutyl mercaptan)

2-Sulfanylethanol(Mercaptoethanol)

99

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Thiols: Physical PropertiesThiols: Physical Properties 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

1177865

1-ButanolEthanolMethanol

98356

1-ButanethiolEthanethiolMethanethiol

bp (°C)Alcoholbp (°C)Thiol

99

9-9-7070

Thiols: Physical PropertiesThiols: Physical Properties Low-molecular-weight thiols = STENCH

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

3-Methyl-1-butanethiol

CH3

CH3CH=CHCH2SHCH3CHCH2CH2SH

2-Butene-1-thiol

99

9-9-7171

Thiols: preparationThiols: preparation The most common preparation of thiols, RSH,

depends on the very high nucleophilicity of hydrosulfide ion, HS-

Sodium hydrosulfide

1-Decanethiol

1-Iododecane

+

+ SN2CH3(CH2)8 CH2I Na

+SH

-

CH3(CH2)8 CH2SH Na+I-

99

9-9-7272

Thiols: acidityThiols: acidity Thiols are stronger acids than alcohols

pKa = 8.5CH3CH2SH CH3CH2S

- + H3O++ H2O

pKa = 15.9CH3CH2OH CH3CH2O

- + H3O+

+ H2O

99

9-9-7373

Thiols: acidityThiols: acidity 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

CH3CH2 SH Na+OH-

CH3CH2 S-Na+ H2 O

99

9-9-7474

Thiols: oxidationThiols: oxidation 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--S-S-

A thiol A disulfide2

+ 1 +2RSH O2 RSSR H2 O

99

9-9-7575

Prob 9.22Prob 9.22 From each pair of compounds, select the one more

soluble in water.

(a) (b) orCH2Cl2 or CH3 OH CH3CCH3 CH3CCH3

(c) CH3CH2 Cl or NaCl

O CH2

(d)

(e)

orCH3CH2 CH2SH CH3CH2 CH2OH

orCH3CH2 CHCH2CH3 CH3CH2 CCH2CH3

OH O

99

9-9-7676

Prob 9.24Prob 9.24 From each pair of compounds, select the one more

soluble in water.

CH2Cl2 CH3CH2OH

CH3CH2OHCH3CH2OCH2CH3

CH3(CH2)3CH3CH3CH2OCH2CH3

CH3CCH3

OCH3CH2OCH2CH3

(a)

(b)

or

or

(c)

(d) or

or

99

9-9-7777

Prob 9.25Prob 9.25 Calculate the percent of each isomer present at

equilibrium. Assume a value of G° (equatorial to axial) for cyclohexanol is 4.0 kJ (0.95 kcal/mol).

HO

OH

Al[OCH(CH3)2)]3

A B

acetone

99

9-9-7878

Prob 9.26Prob 9.26 Complete each acid-base reaction. Use curved arrows to

show the flow of electrons.

(a)+

(b)

CH3CH2OH + HOH

CH3CH2OCH2CH3 + HOSOH

H

O

O

(c)CH3CH2CH2CH2CH2OH + HI

99

9-9-7979

Prob 9.26 (cont’d)Prob 9.26 (cont’d) Complete each acid-base reaction. Use curved arrows to

show the flow of electrons.

(d)CH3CH2CH2COHO

HOSOHO

O

+

+(f)

(e) OH + BF3

CH3 CH= CHCHCH3 + HOH

99

9-9-8080

Prob 9.27Prob 9.27 From each pair, select the stronger acid and write a

structural formula for its conjugate base.(a)

(b)

(c)

(d)

H2O or H2CO3

CH3OH or CH3COOH

CH3CH2OH or CH3CH2SH

CH3CH2OH or CH3C CH

99

9-9-8181

Prob 9.28Prob 9.28 From each pair select the stronger base. Write a

structural formula for its conjugate acid.

CH3CH2O- CH3C C-

OH- or CH3O- (each in H2O)

NH2-

CH3CH2S- CH3CH2O-

CH3CH2O-

or(b)

(a)

(d) or

or(c)

99

9-9-8282

Prob 9.29Prob 9.29 In each equilibrium, label the stronger acid and base, and

the weaker acid and base. Estimate the position of equilibrium.

++(a)CH3CH2O- CH3C CH3CH2OH CH CH3C C–

++(b) CH3CH2O- HCl CH3CH2OH Cl -

++(c)CH3COOH CH3CH2O- CH3COO- CH3CH2OH

99

9-9-8383

Prob 9.32Prob 9.32 Complete each equation, but do not balance

(b)

(a)

OH + SOCl2

OH + H2CrO4

+

(d)

(c) OH HCl

HOOH + HBr

(excess)

99

9-9-8484

Prob 9.32 (cont’d)Prob 9.32 (cont’d) Complete each equation, but do not balance

(e)

(f)

OH

OH

OH

+

+ H2CrO4

HIO4

(g)1. OsO4, H2O2

2. HIO4

(h) OH + SOCl2

99

9-9-8585

Prob 9.34Prob 9.34 When A or B is treated with HBr, racemic 2,3-

dibromobutane is formed. When C or D is treated with HBr, meso 2,3-dibromobutane is formed. Explain.

A B C D

HHO

CH3

Br

CH3

H

OHH

CH3

H

CH3

Br

OHH

CH3

Br

CH3

H

HHO

CH3

H

CH3

Br

A B C D

HHO

CH3

Br

CH3

H

OHH

CH3

H

CH3

Br

OHH

CH3

Br

CH3

H

HHO

CH3

H

CH3

Br

99

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Prob 9.36Prob 9.36 Show how to bring about each conversion.

(a) (b)OH OH OH

OHOH

OH

(c)

(d)

O

HO

(e) CH2 CH2Cl

99

9-9-8787

Prob 9.36 (cont’d)Prob 9.36 (cont’d) Show how to bring about each conversion.

(f) CHCH3 CCH3

(g)

(h)OH OH

OH

CH3(CH2)6CH2OH CH3(CH2)6CHO

O

(i) CH2 COHO

99

9-9-8888

Prob 9.37Prob 9.37 Propose a mechanism for the following pinacol

rearrangement.

+BF3 •Et2O

H2 O

HO OH O

99

9-9-8989

Prob 9.40Prob 9.40 Propose a mechanism for this reaction.

O CH2OH

H ArSO3H

O+ H2 O

DihydropyranTetrahydrofurfuryl alcohol

99

9-9-9090

Prob 9.43Prob 9.43 Show how to bring about this conversion.

OHO

O

99

9-9-9191

Prob 9.44Prob 9.44 Propose a structural formula for the product of this

reaction and a mechanism for its formation.

OH

OTs

NaOHC7H12O

99

9-9-9292

Prob 9.45Prob 9.45 Propose a mechanism for the formation of the products

of this solvolysis.

TsOH2 O

OH

DMSO

OH

Chrysanthemyl tosylate

Artemisia alcohol Yomogi alcohol

+

99

9-9-9393

Prob 9.46Prob 9.46 Show how to convert cyclohexene to each compound.

O

O OH OCH3

(d)

(b) (c)(a)

(e) HO

HO

99

9-9-9494

Alcohols Alcohols and and ThiolsThiols

End of Chapter 9End of Chapter 9

99-1 Organic Chemistry William H. Brown & Christopher S. Foote.

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