10-1 Organic Chemistry William H. Brown Christopher S. Foote Brent L. Iverson William H. Brown Christopher S. Foote Brent L. Iverson

10-10-11

Organic Organic ChemistryChemistry

William H. BrownWilliam H. Brown

Christopher S. FooteChristopher S. Foote

Brent L. IversonBrent L. Iverson

William H. BrownWilliam H. Brown

Christopher S. FooteChristopher S. Foote

Brent L. IversonBrent L. Iverson

10-10-22

AlcoholsAlcoholsand Thiolsand Thiols

Chapter 10Chapter 10

10-10-33

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

108.9°O

CH H

H

H

10-10-44

Nomenclature-AlcoholsNomenclature-Alcohols

IUPAC names• the parent chain is the longest chain that contains the

OH group• number the parent chain to give the OH group the

lowest possible number• change the suffix -e-e to -ol-ol

Common names • name the alkyl group bonded to oxygen followed by

the word alcoholalcohol

10-10-55

Nomenclature-AlcoholsNomenclature-Alcohols

Examples

1-Propanol(Propyl alcohol)

2-Propanol(Isopropyl alcohol)

1-Butanol(Butyl alcohol)

OHOH

OH

2-Butanol(sec-Butyl alcohol)

2-Methyl-1-propanol(Isobutyl alcohol)

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

OHOH

OH

cis-3-Methylcyclohexanol

OH

OH

Bicyclo[4.4.0]decan-3-ol

14

58

10

912 2

3

3

4

56 76

Numbering of thebicyclic ring takes precedence overthe location of -OH

10-10-66

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)

10-10-77

Nomenclature of AlcoholsNomenclature of Alcohols

Unsaturated alcohols • show the double bond by changing the infix from -an-

to -en--en-• show the the OH group 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

10-10-88

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

O

HH

H

CH

δ+δ-

δ+

10-10-99


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

10-10-1010

Hydrogen BondingHydrogen Bonding

10-10-1111


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 resulting in a higher boiling point

• there is no comparable attractive force between molecules of dimethyl ether

bp -24°CEthanolbp 78°C

Dimethyl ether

CH3CH2OH CH3OCH3

10-10-1212


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

10-10-1313


Structural 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

10-10-1414

Acidity of AlcoholsAcidity of Alcohols

In dilute aqueous solution, alcohols are weakly acidic

CH3O H : HOH

[CH3OH]

[CH3O-][H3O+]

CH3O:– O

H

HH+

+

= 10-15.5

pKa = 15.5

Ka =

+

10-10-1515


(CH3)3COH

(CH3)2CHOH

CH3CH2OH

H2O

CH3OH

CH3COOH

HCl

15.5

15.7

15.9

17

18

4.8

Hydrogen 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

10-10-1616


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

10-10-1717

Reaction with MetalsReaction with Metals

Alcohols react with Li, Na, K, and other active metals to liberate hydrogen gas and form metal alkoxides

Alcohols are also converted to metal alkoxides by reaction with bases stronger than the alkoxide ion• one such base is sodium hydride

2CH3OH 2Na 2CH3O- Na+ H2Sodium methoxide

(MeO-Na+)

++

CH3CH2OH Na+ H- CH3CH2O- Na+ H2

Ethanol Sodiumhydride

Sodium ethoxide+ +

10-10-1818

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

reflux1-Bromobutane1-Butanol

++ HBr H2OH2O

OH Br

OH + H2O+HCl 25°C Cl

2-Methyl-2-propanol

2-Chloro-2-methylpropane

10-10-1919


• with HBr and HI, 2° alcohols generally give some rearranged product

• 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

10-10-2020


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

10-10-2121

Reaction with HX - SReaction with HX - SNN11

Step 1: proton transfer to the OH group gives an oxonium ion

Step 2: loss of H2O gives a carbocation intermediate

CH3

CH3

CH3-C-OH:

H

H

H O O

H

H

CH3-C

CH3

CH3

: H

H

O+

+

rapid andreversible+

+

O

H

H

CH3-C

CH3

CH3 CH3

CH3

CH3-C+ :

H

H

O+

A 3° carbocation intermediate

slow, ratedetermining

SN1+

10-10-2222


Step 3: reaction of the carbocation intermediate (an electrophile) with halide ion (a nucleophile) gives the product

CH3

CH3

CH3-C+ :Cl CH3-C-Cl

CH3

CH3

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

fast+

10-10-2323


1° alcohols react with HX by an SN2 mechanism

Step 1: rapid and reversible proton transfer

Step 2: displacement of HOH by halide ion

RCH2-OH:

H

H

H O RCH2-O

H

H

: H

H

O+

rapid andreversible+ +

+

Br:- RCH2-O

H

H

RCH2-Br :H

HO

++

SN2+


10-10-2424


For 1° alcohols with extensive -branching• SN1 is not possible because this pathway would

require a 1° carbocation

• SN2 is 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

10-10-2525

• Step 1: proton transfer gives an oxonium ion

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


+OH

O

H

HH+

rapid and reversible+

O H

H2,2-Dimethyl-1-propanol

An oxonium ion

OH

H+

OH

H slow andrate determining (concerted)

OH

H

+

A 3° carbocationintermediate

10-10-2626


Step 3: reaction of the carbocation intermediate (an electrophile) with halide ion (a nucleophile) gives the product

2-Chloro-2-methylbutane

Cl-

+fast Cl

10-10-2727

Reaction with PBrReaction with PBr33

An alternative method for the synthesis of 1° and 2° bromoalkanes 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-methylpropane(Isobutyl bromide)

OH Br

10-10-2828

Reaction with PBrReaction with PBr33

Step 1: formation of a protonated dibromophosphite converts H2O, a poor leaving group, to a good leaving group

Step 2: displacement by bromide ion gives the alkyl bromide

BrO PBr2R-CH2

H

P BrBr

Br

R-CH2-O-H + +

a good leaving group

+••

Br - O PBr2R-CH2

H

R-CH2-Br HO-PBr2

+++

SN2• • • •

10-10-2929

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+

+ +

10-10-3030


Reaction of an alcohol with SOCl2 in the presence of a 3° amine is stereoselective• it occurs with inversion of configuration

OH

SOCl2

Cl

SO2 HCl+3° amine

+ +(S)-2-Octanol Thionyl

chloride(R)-2-Chlorooctane

10-10-3131


Step 1: formation of an alkyl chlorosulfite

Step 2: nucleophilic displacement of this leaving group by chloride ion gives the chloroalkane

C

R1

HR2

O SO

ClCl +C

R1

HR2

Cl + Cl+ O SOSN2

C

R1

HR2

O H Cl-S-Cl

OC

R1

HR2

O SO

ClH-Cl+ +

An alkylchlorosulfite

10-10-3232

Alkyl SulfonatesAlkyl Sulfonates

Sulfonyl chlorides are derived from sulfonic acids • sulfonic acids, like sulfuric acid, are strong acids

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

10-10-3333

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

10-10-3434


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

10-10-3535


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

10-10-3636


This two-step procedure converts (S)-2-octanol to (R)-2-octyl acetateStep 1: formation of a p-toluenesulfonate (Ts) ester

Step 2: nucleophilic displacement of tosylate

OH

TsCl

OTs

HCl(S)-2-Octanol (S)-2-Octyl tosylate

+ pyridine +

Tosylchloride

O-Na+

O OTs O

O

Na+OTs-

(S)-2-Octyl tosylate

+

Sodiumacetate

ethanol

SN2+

(R)-2-Octyl acetate

10-10-3737

Dehydration of ROHDehydration of ROH

An alcohol can be converted to an alkene by acid-catalyzed dehydration (a type of -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

10-10-3838


180°CCH3CH2OH

H2SO4CH2=CH2 + H2O

140°CCyclohexanol Cyclohexene

OH+ H2O

H2SO4

CH3COH

CH3

CH3

H2SO4 CH3C=CH2

CH3+ H2O

50°C

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

2-Methylpropene(Isobutylene)

10-10-3939


• where isomeric alkenes are possible, the alkene having the greater number of substituents on the double bond (the more stable alkene) usually predominates (Zaitsev rule)

1-Butene (20%)

2-Butene (80%)

2-Butanol

+

heat85% H3PO4

CH3CH=CHCH3

CH3CH2 CHCH3

CH3CH2 CH=CH2 + H2O

OH

10-10-4040


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

10-10-4141


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

10-10-4242


Step 1: proton transfer to the -OH group gives an oxonium ion

Step 2: loss of H2O gives a carbocation intermediate

O

H O

H

H+

+

rapid andreversible O

OH

H+

H H+H


OH H+ slow, rate

determiningH2O+

10-10-4343


Step 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

rapid andreversible

OH

HHH

+ + O

H

++ H H

10-10-4444

•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 O H

H

H O-H

H

O-HH

++

++

1-Butanol

rapid andreversible

H

OH O-HHH H

H O H

H

O H

H

++

++

1-Butene

E2 +

10-10-4545


Step 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

HHHO-HH

+++

1,2-shift of ahydride ion

A 2° carbocation

H O H

H

+ E1+ ++

+

trans-2-Butene cis-2-Butene

HH O

H

10-10-4646


Dehydration with rearrangement occurs by a carbocation rearrangement



H2O

H2O



+ H3O+

+ H3O+

OH

3,3-Dimethyl-2-butanol

-H2O

H+

+

+

10-10-4747


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 reverse reaction as for the forward reaction

An alkene An alcohol

C C C C

H OH

+ H2O

acidcatalyst

10-10-4848

Pinacol RearrangementPinacol Rearrangement

The products of acid-catalyzed dehydration of a glycol are different from those of alcohols

OHHOH2SO4

OH2O

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

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

+

10-10-4949


Step 1: proton transfer to OH gives an oxonium ion

Step 2: loss of water gives a carbocation intermediate

OHHO +

H

H HO+

rapid andreversible OHO

+ H

H

OHH

An oxonium ion

OHO HHHO

+ H2O

A 3o carbocationintermediate

10-10-5050


Step 3: a 1,2- shift of methyl gives a more stable carbocation

Step 4: proton transfer to solvent completes the reaction

A resonance-stabilized cation intermediate

OH OH OH

OHH2O +

O+H3O

+

10-10-5151

Oxidation: 1° ROHOxidation: 1° ROH

Oxidation of a primary alcohol gives 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

10-10-5252

Oxidation of ROHOxidation of 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

K2Cr2O7H2SO4 H2Cr2O7

H2O2H2CrO4

+Chromic acidChromium(VI)

oxide

CrO3 H2O H2CrO4H2SO4

10-10-5353


Oxidation of 1-octanol gives octanoic acid• the aldehyde intermediate is not isolated

OHH2CrO4

H

O

OH

O

1-Hexanol Hexanal(not isolated)

Hexanoic acid

H2O, acetone

10-10-5454


2° alcohols are oxidized to ketones by chromic acid

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

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

acetone+ H2CrO4 + Cr

3+OH O

10-10-5555

Chromic Acid Oxidation of ROHChromic Acid Oxidation of ROH

• Step 1: formation of a chromate ester

• Step 2: reaction of the chromate ester with a base, here shown as H2O

H

OH O

HO-Cr-OH

OH

O-Cr-OH

O

O

H2O

fast and reversible

+ +

An alkyl chromateCyclohexanol

H

O Cr-OH

O

O

OHH

O O H

H

H

O

O -

Cr-OH+ +

Cyclohexanone

chromium(IV)

+


chromium(VI)

10-10-5656

Chromic Acid Oxidation of RCHOChromic Acid Oxidation of RCHO

• chromic acid oxidizes a 1° alcohol first to an aldehyde and then to a carboxylic acid

• in the second step, it is not the aldehyde per se that is oxidized but rather the aldehyde hydrate

OR-C-H H2O

H2CrO4R-C-OH

O-CrO3H

HH2O

R-C-OH

OH

H

R-C-OHO

HCrO3-

+

An aldehyde An aldehyde hydrate

fast andreversible

A carboxylic acid

+ H3O++

10-10-5757

Oxidation: 1° ROH to RCHOOxidation: 1° ROH to RCHO

Pyridinium chlorochromate (PCC):Pyridinium chlorochromate (PCC): a form of Cr(VI) prepared by dissolving CrO3 in aqueous HCl and adding pyridine to precipitate PCC as a solid

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

CrO3 HClN N

H

ClCrO3-

chlorochromate ion

pyridinium ion

Pyridinium chlorochromate (PCC)

Pyridine

+ +

10-10-5858


• PCC oxidizes a 1° alcohol to an aldehyde

• PCC also oxidizes a 2° alcohol to a ketone

PCC

Geraniol GeranialOH H

O

OH PCC O

MenthoneMenthol

10-10-5959

Oxidation of Alcohols by NADOxidation of Alcohols by NAD++

• biological systems do not use chromic acid or the oxides of other transition metals to oxidize 1° alcohols to aldehydes or 2° alcohols to ketones

• what they use instead is a NAD+

• the Ad part of NAD+ is composed of a unit of the sugar D-ribose (Chapter 25) and one of adenosine diphosphate (ADP, Chapter 28)

N

NH2

O

AdN

OH

O

Nicotinic acid(Niacin; Vitamin B6)

Nicotinamide adenine dinucleotide (NAD+)

A pyridinering

An amide group

The plus sign in NAD+

represents this chargeon nitrogen

The businessend of NAD+

10-10-6060


• when NAD+ functions as an oxidizing agent, it is reduced to NADH

• in the process, NAD+ gains one H and two electrons; NAD+ is a two-electron oxidizing agent

AdN

CNH2

O

H+ 2e-

AdN

CNH2

H H O

+

NAD+

(oxidized form)NADH

(reduced form)

reduction

oxidation+ +

10-10-6161


• NAD+ is the oxidizing in a wide variety of enzyme-catalyzed reactions, two of which are

CH3CH2OH NAD+ CH3CHO

NADH H++

alcoholdehydrogenase

+ +Ethanol Ethanal

(Acetaldehyde)

CH3CHCOO-OH

NAD+ CH3CCOO-O

NADH H++ ++

lactatedehydrogenase

Lactate Pyruvate

10-10-6262


• mechanism of NAD+ oxidation of an alcohol

• hydride ion transfer to NAD+ is stereoselective; some enzymes catalyze delivery of hydride ion to the top face of the pyridine ring, others to the bottom face

H

C

O

H

N

C-NH2

O

Ad

H

- B

NAD+ NADH

C-NH2

N

O

Ad

H H

C

OH

BE E

2

3

••

• •••

+

reductionof NAD+

oxidationof NADH

1

••4-5

••• •

10-10-6363

Oxidation of GlycolsOxidation of Glycols

Glycols are cleaved by oxidation with periodic acid, HIO4

OH

OH+ HIO4 CHO

CHO+ HIO3

cis-1,2-Cyclo-hexanediol

HexanedialPeriodicacid

Iodicacid

10-10-6464


The mechanism of periodic acid oxidation of a glycol is divided into two stepsStep 1: formation of a cyclic periodate

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

A cyclic periodate

+C

C

OH

OHIO

OOC

CO

OO

O

IOH OH + H2O

OC

C O

I

O

OH

O

C O

C OO

O

I OH+OC

C O

I

O

OH

O

C O

C OO

O

I OH+

10-10-6565


• this mechanism is consistent with the fact that HIO4 oxidations are restricted to glycols that can form a five-membered cyclic periodate

• glycols that cannot form a cyclic periodate are not oxidized by HIO4

OH

OH

OH

HOHIO4

O

O

The trans isomer isunreactive toward

periodic acid

The cis isomer forms a cyclic periodate and

is cleaved

10-10-6666

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

10-10-6767

NomenclatureNomenclature

IUPAC names:• the parent is the longest chain that contains the -SH

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

group

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

word mercaptanmercaptan

1-Butanethiol(Butyl mercaptan)

2-Methyl-1-propanethiol(Isobutyl mercaptan)

2-Sulfanylethanol(2-Mercaptoethanol)

SH SH OHHS

10-10-6868

Thiols: Physical PropertiesThiols: Physical Properties Because of the low polarity of the S-H bond,

thiols show little association by hydrogen bonding• they have lower boiling points and are less soluble in

water than alcohols of comparable MW

• the boiling points of ethanethiol and its constitutional isomer dimethyl sulfide are almost identical

1177865

1-ButanolEthanolMethanol

98356

1-ButanethiolEthanethiolMethanethiol

bp (°C)Alcoholbp (°C)Thiol

CH3CH2SH CH3SCH3Dimethyl sulfide

(bp 37°C)Ethanethiol(bp 35°C)

10-10-6969

Thiols: Physical PropertiesThiols: Physical Properties Low-molecular-weight thiols = STENCH• the scent of skunks is due primarily to these two thiols

• a blend of low-molecular weight thiols is added to natural gas as an odorant; the two most common of these are

3-Methyl-1-butanethiol(Isopentyl mercaptan)

2-Butene-1-thiol

SHSH

2-Methyl-2-propanethiol(tert-Butyl mercaptan)

2-Propanethiol(Isopropyl mercaptan)

SH SH

10-10-7070

Thiols: preparationThiols: preparation

The most common preparation of thiols depends on the very high nucleophilicity of hydrosulfide ion, HS-

CH3(CH2)8CH2I Na+ SH

-CH3(CH2)8CH2SH Na

+I-

Sodium hydrosulfide

1-Decanethiol1-Iododecane

++SN2ethanol

Na+ SH

-ICH2CO

- Na

+O

HSCH2CO- Na

+O

Na+ I

-

Sodium hydrosulfide

Sodium mercaptoacetate (Sodium thioglycolate)

++SN2

Sodiumiodoacetate

10-10-7171

Thiols: acidityThiols: acidity

Thiols are stronger acids than alcohols

• when dissolved an aqueous NaOH, they are converted completely to alkylsulfide salts

CH3CH2OH +

CH3CH2SH

CH3CH2O-

CH3CH2S-

H3O+

H3O+

H2O

H2O pKa = 8.5

pKa = 15.9+

++

CH3CH2SH Na+OH

- CH3CH2S-Na+ H2O+ +

pKa 8.5(Stronger acid)

pKa 15.7(Weaker acid)

10-10-7272

Thiols: oxidationThiols: oxidation

The sulfur atom of a thiol can be oxidized to several higher oxidation states

• 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

[O]

R-S-H

[O]R-S-OH

O

R-S-S-R

[O]R-S-OH

O

OA sulfonic

acid

A thiol

A disulfide

A sulfinicacid

10-10-7373

Alcohols Alcohols and and

ThiolsThiolsEnd of Chapter 10End of Chapter 10

Documents

10-1 Organic Chemistry William H. Brown Christopher S. Foote Brent L. Iverson William H. Brown Christopher S. Foote Brent L. Iverson