carey organic chemistry chapter 15 alcohols, diols, and thiols slides

Chem 212 B. R. Kaafarani 1

Chapter 15Alcohols, Diols, and Thiols

OH O

H


15.1. Sources of Alcohols

Methanol

Methanol is an industrial chemical.- End uses: solvent, antifreeze, fuel.- Principal use: preparation of formaldehyde.- Prepared by hydrogenation of carbon monoxide.

CO + 2H2 CH3OH


Ethanol is an industrial chemical. Most ethanol comes from fermentation.

Synthetic ethanol is produced by hydration ofethylene.

Synthetic ethanol is denatured (made unfit fordrinking) by adding methanol, benzene, pyridine,castor oil, gasoline, etc.

Ethanol


Other Alcohols

Isopropyl alcohol is prepared by hydration ofpropene. Isopropyl alcohol evaporates quickly fromthe skin (bp. 82 oC) and has a cooling effect. It isused as rubbing alcohol and to sterilize medicalinstruments.

Most alcohols with five or six carbons are readilyavailable.


Hydration of alkenes.

Hydroboration-oxidation of alkenes.

Hydrolysis of alkyl halides.

Syntheses using: - Grignard reagents.- Organolithium reagents.

Reactions discussed in earlier chapters (Table 15.1)

Sources of alcohols


- Reduction of aldehydes and ketones.

- Reduction of carboxylic acids.

- Reduction of esters.

- Reaction of Grignard reagents with epoxides.

- Diols by hydroxylation of alkenes.

New methods in Chapter 15

Sources of alcohols


C

R

H OH

H

C

R

H

O

Reduction of Aldehydes Gives Primary Alcohols

15.2. Preparation of Alcohols by Reduction of Aldehydes and Ketones


Pt, ethanol

(92%)

CH3O CH2OH

O

CH3O CH + H2

Example: Catalytic Hydrogenation

Pt, Pd, Ni, or Ru as effective catalysts.


C

R

H OH

R'

C

R

R'

O

Reduction of Ketones Gives Secondary Alcohols

(93-95%)

+ H2

O

Pt

ethanol

H OHExample: Catalytic Hydrogenation


“H:–”

“H:–”

C

R

H OH

H

C

R

H

O

C

R

H OH

R'

C

R

R'

O

Retrosynthetic Analysis


Sodiumborohydride

Lithiumaluminum hydride

Li+

Na+ –B

H

H

HH–

Al

H

H

HH

act as hydride donors

Metal Hydride Reducing Agents


NaBH4

(82%)

CH2OH

O

CH

O2N

methanol

O2N

O H OH

(84%)

NaBH4

ethanol

Aldehyde

Ketone

Examples: Sodium Borohydride


Lithium Aluminum Hydride

More reactive than sodium borohydride.

Cannot use water, ethanol, methanol etc. assolvents.

Diethyl ether is most commonly usedsolvent.


(84%)

Aldehyde

Ketone

O

CH3(CH2)5CH CH3(CH2)5CH2OH

1. LiAlH4,diethyl ether

2. H2O

O

(C6H5)2CHCCH3


2. H2O

(86%)

OH

(C6H5)2CHCHCH3

Examples: Lithium Aluminum Hydride


H OH

O

1. LiAlH4,diethyl ether2. H2O

(90%)

Selectivity

Neither NaBH4 or LiAlH4reduces isolated double bonds.


Lithium aluminum hydride is the only effective reducing agent.

C

R

H OH

H

C

R

HO

O

Reduction of carboxylic acids gives primary alcohols:

15.3. Preparation of Alcohols By Reductionof Carboxylic Acids and Esters


1. LiAlH4,diethyl ether2. H2OCOH

O

CH2OH

(78%)

Example: Reduction of a Carboxylic Acid


Reduction of EstersGives Primary Alcohols

Lithium aluminum hydride preferred for laboratoryreductions.

Sodium borohydride reduction is too slow to beuseful.

Catalytic hydrogenation of esters used in industrybut conditions difficult or dangerous to duplicatein the laboratory (special catalyst, hightemperature, high pressure).



2. H2O

(90%)

O

COCH2CH3

CH3CH2OHCH2OH +

Example: Reduction of an Ester


CH2 CH2 OMgX

H3O+

H2C CH2

O

R MgX R

RCH2CH2OH

15.4. Reaction of Grignard Reagentswith Epoxides


CH3(CH2)4CH2MgBr H2C CH2

O

+

1. Diethyl ether2. H3O+

CH3(CH2)4CH2CH2CH2OH

(71%)

Example

Hexylmagnesium bromide Ethylene oxide

1-Octanol


Reactions used to prepare alcohols.

Hydroxylation of alkenes.

15.5. Preparation of Diols

Diols are prepared by...


O O

HCCH2CHCH2CH

CH3

H2 (100 atm)

Ni, 125°C

HOCH2CH2CHCH2CH2OH

CH33-Methyl-1,5-pentanediol

(81-83%)

Example: reduction of a dialdehyde

3-Methylpentanedial


Vicinal diols have hydroxyl groups onadjacent carbons.

Ethylene glycol (HOCH2CH2OH) is mostfamiliar example.

Hydroxylation of AlkenesGives Vicinal Diols


syn addition of —OH groups to each carbonof double bond.

C CHO OH

C C

O OOs

OO

CC

Osmium Tetraoxide is Key Reagent

Oxidizing agent

OsO4Osmium tetroxide Cyclic

osmate ester


(CH3)3COOH,OsO4 (cat),

tert-Butyl alcohol,HO–

(73%)

CH2CH3(CH2)7CH

CH3(CH2)7CHCH2OH

OH

Example

tert-Butyl hydroperoxide

OOH


(CH3)3COOHOsO4 (cat)

tert-Butyl alcoholHO–

cis-1,2-cyclohexanediol

(62%)

H

H

H

H

OHHO

Example

cyclohexene

syn dihydroxylation of alkenes


RCH2O

H

CH2R

OH

H+, heat

RCH2O CH2R H OH+

Acid-catalyzed. Referred to as a "condensation”. Equilibrium; most favorable for primary alcohols.

15.7. Conversion of Alcohols to Ethers

About this rxn:


2 CH3CH2CH2CH2OH

H2SO4, 130°C

CH3CH2CH2CH2OCH2CH2CH2CH3

(60%)

Example


Step 1:

CH3CH2O•• ••

H

H OSO2OH

Mechanism of Formation of Diethyl Ether

Ethanol Sulfuric acid

OSO2OH+ –CH3CH2O••

H

H+

Hydrogen sulfate ionEthyloxonium ion


Step 2:

CH3CH2••

H

H

+O

CH3CH2O•• ••

H


Ethanol

Ethyloxonium ion

++CH3CH2

CH3CH2O••

H

••

H

HO••

Diethyloxonium ion

Water


Step 3:

+CH3CH2

CH3CH2O••

HHOCH2CH3••

••


Diethyloxonium ion

Ethanol

+

H OCH2CH3••

CH3CH2

CH3CH2O••••

H

+

Diethyl ether

Ethyloxonium ion


HOCH2CH2CH2CH2CH2OH

H2SO4 130°

O

(76%)

Intramolecular Analog

Reaction normally works wellonly for 5- and 6-memberedrings.


HOCH2CH2CH2CH2CH2OH

H2SO4 130°

O

(76%)

via:

O

H

+O

H

H

••••••

Intramolecular Analog

+ H2O


ROH H2O+H+

+R'COH

O

R'COR

O

15.8. Esterification

About this rxn: Called Fischer esterification. Acid catalyzed condensation reaction of an alcohol and

a carboxylic acid. Reversible. Drive reaction forward by removal of water (i.e.

azeotrop distillation using benzene).


H2O+

CH3OH+COH

O

COCH3

O

H2SO4

0.1 mol 0.6 mol (i.e. excess)

70% yield based on benzoic acid

Example of Fischer Esterification


ROH HCl+ +R'CCl

O

R'COR

O

Reaction of Alcohols with Acyl Chlorides

About this rxn:

- High yields.- Not reversible when carried out in presence of pyridine.


pyridine

+ CClO2N

O

(63%)CH3

NO2

CH3CH2

OC

O

Example: Note the configuration on the alcohol!

(R)-(+)-2-phenyl-2-butanol

(R)-(-)-1-Methyl-1-phenylpropyl-p-nitrobenzoate

CH3

CH3CH2

OH


ROH + +R'COR

OO

R'COCR'

O

R'COH

O

Reaction of Alcohols with Acid Anhydrides

analogous to reaction with acyl chlorides


Pyridine

(83%)

+C6H5CH2CH2OH

O

F3CCOCCF3

O

C6H5CH2CH2OCCF3

O

Example

2-Phenylethanol Trifluoroacetic anhydride

2-Phenylethyl trifluoroacetate

O

F3CCOH+Trifluoroacetic acid


Primary alcohols

Secondary alcohols

from H2O

RCH2OH

O

RCH

O

RCOH

O

RCR'RCHR'

OH

15.9. Oxidation of Alcohols


Aqueous solution

Mn(VII) Cr(VI)

KMnO4 H2CrO4

H2Cr2O7

Typical Oxidizing Agents

Potassium permanganate

Chromic acid (H2CrO4):Prepared by acidification of solutions of chromate and

dichromate

chromate: CrO42-

dichromate: Cr2O72-


FCH2CH2CH2CH2OH

K2Cr2O7H2SO4,H2O

FCH2CH2CH2COH

(74%)

O

Na2Cr2O7H2SO4,H2O

(85%)

H

OH

O

Aqueous Cr(VI)

3-fluoropropanoic acid

3-fluoro-1-propanol


Nonaqueous Sources of Cr(VI)

Allows easy isolation of aldehydes in good yield by oxidation of primary alcohols.

All are used in CH2Cl2:

- Pyridinium dichromate (PDC)

(C5H5NH+)2 Cr2O72–

- Pyridinium chlorochromate (PCC)

C5H5NH+ ClCrO3–


CH3(CH2)5CH2OHPCC

CH2Cl2

O

CH3(CH2)5CH

(78%)

ClCrO3–

N

H

+

Example: Oxidation of aprimary alcohol with PCC(pyridinium chlorochromate)


PDC CH2Cl2

O

(94%)

CH2OH(CH3)3C

CH(CH3)3C

Example: Oxidation of a primary alcohol with PDC(pyridinium dichromate)


MechanismStep 1:

Step 2:

Step 3:A series of redox reactions converts chromium from the 4+ oxidation state in HCrO3

– to the 3+ oxidation state.


alcohol dehydrogenase

CH3CH2OH + NAD (a coenzyme)+

+ + +HNAD HCH3CH O

Enzyme-catalyzed

15.10. Biological Oxidation of Alcohols

Reduced form of NAD coenzymeacetaldehyde

Nicotinamide adenine dinucleotide


Nicotinamide adenine dinucleotide (oxidized form)

HO

HO

OO

NN

NH2

PO

PO

O

HOOH

H

C

O

NH2N

O O O O

+

__

Figure 15.2. Structure of NAD+


CH3CH2OH +N

H

CNH2

O

+

R

Enzyme-catalyzed

CH3CH

O

N

H

CNH2

O

R

H

••

NAD+

NADH


CC

HO OH

HIO4 C O O C+

15.11. Oxidative Cleavage of Vicinal Diols

HIO4: Periodic Acid


HIO4

CH CCH3

CH3

OHHO

CH3CCH3

O

CH

O

+

(83%)

Cleavage of Vicinal Diols by Periodic Acid

benzaldehydeacetone

2-Methyl-1-phenyl-1,2-pentanediol


HIO4

OH

OH

O

HCCH2CH2CH2CH

O

Cyclic Diols are Cleaved

1,2-Cyclopentanediol Pentane-1,5-dial

* Both stereoisomers react* cis faster than trans


1) Analogous to alcohols, but suffix is -thiol rather than –ol.

2) Final -e of alkane name is retained, not dropped as with alcohols.

15.12. Preparation of Thiols

Nomenclature of Thiols

CH3CHCH2CH2SH

CH3

3-Methyl-1-butanethiol

HOCH2CH2SH

2-Mercaptoethanolor

2-Sulfanylethanol


Properties of Thiols

1. Low molecular weight thiols have foul odors.

2. Hydrogen bonding is much weaker in thiols thanin alcohols.

3. Thiols are stronger acids than alcohols.

4. Thiols are more easily oxidized than alcohols;oxidation takes place at sulfur.


Thiols are less polar than alcohols

Methanol Methanethiol

bp: 65°C bp: 6°C


stronger acid(pKa = 10)

waterweaker acid(pKa = 15.7)

HRS••

••

••

••OH••

–RS

••

••H

••

••OH••

–++

Thiols have pKas of about 10; can be deprotonated in aqueous base.

Thiols are stronger acids than alcohols

Hydroxide ion(stronger base)

Alkanethiolate ion (weaker base)

Thiols dissolve in aqueous base.


RS– and HS– are weakly basic and good nucleophiles

H Cl HC6H5SC6H5SNa

SN2(75%)

KSH

SN2(67%)

Br SH

(S)-3-Chlorocyclopentene (R)-2-Cyclopentyl phenyl sulfide


thiol (reduced)

disulfide (oxidized)

RS••

••H RS

••

••SR••

••

Oxidation of thiols takes place at sulfur

- Thiol-disulfide redox pair is important in biochemistry.

- Other oxidative processes place 1, 2, or 3 oxygenatoms on sulfur.


thiol disulfide

sulfinic acid sulfonic acid

RS••

••H RS

••

••SR••

••

sulfenic acid

RS••

••OH RS

••

••OH

O•• ••–

+RS

••

OH

O•• ••–

2+

••O•• ••–

Oxidation of thiols takes place at sulfur


O2, FeCl3

(CH2)4COH -Lipoic acid (78%)

HSCH2CH2CH(CH2)4COH

SH O

OS S

Example: sulfide-disulfide redox pair


O—H stretching: 3200-3650 cm–1 (broad)

C—O stretching: 1025-1200 cm–1 (broad)

15.13. Spectroscopic Analysis of Alcohols

Infrared Spectroscopy


Figure 15.4: Infrared Spectrum of Cyclohexanol


Chemical shift of O—H proton is variable; depends on temperature and concentration

O—H proton can be identified by adding D2O; signal for O—H disappears (converted to O—D)

As S has a lower electronegativity than oxygen, sulfur shields neighboring Hs more.

C OH H 3.3-4 ppm 0.5-5 ppm

1H NMR

CH3CH2CH2CH2-OH CH3CH2CH2CH2SH 3.6 ppm 2.5 ppm


Figure 15.5 (page 674)


CH3CH2CH2CH3 CH3CH2CH2CH2OH

13 ppm 61.4 ppm

13C NMR

Chemical shift of C—OH is 60-75 ppm C—O is about 35-50 ppm less shielded than C—H.


Unless there are other chromophores in themolecule, alcohols are transparent above about 200nm; max for methanol, for example, is 177 nm.

UV-VIS


CH2R OH••

••

CH2R OH•+

••

CH2 OHR•••

+

Molecular ion peak is usuallysmall.

A peak corresponding to lossof H2O from the molecular ion(M - 18) is usually present.

Peak corresponding to lossof an alkyl group to give anoxygen-stabilized carbocation isusually prominent.

Mass Spectrometry of Alcohols

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