Topic 3 Alcohols and Ethers - ww2.chemistry.gatech.educf77/2312/topic3.pdf · 2-methoxypentane 1-ethoxy-4-methylbenzene 1,2 ... 3 > 2 > 1 alcohols; HI > HBr > HCl (HF is ... Competition

1

3-1

Topic 3Alcohols and Ethers

3-2

Alcohols and Ethers

Examples:

R O H R O R'

alcohol ether

11.1

OH

(– )-Menthol

(from peppermint)

H3CO

HO

H

O

Vanillin

(from vanilla beans)

OCH3

Anethole

(from fennel)

O

O O

O

Poly(phenyl ether) (PPE)

nHO O O

nOH

Polyethylene glycol (PEG)

CHEM 2312 Fall 2017 Notes: C.J. Fahrni

2

3-3

Nomenclature: Alcohols

Alcohols are classified as 1� (primary), 2� (secondary), or 3� (tertiary), depending on the number of carbons bonded to the alcohol carbon:

H3C OH

methanol ethanol propanol

R O H

alkane => alkanol ormethyl alcohol ethyl alcohol propionaldehdye alkyl alcohol

OHH3C OH

OHOH OH

propanol 2-propanol 2-methyl-2-propanol(propyl alcohol) (isopropyl alcohol) (tert-buty alcohol)

Compounds with a hydroxyl group attached directly to a benzene ring are called phenols:

OH OH

H3Cphenol p-methyl phenol

(p-cresol)

11.1

F

3-4

Nomenclature: Ethers

For more complicated structures, the IUPAC substitutive name for ethers should be used where the RO– group is named an alkoxy group:

dimethyl ether ethyl methyl ether allyl ethyl ether

R O R'

alkane => alkyl alkyl ether

O CH3 OO CH3H3C H3C

Cyclic ethers can be named based on replacement nomenclature using the prefix oxa. A cyclic 3-membered ether is named oxirane, a 4-membered ether is called oxetane:

11.1

OCH3 H3C

OH3CO

OCH3

2-methoxypentane 1-ethoxy-4-methylbenzene 1,2-dimethoxyethane (DME)

O O

O

O

oxacyclopropane oxacyclobutane 1,4-dioxacyclohexaneoxirane oxetane (1,4-dioxane)

O

oxacyclopentane(tetrahydrofurane)

F


3

3-5

Problem: Give IUPAC names for the following compounds.

OO

OH

OH

3-6

Physical Properties

• Ethers have boiling points that are comparable with those of hydrocarbons of the same molecular weight (MW)

• Alcohols have much higher boiling points than comparable ethers or hydrocarbons

O OH

pentane 1-butanoldiethyl ether

MW 72 MW 72 MW 74b.p. 34.6°C b.p. 36°C b.p. 117.7°C

Water solubility:• Both ethers and alcohols are able to form hydrogen bonds

with water• Ethers have solubilities that are similar to those of alcohols of

the same molecular weight (but are very different from those of hydrocarbons)

• gradually decreases as the hydrocarbon portion of the molecule increases

11.2


4

3-7

Physical Properties: Alcohols

11.2

3-8

Problem: The antifreeze compound 1,2-ethanediol (ethylene glycol) has a higher boiling point than either propyl or isopropyl alcohol (see Table on slide 2-7), even though all compounds have roughly the same molecular weight. Propose an explanation.


5

3-9

Physical Properties: Ethers

11.2

3-10

Ethanol

• Can be made by the fermentation of sugars, and it is the alcohol of all alcoholic beverages.

• Industrial ethanol is produced by acid-catalyzed hydration of ethene:

Note: Ethanol content limited to 12-15% as yeast enzymes are deactivated at higher concentrations

11.3


6

3-11

Diethyl Ether

• Low boiling, highly flammable liquid• Reacts slowly with oxygen by a radical process called autoxidation to form hydroperoxides

and peroxides

11.3

3-12

Synthesis of Alcohols from Alkenes1. Acid-catalyzed hydration:

Mechanism:

cat. H2SO4

H2O

F

11.4

H O H

H

H

O HH

HO HH

HO H


7

3-13

2. Oxymercuration-Demercuration:

Oxymercuration:

Hg(OAc)2, H2O NaBH4, OH–F

11.4

O Hg O

O

O

Hg O

O

H O H

– AcO

OH H

mercurinium ion

HgO

O

3-14

3. Hydroboration-Oxidation:

Mechanism:

F

11.4

BH3, THF H2O2, OH–

H

H HB

alkyl borane

H

BH

H

Ph H

BPh Ph

H

Htrialkyl borane

O OH

Ph H

BR

R

Ph H

B OR R

O H

Ph H

O BR2

Ph H

O


8

3-15

Problem: Predict the major product(s) for each of the following reactions:

cat. H2SO4

H2O

1. BH3-THF

2. H2O2, NaOH

1. Hg(OAc)2, H2O

2. NaBH4, NaOH

3-16

Reactivity of Alcohols11.5

The oxygen of an alcohol polarizes the both the C–O bond and the O–H bond of an alcohol:

Alcohols as bases:

Alcohols as acids:


9

3-17

Problem: Write equations for the acid-base reaction that would occur if ethanol were added to each of the following compounds:

Na

NaNH2

ONa

O

11.6

3-18

Conversion of Alcohols into Alkyl Halides

F

11.7

conc. HCl

25°COH

conc. HBr

refluxOH

PBr3

–10 to 0°COH

SOCl2

pyridineH3CO OH


10

3-19

Alkyl Halides from the Reaction of Alcohols with Hydrogen Halides

F

11.8

Reactivity: 3� > 2� > 1� alcohols; HI > HBr > HCl (HF is generally unreactive)

R OH + HX R X + H2O

Mechanism:

OH H OH

H+

O H

H

fast

slow

fast+ Cl

3-20

Primary alcohols are converted to alkyl halides under acidic conditions by an SN2 mechanism:F

11.8

Notes:

Acid is required:

The carbocation intermediate can undergo a rearrangement reaction:

OH H Br O HHH

BrBr


11

3-21

Alkyl Halides from the Reaction of Alcohols with PBr3

F

11.9

1� or 2�

Mechanism:

R OH + PBr3 R Br + H3PO33

• does not involve carbocation intermediate => occurs without rearrangement• preferred reagent for the conversion of alcohols to alkyl bromides

3-22

Alkyl Halides from the Reaction of Alcohols with Thionylchloride

F

11.9

1� or 2�

Mechanism:

R OH + SOCl2 R Cl + SO2 + HCl


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3-23

Leaving Group Derivatives of Alcohols

F

11.10

Nucleophilic substitution with tosylates, mesylates, and triflates:

3-24

Substitution at the sulfur atom of sulfonyl chloride follows an SN2 mechanism:

11.10

Note:

R S ClO OR O

H

R S OOOR

HN

R S OOOR

SN2


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3-25

Synthesis of Ethers

F

11.11

1. Intermolecular Dehydration of Alcohols:

2. Williamson Ether Synthesis:

3. Alkoxymercuration-Demercuration:

4. tert-Butyl Ethers by Alkylation of of Alcohols:

R OH + RHOHA

–H2OR O R

R O Na + XR' R O R' + NaX

1. Hg(CF3CO2)2t-BuOH

2. NaBH4, OH–

O

R OH +H2SO4

R O

3-26

Intermolecular Dehydration of Alcohols

11.11A

Competition between acid-catalyzed dehydration and nucleophilic substitution:

Mechanism:


14

3-27

Williamson Ether Synthesis

F

11.11B

• Nucleophilic substitution (SN2)• Electrophilic substrate must be unhindered (1� or 2� alkyl halides or sufonates) and bear a good leaving group

R O Na + XR' R O R' + NaX

Example:

O H NaHO Na + H2

I

O

3-28

Problem: Propose a multistep synthesis for the following conversion:

OH O

11.11C


15

3-29

Using Ethers as a Protecting Groups

F

11.11E

tert-Butyl Protecting Group

Challenge:

HO Br + Na HO

HO Br +H2SO4

O Br

3-3011.11F

Silyl Ether Protecting Group

Cl Sit-Bu

Me MeR O

H imidazole

DMF O Sit-Bu

Me Me

R

NNH

imidazole+

Cleavage:

O Sit-Bu

Me Me

RTHF

Bu4N+F–

R OH

+ F Sit-Bu

Me Me

F


16

3-31

Problem: Supply the missing reagents and intermediates A-E. (TBS = tert-butyldimethylsilyl)

11.11F

TBSO Br

CTBSO

D

EHOBu4N+F–

DMF

B

C4H9BrOA

3-32

Cleavage of Ethers

F

11.12

Heating dialkyl ethers with strong acids (HI, HBr, and H2SO4) results in cleavage

O + 2 HBr Br + H2O

Mechanism:

O H Br OH

Br

OH

Br+

OH

+

H Br+ OH

H Br H2O+Br


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3-33

Problem: Propose a mechanism for the following reaction:

11.11F

OCH3

HCl

Cl

3-34

Epoxides

Synthesis:

11.13

an epoxide

O

IUPAC: oxirane

O

ethylene oxide

F

1. Epoxidation with meta-chloroperbenzoic acid

2. Synthesis from bromohydrines:

+

Cl

O

OO H O

+

Cl

OH

O

mCPBA 81%

NBS

H2O

OH

Br

NaOHO

60°C

85%a bromohydrin

F


18

3-3511.13

Epoxidation with mCPBA occurs through a concerted transition state

Mechanism:

Stereochemistry:

R

R mCPBA O

R

R OR

R+

trans product (racemate)

R

mCPBA O

Rcis product

RR

mCPBAR R

HR

RH

ClO

O

OH

HR

RH

O

concertedtransition state

F

3-36

Ring-Opening of EpoxidesAcid-Catalyzed Ring-Opening

11.14

F

FBase-Catalyzed Ring-Opening

O H3O+

H2O1,2-diol

OH

OH

O RONa

ROH

O

OH

R

Note: nucleophilic attack occurs at the more substituted carbon

Note: nucleophilic attack occurs at the less substituted carbon


19

3-37

Problem: Propose a mechanism for the following reaction:

11.11F

O

Ph MeONa

MeOHMeO

OH

Ph

Phenols

Nomenclature:

F

OH OH

Clphenol m-chlorophenol

OH

1-naphthol 2-naphthol

OH

OH

p-cresolCH3

OH OH

CH3

CH3

m-cresol o-cresol

OH

hydroquinoneOH

OH OH

OH

OH

resorcinol catechol

3-38


20

Phenols: Acidity

OH

phenol

+ H2O

O

phenolate anion

+ H3O pKa = 9.89

OH OHOH OH

NO2CH3 Cl

pKa = 18 10.17 8.11 7.15

OH

NO2

NO2

3.96

OH

NO2

NO2

0.38

O2N

3-39

HA + H2O

A– + H3O+

free energy

reactioncoordinate

ΔG

ΔG‡,

∆G = −RT lnKatransition state

Ka =[H3O

+][A– ][HA][H2O]

Electron withdrawing substituents stabilize the negatively charged phenolate anion

Electron donating substituents destabilize the negatively charged phenolate anion

3-40


21

The degree of resonance stabilization depends on the substituent position:

NO

OpKa = 8.28

O

O

NO O

pKa = 7.15

3-41

Problem: Order the following compounds with increasing pKa:

OH

NH

O

OH

N

OH

N

3-42


22

Phenols: Synthesis

1. Hydrolysis of aryldiazonium salts (slide 2-45)

2. Industrial syntheses:

F

NNaNO2

HCl

NH2N

Cu2O, Cu2+ OH

H2O

ClCl2

Fe

NaOH O–Na+

350°Chigh pressure

H3PO4

O2

95-135°C250°C

OOHOHH2SO4

50-90°C

3-43

Phenols: Reactions

1. Phenol oxygen as nucleophile:

F

F

pyridine

OHCl

O

pyridine

OHO

O O

1. NaOH, H2OOH

2. R–Br

conc. HBr

3-44


23

2. Aromatic �-system as nucleophile:

excess Br2

OH

HNO3

OH

H2SO4

OHconc. H2SO4

3-45

Kolbe Reaction:

Mechanism:

OH1. NaOH

O OH2. CO2 O

O3. H3O+

3-46


24

Problem: Starting from phenol, suggest a synthesis for Aspirin

O

O

O

OH Aspirin

3-47

Problem: Starting from phenol, suggest a synthesis for acetaminophen (Tylenol)

Acetaminophen

OH

NH

O

3-48


25

3-49

Epoxy Glues

Two-component expoxy adhesives:

cured epoxy resin

OO

O OOH

O O

n

=

OO OOH

O O O

n

HO OH

bisphenol A

O Cl+NaOH

H2NHN N

HNH2

TETA(hardener)

epichlorohydrin

N

N

N

N

HOO

OOH

N

OHO

OOH

N

HOO

OOH

N

OHO

OHO

N

OHO

OHO

N

OHO

OOH

N


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Topic 3 Alcohols and Ethers - ww2.chemistry.gatech.educf77/2312/topic3.pdf · 2-methoxypentane 1-ethoxy-4-methylbenzene 1,2 ... 3 > 2 > 1 alcohols; HI > HBr > HCl (HF is ... Competition