9.1 IUPAC Nomenclature of Alcohols, Ethers and Phenols 9.1.1 Naming Alcohols 9.1.2 Naming Phenols 9.1.3 Naming Ethers9.2 Preparation of alcohols,Ethers and Phenols 9.2.1 Preparation of alcohols A. Preparation of alcohols by reduction of carbonyl compounds (1) Hydrogenation of aldehydes and ketones by catalysis of metals (2) Reduction of carbonyl compounds by metal hydrides B. Preparation of diols

Chapter 9Alcohols, Ethers and phenols

9.2.2 Preparation of Ethers A. Ethers by intermolecular dehydration of alcohols B. Williamson Synthesis of Ethers 9.2.3 Preparation of phenols A. Laboratory synthesis B. Industrial synthesis9.3 Reactions of Alcohols The sites of reactions of a Alcohol 9.3.1 Acidity and Basicity of Alcohols 9.3.2 Conversion of alcohols to ethers 9.3.3 Oxidation of alcohols A. Oxidation of primary alcohols B. Oxidation of secondary alcohols C. Oxidation of vicinal diols

9.4 Reactions of phenols 9.4.1 Acidity of Phenols9.4.2 Electrophilic aromatic substitutions9.4.3 Acylation of phenols Fries rearrangement9.4.4 Kolbe-Schmitt reaction9.4.5 Preparation of aryl ethers9.4.6 Cleavage of aryl ethers by hydrogen halides 9.4.7 Claisen rearrangement of allyl aryl ethers 9.4.8 Oxidation of phenols: Quinones

9.5 Reactions of Ethers 9.5.1 Acid-catalyzed cleavage of ethers 9.5.2 Preparation of epoxides A.Epoxidation of alkenes by reaction with peroxy acids B. Conversion of vicinal halodrins to epoxides 9.5.3 Reactions of Epoxides A. Base-catalyzed ring opening B. Acid-catalyzed ring opening

Y

Acetyl halides 酰卤 Esters 酯Carboxylic acid anhydrides 酸酐 Amides 酰胺

X,

OR,

CO

R

NR'2

Carboxylic Carboxylic acid acid derivatives 羧酸 羧酸衍生物

Compounds with O-containing functional groups

Alcohol Ether Phenol Aldehyde Ketone 醇 醚 酚 醛 酮

The interplay of these compounds is fundamentalto organic chemistry and biochemistry

ROH ROR' ArOH R C

O

H R C

O

R'

R C

O

OH R C

O

Y

Alcohol Ether Phenol Aldehyde Ketone 醇 醚 酚 醛 酮

ROH ROR' ArOH R C

O

H R C

O

R'

Compounds that have hydroxyl group bonded to a saturated, sp3-C atom－ Alcohols.

OHC

OH Compounds that have hydroxylgroup bonded to a aromaticring－ Phenols.

R O R'Compounds that have a oxygenatom bonded to two carbon atom－ Ethers

Primaryalcohols

Secondaryalcohols

Tertiaryalcohols

Class of Alcohols:RCH2OH RCHR'

OH

RCR'

R''

OH

Class of Ethers:C O C

R O R'H2C CH2

O

Ethers

Epoxides

9.1 IUPAC Nomenclature of Alcohols, Ethers and Phenols

P252,8.1P252,8.19.1.1 Naming AlcoholsCommon name: Alkyl + alcohol

Substitutive name: Suffix: e ol• Number: begin at the end nearer the hydroxyl group.

CH2OH

Benzyl alcohol( 苄醇 )

Phenyl methanol( 苯甲醇 )

H2C CHCH2OHAllyl alcohol

( 烯丙醇 )2-Propen-1-ol(2- 丙烯 -1- 醇 )

CH3COH

CH3

CH3

tert-Butylalcohol( 叔丁醇 )

2-Metyl-2-propanol(2- 甲基 -2- 丙醇 )

5-Chloro-2-methyl-

phenol（ 2- 甲基 -5- 氯

苯酚）

HOCH2CH2OH

Ethyl glycol( 乙二醇 )

1,2-Ethanediol

ClCH2CH2CH2OH

Glycerol( 甘油 )1,2,3-Propanetriol

HOCH2CHCH2OH

OH 3-Chloro-1-propanol(3- 氯 -1- 丙醇 )

9.1.2 Naming PhenolsPhenol is the base name:o-, m-, p-: substitutent

CH3

OH4-Methylphenolp-Methylphenol

p-Cresol （甲酚）CH3

OH

Cl

1,2-BenzenediolCatechol

（儿茶酚）（邻苯二酚）

1,3-BenzenediolResorcinol（间苯二酚）

1,4-BenzenediolHydroquinone

（对苯二酚）（氢醌）

OH

OH

OH

OH OH

OH

OH

CH3

(CH3)3C C(CH3)3

BHT

1-Naphtholα- Naphthol

（ 1- 萘酚）

2-Naphtholβ- Naphthol

（ 2- 萘酚）

OHOHOH

Pyrogallol（连苯三酚）

1,3,5-benzenetriol（均苯三酚）

OH

OHHO

OH

OH

OH

9.1.3 Naming of Ethers

CH3CH2OCH3

Ethyl methyl ether( 甲乙醚 )

C6H5O CCH3

CH3

CH3

P253P253

tert-Butylphenyl ether( 苯叔丁基醚 )

Diethyl ether( 乙醚 )

AnisoleMethyl phenyl ether

( 茴香醚 )( 苯甲醚 )

Tetrahydrofuran (THF)

( 四氢呋喃 )

Functional class IUPAC names

Symmetrical ethers ( 单醚 )Unsymmetrical

(Mixed) ethers ( 混醚 )

CH3CHCH2CH2CH3

OCH3

Substitutive IUPAC

2-Methoxypentane(2- 甲氧基戊烷 )

Alkoxy ( 烷氧基 )

1-Ethoxy-4-methylbenzene(4- 甲基 -1- 乙氧基苯 )

CH3CH2O CH3

Oxane 烷

1,4-Dioxane1,4- 二氧六环

二 烷

O O

OCyclic ethers:Suffix:yl oxy

Transformation of the several functional groups to alcohols:

ROH

C C

RX

C

O

R'(H)

A. Preparation of Alcohols by Reduction of Carbonyl Compounds

C

OReducing agent

C OHC

OReducing agent

C OH

9.2 Preparation of alcohols, Ethers and Phenols9.2.1 Preparation of Alcohols

P258,8.4P258,8.4

(1) Hydrogenation of aldehydes and ketones by Catalysis of metals

Aldehydes Primary alcoholsRC H + H2

OPt, Pd, Ni, or Ru RCH2OH

RC R' + H2

OPt, Pd, Ni, or Ru

RCHR'

OHKetones Secondary alcohols

CH3O CO

HH2, Pt

EtOHCH3O C H

OH

H

p-Methoxy-benzaldehyde

p-Methoxybenzylalcohol(92%)

(2) Reduction of carbonyl compounds by metal hydrides

Na+ BH

H

H

H

Li+ AlH

H

H

H

Metal hydrides:

Sodium borohydride

NaBH4

( 硼氢化钠 )

Lithium aluminum hydride

LiAlH4(LAH)( 四氢铝锂 )

P259,8.5

P259,8.5

•Reaction of NaBH4 with aldehydes and ketones

CH3CH2CH2CHO

NaBH4 CH3CH2CH2CH2OHH2O

Butanal 1-Butanol (87%)

CH3CH2CH2CHO

NaBH4 CH3CH2CH2CH2OHH2O

Butanal 1-Butanol (87%)

ONaBH4

H2O

OH

CH3CCH2C(CH3)3

ONaBH4

EtOHCH3CHCH2C(CH3)3

OH

CH3CCH2C(CH3)3

ONaBH4

EtOHCH3CHCH2C(CH3)3

OH

4,4-Dimethyl-2-pentanone

4,4-Dimethyl-2-pentanol(85%)

An aqueous or alcoholic solution

(CH3)3CCCH3

O

(1) LiAlH4 / Et2O(CH3)3CCHCH3

OH (2) H2O

(CH3)3CCCH3

O

(1) LiAlH4 / Et2O(CH3)3CCHCH3

OH (2) H2O

3,3-Dimethyl-2-butanone 3,3-Dimethyl-2-butanol

•Reaction of LiAlH4 with Aldehydes and Ketones

4 RCO2H + 3 LiAlH4Et2O [(RCH2O)4Al]Li + 4 H2 + 2 LiAlO2

4 RCH2OH + Al (OH)3 + LiOHH2O

4 RCO2H + 3 LiAlH4Et2O [(RCH2O)4Al]Li + 4 H2 + 2 LiAlO2

4 RCH2OH + Al (OH)3 + LiOHH2O

•Reaction of LiAlH4 with carboxylic acids and esters

C OHO

1. LiAlH4 / Et2O

2. H2OCH2OH

CyclopropanecarboxylicAcid ( 环丙基甲酸）

Cyclopropylmethanol（环丙基甲醇） (78%)

COC2H5

O1. LiAlH4 / Et2O

2. H2OCH2OH + C2H5OHCOC2H5

O1. LiAlH4 / Et2O

2. H2OCH2OH + C2H5OH

Ethyl benzoate( 苯甲酸乙酯）

Benzyl alcohol( 苄醇） (90%)

RC OR'O

1. LiAlH4 / Et2O

2. H2ORCH2OH + R'OHRC OR'

O1. LiAlH4 / Et2O

2. H2ORCH2OH + R'OH

Characteristics of reactions:• Selective reduction: NaBH4 does not reduce C=C, and － COOH, － COOR 。 LiAlH4 does not reduce C=C,

C C

C C

RCOOHRCOOR' 1°Alcohols

RC HO

RC R'O

RC OHO

RC OR'O

RC OO

< < < <

Reduced by NaBH4

Reduced by LiAlH4

Ease of reductionO

COC2H5

ONaBH4

CH3OH

H3+O

H OHCOOC2H5

Methyl 2-pentenoate 2-Penten-1-ol(91%)

CH3CH2CH CHCOCH3

O1. LiAlH4,ether

2. H3O+ CH3CH2CH CHCH2OH

+ CH3OH

Solvents: H2O, ROH Et2O, THF

NaBH4 LiAlH4

LiAlH4 reacts violently with water.

• Solvents:

Vicinal diolsCH2CH2

OH OH

CH3CHCH2

OHOH1,2-EthanediolEthylene glycol

1,2- 乙二醇 ( 甘醇）

1,2-PropanediolPropylene glycol

1,2- 丙二醇

B. Preparation of diols

KMnO4 / OH －

(cold)

RCH CH2

CH3C

CH3

CH3

O OH

, OsO4(Cat)

OH, OH

RCHCH2

HO OHOsO4

Osmium tetraoxide( 四氧化锇 )

tert-butyl hydroperoxide( 叔丁基氢过氧化物 )

Alkaline ( 碱性 )

HydroxylationSyn-addition

(CH3)3COOH, OsO4 (Cat)

(CH3)3COH, HO

HO

HO

H

H

(CH3)3COOH, OsO4 (Cat)

(CH3)3COH, HO

HO

HO

H

H

9.2.2 Preparation of EthersA. Ethers by intermolecular dehydration of alcohols

Substrate: Primary alcoholsAcid-catalyzedProducts: symmetric ethers

Substrate: Primary alcoholsAcid-catalyzedProducts: symmetric ethers

B. The Williamson Synthesis of EthersSodium alkoxide,Alkyl halide and derivatives

Mixed ethers

R O Na + R' L R O R' + Na L

L: Br, I, OSO2R'' or OSO2OR''

R O Na + R' L R O R' + Na L

L: Br, I, OSO2R'' or OSO2OR''

P261,8.6

P261,8.6

CH3CH2CH2OH + Na CH3CH2CH2O Na + 1/2 H2Propyl alcohol Sodium propoxide

CH3CH2I

CH3CH2CH2OCH2CH3 + Na IEthyl propyl ether

(70%)

CH3CH2CH2OH + Na CH3CH2CH2O Na + 1/2 H2Propyl alcohol Sodium propoxide

CH3CH2I

CH3CH2CH2OCH2CH3 + Na IEthyl propyl ether

(70%)

The reaction characteristic:1. SN2 reaction2. The best substrate is primary alkyl halide

CH2ONa + (CH3)3CHCl

(CH3)2CHONa + CH2Cl (CH3)2CHOCH2 + NaCl

Alexander W. Williamson(1824-1904)

Alexander W. Williamson was Born in London, England, and received his Ph.D. at the University of Giessen in1846.His ability to work in laboratory was hampered by a childhood injury that caused the loss of an arm.From 1849,utill 1887, he was professor of Chemistryat University College, London.

Bonding in organic compounds at that time was thought to be of either thewater type, as in alcohols, ROH, or of the radical type, as in ethers which would be given the formula RO. But Williamson, by his ether synthesis, showed that mixed ethers, with two different alkyl groups, could be prepared.Ethers thus has to have the water-type formula ROR', and oxygen had the equivalent weight of 8 but the atomic weight of 16. By this type of argument he established and rationalised the structures of many of the families of simple organic compounds. Thus, in 1850 he predicted the existence of acetic anhydride, which was prepared in 1851.We still have some examples of his early apparatus, and his copper pelicans, in which he prepared ether, are shown at right. When you realise the scale on which these reactions were carried out, and the fact that the pelican was heated over a charcoal brazier, it is remarkable that we do not seem to have records of catastrophic accidents taking place. Later on Williamson, again with people such as Liebig, was responsible for the introduction of much of the glassware which we are familiar with today,except that it was usually fitted together with corks rather than ground glass joints. Standard joints, blown in a mould, as we know them todaydid not come into use until the middle of the last (20th) century.Towards the end of his period as Head of Department, Williamson became very much involved in College and University politics, and his research suffered. This was the period when the other London colleges - Kings, Birkbeck, Queen Mary, what is now Imperial College, and so on were combined into a federal university, and presumably Williamson feltthe need to fight the University College corner.

碱熔法 碱熔法

9.2.3 Preparation of phenolsA. Laboratory synthesis From aniline:NH2

NO2

NaNO2, H2SO4

0~5¡æ

N2+

NO2

H3+O£¬¡÷

OH

NO2(80%) B. Industrial synthesis

(1) Reaction of benzenesulfonic acid with NaOHSO3H

CH3

SO3

H2SO4

CH3

1. NaOH, 300¡æ

2. H3+O

OH

CH3

Toluene p-Toluenesulfonic p-methylphenol acid (72%)

(2) Hydrolysis of chlorobenzene

Cl1. NaOH, H2O, 370¡æ

2. H+ OH

3. From cumene （枯烯）

+ CH3CH CH2无水 AlCl385 ~ 95 ¡æ

CHCH3

CH3Cumene 枯烯Friedel-Crafts alkylation

CH3

CH3CH + O2

95 ~ 135 ¡æ CCH3

CH3

O OH

Cumene hydroperxide( 氢过氧化枯烯 )

卤苯水解 卤苯水解

Cumene is oxidized to cumene hydroperoxide

10% H2SO4

~ 90¡æOH + CH3CCH3

OC

CH3

CH3

O OH

9.3. Reactions of Alcohols

异丙苯法 异丙苯法

C O H

H

CH C O H

H

CH

Nucleophilicsubstitution

Weak acidity

Weak basicityWeak basicity

Protona-tion

Protona-tionH A

C O H

H

HC O H

H

H

Nu:

C

O

C

O

OxidationOxidation

•The sites of reactions of a Alcohol:

C CC C

EliminationElimination

OH

H

9.3.1 Acidity and Basicity of Alcohols Like water, alcohols are both weakly basic and weakly acidic.

As a weak base: Reversible protonated by strong acidsto yield oxonium ions( 离子 ):

R O H + H A R O H

H+ A

An alcohol An oxonium ionAs a weak acid:

Acid (base) conjugate conjugate base acid

An alcohol An Alkoxide Hydronium ion( 烷氧负离子 ) ion( 水合离子 )

R O H + OH

HR O O

H

H+ H

P256,8.3P256,8.3

TABLE. pKa Values for some weak acids

ACID pKa

CH3OH 15.5 H2O 15.74CH3CH2OH 16.0(CH3)3COH 18.0

HC CH 25H2 35NH3 38CH3CH3 50

TABLE. pKa Values for some weak acids

ACID pKa

CH3OH 15.5 H2O 15.74CH3CH2OH 16.0(CH3)3COH 18.0

HC CH 25H2 35NH3 38CH3CH3 50

P257, Table 8.1P257, Table 8.1

In any proton-transferprocess:

Strogeracid

+ Strogerbase

Weakeracid

+Weakerbase

K > 1

Relative acidity:H2O > ROH > R H C C

> H2 > NH3 > RH

Relative basicity:

R- > NH2- > H- >

> RO- > OH- RC C-

2 CH3CH2OH + 2 Na 2 CH3CH2O Na + H2

CH3 C

CH3

CH3

OH +2 2 K CH3 C

CH3

CH3

O K + H22

9.3.2 Conversion of Alcohols to Ethers

2CH3CH2OHH2SO4

140 CCH3CH2-O-CH2CH3 + H2O

H2SO4

180 C2 CH 2=CH 2 + 2H2O

2CH3CH2OHH2SO4

140 CCH3CH2-O-CH2CH3 + H2O

H2SO4

180 C2 CH 2=CH 2 + 2H2O

P263.8.7P263.8.7

2 CH3CH2CH2CH2OHH+

¡÷CH3CH2CH2CH2OCH2CH2CH2CH3

+ H2O2 CH3CH2CH2CH2OH

H+

¡÷CH3CH2CH2CH2OCH2CH2CH2CH3

+ H2ODehydrationDehydration

NaH, NaNH2

Characteristics of the reaction:1. Condensation( 缩合反应 )2. Only for primary alcohols3. The temperature of condensation is lowe

r than elimination.4. SN2 mechanism

Characteristics of the reaction:1. Condensation( 缩合反应 )2. Only for primary alcohols3. The temperature of condensation is lowe

r than elimination.4. SN2 mechanism

HOCH2CH2CH2CH2CH2OHH2SO4

¡÷ O+ H2OHOCH2CH2CH2CH2CH2OH

H2SO4

¡÷ O+ H2O

1,5-Pentanediol(1,5- 戊二醇 )

Oxane( 烷 )(76%)

A. Oxidation of primary alcohols

R-CH2OH [O] R-C-H

O[O]

O

R-C-OHR-CH2OH [O] R-C-H

O[O]

O

R-C-OH

FCH2CH2CH2OHK2Cr2O7

H2SO4,H2OFCH2CH2 C OH

O

FCH2CH2CH2OHK2Cr2O7

H2SO4,H2OFCH2CH2 C OH

O

3-Fluoro-1-propanol(3- 氟 -1- 丙醇 )

3-Fluoropropanoic acid(3- 氟丙酸 ) (74%)

RCH2OHPCC

C HO

RRCH2OHPCC

C HO

R

CrO3 + HCl + N N H CrO3Cl-

Pyridinium chlorochromate ( PCC)

CrO3 + HCl + N N H CrO3Cl-

Pyridinium chlorochromate ( PCC)

PCC reagent is soluble in CH2Cl2

P 263P 2639.3.3 Oxidation of alcohols

(C2H5)2C

CH3

CH2OH + PCCCH2Cl225 C

CH3

(C2H5)2C

O

C H(C2H5)2C

CH3

CH2OH + PCCCH2Cl225 C

CH3

(C2H5)2C

O

C H

RCHR'

OH

K2Cr2O7

H2SO4,H2ORCR'

O

RCHR'

OH

K2Cr2O7

H2SO4,H2ORCR'

O

Secondaryalcohols

[O]ketones

B. Oxidation of secondary alcohols

PCC doesn’t attack C=C bond

CH2OHPCC

CH2Cl2C

O

H

Citronellol( 香茅醇 )

Citronellal (82%)( 香茅醛 )

Chromic acidH2CrO4

C. Oxidation of vicinal diolsVicinal diols react with HIO4, the C-C bond is broken to form carbonyl compounds

AgNO3 is added to identify the vicinal diols

AgIO3

RCHOH

R'CHOH+ O I

O

O

OHRCH

R'CH

O

OI

OH

OH

OH

O

-H2O RCHOR'CHO

+ HIO3

Ch.P225,(3)Ch.P225,(3)

OH Na2Cr2O7

H2SO4,H2O

OOH Na2Cr2O7

H2SO4,H2O

O C OHR

R'R"

[O]No rectionC OH

R

R'R"

[O]No rection

Cyclohexanol Cyclohexanone(85%)

9.4 Reactions of phenols

AcidityAcylation

AromaticElectrophilicsubstitution

Formationof aryl ethers

The sites of reactions

9.4.1 Acidity of Phenols

OH OH CH3C

O

OHpKa

= 18 pKa = 9.89 pKa = 4.74

TABLE 1 The acidity constants of phenolsSubsti-tuents

pKa (25 )℃o- m- p-

-H

-CH3

-Cl

-NO2

-OCH3

10.20 10.01 10.17

8.11 8.80 9.20

7.17 8.28 7.15

9.98 9.65 10.21

9.89 9.89 9.89

pKa (25 )℃

2,4-Dinitro

2,4,6-Trinitro(picric acid)

(苦味酸 )

3.96

0.38

Substi-tuents

P256,8.3P256,8.3

Substituted phenols:

Substuentson the position

o- or p-

Substuentson the position

o- or p-

Electron - releasing groupAcidity is decreased

Electron – withdrawing groupAcidity is increased

HO

H

O

+ pka = 10

O O OO OO O OO OElectron delocalization in phenoxide ion:

9.4.2 Electrophilic aromatic substitutions A hydroxyl group is a very powerful activating substituent:

OH

+ 3 Br2H2O

OH

Br Br

Br

(white) + 3HBr

(100%)

Bromination:

Sulfonation:

OH(concd)H2SO4

25¡æ

100¡æ

OHSO3H

SO3H

OH 100¡æ

Rate control

Equilibrium control

P266;Ch.P322,(2)P266;Ch.P322,(2)

9.4.3 Acylation of phenols Acylating agents: acyl halides and carboxylic acid anhydrides

OH

CH3H3CCH3CCl

O

+ pyridine

75£¥ H3C CH3

OCOCH3

+ HCl

Fries rearrangement:

OCC6H5

O

AlCl3

CC6H5

O

OH

+ CC6H5

OOH

Phenol benzoate

p-hydroxylbenzopheone（对 - 羟基二苯酮） (64%)

(9%)

Phenolic Esters

（酚酯）

Phenolic Esters

（酚酯）Conversion of aryl esters to aryl ketones.

Conversion of aryl esters to aryl ketones.

Ch.P319( 丙 )Ch.P319( 丙 )

9.4.4 Kolbe-Schmitt reaction:Carboxylaltion of phenols

Sodium phenoxide CO2

Heated under pressure Acidified

Salicylic acid

ONa+ CO2

120¡æ

100 atm

OH

COONa

H+ OH

COOH

Salicylic acid（水杨酸） (79%)

OCCH3

COOH

O Aspirin（阿斯匹林）

（乙酰水杨酸）

Aspirin（阿斯匹林）

（乙酰水杨酸）

9.4.5 Preparation of aryl ethers Williamson Method

A Phenoxide anion A alkyl halideAlkylation of hydroxyl oxygen a phenol

ArOHNaOH ArO Na R X ArOR + Na+X(X = Cl, Br, I,

OSO2OR')OH

+ NaOHH2O

O NaCH3OSO2OCH3

OCH3

+ NaOSO2OCH3

(Anisole)茴香醚 Why?Me2SO4 － methylating agentMe2SO4 － methylating agent

OCH3 I + CH3ONa

9.4.6 Cleavage of aryl ethers by hydrogen halides

Ar O Rconcd HX

¡÷ OH + RXAr

concd HX¡÷

X + ROHArThe bond of O － R was broken!

The bond of C － O in phenolshas partial double bond character

The bond of C － O in phenolshas partial double bond character CH3

OCH3

+ HBr H2O + CH3Br

OH

CH3HBr

No reaction

9.4.7 Claisen rearrangement of allyl aryl ethers

Heating allyl aryl etherIntramolecular

reactionThe product is o-allylphenol

CH2CH2CHO200¡æ

OH

CH2CH CH2

Ovia

O

Transition state

Claisen was professor in Aachen in 1890, Kiel in 1897 and Berlin in 1904. Several syntheses especially condensation reactions between aldehydes, ketones, and esters (1881-1890) are connected with Claisen´s name. He also carried out research on tautomerism and rearrangement reactions (Umlagerungsreaktionen)

19th CenturyClaisen, LudwigBorn: Köln (Germany), 1851 Died: Godesberg near Bonn (Germany), 1930

http://www.chemsoc.org/networks/enc/FECS/Claisen.htm

9.4.8 Oxidation of phenols: Quinones ( 醌）OH

OH

K2Cr2O7

H2SO4, H2O

O

O

O

O

+ 2 H- 2e

+ 2e

OH

OH

The sructuresof quinones ：

O O

O

O

Hydroquionoe p-Benquinone

P266P266

O

OCH3

CH2CH C(CH2CH2CH2CH)3CH3

CH3 CH3

Vitamin K

9.5.1 Acid-catalyzed cleavage of ethersCH3CH2OCH2CH3 + 2 HBr 2 CH3CH2Br + H2O

CH3CH2OCH2CH3 + HBr CH3CH2O

H

CH2CH3 + Br

CH3CH2O

H

+ CH3CH2Br

Mechanism of the reaction:

CH3CH2OH + HBr Br + CH3CH2 O H

HCH3CH2 Br + O H

H

9.5 Reactions of Ethers P267,8.9P267,8.9

A. Epoxidation of alkenes by reaction with peroxy acids ( 过氧酸 )

Peroxy acids: CH3COOH

O

C6H5COOH

O

Peroxyacetic acide( 过氧乙酸 )

Peroxybenzoic acide( 过氧苯甲酸 )

Syn-addition

R2C CR2X2

H2OR2C CR2

HO X

HOR2C CR2

O

R2C CR2X2

H2OR2C CR2

HO X

HOR2C CR2

O

B. Conversion of vicinal halohydrins (α- 卤代醇 ) to epoxides

RCH CHR + R'C

O

O OH RHC CHR + R'CO

O

OH

9.5.2 Preparation of epoxides

Intramolecular Williamson ether synthesis:

C C

RR

OH

RR

X

HO

HO H + C C

RR

OR

R

X

C C

RR

OH

RR

X

HO

HO H + C C

RR

OR

R

X

C C

RR

OR

R

X

C C

RR

R

R

O+ XC C

RR

OR

R

X

C C

RR

R

R

O+ X

C CH3C

H CH3

H 1. Br2/ H2O

2. HOC C

H3CH CH3

H

OC C

H3CH CH3

H 1. Br2/ H2O

2. HOC C

H3CH CH3

H

O

1. Anti-addition, 2. Inversion of configuration

H2C CHCH3O

CH3CH2O + CH3CH2OCH2CHCH3

OCH3CH2OH

CH3CH2OCH2CHCH3 + CH3CH2O

OH

H2C CHCH3O

CH3CH2O + CH3CH2OCH2CHCH3

OCH3CH2OH

CH3CH2OCH2CHCH3 + CH3CH2O

OH

A. Base-catalyzed ring opening

To the unsymmetric epoxide, in base-catalyzed ring-opening, attack by nucleophileoccurs at less substituted carbon atom.

B. Acid-catalyzed ring opening

CH3OH + CH3 C CH2

CH3

O

HCH3 C

CH3

OCH3

CH2OHCH3OH + CH3 C CH2

CH3

O

HCH3 C

CH3

OCH3

CH2OH

9.5.3 Reactions of epoxides

In the acid-catalyzed ring opening, the nucleophile attacks primarily at the more substituted carbon atom.

CH3OH + CH3 C CH2

CH3

OH

¦Ä

¦Ä CH3 CCH3

OCH3

CH2OH

H

CH3OH + CH3 C CH2

CH3

OH

¦Ä

¦Ä CH3 CCH3

OCH3

CH2OH

H

SN2 reaction With inversion of configuration

Anti-hydroxylation

Anti-hydroxylation

+ CH3COOH

O

O

H

H

+ CH3COOH

H

H

O + H3O OH

H2O

H

H OH2

HOH

H

-H+

OHH

OHH

+ CH3COOH

O

O

H

H

+ CH3COOH

H

H

O + H3O OH

H2O

H

H OH2

HOH

H

-H+

OHH

OHH

Problems to Chapter 9P2768.24 (c), (d)8.25 (b), (c) 8.288.31(a),(b)8.33(a), (c), (e) 8.35(a),(d)8.36(b), (e)8.37(b)8.38(b), (c)

P2768.24 (c), (d)8.25 (b), (c) 8.288.31(a),(b)8.33(a), (c), (e) 8.35(a),(d)8.36(b), (e)8.37(b)8.38(b), (c)

8.408.418.43 8.468.488.518.538.54(b)8.55

8.408.418.43 8.468.488.518.538.54(b)8.55