Chapter 12 Aldehydes and Ketones Nucleophilic Addition to Carbonyl Group

12.1 Nomenclature 12.2 Structure of Carbonyl Group12.3 Preparation of aldehydes and ketones12.4 Nucleophilic addition of aldehydes and ketones 12.4.1 Hydration of aldehydes and ketones 12.4.2 The addition of hydrogen cyanide 12.4.3 The addition of alcohols 12.4.4 The addition of amines

12. 5 The Addition of Ylides: the Wittig Reaction12.5.1 Ylides ( 叶立德 )and Preparation of phosphorous ylides12.5.2 Mechanism of the Wittig reaction 12.5.3 Synthesis of alkenes by Wittig reactions12.6 Oxidation of Aldehydes and ketones12.6.1 Oxidation of Aldehydes12.6.2 Baeyer-Villiger oxidation of ketones12.7 Spectroscopic analysis of aldehydes and ketones

General role:• The longest continuous chain with

carbonyl group is as a parent, suffix: e al or one. To ketones, numbered

the number of carbonyl group.

Aldehydes and KetonesO

CCarbonyl group

羰基Formaldehyde

甲醛Aldehyde

醛Ketone

酮12.1 Nomenclature

C H

OC H

O

Formyl醛基

O

CR

O

CR

Acyl 酰基

H C

O

H R C

O

H R C

O

R

C

O

Ar C

O

ArC

O

PhC

O

Ph

Aroyl芳酰基

Benzoyl芳酰基

Benzyl ethyl ketone乙基苄基甲酮

CH2CCH2CH3

O

CH2CCH2CH3

O

CH2 CHCH CH C H

O

CH3 CH3

CH2 CHCH CH C H

O

CH3 CH3

3-Methylbutanal3- 甲基丁醛

4-Methyl-3-hexanone4- 甲基 -3- 己酮

CH3CHCH2C

O

H

CH3

CH3CHCH2C

O

H

CH3

CH3CH2CCHCH2CH3

O

CH3CH3CH2CCHCH2CH3

O

CH3

2,3-Dimethyl-4-pentenal2,3- 二甲基 -4- 戊烯醛

2. When –CHO is attached to a ring, suffix is -aldehyde or -carbaldehyde ( 以甲醛为母体 )

3. Alkyl groups are as substitutes, “ketone” are as parent

CHOCHO

Benzaldehyde苯甲醛

C

O

C

OBenzophenone

二苯甲酮

O

CH3

O

CH3

P2849.3P2849.3

4-Methylcyclohexanone4- 甲基环己酮

12.2 Structure of Carbonyl GroupC O C C

sp2- hybridizedπbond

C O¦Ä ¦ÄC O

¦Ä ¦Ä

Dipole momentμ = 2.3 ~ 2.9D Dipole momentμ = 2.3 ~ 2.9D

Trigonal plane

C O C OC O C O

A B

Electron delocalization

Resonance structures:

CH3 C

O

CH3

Polar solvent

P283,9.2

P283,9.2

Acetaldehyde( 乙醛 )

Acetone( 丙酮 )

Polarized

C

O+

-

C

O+

- Nucleophilic

ElectrophilicH+,E+

OH-,Nu:-

Reaction sites and reactions of aldehydes and ketones

O

C R (H)C

H

Nucleophilic additionNucleophilic additionOxidation

And reductionOxidation

And reduction

Reaction of α -hydrogenReaction of α -hydrogen

C O

Nu

12.4 Nucleophilic Addition of Aldehydes and Ketones

Nu

C O H Nu +¦Ä ¦Ä

C O H

Nu

H Nu

The trigonal planar structure of C=O is relatively open to attack from above or below by Nu−.:

Nu:−

OH−, H− , R3C − ,H2O, NH3, ROH

:

sp2 sp3

Intermediate:an alkoxide ion

P2889.6

P2889.6

12.4.1 Hydration of Aldehydes and ketones

Geminal diol（同碳二醇）

Hydrate( 水合物 )

Reversible

K =[RCH(OH)2]

[RCHO] [H2O]

R C

O

H (CH3) + H2O COH

OHR

(CH3) H

K

CF3 C

O

CF3 H C

O

H CH3 C

O

H CH3 C

O

CH3 (CH3)3C C

O

C(CH3)3> > > >

Khydr22,000 41 1.8 × 10-2 4.1 × 10-3 2.5 × 10-5

Reactivity decreasesReactivity decreases

P2909.7P2909.7

Factors affecting the reactivity:1. Electronic effects of alkyl groups

CF3 C

O

CF3

CH3 C

O

CH3CH3 C

O

CH3

2. Steric effect of alkyl groups

C

O

R R CH2OOH

OHRR

C

O

R R CH2OOH

OHRR

Hybridization: sp2 sp3

The bond angle: 120° 109.5° H < CH3 < tert-Butyl

The crowding in the products is increased by the larger group

Electron-donating effect of alkylSubstituents stabilizes the carbonyl group;Electron-withdrawing effect destabilizes the carbonyl group

An aldehyde

A ketone

Mechanism of HydrationThe addition of water is subject to catalysis by both an acid and a base.

The mechanism for the base-catalyzed reaction:

A hydroxide ion attacks the carbon of the carbonyl group.

This step is rate-determining.Nucleophile:HO － > H2ONucleophile:HO － > H2O

A hydroxideion

An alkoxideion

HO + CH

H3CO C

OH

OHH3C

slowStep 1

An alkoxide ion attracts a proton from water, yielding geminal diol.

The mechanism for the acid-catalyzed reaction:Step 1

H

ROC + C O

R

H H+HH O

H

¦Ä ¦Ä H2Ofast

H

ROC + C O

R

H H+HH O

H

¦Ä ¦Ä H2Ofast

Protonation of carbonyl group:

HC O

R

HC O

R

HHH

C OR

HC O

R

HH

Step 2C

OH

OHH3C

+ H OHfast C

OH

OHH3C

H + OHC

OH

OHH3C

+ H OHfast C

OH

OHH3C

H + OH

Step 2H O

H

C OR

H H+

Slow

C

H

R

OHH

O HH O

H

C OR

H H+

Slow

C

H

R

OHH

O H

Water as a nucleophile attacks the protonated carbonyl group

The step is rate-determiningStep 3

CH

R

OHH

O H HO

O

R

H C +

H

OH H

O

H

H H

CH

R

OHH

O H HO

O

R

H C +

H

OH H

O

H

H H

Transformation of the proton

The mechanism for the base-catalyzed reaction:

R C

O

H (CH3) + HCN CCN

OHR

(CH3) H

Characteristics of the reaction1. Base-catalyzed,reagent: KCN2. Formation of C － C bond3.－ CN COOH, － NH2

C

O

CH3CH2 CH3HCN CH3CH2 C

OH

CN

CH3

95%H2SO4

¡÷CH3CH2 C

CH3

COOH

12.4.2 The addition of hydrogen cyanide ( 氢氰酸 ) － Cyanohydrin ( 氰基醇 )formation

12.4.3 The addition of alcohols Acid catalysis Aldehydes react with alcohols

to yeld hemiacetals ( 半缩醛 ) or acetals( 缩醛 )

R C

OC

OR'

OHR

HH R'OH / H+ R'OH / H+

COR'

OR'R

H+ H2OR C

OC

OR'

OHR

HH R'OH / H+ R'OH / H+

COR'

OR'R

H+ H2O

Aldehyde hemiacetal acetal

C

O

H + 2 CH3CH2OHHCl CH

OCH2CH3

OCH2CH3C

O

H + 2 CH3CH2OHHCl CH

OCH2CH3

OCH2CH3

Benzaldehyde Ethanol Benzaldehydediethyl acetal

苯甲醛缩 二乙醇 (60%)

Mechanism of the reaction:

H

ROC +¦Ä ¦Ä

C OR

HH + R'O

H

R'H O

H

CH

R

OR'H

O H HO

R'O

R

H C +

H

OH R'

R'O

H

H

O R'

CH

R

O R'

O H

H

OH2

R'O

R

H C-H2O

R'H

ROC

C OR

HR'

R' O H

C

R

O

R'

OH

H

R'HOR'

H O

R'O

R

C R' + R' OH2

The position of equilibrium is favorable for acetal formation from most aldehydes.

For most ketones, the position of equilibrium is unfavorable.

excess alcohol as solvent

Diols react with aldehydes or ketones to formcyclic acetals by removing the water:

O + HOCH2

HOCH2

对甲苯磺酸 CH2

CH2

OOO +

HOCH2

HOCH2

对甲苯磺酸 CH2

CH2

OO

COR'

OR'

R

(R")H+ H2O H C

R

(R")HO + 2 R'OH C

OR'

OR'

R

(R")H+ H2O H C

R

(R")HO + 2 R'OH

Acetal hydrolysis is favored by excess water.Acetals as protecting groupsAcetals as protecting groups

O CH2OH O C

O

OC2H5O CH2OH O C

O

OC2H5

Acetals arestable in basicsolution

Acetals arestable in basicsolution

Acetals are susceptible to hydrolysis in aqueous acid:

O C

O

OC2H5H+

HOCH2CH2OH

C

O

OC2H5OOO C

O

OC2H5H+

HOCH2CH2OH

C

O

OC2H5OO

(a) Protection of carbonyl group

(b) Reduction of the ester group1) LiAlH4 / Et2O

2) H2OCH2OHO

O1) LiAlH4 / Et2O

2) H2OCH2OHO

O(c) Unmasking of the carbonyl group

CH2OHOO

H+

H2O

O CH2OHCH2OHO

O

H+

H2O

O CH2OH

12.4.4 The addition of amines （胺）1. Reaction with primary amines: imides ( 亚胺 )

Aldehydes and ketones react with primary amines to yield imides

Step 1. Nucleophlic addition

Step 2. Elimination

NR H

H

+ C O NR

H

H

C O NR

H

HC O

Primary amine

Aldehydeor ketone

Carbinoamine （氨基甲醇）

NR CNR

H

HC O + H2O Imide（亚胺）

N-Substituted imides:Schiff’s bases ( 西佛碱 )N-Substituted imides:Schiff’s bases ( 西佛碱 )

C O + H+ C OH C OH

The reactions are accelerated by acid-catalysis

C OHNR H

H

+ NR

H

C OH-H+

NR

H

HC OH

NR

H

HC O +H+

NR

H

HC O

H

NR C + H2O

(a) Protonation of carbonyl group

(b) Nucleophile attacks carbonyl group

(c) Elimination with acid-catalysis

Carefulcontrolof pH!

Carefulcontrolof pH!

pH: 4~5pH: 4~5

O + (CH3)2CHCH2NH2

H+

NCH2CH(CH3)2O + (CH3)2CHCH2NH2

H+

NCH2CH(CH3)2

Cyclo-hexanone

Isobutylamine（异丙胺）

N-Cyclohexylide-Isobutylamine

（ N- 亚环己基异丙胺） Reaction with derivatives of ammonia

C O C N YNY H

H

+ + H2O

C O H2N OH C OHN + H2O

Hydroxylamine（羟胺）

An oxime（肟）

C O H2N NH2 C NH2N + H2O

Hydrazine（肼）

A hydrazone（腙）

C O H2NNH CC6H5

HNO2

O2N NNH NO2

O2N

C6H5

H£«H2O

2,4-DinitrophenylHydrazine

（ 2,4- 二硝基苯肼）2,4-dinitrophenylhydrazone ( 腙 )

The products are insoluble and have sharp characteristic melting point. The reaction are often used to identify unknown aldehydes and ketones.

O + H2NNHCNH2 + H2O

O

NNHCNH2

O

Semicarbazine（氨基脲）

Semicarbazone （缩氨基脲）（半卡巴腙）

Reactions with secondary aminesAldehydes and ketones react with secondary amine (R2NH), to form enamines （烯胺）

RCH2CR'

O

+ RCH2CR"2NH

OH

R'

NR"2

-H2O RCH CR'

NR"

Obenzene

¡÷+ H2ON

H

N

Cyclopentanone（环戊酮）

Pyrrolidine（吡咯烷）

N-(1-Cyclopentenyl)Pyrrodine

[N-(1- 环戊烯基 ) 吡咯烷 ]

12. 5 The Addition of Ylides: the Wittig Reaction

CR

R'O + (C6H5)3P C

R"R"'

CR

R'C

R"R"' + (C6H5)3P O

Solvents: THF, DMSO S

O

CH3 CH3

Dimethyl sulfoxide（二甲亚砜）

The characteristics of Wittig reaction: Regioselectivity

Aldehydes and ketones react withphosphorous ylides to yield alkenes and triphenyl phosphine oxide （三苯基氧膦）

O + Ph3P CH2CH3SCH3

O

CH2+ Ph3P O

86%

14.5.1 Ylides and the Preparation of Phosphorous Ylides

Ylides ( 叶立德 ): Molecules with two oppositely charged atoms

(C6H5)3P CR"

R(C6H5)3P C

R"

RA hybrid of the two resonance structures

Preparation of phosphorous ylides:Step1 Alkyl halides Triphenyphosphine

SN2 reaction

(C6H5)3P + CH XR"

R"'(C6H5)3P CH X

R"

R"Substrates: 1°, 2°Alkyl halides

Ch.P346( 己 )Ch.P346( 己 )

X(C6H5)3P C H

R"

R"C6H5 Li (C6H5)3P C

R"

R"+ C6H6 + LiX

Step 2 An acid-base reaction

The strong base: Alkyllithiun or phenyllithium

Br(C6H5)3P CH3 C6H5 Li (C6H5)3P CH2+ C6H6 + LiX

12.5.2 Mechanism of the Wittig reaction

CH3

CCH3

O

+ C

H

CH3

P(C6H5)3

H3C

CCH3

O

C

H

CH3

P(C6H5)3

H3C

CCH3

O

C

H

CH3

P(C6H5)3

Aldehydeor ketone

Triphenylphosphoniumyelid

Oxaphosphetane（氧膦烷）

( 内膦盐 )A betaine( 甜菜碱 )

CCH3

CH3C

H

CH3

+ O P(C6H5)3

TriphenlphosphineOxaide( 三苯基氧膦）

12.5.3 Synthesis of alkenes by Wittig reactions

C6H5CH C

CH3

CH3

CC6H5

HO + C

X

H

CH3

CH3

CC6H5

H X

H+ O C

CH3

CH3

(CH3)2CHBr + (C6H5)3P (C6H5)3P CH(CH3)2Br

RLi (C6H5)3P C(CH3)2C6H5CHO C6H5CH CH(CH3)2 + (C6H5)3P O

Georg F. K. Wittig received the Nobel Prize in Chemistryin 1979.Georg F. K. Wittig received the Nobel Prize in Chemistryin 1979.

CH P(C6H5)3+2 O CH CHO

Synthesis of β-Carotene （ β- 胡萝卜 素）

12.6 Oxidation of Aldehydes and ketones

RCH

OOxidize

RCOH

O The strong oxidizing reagents:K2Cr2O7 / H+, KMnO4 / OH-;The mild oxidizing reagent: Ag2O/OH-.

O

O CHK2Cr2O7

O

O COHH2SO4,H2O

Furfural（糠醛）

Furoic acid（糠酸） (75%)

P2879.5P2879.5

CO

HAgNO3

NH4OH

CO

OH + Ag

Tollens reagent

Georg Wittig 1/2 of the prize

University of Heidelberg Heidelberg, Federal

Republic of Germany b. 1897d. 1987

German chemist whose method of synthesizing olefins (alkenes) from carbonyl compounds is a reaction often termed the Wittig synthesis. For this achievement he shared the 1979 Nobel Prize for Chemistry.Wittig was born in Berlin and studied at Kassel and Marburg. He was professor at Freiburg 1937-44, Tubingen 1944-56, and Heidelberg 1956-67.In the Wittig reaction, which he first demonstrated 1954, a carbonyl compound (aldehyde or ketone) reacts with an organic phosphorus compound, an alkylidene-triphenylphosphorane, (C6H5)3P=CR2, where R is a hydrogen atom or an organic radical. The alkylidene group (=CR2) of the reagent reacts with the oxygen atom of the carbonyl group to form a hydrocarbon with a double bond, an olefin (alkene). In general:(C6H5)3P=CR2 + R2'CO (C6H5)3PO + R2C=CR2The reaction is widely used in organic synthesis, for example to make squalene (the synthetic precursor of cholesterol) and vitamin D3

German chemist whose method of synthesizing olefins (alkenes) from carbonyl compounds is a reaction often termed the Wittig synthesis. For this achievement he shared the 1979 Nobel Prize for Chemistry.Wittig was born in Berlin and studied at Kassel and Marburg. He was professor at Freiburg 1937-44, Tubingen 1944-56, and Heidelberg 1956-67.In the Wittig reaction, which he first demonstrated 1954, a carbonyl compound (aldehyde or ketone) reacts with an organic phosphorus compound, an alkylidene-triphenylphosphorane, (C6H5)3P=CR2, where R is a hydrogen atom or an organic radical. The alkylidene group (=CR2) of the reagent reacts with the oxygen atom of the carbonyl group to form a hydrocarbon with a double bond, an olefin (alkene). In general:(C6H5)3P=CR2 + R2'CO (C6H5)3PO + R2C=CR2The reaction is widely used in organic synthesis, for example to make squalene (the synthetic precursor of cholesterol) and vitamin D3

Bernhard Tollens(1841-1918)

Bernhard Tollens Was born in Hamburg,Germany, receivedHis Ph.D. at University of Göttingen,and thenbecame professorat the same institution.

12.6.2 Baeyer-Villiger oxidation of ketonesKetones react with peroxy acides to give esters:

C6H5 C

OCH3 + RCOOH

OCH3 C O C6H5

O+ RCOH

O

The oxygen atom is inserted between the carbonyl group and the larger of two groups attached to it.

The migratory aptitude of groups: H > phenyl > 3°alkyl > 2°alkyl > 1°alkyl > methyl

CCH3

O

+ PhCOOHO

CHCl3 OCCH3

O+ PhCOH

O

(67%)

Mechanism of the Baeyer-Villiger oxidation:

C

O

CH3

C6H5

+ O O

H

C

O

R C

O

CH3

C6H5

H

O O C

O

R(1)

(2) H+

C

O

CH3

C6H5

H

O O C

O

R

H-RC

O

OH C

O

CH3

C6H5

H

O(3a)

phenylmigration

(3b) CH3C

O

O C6H5 + H+

Adolf von Baeyer was awarded the Nobel Prize in Chemistry in 1905.

Adolf von Baeyer was awarded the Nobel Prize in Chemistry in 1905.

CCH3CH2CH3CH2

C

O

CC

O

NHNH

OCCH3CH2CH3CH2

C

O

CC

O

NHNH

OBabiturate

( 巴比妥 )

Johann Friedrich WilhelmAdolf von Baeyer

Germany Munich University b. 1835d. 1917

A great German organic chemist of histime, he received the 1905 Nobel Prize in Chemistry for his researches on organic dyes and hydroaromatic compounds. Most famous were his researches on theconstitution and synthesis of the plant pigment indigo (1883), the discovery of barbituric acid (1863) phenolphthalein and fluorescein (1871), and the "straintheory" of triple bonds and small carbon rings.Three of his students (E. Fischer, E. Büchner, R. Willstätter) received Nobel prizes.

A great German organic chemist of histime, he received the 1905 Nobel Prize in Chemistry for his researches on organic dyes and hydroaromatic compounds. Most famous were his researches on theconstitution and synthesis of the plant pigment indigo (1883), the discovery of barbituric acid (1863) phenolphthalein and fluorescein (1871), and the "straintheory" of triple bonds and small carbon rings.Three of his students (E. Fischer, E. Büchner, R. Willstätter) received Nobel prizes.

12.7 Spectroscopic analysis of aldehydes and ketonesC

O

1665 ~ 1780 cm -1 (s) Stretching vibration

HC

O

2820, 2720 cm -1 (m) Stretching vibration

(CH3)2CHCH2 C

O

CH3 O (CH3)2C CH CH3C

O O

C H

σ / cm -1 1717 1715 1690 1700

When the carbonyl groups conjugate with carbon-carbon double bond, the location of the pick shifts to the direction of lower frequency （低频）

Ch.P336( 四 )

Ch.P336( 四 )

RCHO ~1730 cm-1 RCOR 1705 ~1720 cm-1

ArCHO 1695 ~1715 cm-1 ArCOR 1680 ~1700 cm-1

C C CHO 1680~1690 cm-1 C C COR 1665~1690cm-1

IR Spectrum of octyl aldehyde

CH3CH2CH2CH2CH2CH2CH2C H

O–CHO–CHO C

O

C

O

IR Spectrum of Acetophenone

Strentching vibration of C = O : 1683 cm -1

CCH3

O

C

O

C

O

The characteristic absorption of aldehydic proton:

HC

O 1H NMR, δ: 9 ~ 10 ppm

1H NMR spectrum of acetaldehyde

1H NMR Spectrum of ButanoneCH3

CH2C

OC

O

1H NMR δ： 2.2 ppm

δ： 2.5 ppm

13C NMR :

200 180 160 140 120 100 80 60 40 20 0

CH3CH2CCH2CH2CH2CH3

O

C

O

CH2

CH2

CH2

CH2 CH3

CH3

Chemical shift (δ, ppm)

190-220 ppm

The signal for the carbon of C=O in aldehydes And ketones appears at verylow field:

Problems to Chapter 12P3039.21(b),(e),(f),(g),(h)9.25(b),(c),(e)9.29(b)~(d)9.32(a),(b)9.34((b),(d)9.36(c)9.38(b)9.39(c)9.40(b)

P3039.21(b),(e),(f),(g),(h)9.25(b),(c),(e)9.29(b)~(d)9.32(a),(b)9.34((b),(d)9.36(c)9.38(b)9.39(c)9.40(b)

9.41(b),(c)9.449.459.48*9.499.509.51

9.41(b),(c)9.449.459.48*9.499.509.51

Ch.P363( 十四 )( 十五 )( 十六 )(B)

Ch.P363( 十四 )( 十五 )( 十六 )(B)

Additional Problems:

1. Show how the Wittig reaction might be used to prepare the following alkene. Identify the alkyl halide and the carbonyl components that would be used.

(a) C6H5CH CH CH CHC6H5

(b)

(c) CH CH2