chapter 16 aldehydes and ketones i. nucleophilic additions to the carbonyl group 16.1 introduction...
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Chapter 16 Aldehydes and Ketones I. Nucleophilic additions to t
he carbonyl group16.1 Introduction
Except for formaldehyde, the simplest aldehyde, all aldehydes have a carbonyl group, C=O, bonded on one side to a carbon, and on the other side to a hydrogen. In ketones, the carbonyl group is
situated between two carbon atoms.
H C
O
H R C
O
H R C
O
R'(Ar) (Ar) (Ar)
Formaldehyde Aldehydes Ketones
¼×È© ͪȩ
16.2 Nomenclature of aldehydes and ketones
In the IUPAC system aliphatic aldehydes are named substitutively by replacing the final e of the
name of the corresponding alkane with al
For example
H C
O
H H3C C
O
H
(Formaldehyde)¼×È© ÒÒÈ©
Methanal Ethanal
(acetaldehyde)
CH3CH2CHO
Propanal
(propionaldehyde)
CH3CH2CH2CHO
Butanal
±ûÈ© ¶¡È©
IUPAC;
Aldehydes in which the –CHO group is attached to a ring system are named substitutively by adding the suffix c
arbaldehyde.
C
O
H C
O
H
(Benzaldehyde)
±½¼×È© »·¼º»ù¼×È©
Benzenecarbaldehyde Cyclohexanecarbaldehyde 2-Naphthalenecarbaldehyde
2-ÝÁ¼×È©
IUPAC;
CHO
Aliphatic ketones are named substitutively by replacing the final e of the name of the corresponding alkane with one
C
O
CH3
(ethyl methyl ketone)
2-¶¡Íª
2-Butanone 4-Penten-2-one
4-ÎìÏ©-2-ͪ
IUPAC;
CH3CH2 CH3COCH2CH2CH3
2-Pentanone
(ethyl propyl ketone)
CH3COCH2CH=CH2
1 2 3 4 5
2-Îìͪ
C
O
CH3
±ûͪ
Acetone Benzophenone
¶þ±½¼×ͪ
CH3
Acetophenone
±½ÒÒͪ
O
CH3
O
(diphenyl ketone)(methyl phenyl ketone)(dimethyl ketone)
4-Ethanoylbenzenesulfonic acid
p-ÒÒõ£»ù±½»ÇËá
2-Methanoylbenzoic acid
2-È©»ù±½¼×Ëá
O
OH H3C
O
(p-acetylbenzenesulfonic acid)(o-formylbenzoic acid)
CHO
SO3H
Some aromatic aldehydes obtained from natural sources have very
pleasant fragrances.
CHO
OH
CHO
OH
OCH3
CHO
Benzaldehyde(from bitter almonds)
Vanillin(from vanilla beans)
Salicylaldehyde(from meadowsweet)
Ïã²ÝÈ©
¡´ Ö²¡µÐåÏß¾Õ
Ë®ÑîÈ©
¿àÐÓÈÊ
±½¼×È©
Ïã²Ý¶¹
CHO
CH=CHCHO
Cinnamaldehyde(from cinnamon)
Piperonal(made from safrole;odor of heliotrope)
ºú½·È©
ÓÉ»ÆÕÁÓ;«ÖƱ¸, [Ö²] ÏòÈÕ¿ûÆøζ,[Ö²Îï ]Èâ¹ð , ¹ð Ƥ,
Èâ¹ð È© (3-±½»ù±ûÏ©È©£©
O
O
16.4 Synthesis of aldehydes1. Oxidation
R CH3OH
N
CrO O
O
HCl PCC
CH2Cl2
R CHO
Aldehyde
CH3(CH2)5CH2OH
CH2Cl2
PCCCH3(CH2)5CHO
Heptanal(93%)
2 Reduction
H Al
OC(CH3)3
OC(CH3)2
OC(CH3)3Li+
_
Lithium tri-tert-butoxy aluminum hydride
ÈýÊå-¶¡Ñõ»ùÇ⻯ÂÁï®
Reduction reagens;
H Al
CHCH2CH3
CHCH2CH3
CH3
Diisobutyl aluminum hydride
¶þÒ춡»ùÇ⻯ÂÁ
(DIBAL-H)
CH3
Aldehydes from Acyl chlorides;
Aldehydes from esters;
Aldehydes from nitriles;
RCOCl RCHO
RCOCl RCHO
RC RCHON[H-]
[H-]
[H-] H2O
H2O
H2O
-78 oCR
O
Cl
R
O
COR'
R C N
HAl(CH(CH3)CH2CH3)2 H2O
-78 oC
HAl(CH(CH3)CH2CH3)2 H2O
-78 oC
HAl(CH(CH3)CH2CH3)2 H2O
R
O
H
-78 oCR
O
ORHAl(CH(CH3)CH2CH3)2
H-
R
OAl(i-Bu)2
OR
H
(-OR)R
O
H
+ Al(i-Bu)2H2O
R
O
H
- +
Reduction of Esters to aldehydes
16.5 Synthesis of ketones
1. Ketones (and aldehydes) by Ozonolysis of alkenes
R
R'
R''
H
1. O3
2. Zn, H2OO
R
R'
O
R''
H
+
Ketone AldehydeAlkenes
2. Ketones from Friedel-Crafts Acylations
+ RCOClAlCl3 COR
+ HCl
+ COClAlCl3 C
+ HCl
O
+AlCl3 COR
+ HCl
O
R
O
R
O
3. Ketones from Oxidations of secondary alcohols
R CH
OH
R'H2CrO4
R C
O
R'
H3C CH
OH
CH3
H2CrO4H3C C
O
CH3
4. Ketones from Alkynes
C C + H2OHgSO4
H2SO4
C C
H
O
A vinylic alcohol (Ï©±û´¼£©(Unstable)
H
C C
OH
H
Keto form
C CH3C CH3 + H2OHgSO4
H2SO4
C CH3C CH3
H
O
A vinylic alcohol (Ï©±û´¼£©(Unstable)
H
H3C C C
O
CH3
H
H
2-Butanone
5. Ketones from Lithium Dialkylcuprates ( 二烷基酮锂）
R2CuLi + R'CCl
O
Lithiumdialkylcuprate
Acyl chloride
R' C R
O
O
Cl + (CH3)2CuLi-78 oC
O
CH3
(81%)
Hexyl methyl ketoneLithium dimethylcuprate
6. Ketones from the reaction of nitriles with RMgX or RLi
R C N + R'MgX R
N+ MgX-
R'
H3O+
R
O
R'
R C N + R' Li R
N+ Li-
R'
H3O+
R
O
R'
C N + Ph
N+ MgBr-
PhH3O+
Ph
O
Ph
Ph C N + Ph
N+ Li-
CH2CH2CH2CH3
H3O+
C6H5
O
CH2CH2CH2CH3
C6H5MgBr
n-BuLi
16.6 Nucleophilic addition to the carbon-oxygen double bond
R
H
O + H-Nu R
H
OH
Nu
Nucleophilic addition
Nucleophilic reagent
H3C
H
O +
H3C
H
OH
OCH2CH3
Nucleophilic addition(a hemiacetal°ëËõÈ©£©
H-OCH2CH3
H3C
H3C
O +
H3C
H3C
OH
CN
Nucleophilic addition
(a cyanohydrinÇè´¼£©
H-CN
16.7 The addition of water and alcohols: Hydrates( 水合物 ), Acetals
（缩醛） , and ketals( 缩酮 )
H3C
H
O +
H3C
H
OH
OH
Nucleophilic addition
Nucleophilic reagent
H-OH
Hydrate( a gem-diol)̼ͬ¶þ´¼
Cl3CC
H
O +
Cl3C
H
OH
OH
Nucleophilic addition
Nucleophilic reagent
H-OH
Chloral Hydrate( a gem-diol)̼ͬ¶þ´¼
Trichloroethanal
ÈýÂÈÒÒÈ©
16.7B Hemiacetals and Hemiketals（半缩醛和半缩酮）
R
H
O +
R
H
OH
OR
Nucleophilic addition
Nucleophilic reagent
H-OR
Hemiacetal °ëËõÈ©
H+
R
H
OH
OR
(unually too unstable to isolate)Aldehyde
R
R
O +
R
H
OH
OR
Nucleophilic addition
Nucleophilic reagent
H-OR
Hemiacetal °ëËõͪ
H+
R
R
OH
OR
(unually too unstable to isolate)
Ketone
16.7C Acetals and cyclic ketals （缩醛和环状缩酮）
R
H
O +
R
H
OH
OR
Nucleophilic addition
Nucleophilic reagent
H-OR
Hemiacetal °ëËõÈ©
H+
R
H
OH
OR
(unually too unstable to isolate)Aldehyde
HCl
ROH
R
H
OR
OR
an acetal ËõÈ©
R
R
O +
R
H
OH
OR
Nucleophilic addition
Nucleophilic reagent
H-OR
Hemiacetal °ëËõͪ
H+
R
R
OH
OR
(unually too unstable to isolate)
Ketone
HCl
ROH
R
R
OR
OR
an acetal ËõͪR
R
O +
Nucleophilic addition
Nucleophilic reagent
Ketone
HCl R
R
an ketal Ëõͪ
HO
HOO
O
R
R
an ketal Ëõͪ
O
O
HCl+ H2O
R
R
O +
HO
HO
Cyclic ketals as protecting groups
16.7D Acetals and cyclic ketals as protecting groups
HO
HO
Cyclic ketals as protecting groups
O
O
OCH2CH3 O CH2OH
LiAlH4 or H2 / Ni HO CH2OH
HCl
O
OCH2CH3
O
O
±ä³ÉËõͪ£¬±£»¤ôÊ»ù
Synthetic application
HO
HO
Cyclic ketals as protecting groups
O
O
OCH2CH3
HCl
O
OCH2CH3
O
O
±ä³ÉËõͪ£¬±£»¤ôÊ»ù
1. LiAlH4, (CH3CH2)2O
2. H2O
CH2OH
O
O
H+
H2O
OCH2OH
È¥±£»¤»ù
16.7E Thioacetals and thioketals;硫缩醛和硫缩酮
Aldehydes and ketones react with thiols to form thioacetals and thioketals.
R
H
O +
HSCH2CH3
HSCH2CH3
R
H
SCH2CH3
SCH2CH3
H+
- H2O
Thioacetal
R
R
O +
R
R
S
S
H+
- H2O
Cyclic Thioketal
HS
HS
Raney Ni
H2
R
R
Zn-Hg, HCl
Clemmensen reduction
16.8 The addition of derivatives of ammonia
Aldehydes and ketones react with a number of derivatives of ammonia in the general way sho
wn in the following sequence:
R
H
O+N H
H
N
H
H
H
R
O-
(R')(R')
+
N
H
H
R
OH
(R')
N
R
H- H2O (R')
- H+
Nucleophilic addition---Elimination
16.8A 2,4-Dinitrophenylhydrazones, Semicarbazones, and oximes
Nucleophilic addition---Elimination
O
+ H2N OH
Aldehyde or ketone
N OH + H2O
HydroxylamineôÇ°·
+ H2NNH2
Hydrazine
N NH2 + H2O
An oxime
A hydrazone
H2NNH
Phenylhydrazine ±½ëÂ
N NHC6H5 + H2O
A phenylhydrazone
ph
ë ëê
ë¿
񫉈
Nucleophilic addition---Elimination
O
Aldehyde or ketone
H2NNH
2,4-Dinitrophenylhydrazine2£¬4-¶þÏõ »ù±½ëÂ
N NHNH + H2O
A 2,4-Dinitrophenylhydrazone2£¬4-¶þÏõ »ù±½ëê
O2N
NO2
O2N
NO2
H2NNHCNH2
O
NNHCNH2
O
+ H2O
Semicarbazide A semicarbazone°±»ùëå Ëõ°±»ùëå
+
Specific ExamplesNucleophilic addition---Elimination
H3C
H
O + H2N OH
Acetaldehyde
H3C
H
N OH + H2O
HydroxylamineôÇ°·
+ H2NNH2
Hydrazine
C6H5
N NH2 + H2O
Acetaldoxime
Propiophenone hydrazone
H2NNH
Phenylhydrazine ±½ëÂ
C6H5
H3C
N NHC6H5 + H2O
Acetophenone phenylhydrazone
ph
ë ±½±ûͪëê
ÒÒÈ©ë¿
±½ÒÒͪ±½ëê
ÒÒÈ©
C6H5
O
Propiophenone±½±ûͪ
C6H5
H3C
O +
Acetophenone±½ÒÒͪ
O + H2NNHCNH2
O
NHNHCONH2
Cyclohexanone Cyclohexanone semicarbazone
»·¼ºÍª »·¼ºÍªËõ°±»ùëå
+ H2O
Semicarbazide
因为产物都是固体，利用此反应可以鉴定未知有机物。
16.8B Imines
Aldehydes and ketones react with primary amines to form imines.
Nucleophilic addition---Elimination
H3C
H
O + H2N CH3
Acetaldehyde
H3C
H
N CH3 + H2O
Methylamine¼×°·
Acetaldimine
ÒÒÈ©ÑÇ°·ÒÒÈ©
£¨Î÷·ð¼î£©£¨Schiff bases)
16.8C Hydrazones: The Wolff-Kishner reduction
Hydrazones are the basis for a useful method to reduce carbonyl groups (C=O) of aldehydes and ketones to – CH2 – groups, called the Wolff-K
ishner reduction
O H2N-NH2
NaOH+
Triethylene glycol, 200 oC
HOCH2CH2OCH2CH2OCH2CH2OH
C N-NH2 CH2
Hydrazone(not isolated)
+ N2 + H2O
O
CH2CH3
NaOH
Triethylene glycol, 200 oC
HOCH2CH2OCH2CH2OCH2CH2OH
CH2CH2CH3
16.9 The addition of hydrogen cyanide (HCN) and of sodium bis
ulfite (NaHSO3)
O
R
H (R')
+ HCN
R
H (R')
OH
CNCyanohydrins
ëæ´¼
ÇâÇèËá
Hydrogen cyanide
O
R
H (R')
+ NaHSO3
R
H (R')
OH
SO3Na
Sodium bisulfite Bisulfite addition product
ÑÇÁòËáÇâÄÆ
Cyanohydrins are useful intermediates in organic
synthesis.
O
H3C
H3C
+ HCN
H3C
H3C
OH
CN
Cyanohydrins
ëæ´¼
ÇâÇèËá
Hydrogen cyanide
HCl, H2OH3C
H3C
OH
COOH
H2SO4
CH3OHH2C
CH3
COOCH3
Hydroxy acid
ôÇ»ùËá
£¬ - Unsaturated acid
CH2 C
CH3
COOCH3
* *n
¾Û±ûÏ©Ëá¼×õ¥2-¼×»ù±ûÏ©Ëá¼×õ¥
HCN
Cyanohydrins
ëæ´¼
ÇâÇèËáHydrogen cyanide
O
NaHSO3
OH
CN
OH
SO3Na
1) LiAlH4
2) H2O
OH
CH2NH2
- amino alcohol
16.10 The addition of ylides( 叶立德） : The wittig （魏悌希） reactio
n
O
R
(R')H
+ (C6H5)3P-C
R'''
R''+ -
Phosphorus ylide
Á×Ò¶Á¢µÂ
R
(R')H
R''
R'''
+ O P(C6H5)3
Triphenylphosphine oxide
Èý±½»ùÑõì¢
This reaction, known as the wittig reaction ， has proved to be a valuable method for synthesizing alkenes. Discovered in 1954 by Geroge Wittig, then at the University of Tubingen. Wittig was a co-winner of the Nobel prize for chemistry in 1979.
How to make phosphorus ylide?
Step 1
Step 2
(C6H5)3P: + CH3 Br (C6H5)3P CH3Br -+
Methyltriphenylphosphonium bromide (89%)
(C6H5)3P CH3Br -+
+ C6H5Li or n-BuLi (C6H5)3P CH2:-+
Betaine£¨ÄÚÑΣ©
Phosphorus ylide ì¢Ò¶Á¢µÂ
(C6H5)3P CH2:-+
(C6H5)3P CH2
Resonance structures
(C6H5)3P CH2:-+
O+ CH2
O- P(C6H5)3+
O P(C6H5)3
CH2 + O P(C6H5)3
Triphenylphosphine
Methylenecyclohexane
(C6H5)3P CHCH3
++
HC
O- P(C6H5)3+
O P(C6H5)3
C + O P(C6H5)3
Triphenylphosphine
O
H
- CH3
CH3
C6H5
H
H
CH3
C
C6H5
H
CH3
H
E-
Z-
16.11 The addition of organometallic reagents: The reformatsky reaction
Grignard reagent;
RMgX + O R OMgXH3O+
R OH
Organolithium reagent;
RLi + O R OLiH3O+
R OH
Sodium alkynides;
RC CNa + O ONaH3O+
R
OHR
The Nucleophilic Addition of organometallic reagents are as follows
The addition of an organo zinc reagent to the carbonyl group of an aldehyde or ket
one is called the Reformatsky reaction
O
H2C OZnBrH3O+
The Reformatsky reaction;
BrCH2COOCH2CH3 + ZnBenzene
BrZnCH2COOCH2CH3
Bromoester
H3CH2COOC CH2 OHH3CH2COOC
-Hydroxy ester
Examples of the Reformatsky reaction are the following:
The Reformatsky reaction;
BrCH2COOCH2CH3 + ZnBenzene
BrZnCH2COOCH2CH3
Bromoester
CH3CHO BrZnCH2COOCH2CH3
+
Similar Grignard reagent
H3O+
CH3CHCH2COOCH2CH3
OH
BrZnCH2COOCH2CH3
H3O+
CH3CCH2COOCH2CH3
OH
CH3C
CH3
O +
CH3
16.12 Oxidation of aldehydes and ketones
O
H
KMnO4, NaOHO
ONa
O
OH
HCl
or Ag2O, NaOH
O
CH3
KMnO4, NaOH
or Ag2O, NaOHNo reaction
Benzoic acid
16.12A The Baeyer-Villiger oxidation of aldehydes and ketones
Both aldehydes and ketones are oxidized by peroxy acids. This reaction, called the Baey
er-Villiger oxidation.
O
CH3
Acetophenone
RCOOH
O
O
O
CH3
Phenyl acetate ÒÒËá±½õ¥
The mechanism proposed for this reaction involves the following steps:
O
CH3
Acetophenone
Phenyl acetate ÒÒËá±½õ¥
+ HO O
O
R
CH3
OH
O O
O
R
H+
CH3
OH
O O
+OH
R
CH3
O
O+
O
OH
R
H
phenyl migration
H3C
O
O + H+
Peroxy acid
16.13 Chemical and spectroscopic analysis for aldehydes and ketones
16.13A Tollens’test( 托伦测试） (silver mirror test 银镜测试）
R
O
H(Ar)
(H)Ag(NH3)2OH+ R
O
O-(Ar)
(H)+ Ag
Silver mirrorTollen' reagent
Aldehyde or ketones
R
O
R(Ar)
Ag(NH3)2OH+
Tollen' reagent
No reaction
KetonesTollen’s test can distinguish with aldehydes and ketones
16.13B Spectroscopic properties of aldehydes and ketones
Carbonyl stretching bands of aldehydes and ketones
C=O stretching frequencies
RCHO 1720 cm-1
ArCHO 1695 cm-1
ArCH=CHCHO 1680 cm-1
RCOR 1710
ArCOR 1680
C=CCOR 1665
cm-1
cm-1
cm-1
Additional problems---Homework
16.24, 16.26, 16.28, 16.31, 16.32, 16.42