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Chapter 12.Carboxylic Acid Derivatives
(羧酸衍生物)
Text 1: chapter 21
Test 2: 第 13 章
esters
酯 R
O
OR'
acid anhydride
酸酐 R
O
O R
O
acid halides
酰卤 R
O
Cl
amides
酰胺 R
O
NR1R2
nitriles
腈R CN
Acid or base
waterCarboxylic acids
12.1 Nomenclature
Esters -yl (-oic acid)-ate× 酸 ×酯
CH3COCH2CH3
O
CH3COCH=CH2
O
CH3CH2COC(CH3)3
O
ethyl acetate ethyl ethanoate乙酸乙酯
vinyl acetate ethenyl ethanoate乙酸乙烯酯
tert-butyl propanoate丙酸叔丁酯
CH3COCH2CH2CH(CH3)2
OCH3CH2CH2CH2C
O
OCH2CH2CHCH3
CH3isopentyl acetate(used in synthetic banana flavor)乙酸异戊酯
isopentyl pentanoate(used in synthetic apple flavor)戊酸异戊酯
CO
OCH3 CO
OCH3Cl
methyl benzoate苯甲酸甲酯
methyl p-chlorobenzoate对 - 氯苯甲酸甲酯
CH3CH2OOCCH2COOCH2CH3
diethyl malonate丙二酸二乙酯
Cyclic Esters Are Known as Lactones
6-methyl-tetrahydropyran-2-one
5-hydroxyhexanoic acid lactone
OHO H
CH2OH
Vitamin CH
HOOH
άÉúËØ C
O
O
O
OHHO
H
O
OH
O
O
O
O
HO
N(CH3)2
CH3
CH3OH
CH3
OCH3
Erythromycin A ºì ùËØ
acid anhydrides酸酐
CO
O
O
H3C
H3C CO
O
O
H2C
H2C
CO
O
O
HC
HCO
O
O
--oic acid ——— --oic anhydride
acetic anhydride乙酐醋酐
succinic anhydride环丁酐丁二酸酐琥珀酸酐
maleic anhydride环丁烯酐顺丁烯二酸酐马来酐
phthalic anhydride邻苯二甲酸酐
acyl chlorides (acid chlorides酰氯 )
R C
O
CH3C
O
Cl CH3CH2C
O
Cl C
O
Cl
Acyl group酰基
acetyl chloride乙酰氯
propanoyl chloride丙酰氯
benzoyl chloride苯甲酰氯
--ic acid ——--yl chloride
amides --ic acid——--amide
CH3C
O
NH2CH3CH2C
O
NH2 C
O
NH2
acetamide酰胺
propanamide丙酰胺 benzamide
苯甲酰胺
HC
O
N(CH3)2
N,N-dimethylformamideN,N- 二甲基甲酰胺DMF
N-phenylacetamideN- 苯基乙酰胺
CH3C
O
NH C6H5
primary amide 伯酰胺 secondary amide 仲酰胺 tertiary amide 叔酰胺
Cyclic Amides Are Known as Lactams( 内酰胺 )
-valerolactam- 戊内酰胺
-butyrolactam- 丁内酰胺
-propiolactam- 丙内酰胺
NH
O
NH
O
NH
O
N
SNHC
O
R
OCH3
CH3
COOH
R = C6H5CH2 -
R =
NH2
R = C6H5OCH2 -
( penicillin G)
(ampicillin)
(penicillin V)
(ÇàùËØ G)
( penicillin)
C6H5CH
Nitriles alkanenitrile
CH3 C N CH3CH2CH2C N H2C CH C N
ethanenitrile(acetonitrile)乙腈
butanenitrile丁腈
propenenitrile丙烯腈
C N C N
benzenecarbonitrile(benzonitrile)苯甲腈
cyclohexanecarbonitrile环己基甲腈
Functional group Name as main group Name as substituent
carboxylic acids 羧酸
-oic acid carboxy( 羧基 )
esters 酯 -oate alkoxycarbonyl( 烷氧羰基 )
amides 酰胺 -amide amido( 酰氨基 )
nitriles 腈 -nitrile cyano( 氰基 )
aldehydes 醛 -al formyl( 甲酰基 )
ketones 酮 -one oxo( 氧代 )
alcohols 醇 -ol hydroxy( 羟基 )
amines 胺 -amine amino( 氨基 )
alkenes 烯 -ene alkenyl( 烯基 )
alkynes 炔 -yne alkynyl( 炔基 )
alkanes 烷 -ane alkyl( 烷基 )
ethers 醚 alkoxy( 烷氧基 )
halides 卤代烷 halo( 卤 )
Main groups in order of decreasing priority
12.2 Structure and physical properties
CN
OC
N
O
bp, mp: (Figure 21-2, p 948)
amide > acid > nitrile > alcohol > ester≈acid chloride ≈alkane
amide: primary > secondary > tertiary
CN
O
HO
N
H
Solubility: (Table 21-2)
All are soluble in common organic solvents.
Some are common organic solvents.
ethyl acetate (EtOAc ,乙酸乙酯, bp 77 , 10%℃ )
acetonitrile (CH3CN , 乙腈, bp 82 ℃, misible with water)
DMF (N,N-dimethylformamide, N,N- 二甲基甲酰胺, bp 153 , misible with water,℃ )
IR
12.3 Spectroscopy
Compounds Stretching frequency of C=O (cm-1)
RCOCl(RCO)2O
RCO2R
RCONH2
RC≡N
1815~17851850~1800 and 1780~174017351680~16302210~2260
Esters ,Carboxylic acid , anhydrides
1310 ~1050 cm-1 C- O- C
Amides 3500 ~3200 cm-1 N–H
Ring strain in a lactone or lactam increases the carbonyl streching frequency.
NH
O
NH
O
NH
O
1670 1700 1745 ( cm-1 ) .
O
O
O
O
O
O
1735 1770 1800 ( cm-1 ) .
1743
1827 1766
33483173 1681
CH3C
O
L RCH2C N
α - H δ: 2 ~ 3 ppm
1H NMR
13C NMR
C Nδ: ~120 ppm
N - H δ: 5 ~8 ppm
Amide:
C=O
δ: ~ 170 ppm
1H NMR:
13C NMR:
CH3
O
O
H2C
H3C 1.25
2.05
4.15
CH3
O
O
H2C
H3C
171
60
20
14
12.4 Interconversion of acid derivatives by nucleophilic acyl substitution ( 亲核酰基取代 )
Reactivity and interconversion of acid derivatives:
More reactive Less reactive
R C
O
Cl R C
O
O R C
O
OR'C
O
R R C
O
NH2 R C
O
O
R C
O
Cl + R'OH + HClR C
O
OR'
R C
O
Cl + R'NH2 + HClR C
O
NHR'
R C
O
Cl + + HClR C
O
OR' C
O
OH C
O
R'
R C
O
O +C
O
R R C
O
OR'R'OH R C
O
OH+
R C
O
O +C
O
R R C
O
NHR'R'NH2 R C
O
OH+
R C
O
OR' +
R C
O
OR' + + ROHR"NH2 R C
O
NHR"
R"OH + R'OHR C
O
OR"
transesterification酯交换反应
ammonolysis酯氨解反应
acid chlorides and anhydrides are used as acylation reagents.( 酰化试剂 )
Mechanism: nucleophilic acyl substitution (亲核酰基取代)
addition elimination deprotonation
R C
O
L + NuH R C
O
L
NuH
R C
ONu + HLR C
O
NuH
+ L
acid-catalyzed mechanism: protonation of carbonyl oxygen, addition, elimination
base-catalyzed mechanism : addition, elimination
Acid-catalyzed transesterification 酸催化的酯交换反应
RC
O
OR'
H+
RC
OH
OR'
HOR"R C
OH
OR'
OR"H
R C
OH
OR'
OR"
- H+
R C
OH
OR'
OR"
H+
R C
OH
OR'
OR"
H
RC
OH- HOR'
OR"
- H+
RC
O
OR"
RC
O
OR'
OR"R C
O
OR'
OR"
- OR'
RC
O
OR"
Base-catalyzed transesterification 碱催化的酯交换反应
12.5 Hydrolysis of acid derivatives
Neutral hydrolysis
Acid-catalyzed hydrolysis
Base-catalyzed hydrolysis
Mechanism: nucleophilic acyl substitution
1. Hydrolysis of acid halides and anhydrides
Acid chlorides and anhydrides hydrolyze under neutral condition.
R C
O
Cl + R C
O
Cl
OH2
R C
OOH +R C
O
OH2
+ ClH2O HCl
R C
O
O + R C
OOHH2OC
O
R 2
2. Hydrolysis of esters
Acid–catalyzed hydrolysis of esters is the reverse of the Fisher esterification, is a equilibrium.
Base–catalyzed hydrolysis of esters is also called saponification ( 皂化反应 ), avoids the equilibrium of the Fisher esterification.
RCO
OR'
OHR C
O
OR'OH
- OR'
RC
O
OH
OR'
RC
O
O+ ROH
3. Hydrolysis of amides
Acid–catalyzed hydrolysis of amides: 6 mol/L HCl
RC
O
NH2
H+
RC
OH
NH2
HOHR C
OH
NH2
OHH
R C
OH
NH2
OH
- H+
R C
OH
NH2
OH
H+
R C
OH
NH2
OH
H
RC
OH- NH3
OH RC
O
OH
NH3
+ NH4
Base–catalyzed hydrolysis of amides: 40% aqueous NaOH
RCO
NH2
OHR C
O
NH2
OH
- NH2
RC
O
O RC
O
O+ NH3
NH2
H
4. Hydrolysis of nitriles
R C NH+
R C NH R C NHHOH
R C
OH
NH
H
R C
OH
NH- H+
Acid–catalyzed hydrolysis of nitriles
amides
Amides can be hydrolyzed to carboxylic acid under stronger conditions.
R C
OH
NHH+
R C
OH
NH2 R C
OH
NH2- H+
R C
OH
NH2 R C
O
NH2
Base–catalyzed hydrolysis of nitriles
R C N R C
OH
NOH OH
R C
OH
NH OH+H
R C
O
NH R C
O
NH R C
O
NH R C
O
NH2
OHH
H O HOH+
amides
Amides can be hydrolyzed to carboxylic acid under stronger conditions.
12.6 Reduction of acid derivatives
1. Reduction to alcohols
estersacid chloridescarboxylic acid
aldehydes 1° alcoholsLiAlH4 LiAlH4
2. Reduction to aldehydes
LiAl(OC(CH3)3)Hacid chlorides aldehydes
RCOClLiAl[OC(CH3)3]3H
RCHO
3. Reduction to amines
amidesnitriles
aminesLiAlH4
R C N R CH2 NH2
i. LiAlH4
ii. H2O
R C
O
NH2
i. LiAlH4
ii. H2OR C
O
NHR'
R C
O
NR'2
R CH2 NH2
R CH2 NHR'
R CH2 NR'2
12.7 Reaction of acid derivatives with organometallic reagents
O
COR'R
O
CClR
i. R"MgX
ii. H3O+ R R"
OHR"
esters:
acid chlorides:
tertiary alcohols三级醇
nitriles:i. R"MgX
ii. H3O+R C NR
C
O
R"
amides: NO reaction.
1. Synthesis of acyl chlorides
12.8 The chemistry of acyl chlorides
R C
O
OH
SOCl2
R C
O
Clor PCl3or PCl5
or (CO)2Cl2
2. Reactions of acyl chlorides
Acyl chloride
R C
O
Cl
R'COONa
(- NaCl)R'COOOCRAnhydride
R'OH, Base
(-HCl)RCOOR'
Ester
R'R''NHRCONR'R''amide
(R'=H, alkyl
(R', R"=H, alkyl(-HCl)
Acid chloride is important acylation reagent ( 酰化试剂 )
O
CClR
i. R"MgX
ii. H3O+ R R"
OHR"
i. LiAlH4
ii. H2O
LiAl[OC(CH3)3]3HRCHO
RCH2OH
R'2CuLi O
CR'R
Z
AlCl3Z
C
O
R
Z = H, alkyl, activating groups
1. Synthesis of carboxylic acid anhydrides
12.9 The chemistry of acid anhydrides
HO C
O
R'
Acyl chloride
õ£ÂÈ
R C
O
Cl +N
R C
O
O C
O
R' +N+H
Cl-
NaO C
O
R'
Acyl chloride
õ£ÂÈ
R C
O
Cl + R C
O
O C
O
R'(- NaCl)
HOOCCH2(CH2)nCOOH O
O
On
heatn=0, 1
2. The reactions of acid anhydride
R CO
O
R'OHRCOOR' + RCOOH
Esteracid, R' = H
RCONR'R''R'R''NH
amideCO
R
Z
AlCl3Z
C
O
R
Z = H, alkyl, activating groups
(R', R"=H, alkyl
Useful anhydrides:
acetic anhydrides( 醋酐 ) acetic formic anhydrides (甲乙酐)
cyclic anhydrides (环状酸酐)
H3CC
O
O
CCH3
O
H3CC
O
O
CH
O
ORC
H
O
H3CC
O
O
CH
O
+ ROH + CH3COOH
+ ROHCO
OC
O
H2C
H2C CO
C
O
H2C
H2C OR
OH
CO
OC
O
H2C
H2C
12.10 The chemistry of esters
• 1. Synthesis of esters
C
O
Cl + HOCH2CH3 C
O
OCH2CH3
Ethyl benzoate(80%)
Benzoyl chloride
Py
O
O
O
+ CH3CHCH2CH3
OH
C
C
O
O
OH
OCHCH2CH3
CH3
R C
O
OH
carboxylic acidR C
O
OCH3+ CH2N2
diazomethane methyl ester+ N2
R C
O
OH + HOR'H+
R C
O
OR' + H2OEster
2. The reactions of esters
R C
O
OR'i. R"MgX
ii. H3O+ R R"
OHR"
i. LiAlH4
ii. H2ORCH2OH
H2O
H+, or HO- R C
O
OH R C
O
Oor
R"OHRCOOR"
R'R''NH RCONR'R'' (R', R"=H, alkyl
H+, or RO-
+ R'OH
12.11 The chemistry of amides
1. Synthesis of amides
RCOClHNR'R" R C
O
NR'R"or anhydridesor acids (R', R"=H, alkyl
or esters
H2O
H+, or HO- R C
O
NH2R C N
2. The reactions of amides
R C
O
NH2
H2O
H+, or HO-
R C N
i. LiAlH4
ii. H2ORCH2NH2
R C
O
OH R C
O
Oor
or P2O5, or Ac2O
Br2, -OHRNH2
POCl3 only primary amides
Hoffmann rearrangement( 霍夫曼重排,霍夫曼降解 )only primary amides
Polyamides (聚酰胺)
NH
O
H2O-OC(CH2)5NH2
O
C
O
(CH2)5NH C
O
(CH2)5NHn
+ n H2N (CH2)6NH2HO C
O
(CH2)4 C
O
OHn
NH C
O
(CH2)4 C
O
NH (CH2)6(H2C)6 NHHNn
Nylon 6
Nylon 6,6
12.12 The chemistry of Nitriles
1. Synthesis of nitriles
R C
O
NH2 R C Nor P2O5, or Ac2O
POCl3
R X (1 °)NaCN
R C N
R C
O
R'HCN
KCNR C
OH
R'
CN
2. The reactions of nitriles
H2O
H+, or HO- R C
O
NH2
R C N
H2O
H+, or HO-
i. LiAlH4
ii. H2O RCH2NH2
R C
O
OH R C
O
Oor
i. R"MgX
ii. H3O+ RC
O
R"
12.13 Thioesters ( 硫酯 ) 21-15, p 988
R C
O
OH + HSR' R C
O
SR' + H2O
thiol硫醇
thioesters硫酯
Reactivity as acylating reagents:
acid chlorides > acid anhydrides > thioesters > esters
Thioesters are common acylating reagents in living systems.
常用来代替在水中不稳定的酰氯和酸酐作酰化试剂。
12.14 Derivatives of carbonic acid(碳酸的衍生物)
HO C
O
OH
carbonic acid碳酸
Cl C
O
Cl RO C
O
OR H2N C
O
NH2
carbonyl dichloridephosgene
碳酰氯,光气
carbonate esters碳酸酯
urea尿素,脲
RHN C
O
OH RHN C
O
OR'
carbamic acid氨基甲酸unstable
carbamate , urethane氨基甲酸酯
Cl C
O
Cl + CH3CH2OCOCH2CH3
O
Diethyl carbonate
+ 2 HCl
2 H2O
HO C
O
OH + 2 HCl
air
2 HOCH2CH3
Cl C
O
Cl + 4 NH3 H2N C
O
NH2 +
Urea
2 NH4Cl
Assignments
Text 1: 48, 49, 50, 53, 55, 57