Chapter 21 Acid Der

Chapter 21
Lecture
Carboxylic Acid
Derivatives
羧酸衍⽣物
© 2017 Pearson Education, Ltd.
© 2014 Pearson Education, Inc.

21-1 Introduction
Carboxylic Acid Derivatives
• Carboxylic acid derivatives are defined as compounds

with functional groups that can be converted to
carboxylic acids by a simple acidic or basic hydrolysis.
• 羧酸衍⽣物被定義為具有可以通過簡單的酸性或鹼性
⽔解轉化為羧酸的官能團的化合物。
© 2014 Pearson Education, Inc.

Some Naturally Occurring Esters and Amides

21-2 Structure and Nomenclature of Acid Derivatives
• Esters are carboxylic acid derivatives in which the

hydroxy group (—OH) is replaced by an alkoxy
(—OR).
酯是其中羥基（-OH）被烷氧基（-OR）取代的羧酸
衍⽣物。

Common and Systematic Names for Some
Acids, Alcohols, and Esters

Lactones
• Cyclic esters are called lactones. 環酯被稱為內酯

• The IUPAC names of lactones are derived by adding the term
lactone at the end of the parent acid.
內酯的IUPAC名稱是通過在⺟體酸的末端加入內酯⼀
詞⽽得到的。
Amides
• An amide is a composite of a carboxylic acid and

ammonia or an amine.
酰胺是羧酸和氨或胺的複合物。
• Ammonium salts are converted to amides at high
temperatures.
銨鹽在⾼溫下轉化為酰胺。

Resonance Representation of Amides

Amide Substitution and Naming
Problem 1
Lactams
• Cyclic amides are called lactams.

環酰胺被稱為內酰胺
• Lactams are named by adding the term lactam at the
end of the IUPAC name of the parent acid.
內酰胺通過在⺟體酸的IUPAC名稱末尾添加術語
內酰胺來命名。
Nitriles
• Nitriles contain the cyano group.

腈含有氰基。

Electronic Structure of Nitriles
• The atoms at the ends of the triple bonds are sp

hybridized, and the bond angle is 180°.
三鍵末端的原⼦是sp雜化的，鍵⾓為180°。

Acid Halides
• Acid halides are named by replacing the -ic acid suffix name with
-yl and the halide name.
酰⿄通過⽤ - 基和⿄化物名稱代替-ic酸後綴名來命名。
• Acid halides are also called acyl halides.

酰⿄也被稱為酰⿄。
• Acid halides are activated derivatives used in the synthesis of
other acyl compounds such as an ester.
酰⿄是⽤於合成其它酰基化合物如酯的活化衍⽣物。
Acid Anhydrides
• The word anhydride means “without water.”

酸酐這個詞的意思是“沒有⽔”。
• An acid anhydride contains two molecules of acid, with loss of a
molecule of water.
酸酐含有兩個酸分⼦，失去⼀個⽔分⼦。
• Acid anhydrides are activated derivatives of carboxylic acids.

酸酐是羧酸的活化衍⽣物。

Naming Acid Anhydrides
• Acid anhydrides are named by replacing the word acid

with anhydride.
酸酐通過⽤酸酐代替酸來命名。

Nomenclature of Multifunctional Compounds
acid > ester > amide > nitrile > aldehyde > ketone > alcohol > amine > alkene, alkyne

21-3 Physical Properties of Carboxylic Acid Derivatives
• The physical properties of acid derivatives largely depend on their

polarity and their hydrogen-bonding properties.
酸衍⽣物的物理性質在很⼤程度上取決於它們的極性和它們的氫
鍵性質。
Resonance
• The resonance picture of an amide shows its strongly polar

nature.
酰胺的共振圖顯⽰其強極性。

Solubility of Carboxylic Acid Derivatives
• Acid derivatives (esters, acid chlorides, anhydrides, nitriles,

and amides) are soluble in common organic solvents.
酸衍⽣物（酯，酰氯，酸酐，腈和酰胺）可溶於普通
有機溶劑。

21-5 Interconversion of Acid Derivatives
Nucleophilic Acyl Substitution
• Interconversion of acid derivatives occurs by nucleophilic acyl
substitution.
通過親核酰基取代發⽣酸衍⽣物的互變。
• The nucleophile adds to the carbonyl, forming a tetrahedral
intermediate.
親核試劑加成羰基，形成四⾯體中間體。
• Elimination of the leaving group regenerates the carbonyl.
消除離去基團再⽣羰基。
• This is an addition–elimination mechanism.
這是⼀個加成消除機制。
• Nucleophilic acyl substitutions are also called acyl transfer reactions
because they transfer the acyl group to the attacking nucleophile.
親核酰基取代也被稱為酰基轉移反應，因為它們
將酰基轉移到攻擊的親核試劑上。
Mechanism of Acyl Substitution
Step 1: Addition of the nucleophile forms the tetrahedral intermediate.
親核試劑的加成形成四⾯體中間體
Step 2: Elimination of the leaving group regenerates the carbonyl

group.
消除離去基團再⽣羰基

Reactivity of Acid Derivatives

Interconversion of Derivatives
• More reactive
derivatives can be
converted to less
reactive derivatives.
反應性更好的衍⽣物可
以轉化為反應性較⼩的
衍⽣物

Acid Chloride to Anhydride
• The carboxylic acid attacks the acyl chloride, forming the tetrahedral intermediate.
羧酸攻擊酰氯，形成四⾯體中間體。
• Chloride ion leaves, restoring the carbonyl.
氯離⼦離開，恢復羰基。
• Deprotonation produces the anhydride.
去質⼦化產⽣酸酐
Acid Chloride to Ester
• The alcohol attacks the acyl chloride, forming the

tetrahedral intermediate.
酒精攻擊酰氯，形成四⾯體中間體。
• Chloride ion leaves, restoring the carbonyl.
氯離⼦離開，恢復羰基。
• Deprotonation produces the ester.
去質⼦化產⽣酯。
Acid Chloride to Amide
• Ammonia yields a 1° amide.

氨產⽣1°的酰胺。
• A 1° amine yields a 2° amide.
1°的胺產⽣2°的酰胺。
• A 2° amine yields a 3° amide.
2°胺產⽣3°酰胺。

Anhydride to Ester
• Alcohol attacks one of the carbonyl groups of the anhydride, forming

the tetrahedral intermediate.
醇攻擊酸酐的羰基之⼀，形成四⾯體中間體。
• The other acid unit is eliminated as the leaving group.
另⼀個酸單位作為離去基團被消除。

Anhydride to Amide
• Ammonia yields a 1° amide; a 1° amine yields a 2° amide; and a 2°

amine yields a 3° amide.
氨產⽣1°酰胺; 1°胺產⽣2°酰胺;和2°的胺產⽣3°的酰胺

Ester to Amide: Ammonolysis
• The nucleophile must be NH3 or 1° amine.

親核試劑必須是NH3或1°胺
• Prolonged heating is required.
需要延長加熱時間。

Leaving Groups in Nucleophilic Acyl Substitution
• A strong base, such as an alkoxide (–OR), is not usually a

leaving group, except in an exothermic step.
除了放熱步驟之外，強鹼（如醇鹽–OR）
通常不是離去基團。

Energy Diagram
In the nucleophilic acyl substitution, the elimination of the alkoxide

is highly exothermic, converting the tetrahedral intermediate into a
stable molecule.
在親核酰基取代中，醇鹽的消除是⾼度放熱的，將四⾯體中間體
轉化為穩定的分⼦。
Problem 7, 8, 9, 10
Problem 7

Problem 8

Problem 9

Problem 10

21-6 Transesterification
• One alkoxy group can be replaced by another with acid or

base catalyst.
⼀個烷氧基可以被另⼀個⽤酸或鹼催化劑替代。
• Use large excess of desired alcohol.
使⽤⼤量的所需酒精。
Acid-Catalyzed Transesterification Mechanism
Problem 14
Problem 14

Base-Catalyzed Transesterification Mechanism

21-7 Hydrolysis of Carboxylic Acid Derivatives
• Hydrolysis occurs quickly, even in moist air with no

acid or base catalyst.
即使在沒有酸或鹼催化劑的潮濕空氣中，⽔解也很
快發⽣。
• Reagents must be protected from moisture.
試劑必須防潮。

Hydrolysis of Esters: Saponification
• The base-catalyzed hydrolysis of ester is known as

saponification.
酯的鹼催化⽔解被稱為皂化。
• Saponification means “soap-making.”
皂化意味著“製皂”。

Saponification
• Soaps are made by heating NaOH with a fat (triester of glycerol)

to produce the sodium salt of a fatty acid—a soap.
肥皂是通過加熱氫氧化鈉與脂肪（⽢油三酯）來⽣產脂肪酸的
鈉鹽 - 肥皂。
Problem 16, 18
Problem 16

Problem 16

Hydrolysis of Amides
Amides are hydrolyzed to the carboxylic acid under acidic or basic

conditions.
酰胺在酸性或鹼性條件下⽔解成羧酸。

Basic Hydrolysis of Amides
• Similar to the hydrolysis of an ester.

類似於酯的⽔解。
• The hydroxide ion attacks the carbonyl, forming a tetrahedral
intermediate.
氫氧根離⼦攻擊羰基，形成四⾯體中間體。
• The amino group is eliminated and a proton is transferred to the
nitrogen to give the carboxylate salt.
氨基被除去，質⼦被轉移到氮上，得到羧酸鹽。

Acid Hydrolysis of Amides
Problem 20
Problem 20

Hydrolysis of Nitriles
• Heating with aqueous acid or base will hydrolyze a nitrile

to a carboxylic acid.
⽤含⽔酸或鹼加熱會將腈⽔解成羧酸。

Base-Catalyzed Hydrolysis of a Nitrile
Problem 22

21-8 Reduction of Acid Derivatives
Reduction of Esters to Alcohols
• Lithium aluminum hydride (LiAlH4) reduces esters,

acids, and acyl chlorides to primary alcohols.
氫化鋁鋰（LiAlH4）將酯，酸和酰氯還原成伯醇。

Mechanism of Reduction of Esters

Reduction of Acyl Halides to Aldehydes
• Lithium tri-tert-butoxyaluminum hydride is a milder

reducing agent.
三叔丁氧基氫化鋁鋰是⼀種溫和的還原劑。
• Reacts faster with acyl chlorides than with aldehydes.
與酰氯反應比⽤醛反應更快。

Reduction to Aldehydes with DIBAL
• Di-isobutylaluminum hydride, commonly called DIBAL

or DIBAL-H, is another mild reducing agent that can
reduce esters to aldehydes.
通常稱為DIBAL或DIBAL-H的氫化⼆異丁基鋁是另
⼀種能將酯還原成醛的溫和還原劑

Reduction of an Amide to an Amine
• Amides will be reduced to the corresponding amine by

LiAlH4.
酰胺將被LiAlH4還原為相應的胺。

Reduction of an Amide

Reduction of Nitriles to Primary Amines
• Nitriles are reduced to primary amines by catalytic hydrogenation or

by lithium aluminum hydride reduction.
腈通過催化氫化或氫化鋁鋰還原為伯胺。
Problem 25

21-9 Reactions of Acid Derivatives with Organometallic Reagents
• Grignard and organolithium reagents add twice to acid chlorides and

esters to give alcohols after protonation.
Grignard試劑和有機鋰試劑兩次加入酰氯和酯，質⼦化後得到
醇。

Mechanism of Grignard Addition
• Esters react with two moles of Grignards or organolithium reagents to

produce an alcohol.
酯與兩摩爾Grignard或有機鋰試劑反應⽣成醇。
• The ketone intermediate will react with a second mole of
organometallic to produce the alcohol.
酮中間體將與第⼆摩爾有機⾦屬化合物反應⽣成醇。

Dialkylcuprate Reagents
• Acid chlorides react just once with dialkylcuprates

(Gilman reagents) to give ketones.
酰氯與⼆烷基飽和物（Gilman試劑）反應⼀次得到
酮。

Reaction of Nitriles with Grignards
• A Grignard reagent or organolithium reagent attacks the

cyano group to form an imine, which is hydrolyzed to a
ketone.
Grignard試劑或有機鋰試劑攻擊氰基形成亞胺，將其⽔
解成酮。
Problem 28
Problem 28

21-10 Summary of the Chemistry of Acid Chlorides
Synthesis of Acid Chlorides
• Thionyl chloride (SOCl2) and oxalyl chloride (COCl2) are

the most convenient reagents because they produce only
gaseous side products.
亞硫酰氯（SOCl2）和草酰氯（COCl2）是最⽅便的試
劑因為它們只產⽣氣態副產物

Acid Chloride Reactions (1)

Acid Chloride Reactions (2)

Friedel–Crafts Acylation
Problem 30
Problem 30

21-11 Summary of the Chemistry of Anhydrides
General Anhydride Synthesis
• The most generalized method for making anhydrides is the reaction of an

acid chloride with a carboxylic acid or a carboxylate salt.
製造酸酐的最普遍的⽅法是酰氯與羧酸或羧酸鹽的反應。
• Pyridine is sometimes used to deprotonate the acid and form the carboxylate.
有時⽤吡啶去質⼦酸並形成羧酸鹽。
Reaction of Anhydrides

Friedel–Crafts Acylation Using Anhydrides
• Using a cyclic anhydride allows for only one of the acid

groups to react, leaving the second acid group free to
undergo further reactions.
使⽤環狀酸酐僅允許⼀個酸基團反應，使第⼆個酸基團
⾃由進⾏進⼀步的反應。
Acetic Formic Anhydride
• Acetic formic anhydride, made from sodium formate and

acetyl chloride, reacts primarily at the formyl group.
⼄酸甲酸酐由甲酸鈉和⼄酰氯製成，主要在甲酰基上反
應。
• The formyl group is more electrophilic because of the lack
of alkyl groups.
由於缺少烷基，甲酰基更具親電⼦性。
Problem 32
Problem 32

21-12 Summary of the Chemistry of Esters
Synthesis of Esters

Reactions of Esters

Formation of Lactones
• Formation is favored for five- and six-membered rings.
形成有利於五元和六元環
For larger rings, remove water to shift equilibrium toward

products.
對於較⼤的戒指，取出⽔以平衡產品。
Problem 34
Problem 34

21-13 Summary of the Chemistry of Amides

Reactions of Amides

Dehydration of Amides to Nitriles
• Strong dehydrating agents can eliminate the elements of water

from a primary amide to give a nitrile.
強脫⽔劑可以從伯酰胺中除去⽔中的元素，得到腈。
• Phosphorus oxychloride (POCl3) or phosphorus pentoxide
(P2O5) can be used as dehydrating agents.
磷酰氯（POCl 3）或五氧化⼆磷（ P2O5 ）可⽤作脫
⽔劑。

Formation of Lactams
• Five-membered lactams ( -lactams) and six-membered lactams

( -lactams) often form on heating or adding a dehydrating agent
to the appropriate -amino acid or -amino acid.
五元內酰胺（ -內酰胺）和六元內酰胺（ -內酰胺）
通常在加熱或向適當的 -氨基酸或 -氨基酸中加入脫
⽔劑⽽形成。

-Lactams
• Unusually reactive, four-membered ring amides are capable of

acylating a variety of nucleophiles.
異常反應性的四元環酰胺能夠酰化各種親核試劑
• They are found in three important classes of antibiotics: penicillins,
cephalosporins, and carbapenems.
他們被發現在三個重要類別的抗⽣素：青黴素，頭孢菌素和碳
青黴烯類。
Problem 36, 37
Problem 36

Problem 37

21-14 Summary of the Chemistry of Nitriles
Synthesis of Nitriles

Reactions of Nitriles
Problem 38
Problem 38

21-15 Thioester
• A thioester is formed from a carboxylic acid and a thiol.

硫酯由羧酸和硫醇形成。
• Thioesters are also called thiol esters to emphasize that they
are derivatives of thiols.
硫酯也被稱為硫醇酯，以強調它們是硫醇的衍
⽣物。
Resonance Overlap in Esters and Thioesters
• The resonance overlap in a thioester is not as effective as

that in an ester.
硫酯中的共振重疊不如酯中那樣有效。
• Thioesters are more reactive toward nucleophilic acyl
substitution than are normal esters.
硫酯對親核酰基取代比正常酯更具反應性。
21-16 Esters and Amides of Carbonic Acid
Synthesis of Carbamate Esters from Isocyanates
Problem 40, 41
Problem 41

Problem 41

Polycarbonate Synthesis
• Polycarbonates are polymers bonded to the carbonate ester linkage.

聚碳酸酯是鍵合到碳酸酯鍵上的聚合物。
• The diol used to make Lexan® is a phenol called
bisphenol A, a common intermediate in polyester and polyurethane
synthesis.
⽤於製造Lexan®的⼆醇是⼀種名為雙酚A的酚，它是聚酯和聚
氨酯合成中常⾒的中間體
Synthesis of Polyurethanes
• Reaction of toluene diisocyanate with ethylene glycol produces one

of the most common forms of polyurethanes.
甲苯⼆異氰酸酯與⼄⼆醇的反應產⽣聚氨酯的最常⾒形式之⼀

Polyesters
• Dacron® thread • Glyptal resin
• Mylar® tape • PET bottles

Name: 42, 43

Problem 47, 48

Problem 48

Problem 49

Problem 50

Problem 50

Problem 51
Problem 53

Problem 54

Problem 55

Problem 56

Problem 57

Problem 58, 59

Chapter 21 Acid Der

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Chapter 21 Acid Der

Uploaded by

Copyright:

Available Formats

Chapter 21

© 2017 Pearson Education, Ltd.

© 2014 Pearson Education, Inc.

• Carboxylic acid derivatives are defined as compounds

© 2014 Pearson Education, Inc.

© 2017 Pearson Education, Ltd.

• Esters are carboxylic acid derivatives in which the

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

• Cyclic esters are called lactones. 環酯被稱為內酯

• An amide is a composite of a carboxylic acid and

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

• Cyclic amides are called lactams.

• Nitriles contain the cyano group.

© 2017 Pearson Education, Ltd.

• The atoms at the ends of the triple bonds are sp

© 2017 Pearson Education, Ltd.

• Acid halides are also called acyl halides.

• The word anhydride means “without water.”

• Acid anhydrides are activated derivatives of carboxylic acids.

© 2017 Pearson Education, Ltd.

• Acid anhydrides are named by replacing the word acid

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

• The physical properties of acid derivatives largely depend on their

• The resonance picture of an amide shows its strongly polar

© 2017 Pearson Education, Ltd.

• Acid derivatives (esters, acid chlorides, anhydrides, nitriles,

© 2017 Pearson Education, Ltd.

Step 2: Elimination of the leaving group regenerates the carbonyl

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

• The alcohol attacks the acyl chloride, forming the

• Ammonia yields a 1° amide.

© 2017 Pearson Education, Ltd.

• Alcohol attacks one of the carbonyl groups of the anhydride, forming

© 2017 Pearson Education, Ltd.

• Ammonia yields a 1° amide; a 1° amine yields a 2° amide; and a 2°

© 2017 Pearson Education, Ltd.

• The nucleophile must be NH3 or 1° amine.

© 2017 Pearson Education, Ltd.

• A strong base, such as an alkoxide (–OR), is not usually a

© 2017 Pearson Education, Ltd.

In the nucleophilic acyl substitution, the elimination of the alkoxide

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

• One alkoxy group can be replaced by another with acid or

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

• Hydrolysis occurs quickly, even in moist air with no

© 2017 Pearson Education, Ltd.

• The base-catalyzed hydrolysis of ester is known as

© 2017 Pearson Education, Ltd.

• Soaps are made by heating NaOH with a fat (triester of glycerol)

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

Amides are hydrolyzed to the carboxylic acid under acidic or basic

© 2017 Pearson Education, Ltd.

• Similar to the hydrolysis of an ester.

© 2017 Pearson Education, Ltd.