Download Chapter 21: Carboxylic Acids and Their Derivatives

Chem A225 Notes
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Chapter 21: Carboxylic Acids and Their Derivatives
I. Nomenclature
A. IUPAC Nomenclature of Carboxylic Acids
1) Find the longest carbon chain which contains the carboxylic acid (COOH) carbon.
2) Count the number of carbon in this chain and determine the parent stem name.
3) Add the suffix “-anoic acid”.
4) Number the carbon chain starting from the carboxylic acid (COOH) carbon.
5) Add substituent names, with appropriate numbers, in from of the acid name.
B. Common Names of Carboxylic Acids (MEMORIZE)
C. IUPAC Names of Dicarboxylic Acids
1) Find the longest carbon chain which contains both carboxylic acid (COOH) carbons.
2) Count the number of carbon in this chain and name it as the corresponding alkane.
3) Add the suffix “-dioic acid”.
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Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
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D. Common Names of Dicarboxylic Acids (MEMORIZE)
E. Nomenclature of Carboxylate Salts
•
Carboxylic acids react with bases to form carboxylate salts.
•
These salts have two ions: the deprotonated carboxylic acid forms a negative ion that
is paired up with a positive counter ion (such as sodium, potassium, or ammonium).
•
To name the deprotonated (carboxylate) form of a carboxylic acid:
1) Name the related carboxylic acid.
2) Replace the “-ic acid” suffix with “-ate”.
•
Add the name of the positive counter ion in front to complete the name of the
carboxylate salt:
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Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
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II. Synthesis of Carboxylic Acids
A. Oxidation of 1o Alcohols and Aldehydes (review 13-10)
•
Observed Reactions
B. Oxidative Cleavage of Alkenes (review Chap. 9 Notes)
•
Observed Reaction
C. Oxidation of Alkylbenzenes (review 18.6)
•
Observed Reaction
D. Reduction of CO2 with Grignard Reagents
•
Observed Reaction
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Chem A225 Notes
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Ch 21: Carboxylic Acids and Their Derivatives
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Mechanism
E. Hydrolysis of Nitriles (Heteroatom Exchange)
•
Observed Reaction
•
Mechanism: Add H2O --> Add H2O --> Remove NH2
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Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
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o
•
Nitriles can be prepared by SN2 reaction of cyanide ion on 1 alkyl halides:
•
Cyanohydrins are also nitriles:
III.Introduction Carboxylic Acid Derivatives
•
These functional groups are called derivatives of carboxylic acids because their
structures are derived by replacing the OH of the acid with another heteroatom group.
Derivatives
O
R
C
Cl
acid chloride
O
O
R
C
R
OH
carboxylic acid
replace OH
C
O
O
C
R
acid anhydride
O
R
C
OR
ester
O
R
C
NR2
amide
•
Nitriles are technically not derivatives of carboxylic acids, but they can be converted to
carboxylic acids by hydrolysis, so they have been included in this chapter:
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Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
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IV.Nomenclature of Carboxylic Acid Derivatives
A. Nomenclature of Acid Chlorides
1) Name the related carboxylic acid.
2) Replace the “-ic acid” suffix with “-yl chloride”.
B. Nomenclature of Acid Anhydrides
•
Acid anhydrides are treated as two carboxylic acids that have been joined by
connecting the OH of one acid to the C=O carbon of the other and removing a
molecule of water.
•
To name acid anhydrides:
1) Name each carboxylic acid half, then drop the “acid” part of the names.
2) Put the names in alphabetical order, separated by a space.
3) Add the word “anhydride”, separated by a space, following the names.
4) If the two halves are the same, only write the name once.
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Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
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C. Nomenclature of Esters
•
Esters are treated as carboxylates that are attached to alkyl groups.
•
To name esters:
1) Name the carboxylate part of the compound.
2) Add the name of the carbon group of the –OR as an alkyl (-yl ending) in front of the
carboxylate name, separated by a space.
D. Nomenclature of Amides
1) Name the related carboxylic acid.
2) Replace the “-oic acid” (for IUPAC names) or the “-ic acid” suffix (for common
names) with “-amide”.
3) If the are alkyl groups on the nitrogen, put the name of each alkyl group in front with
an “N-” prefix (for example: N-ethyl).
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Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
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E. Nomenclature of Nitriles
1) Count the number of carbons in the longest carbon chain that contains the nitrile (C≡N)
carbon. Include the nitrile carbon in the count.
2) Name the alkane that has the same number of carbons.
3) Add the suffix “-nitrile” to the alkane name, with no space in between.
V. Nucleophilic Acyl Substitution
A. Nucleophilic Acyl Substitution (SNAc) Mechanism
•
When there is a heteroatom leaving group attached to a C=O carbon, the leaving group
can be replaced in a two-step nucleophilic substitution:
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Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
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B. Reactivity of Carboxylic Acid Derivatives in SNAc Reactions
•
All of the derivatives of carboxylic acids have leaving groups in place of the OH group.
•
The derivatives with the better leaving groups are more reactive. What makes a better
leaving group? Groups with a lower basicity are better leaving groups. Use the pKa
table to compare possible leaving groups.
Derivative Name
Structure
Leaving Group
O
Acid Chloride
R
C
O
Acid Anhydride
R
C
Cl
O
O
C
R
O
Ester
R
C
OR
O
Amide
•
R
C
NR2
Derivatives with better leaving groups can be used to prepare derivatives with poorer
leaving groups. In other words, a derivative can be prepared from any other
derivative that is above it on the table.
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Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
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VI.Synthesis and Reactions of Acid Chlorides and Acid Anhydrides
•
Acid chlorides and acid anhydrides have similar chemistry (acid chlorides are
somewhat more reactive). Their reactions follow similar mechanisms (the only
difference is the identity of the leaving groups). Therefore, they are grouped together.
A. Synthesis of Acid Chlorides from Carboxylic Acids and SOCl2
•
Observed Reaction
•
We will not cover the mechanism.
B. Synthesis of Acid Anhydrides from Acid Chlorides
•
Observed Reaction
•
It is difficult to make mixed anhydrides, where each half comes from a different acid.
Usually, a mixture of anhydrides with all possible combinations of the acids is formed.
•
This reaction follows an SNAc mechanism with Cl– as the leaving group:
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Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
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C. Hydrolysis of Acid Chlorides and Acid Anhydrides
•
Observed Reaction
(acid chloride: LG = Cl ; acid anhydride: LG = RC(=O)O)
•
Hydrolysis is a general term for heteroatom exchange reactions where a heteroatom
group is cut off of a compound and replaced with water (or an OH derived from water).
•
Mechanism of acid chloride and acid anhydride hydrolysis (SNAc with H2O nuc.)
•
Acid Chlorides are not stable in water. They react instantly with water. Even
moisture in the air will cause reaction when they are exposed to the atmosphere.
•
Acid anhydrides are less reactive and can be handled in the atmosphere for brief
periods without a large amount of hydrolysis.
D. Reaction of Acid Chlorides with Dialkylcuprates (Cuprate Coupling) (Review)
•
Observed Reaction
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Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
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VII. Synthesis and Reactions of Esters
A. Synthesis of Esters from Acid Chlorides and Acid Anhydrides
•
Observed Reactions
(acid chloride: LG = Cl ; acid anhydride: LG = RC(=O)O)
•
Pyridine is added to the reactions to absorb H+ (acid) from the weak nucleophile after it
attacks the acyl carbon.
•
These reactions follow the general SNAc mechanism. The only difference is that the
neutral alcohol nucleophile must be deprotonated at the end to become stable.
B. Synthesis of Esters from Alcohols and Carboxylic Acids (Fischer Ester Synthesis)
•
Observed Reaction
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Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
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Mechanism: Add ROH --> Remove Oxygen (H2O)
•
The reaction is an equilibrium reaction. Water is formed as a by-product of the
reaction. We can use Le Chatelier’s Principle to obtain the desired product.
•
To obtain a high yield of the ester:
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1) use excess alcohol (ROH) or excess carboxylic acid to push the left side of the
reaction, and
2) remove water (H2O) to pull on the right side of the equilibrium.
Lecture Notes © 2017 Dr. Thomas Mucciaro. All rights reserved.
Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
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C. Acid-Catalyzed Hydrolysis of Esters
•
Observed Reaction
•
Mechanism: The mechanism is the exact reverse of the Fischer Ester Synthesis
mechanism. Practice by writing the mechanism of acid-catalyzed hydrolysis in the
space below:
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Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
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D. Base-Promoted Hydrolysis (Saponification)
•
Observed Reaction
•
Mechanism:
•
The reaction is promoted by base because the base increases the rate of reaction but is
consumed (unlike a catalyst which is not consumed).
E. Transesterification of Esters
•
Observed Reactions
•
Base (Strong Nucleophile) Mechanism:
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Chem A225 Notes
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Ch 21: Carboxylic Acids and Their Derivatives
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Acid-Catalyzed (Weak Nucleophile) Mechanism: Add ROH --> Remove OR
F. Hydride Reduction of Esters to Alcohols
•
Observed Reaction
•
Mechanism of Hydride Reduction of Esters:
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Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
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G. Addition of Grignard Reagents to Esters (Reduction with Grignard Reagents)
•
Observed Reaction
•
Mechanism (note the similarity to the hydride reduction mechanism):
H. Cyclic Esters (Lactones)
•
If a carboxylic acid and a hydroxyl group (alcohol) are in the same molecule, then a
cyclic ester can be formed by intramolecular reaction:
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Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
Page 118
•
Cyclic esters are called lactones. They are classified by the carbon to which the
hydroxyl group is attached (which affects the ring size):
•
Most natural lactones are gamma (γ) or delta (δ) lactones, because 5- and 6-membered
rings are the most stable. For example, vitamin C is a gamma (γ) lactone:
Lactones react like normal esters in hydrolysis, hydride reduction, and Grignard
addition, except that the ring opens during the reactions:
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Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
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VIII. Synthesis and Reactions of Amides
A. Synthesis of Amides from Acid Chlorides, Acid Anhydrides, and Esters
•
Observed Reactions
•
LG = Cl (acid chloride), R'C(=O)O (acid anhydride), or R'O (ester)
•
Pyridine is added to the reactions to absorb H+ (acid) from the weak nucleophile after it
attacks the acyl carbon. Excess amine can be used instead (for example, excess NH3)
•
Mechanism (follows the SnAc mechanism):
•
Most amides cannot be made by direct reaction of a carboxylic acid and an amine
(in contrast to esters, which can be made directly from the carboxylic acids).
Amines are more basic than alcohols, and they react with the carboxylic acid by acidbase reaction. The resulting ammonium ions do not have lone pairs, and therefore do
not act as nucleophiles. This prevents the amine from reacting with the carbonyl
(C=O) carbon and forming the amide.
Lecture Notes © 2017 Dr. Thomas Mucciaro. All rights reserved.
Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
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B. Acid-Catalyzed Hydrolysis of Amides
•
Observed Reaction
•
Mechanism: Add H2O --> Remove NR2
C. Base-Promoted Hydrolysis of Amides
•
Observed Reaction
•
Mechanism [NOTE: VERY DIFFERENT FROM BOOK]:
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Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
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D. Hydride Reduction of Amides
•
Observed Reaction:
•
Use H2O instead of H3O+ so that amine product is not protonated.
E. Cyclic Amides (Lactams)
•
Cyclic amides are called lactams, and they are classified in the same way as lactones:
•
Penicillin is a beta (β) lactam; its mechanism of action involves acylating a
nucleophilic atom on an enzyme:
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Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
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IX.Synthesis and Reactions of Nitriles
A. Synthesis of Nitriles by SN2 Reaction
•
Observed Reaction:
•
The R group on the substrate (R–X) must be CH3, 1o, or unhindered 2o (no SN2
reaction on 3o substrates).
•
Usually polar aprotic solvents (like DMSO) are used to favor SN2 reaction.
•
Mechanism (Review, SN2 reaction)
B. Acid-Catalyzed Hydrolysis of Nitriles
•
Observed Reaction:
•
The mechanism was covered earlier (Notes 21.III.E, p. 99)
•
The phases are: Add H2O --> Add H2O --> Remove NH2
C. Hydride Reduction of Nitriles
•
Observed Reaction:
•
We will not cover the mechanism of this reaction.
Lecture Notes © 2017 Dr. Thomas Mucciaro. All rights reserved.
Chem A225 Notes
Ch 21: Carboxylic Acids and Their Derivatives
Page 123
X. Carbonic Acid and Its Derivatives
•
Carbonic acid is unstable in acid. It decomposes to form CO2 and H2O:
•
Many higher organisms use the CO2/carbonic acid equilibrium to regulate pH:
•
CO2 is readily available in biological organisms. Mammals use a carbonic acid
derivative to dispose of excess NH3 (which often comes from metabolizing proteins/
amino acids):
•
Diesters of carbonic acid are called carbonates:
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