Resumo das reações ácido carboxílico e derivados

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1034 CHAPTER 21 Carboxylic Acids and Their Derivatives
REVIEW OF REACTIONS 
R Br
R
OH
O
2) H3O
+, heat 
1) NaCN
R Br
R OH
O
2) CO2
3) H3O
+
1) Mg
Preparation of Carboxylic Acids Reactions of Carboxylic Acids
R OH
O
R OH
H H
1) xs LAH
2) H3O
+
BH3 THF
Preparation and Reactions
of Acid Chlorides
Preparation and Reactions
of Acid Anhydrides
OR
O
NH2
O
Cl
O
OH
O
O
H
OH
R
R
O
R
N
O
R
H
OH
H
H
N
O
R
R
xs
NH3
xs
NH3
ROH
Pyridine
xs 
RNH2
xs 
RNH2
R2NH
1) xs LAH
2) H2O 
1) xs RMgBr
2) H2O
R2CuLi
SOCl2
H2O
Pyridine
1) LiAl(OR)3H
2) H2O
ROH
OR
O
NH2
O
O
H
OH
R
R
O
R
N
O
R
H
OH
H
H
N
O
R
R
OH
O 1) NaOH
O
O O
2) CH3COCl
Heat
R2NH
1) xs LAH
2) H2O 
1) xs RMgBr
2) H2O
R2CuLi
H2O
1) LiAl(OR)3H
2) H2O
xs 
xs 
Preparation of Esters Reactions of Esters
R OH
O
R
O
O
CH3
R OH
O
R Cl
O
R OR
O
1) NaOH
2) CH3I 
MeOH
[H+]
ROH
Pyridine
R OMe
O
H2O+
R OR
O
R OH
O ROH
H3O
+
NH3
R NH2
O
1) xs
R
OH
2) H2O 
2) H2O 
2) H2O 
1) DIBAH
R
O
H
1) xs RMgBr 
R
OH
R
R
+1) NaOH, heat
2) H3O
+
LAH
 Review of Concepts and Vocabulary 1035
R OH
O
R
O
NH2
R NH2
H3O
+
1) NaOH, heat
2) H3O
+
1) xs LAH
2) H2O 
R Cl
O
R NH2
O
NH3
(two equivalents)
Preparation of Amides Reactions of Amides
R NH2
O
R Br
SOCl2
NaCN
R C N
SO2
2 HCl
R C
N
NaBr R C N
R C N
R C N
R OH
O
H3O
+
1) NaOH, heat
2) H3O
+
R NH2
H H
1) xs LAH
2) H3O
+ 
R R
O
1) RMgBr 
2) H3O
+
Preparation of Nitriles Reactions of Nitriles
+
+
+
REVIEW OF CONCEPTS AND VOCABULARY
SECTION 21.1
• Carboxylic acids are abundant in nature, and they are widely 
used in the pharmaceutical and other industries.
• For industrial purposes, acetic acid is converted into vinyl 
acetate, which is a carboxylic acid derivative.
SECTION 21.2
• Compounds containing a carboxylic acid group are named 
with the suffix “oic acid.”
• Compounds containing two carboxylic acid groups are 
named with the suffix “dioic acid.”
• Many simple carboxylic acids and diacids have common 
names accepted by IUPAC.
SECTION 21.3
• Carboxylic acids can form two hydrogen-bonding interactions.
• Treatment of a carboxylic acid with a strong base, such as 
sodium hydroxide, yields a carboxylate salt.
• Carboxylate ions are named by replacing the suffix “ic acid” 
with “ate.”
• The pKa of most carboxylic acids is between 4 and 5.
• The acidity of carboxylic acids is due to the stability of the 
conjugate base, which is resonance stabilized.
• Using the Henderson-Hasselbalch equation, it can be shown 
that carboxylic acids exist primarily as carboxylate salts at 
physiological pH.
• Electron-withdrawing substituents can increase the acidity of 
a carboxylic acid; the strength of this effect depends on the 
distance between the electron-withdrawing substituent and 
the carboxylic acid group.
SECTION 21.4
• When treated with aqueous acid, a nitrile will undergo 
hydrolysis, yielding a carboxylic acid.
• Carboxylic acids can also be prepared by treating a Grignard 
reagent with carbon dioxide.
SECTION 21.5
• Carboxylic acids are reduced to alcohols upon treatment with 
lithium aluminum hydride or borane.
1036 CHAPTER 21 Carboxylic Acids and Their Derivatives
SECTION 21.6
• Carboxylic acid derivatives exhibit the same oxidation state 
as carboxylic acids.
• Acid halides are named by replacing the suffix “ic acid” with 
“yl halide.”
• Acid anhydrides are named by replacing the suffix “ic acid” 
with “anhydride.”
• Esters are named by first indicating the alkyl group attached 
to the oxygen atom, followed by the carboxylic acid, for 
which the suffix “ic acid” is replaced with “ate.”
• Amides are named by replacing the suffix “ic acid” or “oic 
acid” with “amide.”
• Nitriles are named by replacing the suffix “ic acid” with “nitrile.”
SECTION 21.7
• Carboxylic acid derivatives differ in reactivity, with acid halides 
being the most reactive and amides the least reactive.
• The C!N bond of an amide has double-bond character and 
exhibits a relatively high barrier to rotation.
• When a nucleophile attacks a carboxylic acid derivative, 
a nucleophilic acyl substitution can occur in which the 
nucleophile replaces the leaving group. The mechanism 
of this reaction involves two core steps and often utilizes 
several proton transfer steps as well (especially in acidic 
conditions).
• When drawing a mechanism, avoid formation of a strong 
base in acidic conditions and avoid formation of a strong acid 
in basic conditions.
• When a nucleophile attacks a carbonyl group to form a tet-
rahedral intermediate, always re-form the carbonyl group if 
possible but avoid expelling H- or C-.
SECTION 21.8
• Acid chlorides can be formed by treating carboxylic acids 
with thionyl chloride.
• When treated with water, acid chlorides are hydrolyzed to 
give carboxylic acids.
• When treated with an alcohol, acid chlorides are converted 
into esters.
• When treated with ammonia, acid chlorides are converted 
into amides. Two equivalents of ammonia are required: one 
to serve as a nucleophile and the other to serve as a base.
• When treated with excess LAH, acid chlorides are reduced 
to give alcohols because two equivalents of hydride 
attack. Selective hydride-reducing agents, such as lithium 
tri(t-butoxy) aluminum hydride, can be used to prepare the 
aldehyde.
• When treated with a Grignard reagent, acid chlorides are con-
verted into alcohols with the introduction of two alkyl groups. 
Two equivalents of Grignard reagent attack. Preparing a 
ketone requires the use of a more selective organometal-
lic reagent, such as a lithium dialkyl cuprate, also called a 
Gilman reagent.
SECTION 21.9
• Acetic acid can be converted into acetic anhydride with 
excessive heating.
• Acid anhydrides can be prepared by treating an acid chloride 
with a carboxylate ion.
• The reactions of anhydrides are the same as the reactions of 
acid chlorides except for the identity of the leaving group.
SECTION 21.10
• When treated with a strong base followed by an alkyl halide, 
carboxylic acids are converted into esters.
• In a process called the Fischer esterification, carboxylic acids 
are converted into esters when treated with an alcohol in the 
presence of an acid catalyst. This process is reversible.
• Esters can also be prepared by treating an acid chloride with 
an alcohol in the presence of pyridine.
SECTION 21.11
• Esters can be hydrolyzed to yield carboxylic acids upon treat-
ment with either aqueous base or aqueous acid. Hydrolysis 
under basic conditions is also called saponification.
• When treated with lithium aluminum hydride, esters are 
reduced to yield alcohols. If the desired product is an alde-
hyde, then DIBAH is used as a reducing agent instead of LAH.
• When treated with a Grignard reagent, esters are reduced to 
yield alcohols, with the introduction of two alkyl groups.
SECTION 21.12
• Amides can be efficiently prepared from acid chlorides.
• Amides are hydrolyzed to yield carboxylic acids by treatment 
with either aqueous base or aqueous acid.
• When treated with excess LAH, amides are converted into 
amines.
SECTION 21.13
• Nitriles can be prepared by treating an alkyl halide with a 
cyanide ion or via the dehydration of an amide.
• Nitriles can be hydrolyzed to yield carboxylic acids by treat-
ment with either aqueous base or aqueous acid.
• A ketone is obtained when a nitrile is treated with a Grignard 
reagent, followed by aqueous acid.
• Nitriles are converted to amines when treated with LAH.
SECTION 21.14
• Carboxylic acids, their derivatives, aldehydes, alcohols, and 
amines can be readily interconverted using reactions covered 
in this chapter.
• When forming a C!C bond, always consider where you 
want the functional group to be located, as that will dictate 
which C!C bond-forming reaction to choose.
SECTION 21.15
• In IR spectroscopy, the precise location of a carbonyl stretch-
ing signal, which appearsbetween 1650 and 1850 cm-1, 
can be used to determine the type of carbonyl group in an 
unknown compound.
• Conjugated carbonyl groups produce signals at lower 
 frequencies.
• In a 13C NMR spectrum, the carbonyl group of a carboxylic 
acid derivative will generally appear in the region between 
160 and 185 ppm, and the carbon atom of a nitrile produces 
a signal between 115 and 130 ppm.
• In a 1H NMR spectrum, the proton of a carboxylic acid 
 produces a signal at approximately 12 ppm.
 SkillBuilder Review 1037
21.2 INTERCONVERTING FUNCTIONAL GROUPS
H2O
O
H
SOCl2
Pyridine
1) LAH
2) H2O
OH
H2O
1) LiAl(OR)3H
2) H2O 
1) LAH
2) H2O 
ROH, pyridine
Excess NH3
1) DIBAH
2) H2O
[H+]
H2O
[H+]
H2O
heat
heat
[H+]
H2O
OH
O
[H+]
ROH
1) xs LAH
2) H2O 
NH2
1) xs LAH
2) H2O
Cl
O
O
O O
OR
O
NH2
O
C N
Cl
O
Pyridine
1) xs LAH
2) H2O H2SO4, H2O
Na2Cr2O7
Pyridine
ROH NH3 SOCl2OH
O
Try Problems 21.32–21.34, 21.45a,b, 21.46a, 21.52, 21.53a,c,e, 21.57
SKILLBUILDER REVIEW
21.1 DRAWING THE MECHANISM OF A NUCLEOPHILIC ACYL SUBSTITUTION REACTION
In acidic conditions,
the carbonyl group
is first protonated
Every nucleophilic acyl substitution reaction exhibits these
two steps, which must be drawn separately.
In acidic conditions,
the leaving group is
protonated before
it leaves
Required in order
to obtain a
neutral product
Nucleophilic attackProton transfer Loss of a leaving groupProton transfer Proton transfer
Try Problems 21.14–21.17, 21.61, 21.72
1038 CHAPTER 21 Carboxylic Acids and Their Derivatives
21.3 CHOOSING THE MOST EFFICIENT C!C BOND-FORMING REACTION
Z
O OH
R
R
Cl
O O
R
C N
R
O
1) Excess RMgBr
2) H2O 
R2CuLi
1) RMgBr 
2) H3O
+ 
Br
OH
O
2) CO2
3) H3O
+
1) Mg
C
N
NaCN
H3O
+
Heat
C C Bond-Forming Reactions
for Which the Functional Group
Remains in the Same Location
C C Bond-Forming Reactions
Involving a Change in the
Location of the Functional Group
— —
Try Problems 21.35–21.37, 21.45b, 21.53b,d,f, 21.54, 21.55, 21.58, 21.74
PRACTICE PROBLEMS
21.39 Rank each set of compounds in order of increasing acidity:
COOH
O2N
COOH
H3C
COOH
O
COOH
Br
COOH
O
(a)
OH
OBr
OH
O
Br OH
O
Br(b)
21.40 Malonic acid has two acidic protons:
OH
O
HO
O
Malonic acid
The pKa of the first proton (pK1) is measured to be 2.8, while the pKa 
of the second proton (pK2) is measured to be 5.7.
(a) Explain why the first proton is more acidic than acetic acid 
(pKa = 4.76).
(b) Explain why the second proton is less acidic than acetic acid.
(c) Draw the form of malonic acid that is expected to predominate at 
physiological pH.
(d) For succinic acid (HO2CCH2CH2CO2H), pK1 = 4.2 (which is higher 
than pK1 for malonic acid) and pK2 = 5.6 (which is lower than pK2 
for malonic acid). In other words, the difference between pK1 and 
pK2 is not as large for succinic acid as it is for malonic acid. Explain 
this observation.
21.41 Identify a systematic (IUPAC) name for each of the following 
compounds:
OH
O
(a) 
NH2
O
(b) 
Cl
O
(c)
Note: Most of the Problems are available within , 
an online teaching and learning solution.
O
O
(d) (e) CH3(CH2)4CO2H 
(f ) CH3(CH2)3COCl (g) CH3(CH2)4CONH2
21.42 Identify the common name for each of the following compounds:
O
O O
(a) OH
O
(b) H OH
O
(c) HO OH
OO
(d)
21.43 Draw the structures of eight different carboxylic acids with 
molecular formula C6H12O2. Then, provide a systematic name for each 
compound and identify which three isomers exhibit chirality centers.
21.44 Draw and name all constitutionally isomeric acid chlorides with 
molecular formula C4H7ClO. Then provide a systematic name for each 
isomer.
21.45 Identify the reagents you would use to convert pentanoic acid 
into each of the following compounds:
(a) 1-Pentanol (b) 1-Pentene (c) Hexanoic acid
21.46 Identify the reagents you would use to convert each of the fol-
lowing compounds into pentanoic acid:
(a) 1-Pentene (b) 1-Bromobutane