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Chapter 21: Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions
26 problems · 51 figures21-1 §21.1 source ↗
Give IUPAC names for the following substances:
(a)
(b)
(c)
(d)
(e)
(f)
(g)
(h)
(i)
Answer (9 parts)
(a)
4-Methylpentanoyl chloride
(b)
Cyclohexylacetamide
(c)
Isopropyl 2-methylpropanoate
(d)
Benzoic anhydride
(e)
Isopropyl cyclopentanecarboxylate
(f)
Cyclopentyl 2-methylpropanoate
(g)
N-Methyl-4-pentenamide
(h)
(R)-2-Hydroxypropanoyl phosphate
(i)
Ethyl 2,3-dimethyl-2-butenethioate
21-2 §21.1 source ↗
Draw structures corresponding to the following names:
(a)
Phenyl benzoate
(b)
N-Ethyl-N-methylbutanamide
(c)
2,4-Dimethylpentanoyl chloride
(d)
Methyl 1-methylcyclohexanecarboxylate
(e)
Ethyl 3-oxopentanoate
(f)
Methyl p-bromobenzenethioate
(g)
Formic propanoic anhydride
(h)
cis-2-Methylcyclopentanecarbonyl bromide
Answer (8 parts)
(a)
(b)
(c)
(d)
(e)
(f)
(g)
(h)
21-3 §21.2 source ↗
Show the mechanism of the following nucleophilic acyl substitution reaction, using curved arrows to indicate the electron flow in each step:
Answer
21-4 §21.2 source ↗
Rank the compounds in each of the following sets in order of their expected reactivity toward nucleophilic acyl substitution:
(a)
(b)
Answer (2 parts)
(a)
Acetyl chloride > Methyl acetate > Acetamide
(b)
Hexafluoroisopropyl acetate > 2,2,2-Trichloroethyl acetate > Ethyl acetate
21-5 §21.2 source ↗
Predict the products of the following nucleophilic acyl substitution reactions:
(a)
(b)
(c)
(d)
Answer (4 parts)
(a)
CH3CO2– Na+
(b)
CH3CONH2
(c)
CH3CO2CH3 + CH3CO2– Na+
(d)
CH3CONHCH3
21-6 §21.2 source ↗
The following structure represents a tetrahedral alkoxide ion intermediate formed by addition of a nucleophile to a carboxylic acid derivative. Identify the nucleophile, the leaving group, the starting acid derivative, and the ultimate product.
Answer
21-7 §21.3 source ↗
How might you prepare the following esters from the corresponding acids?
(a)
(b)
(c)
Answer (3 parts)
(a)
Acetic acid + 1-butanol
(b)
Butanoic acid + methanol
(c)
Cyclopentanecarboxylic acid + isopropyl alcohol
21-8 §21.3 source ↗
If the following molecule is treated with acid catalyst, an intramolecular esterification reaction occurs. What is the structure of the product? (Intramolecular means within the same molecule.)
Answer
21-9 §21.4 source ↗
How might you prepare the following esters using a nucleophilic acyl substitution reaction of an acid chloride?
(a)
CH3CH2CO2CH3
(b)
CH3CO2CH2CH3
(c)
Ethyl benzoate
Answer (3 parts)
(a)
Propanoyl chloride + methanol
(b)
Acetyl chloride + ethanol
(c)
Benzoyl chloride + ethanol
21-10 §21.4 source ↗
Which method would you choose if you wanted to prepare cyclohexyl benzoate—Fischer esterification or reaction of an acid chloride with an alcohol? Explain.
Answer
Benzoyl chloride + cyclohexanol
21-11 §21.4 source ↗
Write the mechanism of the reaction just shown between 3,4,5-trimethoxybenzoyl chloride and morpholine to form trimetozine. Use curved arrows to show the electron flow in each step.
Answer
This is a typical nucleophilic acyl substitution reaction, with morpholine as the nucleophile and chloride as the leaving group.
21-12 §21.4 source ↗
How could you prepare the following amides using an acid chloride and an amine or ammonia?
(a)
CH3CH2CONHCH3
(b)
N,N-Diethylbenzamide
(c)
Propanamide
Answer (3 parts)
(a)
Propanoyl chloride + methylamine
(b)
Benzoyl chloride + diethylamine
(c)
Propanoyl chloride + ammonia
21-13 §21.4 source ↗
How could you prepare the following ketones by reaction of an acid chloride with a lithium diorganocopper reagent?
(a)
(b)
Answer (2 parts)
(a)
Benzoyl chloride + [(CH3)2CH]2CuLi, or 2-methylpropanoyl chloride + Ph2CuLi
(b)
2-Propenoyl chloride + (CH3CH2CH2)2CuLi, or butanoyl chloride + (H2C = CH)2CuLi
21-14 §21.5 source ↗
Write the mechanism of the reaction between p-hydroxyaniline and acetic anhydride to prepare acetaminophen.
Answer
This is a typical nucleophilic acyl substitution reaction, with p-hydroxyaniline as the nucleophile and acetate ion as the leaving group.
21-15 §21.5 source ↗
What product would you expect from reaction of one equivalent of methanol with a cyclic anhydride, such as phthalic anhydride (1,2-benzenedicarboxylic anhydride)? What is the fate of the second “half” of the anhydride?
Answer
Monomethyl ester of benzene-1,2-dicarboxylic acid
21-16 §21.6 source ↗
Why is the saponification of an ester irreversible? In other words, why doesn’t treatment of a carboxylic acid with an alkoxide ion yield an ester?
Answer
Reaction of a carboxylic acid with an alkoxide ion gives the carboxylate ion.
21-17 §21.6 source ↗
What product would you expect from the reaction of butyrolactone with LiAlH4? With DIBAH?
Answer
LiAlH4 gives HOCH2CH2CH2CH2OH; DIBAH gives HOCH2CH2CH2CHO.
21-18 §21.6 source ↗
Show the products you would obtain by reduction of the following esters with LiAlH4:
(a)
(b)
Answer (2 parts)
(a)
CH3CH2CH2CH(CH3)CH2OH + CH3OH
(b)
PhOH + PhCH2OH
21-19 §21.6 source ↗
What ester and what Grignard reagent might you start with to prepare the following alcohols?
(a)
(b)
(c)
Answer (3 parts)
(a)
Ethyl benzoate + 2 CH3MgBr
(b)
Ethyl acetate + 2 PhMgBr
(c)
Ethyl pentanoate + 2 CH3CH2MgBr
21-20 §21.7 source ↗
How would you convert N-ethylbenzamide to each of the following products?
(a)
Benzoic acid
(b)
Benzyl alcohol
(c)
C6H5CH2NHCH2CH3
Answer (3 parts)
(a)
H2O, NaOH
(b)
Benzoic acid + LiAlH4
(c)
LiAlH4
21-21 §21.7 source ↗
How would you use the reaction of an amide with LiAlH4 as the key step in going from bromocyclohexane to (N,N-dimethylaminomethyl)cyclohexane? Write all the steps in the reaction sequence.
Answer
1. Mg; 2. CO2, then H3O+; 3. SOCl2; 4. (CH3)2NH; 5. LiAlH4
21-22 §21.8 source ↗
Write the mechanism of the reaction shown in Figure 21.10 between coenzyme A and acetyl adenylate to give acetyl CoA.
Formation of the thioester acetyl CoA by nucleophilic acyl substitution reaction of coenzyme A (CoA) with acetyl adenylate.
Answer
21-23 §21.9 source ↗
Draw structures of the step-growth polymers you would expect to obtain from the following reactions:
(a)
(b)
(c)
Answer (3 parts)
(a)
(b)
(c)
21-24 §21.9 source ↗
Kevlar, a nylon polymer prepared by reaction of 1,4-benzenedicarboxylic acid (terephthalic acid) with 1,4-benzenediamine (p-phenylenediamine), is so strong that it’s used to make bulletproof vests. Draw the structure of a segment of Kevlar.
Answer
21-25 §21.10 source ↗
What kinds of functional groups might compounds have if they show the following IR absorptions?
(a)
Absorption at 1735 cm–1
(b)
Absorption at 1810 cm–1
(c)
Absorptions at 2500 to 3300 cm–1 and 1710 cm–1
(d)
Absorption at 1715 cm–1
Answer (4 parts)
(a)
Ester
(b)
Acid chloride
(c)
Carboxylic acid
(d)
Aliphatic ketone or cyclohexanone
21-26 §21.10 source ↗
Propose structures for compounds that have the following formulas and IR absorptions:
(a)
C6H12O2, 1735 cm–1
(b)
C4H9NO, 1650 cm–1
(c)
C4H5ClO, 1780 cm–1
Answer (3 parts)
(a)
CH3CH2CH2CO2CH2CH3 and other possibilities
(b)
CH3CON(CH3)2
(c)
CH3CH = CHCOCl or H2C = C(CH3)COCl
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Problems and answers are adapted from Organic Chemistry: A Tenth Edition by John McMurry, OpenStax, and are used under the CC BY-NC-SA 4.0 licence. Access for free at https://openstax.org/books/organic-chemistry/pages/1-why-this-chapter. Illustrations: Copyright Rice University, OpenStax, under CC BY-NC-SA 4.0 license. This adaptation is released under the same licence, is non-commercial, and is neither affiliated with nor endorsed by OpenStax or Rice University.