21.12 Preparation and Reactions of
Amides
• Nylon is a polyamide
• Polyester is made similarly. HOW?
Copyright 2012 John Wiley & Sons, Inc.
21-1
21.12 Preparation and Reactions of
Amides
• Amides can be hydrolyzed with H3O+, but the process is
slow and requires high temperature
• The mechanism is very similar to that for the hydrolysis
of an ester
• Show a complete mechanism
• WHY is the process generally slow?
Copyright 2012 John Wiley & Sons, Inc.
21-2
21.12 Preparation and Reactions of
Amides
• Amides can be hydrolyzed with H3O+, but the process is
slow and requires high temperature
• Should the equilibrium favor reactants or products?
WHY?
• Where does the NH4+ come from?
• Amide hydrolysis can also be promoted with NaOH,
although the process is very slow
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21-3
21.12 Preparation and Reactions of
Amides
• LiAlH4 can reduce an amide to an amine
• The mechanism is
quite different from
the others we have
seen in this chapter
• When the H- attacks,
which is the best
leaving group?
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21-4
21.12 Preparation and Reactions of
Amides
• The iminium is reduced with a second equivalent of
hydride
• Practice with conceptual checkpoints
21.26 through 21.28
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21-5
21.13 Preparation and Reactions of
Nitriles
• When a 1° or 2° alkyl halide is treated with a cyanide
ion, the CN- acts as a nucleophile in an SN2 reaction
• Nitriles can also be made by dehydrating an amide using
a variety of reagents including SOCl2
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21-6
21.13 Preparation and Reactions of
Nitriles
• What base might you use?
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21-7
21.13 Preparation and Reactions of
Nitriles
• An aqueous strong acid solution can be used to
hydrolyze a nitrile
• In the mechanism, the nitrogen is protonated multiple
times and water acts as a nucleophile
• Draw a complete mechanism
Copyright 2012 John Wiley & Sons, Inc.
21-8
21.13 Preparation and Reactions of
Nitriles
• Basic hydrolysis of a nitrile can also be achieved
• Which group in the reaction acts as a nucleophile?
• Which group acts to protonate the nitrogen?
• Draw a complete mechanism
Copyright 2012 John Wiley & Sons, Inc.
21-9
21.13 Preparation and Reactions of
Nitriles
• Nitriles can also react with Grignards
• After the nitrile is consumed, H3O+ is added to form an
imine, which can be hydrolyzed with excess H3O+ (aq) to
form a ketone. SHOW a mechanism
Copyright 2012 John Wiley & Sons, Inc.
21-10
21.13 Preparation and Reactions of
Nitriles
• Similar to how carboxylic acids can be converted to
alcohols using LAH (section 21.5), nitriles can be
converted to amines
• Practice with conceptual checkpoints 21.29 through
21.31
Copyright 2012 John Wiley & Sons, Inc.
21-11
21.14 Synthetic Strategies
• When designing a synthesis, there are two general
considerations that we make
1. Is there a change in the carbon skeleton?
2. Is there a change in functional groups?
• We have learned many new functional group
transformations in this chapter – see next slide
• Practice with SkillBuilder 21.2
Copyright 2012 John Wiley & Sons, Inc.
21-12
21.14 Synthetic Strategies
Copyright 2012 John Wiley & Sons, Inc.
21-13
21.14 Synthetic Strategies
• Give necessary reagents for the conversion below.
Multiple steps will be necessary
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21-14
21.14 Synthetic Strategies
• There are 2 categories of bond-forming reactions
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21-15
21.14 Synthetic Strategies
• When forming new carbon-carbon bonds, it is critical to
install functional groups in the proper location
• Give necessary reagents for the conversion below.
More than one step will be necessary
• Practice with SkillBuilder 21.3
Copyright 2012 John Wiley & Sons, Inc.
21-16
21.15 Spectroscopy of Carboxylic Acids
and Their Derivatives
• Recall that C=O stretching is a prominent peak in IR
spectra
• Recall that conjugated carbonyl signals appear at lower
wavenumbers (about 40 cm-1 less)
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21-17
21.15 Spectroscopy of Carboxylic Acids
and Their Derivatives
• The O-H stretch of an acid gives a very broad peak
(2500-3300 cm-1)
• The CΞN triple bond stretch appears around 2200 cm-1
• Carbonyl 13C peaks appear around 160-185 ppm
• Nitrile 13C peaks appear around 115-130 ppm
• The 1H peak for a carboxylic acid proton appears around
12 ppm
• Practice with conceptual checkpoint 21.38
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21-18
21.15 Spectroscopy of Carboxylic Acids
and Their Derivatives
• Predict the number and chemical shift of all 13C peaks
for the molecule below
• Predict the number, chemical shift, multiplicity, and
integration of all 1H peaks for the molecule below
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21-19
22.1 Introduction Alpha Carbon
Chemistry: Enols and Enolates
• For carbonyl compounds, Greek letters are often used to
describe the proximity of atoms to the carbonyl center
• This chapter will primarily explore reactions that take
place at the alpha carbon
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22-20
22.1 Introduction Alpha Carbon
Chemistry: Enols and Enolates
• The reactions we will explore proceed though either an
enol or an enolate intermediate
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22.1 Introduction Alpha Carbon
Chemistry: Enols and Enolates
• Trace amounts of acid or base catalyst provide
equilibriums in which both the enol and keto forms are
present
• How is equilibrium different from resonance?
• At equilibrium, >99% of the molecules exist in the keto
form. WHY?
Copyright 2012 John Wiley & Sons, Inc.
22-22
22.1 Introduction Alpha Carbon
Chemistry: Enols and Enolates
• In rare cases such as the example below, the enol form
is favored in equilibrium
• Give two reasons to explain WHY the enol is favored
• The solvent can affect the exact percentages
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22-23
22.1 Introduction Alpha Carbon
Chemistry: Enols and Enolates
• Phenol is an example where the enol is vastly favored
over the keto at equilibrium. WHY?
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22-24
22.1 Introduction Alpha Carbon
Chemistry: Enols and Enolates
• The mechanism for the tautomerization depends on
whether it is acid catalyzed or base catalyzed
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22-25
22.1 Introduction Alpha Carbon
Chemistry: Enols and Enolates
• The mechanism for the tautomerization depends on
whether it is acid catalyzed or base catalyzed
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22-26
22.1 Introduction Alpha Carbon
Chemistry: Enols and Enolates
• As the tautomerization is practically unavoidable, some
fraction of the molecules will exist in the enol form
• Analyzing the enol form, we see there is a minor (but
significant) resonance contributor with a nucleophilic
carbon atom
• Practice with conceptual checkpoints 22.1
through 22.3
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22-27
22.1 Introduction Alpha Carbon
Chemistry: Enols and Enolates
• In the presence of a strong base, an enolate forms
• The enolate is much more nucleophilic than the enol.
WHY?
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22-28
22.1 Introduction Alpha Carbon
Chemistry: Enols and Enolates
• The enolate can
undergo C-attack or
O-attack
• Enolates generally
undergo C-attack.
WHY?
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22-29
22.1 Introduction Alpha Carbon
Chemistry: Enols and Enolates
• Alpha protons are the only protons on an aldehyde or
ketone that can be removed to form an enolate
• Removing the aldehyde proton or the beta or gamma
proton will NOT yield a resonance stabilized
intermediate
• Practice with SkillBuilder 22.1
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22-30
22.1 Introduction Alpha Carbon
Chemistry: Enols and Enolates
• Draw all possible enolates that could form from the
following molecule
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22-31
Study Guide for Sections 21.12-21.15, 22.1
DAY 23, Terms to know:
Sections 21.12-21.15, 22.1 alpha carbon, enol, enolate, enol-keto tautomerization
DAY 23, Specific outcomes and skills that may be tested on exam 4:
Sections 21.12-21.15, 22.1
•Given reactants, be able to predict products and give complete mechanisms for nucleophilic
substitution reactions on acids and acid derivatives
•Given a precursor, be able to give sets of reagents and reaction conditions that could yield a
given carboxylic acid derivative
•Given a carboxylic acid derivative, be able to predict products and give complete mechanisms
for any of the reactions we discussed that acid derivatives undergo
•Be able to solve syntheses with up to 3 steps including setting the syntheses up
retrosynthetically
•Be able to fill in blank reagents, intermediates, or products in a synthesis involving any of the
reactions discussed in this chapter
•Be able to predict NMR peaks and IR peaks for carboxylic acids and their derivatives
•Given IR and NMR data, be able to give a reasonable molecular structure that could match the
data
•Be able to give a complete mechanism for either direction of the enol-keto tautomerization
equilibrium with either an acid or a base catalyst
•Be able to explain why enolate nucleophiles generally attack from the alpha carbon rather than
the oxygen
Extra Practice Problems for Sections 21.12-21.15, 22.1
Complete these problems outside of class until you are confident you have
learned the SKILLS in this section outlined on the study guide and we will
review some of them next class period. 21.26 21.27 21.28 21.29 21.30
21.31 21.32 21.35 21.38 21.50 21.52 21.54 21.55 21.61 21.65 21.80
22.1 22.2 22.3 22.4 22.5
Prep for Day 24
Must Watch videos:
https://www.youtube.com/watch?v=CHT7keygh80 (enolates, FLC) start at 9:30 minute mark
https://www.youtube.com/watch?v=4bgXyJE-oNA (aldol, FLC) watch first 15 minutes
https://www.youtube.com/watch?v=libJJqT5mqk (aldol, JP McCormick)
Other helpful videos:
https://www.youtube.com/watch?v=PIt9ZfWux1I (alpha halogenation, JP McCormick)
https://www.youtube.com/watch?v=NsvO3WW13h8&list=PLjcZNd83xWLkDcJ8Fx1myEvOwB25b5rW (aldol playlist, Despain)
https://www.youtube.com/watch?v=ea1iYgxVCn0 (haloform, UC-Irvine) watch first 53 minutes
https://www.youtube.com/watch?v=iP7GORVCA9M (aldol, UC-Irvine) watch first 63 minutes
Read Sections 22.1-22.3