CARBOXYLIC ACIDS AND DERIVATIVES Dr. Sheppard CHEM 2412 Summer
2015 Klein (2 nd ed.) sections: 21.1, 21.2, 21.6, 21.3, 21.15,
21.4, 21.5, 21.10, 21.7, 21.8, 21.9, 21.11, 21.12, 21.13,
21.14
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Carboxylic Acids and Derivatives Carboxylic acids Found in
nature Carboxylic acid derivatives:
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Carboxylic Acids and Derivatives I. Nomenclature Review II.
Physical Properties III. Acidity of Carboxylic Acids IV.
Spectroscopy V. Preparation of Carboxylic Acids VI. Reactions of
Carboxylic Acids VII. Nucleophilic Acyl Substitution
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I. Nomenclature (Review) Carboxylic acids Parent chain contains
carbon of CO 2 H Suffix is -oic acid CO 2 H is carbon 1 Cyclic
molecules with CO 2 H substituents CO 2 H is bonded to carbon 1 of
ring Add carboxylic acid to end of ring parent name
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Examples StructureName
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Naming Acid Chlorides Name corresponding carboxylic acid Change
-ic acid to -yl chloride Examples: StructureName
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Naming Acid Anhydrides If R = R, name carboxylic acid RCO 2 H.
Replace acid with anhydride If R R, list the two acids
alphabetically and add the word anhydride Examples:
StructureName
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Naming Esters Name alkyl group bonded to oxygen (R) Name
carboxylic acid RCO 2 H Change -ic acid to -ate Examples:
StructureName
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Naming Amides Name corresponding carboxylic acid Change -oic
acid to -amide Examples: StructureName
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Naming Nitriles Two methods 1. Nitrile carbon is carbon 1 of
parent chain. Add -nitrile to end of alkane name. 2. Name as
carboxylic acid derivative. Replace -ic acid with -onitrile
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II. Physical Properties Carboxylic acids form a hydrogen bond
dimer Boiling points Carboxylic acids are very high CA >
alcohols > aldehyde/ketones > hydrocarbons Carboxylic acid
derivatives are less predictable Generally amides > carboxylic
acids > acid halides/esters Tertiary amides < primary and
secondary amides no H-bonding in liquid phase (neat)
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II. Physical Properties Solubility in water Low MW CAs and CADs
are soluble Solubility decrease as MW increases Salts of carboxylic
acids are more soluble CADs also react with water (to form
carboxylic acids) Odor Esters = sweet or floral Carboxylic acids =
unpleasant
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III. Acidity of Carboxylic Acids Weak acids (pK a ~ 4-5)
Stronger than alcohols because conjugate base is
resonance-stabilized
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III. Acidity of Carboxylic Acids Conjugate base can be further
stabilized if electronegative atom is present Inductive effect
Position of en atom affects pK a
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III. Acidity of Carboxylic Acids Substituted benzoic acids If Z
= electron-donating group, acid is weaker If Z =
electron-withdrawing group, acid is stronger
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IV. Spectroscopy of CAs: IR Absorption at 2500-3300 cm -1 for
COOH Absorption at 1710-1760 cm -1 for C=O
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13 C-NMR: 1 H-NMR: COOH signal 11-12 IV. Spectroscopy of CAs:
NMR
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IV. Spectroscopy of CADs: IR Absorption at 1650-1820 cm -1 for
C=O
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13 C-NMR: Carbonyl carbon slightly upfield from aldehydes and
ketones 1 H-NMR: H adjacent to C=O around 2, but doesnt always help
you determine functional group Look for OH (CA), NH (amide), or OR
(ester) IV. Spectroscopy of CADs: NMR
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V. Preparation of Carboxylic Acids 1. Oxidation of primary
alcohols and aldehydes (section 13.10)
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V. Preparation of Carboxylic Acids 2. Oxidative cleavage of
alkenes or alkynes (section 10.9)
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V. Preparation of Carboxylic Acids 3. Oxidation of
alkylbenzenes We will see this in the aromatic chapters
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V. Preparation of Carboxylic Acids 4. Hydrolysis of nitriles
Requires aqueous acid and heat
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V. Preparation of Carboxylic Acids 5. Carboxylation of Grignard
reagents Addition of CO 2, followed by H 3 O + Mechanism:
Example:
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Show two methods that could be used to make butanoic acid from
1-bromopropane
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VI. Reactions of Carboxylic Acids Types of reactions
Deprotonation -Substitution Oxidation? Reduction? Conversion to
CADs
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Reduction Need a strong reducing agent LAH Reduce to primary
alcohol Remember reducing agent chart from alcohol chapter
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Conversion to CADs 1. Fischer esterification Carboxylic acid +
alcohol ester + water Needs acid catalyst (H 2 SO 4 or HCl)
Reaction is reversible Push to the right with excess alcohol or
remove water
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Conversion to CADs 2. Formation of acid chlorides Reagent =
SOCl 2 Where have we seen this reagent before?
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Conversion to CADs 3. Formation of acid anhydrides Anhydride =
without water Apply heat to carboxylic acids to remove water
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Conversion to CADs 4. Formation of amides Reaction is difficult
with N nucleophile because the N (base) reacts with the carboxylic
acid (acid)
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VII. Nucleophilic Acyl Substitution Include all of the CA CAD
reactions Also used to make CAs from CADs and convert between CADs
Z is leaving group Compare to nucleophilic addition
(aldehydes/ketones)
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VII. Nucleophilic Acyl Substitution Mechanism Acid or base
catalyst typically needed Acid makes electrophile more
electrophilic Base makes nucleophile more nucleophilic
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VII. Nucleophilic Acyl Substitution Reactivity: Less
substituted molecules are more reactive
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VII. Nucleophilic Acyl Substitution Reactivity: Molecules with
better leaving groups are more reactive Less reactive compounds
need heat or catalyst to react and are limited in the number of
reactions they will undergo Example: amides only undergo hydrolysis
and reduction
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VII. Nucleophilic Acyl Substitution Reactivity: More reactive
compounds can be converted to less reactive compounds Can an ester
be converted into an amide? Can an amide be converted into an
ester?
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VII. Nucleophilic Acyl Substitution Types of reactions
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VII. Nucleophilic Acyl Substitution Types of reactions:
ReactionNucleophileProductSpecial Notes HydrolysisH2OH2OCarboxylic
acid AlcoholysisROHEster AminolysisNH 3 1 amine 2 amine 1 amide 2
amide 3 amide With acid chlorides, 2 eq. of amine are needed: 1.the
nucleophile 2.neutralizes HCl byproduct ReductionHydride from LAHCA
1 ROH Ester 1 ROH Anhydride 1 ROH Acid chloride 1 ROH Amides amines
ReductionHydride from DIBALHaldehydeEster only GrignardRMgX3
alcoholEster and acid halide only
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VII. Nucleophilic Acyl Substitution Summary of reactions: acid
halide Also Grignard Anhydride formation:
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VII. Nucleophilic Acyl Substitution Summary of reactions:
anhydrides Example: commercial preparation of aspirin
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VII. Nucleophilic Acyl Substitution Summary of reactions:
esters Hydrolysis Alcoholysis Aminolysis Reduction (to 1 alcohols
and aldehydes) Grignard Alcoholysis of esters =
transesterification
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VII. Nucleophilic Acyl Substitution Summary of reactions:
amides Hydrolysis Acid or base catalyst Heat Reduction
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VII. Nucleophilic Acyl Substitution Summary of reactions:
nitriles Hydrolysis Acid or base catalyst Heat Reduction
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VII. Nucleophilic Acyl Substitution Complete the chart with the
functional group that will form from the following reactions.
H2OH2OROHNH 3 LAHGrignard Carboxylic acid Acid halide Acid
anhydride Ester Amide Nitrile
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VII. Nucleophilic Acyl Substitution Specific reactions: 1.
Saponification (soap-making) Hydrolysis of ester in base
Irreversible reaction
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VII. Nucleophilic Acyl Substitution 2. Condensation
polymerization A step-growth reaction Example: polyamide What is a
polyester? How could a polyester be synthesized?
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VII. Nucleophilic Acyl Substitution 2. Step-growth
polymerization Compare Fischer esterification to
polymerization
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VII. Nucleophilic Acyl Substitution 2. Step-growth
polymerization Biodegradable polymers
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What is the order of decreasing activity (most reactive = 1,
least reactive = 4) toward nucleophilic acyl substitution for the
following carboxylic acid derivatives?
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Draw the products of these reactions. a) b) c) d)
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Synthesis 1. Propose a synthesis for ethyl acetate from
ethanol. 2. 3.
