chapter 21 the chemistry of carboxylic acid derivatives
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Chapter 21 The Chemistry of Carboxylic Acid Derivatives. Carboxylic Acid Derivatives. Carboxylic acid derivative : a compound that has an acyl group bonded to an electronegative atom or substituent that can act as a leaving group in a substitution reaction - PowerPoint PPT PresentationTRANSCRIPT
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Chapter 21The Chemistry of Carboxylic Acid Derivatives
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Carboxylic Acid Derivatives• Carboxylic acid derivative: a compound that has an acyl group
bonded to an electronegative atom or substituent that can act as a leaving group in a substitution reaction– can be hydrolyzed under acidic of basic conditions to give a
carboxylic acid
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Structures of Carboxylic Acid Derivatives
321.1 Nomenclature and Classification of Carboxylic Acid Derivatives
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Reactions of Carboxylic Acid Derivatives• Chemistry dominated by nucleophilic acyl substitution rxns:
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Hydrolysis Reactions1) Hydrolysis of Esters
a) Basic Hydrolysis (Saponification)b) Acid Catalyzed Hydrolysis
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Basic Hydrolysis
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Acid Catalyzed Hydrolysis
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2) Hydrolysis of Amides
• Happens under both acidic and basic conditions• Conditions harsher than those of ester hydrolysis
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+ NH4+/NH2
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• Basic Hydrolysis
• Acidic Hydrolysis
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3) Hydrolysis of Nitriles• Occurs in both acidic and basic environments• More extreme conditions are required compared to those of esters
and amides
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• Basic hydrolysis
1121.7 Hydrolysis of Carboxylic Acid Derivatives
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• Acidic hydrolysis
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• Imidic acids can be viewed as the nitrogen-analogs of enols
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Problem• Write out the mechanism for the following rxn:
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Nucleophilic Acyl Substitution Reactions
• The conditions for hydrolysis for these derivatives can differ considerably
1521.7 Hydrolysis of Carboxylic Acid Derivatives
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Reactions of Acid Chlorides with Amines: Aminolysis
1821.8 Reactions of Carboxylic Acid Derivatives with Nucleophiles
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Conversion of Acid Chlorides into Esters: Alcoholysis
1921.8 Reactions of Carboxylic Acid Derivatives with Nucleophiles
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Reactions of Acid Chlorides with Carboxylate Salts: Preparation of Anydrides
2021.8 Reactions of Carboxylic Acid Derivatives with Nucleophiles
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Problems
1) Give the products for the following rxns:
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2) Draw the mechanism for the following reaction:
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Reactions of Anhydrides with Nucleophiles
2321.8 Reactions of Carboxylic Acid Derivatives with Nucleophiles
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Reactions of Esters with Nucleophiles
• Transesterification:
2421.8 Reactions of Carboxylic Acid Derivatives with Nucleophiles
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Problems
• Give the products for the following rxns:
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Reduction Carboxylic Acid Derivatives
1) Reduction of Esters• LiAlH4 preferred over NaBH4
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-78°C, DIBAH = Diisobutyl aluminum hydride
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2) Reduction of Amides to Amines– Net effect is conversion of C=O to CH2
2821.9 Reduction of Carboxylic Acid Derivatives
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Reduction of Amides to Amines
• Note how the amide reduction differs from that of ester reduction
2921.9 Reduction of Carboxylic Acid Derivatives
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• Note that a protonolysis step with aqueous acid follows the LiAlH4 reduction
• This is followed by base to free the amine
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3121.9 Reduction of Carboxylic Acid Derivatives
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3221.9 Reduction of Carboxylic Acid Derivatives
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3) Reduction of Nitriles to Primary Amines
3321.9 Reduction of Carboxylic Acid Derivatives
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• Two successive nucleophilic additions occur
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• Intermediate imine not isolated
3521.9 Reduction of Carboxylic Acid Derivatives
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4) Reduction of Acid Chlorides to Aldehydes– The Rosenmund reduction:
– H2 gas over Pd on C• Poisoned with BaSO4 or quinoline
– Keeps aldehyde from further reducing to alcohol
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• Derivatives of LiAlH4 can also be used
• Can also use DIBAH
3721.9 Reduction of Carboxylic Acid Derivatives
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Problems
• Draw the products for the following rxns:
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Reactions of Esters with Grignard Reagents
• Tertiary alcohol produced• Two substituents are identical
4021.10 Reactions of Carboxylic Acid Derivatives with Organometallic Reagents
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Reactions of Acid Chlorides Grignard Reagents
4121.10 Reactions of Carboxylic Acid Derivatives with Organometallic Reagents
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Reactions of Acid Chlorides with R2CuLi
• R2CuLi = Gilman reagent
• Dialkylcuprates are less reactive than Grignard reagents• Allow rxn to stop at ketone• Only works with acid chlorides, not with other carboxylic acid
derivatives
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Problems
• Draw the product for the following rxns:
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