Chapter 20:Chapter 20:Carboxylic AcidsCarboxylic AcidsCarboxylic AcidsCarboxylic Acids

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� Class I carbonyl are known as Carboxylic Acids and Carboxylic acid Derivatives. Their reactions follow the same pattern and it is easy to go from one structure to the next within the class itself by Nucleophilic Acyl Substitution.

O O

cannot be replaced by a nucleophile

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R H

O

R R

O

Class IIaldehyde ketone

R OH

O

R OR

O

R O

O

R X

O

R NH2

OO

R

carboxylicacid

ester anhydride acyl halides amides

compounds with groups that can be replaced by a nucleophile

Class I

•• Physical PropertiesPhysical Properties (20(20--3)3)

� Boiling point of carbonyl usually follow this trend:

Amide > acid > nitrile >> ester > acid chloride > aldehyde > ketone

� The high boiling points of amide, acid and nitrile is due to strong dipole interactions that exist in all

� The high boiling points of amide, acid and nitrile is due to strong dipole interactions that exist in all three types.

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� Acidity: pKa of carboxylic acid is about 5. They can therefore be easily deprotonated forming the carboxylate anion.

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� The acidity of carboxylic acids can be influenced by the nature of the substituent bonded to the carboxyl group:

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Synthesis of Carboxylic Acids Synthesis of Carboxylic Acids (Review)(Review)

• Oxidation

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Other reagents such as KMnO4, HNO3 etc… will also oxidize a 1o

alcohol to the corresponding carboxylic acid.

• Oxidative cleavageAlkenes and Alkynes can give carboxylic acid by oxidative cleavage: either with ozone or KMnO4.

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• Oxidation of alkyl benzeneAlso provides carboxylic acids as the product. Must have at least one benzylic hydrogen.

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New Synthesis of Carboxylic AcidsNew Synthesis of Carboxylic Acids

• Carboxylation of Grignard Reagents (20-8)Grignard reagents react with CO2 like they do with any other carbonyl compound. Once protonated, the product is a carboxylic acid.

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• Hydrolysis of Nitriles (20-8)Nitriles can be hydrolyzed to the corresponding carboxylic acid, either under acidic or basic conditions. (mechanisms will be discussed in Chapter 21) We have seen that they can easily formed by SN2 reactions with primary halides.

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Practice QuestionsPractice Questions� Complete the following reactions.

1) KMnO4

2) H3O+

269

CN H3O+

heat

� Provide a detailed stepwise mechanism for the last reaction from the previous slide.

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Reactions of Carboxylic AcidsReactions of Carboxylic Acids(Review)(Review)

• Alkylation of Acids to form Ketones (20-14)

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• Reduction of Acids to Primary Alcohols (20-13)

272

� Nucleophilic Acyl Substitution (20-9)Most reactions of carboxylic acids are classified as “acyl substitutions” and usually produce acid derivatives.

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� The hydrolysis of an ester under basic conditions is a good example of acyl substitution.

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� The Fisher Esterification (20-10)Reaction of a carboxylic acid with an alcohol under acidic conditions produces an ester.Reaction is an equilibrium, the yield of ester is not high.To drive the equilibrium to the formations of products use a large excess of alcohol.

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Mechanism of Fisher Mechanism of Fisher EsterificationEsterification

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� Esterification Using Diazomethane (20-11)One of the best way to make methyl ester is to react the corresponding carboxylic acid with Diazomethane. The reaction is quantitative and very easy…but diazomethane has a tendency to explode….

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Mechanism of Diazomethane Mechanism of Diazomethane EsterificationEsterification

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� Condensation of acids with amines (20-12)The reaction of carboxylic acids with amines is a simple acid/base reaction forming an ammonium salt. However, under more extreme conditions, when heat is applied it is possible to eliminate water from this salt and form amide.

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� Synthesis and Use of Acid Chlorides (20-15)Acid chlorides are the most versatile acid derivatives because they can be transformed into all other acid derivatives by acyl substitution. This is due to the presence of a good leaving group, chloride ion.

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� The best reagent for converting carboxylic acids to acid chlorides are thionyl chloride (SOCl2) and oxalyl chloride (COCl2) because they form gaseous by-products that do not contaminate the product.

� Thionyl chloride reaction produces SO2 while the oxalyl chloride reaction produces HCl, CO, and CO2 (all gaseous).

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Mechanism of Acid Chloride FormationMechanism of Acid Chloride Formation

282

� As mentioned before, reactions of acid chlorides lead to acid derivatives such as esters, amide and others.

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