Modified slides of William Tam & Phillis Chang Ch Chapter 17 Carboxylic Acids and Their Derivatives NucleophilicAddition–Elimination at the Acyl Carbon

Ch Carboxylic Acid Derivatives Introduction

Ch Nomenclature Rules Carboxylic acid as parent (suffix): ending with “–oic acid” Carboxylate as parent (suffix): ending with “–oate”

Ch Anhydrides are named by dropping the acid and adding the word “anhydride” Acid chloride suffix: “–oyl chloride” Ester suffix: ending with “–oate” Amide suffix: ending with “amide” Nitrile suffix: ending with “nitrile”

Ch Examples

Ch Examples

Ch Acidity of Carboxylic Acids pK a ~ 4-5 Compare pK a of H 2 O ~ 16 pK a of H 2 CO 3 ~ 7 pK a of HF ~ 3

Ch  When comparing acidity of organic compounds, we compare the stability of their conjugate bases. The more stable the conjugate base, the stronger the acid

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Ch  The conjugate base B 1 is more stable (the anion is more delocalized) than B 2 due to resonance stabilization ●Thus, A 1 is a stronger acid than A 2

Ch Acidity of Carboxylic Acids, Phenols & Alcohols

Ch  Acidity of Carboxylic Acids, Phenols and Alcohols

Ch  Acidity of Carboxylic Acids, Phenols and Alcohols

Ch  Acidity of Carboxylic Acids, Phenols and Alcohols (NO resonance stabilization)

Ch Question How could you distinguish these 3 by simple chemical tests? (acidity)

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Ch  Stability of conjugate bases > > > > >>

Ch > > > > > > > > >

Ch Dicarboxylic Acids

Ch J.Spectroscopic Properties of Acyl Compounds  IR Spectra ●The C=O stretching band occurs at different frequencies for acids, esters, and amides, and its precise location is often helpful in structure determination ●Conjugation and electron-donating groups bonded to the carbonyl shift the location of the C=O absorption to lower frequencies

Ch  IR Spectra ●Electron-withdrawing groups bonded to the carbonyl shift the C=O absorption to higher frequencies ●The hydroxyl groups of carboxylic acids also give rise to a broad peak in the cm -1 region arising from O– H stretching vibrations ●The N–H stretching vibrations of amides absorb between 3140 and 3500 cm -1

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Ch  1 H NMR Spectra ●The acidic protons of carboxylic acids are highly deshielded and absorb far downfield in the  region ●The protons of the a carbon of carboxylic acids absorb in the  region

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Ch  13 C NMR Spectra ●The carbonyl carbon of carboxylic acids and their derivatives occurs downfield in the  region (see the following examples), but not as far downfield as for aldehydes and ketones (  ) ●The nitrile carbon is not shifted so far downfield and absorbs in the  region

Ch  13 C NMR chemical shifts for the carbonyl or nitrile carbon atom

Ch Preparation of Carboxylic Acids Oxidation cleavage of alkenes KMnO 4 ozonolysis

Ch Oxidation of aldehydes & 1 o alcohols

Ch Oxidation of alkyl benzene

Ch Oxidation of benzene ring

Ch Hydrolysis of cyanohydrins & nitriles

Ch Carbonation of Grignard reagents

Ch Nucleophilic Addition-Elimination at the Acyl Carbon Acyl substitution through nucleophilic addition- elimination

Ch Acyl derivatives

Ch aldehydes & ketones usually do not undergo this type of nucleophilic acyl substitution, lack an acyl leaving group A good leaving group Not a good leaving group

Ch  Relative reactivity of carboxylic acid derivatives towards nucleophilic acyl substitution reactions ●There are 2 steps in a nucleophilic acyl substitution  The addition of the nucleophile to the carbonyl group  The elimination of the leaving group in the tetrahedral intermediate

Ch Usually the addition is the rate- determining step (r.d.s.). Elimination usually occurs spontaneously to regenerate the carbonyl group Both steric and electronic factors that effect addition of a nucleophile

Ch Steric factor Electronic factor strongly polarized acid derivatives react more readily than less polar ones

Ch Thus, reactivity of It is usually possible to convert a more reactive acid derivative to a less reactive one, but not vice versa

Ch Acyl Chlorides Synthesis of Acyl Chlorides From carboxylic acids reagents SOCl 2 (COCl) 2 PCl 3 or PCl 5

Ch Mechanism

Ch Conversion of acid chlorides to carboxylic acids

Ch Mechanism

Ch Conversion to other carboxylic derivatives

Ch Carboxylic Acid Anhydrides Synthesis of Anhydrides

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Ch Reactions of Anhydrides Conversion to carboxylic acids

Ch Mechanism

Ch Conversion to other carboxylic derivatives

Ch Esters Esterification

Ch Mechanism

Ch Esters from acyl chlorides

Ch Esters from anhydrides

Ch Base-Promoted Hydrolysis of Esters Hydrolysis under basic conditions: saponification

Ch Mechanism

Ch Hydrolysis of esters under acidic conditions

Ch Mechanism

Ch Lactones Carboxylic acids whose molecules have a hydroxyl group on a  or  carbon undergo intramolecular esterification (cyclic esters) or  - or  -lactones

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Ch Lactones are hydrolyzed by aqueous base just as other esters are

Ch Amides Amides from Acyl Chlorides

Ch Amides from Carboxylic Anhydrides

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Ch Amides from Esters

Ch Amides from Carboxylic Acids & Ammonium Carboxylates

Ch DCC-Promoted amide synthesis

Ch Mechanism

Ch Mechanism (Cont’d)

Ch Hydrolysis of Amides Acid hydrolysis of amides

Ch Mechanism

Ch Basic hydrolysis of amides

Ch Mechanism

Ch Nitriles from the Dehydration of Amides useful preparing nitriles not available by S N 2

Ch dehydration

Ch Synthesis 1 o alkyl bromide  S N 2

Ch But synthesis of 3 o alkyl bromide

Ch Solution dehydration

Ch Hydrolysis of Nitriles Catalyzed by both acid and base

Ch Examples

Ch Mechanism protonated nitrile protonated amide tautomer

Ch Mechanism

Ch Lactams

Ch Derivatives of Carbonic Acid Alkyl Chloroformates & Carbamates (Urethan es) Alkyl chloroformate

Ch e.g.

Ch Carbamates or urethanes

Ch Protection Deprotection protected amine

Ch Decarboxylation of Carboxylic Acids

Ch There are 2 reasons for decarboxylation

Ch Chemical Tests for Acyl Compounds Recall: acidity of

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Ch Polyesters, Polyamides, Step-Growth Polymers Polyesters

Ch Polyamides

Ch Nylon 66

Ch Dacron (Mylar) Applications: film, recording tape

Ch Summary of the Reactions Reactions of carboxylic acids

Ch Reactions of acyl chlorides

Ch Reactions of acyl chlorides (Cont’d)

Ch Reactions of acid anhydrides

Ch Reactions of esters

Ch Reactions of nitriles

End- 105 Reactions of amides