ch17

5 Carboxylic Acid Derivatives (Priority Order)

Acid/Acyl chloride, Anhydride, Ester, Amide, Nitrile

• You can form right from left, but not left from right

• GOOD: (→); BAD: (←)

Oxidation of Alkenes for Carboxy (Oxidative Cleavage)

• Cleaves C=C and adds O and OH on both sides for 2 carboxylic acids

1. KMnO4, OH-, H2O, heat
—————————————————————————>
2. H3O+

Oxidation of Aldehydes to Carboxys (Tollen’s Reagent)

1. Ag2O or Ag(NH3)2OH
———————————>
2. H3O+

Oxidation of Primary Alcohols to Carboxy (1 Alc)

1. KMnO4, OH-, heat
————————————>
2. H3O+

• Diff from Oxidative Cleavage with KMnO4 because no H2O

Oxidation of Aldehydes and Primary Alcohols to Carboxy

H2CrO4 aka Jones Reagent

Benzylic Oxidation to Carboxy

• Replaces R group of Benzyl Carbon into a Carboxylic Acid

• R CANNOT be a Phenyl

1. KMnO4, OH-, heat
————————————————————>
2. H3O+

Hydrolysis of Nitriles

• Hydrolysis: hydro- water, lysis- break → Using water (H2O) to break something

• Replaces CN with carboxylic acid

HCl
———>
H2O

Hydrolysis of Nitriles Starting from Primary/Secondary Halide for Carboxylic Acid

• Alkyl Halide + NaCN = Nitrile + NaOH/H2O, heat = Carboxy

• Primary Alkyl + NaCN = SN2 reaction which replaces the halogen with a nitrile

• React nitrile with NaOH, H2O, and heat = replace CN with carboxy

Carbonation of Grignard Reagents

R—MgBr + CO2/H3O+ = Replacement of MgBr with Carboxy

• R CANNOT be Terminal Alkyne or Carbonyl

Nucleophilic Addition-Elimination at Carbonyl C Rxns

Reactions need a good LG and so it cannot happen with aldehydes or ketones.

Reactions of Acyl Chlorides

1. + Carboxylate = Acid Anhydride

2. + Alcohol/Base = Ester

3. + Amine NHR2 (Primary, Secondary, Ammonia) = Amide

Acyl Chloride + Carboxylate =

Acid Anhydride

Acyl Chloride + Alcohol/Base =

Ester

Acyl Chloride + Amine NHR2 (Primary, Seocndary, Ammonia) =

Amide

Anhydrides can be made from Dicarboxylic Acids when a 5-6 membered ring is created.

True; heat up a dicarboxylic acid and minus H2O to make the bonds connect by an Oxy

Reactions of Anhydrides

1. + Alcohol = Ester

2. + EXCESS AMINE NHR2 (Primary, Secondary, Ammonia) = Amide

• The second anhydride is a good LG, so toss it out with the connector Oxy to put in your new functional group

Closed Anhydride Ring Split Reaction

• 1 EQ of R-OH or HNR’R” or etc = Break the bond with the Oxy and split it into 2, one is OR the other is OH; or one into NR’R'“ the other is OH

• If 2 EQ, add the thing to both sides

Acid-Catalyzed Esterification

Carboxylic Acid +<=> Primary Alc/HA <=>+ Ester + Water byproduct

• PRODUCT FAVORED: Excess alcohol and removal of water

• REACTANTS FAVORED: Excess of water and dilute acid

Saponification of Esters into Carboxylic Acids

1. NaOH, H2O

2. For Esters in Rings = OH-, H2O

Amides from Carbodiimide Coupling Reactions

• Acid-Base Reaction

• Carboxylic acid + DCC + NHR’R” (Secondary amine) = Amide

• DCC = Dicyclo(hexyl?)carbodiimide

DCC

Dicyclo(hexyl?)carbodiimide

Acid Hydrolysis of Amides to Carboxylic Acids

1. H3O+
—————>
2. H2O, heat

Base Hydrolysis of Amides to Carboxylic Acids

1. OH-, H2O, heat
————————>
2. H3O+

• if no #2, then would just be a carboxylate, needs stabilizer

Nitriles from Dehydration of Amides

• P4O10 or (CH3CO)2O and heat

• Only works with PRIMARY AMIDES