Chapter 20 Reagents/Reactions

Acyl Halide + ? —> anhydride

Carboxylic Acid

• pyridine or NEt₃

Acyl Halide + ? —> Carboxylic Acid

HOH

• pyridine or NEt₃

Acyl Halide + ? —> Ester

HO-R

• pyridine or NEt₃

Acyl Halide + ? —> Amide

H - NR₂

• pyridine or NEt₃

Acyl Halide + Organolithiums/Gringards

Reaction keeps going, gringard adds twice

• forms an alcohol with 2 R groups attached

Acyl Halide + Organocuperate

Adds R group once

Acyl Halide Mechanism

Addition-Elimination (deprotonation)

• LG is the X-

Anhydride + ? —> Carboxylic Acid

HOH

Anhydride + ? —> Ester

R-OH

Anhydride + ? —> Amide

R-NH₂

(amine)

Anhydride Mechanism

Addition-Elimination (deprotonation)

• LG = -OCOR

• Do to the 2 carbonyls on the anhydride, there is no control over which one the nucleophile will attack

• results in two products

Ester Hydrolysis - Acidic Conditions

Formation of carboxylic acid

• TsOH, Heat, H2O, Acetone

• via PADPED

  • H₃O+ protonates carbonyl O

Ester Hydrolysis - Basic Conditions (Saponification)

Forms carboxylate anion

• OH-, H2O, Heat

• via PADPED

  • OH- will add to carbonyl

transesterification

Swaps ester for another functional group

• ROH, TsOH, Heat

Esters with Gringard

1. R-MgBr

2. H3O+, H2O

Reacts twice

• you get 2R groups and an OH in place of the ester and carboxyl group

Amide Reactions - Hydrolysis in Acid vs basic

Reduces to carboxylic acid

• H2O, heat, H2SO4

• H2O, heat, NaOH

Hoffman Rearrangements

reagents: X₂, NaOH, H₂O

• forms amide without carbonyl group (carbonyl C gets replaces with the amide)

• forms CO₂

Reactions with Nitriles - Hydrolysis

• forms carboxylic

Under acidic conditions: H₂SO₄, H₂O, heat, Acetone

• Mechanism: PADPED - T

Under basic conditions: OH, H2O, Heat, Acetone

• Mechanism: APDEP - T

Reactions with Nitriles - Organometallics

Organolithiums:

1. Ch3Li, THF 2. H3O+, H2O

Gringards:

1. R-MgBr, THF 2. H3O+, H2O

Mechanism:

• AP - Hydrolysis of Imines

Acyl Halide Reductions

Alcohol Formation:

1. LiAlH4, Et2O 2. H3O+, H2O

Aldehyde Formation: Bulky reagent needed

1. LiAl(OtBu)3H

2. H3O+, H2O

Ester Reductions

Alcohol formation:

1. LiAlH4, Et2O 2. H3O+, H2O

Aldehyde formation:

1. DIBAL, -78°C 2. H3O+, H2O

Alcohol + 2 R groups:

1. R-MgBr, THF 2. H3O+, H2O

Amide Reductions

carbonyl to 2H —> amine production

1. LiAlH4, Et2O 2. H3O+, H2O

Aldehyde formation:

1. DIBAL, -78°C 2. H3O+, H2O

Nitrile Reductions

Aldehyde Formation:

1. DIBAL, -78°C 2. H₃O+, H2O

2H Addition —> Amine Formation

1. LiAlH4, Et2O 2. H3O+, H2O

2. H₂, cat. pt