Chemistry 212 --- Things-To-Study
Chapter 20: Carboxylic Acid Derivatives

Focus on the overall reactions! Many mechanisms are simple variations of add.-elim. mechanism. Study in detail the mechanisms indicated.

Reactivities, Structures and Spectra
Relative reactivities in add.-elim. reactions: Amide < Ester < Anhydride < Halide.
Reflects inductive-withdrawing and pi-donating effects.
Pi-donating ability reflected in (a) CO stretching frequencies, (b) rotational barriers (know value of 21 kcal/mol in dimethylformamide), (c) basicity of carbonyl-oxygen, (d) acidity of the alpha-hydrogen (know: amides 30, ester 25, ketone 20, halide 16).

ACYLHALIDES

Nomenclature
alkanoic acid ---> alkanoyl halide; cycloalkanoic acid ---> cycloalkanecarbonyl halide

Reactions of Acylhalides to make other Acid Derivatives
Hydrolysis: Propanoyl chloride and water ---> propanoic acid + HCl
Alcoholysis: Acetylchloride and 1-propanol ---> propylacetate + HCl
Aminolysis: Benzoyl chloride and ammonia ---> benzamide + ammonium chloride

Reductions of Acylhalides
Reaction 1: Reaction of diorganocuprates R2CuLi to make ketones.
Reaction 2: Reduction with LAH to primary alcohol.
Reaction 3: With modified LAHs to aldehyde (LiAlH(OtBu)3).

CARBOXYLIC ANHYDRIDES

Nomenclature
Name of the acid or of the diacid followed by the word anhydride.

Reactions of Anhydrides to make other Acid Derivatives
Hydrolysis and alcoholysis just like with the halides except that now a carboxylic acid is formed instead of the HX. The carboxylic acid is removed with basic water.

ESTERS

Names and Properties of Esters
Alkyl alkanoates - alkyl is the R in OR and alkanoate is the carboxylic acid.
Lactones are cyclic esters (alpha, beta, aso indicate ring size), aka oxa-2-cycloalkanones.
Esters are important for flavors, waxes (know what that is), as fats and oils (know fatty acids, glycerin etc), and phospholipids (be able to recognize such things). Know basics (be able to draw cartoons) about bilayers and micelles.

Reactions of Esters to make Acid and Other Acid Derivatives
Hydrolysis: Base-cat. ester hydrolysis (saponification) in every detail.
Aminolysis
The other acid derivatives are not made directly from the ester.

Reductions of Acylhalides
(1) Alcohols made from Esters. Important! Know mechanism.
Route to tertiary alcohol containing TWO of the R groups from the Grignard reagent.
Route to secondary alcohols if ester of formic acid is used.
(2) Reduction of esters to alcohols with LAH.
(3) Reduction of esters to aldehydes with diisobutylaluminiumhydride.

AMIDES

Nomenclature
Trivial and IUPAC names for acyclic and cyclic systems.
Nomenclature for primary, secondary, and tertiary amides.
Ability to recognize amides and the amides of carbonic acids (ureas, carbamic acid, carbamic esters = urethane).

Reactions of Amides to Make Acid
Amide hydrolysis: The hardest hydrolysis of them all! Heating in conc. acid or base!
The other acid derivatives are not made directly from the amide.

Reductions of Amides
(1) Reduction to primary amine using LAH.
(2) Reduction to aldehyde (using diisobutyaluminium hydride).

The Hofmann Rearrangment of Amidates
A method for the generation of primary amines from primary amides.
Know mechanism in detail.

ALKANENITRILES

The Functional Group
Hybridization (as in acetylene).
C-N bond lengths, single is 1.462, triple is 1.157
CN stretch at 2250 1/cm

Nomenclature
IUPAC nomenclature for mono and dinitriles. Carbonitrile nomenclature.

Preparations of Nitriles
Preparation 1: Nucl. substitution reactions of halides
Preparation 2: Dehydration of primary amines. (Not important)

Hydrolysis of Nitriles
Know mechanisms of acid- and base-catalyzed hydrolyses.

Reductions of Nitriles
(1) Nitriles to ketones using organometallic reagents.
(2) Reduction of nitriles to amines with LAH.
(3) Reduction of nitriles to amines with hydrogen gas.
(4) Reduction of nitriles to aldehydes (diisobutylaluminium hydride).