Chapter 16

I.  Reaction of Acyl Halides
    A.  Most reactive, will form all other carboxylic acid derivatives.
    B.  Reaction with ammonia and primary and secondary amines must be carried out with two equivalents.

II.  Reactions of Acid Anhydrides
    A.  No reaction with chloride ion.
    B.  Will react with an alcohol, water, and amines.

III.  Reaction of Esters
    A.  Slow reaction with water:  hydrolysis, slow reaction with an alcohol:  transesterification.
        1.  Must be acid catalyzed or base enhanced.
        2.  Equilibrium reaction can be driven to the right by adding more reactant.
    B.  Reaction with amines, only one equivalent is required
    C.  Mechanism of Acid-Catalyzed Ester Hydrolysis
        1.  The carbonyl oxygen is protonated, the nucleophile, water, attacks the protonated carbonyl group.  The resulting protonated tetrahedral intermediate is in equilibrium with the nonprotonated form.  The -OH or the -OR can be protonated and lost, resulting in the carboxylic acid or the original ester.
        2.  The H+ increases the rate of formation of the tetrahedral intermediate, because the protonation of the carbonyl carbon increases the susceptibility of a nucleophilic attack.  The H+ increases the rate of collapse of the tetrahedral intermediate by decreasing the basicity of the leaving group.
    D.  Hydroxide-ion promoted ester hydrolysis
        1.  Hydroxide ion increases the rate of formation of the tetrahedral intermediate because HO- is a better nucleophile.  HO- ion also increases the rate of collapse, because a smaller fraction of the negative tetrahedral intermediate become protonated.
        2.  The final product is a carboxylate rather than a carboxylic acid.  The carboxylate ion is not attacked by a nucleophile, thus the reaction is not reversible.
        3.  Studies with O18 proves the existence of the tetrahedral intermediate.

IV.  Reaction of Carboxylic acids.
    A.  Fischer esterification, acid catalyzed equilibrium reaction.
    B.  Reaction with amines, acid-base reaction at room temperature, with heat amides are formed.
    C.  The carboxylate form very unreactive.

V.  Reactions of Amides
    A.  Very unreactive
        1.  Will react with water in the presence of acid or base and heat.
        2.  Will react with alcohol with acid and heat
        3.  Will react with dehydration reagents, P2O5, POCl3, SOCl2, to form nitriles.
    B.  Mechanism of acid-catalyzed and base promoted hydrolysis of amides.
        1.  H+ catalyzes the nucleophilic attack and decreases the basicity of the leaving group.
        2.  OH- increases the rate of nucleophilic attack.  If an occasional NH2- group leaves, it immediately deprotonates the carboxylic acid, driving the equilibrium to the right.

VI.  The Gabriel Synthesis of Primary Amines

VII.  Hydrolysis of Nitriles

VIII.  Soaps, detergents, and Micelles

IX.  Activation of carboxylic acids in the laboratory and in biological systems

X.  Dicarboxylic acid derivatives

Chapter 17, Carbonyl Compounds II

I.  Nomenclature
    A.  Aldehydes
        1.  "al" and carbaldehyde
        2.  formyl group
    B.  Ketones
        1.  "one"
        2.  oxo group
    C.  Order of priority:  carboxylic acid (carboxy), ester (alkoxycarbonyl), amide (amido), nitrile (cyano), aldehyde (formyl), ketone (oxo), alcohol (hydroxy), amine (amino), alkene (alkenyl), alkyne (alkynyl), alkane (alkyl), ether (alkoxy), alkyl halide (halo).

II.  Relative Reactivities of Carbonyl Compounds
    A.  formaldehyde, aldehyde, ketone
    B.  Steric Hindrance impede reactivity
    C.  most reactive:  acyl halide, acid anhydride, aldehyde, ketone, ester ~ carboxylic acid, amide least reactive

III.  Nucleophilic Addition Reactions
    A.  After the nucleophilic attack on the carbonyl carbon, an alkoxide ion is formed that can be protonated by the solvent.
    B.  Reaction can be acid catalyzed.
    C.  Nucleophilic addition-elimination may be possible

IV.  Additions of Carbon Nucleophiles, formation of a C-C bond.
    A.  Grignard, like the reaction in lab.
    B.  Addition of Acetylide ion.
    C.  Addition of Hydroden Cyanide