Finish Briefly from Chapter 16

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

II.  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 Hydrogen Cyanide

V.  Reactions with a Hydride Donor (reduction)
    A.  LiAlH4 will reduce esters, carboxylic acids and acyl chlorides to alcohols.
        1.  In the reduction, the first step is an aldehyde.
        2.  The reaction can be stopped at the aldehyde if diisobutyl aluminum hydride is used.
    B.  LiAlH4 will convert an amide to an amine. (carbonyl group to methylene)

VI.  Addition of Nitrogen Nucleophiles to Aldehydes and Ketones
    A.  With primary amines product is an imine ( carbon-nitrogen double bond)
        1.  carbonyl compound and a primary amine is a Schiff base
        2.  carbonyl compound and a hydroxylamine (NH2OH) is an oxime
        3.  carbonyl compound and a hydrazine (NH2NH2)is a hydrazone
        4.  carbonyl compound and a semicarbazide (H2NNHCONH2) is a semicarbazone
    B.  Mechanism
        1.  Aldehydes and ketones undergo nucleophilic addition reaction with carbon and hydrogen nucleophiles
        2.  Aldehydes and ketones undergo nucleophilic addition-elimination (H2O) with nitrogen nucleophiles
        3.  Imine formation is a reversible reaction, pH controlled, and important in biological systems
    C.  With secondary amines enamines (alpha-beta unsaturated tertiary amine) are formed.
    D.  Imines and enamines can be reduced by reductive amination to secondary and tertiary amines
    E.  Wolf-Kishner Reduction:  an aldehyde and ketone is converted to a methylene group if heated in a basic solution of hydrazine.

VII.  Addition of Oxygen Nucleophiles to Aldehydes and Ketones
    A.  Addition of Water
        1. slow, should be acid catalyzed
        2. hydrate (gem diol) is formed
        3. % of hydrate at equilibrium depends on electronic and steric effects
    B.  Addition of Alcohol
        1.  with an aldehyde a hemiacetal (1 equiv.) or acetal (2 equi.) is formed
        2.  with a ketone a hemiketal or ketal is formed
        3.  rate is increased by acid catalysis
        4.  product is increased by the removal of water
    C.  Protecting Group

VII.  Addition of Sulfur Nucleophiles
    A.  Aldehydes form thioacetals and ketones form thioketals
    B.  Thioacetals and thioketals are desulfurized with H2 and Rainey Nickel.
    C.  Three ways of converting a carbonyl to a methylene:  1.  the reaction above, 2.  the Wolfe-Kishner, 3.  the Clemenson Reduction (Zn(Hg), HCL)

VIII.  The Wittig Reaction:  a reaction of an aldehyde or ketone with phosphonium ylide to form an alkene.
    A.  The phosphonium ylide is obtained by an SN2 reaction between triphenylphosphine and an alkyl halide.
    B.  Regioselective and Stereoselective

IX.  Designing the Synthesis of Cyclic Compounds

X.  Addition to alpha-beta-unsaturated aldehydes and ketones