1. Ch. 19-20 Lect. 2 Carboxylic Acids and Derivatives
Alkanoyl Halides
Preparation
Inorganic esters utilized, just as in conversion of alcohols to alkyl halides
PBr3, SOCl2 convert carboxylic acids to alkanoyl halides
Nomenclature
Pentanoic acid becomes pentanoyl chloride
Cyclohexane carboxylic acid becomes cyclohexanecarbonyl chloride

2. Reactivity: most reactive and useful derivative
Modified LiAlH4 reagent LiAl[OC(CH3)3]3H required to prevent over-reduction to alcohols
Organocuprates are less reactive alkyl metal reagents to prevent second addition to ketone
Amines do addition-elimination to give amides
Alcohols do addition-elimination to give esters
Acids do addition-elimination to give anhydrides
Water does addition-elimination to give acids

3. Anhydrides Preparation
As just seen, the reaction of an acid and an alkanoyl halide form anhydrides
The –OH group of the acid is a weak nucleophile for the reactive alkanoyl halide
Dehydration of two carboxylic acids can also work if 5-6 membered ring forms
Nomenclature
Replace “acid” with “anhydride” for the components
Acetic anhydride; Butanedioc anhydride
Unsymmetric anhydrides or mixed anhydrides are possible
Reactivity
All the alkanoyl halides reactions work for anhydrides, but are slower
Leaving group is a carboxylate anion, removed by aqueous extraction
Use anhydride as an activated substitute for reactions with carboxylic acids
Acetic propanoic anhydride
Acetic anhydride

4. Esters
Preparation
As seen, alcohols do addition-elimination to alkanoyl halides to give esters
Acid catalyzed addition-elimination of alcohols to carboxylic acids is also useful
Esterification (and Ester Hydrolysis) Mechanism
Intramolecular esterifications give cyclic esters called lactones
Favored for 5-6
membered rings

5. Nomenclature: named as alkyl alkanoates
Reactivity
Ester hydrolysis forms the component alcohol and carboxylic acid
Acid catalyzed reaction is the reverse of esterification shown above
Base catalyzed ester hydrolysis is also possible
Transesterification occurs with alcohols
Acid or base catalyzed conversion of one ester to another
Control the equilibrium by adding a large excess of the new alcohol

6. Ester + Amine + Heat gives Amides (amines are more nucleophilic than alcohols)
Grignard Reagents + Esters give Alcohols
The first reaction is an addition-elimination giving a Ketone product
The Ketone reacts with another Grignard molecule giving the alcohol
Esters can be reduced by hydrides to alcohols or aldehydes
LiAlH4 fully reduced the ester to an alcohol (similar to Grignard above)
DIBAL reduces ester only to an aldehyde
DIBAL = diisobutylaluminum hydride

7. Esters in Nature
Esters are important aroma and flavor agents in natural foods
Isopentyl acetate = banana oil
Octyl acetate = orange oil
Methyl salicylate = oil of wintergreen
Waxes are long chain esters
Beeswax
Spermaciti: sperm whale wax
Fats and Oils = triesters of glycerol (1,2,3-propanetriol)

8. Amides
Preparation
Amines react with carboxylic acids as bases and as nucleophiles
Heating favors the thermodynamic product: amide
Amino acids cyclize to give lactams
Nomenclature: alkanamides or cycloalkanecarboxamides
Kinetic product
Thermodynamic product

9. Reactivity: least reactive of the carboxylic acid derivatives
Resonance structures prevent rotation around C—N bond
Ea = 21 kcal/mol for rotation about this single bond
Two peaks seen in the proton NMR
Hydrolysis requires heat and concentrated acid or base
Proteins are held together by strong amide bonds; they don’t break easily
Reduction to Amine by LiAlH4

10. Alkanenitriles Preparation: SN1 or SN2 reaction of haloalkanes
Nomenclature
Alkanenitriles or cycloalkanenitriles
Reactivity: synthesis of carboxylic acids
Acid catalyzed mechanism
Similar Base catalyzed mechanism
Adds one carbon to the haloalkane, then turns it into carboxylic acid
Make derivatives from there; take advantage of all of their reactions