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

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

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

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

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

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

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)

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

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

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