1. Ch. 19-20 Lect. 2 Carboxylic Acids and Derivatives I.Alkanoyl Halides A.Preparation 1)Inorganic esters utilized, just as in conversion of alcohols to alkyl halides 2)PBr 3, SOCl 2 convert carboxylic acids to alkanoyl halides B.Nomenclature 1)Pentanoic acid becomes pentanoyl chloride 2)Cyclohexane carboxylic acid becomes cyclohexanecarbonyl chloride

2. C.Reactivity: most reactive and useful derivative 1.Modified LiAlH 4 reagent LiAl[OC(CH 3 ) 3 ] 3 H required to prevent over-reduction to alcohols 2.Organocuprates are less reactive alkyl metal reagents to prevent second addition to ketone 3.Amines do addition-elimination to give amides 4.Alcohols do addition-elimination to give esters 5.Acids do addition-elimination to give anhydrides 6.Water does addition-elimination to give acids

3. II.Anhydrides A.Preparation 1)As just seen, the reaction of an acid and an alkanoyl halide form anhydrides 2)The –OH group of the acid is a weak nucleophile for the reactive alkanoyl halide 3)Dehydration of two carboxylic acids can also work if 5-6 membered ring forms B.Nomenclature 1)Replace “acid” with “anhydride” for the components 2)Acetic anhydride; Butanedioc anhydride 3)Unsymmetric anhydrides or mixed anhydrides are possible C.Reactivity 1)All the alkanoyl halides reactions work for anhydrides, but are slower 2)Leaving group is a carboxylate anion, removed by aqueous extraction 3)Use anhydride as an activated substitute for reactions with carboxylic acids Acetic propanoic anhydride Acetic anhydride

4. III.Esters A.Preparation 1)As seen, alcohols do addition-elimination to alkanoyl halides to give esters 2)Acid catalyzed addition-elimination of alcohols to carboxylic acids is also useful 3)Esterification (and Ester Hydrolysis) Mechanism 4)Intramolecular esterifications give cyclic esters called lactones Favored for 5-6 membered rings

5. B.Nomenclature: named as alkyl alkanoates C.Reactivity 1.Ester hydrolysis forms the component alcohol and carboxylic acid a.Acid catalyzed reaction is the reverse of esterification shown above b.Base catalyzed ester hydrolysis is also possible 2.Transesterification occurs with alcohols a.Acid or base catalyzed conversion of one ester to another b.Control the equilibrium by adding a large excess of the new alcohol

6. 3.Ester + Amine + Heat gives Amides (amines are more nucleophilic than alcohols) 4.Grignard Reagents + Esters give Alcohols a.The first reaction is an addition-elimination giving a Ketone product b.The Ketone reacts with another Grignard molecule giving the alcohol 5.Esters can be reduced by hydrides to alcohols or aldehydes a.LiAlH 4 fully reduced the ester to an alcohol (similar to Grignard above) b.DIBAL reduces ester only to an aldehyde DIBAL = diisobutylaluminum hydride

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

8. IV.Amides A.Preparation 1)Amines react with carboxylic acids as bases and as nucleophiles 2)Heating favors the thermodynamic product: amide 3)Amino acids cyclize to give lactams B.Nomenclature: alkanamides or cycloalkanecarboxamides Kinetic product Thermodynamic product

9. C.Reactivity: least reactive of the carboxylic acid derivatives 1.Resonance structures prevent rotation around C—N bond a.E a = 21 kcal/mol for rotation about this single bond b.Two peaks seen in the proton NMR 2.Hydrolysis requires heat and concentrated acid or base a.Proteins are held together by strong amide bonds; they don’t break easily 3.Reduction to Amine by LiAlH 4

10. V.Alkanenitriles A.Preparation: S N 1 or S N 2 reaction of haloalkanes B.Nomenclature 1)Alkanenitriles or cycloalkanenitriles C.Reactivity: synthesis of carboxylic acids 1)Acid catalyzed mechanism 2)Similar Base catalyzed mechanism 3)Adds one carbon to the haloalkane, then turns it into carboxylic acid 4)Make derivatives from there; take advantage of all of their reactions