Ch 17 Aldehyde and Ketone Reactions I.Addition Reactions to Carbonyls A.Hydration can be Acid or Base Catalyzed 1)General Hydration Reaction 2)Base Catalyzed Mechanism 3)Acid Catalyzed Mechanism

4.Hydrations are reversible 1.K < 1 for ketones 2.K > 1 for formaldehyde and aldehydes with inductive accepting groups 3.K = 1 for unsubstituted aldehydes 4.Donating R groups of Ketones stabilize the carbonyl form 5.Accepting groups destabilize the carbonyl, which favors alcohol formation 6.This same trend will hold for other XY addition reactions

B.Addition of Alcohols 1.ROH adds to carbonyls to give Hemiacetals 2.This reaction can be acid or base catalyzed 3.A Hemiacetal has an –OH and and –OR group on the same carbon 4.Only reactive carbonyls (those with accepting substitutents or formaldehyde) give a reasonable amount of the hemiacetal 5.Strain-free 5- and 6-membered cyclic hemiacetals are common and stable

6.Acids Catalyze Acetal Formation a)An acetal has 2 –OR groups on the same carbon b)General acetal formation reaction: c)Mechanism d)All steps are reversible e)We can shift the equilibrium position towards the acetal by adding excess R’OH or by removing H 2 O during the reaction

C.Use of Acetals as Protecting Groups for Carbonyls 1.Acetals are relatively unreactive ether functional groups 2.To protect a reactive carbonyl group from a reaction you want to do on another part of the molecule (ex: Grignard Rxn) we can make it an acetal 3.Cyclic Acetals are more stable than acyclic ones a)Entropy disfavors normal acetal formation (3 particles  2 particles) b)Entropy doesn’t disfavor cyclic acetals (2 particles  2 particles) 4.Removing the protecting acetal group is achieved easily by adding H +

5.A carbonyl compound can also be used to protect a diol 6.Thioacetals are even stronger protecting groups than acetals a)Thioacetals are stable to acid b)A thioacetal is formed in the presence of ZnCl 2 c)The dithio protecting group can be removed with HgCl 2. The product Hg(SCH 2 CH 2 S) precipitates.

d)Thioacetals can be Desulfurized by Raney Ni, H 2. This is a very effective way to remove a carbonyl oxygen. D.Addition of Substituted Amines to Carbonyl Groups 1.Imine (Schiff Base) Formation a)An amine adds to a carbonyl to form a hemiaminal b)The hemiaminal quickly loses H 2 O to form an Imine or Schiff Base c)Condensation = reaction where 2 molecules are joined and H 2 O is lost

d)Primary Amine is needed, and will react with an aldehyde or ketone 2.Special Imines aid in the identification of carbonyls a)These imines are well characterized solid derivatives of the carbonyl b)The melting points are known and can be used in identification c)Oximes d)Hydrazones

e)Semicarbazones 3.Secondary Amines form Enamines with carbonyls a)The nitrogen can’t form a double bond to the carbonyl carbon because it would then be quaternary and (+1) charged b)H is lost from C, not from N as in the primary amine case II.Deoxygenation of Carbonyl Groups

A.Review 1)Clemmenson Reduction 2)Thioacetal Formation and Reduction B.Wolff-Kishner Reduction 1)Strong base converts hydrazones to hydrocarbons 2)Usual conditions: 1. H 2 NNH 2, H 2 O, diethylene glycol (high boiling point alcohol) NaOH, Heat. 2. Water (Don’t isolate the hydrazone)

3)Mechanism 4)Wolff-Kishner doesn’t affect acid sensitive groups (like Clemmenson does) or double bonds (like thioacetal does). III.Addition of Carbon Nucleophiles to Carbonyls A.Review: Alkyl Metal reagents add to carbonyls

B.Cyanohydrins 1.Hydrogen Cyanide (HCN) reversibly adds to carbonyls a)HCN is very toxic b)Formation in situ by H + addition to NaCN or HCN is safer c)Example reactions: 2.Mechanism 3.The reaction is reversed by adding base

C.The Wittig Reaction 1.Phosphorous Ylide is a stabilized carbanion 2.A Carbonyl plus an Ylide forms an alkene

3.Wittig-formed alkenes are unambiguous a)Wittig b)Elimination 4.Mechanism

5.Sometimes you do get mixtures of E/Z isomers 6.This reaction has no effect on many other functional groups: ethers, esters, halogens, alkenes, alkynes IV.Oxidation of Carbonyls A.Baeyer-Villiger Oxidation 1)Ketones + Peroxycarboxylic Acids give Esters 2)Mechanism 3)Cyclic Ketone will give a cyclic ester product 4)Double bonds are unaffected 5)Unsymmetric Ketones lead to only one product: some groups migrate more easily than others = Migratory Aptitude

6.Migratory Aptitudes: Methyl < primary < phenyl ~ secondary < cyclohexyl < tertiary B.Oxidation Tests for Aldehydes 1.Fehling’s Test 2.Tollens’s Test