双语有机化学 aldol reaction

1、Chapter 17 Aldehydes and Ketones II. Aldol Reactions17.1 The acidity of the -hydrogens of carbonyl compounds: enolate anions.17.2 Keto and enol tautomersInterconvertible keto and enol forms are said to be tautomers, and their interconversion is called tautomerization.17.3 Reactions via enols and eno

2、late anions17.3.1 Racemization:Mechanism of acid catalysed enolization:Base catalyzes the formation of an enol through the intermediate formation of an enolate anion:-amino acids do not racemize in aqueous acid or base.17.3.2 Halogenation of ketones:17.3.2.1 Acid-catalysed halogenation:Mechanism:Aci

3、d-catalysed halogenation can be made to stop after one halogen is introduced if only one equivalent of halogen is used.17.3.2 Base-promoted halogenation of aldehydes and ketones.17.3.3 the Haloform reaction:Regioselectivity:Iodoform reaction:17.4 The aldol reaction: the addition of enolate anions to

4、 aldehydes and ketones.Mechanism:Depending on reaction conditions and the structure of reagents, based-catalysed aldol reaction give either addition product or condensation product.Dehydration is easier in acid solution.The reversibility of Aldol Addition.Mechanism:Synthetic applications of the aldo

5、l reaction.17.5 Crossed aldol reactions17.5A Practical crossed Aldol reaction:One reactant ONLY must be capable of eolization;1) 2) The other reactant must be incapable of enolization and be MORE electrophilic than the enolizable reactant.17.5B Claisen-Schmidt reactionsWhen ketones are used as one c

6、omponent, the crossed aldol reactions are called claisen-Schmidt reactions.Vitamin AThe Cannizzaro reaction.Aldol reactionCannizzaro reaction: disproportionation of two molecules of aldehyde to one of carboxylate and one of alcohol.The Cannizzaro reaction works only with unenolizable aldehydes.The M

7、annich reaction.Mechanism:The Mannich products can be converted to enones.17.5C Condensations with Nitroalkanes.Nitroalkenes as termite defence compounds.17.6 cyclizations via aldol condensationsSymmetrical diketones:Unsymmetrical diketones:90% yieldAn alternative cyclization to give a six-membered

8、ring:Thermodynamic productKinetic product*The aldol addition is reversible.17.7 Controlling aldol reactions with specific enol equivalents.Specific enol equivalents: Internediates that still have the reactivity of enols or enolates but are stable enough to be prepared in good yield from the carbonyl

9、 compound without any aldol reaction.17.7.1 Lithium enolatesLDA: lithium diisopropylamide Regioselective formation of enolate anions.Lithium enolates in aldol reactionsSix-membered ring mechanismZimmerman-TraxlermodelLithium enolates in directed aldol reactionsHard electrophiles react at oxygen,soft

10、 electrophiles react at carbon.Alkylations of lithium enolates17.7.2 Silyl enol ethersMechanism17.7.3 EnaminesThe choice of secondary amine for formation of the enamine is not completely arbitary even though it does not end up in the final alkylated product.The ring structure makes both the starting

11、 amine and the enamine more nucleophilic.ii) The higher boiling points of these amines allow the enamine to be formed by heating.Stork enamineRegioselective formation of enamineExample17.8 -Selenation: A synthesis of ,-unsaturated carbonyl compounds17.9 Additions to ,-unsaturated aldehydes and keton

12、esconjugate additionAlkenes conjugated with carbonyl groups are polarizedA wrong representation of conjugationPolarization is detectable spectroscopicallyAmmonia and amines undergo conjugate additionConjugation addition VS direction additioni) Reaction conditionsii) Structural factorsiii) Nature of nucleophile: hard and softHard nucleophiles (HO- , NH3, RMgBr, F-, etc) tend to react at the carbonyl carbon (hard) of an enone;Soft nucleophiles (RS-, I-, R3P, RCu, etc) tend to react at th