CH8: Aldehydes and Ketones-Aldol Reactions Flashcards
What are properties of alpha hydrogens in carbonyl compounds and why
Alpha H are super acidic due to the resonance stabilized enolate anion that forms
What forms during protonation of the enolate anion
It can be protonated at the O or the C forming keto or enol forms. This is tautomerization.
Keto enolate anion enol form
Keto enol tautomers are:
Constitutional isomers, ketones and aldehydes almost always exist in the keto form
What form do beta-dicarbonyl systems primarily exist in and why?
In the enol form due to conjugation
Racemization via enols and enolate anions
An optically active aldehyde or ketone with a stereocenter at the alpha carbon can lead to racemization if in keto form or an achiral molecule in the enol when reacted with acid or base
Base and acid catalyzed racemization
A base is more important…OR- removes H from Alpha carbon forming enolate anion which then gets its O protonated forming an enol
Enols are
achiral
Ketone halogenation
Ketones can be halogenated at the alpha carbon in the presence of acid or base.
Acid-Goes via enol
Base-Goes via enolate anion
Haloform reaction
Reaction of ketone with 3 alpha hydrogens in the presence of excess base
1) Remove H with base
2) Grab X with a carbanion
NO SHIFTING OF O UNTIL HALOFORM IS FORMED
3) Base attacks carbonyl carbon
Haloform
CHX3 + carboxylate anion. Haloform is a good L.G.
What is the Aldol rxn
Ketone + aldehyde via enolate anion. Aldol=Aldehyde and alcohol. It is 2 of an aldehyde or ketone with dilue NaOH
Dehydration of Aldol product
If it is heated with base present, dehydration to an unsaturated Alpha,beta-unsaturated carbonyl compound. It is stabilized because of conjugation.
Alpha, beta-Unsaturated carbonyl compound
From dehydration of an aldol product with heat leading to db in conjugation
How to undo the aldol rxn
Strong base
What does acid catalyzed acid yield
The condensation product. Key step: The db of the enol formed attacks the carbonyl carbon that has been protonated. Goes via the enol.
How mny products can be formed during crossed aldol reactions
4
What are practical crossed aldol reactions
They give predictable reactions when one of the compounds has no alpha hydrogens. The one without any alpha H is put in basic solutions and the one with is added slowly. Dehydration normally occurs immediately.
Claisen-Schmidt reactions
These are crossed aldol reactions in which one of the reactants is a ketone. Ketone self-condensation is not observed…only 1 product.
Cyclization via aldol condensations
Dicarbonyl compounds can react to form 5 or 6 membered rings in the presence of base. The aldehyde is attacked over the carbon. The condensation product forms.
Lithium enolates
In the presence of a strong base such as LDA, enolate formation is greatly favoured
LDA
Strong, sterically hindered base
Regioselective enolates
Unsymmetrical ketones have 2 places to remove alpha H from there can be the kinetic and thermodynamic products.
Thermodynamic enolate
Favoured by using weak base because an eq forms
Kinetic enolate
Favoured with LDA, THF -78degrees
LDA and ketones in crossed aldol
Rxns work best when LDA and aldehyde are added slowly
Direct alkylation of enolates with LDA and SN2
1) LDA forms kinetic enolate
2) SN2 of DB on an alkyl halide
