Ch. 7: Aldehydes and Ketones II: Enolates Flashcards
defn: alpha-carbon
defn: alpha-hydrogens
alpha-carbon = adjacent to the carbonyl carbon
alpha-hydrogens = the hydrogens connected to the alpha carbon
why is it relatively easy to deprotonate the alpha-carbon of an aldehyde or ketone?
through induction, oxygen pulls some of the electron density out of the C-H bonds of the alpha-C and alpha-H, weakening them
how is the acidity of alpha-hydrogen augmented by resonance stabilization of the conjugate base?
when the alpha-hydrogen is removed, the extra electrons that remain can resonate between the alpha-carbon, the carbonyl carbon, and the carbonyl oxygen
this increases the stability of the enolate intermediate
through this resonance, the negative charge can be distributed to the more electronegative oxygen atom. the electron-withdrawing oxygen atom thereby helps stabilize the carbanion
defn: carbanion
a molecule with a negatively charged carbon atom
effect on stability: electron-withdrawing and electron-donating groups
electron-withdrawing groups like oxygen stabilize organic anions
electron-donating groups like alkyl groups destabilize organic anions
why do the alpha-hydrogens of ketones tend to be slightly less acidic than those of aldehydes?
what other effect does this property have?
due to the electron-donating properties of the additional alkyl group in a ketone
this is the same reason that alkyl groups help to stabilize carbocations, but in this case they destabilize the carbanion
why are aldehydes slightly more reactive to nucleophiles than ketones in reactions?
in part: steric hindrance in the ketone, which arises from the additional alkyl group that ketones contain
when the nucleophile approaches the ketone or aldehyde in order to react, the additional alkyl groups on the ketone are in the way, more so than the single hydrogen of the aldehyde
this makes for a higher-energy, more crowded intermediate step
where does the enol form get its name?
en- = the presence of a carbon-carbon double bond
-ol = the presence of an alcohol
defn: tautomers
the two isomers (keto and enol) which differ in the placement of a proton and the double bond
to which side does the equilibrium between the tautomers lie?
far to the keto side, so there will be many more keto isomers in solution
defn + difference: tautomerization or enolization
the process of interconverting from the keto to the enol tautomer
tautomerization is more general
defn: alpha-racemization
any aldehyde or ketone with a chiral alpha-carbon will rapidly become a racemic mixture as the keto and enol forms interconvert
what does the enolate carbanion result from?
from the deprotonation of the alpha-carbon by a strong base
what are 3 common strong bases?
- the hydroxide ion
- LDA (lithium diisopropyl amide)
- KH (potassium hydride)
why is a 1,3-dicarbonyl often used to form enolate carbanions?
because it is particularly acidic because there are two carbonyls to delocalize negative charge
defn + steps: Michael addition
the carbanion attacks an alpha-beta-unsaturated carbonyl compound (a molecule with a multiple bond between the alpha- and beta-carbons next to a carbonyl)
- the base deprotonates the alpha-carbon, making it a good nucleophile
- the carbanion attacks the double bond, resulting in a Michael addition
why can two forms of a ketone enolate form? what are the two forms?
a ketone has two different alkyl groups each of which may have alpha hydrogens
so two forms of the enolate can form: with the carbon-carbon double bond between the carbonyl carbon and either the more or less substituted carbon
what is the equilibrium between the enolate forms determined by?
it is dictated by the kinetic and thermodynamic control of the reaction
explain the kinetically controlled enolate
does it form quickly or slowly?
is it stable or unstable?
does it have a double bond with the more or less substituted alpha carbon?
how does it form?
formed more rapidly, but less stable
has the double bond to the less substituted alpha-C
formed by the removal of the alpha-H from the less-substituted alpha-C because it offers less steric hindrance
explain the thermodynamically controlled enolate
does it form quickly or slowly?
is it stable or unstable?
does it have a double bond with the more or less substituted alpha carbon?
how does it form?
formed more slowly, but is more stable
the double bond is formed with the more substituted alpha-C
formed by the removal of the alpha-H from the more substituted alpha-C
what conditions favor the kinetic enolate? what conditions favor the thermodynamic enolate?
KINETIC –> favored in rapid, irreversible, lower temperature reactions with a strong, sterically hindered base
THERMODYNAMIC –> higher temperature, slow, reversible reactions, and weaker, smaller bases
if the reaction is reversible what can happen to the kinetic product?
it can revert to the original reactant and react again to form the thermodynamic product
enol is to carbonyl as enamine is to …
imine
defn: imine
a compound that contains a C=N bond
the N may or may not be bonded to an alkyl group or other substitutent
how can imines be converted to enamines?
through tautomerization (movement of a H and a double bond)
which form is thermodynamically favored: imine or enamine?
imine!
basic mechanism + difference + result: aldol condensation
- follows same general mechanism of nucleophilic addition to a carbonyl as previously described
- however, an aldehyde or ketone acts as both an electrophile (in its keto form) and a nucleophile (in its enolate form), and the end result is the formation of a carbon-carbon bond
walk through the actual steps of aldol condensation?
- FORM THE ALDOL –> when for ex, an aldehyde is treated with a catalytic amount of base, an enolate ion is formed, which then attacks the carbonyl carbon, forming an aldol
This nucleophilic enolate ion can react with the electrophilic carbonyl group of another acetaldehyde molecule The key is that both species are in the same flask
- DEHYDRATION OF THE ALDOL –> with a strong base and high temps, dehydration occurs by an E1 or E2 mechanism (we kick off a water molecule and form a double bond, producing an alpha-beta-unsaturated carbonyl)
The -OH is removed as water, forming a double bond
what is an aldol?
contains both ALDehyde and alcohOL funcitonal groups
is the reaction still called an aldol reaction when the reactants are ketones?
yes
when are aldol condensations most useful?
if we only use one type of aldehyde or ketone
why is using multiple aldehydes or ketones bad?
is there any way to prevent that?
we cannot easily control which will act as the nucleophile and which will act as the electrophile, and a mixture of the products will result
can be prevented if one of the molecules has no alpha-H because the alpha-C are quarternary
why is the aldol condensation called a condensation?
why is it also a dehydration reaction?
CONDENSATION: because two molecules are joined with the loss of a small molecule
DEHYDRATION: because the small molecule that is lost is water
defn + how does this occur: retro-aldol reaction
the reverse of an aldol condensation
to push the reaction to a retro-aldol direction, aqueous base is added and heat is applied
what is a retro-aldol reaction useful for?
breaking bonds between the alpha and beta carbons of a carbonyl
what facilitates a retro-aldol reaction?
if the intermediate can be stabilized in the enolate form