Ch. 7: Aldehydes and Ketones II: Enolates

Question 1

defn: alpha-carbon

defn: alpha-hydrogens

Answer 1

alpha-carbon = adjacent to the carbonyl carbon

alpha-hydrogens = the hydrogens connected to the alpha carbon

Question 2

why is it relatively easy to deprotonate the alpha-carbon of an aldehyde or ketone?

Answer 2

through induction, oxygen pulls some of the electron density out of the C-H bonds of the alpha-C and alpha-H, weakening them

Question 3

how is the acidity of alpha-hydrogen augmented by resonance stabilization of the conjugate base?

Answer 3

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

Question 4

defn: carbanion

Answer 4

a molecule with a negatively charged carbon atom

Question 5

effect on stability: electron-withdrawing and electron-donating groups

Answer 5

electron-withdrawing groups like oxygen stabilize organic anions

electron-donating groups like alkyl groups destabilize organic anions

Question 6

why do the alpha-hydrogens of ketones tend to be slightly less acidic than those of aldehydes?

what other effect does this property have?

Answer 6

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

Question 7

why are aldehydes slightly more reactive to nucleophiles than ketones in reactions?

Answer 7

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

Question 8

where does the enol form get its name?

Answer 8

en- = the presence of a carbon-carbon double bond

-ol = the presence of an alcohol

Question 9

defn: tautomers

Answer 9

the two isomers (keto and enol) which differ in the placement of a proton and the double bond

Question 10

to which side does the equilibrium between the tautomers lie?

Answer 10

far to the keto side, so there will be many more keto isomers in solution

Question 11

defn + difference: tautomerization or enolization

Answer 11

the process of interconverting from the keto to the enol tautomer

tautomerization is more general

Question 12

defn: alpha-racemization

Answer 12

any aldehyde or ketone with a chiral alpha-carbon will rapidly become a racemic mixture as the keto and enol forms interconvert

Question 13

what does the enolate carbanion result from?

Answer 13

from the deprotonation of the alpha-carbon by a strong base

Question 14

what are 3 common strong bases?

Answer 14

1. the hydroxide ion
2. LDA (lithium diisopropyl amide)
3. KH (potassium hydride)

Question 15

why is a 1,3-dicarbonyl often used to form enolate carbanions?

Answer 15

because it is particularly acidic because there are two carbonyls to delocalize negative charge

Question 16

defn + steps: Michael addition

Answer 16

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)

1. the base deprotonates the alpha-carbon, making it a good nucleophile
2. the carbanion attacks the double bond, resulting in a Michael addition

Question 17

why can two forms of a ketone enolate form? what are the two forms?

Answer 17

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

Question 18

what is the equilibrium between the enolate forms determined by?

Answer 18

it is dictated by the kinetic and thermodynamic control of the reaction

Question 19

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?

Answer 19

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

Question 20

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?

Answer 20

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

Question 21

what conditions favor the kinetic enolate? what conditions favor the thermodynamic enolate?

Answer 21

KINETIC –> favored in rapid, irreversible, lower temperature reactions with a strong, sterically hindered base

THERMODYNAMIC –> higher temperature, slow, reversible reactions, and weaker, smaller bases

Question 22

if the reaction is reversible what can happen to the kinetic product?

Answer 22

it can revert to the original reactant and react again to form the thermodynamic product

Question 23

enol is to carbonyl as enamine is to …

Answer 23

imine

Question 24

defn: imine

Answer 24

a compound that contains a C=N bond

the N may or may not be bonded to an alkyl group or other substitutent

Question 25

how can imines be converted to enamines?

Answer 25

through tautomerization (movement of a H and a double bond)

Question 26

which form is thermodynamically favored: imine or enamine?

Answer 26

imine!

Question 27

basic mechanism + difference + result: aldol condensation

Answer 27

1. follows same general mechanism of nucleophilic addition to a carbonyl as previously described
2. 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

Question 28

walk through the actual steps of aldol condensation?

Answer 28

1. 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

2. 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

Question 29

what is an aldol?

Answer 29

contains both ALDehyde and alcohOL funcitonal groups

Question 30

is the reaction still called an aldol reaction when the reactants are ketones?

Answer 30

yes

Question 31

when are aldol condensations most useful?

Answer 31

if we only use one type of aldehyde or ketone

Question 32

why is using multiple aldehydes or ketones bad?

is there any way to prevent that?

Answer 32

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

Question 33

why is the aldol condensation called a condensation?

why is it also a dehydration reaction?

Answer 33

CONDENSATION: because two molecules are joined with the loss of a small molecule

DEHYDRATION: because the small molecule that is lost is water

Question 34

defn + how does this occur: retro-aldol reaction

Answer 34

the reverse of an aldol condensation

to push the reaction to a retro-aldol direction, aqueous base is added and heat is applied

Question 35

what is a retro-aldol reaction useful for?

Answer 35

breaking bonds between the alpha and beta carbons of a carbonyl

Question 36

what facilitates a retro-aldol reaction?

Answer 36

if the intermediate can be stabilized in the enolate form