Aldehydes And Ketones II

Question 1

Alpha Carbon

Answer 1

Any carbon attached to a carbonyl carbon

Question 2

Alpha hydrogen

Answer 2

Hydrogen atoms connected to alpha carbons

Question 3

What quality makes it relatively easy to deprotonate the α-C of an aldehyde or ketone?

Answer 3

• O weakens C-H bonds when it pulls some of the electron density out of the C-H bonds through induction

Question 4

Acidity of α-hydrogens

Answer 4

• acidity is augmented by resonance stabilization of the conjugate base
• when the α-H is removed, the extra electrons that remain can resonate between the α-C, the carbonyl carbon, and the carbonyl oxygen
• this increases the stability of this enolate intermediate
• through this resonance, the negative charge can be distributed to the more electronegative oxygen atom
• the electron-withdrawing oxygen atom helps to stabilize the carbanion (molecule with negatively charged carbon atom)
• when in basic solutions, α-hydrogens will easily deprotonate

Question 5

Key concept: Electron withdrawing and donating groups (stabilization/destabilization)

Answer 5

• electron-withdrawing groups like oxygen stabilize organic anions
• electron-donating groups like alkyl groups destabilize organic anions

Question 6

Are α-H of aldehydes or ketones more acidic?

Answer 6

• α-hydrogens of ketones are slightly less acidic than aldehydes due to electron-donating properties of the additional alkyl group in a ketone
• this property is the same reason that alkyl groups help to stabilize carbocations/destabilize carbanion

Question 7

Are aldehydes or ketones more reactive to nucleophines?

Answer 7

• aldehydes are slightly more reactive because of the additional alkyl group that ketones have (steric hindrance in the ketone which causes a higher-energy, more crowded intermediate step)

Question 8

Due to the acidity of the α-hydrogen, aldehydes and ketones exist in solution as a mixture of which 2 isomers?

Answer 8

1) keto form (C=O)
2) enol form (ene + ol = C=O + -OH group)
- the two isomers differ in the placement of a proton and the double bond are tautomers

Question 9

Tautomers

Answer 9

• isomers that can be interconverted by moving a H and a double bond
• keto and enol forms are tautomers of each other
• not resonance structures because they ahve different connectivity of their atoms

Question 10

Enol

Answer 10

• Presence of a carbon-carbon double bond (en-) and an alcohol (-ol)
• important intermediates in many reactions of aldehydes and ketones

Question 11

Enolate

Answer 11

• intermediate
• stabilized by resonance
• enol+base–>enolate
• enolate carbanion results from the deprotonation of the α-C by a strong base

Question 12

Common strong bases to deprotonate α-C

Answer 12

• hydroxide ion
• lithium diisopropyl amide (LDA)
• potassium hydride (KH)

Question 13

keto-enol tautomerization
enolization/tautomerization

Answer 13

-keto form is preferred
-enols are critical intermediates for aldehydes/ketones reactions
- process of interconverting from the keto to the enol tautomer
- picture: keto: right; enol: left

Question 14

α-racemization

Answer 14

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

Question 15

Why is the 1,3-dicarbonyl often used to form enolate carbanions?

Answer 15

• it is particularly acidic (because of the two carbonyls that delocalize negative charge)
• once formed, the nucleophilic carbanion reacts readily with electrophiles (ex: aldol condensation and Michael addition)

Question 16

Michael addition

Answer 16

• nucleophilic carbanion reacts readily with electrophiles
• carbanion attacks an α,β-unsaturated carbonyl compound (molecule with a multiple bond between α- and β-carbons next to a carbonyl
• proceeds due to the resonance stabilization of the intermediates
  In picture:
  a) base deprotonates the α-carbon, making it a good nucleophile
  b) carbanion attacks the double bond, resulting in a Michael addition

Question 17

Kinetic enolate

Answer 17

• favored by fast, irreversible reactions at lower temperatures with strong, sterically hindered bases
• less stable product
• double bond to less substituted α-hydrogen from the less substituted α-carbon because it has less steric hindrance

Question 18

Thermodynamic enolate

Answer 18

• favored by slower, reversible reactions at higher temperatures with weaker, smaller bases
• more stable
• double bond formed with more substituted α-carbon (formed by the removal of α-hydrogen from the more substituted α-carbon

Question 19

Enol vs enamine

Answer 19

• Enol: tautomer of carbonyl
• Enamine: tautomer of imines

Question 20

Enamine

Answer 20

• formed by a tautomerized imine
• An amino group attached to a carbon that is double-bonded to another carbon.

Question 21

Imine

Answer 21

• A double bond between a carbon and a nitrogen (C=N)
• N in the imine may or may not be bonded to an alkyl group or other substituent
• through tautomerization (movement of a H and double bond), imines can be converted into enamines

Question 22

Enamination (Tautomerization)

Answer 22

Right: imine (thermodynamically favored
Left: enamine

Question 23

Aldol condensation

Answer 23

• aldehyde or ketone acts as both nucleophile (in enolate form) and electrophile (in keto form), resulting in the formation of a C-C bond in a new molecule called an aldol
• same nucleophilic addition reaction seen before with carbonyl compounds–just with the carbonyl-containing compound acting as both a nucleophile and electrophile
• nucleophile: enolate formed from deprotonation of α-H
• electrophile: aldehyde or ketone in the form of the keto tautomer
  1) condenstaion reaction occurs when the two molecules come together
  2) after the aldol is formed, a dehydration reaction (loss of a water molecule) occurs, which results in an α,β-unsaturated carbonyl

Question 24

Aldol

Answer 24

• Contains both aldehyde and alcohol functional groups.

Question 25

Aldol condensation, step 1

Answer 25

• formation of the aldol
• enolate ion is formed, which then attacks the carbonyl carbon, forming an aldol
• in picture: when ethanal is treated with a catalytic amount of base, an enolate ion is produced. The enolate is more nucleophilic than the enol because it is negatively charged; nucleophilic enolate ion can react with the electrophilic carbonyl group of another acetaldehyde (ethanol) molecules; product is an aldol (aldehyde and alcohol groups; keep in mind that it is still an aldol reaction when reactants are ketones)

Question 26

Aldol condensation, step 2

Answer 26

• dehydration of the aldol
• the -OH is removed as water (dehydration), forming a double bond

Question 27

When are aldol condensations most useful

Answer 27

• if we only use one type of aldehyde or ketone
• if there are multiple types, we won’t be able to control what acts as the nucleophile and what acts as the electrophile as well and a mixture of products will result (can be prevented if one of the molecules has no α-hydrogens because the α-carbons are quaternary [like benzadehyde])

Question 28

Why is an aldol condensation both a condensation and dehydration reaction?

Answer 28

• condensation: two molecules are joined with the loss of a small molecule
• dehydration: small molecule lost is water

Question 29

Retro-aldol reaction

Answer 29

• The reverse of an aldol condensation reaction, in which a carbon-carbon bond is cleaved with heat and an aqueous base
• a bond is broken between α- and β-carbons of a carbonyl, forming two aldehydes, two ketones, or one aldehyde and one ketone
• useful in breaking bonds between α- and β-carbons of a carbonyl
• reaction occurs if the intermediate can be stabilized in the enolate form, just as in the forward reaction