Ch 23 - Substitution Rxns of Carbonyl Compds At Alpha C

Question 0

Tautomerization between keto form & enol form of carbonyl group:

Steps in acid? In base?

Answer 0

Acid: protonate carbonyl O, deprotonate alpha C

Base: deprotonate alpha C, protonate carbonyl O

Question 1

Rxns at alpha C to carbonyl C:

Rxt w/?
Results in?

Answer 1

Rxts w/enols or enolates

➡ Substitution of electrophile for a H

Question 2

How are enolates formed?

Answer 2

Base removes H on alpha C

Question 3

General rxn of enolates?

Answer 3

Rxt as nucleophiles:
• electron pair on alpha C attacks electrophile
• Overall: H on alpha C replaced by E+

Question 5

What is a beta-dicarbonyl?

Answer 5

2 C=O separated by one C

Question 6

What is the kinetic enolate? How is it formed?

Answer 6

• Less sub, formed faster

* formed w/ nonnucleophilic base in polar aprotic solvent, low temp (LDA/THF)

Question 7

What is the thermodynamic enolate? How is it formed?

Answer 7

• More sub, ⬇ in energy

* formed w/strong base in polar solvent, high temp (-OR/ROH)

Question 8

What happens if alpha C is a stereogenic ctr?

Answer 8

Forms achiral enolate ➡ equal amt of 2 enantiomers

Question 9

Rxn of ketone/aldehyde w/X2 and acid or base ➡ ?

Answer 9

Substitution of X for H on alpha C = alpha-halo aldehyde/ketone

Question 10

Halogenation of aldehydes/ketones in acid, main mechanism (4)?

Answer 10

Part 1: tautomerization ➡ enol

Part 2: double bond picks up one X & form C=OH, X- deprotonates carbonyl O

Question 11

Halogenation of aldehydes/ketones in base, main mechanism?

Answer 11

1) deprotonation ➡ enolate
2) enolate picks up one X
Repeat 1 + 2 ➡ multiple Halogenation

Question 12

Halogenation of methyl ketone ➡ ?

Answer 12

Carboxylate anion & haloform (HCX3)

Question 13

General rxn of enolate alkylation?

Answer 13

1) LDA/THF, low temp ➡ enolate

2) enolate attacks R-X

Question 14

Stereochemistry of alkylation of enolates?

Answer 14

Symmetrical carbonyl or nitrile ➡ achiral product or chiral product in racemic mix of 2 enantiomers

Question 15

How are unsymmetrical ketones regioselectively alkylated?

Answer 15

1) alkylate on less sub alpha C: use LDA/THF, low temp ➡ kinetic enolate, alkylate
2) alkylate on more sub alpha C: use -OR/ ROH, higher temp ➡ thermodynamic enolate, alkylate

Question 16

Malonic ester synthesis ➡?

Answer 16

Alpha-sub carboxylic acids

Question 17

Main parts of mechanism for malonic ester synthesis?

Answer 17

1) SM = CH2(CO2Et) (diethyl malonate): use NaOEt ➡ enolate
2) alkylate enolate w/RX ➡ ester
3) hydride ester with H3O+, heat ➡ beta-diacid + 2EtOH
4) beta-diacid lose CO2 with heat ➡ carboxylic acid

Question 18

What base ➡ formation of high amt of enolate?

Answer 18

H:-
-NH2
-NR2
LDA (strong, nonnucleophilic)

Question 19

Main parts of mechanism for Acetoacetic ester synthesis?

Answer 19

1) SM = ethyl acetoacetate CH3(CO)CH2CO2Et: use NaOEt ➡ enolate
2) alkylate enolate w/RX ➡ ester
3) hydrolyze ester w/acid, heat ➡ beta-keto acid
4) decarboxylate beta-keto acid ➡ ketone

Question 20

Acetoacetic ester synthesis ➡ ?

Answer 20

Alpha-sub ketones