Ch 24 - Carbonyl Condensation Rxns

Question 0

3 main steps of aldol rxn?

Answer 0

1) deprotonate alpha C w/base ➡ enolate
2) enolate attacks 2nd carbonyl (nuc addn)
3) protonate O on beta C (former carbonyl O of 2nd carbonyl)

Question 1

General rxn of aldol rxn?

Answer 1

• 2 aldehydes/ketones rxt w/each other in base ➡ beta-hydroxy carbonyl compd
• nuc addition of enolate (nucleophile) to aldehyde/ketone

Question 2

Dehydration of aldol ➡ ?

Answer 2

Alpha,beta-unsaturated carbonyl compd (C=C bet alpha & beta C)

Question 3

General mechanism for dehydration of aldol in base?

Answer 3

1) deprotonate alpha C w/base ➡ enolate
2) form C=C w/enolate C, elim of LG (-OH)
“E1CB”

Question 4

When is crossed aldol rxn (use of 2 diff carbonyls) useful?

Answer 4

1) when only one of the carbonyl compds has an alpha H

2) when one carbonyl compd has very acidic H’s (Y-CH2-Z, Y,Z = C=O or nitrile)

Question 5

Aldol rxn w/? ➡ 5 membered ring

Answer 5

1,4-dicarbonyl compd (CH2CH2 bet two C=O)

Question 6

Aldol rxn w/? ➡ 6 membered ring

Answer 6

1,5-dicarbonyl compd

(CH2)3 bet 2 C=O

Question 8

General rxn of Claisen rxn?

Answer 8

• 2 esters rxt w/each other in alkoxide base ➡ beta-keto ester
• nuc sub of OEt w/enolate

Question 9

Mechanism of Claisen rxn?

Answer 9

1) -OEt deprotonates alpha C ➡ enolate
2) enolate attacks carbonyl C of 2nd ester (nuc addn)
3) elim of LG (-OEt)
4) deprotonate CH2 between 2 C=O ➡ enolate (drives equilibrium)
5) protonate enolate w/acid

Question 10

When is crossed Claisen rxn (two diff carbonyls) used?

Answer 10

1) bet 2 diff esters when only 1 ester has alpha H’s

2) bet an ester and a ketone (enolate)

Question 11

Dieckmann (intramecular Claisen) w/? ➡ 5 membered ring

Answer 11

1,6-diester

(CH2)4 bet two C=O

Question 12

Diekmann rxn (intramolecular Claisen) w/? ➡ 6 membered ring

Answer 12

1,7-diester

(CH2)5 bet 2 C=O

Question 13

General rxn of Michael addn?

Answer 13

1,4 addn of enolate to beta C of alpha, beta-unsaturated carbonyl compd

Question 14

Mechanism of Michael addn?

Answer 14

1) -OEt deprotonates alpha C of carbonyl compd ➡ enolate
2) enolate attacks beta C of alpha, beta unsat. ➡ new enolate (on alpha C)
3) protonate alpha C w/water

Question 15

Robinson annulation: alpha,beta-unsaturated CO + enolate ➡ ?

Answer 15

• Six membered ring & 2 new sigma bonds, 1 new pi bond

* 2-cyclohexenone ring

Question 16

Mechanism of Robinson annulation:
Part 1 (Michael addn ➡ 1,5-dicarbonyl compd)

Answer 16

1) base deprotonates alpha C of carbonyl compd ➡ enolate
2) enolate attacks beta C of alpha, beta-unsat. ➡ new enolate (on alpha C)
3) protonate enolate w/H2O ➡ 1,5-dicarbonyl compd

Question 17

Mechanism of Robinson annulation:
Part 2 (intramolecular aldol rxn ➡ 2-cyclohexenone)

Answer 17

4) base deprotanates alpha C of part not in ring ➡ enolate
5) enolate attacks carbonyl C ➡ form 6 membered ring (1 new sigma)
6) protonate carbonyl O
7) deprotonate same alpha C ➡ enolate
8) form C=C with enolate C, loss of LG (-OH) ➡ 2-cyclohexenone

Question 18

Mechanisms to know for ch. 24!

Answer 18

• intramolecular aldol

* Robinson annulation

Question 19

Mechanism of intermolecular aldol?

Answer 19

1) -OEt deprotonates outer alpha C ➡ enolate
2) nuc addn of “2nd carbonyl compd” (other C=O in same compd)
3) protonation of 2nd carbonyl O
4) -OEt deprotonates alpha C again
5) form C=C w/enolate C, elim of LG (-OH)