“Crossed” Aldol Condensation
Synthetically Useful Crossed-Aldols: one component has no α-H's
Scheme:
O
O
! C
H3C
CH3
C
+
2
H
O
"
NaOH
"
C
!
!
Dibenzalacetone
MW 234.26
trans,trans major product
mp 110-111 oC
H
O
C
C
C
H
O
C
C
H
H
H
C
C
H
C
C
C
H
H
α-Carbons - carbon next to the carbonyl group is designated as being in the α position
α-Hydrogens – hydrogen atoms attached to α-carbons
O
O
C
C
H
H
C
CH3
O
H !
C
C
C
" H CH3
NaOEt
EtOH
- H2O
CH3
O
O
C !
C
CH3
H
+
H
C
NaOEt
EtOH
- H2O
H
C
loss of H2O can be
spontaneous when
aryl aldehyde. Why?
O
C
H
C
C
H
H
C
Possible Side Reactions
O
CH3
C
O
CH3
+
!
CH3
C
NaOH
CH3
- H2O
CH3
CH3 O
C ! C
" C CH3
H
CH3 O
Arising from acetone self-condensation(s)
H3C
C
C
H
C
CH3
C
H
C
CH3
Mechanism
Step 1: abstraction of an α-hydrogen to produce conjugate base of acetone
O
H3C
O
C
!C
H
O H
H3C
H
H
pKa ~ 20
O
C
!C
H
H 3C
H
C
!C
H
enolate anion
+
H O H
H
Step 2: nucleophilic attack by conjugate base (enolate anion) on carbonyl carbon of
benzaldehyde
O
H3C
C
!C
H
+
H
H
O
O
O
C
C
C
H3C
"+
!C
H
Step 3: proton abstraction from water
O
H3C
O
C
!C
H
C
H
H
H3C
O
O
C
C
!C
H
H
H
An “aldol”
β-hydroxy carbonyl
H
H O H
H
H
+
O H
Mechanism
Step 4: loss of water (dehydration to α,β-unsaturated carbonyl)
H
H3C
O
O
C
C
!C
H
O
H
H
C ! C
H3C
C "
H
+
H O H
H
H O
Note that this is not a typical acid catalyzed alcohol dehydration. This is actually an E2 reaction.
While –OH is normally a very poor leaving group, the driving force behind this elimination is
the formation of a C-C double bond in conjugation with the carbonyl group and the benzene ring.
Step 5: repeat
H
C
O
O
C !
C
CH3
H
+
H
C
NaOH
- H2O
H
C
O
C
H
C
C
H
H
C
Procedure:
1.To ethanol (5 mL) add benzaldehyde (3 mL) and 10% aqueous NaOH (3 mL)
2.Warm the mixture and add acetone (1 mL) dropwise with occasional swirling
3.Continue warming the mixture for 20 min with occasional swirling
4.Cool the mixture in an ice bath for 10 min and collect the precipitate
5.Recrystallize from ethanol (~20 mL)
6.Calculate percent yield on the basis of acetone, take a melting point and run IR.
Look for the presence of a carbonyl stretch at ~1650 cm-1