Transcript ppt

Chemistry 125: Lecture 66
April 6, 2011
Carbonyl Chemistry:
Imines & Enamines
This
Oxidation/Reduction
& Electron Transfer
For copyright
notice see final
page of this file
Allylic :
Ketone to Imine
R
H
H
R + H
R
Unfavorable
Equilibrium
Constant
-OH
::
Overlap
?
Oxime
Iminium
Imine
Ion
2,4-DNP
(e.g. J&F Sec. 16.11)
(dinitrophenylhydrazone)
Ketone to Imine
+
Cl-
(cortisone)
Girard’s Reagent
makes steroidal ketones
soluble in water
as cationic imines
(hydrazones)
to Imineof
n-*Ketone
Transitions
Organic “Chromophores”
* mix approaches energy of 2p orbital
+
+
-
-
-
+
C X :
Imine Holds
Retinaldehyde
+
n-*
to the Protein
Opsin
With sufficient
“conjugation” the *
-
-
+
+
Oscillating electric
field wags electrons
up and down by
mixing n with *.
LUMO energy shifts close enough to n
that the transition is at visible wavelength.
e.g. the retinaldehyde imine
of rhodopsin, which is the
R visual pigment in our eyes.
Imine in Synthesis of Alanine (1854)
by Adolph Strecker (1822-1871)
CN-+ NH4Cl + K+CN
+ HCl
+
Often cited in
discussing the
“Origin of Life”
+
+
OH22
OH
D
H+
Note: RCN gives RCOOH
alanine
50-60% yield
An Imine in the Amino Acid Synthesis
Catalyzed by L-Glutamate Dehydrogenase
a-ketoglutaric acid
+
+ NH3 + NADH H-
H+
H
+
Not an “essential” amino acid for mammals
glutamic acid
Transamination
a-ketoglutaric acid
NH2
Not an “essential”
amino acid
Alanine
OH
O
O
O
H
HO
OH
N
OH
H
O
H
glutamic acid
C
DNA
chain
C
What functional group
does this hemiaminal
remind you of?
Ketal
C
NH2
H
O
H
C
C
C
O H
N
NOR
C
CH
C O
O
C
C
HO
sugar
C
Protecting Group
for Sugar
base
a-Substitution via Enamine
(Stork Enamine Acylation)
OH +
+
H
R
-
with permission F. E. Ziegler
by +distilling H2O
can’t lose H from N to give imine
but can lose this a-H+
(Stork Enamine
Alkylation)
H2O
O
R
R
Cl
Iminium
Enamine
Ionyield
85-90%
(nucleophilic
carbon)
+
R
b-diketone
+
O
65-70% for
R = C5H11
H2O
R
55% for
Gilbert Stork (Columbia Univ.) R = PhCH2
-H+
-
Enamine Lore
(Stork Enamine Acylation)
Requires
2 moles of
Enamine!
or add Et3N:
to soak up H+
+
+
H
R
+
-
(acidic)
O
H+
R
R
Enamine
b-diketone
(nucleophilic carbon)
65-70% for
R = C5H11
(also Basic!)
Enamine Lore
(Stork Enamine Alkylation)
+
Actually:
71% yield
O
+
H
-
-
enolate
Oxidation/Reduction as e Transfer
*
CH3-Br
“reduction”
CH33-Br
CH
Br
Grignard Reagent
(like CH3- sec. 16.13)
+
CH3-Mg Br
Mg+
Mg
*
Mg
Nobel Prize (1912)
(CH3)2C=O
(CH3)2C O
(CH3)2C OH
“reduction”
HO
Mg+2 ~50%
Mg
(CH3)2C OH
(CH3)2C O
(CH3)2C=O
H
“Pinacol”
O
(CH3)3C C CH3 “Pinacolone”
2
+
Oxidation/Reduction as Bookkeeping
Arbitrarily assign shared electron pairs
to the more electronegative element
Oxidation/Reduction as Bookkeeping
(for purposes of reagent selection)
Need a “reducing agent”
-3
-3
?
O
-3
0
(CH3)3C C CH3
+2
“reduction”
OH
0
-3
(CH3)3C C CH3
0
H
Oxidation/Reduction as Bookkeeping
(for purposes of reagent selection)
Need a “reducing agent”
O
(CH3)3C C CH3
+2
?
“reduction”
OH
(CH3)3C C CH3
0
H
+1+6
+3
-2
-1
+1
+1
+1
0-1
-2
1-1
-1
-1
0-1
-4
0
+1
NaH
H
O
K 43 +KCl
Reducing:
CrO
Br-Br
RS-SR
H-Cl
CH
2
Br
Li
AlH
Not-2
all
reducing
agents
4
-1
Certainly +4
reduces
O 2,
satisfactorily,
CH4
Br-Br H2would
C CHwork
2
H
and Fe2isOusually
great
heat;
3 at -2
-1
-2
-1 but itHOCrO
2futile
Brtry
RS-H
H-SR
to RS-SR) LiAlH4
Br2 into
free-radical
halogenation;
RS-SR (oxidizes
But
photosynthesis
C
CH
aHa2reagent
2from
is
stable
ion
but
not
generally
reactive.
-2
-3H
changes
into
O2
the
wrong
redox
class.
2O
OH
NaH
CrO3
+
and “H ” (NAD  NADH)
Oxidizing:
Neither: H-Cl
KCl
H 2O
K
RSH
End of Lecture 66
April 6, 2011
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J. M. McBride, Chem 125. License: Creative Commons BY-NC-SA 3.0