1. Imines & Enamines Oxidation/Reduction & Electron Transfer
Chemistry 125: Lecture 66 April 6, Carbonyl Chemistry:
Imines & Enamines Oxidation/Reduction & Electron Transfer
This
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2. ? Ketone to Imine -OH Iminium Imine Ion Allylic : R H H R H Oxime R+
Oxime ?
: :
Overlap
Iminium
Ion
Imine
Unfavorable Equilibrium Constant
2,4-DNP
(dinitrophenylhydrazone)
(e.g. J&F Sec )

3. makes steroidal ketones
Ketone to Imine
makes steroidal ketones
soluble in water
(cortisone) +
Cl-
Girard’s Reagent
as cationic imines
(hydrazones)

4. n-* Transitions of Organic “Chromophores”
Imine Holds Retinaldehyde
to the Protein Opsin
Ketone to Imine
n-* Transitions of Organic “Chromophores”
* mix approaches energy of 2p orbital + - + - + - :
n-*
Oscillating electric field wags electrons up and down by mixing n with *. C X :
With sufficient “conjugation” the * LUMO energy shifts close enough to n that the transition is at visible wavelength. R
e.g. the retinaldehyde imine of rhodopsin, which is the visual pigment in our eyes.

5. Imine in Synthesis of Alanine (1854) by Adolph Strecker (1822-1871)
CN-
+ NH4Cl + K+CN-
+ HCl +
OH2 D
OH2 + + H+
Often cited in discussing the
“Origin of Life”
Note: RCN gives RCOOH
alanine
50-60% yield

6. An Imine in the Amino Acid Synthesis Catalyzed by L-Glutamate Dehydrogenase
a-ketoglutaric acid +
+ NH3 + NAD H H- H+ H +
glutamic acid
Not an “essential” amino acid for mammals

7. Not an “essential” amino acid
Transamination
a-ketoglutaric acid
Alanine
Not an “essential” amino acid H H
glutamic acid H

8. C What functional group does this hemiaminal remind you of? Ketal DNA
chain
What functional group does this hemiaminal remind you of?
Ketal N
NH2 O C H C O H O H OR
Protecting Group for Sugar
sugar base

9. a-Substitution via Enamine
(Stork Enamine Acylation) + - R + OH
H2O + O R R H R Cl
Iminium
Ion
Enamine
b-diketone +
85-90% yield
by distilling H2O
65-70% for R = C5H11
(nucleophilic carbon)
H2O
with permission F. E. Ziegler O
can’t lose H+ from N to give imine R
but can lose this a-H+ -
(Stork Enamine Alkylation) H+ -
55% for
R = PhCH2
Gilbert Stork (Columbia Univ.)

10. (nucleophilic carbon)
Enamine Lore
(Stork Enamine Acylation) + - R O
(acidic)
Requires
2 moles of Enamine! + H + H+ H R R
or add Et3N:
to soak up H+
Enamine
b-diketone
65-70% for R = C5H11
(nucleophilic carbon)
(also Basic!)

11. (Stork Enamine Alkylation)
Enamine Lore
(Stork Enamine Alkylation) +
71% yield
Actually: O - H + -
enolate

12. Oxidation/Reduction as e- Transfer
Grignard Reagent
(like CH3- sec ) *
CH3-Br
CH3-Br
CH3-Mg Br + Mg
CH3 Br
“reduction” Mg + Mg
Nobel Prize (1912) *
(CH3)2C=O Mg
(CH3)2C O
(CH3)2C OH
“Pinacol”
“reduction”
H2O
~50%
Mg+2
(CH3)2C O
(CH3)2C=O H+
“Pinacolone”
(CH3)3C C CH3 O

13. Oxidation/Reduction as Bookkeeping
Arbitrarily assign shared electron pairs to the more electronegative element

14. Oxidation/Reduction as Bookkeeping
(for purposes of reagent selection)
Need a “reducing agent”
(CH3)3C C CH3 O
(CH3)3C C CH3 OH H -3 -3 ? -3 -3 C C
“reduction” +2

15. Oxidation/Reduction as Bookkeeping
(for purposes of reagent selection)
Need a “reducing agent”
(CH3)3C C CH3 O
(CH3)3C C CH3 OH H ? C C
“reduction” +2 +1 +1 +6 +1 +1 +3 -2 -1 -1 -1 -4 +1 -1 -2 1 -1 -1
Li+AlH4-
H2O
CrO3
NaH
KCl K
Oxidizing:
RS-SR
Br-Br
CH4
H-Cl
Reducing: Br
Not all reducing agents would work satisfactorily, but it is usually futile
to try a reagent from
the wrong redox class. -2 -1
Br-Br
Certainly reduces O2,
and Fe2O3 at great heat;
Br2 in free-radical halogenation; but not generally reactive.
CH4
H2C CH2 +4 H OH
HOCrO2-
is a stable ion -2 -3 -1
RS-SR
LiAlH4
(oxidizes RS-H H-SR to RS-SR)
But photosynthesis
changes H2O into O2
and “H-” (NAD+  NADH)
H2C CH2
CrO3
NaH K
H-Cl
Neither:
KCl
H2O
RSH

16. End of Lecture 66 April 6, 2011
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