Chemistry 125: Lecture 66April 6, 2011

Carbonyl Chemistry:Imines & EnaminesOxidation/Reduction & Electron Transfer This

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Ketone to Imine

+

IminiumIon

Imine

Unfavorable Equilibrium Constant

R

R

H R H

-OH H

(e.g. J&F Sec. 16.11)

Allylic :

2,4-DNP(dinitrophenylhydrazone)

Oxime: :

Overlap ?

Ketone to Imine

+

Cl-

Girard’s Reagent makes steroidal ketones soluble in water

(cortisone)

as cationic imines(hydrazones)

:

n-*

R

n-* Transitions ofOrganic “Chromophores”

:C X+

+ -

- Oscillating electric field wags electrons

up and down by mixing n with *.

With sufficient “conjugation” the * LUMO energy shifts close enough to n

that the transition is at visible wavelength.e.g. the retinaldehyde imine

of rhodopsin, which is the visual pigment in our eyes.

+

+ -

-+

+ -

-

* mix approaches energy of 2p orbital

Imine Holds Retinaldehydeto the Protein Opsin

Ketone to Imine

+ NH4Cl + K+CN-

Imine in Synthesis of Alanine (1854)

by Adolph Strecker (1822-1871)

alanine

+

CN-

+ HCl + OH2 D

OH2

+

H+

50-60% yield

Often cited in discussing the“Origin of Life” Note: RCN gives RCOOH

a-ketoglutaric acid

+ NH3 + NADH

An Imine in the Amino Acid Synthesis Catalyzed by L-Glutamate Dehydrogenase

+

+

H-

H

Not an “essential” amino acid for mammals

H+

glutamic acid

Transamination

a-ketoglutaric acid

H

Not an “essential” amino acid

glutamic acid

Alanine

H

H

H C

C

C

C

C

O O

O

N

NH2

O

N C

C C

C

H

H

H

H O

What functional group does this hemiaminal

remind you of?

OR

Ketal

C

C

C

DNAchain

sugar base

Protecting Group for Sugar

a-Substitution via Enamine

+

IminiumIon

can’t lose H+ from N to give imine

Enamine(nucleophilic carbon)

O+

b-diketone

but can lose this -a H+

(Stork Enamine Acylation)

Gilbert Stork (Columbia Univ.)

O+

(Stork Enamine Alkylation) -

-H+

with perm

ission F. E. Z

iegler

+-

R RR

65-70% for R = C5H11

55% forR = PhCH2

RCl

R

OH

H

85-90% yieldby distilling H2O

H2O

H2O

Enamine

Enamine Lore

(nucleophilic carbon)

b-diketone

(Stork Enamine Acylation)

+-

R

+

R

65-70% for R = C5H11

H

+

H

R

(acidic)

H+

ORequires 2 moles of Enamine!

or add Et3N:

to soak up H+

(also Basic!)

Enamine Lore

+

(Stork Enamine Alkylation)

-

O

71% yield

Actually:

enolate-

H

+

Oxidation/Reduction as e- Transfer

CH3-Br*

Mg

CH3-Br

Mg+

CH3 Br CH3-Mg Br+

Mg

Grignard Reagent(like CH3

- sec. 16.13)

Nobel Prize (1912)*

(CH3)2C=O

Mg

(CH3)2C=O

(CH3)2C O

“reduction”

Mg+2“reduction”

(CH3)2C O

H2O

~50%

(CH3)2C OH

(CH3)2C OH

“Pinacol”

“Pinacolone”(CH3)3C C CH3

OH+

Oxidation/Reduction as Bookkeeping

Arbitrarily assign shared electron pairs to the more electronegative

element

(CH3)3C C CH3

OH

H0

Oxidation/Reduction as Bookkeeping(for purposes of reagent selection)

(CH3)3C C CH3

O

“reduction”+2C C

-3 0 -3 -3 -30

Need a “reducing agent”

?

Oxidation/Reduction as Bookkeeping(for purposes of reagent selection)

(CH3)3C C CH3

O

“reduction”(CH3)3C C CH3

OH

H+2C C

0

Need a “reducing agent”

Oxidizing: Reducing:

Neither:

H-Cl+1 -1

H-Cl

Br-Br0 0

Br-BrCH4

-4 1

CH4

Li+AlH4-

+1 +3 -1

LiAlH4

NaH+1 -1

NaH

K0

K

KCl+1 -1

KCl

RS-SR-1 -1

RS-SR

CrO3

+6 -2

CrO3

?

HOCrO2-

is a stable ion

+4

Not all reducing agents would work satisfactorily,

but it is usually futile to try a reagent from

the wrong redox class.

H2C CH2

Br

Br-2

-2

-1

-1

(oxidizes RS-H H-SR to RS-SR)

Certainly reduces O2, and Fe2O3 at great heat;

Br2 in free-radical halogenation; but not generally reactive.

+1 -2

H2O

H2O

But photosynthesischanges H2O into O2

and “H-” (NAD+ NADH)

RSH

H2C CH2

H

OH-2

-2

-3

-1

End of Lecture 66April 6, 2011

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