Addition Reactions of Aldehydes and Ketones cont'd. - Nitrogenous Nucleophiles
Recall that, generally, N atoms are more basic and more nucleophilic than O atoms.
Common N Nucleophiles:
NH2
R
NH
2
NH3
H2N NH2
HO NH2
Ammonia Hydrazine
1° Alkylamines
Hydroxylamine
(eg. CH3CH2NH2)
Aniline
O
H3C C CH3
Bp: 56°
"H+"
HO NH2
N
NO2
H
N NH2
O2N
2,4-Dinitrophenylhydrazine
(Brady's Reagent)
OH
With all of these nucleophiles, the product contains
+ H2O a C=N. Carbon-nitrogen double bonds are the same
C
H3C
CH3
strength as carbon-carbon double bonds.
An Oxime.
Mp: 59°
Mechanism: The process here is one of nucleophilic addition, followed by the elimination of a water molecule.
B
H
H
H
H B
O
O
O
O
Addition
Product
H3C C CH3
H3C C CH3
H3C C CH3
H3C C CH3
BH
O
H
H3C C CH3
B
H
H3C C CH3
N
HO
O
H
H
H
O
H3C
C
N
HO
N
N H
HO H
N H
HO H
HO
H
H B
H
H3C
CH3
C
CH3 Elimination
Product
N
N
H
HO
B
H
B
HO
H B
Examples of the products:
O
C
N
C
H
H2NCH2CH2CH3
CH2CH2CH3
H
An Imine.
O
NH2
C
Another Imine.
N
CH3CH2CH2
O
N
C
C
H
H2N NH2
CH3CH2CH2
Useful derivatives:
H3C
C
CH3
O
Bp: 102°C
C
Bp: 100°C
H3C
H
H2N N
NO2
NH2
A Hydrazone.
H
H
C N N
NO2
H3C
NO2
Mp: 144°C
2,4-Dinitrophenylhydrazones
H3C
aka Brady's derivatives.
H
C N N
H3C
O
H3C
C
NO2
NO2
CH3
Mp: 117°C
NO2
C=N bonds can be hydrolyzed in the reverse reaction:
H
H
C NH
R
H
NH2
H
O H
H
R
O H
H
H
NH3
R C
R C
C NH2
C
R
H+
R
O
H
C N
H
O
NH3
C
O H
H
1) DIBAL-H
THF
H
C NH
C O
2) H2O
Other uses for these compounds; the Beckmann rearrangement of oximes:
OH
O
O
N
O
H
C
C
C
N
H+
H+
N C
HO NH2
(CH2)5
H
n
As intermediates in the preparation of heterocyclic compounds:
H
O
O
N N
H+
+ 2 H2O
H2N NH2
C
C
H3C
H3C
CH3
CH3
3,5-Dimethylpyrazole
OH
O
C
N
H
HO NH2
H+
C
P2O5, ∆
or
∆, H3PO4 on
diatomaceous earth
H
C N
The Wolff-Kischner reduction:
O
HO2 C
CO2 H
H2 NNH2 , KOH, ∆
HO2 C
CO2 H
Red u ction of im in es to am in es...
Ph
N
R
Ph
LAH or H2 , Ra n ey Ni
HN
CH2
H
R
O
1 ) CH3 CH2 CH2 NH2
2 ) H2 , Ni
NHCH2 CH2 CH3
O
C
H
1 ) H2 NOH
2 ) LAH
3 ) H+
H2
C
NH2
The Role of Pyridoxal Phosphate in Transamination Reactions
Enz
Enz
NH2
H
C
O
O
H
O
O3POH2C
H3C
C
CH
H
OH
NH2 Alanine
H
OH
C
O3POH2C
CH3
N
CH3
N
N
C
O3POH2C
OH
H3C
H
C
OH
H2N
N
Enz
OH
N
H
C
CH3
H
Pyridoxal phosphate
O
O
B
H3C
H
B
C
C
H
C
O3POH2C
B
N
H
H
H
H
OH
N
H3C
B
OH
H
CH3
H3C
O
C
O3POH2C
C
C
C
OH
C
O
OH
H
NH2
C
H
N
H2O
OH
O3POH2C
OH
-H2O
N
H
CH3
N
CH3
H
Pyridoxamine phosphate
Carbohydrates ... a r e h em iaceta ls
O
O
D-Glu cose in
Fisch er Pr ojection
CHO
H
OH
H
HO
OH
H
H OH
H
OH
H
OH
CH2 OH
Con for m ation al
d iagr a m s
O
Tetr a h yd r ofu r an 2 H-Pyr an
Fu r an
H
HO
HO
H
H
OH O
H
OH
H
H O
HO
HO
36%
H
H
HO
HO
OH
OH
H
OH
H
OH
HO
H
H
OH
H
O
OH
HO
HO
OH
H
H HO
H
H
OH
OH
H
HO
α-D-Glu cop yr a n ose
OH
Hawor th p r ojection
H
H
O
H
H
OH
H
HO
H
O
H
HO
64%
CH2 OH
H
CH2 OH
HO
OH
H
H
β-D-Glu cop yr a n ose
H O
H
OH
H O
α-D-Glu cop yr a n ose
H
0 .0 0 3 %
H
OH
OH
H
α-D-Glu cofu r a n ose
HO
OH
O
HO
HO
H
H
H
H
OH
β-D-Glu cofu r a n ose
CHO
CHO
CHO
H
OH HO
H
H
OH HO
H
H
H
OH
H
OH
HO
H
OH
H
OH HO
H
OH
H
OH
H
OH
H
OH HO
H
OH
H
OH
H
OH
H
OH
H
CH2 OH
CH2 OH
D-Allose
D-Altr ose
H
OH
H
H
OH
HO
H
OH
H
D-Rib ose
HO
H
H
D-Glu cose
D-Man n ose
CHO
OH
HO
OH
CH2 OH
D-Glu cose
D-Fr u ctose
CH2 OH
OH
CH2 OH
CH2 OH
D-Er yth r ose
OH
H
OH
CH2 OH
CH2 OH
D-Galactose
D-Talose
CHO
H
H
OH
CH2 OH
D-Th r eose
CHO
H
OH
CH2 OH
D-Glycer ald eh yd e
D-Lyxose
HOH2 C
H
CH2 OH
H
CHO
CH2 OH
OH
H
OH
D-Ar ab in ose
OH
HO
H
CH2 OH
H
H
H
H
OH
HO
HO
OH
H
H
OH
H
OH
H
H
OH
HO
HO
D-Id ose
D-Gu lose
H
H
OH
CH2 OH
HO
HO
H
HO
O
H
OH
OH
HO
OH
OH
H
H
H
H
H
D-Xylose
HO
H
CHO
CHO
H
H
CHO
H
CHO
H
CH2 OH
CH2 OH
CH2 OH
HO
CH2 OH
CHO
CHO
CHO
CHO
CHO
OH
O
HO
H
H
CH2 OH
H
OH
β-D-Fr u ctose
Hexose: 6 ca r b on s
Pen tose: 5 ca r b on s etc.
A Ketose, as op p osed to
th e oth er su gar s wh ich
a r e a ld oses.
Su ga r s ca n for m a cetals with alcoh ols...
CH2 OH
HHO
O
H H
HO
H
CH2 OH
CH2 OH
H
HHO
CH3 OH, H+
OH
HO
OH
H
O
H H
HHO
O
H H
HO
OCH3
a n d with oth er su gar s to for m d isach a r id es ...
HO
O
H HO
H O
HO
HO
H
H
HOH2 C
OH
OH
H
CH2 OH
H
HO
H
β-D-Fr u ctose
H OH
H O
HO
HO
H
H
H
OH
O
CH2 OH
O
H
OH
H
HOH2 C
HO
H
α-D-Glu cop yr a n osyl-β-D-fr u ctofu r an osid e
Su cr ose
HO
HO
H OH
H O
O
H O
H
OH
H
HO
HO
H
H
OH
H
H
H
OH
4 -O-( β-D-Ga la ctop yr an osyl)-α-D-glu cop yr a n ose
α-Lactose
H
OH
H
Meth yl β-D-glu cop yr an osid e
OH
H
Meth yl α-D-glu cop yr an osid e
H OH
OCH3
or m or e su gar s t o for m p olysach ar id es...
HO
H
HO
H
H O
HO
H
HO
H O
H
H O
H O
H
H
O
OH
H
H
HO
HO
H
H
OH
H
H O
H
H
O
H
H
H
H O
O
HHO
HO
H
Cellu lose
H
OH
H
HO
H O
H
HO
OH
H
H OH
O
OH
HO
OH
H
HO
H
H
H
Am ylose
H
HO
OH
O
OH
H
O
O
O
OH
H
H O
H
HHO
NH2
HO
HO
N
OH
NH2
N
O
H
H
OH
H
OH
H
H
N
N
H
HO
OH
O
D-Rib ose
H
H
OH
H
OH
H
Rib on u cleic acid
(RNA)
N
H
N
H
N
N
H
H
O
H
N
N
Ad en in e
Th e "b ase".
N
HO
2 -Deoxyr ib ose
NH2
N
OH
O
H
H
OH
H
H
2 ' -Deoxyr ib on u cleic acid
(Ad en osin e, m on om er of DNA)
Su ga r s ca n b e r ed u ced ...
CHO
HO
H
HO
H
H
OH
H
OH
CHO
CH2 OH
HO
H
HO
H
H
HO
Na BH4
H
OH
H
CH2 OH
H
CH2 OH
OH Na BH
4
H
H
OH
HO
OH
H
H
OH
CH2 OH
CH2 OH
Xylose
OH
Xylit ol
CH2 OH
Man n ose
Man n itol
CO2 H
or oxid ized ...
Cu
2+
HO
CHO
HO
H
CO2 H
"Red u cin g su ga r s"
Ag
CHO
H
HO
+ Cu 2 O
H
+
HO
Ag
H
CH2 OH
CO2 H
OH
H
H
OH
H
OH
CH2 OH
H HO
Br 2 , H2 O,
p H 5 -6
H
HO
OH
HO
H
H
H
O
H
O
OH
H
D-Glu con ic acid δ-lacton e
OH
H
H
D-Glu con ic acid
OH
CH2 OH
HNO3
H
HO
CO2 H
OH
H
H
OH D-Glu ca r ic acid
H
OH
CO2 H
HO
O
HO
HO
H
O
H
OH
H
D-Glu con ic acid γ-lacton e