Week 7 – Nucleophilic Addition to Aldehydes and Ketones Worksheet
Electrophiles
Electrophiles (E+) are Lewis acids (electron acceptors).
For this course, any atom double-bonded (or triple-bonded) to a more electronegative atom will
be an electrophile.
•
Highlight or circle the E+ (electrophilic) atom in these molecules.
O
O
Cl
S
O
NH
OH
N
C
OH
O
HO
OH
OH
D-glucose
Some molecules have more than one electrophile.
•
Highlight or circle all electrophilic atoms in these molecules.
adenosine
O
O
P O P
O
O
O
O P O
O
O
H
O
O
CH3
ATP
Even if there is a positive charge, the atom double bonded to more EN atom is the E+.
•
Highlight or Circle the electrophilic atoms in these molecules.
CH3
N
1
OH
NH2
OH
Nucleophiles
Nucleophiles are Lewis bases.
A Nucleophile (Nu:) MUST have a lone pair of electrons.
•
Highlight or circle the nucleophilic atoms in this
compound.
C
P
Some nucleophilic atoms are neutral.
•
Highlight or circle the nucleophilic atoms in
these compounds.
NH2
OH
Many nucleophiles are ionic or partially ionic. However, it appears neutral with the
counterion (usually an alkali or alkaline earth metal).
•
Highlight or circle the nucleophilic atom in these compounds. You may need to redraw
the molecule with charges.
MgCl
g ng
SNa
Li
o
at
Challenge: This molecule has no lone pairs and is not a nucleophile as drawn. It must
dissociate first.
o Draw the molecule after it dissociates.
o Highlight or circle the nucleophilic atom in these compounds.
Li
H
Al
H
2
H
Aly
t Li
Anionic Nucleophilic Addition Reactions
•
Write a generalized mechanism for this reaction.
O
•
Na Nuc
O
Nuc
Use a dipole to explain why the ketone shown above is electrophilic.
as an electrophile
IF YE if It
be of the ctschange on
•
Practice drawing arrows for Nu: Addition to these electrophiles.
o Draw the product for each of these Nu: Additions (using Nu:).
o Determine if there is a formal charge on the product.
J
O
H 3C
C
H 3C
N
eC
f
Nu
eC
3
H
Nu
CH3
O
H 3C
045Etc
CH3
O
eC
Nu
CH3
r
OCH3
Nu
ath
p
Ent
EI
iotas
CHIEOchs
Acidic Reaction Work-ups
Most organic reactions have an aqueous work-up (this step is often assumed and is NOT always
shown).
This means that once the reaction is finished, water and acid/base are added. This serves two
purposes 1) to neutralize a charged species and 2) to do a liquid-liquid extraction to remove very
polar side products.
•
Draw reaction mechanisms that show how an acidic work-up would neutralize the
reaction products.
O
S
NCH3
J
4
CH3
H
O
Ttt
It
ijÉ
H
H
b
H
Hii
oh
Tif
Common Carbon Nucleophiles:
•
Highlight or circle the Nu: (nucleophilic) carbon atom in each of these examples of carbon
nucleophiles.
electro
so
nu
highly
1) sp hybridized carbon nucleophiles include
a. cyanide ion:
neg
strong
N C
b. acetylide ion:
HC C
2) Organometallic Reagents. Another way to stabilize a carbon base is to form an
alkyllithium or alkylmagnesium (aka Grignard reagent) bond in which the metal actually
bonds to the carbanion (see structures below).
a. Alkyllithium (R-Li) For example, methyl lithium:
Li
~
CH3
Li
b. Grignard (RMgBr): For example, ethyl grignard:
MgBr
5
~
CH2
H3C
Mg+2 Br
Nucleophilic Additions: Carbon Nucleophiles
•
O
Predict the products for each of these reactions.
RCH2
HO
CH2R
o Circle the atom that will act as the E+.
satisfy
atzatac.pk
o Put a box around the atom that will act as a Nu:.
o Draw the mechanism (using curved arrows).
tzeitjEipnas
E
Li
O
Ph
of
Ph
“EtLi”
ph
f
H+
Ph
gits
cats
It
Clt
fI
IIIT
O
O
NaCN
gfftali
NCH3
EtLi
6
a
on
put ph
it
H+
ly
STH
ft
O'Nat
Ian
n elt
t
Tt
H+
H+
CEN
Nottz
t
Tt
Nucleophilic Additions: Hydride Nucleophiles
Hydride nucleophiles (H-) are usually introduced with a reagent
like NaBH4 or LiAlH4.
H
H
O
H
HO
H
H
B
H
Al
H
H
H
H
These molecules will ionize to form a hydride ion.
H
B
H
H
H
H
•
H
B
H
H
Predict the products for each of these hydride reactions.
o Circle the E+.
o Put a box around the Nu:.
o Draw the mechanism (using curved arrows).
O
H
NaBH4
fI ajit
É
O
t.at fII
a
at
H+
LiAlH4
H+
FIT
H NCH
3
NaCNBH3
O
C
in
I
E
WEN
N
LiAlH4
it
It
Meng
H+
Li
LiAlH4
EI
AAMI
netty's
it
H+
AMNH
areas
nitwit
AMNH
7
MANAS
I