Targets
Functional groups
• How do we look at the molecule in a right way
Transformations
• How do we think the reaction in a right track
i. Ask yourself what are their roles once you know more
than one kind of molecules have been generated in situ
• How do we solve the problem as efficient as possible
i. Predict their roles from the “environment” of reaction
ii. Draw the structures from the generalized names
iii. How to carry the distracting features through
B.C. 1400
Ancient Chinese Words
A.C. 1950
Simplified
Chinese
Words
B.C. 220
Traditional
Chinese Words
B.C. 1400
Words were engraved
on tortoise shells
B.C. 220
Traditional Chinese Words
?
B.C. 1400
Words were engraved
on tortoise shells
B.C. 220
Traditional Chinese Words
B.C. 1400
Words were engraved
on tortoise shells
B.C. 220
Traditional
Chinese Words
H2O
A.C. 1950
Simplified
Chinese Words
B.C. 1400
Words were engraved
on tortoise shells
B.C. 220
Traditional
Chinese Words
H2O
?
A.C. 1950
Simplified
Chinese Words
B.C. 1400
Words were engraved
on tortoise shells
B.C. 220
Traditional
Chinese Words
H2O
A.C. 1950
Simplified
Chinese Words
B.C. 1400
Words were engraved
on tortoise shells
B.C. 220
Traditional
Chinese Words
?
River
A.C. 1950
Simplified
Chinese Words
B.C. 1400
Words were engraved
on tortoise shells
B.C. 220
Traditional
Chinese Words
River
A.C. 1950
Simplified
Chinese Words
B.C. 1400
Words were engraved
on tortoise shells
B.C. 220
Traditional
Chinese Words
Mum
?
River
A.C. 1950
Simplified
Chinese Words
Mum
?
River
Mum
Sea
River
5. Haloform Reaction***
When a methyl ketone is treated with excess base and excess halogen, a reaction
occurs in which a carboxylic acid and a haloform are produced after acidic workup.
Blah~ blah~ blah~
This process is synthetically useful for converting methyl ketones into carboxylic acids.
a) Provide the structure in the box (please draw in next page). (6 pts)
b) Why this ketone can be converted into a carboxylic acid, in another word, why the
reaction does not stop after mono-bromination or di-bromination steps. (2 pts)
What is the
difference
between those
α-Hs???
The presence of electron-withdrawing substituents can have a
profound impact on the acidity of (pKa values) one compound
Neutral
More reactive
The reactivity of
the carbonyl
impact its acidity
Less reactive
The presence of electron-withdrawing substituents can have a
profound impact on the acidity of (pKa values) one compound
Neutral
At pKa standing point
~ 17
~ 16
~ 19
~ 17
~ 25
At pKa standing point
~ 17
~ 16
~ 19
~ 17
~ 25
• Generating a more reactive
carbonyl intermediate
At pKa standing point
~ 17
~ 16
P.T. Step
~ 25
~ 19
~ 17
• Not just those charges generated in the reaction
want be neutralized!
At pKa standing point
~ 17
~ 16
P.T. Step
~ 25
~ 19
Closer to
H2O’s pka
~ 17
• Not just those charges generated in the reaction
want be neutralized!
• But also the product tend to become as neutral
as possible!!
What is the
difference
between those
α-Hs???
Under the basic condition (OH¯)
More acidic of the α−H means a
more reactive intermediate
pKa ~ 19
H2O (pKa ~16) is in
the flask all the
time!!!
Even water can be
basic enough to
pull of the α−H, so
does the enolate
generated in situ.
pKa ~ 17
Under the basic condition (OH¯)
pKa ~ 15
More acidic of the α−H means a more
reactive intermediate
Acid & Base are relative terms!!!
Base (pKa: -1)
Acid (pKa: -3)
6. Sometimes we don’t want to see the over
brominated product, how would you tune the condition
in order to get mono-halogenated product? (3 pts)
Targets
Functional groups
• How do we look at the molecule in a right way
Transformations
• How do we think the reaction in a right track
i. Ask yourself what are their roles once you know more
than one kind of molecules have been generated in situ
• How do we solve the problem as efficient as possible
i. Predict their roles from the “environment” of reaction
ii. Draw the structures from the generalized names
iii. How to carry the distracting features through
22.5 The Acetoacetic Ester Synthesis
1st step: Enolate formation of the acetoacetic ester under the basic condition
2nd Step: Sn2 with alkyl halide
3rd Step:
22.5 The Acetoacetic Ester Synthesis
1st step: Enolate formation of the acetoacetic ester under the basic condition
2nd Step: Sn2 with alkyl halide
3rd Step: Acid hydrolysis of the ester moiety
4th Step: Decarboxylation by heating the reaction up
22.5 The Acetoacetic Ester Synthesis
1st step: Enolate formation of the acetoacetic ester under the basic condition
2nd Step: Sn2 with alkyl halide
3rd Step: Acid hydrolysis of the ester moiety
4th Step: Decarboxylation by heating the reaction up
Q: what is the functional group readily going to turn into?
(Driven by the favorable side of the equilibrium)
22.5 The Acetoacetic Ester Synthesis
1st step: Enolate formation of the acetoacetic ester under the basic condition
2nd Step: Sn2 with alkyl halide
3rd Step: Acid hydrolysis of the ester moiety
4th Step: Decarboxylation by heating the reaction up
Keto form
Enol form
Q: what is the functional group readily going to turn into?
(Driven by the favorable side of the equilibrium)
They are tautomers, not resonance structures to each other