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17.4 How Aldehydes and Ketones
React (Part III)
d-
Electron rich (Lewis base, Nu)
d+
Electron deficient (Lewis acid, E+)
R = alkyl or aryl (C)
Y = alkyl, aryl or H (class II) (No leaving group)
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Nucleophilic Addition (Class II)
1. General mechanism in basic condition:
2. General mechanism in acidic condition:
2
Important pKa to Remember
Acids
H-Z
Names
Alkane (2°)
Amine
H3C
CH
H
H3C
H
N
H
H
Hydrogen
Thiol
51
38
Conjugate
Base, :Z
H3C
CH
H3C
H
N
H
H
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H
Base as Li+ salt
Nucleophile as Grignard reagent
Base and Nucleophile
R
NH
H
H
S
Carboxylic
Acid
RCO 2
Hydrochloric
Acid
Cl
10-11
H
10-11
H
4-5
H
-7
Base in NaH, CaH2
Nucleophile in LiAlH4, NaBH4
Often as a base but can be a
nucleophile
15-16
R
General Roles of :Z
H
Alcohol
water
Ammonium
Approx.
pKa
R
NH
H
R S
RCO 2
Cl
Weak base, but can be a
nucleophile
Nucleophile
Weak base, poor leaving group
Leaving group, poor nucleophile
3
Types of Nucleophile for
Class II Carbonyl Groups
1. Carbon as the nucleophilic atom
Basic condition
pKa = 25
pKa = 50
carboanion
Acetylide ion
2. Hydrogen as the nucleophilic atom
hydride
Mostly basic condition
3. Nitrogen as the nucleophilic atom
1° and 2° amines
Mostly acidic condition
4. Oxygen as the nucleophilic atom
1° alcohols
Acidic condition
4
Oxygen as the Nucleophilic Atom
pKa of alcohol.
pKa = -2
pKa = 15-16
1° and 2° Alcohols function as weak acids, weak bases or
nucleophiles.
3° Alcohols function as weak acids or weak bases.
5
Reactions of Aldehydes and Ketones
with Alcohols
General reaction with primary alcohols:
2° and 3° Alcohols
are too hindered
to react.
H+
2
1° Alcohols
Ketal or acetal
General reaction with water:
H+
Geminal diol (gem-diol)
6
Reactions of Aldehydes and Ketones
with Water
Example:
H+
Mechanism:
7
Reactions of Aldehydes and Ketones
with Alcohols
Examples:
2
2
1
H+
H+
H+
8
Reactions of Aldehydes and Ketones
with Alcohols
Mechanism:
hemiacetal
acetal
9
Application of Ketal or Acetal
Synthesis using protecting group
?
LiAlH4 or DIBAL will reduce the
ketone as well.
Ketal as the protecting group for ketone:
Ketals like ethers are relatively stable in basic condition.
10
Mechanism for the Formation of
Cyclic Ketal
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More Examples on the Use of
Protecting Groups
?
SOCl2 (PBr3 or PCl3) will convert
carboxylic acids into acyl halides as
well.
Ester as the protecting group for carboxylic acid:
Ester will not react with SOCl2 (from
compound 3 to compound 4).
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More Examples on the Use of
Protecting Groups
NH2
NH2
?
Amines under acidic condition may
turn into an EWG in the form of
ammoniim ions.
NO2
Amide as the protecting group for amine:
Amide in compound 3 will act as EGD..
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Formation of Cyclic Hemiacetals or
Ketals
Intramolecular reaction: formation of 5 or 6-membered rings
14
Cyclic Hemiacetals in Carbohydrates
Intramolecular formation of 5 or 6-membered rings
1
CHO
2
H
OH
3
HO
D-Glucose
H
5-OH
5
5
O
HO
HO
4
H
OH
OH
1
OH
OH
+
O
HO
HO
1
OH
OH
OH
5
H
OH
6 CH OH
2
1
CHO
2
H
OH
3
HO
H
4
H
4-OH
OH
4
HO
OH
OH
HO
O
1
OH
5
H
OH
HO
+
4
HO
O
1
OH
OH
OH
6 CH OH
2
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Learning Check
1. What could be the reagent and reaction condition for the following
transformation?
O
(a) ethanol, NaOH
H3CH2CO
OCH2CH3
?
(b) ethanol, H+
CH3
CH3
(c) methanol, NaOH
(d) methanol, H+
(e) None of the above
2. What should be the product from the following reaction?
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Learning Check
3. What could be the product for the following reaction?
OH
O
OH
Product?
H+
removal of water
(a)
(b)
O
O
OH
O
O
(c)
O
O
OH
(d)
OH
O
O
O
(e) None of the above
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Learning Check
4. Which hydroxy group when added to the aldehyde functional group (C-1) of
open chain glucose will produce the cyclic hemiacetal form shown below?
(a) The one that locates on C-2.
(b) The one that locates on C-3.
(c) The one that locates on C-4.
(d) The one that locates on C-5.
(e) None of the above
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Learning Check
Main Menu
5. Which hydroxy group when added to the aldehyde functional group (C-1) of
open chain glucose will produce the cyclic hemiacetal form shown below?
(a) The one that locates on C-2.
(b) The one that locates on C-3.
(c) The one that locates on C-4.
(d) The one that locates on C-5.
(e) None of the above
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