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Acid Derivatives
CR
O
Cl
CR
O
CR
O
OCR
O
OR'CR
O
NH2
Acid
chloride
Acid
anhydride
Ester Acid
amide
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Acid Derivatives
All of them undergo nucleophilic reactions:
Nucleophilic addition followed by
elimination.
Mechanism:
CR
O
GNu
CR G
Nu
O
CR
O
Nu
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Acid Derivatives
Reactivity depends on:
1. Structure of acid derivatives
a. Inductive effect of G exert on the
carbonyl carbon
The more negative the inductive
effect, the more reactive the
compound.However, the effect is small since
difference of electronegativity between
Cl, N and O is small.
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Acid Derivatives
b. Mesomeric effect of G exert on thecarbonyl carbon
From the orbital approach, resonanceenergy is higher in acid amide, ester
and acid anhydride due to the betterinteraction of the 2p orbitals of N andO with 2p orbital of C.
C
O
RN
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While in acid chloride, resonance energy
is least as 3p-2p interaction is weaker.
Also, if the overlapping is more effective,
the carbonyl carbon will be less positive,
i.e. less reactive.
Acid Derivatives
CO
RCl
3p orbital
2p orbital
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Acid Derivatives
Reactivity depends on:
2. Leaving group ability of G
Less basic the anion, the better it acts
as a leaving group.Basic strength:
NH2- > OR- > OH- > RCOO- > Cl-
Leaving ability:Cl- > RCOO- > OH- > OR- > NH2-
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Acid Derivatives
From the 2 factors above (Structure of
acid derivatives and Leaving group
ability of G), the reactivity of the acid
derivatives towards nucleophile decreasein the order:
Acid chloride > Acid anhydride > Ester >
Acid amide
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Acid Derivatives
Acid Chloride
1. Preparation
CR
O
ClCR
O
OH
PCl5
+ POCl3 + HCl
CR
O
Cl
CR
O
OH
PCl3
CR
O
Cl
CR
O
OH
SOCl2
+ H3PO
3
+ SO2
+ HCl
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Acid Derivatives
Acid Chloride
2. Physical properties
a. Lower members are colourless liquid.
b. It has a pungent and irritating smell.
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Acid Derivatives
Acid Chloride
3. Chemical properties
Nucleophilic reaction occurs easily because
a. Carbonyl carbon is more positive since it
attaches to 2 electronegative atoms (O &
Cl).
b. The lateral overlapping of Cl with carbonyl
carbon is the least among the acidderivatives.
c. Cl- is a weak base and thus a good
leaving group.
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Acid Derivatives
Acid Chloride
3. Chemical properties
CR
O
Cl
CR
O
OH
CR
O
Cl
CR
O
Cl
CR
O
Cl
CR
O
Cl
CR
O
OR'
CR
O
NH2
OH2
R'OH / phenol
NH3
/ R'NH2
R'COONa CR
O
CR'
O
O
LiAlH4 CR H
H
OH
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Acid Derivatives
Acid Chloride
3. Chemical propertiesReduction
a. With LiAlH4
CR
O
Cl
LiAlH4 /dry etherCR H
H
OH
1.
2. water
LiAlH4 is a very strong reducing agent,so it will reduce acid chloride to alcohol.
Another reducing agent has the same result:
H2, Pd / Pt
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Acid Derivatives
Acid Chloride
3. Chemical propertiesReduction
b. To aldehyde
CR
O
Cl
+ H2
Pd / BaSO4
CR
O
H
+ HCl
It is a very good method to prepare aldehyde.
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Acid Derivatives
Acid Anhydride
CR
O
CR
O
O
Simpleanhydride
CR
O
CR'
O
O
Mixedanhydride
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Acid Derivatives
Acid Anhydride
1. Preparation
a. Dehydration of acid (for simple
anhydride only)
CR
O
CR
O
ORCOOHZnO
250 Co
2
OR P2O
5
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Acid Derivatives
Acid Anhydride
1. Preparation
b. From acid chloride
CR
O
Cl
CRO
CR'
O
O
R'COONa
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Acid Derivatives
Acid Anhydride
2. Physical properties
a. Lower members are colourless liquid.
b. It is slightly soluble in water.c. It has a pungent odour.
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Acid Derivatives
Acid Anhydride
3. Chemical properties
Also undergo nucleophilic addition
followed by eliminated. Carboxylate
anion is a good leaving group andreaction of anhydride parallel those of the
acid chloride. However, the lateral overlap
of O with carbonyl carbon is more effective,
and that the large carboxylate groupincrease steric crowding in forming the
intermediate, so the anhydride are generally
less reactive than acid chloride.
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Acid Derivatives
Acid Anhydride
3. Chemical properties
a. Hydrolysis
CRO
CR
O
O + H2O CR
O
OH
2
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Acid Derivatives
Acid Anhydride
3. Chemical properties
b. Ammonolysis
CR
O
CR
O
O CR
O
NH2
+ NH3 + RCOO NH4
+-
CRO
CR
O
O + R'NH2 CR
O
NH
R'
+ RCOOH
R'NH2
RCOO NH3R'
+-
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Acid Derivatives
Acid Anhydride
3. Chemical properties
c. Alcoholysis
CR
O
CR
O
O + R'OH2 RCOOR' + H2O2
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Acid Derivatives
Ester
Chloromethyl but-3-enoate
Methyl 2-bromopropanoate
CH3CHC OCH3
O
Br
CH2=CHCH
2C OCH
2
O
Cl
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Acid Derivatives
Ester
1. Preparation
a. Esterification
CR
O
OH
+ R'OH CR
O
OR'
+ H2O
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Acid Derivatives
Ester
1. Preparation
b. Acylation of alcohol / phenol
CRO
Cl
+ R'OH CRO
OR'
CR
O
Cl+
OH
CR
O
OR'
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Acid Derivatives
Ester
1. Preparation
c. From alkyl iodide
CR
O
O Ag
CR
O
OR'+-
+ R'I
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Acid Derivatives
Ester
2. Physical properties
a. It is oily liquid solid.
b. It has a fragrant fruity smell.c. It is insoluble in water.
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Acid Derivatives
Ester
3. Chemical properties
a. Hydrolysis
CR
O
OR'
+ H2O CR
O
OH
+ R'OH
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Acid Derivatives
Ester
3. Chemical properties
CR
O
OR'
CR
O
O + R'OH+ OH
-
-
CR
O
O CH21
CR
O
O CH2
CR
O
O CH23
+ NaOH3
CR
O
O-
CR
O
O-
CR
O
O-
1
2
3
+
OH CH2
OH CH
OH CH2
Saponification
(And preparation of soapy detergent)
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Acid Derivatives
Ester
3. Chemical properties
b. Ammonolysis
CRO
OR'
+ R'OH+ NH3
CRO
NH2
CR
O
OR'
+ R'OHCR
O
NHR"
+ R"NH2
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Acid Derivatives
Ester
3. Chemical properties
c. Alcoholysis / trans-esterification
n HOCH2CH
2OH + n C C OO
O O
CH3
CH3
C CO
O O
OCH2CH
2+ nCH
3OH
n
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Acid Derivatives
Ester
3. Chemical properties
d. Reduction
CR
O
OR'
RCH2OH + R'OH
Reducing agents may be:
1. LiAlH4 / ether followed by H+
2. Na / alcohol
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Acid Derivatives
Acid Amide
CR
O
NH2
CR
O
NHR'CR
O
NR'R"
primary secondary tertiary
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Acid Derivatives
Acid Amide
1. Preparation
a. Ammonolysis
CR
O
Cl
+ NH3
CR
O
NH2
+ HCl
CR
O
OR'
+ NH3
CR
O
NH2
+ R'OH
C
ORC
R
O O
+ NH3 CR
O
NH2
CR
O
O NH4
++-
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Acid Derivatives
Acid Amide
1. Preparation
b. From acid
RCOOH + NH3 RCOO NH4-
RCOO NH4+-
CR
O
NH2
+ H2O
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Acid Derivatives
Acid Amide
1. Preparation
c. From acid nitrile
RCNalcoholic NaOH
CR
O
NH2
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Acid Derivatives
Acid Amide
2. Physical properties
a. All 1o and 2o acid amides except
methanamide are colourless solides
because of the strong intermolecular H-bond. They have high m.p. and b.p.
But 3o amides have normal m.p. and b.p..
(Why?)
b. Lower members are soluble in water due to
the formation of extensive H-bond with
water.
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Acid Derivatives
Acid Amide
3. Chemical properties
a. Hydrolysis
CRO
NH2
+ OH-
CRO
O
+ NH3
-
CR
O
NH2
CR
O
OH
+ H3O+ + NH
4+
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Acid Derivatives
Acid Amide
3. Chemical properties
b. Dehydration
CRO
NH2
P2O
5
heatCR N
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Acid Derivatives
Acid Amide
3. Chemical properties
c. Reduction
CR
O
NH2
LiAlH4
/ dry ether
(or Na / ethanol)RCH
2NH
2
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Acid Derivatives
Acid Amide
3. Chemical properties
d. Hofmann Degradation
(Reduce one carbon atom)
CR
O
NH2
+ Br2
+ KOH RNH2
+ KBr + K2CO
34 2