dr. wolf's chm 201 & 202 20-1 20.4 nucleophilic substitution in acyl chlorides
TRANSCRIPT
Dr. Wolf's CHM 201 & 202 20-1
20.420.4
Nucleophilic SubstitutionNucleophilic Substitution
in Acyl Chloridesin Acyl Chlorides
Dr. Wolf's CHM 201 & 202 20-2
Preparation of Acyl ChloridesPreparation of Acyl Chlorides
from carboxylic acids and thionyl chloridefrom carboxylic acids and thionyl chloride(Section 12.7)(Section 12.7)
(CH(CH33))22CHCCHCOHOH
OOSOSOClCl22
heatheat(CH(CH33))22CHCCHCClCl
OO
++ SOSO22 ++ HHClCl
(90%)(90%)
Dr. Wolf's CHM 201 & 202 20-3
RCOCR'RCOCR'
OO OORCRCClCl
OO
RCOR'RCOR'
OO
RCNR'RCNR'22
OO
RCORCO––
OO
Reactions of Acyl ChloridesReactions of Acyl Chlorides
Dr. Wolf's CHM 201 & 202 20-4
RCRCClCl
OO
Reactions of Acyl ChloridesReactions of Acyl Chlorides
++ R'CR'COOHH
OO
RCRCOOCR'CR'
OO OO
++ HHClCl
Acyl chlorides react with carboxylic acids to giveAcyl chlorides react with carboxylic acids to giveacid anhydrides:acid anhydrides:
via:via: CCRR
OO
ClCl
OOCR'CR'
HHOO
Dr. Wolf's CHM 201 & 202 20-5
CHCH33(CH(CH22))55CCClCl
OO
ExampleExample
++ CHCH33(CH(CH22))55CCOOHH
OO
pyridinepyridine
CHCH33(CH(CH22))55CCOOC(CHC(CH22))55CHCH33
OO OO
(78-83%)(78-83%)
Dr. Wolf's CHM 201 & 202 20-6
RCRCClCl
OO
Reactions of Acyl ChloridesReactions of Acyl Chlorides
++ RCRCOOR'R'
OO
++ HHClCl
Acyl chlorides react with alcohols to give esters:Acyl chlorides react with alcohols to give esters:
R'R'OOHH
via:via: CCRR
OO
ClCl
OOR'R'
HH
Dr. Wolf's CHM 201 & 202 20-7
ExampleExample
CC66HH55CCClCl
OO
++ (CH(CH33))33CCOOHHpyridinepyridine
(80%)(80%)
CC66HH55CCOOC(CHC(CH33))33
OO
Dr. Wolf's CHM 201 & 202 20-8
RCRCClCl
OO
Reactions of Acyl ChloridesReactions of Acyl Chlorides
++ RCRCNNR'R'22
OO
++ HH22OO
Acyl chlorides react with ammonia and aminesAcyl chlorides react with ammonia and aminesto give amides:to give amides:
R'R'22NNHH + HO+ HO––
++ ClCl––
via:via: CCRR
OO
ClCl
NNR'R'22
HH
Dr. Wolf's CHM 201 & 202 20-9
ExampleExample
CC66HH55CCClCl
OO
++NaOHNaOH
(87-91%)(87-91%)
HH22OO
HHNN
CC66HH55CCNN
OO
Dr. Wolf's CHM 201 & 202 20-10
RCRCClCl
OO
Reactions of Acyl ChloridesReactions of Acyl Chlorides
++ RCRCOOHH
OO
++ HHClCl
Acyl chlorides react with water to giveAcyl chlorides react with water to givecarboxylic acids (carboxylate ion in base):carboxylic acids (carboxylate ion in base):
HH22OO
RCRCClCl
OO
++ RCRCOO––
OO
++ ClCl––2H2HOO––
++ HH22OO
Dr. Wolf's CHM 201 & 202 20-11
RCRCClCl
OO
Reactions of Acyl ChloridesReactions of Acyl Chlorides
++ RCRCOOHH
OO
++ HHClCl
Acyl chlorides react with water to giveAcyl chlorides react with water to givecarboxylic acids (carboxylate ion in base):carboxylic acids (carboxylate ion in base):
HH22OO
via:via: CCRR
OO
ClCl
OOHH
HH
Dr. Wolf's CHM 201 & 202 20-12
ExampleExample
CC66HH55CHCH22CCClCl
OO
++ HH22OO CC66HH55CHCH22CCOOHH
OO
++ HHClCl
Dr. Wolf's CHM 201 & 202 20-13
ReactivityReactivity
CC66HH55CCClCl
OO
CC66HH55CHCH22ClCl
Acyl chlorides undergo nucleophilic Acyl chlorides undergo nucleophilic
substitution much faster than alkyl chlorides.substitution much faster than alkyl chlorides.
Relative rates ofRelative rates ofhydrolysis (25°C)hydrolysis (25°C) 1,0001,000 11
Dr. Wolf's CHM 201 & 202 20-14
20.520.5
Nucleophilic Acyl Substitution in Nucleophilic Acyl Substitution in
Carboxylic Acid AnhydridesCarboxylic Acid Anhydrides
Anhydrides can be prepared from acyl Anhydrides can be prepared from acyl
chlorides as described in Table 20.1chlorides as described in Table 20.1
Dr. Wolf's CHM 201 & 202 20-15
Some anhydrides are industrial chemicalsSome anhydrides are industrial chemicals
CHCH33CCOOCCHCCH33
OO OO
AceticAceticanhydrideanhydride
OO
OO
OO
OO
OO
OO
PhthalicPhthalicanhydrideanhydride
MaleicMaleicanhydrideanhydride
Dr. Wolf's CHM 201 & 202 20-16
From dicarboxylic acidsFrom dicarboxylic acids
Cyclic anhydrides with 5- and 6-membered Cyclic anhydrides with 5- and 6-membered
rings can be prepared by dehydration of rings can be prepared by dehydration of
dicarboxylic acidsdicarboxylic acids
CC
CC
HH
HH COHCOH
COHCOH
OO
OO
OO
OO
OO
HH
HH
tetrachloroethanetetrachloroethane
130°C130°C
(89%)(89%)
+ H+ H22OO
Dr. Wolf's CHM 201 & 202 20-17
RCOCR'RCOCR'
OO OO
RCOR'RCOR'
OO
RCRCNR'NR'22
OO
RCORCO––
OO
Reactions of AnhydridesReactions of Anhydrides
Dr. Wolf's CHM 201 & 202 20-18
Reactions of Acid AnhydridesReactions of Acid Anhydrides
++ RCRCOOR'R'
OO
++
Carboxylic acid anhydrides react with alcoholsCarboxylic acid anhydrides react with alcoholsto give esters:to give esters:
R'R'OOHHRCRCOOCRCR
OO OO
RCOHRCOH
OO
normally, symmetrical anhydrides are usednormally, symmetrical anhydrides are used
(both R groups the same)(both R groups the same)
reaction can be carried out in presence of reaction can be carried out in presence of
pyridine (a base) or it can be catalyzed by acidspyridine (a base) or it can be catalyzed by acids
Dr. Wolf's CHM 201 & 202 20-19
Reactions of Acid AnhydridesReactions of Acid Anhydrides
++ RCRCOOR'R'
OO
++
Carboxylic acid anhydrides react with alcoholsCarboxylic acid anhydrides react with alcoholsto give esters:to give esters:
R'R'OOHHRCRCOOCRCR
OO OO
RCOHRCOH
OO
via:via:
CCRR
OO
OCROCR
OOR'R'
HH
OO
Dr. Wolf's CHM 201 & 202 20-20
ExampleExample
(60%)(60%)
HH22SOSO44
++CHCH33COCCHCOCCH33
OO OO
CHCH33CHCHCHCH22CHCH33
OOHH
CHCH33CCOOCHCHCHCH22CHCH33
OO
CHCH33
Dr. Wolf's CHM 201 & 202 20-21
Reactions of Acid AnhydridesReactions of Acid Anhydrides
++ RCRCNNR'R'22
OO
++
Acid anhydrides react with ammonia and aminesAcid anhydrides react with ammonia and aminesto give amides:to give amides:
2R'2R'22NNHHRCRCOOCRCR
OO OO
RCORCO––
OO
R'R'22NNHH22
++
via:via:
CCRR
OO
OCROCR
NNR'R'22
HH
OO
Dr. Wolf's CHM 201 & 202 20-22
ExampleExample
(98%)(98%)
++CHCH33COCCHCOCCH33
OO OO HH22NN CH(CHCH(CH33))22
OO CHCH33CCNNHH CH(CHCH(CH33))22
Dr. Wolf's CHM 201 & 202 20-23
Reactions of Acid AnhydridesReactions of Acid Anhydrides
++ 2RC2RCOOHH
OO
Acid anhydrides react with water to giveAcid anhydrides react with water to givecarboxylic acids (carboxylate ion in base):carboxylic acids (carboxylate ion in base):
HH22OO
++ 2RCO2RCO––
OO
++2H2HOO–– HH22OO
RCRCOOCRCR
OO OO
RCRCOOCRCR
OO OO
Dr. Wolf's CHM 201 & 202 20-24
Reactions of Acid AnhydridesReactions of Acid Anhydrides
++ 2RC2RCOOHH
OO
Acid anhydrides react with water to giveAcid anhydrides react with water to givecarboxylic acids (carboxylate ion in base):carboxylic acids (carboxylate ion in base):
HH22OORCRCOOCRCR
OO OO
CCRR
OO
OCROCR
OHOH
HH
OO
Dr. Wolf's CHM 201 & 202 20-25
ExampleExample
++ HH22OO
OO
OO
OO
COHCOH
OO
COHCOH
OO
Dr. Wolf's CHM 201 & 202 20-26
20.620.6Sources of EstersSources of Esters
Dr. Wolf's CHM 201 & 202 20-27
CHCH33CCOOCHCH22CHCH22CH(CHCH(CH33))22
OO
Esters are very common natural productsEsters are very common natural products
3-methylbutyl acetate3-methylbutyl acetate
also called "isopentyl acetate" and "isoamyl also called "isopentyl acetate" and "isoamyl
acetate” acetate”
contributes to characteristic odor of bananascontributes to characteristic odor of bananas
Dr. Wolf's CHM 201 & 202 20-28
Esters of GlycerolEsters of Glycerol
R, R', and R" can be the same or differentR, R', and R" can be the same or different
called "triacylglycerols," "glyceryl triesters," or called "triacylglycerols," "glyceryl triesters," or
"triglycerides""triglycerides"
fats and oils are mixtures of glyceryl triestersfats and oils are mixtures of glyceryl triesters
RCRCOOCHCH
CHCH22OOCR'CR'OO
CHCH22OOCR"CR"
OO
OO
Dr. Wolf's CHM 201 & 202 20-29
Esters of GlycerolEsters of Glycerol
CHCH33(CH(CH22))1616CCOOCHCH
CHCH22OOC(CHC(CH22))1616CHCH33OO
CHCH22OOC(CHC(CH22))1616CHCH33
OO
OO
Tristearin: found in manyTristearin: found in manyanimal and vegetable fatsanimal and vegetable fats
Dr. Wolf's CHM 201 & 202 20-30
Cyclic Esters (Lactones)Cyclic Esters (Lactones)
(Z)-5-Tetradecen-4-olide(Z)-5-Tetradecen-4-olide(sex pheromone of female Japanese beetle)(sex pheromone of female Japanese beetle)
OO
OO
HH
HH
CHCH22(CH(CH22))66CHCH33
Dr. Wolf's CHM 201 & 202 20-31
Fischer esterification (Sections 15.8 and 19.14)Fischer esterification (Sections 15.8 and 19.14)
from acyl chlorides (Sections 15.8 and 20.4)from acyl chlorides (Sections 15.8 and 20.4)
from carboxylic acid anhydrides (Sections 15.8from carboxylic acid anhydrides (Sections 15.8and 20.6)and 20.6)
Baeyer-Villiger oxidation of ketones (Section 17.16) Baeyer-Villiger oxidation of ketones (Section 17.16)
Preparation of EstersPreparation of Esters
Dr. Wolf's CHM 201 & 202 20-32
20.720.7Physical Properties of EstersPhysical Properties of Esters
Dr. Wolf's CHM 201 & 202 20-33
Boiling PointsBoiling Points
Esters have higher Esters have higher
boiling points than boiling points than
alkanes because they alkanes because they
are more polar.are more polar.
Esters cannot form Esters cannot form
hydrogen bonds to hydrogen bonds to
other ester molecules, other ester molecules,
so have lower boiling so have lower boiling
points than alcohols.points than alcohols.
CHCH33CHCHCHCH22CHCH33
CHCH33
CHCH33CCOOCHCH33
OO
CHCH33CHCHCHCH22CHCH33
OHOH
28°C28°C
57°C57°C
99°C99°C
boilingboilingpointpoint
Dr. Wolf's CHM 201 & 202 20-34
Solubility in WaterSolubility in Water
Esters can form Esters can form
hydrogen bonds to hydrogen bonds to
water, so low molecular water, so low molecular
weight esters have weight esters have
significant solubility in significant solubility in
water. water.
Solubility decreases Solubility decreases
with increasing number with increasing number
of carbons.of carbons.
CHCH33CHCHCHCH22CHCH33
CHCH33
CHCH33CCOOCHCH33
OO
CHCH33CHCHCHCH22CHCH33
OHOH
~0~0
3333
12.512.5
SolubilitySolubility(g/100 g)(g/100 g)
Dr. Wolf's CHM 201 & 202 20-35
20.820.8Reactions of Esters:Reactions of Esters:
A Review and a PreviewA Review and a Preview
Dr. Wolf's CHM 201 & 202 20-36
with Grignard reagents (Section 14.10)with Grignard reagents (Section 14.10)
reduction with LiAlHreduction with LiAlH4 4 (Section 15.3)(Section 15.3)
with ammonia and amines (Sections 20.12)with ammonia and amines (Sections 20.12)
hydrolysis (Sections 20.10 and 20.11) hydrolysis (Sections 20.10 and 20.11)
Reactions of EstersReactions of Esters
Dr. Wolf's CHM 201 & 202 20-37
20.920.9Acid-Catalyzed Ester HydrolysisAcid-Catalyzed Ester Hydrolysis
Dr. Wolf's CHM 201 & 202 20-38
maximize conversion to ester by removing watermaximize conversion to ester by removing water
maximize ester hydrolysis by having large excess of watermaximize ester hydrolysis by having large excess of water
equilibrium is closely balanced because carbonyl group ofequilibrium is closely balanced because carbonyl group of
ester and of carboxylic acid are comparably stabilizedester and of carboxylic acid are comparably stabilized
Acid-Catalyzed Ester HydrolysisAcid-Catalyzed Ester Hydrolysis
RCOHRCOH
OO
++ R'R'OOHHRCRCOOR'R'
OO
++ HH22OOHH++
is the reverse of Fischer esterificationis the reverse of Fischer esterification
Dr. Wolf's CHM 201 & 202 20-39
ExampleExample
HCl, heatHCl, heat
++ HH22OO
OO
CHCCHCOOCHCH22CHCH33
ClCl
++ CHCH33CHCH22OOHH
OO
CHCOHCHCOH
ClCl
(80-82%)(80-82%)
Dr. Wolf's CHM 201 & 202 20-40
Is the reverse of the mechanism for acid-Is the reverse of the mechanism for acid-
catalyzed esterification.catalyzed esterification.
Like the mechanism of esterification, it involves Like the mechanism of esterification, it involves
two stages: two stages:
1)1) formation of tetrahedral intermediateformation of tetrahedral intermediate
(3 steps)(3 steps)
2)2) dissociation of tetrahedral intermediate dissociation of tetrahedral intermediate
(3 steps)(3 steps)
Mechanism of Acid-CatalyzedMechanism of Acid-CatalyzedEster HydrolysisEster Hydrolysis
Dr. Wolf's CHM 201 & 202 20-41
First stage: First stage: formation of tetrahedral intermediateformation of tetrahedral intermediateFirst stage: First stage: formation of tetrahedral intermediateformation of tetrahedral intermediate
RCRC
OHOH
OHOH
OOR'R'
++ HH22OORCRCOOR'R'
OO
HH++
water adds to the water adds to the
carbonyl group of the carbonyl group of the
esterester
this stage is analogous this stage is analogous
to the acid-catalyzed to the acid-catalyzed
addition of water to a addition of water to a
ketoneketone
Dr. Wolf's CHM 201 & 202 20-42
Second stage: Second stage: cleavage of tetrahedralcleavage of tetrahedralintermediateintermediate
Second stage: Second stage: cleavage of tetrahedralcleavage of tetrahedralintermediateintermediate
RCRC
OHOH
OHOH
OOR'R'
++ R'R'OOHH
HH++
RCOHRCOH
OO
Dr. Wolf's CHM 201 & 202 20-43
Mechanism of formationMechanism of formationofof
tetrahedral intermediatetetrahedral intermediate
Dr. Wolf's CHM 201 & 202 20-44
Step 1Step 1Step 1Step 1
RCRC
OO
OO R'R'
•••• ••••
••••••••
OO ••••++HH
HH
HH
••••
RCRC
OO
OO R'R'
••••
••••
++ HH •••• OO ••••
HH
HH
Dr. Wolf's CHM 201 & 202 20-45
Step 1Step 1Step 1Step 1
••••
RCRC
OO
OO R'R'
••••
••••
++ HH
carbonyl oxygen is carbonyl oxygen is
protonated because protonated because
cation produced is cation produced is
stabilized by electron stabilized by electron
delocalization delocalization
(resonance)(resonance)
RCRC
OO
OO R'R'
••••••••
++
HH
••••
Dr. Wolf's CHM 201 & 202 20-46
Step 2Step 2Step 2Step 2
••••
•••• OO ••••
HH
HH
RCRC
OO
OO R'R'
••••
••••
++ HH RCRC
OHOH
OOR'R'
••••••••
••••••••
OO ••••++
HH
HH
Dr. Wolf's CHM 201 & 202 20-47
Step 3Step 3Step 3Step 3
•••• OO ••••
HH
HH••••
RCRC
OHOH
OOR'R'
••••••••
••••
OO ••••
HH
HH
++ OO ••••
HH
HH
HH++
••••
RCRC
OHOH
OOR'R'
••••••••
••••
OO ••••
HH
••••
Dr. Wolf's CHM 201 & 202 20-48
Cleavage of tetrahedralCleavage of tetrahedralintermediateintermediate
Dr. Wolf's CHM 201 & 202 20-49
Step 4Step 4Step 4Step 4
OO ••••
HH
HH
HH++••••
RCRC
OHOH
OO
••••••••
••••
OHOH••••
••••
R'R'
••••RCRC
OHOH
OO
••••••••
OHOH••••
••••
R'R' HH++ •••• OO ••••
HH
HH
Dr. Wolf's CHM 201 & 202 20-50
Step 5Step 5Step 5Step 5
••••
RCRC
OHOH
OO
••••••••
OHOH••••
••••
R'R' HH++
••••OO••••R'R' HH
++RCRC
OHOH••••••••
OHOH••••
••••
++
Dr. Wolf's CHM 201 & 202 20-51
Step 5Step 5Step 5Step 5
RCRC
OHOH••••
OHOH••••
••••
++
RCRC
OHOH••••••••
OHOH••••
••••
++
Dr. Wolf's CHM 201 & 202 20-52
Step 6Step 6Step 6Step 6
RCRC
OO••••
OHOH••••
••••
++ HH
OO••••
HH HH•••• ++OOHH HH••••
HH
RCRC
OO••••
OHOH••••
••••
••••
Dr. Wolf's CHM 201 & 202 20-53
Activation of carbonyl group by protonation of Activation of carbonyl group by protonation of carbonyl oxygencarbonyl oxygen
Nucleophilic addition of water to carbonyl groupNucleophilic addition of water to carbonyl groupforms tetrahedral intermediateforms tetrahedral intermediate
Elimination of alcohol from tetrahedral intermediate Elimination of alcohol from tetrahedral intermediate restores carbonyl grouprestores carbonyl group
Key Features of MechanismKey Features of Mechanism
Dr. Wolf's CHM 201 & 202 20-54
1818O Labeling StudiesO Labeling Studies
++ HH22OO
COCHCOCH22CHCH33
OO
COCHCOCH22CHCH33
OO
++ HH22OO
Ethyl benzoate, labeled with Ethyl benzoate, labeled with 1818O at the carbonyl O at the carbonyl
oxygen, was subjected to acid-catalyzed hydrolysis.oxygen, was subjected to acid-catalyzed hydrolysis.
Ethyl benzoate, recovered before the reaction had Ethyl benzoate, recovered before the reaction had
gone to completion, had lost its gone to completion, had lost its 1818O label.O label.
This observation is consistent with a tetrahedral This observation is consistent with a tetrahedral
intermediate.intermediate.
HH++
Dr. Wolf's CHM 201 & 202 20-55
1818O Labeling StudiesO Labeling Studies CC
OOHH
OHOH
OCHOCH22CHCH33
COCHCOCH22CHCH33
OO
HH++
++ HH22OO
++ HH22OO
COCHCOCH22CHCH33
OO
HH++