20.3 Nucleophilic Substitution in Acyl Chlorides
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Transcript of 20.3 Nucleophilic Substitution in Acyl Chlorides
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20.320.3
Nucleophilic SubstitutionNucleophilic Substitution
in Acyl Chloridesin Acyl Chlorides
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General Mechanism for Nucleophilic Acyl SubstitutionGeneral Mechanism for Nucleophilic Acyl Substitution
involves formation and dissociationinvolves formation and dissociationof a tetrahedral intermediateof a tetrahedral intermediate
OO•••• ••••
CCRR XX
HHYY
CC
RROHOH
XX
YY
OO•••• ••••
CCRR YY
-H-HXX
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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
OOSOClSOCl22
heatheat(CH(CH33))22CHCCHCClCl
OO
++ SOSO22 ++ HClHCl
(90%)(90%)
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RCOCR'RCOCR'
OO OORCRCClCl
OO
RCOR'RCOR'
OO
RCRCNR'NR'22
OO
RCORCO––
OO
Reactions of Acyl ChloridesReactions of Acyl Chlorides
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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:
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RCRCClCl
OO
Reactions of Acyl ChloridesReactions of Acyl Chlorides
++ R'COHR'COH
OO
RCOCR'RCOCR'
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
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CHCH33(CH(CH22))55CClCCl
OO
ExampleExample
++ CHCH33(CH(CH22))55CCOOHH
OO
pyridinepyridine
CHCH33(CH(CH22))55CCOOC(CHC(CH22))55CHCH33
OO OO
(78-83%)(78-83%)
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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
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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
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ExampleExample
CC66HH55CCClCl
OO
++ (CH(CH33))33CCOOHHpyridinepyridine
(80%)(80%)
CC66HH55CCOOC(CHC(CH33))33
OO
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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––
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RCClRCCl
OO
Reactions of Acyl ChloridesReactions of Acyl Chlorides
++ RCNR'RCNR'22
OO
++ HH22OO
Acyl chlorides react with ammonia and aminesAcyl chlorides react with ammonia and aminesto give amides:to give amides:
R'R'22NHNH + HO+ HO––
++ ClCl––
via:via: CCRR
OO
ClCl
NNR'R'22
HH
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ExampleExample
CC66HH55CCClCl
OO
++NaOHNaOH
(87-91%)(87-91%)
HH22OO
HHNN
CC66HH55CCNN
OO
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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
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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
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ExampleExample
CC66HH55CHCH22CCClCl
OO
++ HH22OO CC66HH55CHCH22CCOOHH
OO
++ HHClCl
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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
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20.420.4
Preparation ofPreparation of
Carboxylic Acid AnhydridesCarboxylic Acid Anhydrides
Anhydrides can be prepared from acyl Anhydrides can be prepared from acyl
chlorides as described in Table 20.2 chlorides as described in Table 20.2
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Some anhydrides are industrial chemicalsSome anhydrides are industrial chemicals
CHCH33COCCHCOCCH33
OO OO
AceticAceticanhydrideanhydride
OO
OO
OO
OO
OO
OO
PhthalicPhthalicanhydrideanhydride
MaleicMaleicanhydrideanhydride
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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
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20.520.5
Reactions ofReactions of
Carboxylic Acid AnhydridesCarboxylic Acid Anhydrides
Table 20.3Table 20.3
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RCOCR'RCOCR'
OO OO
RCOR'RCOR'
OO
RCRCNR'NR'22
OO
RCORCO––
OO
Reactions of AnhydridesReactions of Anhydrides
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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
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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
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ExampleExample
(60%)(60%)
HH22SOSO44
++CHCH33COCCHCOCCH33
OO OO
CHCH33CHCHCHCH22CHCH33
OOHH
CHCH33CCOOCHCHCHCH22CHCH33
OO
CHCH33
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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
++
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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
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ExampleExample
(98%)(98%)
++CHCH33COCCHCOCCH33
OO OO
HH22NN CH(CHCH(CH33))22
OO
CHCH33CNHCNH CH(CHCH(CH33))22
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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
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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
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ExampleExample
++ HH22OO
OO
OO
OO
COHCOH
OO
COHCOH
OO