20.3 Nucleophilic Substitution in Acyl Chlorides

transcript

20.320.3

Nucleophilic SubstitutionNucleophilic Substitution

in Acyl Chloridesin Acyl Chlorides

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

RROHOH

OO•••• ••••

CCRR YY

-H-HXX

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

++ SOSO22 ++ HClHCl

(90%)(90%)

RCOCR'RCOCR'

OO OORCRCClCl

RCOR'RCOR'

RCRCNR'NR'22

RCORCO––

Reactions of Acyl ChloridesReactions of Acyl Chlorides

RCRCClCl

++ R'CR'COOHH

RCRCOOCR'CR'

++ HHClCl

Acyl chlorides react with carboxylic acids to giveAcyl chlorides react with carboxylic acids to giveacid anhydrides:acid anhydrides:

RCRCClCl

++ R'COHR'COH

RCOCR'RCOCR'

++ HHClCl

Acyl chlorides react with carboxylic acids to giveAcyl chlorides react with carboxylic acids to giveacid anhydrides:acid anhydrides:

via:via: CCRR

OOCR'CR'

CHCH33(CH(CH22))55CClCCl

ExampleExample

++ CHCH33(CH(CH22))55CCOOHH

pyridinepyridine

CHCH33(CH(CH22))55CCOOC(CHC(CH22))55CHCH33

(78-83%)(78-83%)

RCRCClCl

++ RCRCOOR'R'

++ HHClCl

Acyl chlorides react with alcohols to give esters:Acyl chlorides react with alcohols to give esters:

R'R'OOHH

RCRCClCl

++ RCRCOOR'R'

++ HHClCl

Acyl chlorides react with alcohols to give esters:Acyl chlorides react with alcohols to give esters:

R'R'OOHH

via:via: CCRR

OOR'R'

ExampleExample

CC66HH55CCClCl

++ (CH(CH33))33CCOOHHpyridinepyridine

(80%)(80%)

CC66HH55CCOOC(CHC(CH33))33

RCRCClCl

++ RCRCNNR'R'22

++ 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––

RCClRCCl

++ RCNR'RCNR'22

++ 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

NNR'R'22

ExampleExample

CC66HH55CCClCl

++NaOHNaOH

(87-91%)(87-91%)

HH22OO

CC66HH55CCNN

RCRCClCl

++ RCRCOOHH

++ 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

++ RCRCOO––

++ ClCl––2H2HOO––

++ HH22OO

RCRCClCl

++ RCRCOOHH

++ 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

ExampleExample

CC66HH55CHCH22CCClCl

++ HH22OO CC66HH55CHCH22CCOOHH

++ HHClCl

ReactivityReactivity

CC66HH55CCClCl

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

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

Some anhydrides are industrial chemicalsSome anhydrides are industrial chemicals

CHCH33COCCHCOCCH33

AceticAceticanhydrideanhydride

PhthalicPhthalicanhydrideanhydride

MaleicMaleicanhydrideanhydride

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

HH COHCOH

COHCOH

tetrachloroethanetetrachloroethane

130°C130°C

(89%)(89%)

+ H+ H22OO

20.520.5

Reactions ofReactions of

Carboxylic Acid AnhydridesCarboxylic Acid Anhydrides

Table 20.3Table 20.3

RCOCR'RCOCR'

RCOR'RCOR'

RCRCNR'NR'22

RCORCO––

Reactions of AnhydridesReactions of Anhydrides

Reactions of Acid AnhydridesReactions of Acid Anhydrides

++ RCRCOOR'R'

Carboxylic acid anhydrides react with alcoholsCarboxylic acid anhydrides react with alcoholsto give esters:to give esters:

R'R'OOHHRCRCOOCRCR

RCOHRCOH

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

++ RCRCOOR'R'

Carboxylic acid anhydrides react with alcoholsCarboxylic acid anhydrides react with alcoholsto give esters:to give esters:

R'R'OOHHRCRCOOCRCR

RCOHRCOH

via:via:

OCROCR

OOR'R'

ExampleExample

(60%)(60%)

HH22SOSO44

++CHCH33COCCHCOCCH33

CHCH33CHCHCHCH22CHCH33

CHCH33CCOOCHCHCHCH22CHCH33

CHCH33

++ RCRCNNR'R'22

Acid anhydrides react with ammonia and aminesAcid anhydrides react with ammonia and aminesto give amides:to give amides:

2R'2R'22NNHHRCRCOOCRCR

RCORCO––

R'R'22NNHH22

++ RCRCNNR'R'22

Acid anhydrides react with ammonia and aminesAcid anhydrides react with ammonia and aminesto give amides:to give amides:

2R'2R'22NNHHRCRCOOCRCR

RCORCO––

R'R'22NNHH22

via:via:

OCROCR

NNR'R'22

ExampleExample

(98%)(98%)

++CHCH33COCCHCOCCH33

HH22NN CH(CHCH(CH33))22

CHCH33CNHCNH CH(CHCH(CH33))22

++ 2RC2RCOOHH

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––

++2H2HOO–– HH22OO

RCRCOOCRCR

++ 2RC2RCOOHH

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

OCROCR

ExampleExample

++ HH22OO

COHCOH

20.3 Nucleophilic Substitution in Acyl Chlorides

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