dr. wolf's chm 201 & 202 20-1 chapter 20 carboxylic acid derivatives nucleophilic acyl...

Dr. Wolf's CHM 201 & 202 20-1

Chapter 20Chapter 20Carboxylic Acid DerivativesCarboxylic Acid Derivatives

Nucleophilic Acyl SubstitutionNucleophilic Acyl Substitution

Dr. Wolf's CHM 201 & 202 20-2

20.120.1

Nomenclature of Carboxylic Acid DerivativesNomenclature of Carboxylic Acid Derivatives

Dr. Wolf's CHM 201 & 202 20-3

Acyl HalidesAcyl HalidesAcyl HalidesAcyl Halides

RCRC

OO

XX

name the acyl group and add the word name the acyl group and add the word chloridechloride, , fluoridefluoride, , bromidebromide, or , or iodideiodide

as appropriateas appropriate

acyl chlorides are, by far, the most frequently encountered of the acyl halidesacyl chlorides are, by far, the most frequently encountered of the acyl halides

Dr. Wolf's CHM 201 & 202 20-4

Acyl HalidesAcyl HalidesAcyl HalidesAcyl Halides

CHCH33CClCCl

OO

acetyl chlorideacetyl chloride

3-butenoyl chloride3-butenoyl chloride

OO

HH22CC CHCHCHCH22CClCCl OO

CBrCBrFF pp-fluorobenzoyl bromide -fluorobenzoyl bromide

Dr. Wolf's CHM 201 & 202 20-5

Acid AnhydridesAcid AnhydridesAcid AnhydridesAcid Anhydrides

when both acyl groups are the same, name the when both acyl groups are the same, name the

acid and add the word acid and add the word anhydrideanhydride

when the groups are different, list the names of the when the groups are different, list the names of the

corresponding acids in alphabetical order and add corresponding acids in alphabetical order and add

the word the word anhydrideanhydride

RCOCR'RCOCR'

OO OO

Dr. Wolf's CHM 201 & 202 20-6

Acid AnhydridesAcid AnhydridesAcid AnhydridesAcid Anhydrides

acetic anhydrideacetic anhydride

benzoic anhydridebenzoic anhydride

benzoicbenzoic heptanoicheptanoic anhydride anhydride

CHCH33COCCHCOCCH33

OO OO

CC66HH55COCCCOCC66HH55

OO OO

CC66HH55CCOOC(CHC(CH22))55CHCH33

OO OO

Dr. Wolf's CHM 201 & 202 20-7

EstersEstersEstersEsters

name as name as alkyl alkanoatesalkyl alkanoates

cite the alkyl group attached to oxygen first (R')cite the alkyl group attached to oxygen first (R')

name the acyl group second; substitute the suffixname the acyl group second; substitute the suffix

-ate-ate for the for the -ic -ic ending of the corresponding acidending of the corresponding acid

RCOR'RCOR'

OO

Dr. Wolf's CHM 201 & 202 20-8

EstersEstersEstersEsters

CHCH33COCOCHCH22CHCH33

OO

ethylethyl acetate acetate

methylmethyl propanoate propanoate

2-chloroethyl 2-chloroethyl benzoate benzoate

OO

CHCH33CHCH22COCOCHCH33

COCOCHCH22CHCH22ClCl

OO

Dr. Wolf's CHM 201 & 202 20-9

Amides having an NHAmides having an NH22 group groupAmides having an NHAmides having an NH22 group group

identify the corresponding carboxylic acididentify the corresponding carboxylic acid

replace the replace the -ic acid -ic acid or or -oic acid -oic acid ending by -amide.ending by -amide.

RCRCNNHH22

OO

Dr. Wolf's CHM 201 & 202 20-10

Amides having an NHAmides having an NH22 group groupAmides having an NHAmides having an NH22 group group

CHCH33CCNNHH22

OO

acetamideacetamide

3-methylbutanamide3-methylbutanamide

OO

(CH(CH33))22CHCHCHCH22CCNNHH22

CCNNHH22

OO benzamidebenzamide

Dr. Wolf's CHM 201 & 202 20-11

Amides having substituents on NAmides having substituents on NAmides having substituents on NAmides having substituents on N

name the amide as beforename the amide as before

precede the name of the amide with the name of precede the name of the amide with the name of

the appropriate group or groupsthe appropriate group or groups

precede the names of the groups by the letter precede the names of the groups by the letter N- N-

(standing for nitrogen and used as a locant)(standing for nitrogen and used as a locant)

RCRCNNHHR'R'

OO

andand RCRCNNR'R'22

OO

Dr. Wolf's CHM 201 & 202 20-12

Amides having substituents on NAmides having substituents on NAmides having substituents on NAmides having substituents on N

CHCH33CCNNHHCHCH33

OO

NN--methylmethylacetamideacetamide

NN--isopropylisopropyl--NN--methylmethylbutanamidebutanamide

CCNN(CH(CH22CHCH33))22

OO NN,,NN--diethyldiethylbenzamidebenzamide

OO

CHCH33CHCH22CHCH22CCNNCH(CHCH(CH33))22

CHCH33

Dr. Wolf's CHM 201 & 202 20-13

NitrilesNitrilesNitrilesNitriles

add the suffix add the suffix -nitrile -nitrile to the name of the parent to the name of the parent

hydrocarbon chain (including the triply bonded hydrocarbon chain (including the triply bonded

carbon of CN)carbon of CN)

or: replace the or: replace the -ic acid -ic acid or or -oic acid -oic acid name of the name of the

corresponding carboxylic acid by corresponding carboxylic acid by -onitrile-onitrile

or: name as an or: name as an alkyl cyanide alkyl cyanide (functional class (functional class

name)name)

RCRC NN

Dr. Wolf's CHM 201 & 202 20-14

NitrilesNitrilesNitrilesNitriles

CHCH33CC NNethanenitrileethanenitrileor: acetonitrileor: acetonitrileor: methyl cyanideor: methyl cyanide

CC66HH55CC NN benzonitrilebenzonitrile

NNCC

CHCH33CHCHCHCH33 2-methylpropanenitrile2-methylpropanenitrileor: isopropyl cyanideor: isopropyl cyanide

Dr. Wolf's CHM 201 & 202 20-15

20.220.2

Structure of Carboxylic Acid DerivativesStructure of Carboxylic Acid Derivatives

Dr. Wolf's CHM 201 & 202 20-16

The key to this chapter is the next The key to this chapter is the next slide.slide.

It lists the various carboxylic acids in It lists the various carboxylic acids in order of decreasing reactivity toward order of decreasing reactivity toward their fundamental reaction type their fundamental reaction type (nucleophilic acyl substitution).(nucleophilic acyl substitution).

The other way to read the list is in The other way to read the list is in order of increasing stabilization of the order of increasing stabilization of the carbonyl group.carbonyl group.

The key to this chapter is the next The key to this chapter is the next slide.slide.

It lists the various carboxylic acids in It lists the various carboxylic acids in order of decreasing reactivity toward order of decreasing reactivity toward their fundamental reaction type their fundamental reaction type (nucleophilic acyl substitution).(nucleophilic acyl substitution).

The other way to read the list is in The other way to read the list is in order of increasing stabilization of the order of increasing stabilization of the carbonyl group.carbonyl group.

Dr. Wolf's CHM 201 & 202 20-17

CHCH33CC

OO

ClCl

CHCH33CC

OO

OOCCHCCH33

OO

CHCH33CC

OO

SCHSCH22CHCH33

CHCH33CC

OO

OOCHCH22CHCH33

CHCH33CC

OO

NHNH22

MostMost

reactivereactive

LeastLeast

reactivereactive

LeastLeast

stabilizedstabilized

MostMost

stabilizedstabilized

Dr. Wolf's CHM 201 & 202 20-18

Electron Delocalization and the Carbonyl GroupElectron Delocalization and the Carbonyl Group

The main structural feature that distinguishes acyl The main structural feature that distinguishes acyl

chlorides, anhydrides, thioesters, esters, and chlorides, anhydrides, thioesters, esters, and

amides is the interaction of the substituent with the amides is the interaction of the substituent with the

carbonyl group. It can be represented in carbonyl group. It can be represented in

resonance terms as:resonance terms as:

RCRC

OO

XX••••

•••••••• ––

RCRC

OO

XX••••

••••••••••••

++

RCRC

OO

XX

••••••••••••

++

––

Dr. Wolf's CHM 201 & 202 20-19

Electron Delocalization and the Carbonyl GroupElectron Delocalization and the Carbonyl Group

The extent to which the lone pair on X can be The extent to which the lone pair on X can be

delocalized into C=O depends on:delocalized into C=O depends on:

1) the electronegativity of X1) the electronegativity of X

2) how well the lone pair orbital of X interacts 2) how well the lone pair orbital of X interacts

with the with the orbital of C=O orbital of C=O

RCRC

OO

XX••••

••••••••

RCRC

OO

XX••••

••••••••••••

++RCRC

OO

XX

••••••••••••

++

––––

Dr. Wolf's CHM 201 & 202 20-20

Orbital overlaps in carboxylic acid derivativesOrbital overlaps in carboxylic acid derivatives

orbital of carbonyl grouporbital of carbonyl group

Dr. Wolf's CHM 201 & 202 20-21


lone pair orbitallone pair orbital

of substituentof substituent

Dr. Wolf's CHM 201 & 202 20-22


electron pair of substituent delocalized into electron pair of substituent delocalized into

carbonyl carbonyl orbitalorbital

Dr. Wolf's CHM 201 & 202 20-23

acyl chlorides have the least stabilized carbonylacyl chlorides have the least stabilized carbonyl

groupgroup

delocalization of lone pair of Cl into C=O group isdelocalization of lone pair of Cl into C=O group is

not effective because C—Cl bond is too longnot effective because C—Cl bond is too long

Acyl ChloridesAcyl Chlorides

••••

CC

OO

RR

ClCl•••• ••••

••••••••

••••

CC

OO

RR

ClCl••••

•••• ••••••••

++

––

Dr. Wolf's CHM 201 & 202 20-24

RCRCClCl

OO

least stabilized C=Oleast stabilized C=O

most stabilized C=Omost stabilized C=O

Dr. Wolf's CHM 201 & 202 20-25

lone pair donation from oxygen stabilizes thelone pair donation from oxygen stabilizes the

carbonyl group of an acid anhydridecarbonyl group of an acid anhydride

the other carbonyl group is stabilized in anthe other carbonyl group is stabilized in an

analogous manner by the lone pairanalogous manner by the lone pair

Acid AnhydridesAcid Anhydrides

••••CCRR

OO•••• ••••

OO••••

CC

OO•••• ••••

RR

OO•••• ••••

••••••••

++

––

CCRR

OO ••••

OO••••

CCRR

Dr. Wolf's CHM 201 & 202 20-26

RCRCOOCR'CR'

OO OORCRCClCl

OO



Dr. Wolf's CHM 201 & 202 20-27

Sulfur (like chlorine) is a third-row element.Sulfur (like chlorine) is a third-row element.

Electron donation to C=O from third-row elementsElectron donation to C=O from third-row elements

is not very effective.is not very effective.

Resonance stabilization of C=O in thioesters isResonance stabilization of C=O in thioesters is

not significant.not significant.

ThioestersThioesters

••••••••

++

––

CCRR

OO ••••

SSR'R'••••

OO•••• ••••

••••CCRR SSR'R'

••••

Dr. Wolf's CHM 201 & 202 20-28

RCRCOOCR'CR'

OO OORCRCClCl

OO



RCSR'RCSR'

OO

Dr. Wolf's CHM 201 & 202 20-29

lone pair donation from oxygen stabilizes thelone pair donation from oxygen stabilizes the

carbonyl group of an estercarbonyl group of an ester

stabilization greater than comparable stabilizationstabilization greater than comparable stabilization

of an anhydride or thioesterof an anhydride or thioester

EstersEsters

••••••••

++

––

CCRR

OO ••••

OOR'R'••••

OO•••• ••••

••••CCRR OOR'R'

••••

Dr. Wolf's CHM 201 & 202 20-30

RCRCOOCR'CR'

OO OORCRCClCl

OO

RCRCOOR'R'

OO



RCSR'RCSR'

OO

Dr. Wolf's CHM 201 & 202 20-31

lone pair donation from nitrogen stabilizes thelone pair donation from nitrogen stabilizes the

carbonyl group of an amidecarbonyl group of an amide

N is less electronegative than O; therefore, N is less electronegative than O; therefore,

amides are stabilized more than esters and amides are stabilized more than esters and

anhydridesanhydrides

AmidesAmides

••••••••

++

––

CCRR

OO ••••

NNR'R'22

OO•••• ••••

••••CCRR NNR'R'22

Dr. Wolf's CHM 201 & 202 20-32

amide resonance imparts significant double-bondamide resonance imparts significant double-bond

character to C—N bondcharacter to C—N bond

activation energy for rotation about C—N bondactivation energy for rotation about C—N bond

is 75-85 kJ/molis 75-85 kJ/mol

C—N bond distance is 135 pm in amides versusC—N bond distance is 135 pm in amides versus

normal single-bond distance of 147 pm in aminesnormal single-bond distance of 147 pm in amines

AmidesAmides

••••••••

++

––

CCRR

OO ••••

NNR'R'22

OO•••• ••••

••••CCRR NNR'R'22

Dr. Wolf's CHM 201 & 202 20-33

RCRCOOCR'CR'

OO OORCRCClCl

OO

RCRCOOR'R'

OO

RCRCNNR'R'22

OO



RCSR'RCSR'

OO

Dr. Wolf's CHM 201 & 202 20-34

very efficient electron delocalization and dispersalvery efficient electron delocalization and dispersal

of negative chargeof negative charge

maximum stabilizationmaximum stabilization

Carboxylate ionsCarboxylate ions

OO•••• ••••

••••CCRR

––

OO••••

••••

••••••••––

CCRR

OO ••••

••••••••OO

Dr. Wolf's CHM 201 & 202 20-35

RCRCOOCR'CR'

OO OORCRCClCl

OO

RCRCOOR'R'

OO

RCRCNNR'R'22

OO

RCRCOO––

OO



RCSR'RCSR'

OO

Dr. Wolf's CHM 201 & 202 20-36

Reactivity is related to structureReactivity is related to structure

RCRCOOCR'CR'

OO OORCRCClCl

OO

RCRCOOR'R'

OO

RCRCNNR'R'22

OO

StabilizationStabilization

very smallvery small

smallsmall

largelarge

moderatemoderate

Relative rateRelative rate

of hydrolysisof hydrolysis

10101111

101077

< 10< 10-2-2

1.01.0

The more The more

stabilized the stabilized the

carbonyl group, carbonyl group,

the less reactive the less reactive

it is.it is.

Dr. Wolf's CHM 201 & 202 20-37


In general:In general:

OO•••• ••••

CCRR XX

+ H+ HYY

OO•••• ••••

CCRR YY

+ H+ HXX

Reaction is feasible when a less stabilized Reaction is feasible when a less stabilized

carbonyl is converted to a more stabilized carbonyl is converted to a more stabilized

one one (more reactive to less reactive)(more reactive to less reactive)..

Dr. Wolf's CHM 201 & 202 20-38

RCRCOOCR'CR'

OO OORCRCClCl

OO

RCRCOOR'R'

OO

RCRCNNR'R'22

OO

RCRCOO––

OO

RCSR'RCSR'

OO

most reactivemost reactive

least reactiveleast reactive

a carboxylic acid a carboxylic acid derivative can be derivative can be converted by converted by nucleophilic acyl nucleophilic acyl substitution to any other substitution to any other type that lies below it in type that lies below it in this tablethis table

Dr. Wolf's CHM 201 & 202 20-39

20.320.3

General MechanismGeneral Mechanism

forfor


Dr. Wolf's CHM 201 & 202 20-40


OO•••• ••••

CCRR XX

+ H+ HNuNu

OO•••• ••••

CCRR NuNu

+ H+ HXX

Reaction is feasible when a less stabilized Reaction is feasible when a less stabilized

carbonyl is converted to a more stabilized carbonyl is converted to a more stabilized

one one (more reactive to less reactive)(more reactive to less reactive)..

Dr. Wolf's CHM 201 & 202 20-41

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

HHNuNu

CC

RROHOH

XX

NuNu

OO•••• ••••

CCRR NuNu

-H-HXX

Both stages can involve several elementary steps.Both stages can involve several elementary steps.

Dr. Wolf's CHM 201 & 202 20-42


first stage of mechanism (formation of tetrahedralfirst stage of mechanism (formation of tetrahedralintermediate) is analogous to nucleophilic additionintermediate) is analogous to nucleophilic additionto C=O of aldehydes and ketonesto C=O of aldehydes and ketones

OO•••• ••••

CCRR XX

HHNuNu

CC

RROHOH

XX

NuNu

Dr. Wolf's CHM 201 & 202 20-43


second stage is restoration of C=O by eliminationsecond stage is restoration of C=O by elimination

OO•••• ••••

CCRR XX

HHNuNu

CC

RROHOH

XX

NuNu

OO•••• ••••

CCRR NuNu

-H-HXX

complicating features of each stage involvecomplicating features of each stage involveacid-base chemistryacid-base chemistry

Dr. Wolf's CHM 201 & 202 20-44


OO•••• ••••

CCRR XX

HHNuNu

CC

RROHOH

XX

NuNu

OO•••• ••••

CCRR NuNu

-H-HXX

Acid-base chemistry in first stage is familiar in thatAcid-base chemistry in first stage is familiar in thatit has to do with acid/base catalysis of nucleophilic it has to do with acid/base catalysis of nucleophilic addition to C=O.addition to C=O.

Dr. Wolf's CHM 201 & 202 20-45


OO•••• ••••

CCRR XX

HHNuNu

CC

RROHOH

XX

NuNu

OO•••• ••••

CCRR NuNu

-H-HXX

Acid-base chemistry in second stage concernsAcid-base chemistry in second stage concernsform in which the tetrahedral intermediate existsform in which the tetrahedral intermediate existsunder the reaction conditions and how it dissociatesunder the reaction conditions and how it dissociatesunder those conditions.under those conditions.

Dr. Wolf's CHM 201 & 202 20-46

The Tetrahedral IntermediateThe Tetrahedral Intermediate

tetrahedral intermediate (TI)tetrahedral intermediate (TI) CC

RROO

XX

NuNu ••••

HH•••• ••••

••••

CC

RROO

XX

NuNu ••••

HH•••• ••••

HH ++

Conjugate acid of tetrahedral Conjugate acid of tetrahedral

intermediate (TIintermediate (TI++))

••••

OO••••

••••

CC

RR

XX

NuNu

•••• ••••––

Conjugate base of tetrahedral Conjugate base of tetrahedral

intermediate (TIintermediate (TI––))

Dr. Wolf's CHM 201 & 202 20-47

Dissociation of TI—HDissociation of TI—H++

•••• CC

RROO

XX

NuNu••••

HH ••••

HH++

++B—HB—H ++CC

OO

RR NuNu ••••

•••• ••••++ XX HH••••

BB••••

Dr. Wolf's CHM 201 & 202 20-48

Dissociation of TIDissociation of TI

BB••••

•••• CC

RROO

XX

NuNu••••

HH ••••

••••

++B—HB—H ++CC

OO


•••• ••••++ XX•••• ••••

––

Dr. Wolf's CHM 201 & 202 20-49

Dissociation of TIDissociation of TI––

CC

OO


•••• ••••++ XX•••• ••••

––

••••

CC

RROO

XX

NuNu••••

••••

••••

••••––

dr. wolf's chm 201 & 202 20-1 chapter 20 carboxylic acid derivatives nucleophilic acyl...

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