introduction to organic chemistry 2 ed william h. brown

1313

13-1Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.

Introduction to Introduction to Organic Organic

ChemistryChemistry2 ed2 ed

William H. BrownWilliam H. Brown

1313


Chapter 13Chapter 13

CarboxylCarboxylDerivativesDerivatives

1313


Carboxyl DerivativesCarboxyl Derivatives• In this chapter, we study four classes of organic

compounds. • under the structural formula of each is a drawing to

help you see its relationship to the carboxyl group.

O

RC-OH H-Cl

O

RC-OH H-OCR'

O

RC-OH H-OR'

O

O

RC-OH H-NH2

An amide

O

RCNH2An acid chloride

An esterAn acid anhydride

O OOO

RCCl RCOR'RCOCR'

1313


Structure: Acid ChloridesStructure: Acid Chlorides• The functional group of an acid halide is an acyl

group bonded to a halogen• to name, change the suffix --ic acid ic acid to --yl halideyl halide

Benzoyl chloride

Ethanoyl chloride(Acetyl chloride)

An acyl chloride(An acid chloride)

An acyl group

O O

O O

CCl

RC- RCCl

CH3CCl ClC(CH2)4CCl

O O

Hexanedioyl chloride (Adipoyl chloride)

1313


Acid AnhydridesAcid Anhydrides• The functional group of an acid anhydride is two

acyl groups bonded to an oxygen atom• the anhydride may be symmetrical (two identical acyl

groups) or mixed (two different acyl groups)• to name, replace acidacid of the parent acid by anhydrideanhydride

CH3COCCH3

O O

Aceticanhydride

COC-

O O

CH3COC

O O

Benzoic anhydride Acetic benzoicanhydride

1313


Acid AnhydridesAcid Anhydrides• Cyclic anhydrides are named from the

dicarboxylic acids from which they are derived

Phthalic anhydride

Succinic anhydride

O

O

O

O

O

O

1313


Acid AnhydridesAcid Anhydrides• A phosphoric acid anhydride contains two

phosphoryl groups bonded to an oxygen atom

Triphosphoric acid

Diphosphate ion(Pyrophosphate ion)

Diphosphoric acid(Pyrophosphoric acid)

O O OO

O O

O-

O-

O

OH OH

OH OH OH

O-

O-

O O O

O-

HO-P-O-P-OH-O-P-O-P-O

-

HO-P-O-P-O-P-OH-O-P-O-P-O-P-O

-

Triphosphate ion

1313


Esters Esters • The functional group of an ester is an acyl group

bonded to -OR or -OAr• name the alkyl or aryl group bonded to oxygen; follow

by the name of the acid but with the suffix --icic acid acid changed to -ateate

Ethyl ethanoate(Ethyl acetate)

Isopropyl benzoate

COCH(CH3 )2

O O

CH3 COCH2CH3

1313


Lactones Lactones • Cyclic esters are called lactones• Name the parent carboxylic acid, drop the suffix

--ic acidic acid, and add -olactoneolactone

6-Hexanolactone(ε- )Caprolactone

4-Butanolactone(γ- )Butyrolactone

εδγ

βα

γβ

α O O

O O1

2

213

3 44

5 6

1313


Phosphoric EstersPhosphoric Esters• Phosphoric acid has three -OH groups and forms

mono-, di-, and triesters• name the alkyl or aryl group bonded to oxygen

followed by the word phosphate

Dimethyl phosphate

OCH3

O

CH3OPOH

OCH2CH3

O

CH3CH2OPOCH2CH3

Triethyl phosphate

1313


Phosphoric EstersPhosphoric Esters• to name more complex phosphoric esters, name the

organic molecule followed by the name phosphate

D-Glucose 6-phosphate(in the first step of glycolysis,

glucose is converted to its6-phosphoric ester

CH2-O-P-O-OHHOHHHHOOHH

CHO

O

O- N

HO

H3C

CH2OPO-CHO O

O-

Pyridoxal phosphate(one of the metabolicallyactive forms of vitamin B6

1313


AmidesAmides• The functional group of an amide is an acyl group

bonded to a nitrogen atom• to name, drop --oic acid oic acid from the name of the parent

acid and add -amideamide• if the amide nitrogen is bonded to an alkyl or aryl

group, name the group and show its location on nitrogen by NN-

N-Methylacetamide(a 2° amide)

Acetamide(a 1° amide)

Benzamide(a 1° amide)

O

CNH2

O O

CH3 CNH2 CH3 CNHCH3

1313


AmidesAmides• Cyclic amides are called lactams

• name the parent carboxylic acid, drop the suffix --icic acidacid, and add -lactamlactam α

β

γδ ε

6-Hexanolactam(ε-Caprolactam)

α

βH3C

O

NH

O

NH1

2 1

234

5 63

3-Butanolactam(β-Butyrolactam)

1313


AmidesAmides• The penicillins are a family of β-lactam antibiotics

N

S CH3

CH3

CO2HO

NC

H

O

CH2

Penicillin G

H H

the penicillins differin the group bondedto the acyl carbon

1313


Penicillin GPenicillin G

N

S CH3

CH3

CO2HO

NC

H

O

CH2

H H

1313


AmidesAmides• The cephalosporins are also β-lactam

antibiotics

NO

NC

H

N

S

CO2HCH3

S

NH2N

Cefetamet

H

OCH3

H

the cephalosporins differin the group bonded to theacyl carbon and the side chainbonded to the thiazine ring

1313


CefetametCefetamet

NO

NC

H

N

S

CO2HCH3

S

NH2N

H

OCH3

H

1313


Characteristic ReactionsCharacteristic Reactions• Nucleophilic acyl substitutionNucleophilic acyl substitution: an addition-

elimination sequence resulting in substitution of one nucleophile for another

•• •• ••

••

•••• ••••

••

Tetrahedral carbonyladdition intermediate

-

-

- ++ CNuR

CY R

CNuR

O

Y

O O

Nu Y

Substitution product

1313


Characteristic ReactionsCharacteristic Reactions• The leaving group as an anion, Y-, to illustrate an

important point: the weaker the base, the better the leaving group

Increasing basicity

Increasing leaving ability

O

X -- OR- NR2- O-CR

1313


Characteristic ReactionsCharacteristic Reactions• halide ion is the weakest base and the best leaving

group; acid halides are the most reactive toward nucleophilic acyl substitution

• amide ion is the strongest base and the poorest leaving group; amides are the least reactive toward nucleophilic acyl substitution

Reactivity toward nucleophilic acyl substitution

OOOOO

RCXRCOCRRCOR'RCNH2Amide Ester Anhydride Acid halide

1313


Rexn with HRexn with H22O - RCOClO - RCOCl• Low-molecular-weight acid chlorides react rapidly

with water• Higher-molecular weight acid chlorides are less

soluble in water and react less readily

++

O O

CH3 CCl H2 O CH3 COH HCl

1313


Rexn with HRexn with H22O - EstersO - Esters• Low-molecular-weight acid anhydrides react

readily with water to give two molecules of carboxylic acid

• Higher-molecular-weight acid anhydrides also react with water, but less readily

++

O O O O

CH3 COCCH3 H2 O CH3 COH HOCCH3

1313


Rexn with HRexn with H22O - EstersO - Esters• Esters are hydrolyzed only slowly, even in boiling

water• hydrolysis becomes more rapid if they are heated with

either aqueous acid or base

• Hydrolysis in aqueous acid is the reverse of Fischer esterification• the acid catalyst protonates the carbonyl oxygen and

increases its electrophilic character toward attack by water to form a tetrahedral carbonyl addition intermediate

• collapse of this intermediate gives the carboxylic acid and alcohol

1313


Rexn with HRexn with H22O - EstersO - Esters• Acid-catalyzed ester hydrolysis

O

CH+

R OCH3

OH

CR

OCH3

OH

+ H2O

H+O

CR OH

+ CH3OH

Tetrahedral carbonyladdition intermediate

1313


Rexn with HRexn with H22O - EstersO - Esters• Hydrolysis of an esters is aqueous base is often

called saponificationsaponification• each mol of ester hydrolyzed requires 1 mol of base;

for this reason, ester hydrolysis in aqueous base is said to be base-promoted

• hydrolysis of an ester in aqueous base involves formation of a tetrahedral carbonyl addition intermediate followed by its collapse and proton transfer

++

O O

RCOCH3 NaOH RCO- Na

+ CH3 OHH2 O

1313


Rexn with HRexn with H22O - EstersO - Esters• base-promoted ester hydrolysis

••

••

••

••

••

••

••

••

••

••

••

••

••

•• ••

••

••

••

••

•• ••

••

••

••

••

•• ••

••++

-

+

O O

OH

O CH3

O

O H HO

O

R-C-O-CH3 OH R-C

R-C O-CH3 R-C O-CH3

-

-

-

-

1313


Rexn with HRexn with H22O - AmidesO - Amides• hydrolysis of an amide in aqueous acid requires 1 mol

of acid per mol of amide

2-Phenylbutanoic acid

2-Phenylbutanamide+

+ +heat

Ph

O

O

Ph

CH3 CH2CHCNH2 H2 O HClH2 O

CH3 CH2CHCOH NH4+Cl

-

1313


Rexn with HRexn with H22O - AmidesO - Amides• hydrolysis of an amide in aqueous base requires 1 mol

of base per mol of amide

AnilineSodium acetate

N-Phenylethanamide(N-Phenylacetamide,

Acetanilide) +

+heat

O

H2 N

CH3 CNH

O

CH3 CO-

Na+

NaOHH2 O

1313


Rexn with AlcoholsRexn with Alcohols• Acid halides react with alcohols to give esters

• because acid halides are so reactive toward even weak nucleophiles such as alcohols, no catalyst is necessary

Butanoyl chloride

Cyclohexyl butanoate

+

Cyclohexanol

+ HO

O

O

CH3CH2CH2CCl

HClCH3CH2CH2CO

1313


Rexn with AlcoholsRexn with Alcohols• Acid anhydrides react with alcohols to give one

mol of ester and one of carboxylic acid

CH3COCCH3 + HOCH2CH3

CH3COCH2CH3 + CH3COH

O O

O

Acetic anhydride Ethanol

Ethyl acetate Acetic acid

O

1313


Rexn with AlcoholsRexn with Alcohols• Synthesis of aspirin synthesized

Acetylsalicylic acid (Aspirin)

2-Hydroxybenzoic acid

(Salicylic acid)

+

+

Acetic acid

Acetic anhydride

OO

CO2 HOCCH3

OHCO2 H

OO

CH3 COH

CH3 COCCH3

1313


Rexn with Ammonia, etc.Rexn with Ammonia, etc.• Acid halides react with ammonia, and 1° and 2°

amines to form amides• 2 moles of the amine are required per mole of acid

chloride

+

+

Hexanoyl chlorideAmmonia

Hexanamide Ammonium chloride

2NH3

NH4+ Cl -

O

CH3(CH2)4CCl

O

CH3(CH2)4CNH2

1313


Rexn with Ammonia, etc.Rexn with Ammonia, etc.• Acid anhydrides react with ammonia, and 1° and

2° amines to form amides.• 2 moles of ammonia or amine are required per mole of

anhydride

Ammonia+

Ammonium acetateEthanamide(Acetamide)

+

Acetic anhydride

O O

O O

CH3 COCCH3 2NH3

CH3 CNH2 CH3 CO- NH4

+

1313


Rexn with Ammonia, etc.Rexn with Ammonia, etc.• Esters react with ammonia, and 1° and 2° amines

to form amides• esters are less reactive than either acid halides or acid

anhydrides

• Amides do not react with ammonia, or 1° or 2° amines

Phenylacetamide

Ethyl phenylacetate

+

+

O

O

C6H5CH2COCH2 CH3 NH3

C6H5CH2CNH2 CH3 CH2OH

1313


InterconversionInterconversion• Relative reactivities of carboxyl derivatives

RC-Cl

O

RC-OCR'

O O

RC-OR'

O

RC-NH2

O

RC-O-

O

SOCl2

Decreasing reactivity

~ RC-OH

O

1313


Esters with RMgXEsters with RMgX• A formic ester with 2 moles of RMgX followed by

hydrolysis gives a 2° alcohol

+

magnesium alkoxide salt

A 2° alcohol

An ester offormic acid

HCOCH3 2RMgX

HClHC-R + CH3OH

O

R

OH

H2 O

1313


Esters with RMgXEsters with RMgX• An ester than a formate with 2 moles of RMgX

gives a 3° alcohol

magnesium alkoxide salt

+

A 3° alcohol

An ester of any acidother than formic acid

O

R

OH

CH3 COCH3 2RMgX

HClCH3 C-R + CH3OH

H2 O

1313


Esters with RMgXEsters with RMgX• Steps 1 & 2

+

••

+

A magnesium salt(a tetrahedral carbonyladdition intermediate)

A ketone

••

•• ••••••

••

R MgXCH3 -C-OCH3

CH3 -C CH3 O - [ MgX]+

1

1

2

2

••

••

••

••

••

••

••O

CH3-C-OCH3

R

O -[MgX]+ O

R

1313


Esters with RMgXEsters with RMgX• Steps 3 & 4

•••• ••••••

••••

Magnesium salt

A ketone

+

A 3° alcohol

R

O

R MgX

OH

RR

O - [MgX]+

CH3 -C

H2 O, HCl CH3 -C-RCH3 -C-R

33

(4)

1313


Red'n - Esters by LiAlHRed'n - Esters by LiAlH44• Most reductions of carbonyl compounds are now

accomplished by hydride reducing agents

• Esters are reduced by LiAlH4 to two alcohols• the alcohol derived from the carbonyl group is primary

Methanol2-Phenyl-1-propanol

Methyl 2-phenyl-propanoate

+

O

CH3

CHCH2 OH

CHCOCH3

CH3

1. LiAlH4 , ether

2. H2 O, HCl

CH3 OH

1313


Red'n - Esters by LiAlHRed'n - Esters by LiAlH44• NaBH4 does not normally reduce esters, but it

does reduce aldehydes and ketones• Selective reduction is often possible by the

proper choice of reducing agents and experimental conditions

O O

OOH

CH3 CCH2COCH2 CH3NaBH4

CH3 CHCH2COCH2 CH3

1313


Red'n - Amides by LiAlHRed'n - Amides by LiAlH44• LiAlH4 reduction of an amide gives a 1°, 2°, or 3°

amine, depending on the degree of substitution of the amide

Octanamide 1-Octanamine

O

CH3 (CH2)6 CNH2 CH3 (CH2)6 CH2 NH21. LiAlH4

2. H2 O

N,N-Dimethy-benzamide

N,N-Dimethyl-benzylamine

CN(CH3 )2

OCH2 N(CH3)2

1. LiAlH4

2. H2 O

1313


InterconversionsInterconversions• ProblemProblem: show reagents and experimental

conditions to bring about each conversion

O

PhCH2 COCH3PhCH2 CH2NH2

PhCH2 CH2OH

O

PhCH2 COH

O

PhCH2 CNH2

O

PhCH2 CCl

O

PhCH2 CH

1

3

2

4

6

5

7

810

9

1313


Carboxyl Carboxyl

DerivativesDerivativesEnd Chapter 13End Chapter 13

introduction to organic chemistry 2 ed william h. brown

Documents