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Organic Chemistry, 6 th Edition L. G. Wade, Jr.

Chapter 19

Amines

Jo Blackburn Richland College, Dallas, TX Dallas County Community College District © 2006, Prentice Hall

Biological Activity

• Neurotransmitters: dopamine

• Bioregulators: epinephrine

• Vitamins: niacin, B 6

• Alkaloids: nicotine, morphine, cocaine

• Amino acids

Chapter 19

=>

3

Organic derivatives of ammonia.cocaine • Amino acids Chapter 19 => 3 • • Introduction Many are biologically active.

Introduction

Many are biologically active.

• • Introduction Many are biologically active. => Chapter 19 2
=> Chapter 19 2
=>
Chapter 19
2
• Primary (1 ° ): one C-N bond, 2 N-H bonds. • Secondary (2 °

• Primary (1°): one C-N bond, 2 N-H bonds.

• Secondary (2°): two C-N bonds, 1 N-H bond. • Tertiary (3°): three C-N bonds, no N-H bond.

• Quaternary (4°): four C-N bonds, nitrogen has a + formal charge.

Chapter 19

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4

Classes of Aminesno N-H bond. • Quaternary (4 ° ): four C-N bonds, nitrogen has a + formal

Classify: CH 3 N CH 3 N H CH 3 _ CH 3 C NH
Classify:
CH 3
N
CH 3
N
H
CH 3
_
CH 3
C
NH 2
+
CH 3 CH 2 N
Br
CH 2 CH 3
CH 3
=>
CH 3
Chapter 19
5

Amine as Substituent

Amine as Substituent • On a molecule with a higher priority functional group, the amine is

• On a molecule with a higher priority functional group, the amine is named as a substituent.

NH 2 CH 2 CH 2 CH 2 COOH

γ-aminobutyric acid or 4-aminobutanoic acid

Chapter 19

OH NHCH 3
OH
NHCH 3

2-methylaminophenol

=>

7

Common Names Name the alkyl or aryl groups bonded to nitrogen, then add suffix -

Common Names

Common Names Name the alkyl or aryl groups bonded to nitrogen, then add suffix - amine

Name the alkyl or aryl groups bonded to nitrogen, then add suffix -amine.

or aryl groups bonded to nitrogen, then add suffix - amine . diethylmethylamine diphenylamine Chapter 19

diethylmethylamine

bonded to nitrogen, then add suffix - amine . diethylmethylamine diphenylamine Chapter 19 cyclohexyldimethylamine => 6

diphenylamine

Chapter 19

bonded to nitrogen, then add suffix - amine . diethylmethylamine diphenylamine Chapter 19 cyclohexyldimethylamine => 6

cyclohexyldimethylamine

=>

6

Aromatic Amines Amino group is bonded to a benzene ring. Parent compound is called aniline.

Aromatic Amines

Aromatic Amines Amino group is bonded to a benzene ring. Parent compound is called aniline. Chapter

Amino group is bonded to a benzene ring. Parent compound is called aniline.

Aromatic Amines Amino group is bonded to a benzene ring. Parent compound is called aniline. Chapter

Chapter 19

Aromatic Amines Amino group is bonded to a benzene ring. Parent compound is called aniline. Chapter

=>

8

Heterocyclic Amines

Heterocyclic Amines

Heterocyclic Amines

The nitrogen is assigned the number 1.

Heterocyclic Amines The nitrogen is assigned the number 1.   =>   Chapter 19 9  
Heterocyclic Amines The nitrogen is assigned the number 1.   =>   Chapter 19 9  
 

=>

 

Chapter 19

9

assigned the number 1.   =>   Chapter 19 9   Structure of Amines Nitrogen is
 

Structure of Amines

  Structure of Amines

Nitrogen is sp 3 hybridized with a lone pair of electrons in an sp 3 orbital.

is sp 3 hybridized with a lone pair of electrons in an sp 3 orbital.  
 

=>

 

Chapter 19

11

IUPAC Names

IUPAC Names

IUPAC Names

• Name is based on longest carbon chain.

• -e of alkane is replaced with -amine.

 

• Substituents on nitrogen have N- prefix.

Br

N(CH 3 ) 2 CH 3 CH 2 CHCH 2 CH 2 CH 3

NH 2 CH 2 CH 2 CHCH 2 CH 3

3-bromo-1-pentanamine

N,N-dimethyl-3-hexanamine

 

=>

 

Chapter 19

10

-dimethyl-3-hexanamine   =>   Chapter 19 10   Chirality of Amines1` Nitrogen may have 3 different
 

Chirality of Amines1`

  Chirality of Amines1`

Nitrogen may have 3 different groups and a lone pair, but enantiomers cannot be isolated due to inversion around N.

and a lone pair, but enantiomers cannot be isolated due to inversion around N.   =>
 

=>

 

Chapter 19

12

  Chiral Amines • Amines with chiral carbon: 2-butanamine. • Quaternary ammonium salts with four
 
Chiral Amines • Amines with chiral carbon: 2-butanamine.

Chiral Amines

• Amines with chiral carbon: 2-butanamine.

• Quaternary ammonium salts with four different groups bonded to nitrogen.

• Amines in which the nitrogen is restricted in rotation so it cannot interconvert.

=>

=>

Chapter 19

13

rotation so it cannot interconvert. => Chapter 19 13   Solubility and Odor • Small amines
 

Solubility and Odor

Solubility and Odor

• Small amines (<6 C) soluble in water.

• All amines accept hydrogen bonds from water and alcohol.

• Branching increases solubility.

• Most amines smell like rotting fish.

NH 2 CH 2 CH 2 CH 2 CH 2 CH 2 NH 2

1,5-pentanediamine or cadaverine

=>

Chapter 19

15

Boiling Points

Boiling Points

Boiling Points

• N-H less polar than O-H.

• Weaker hydrogen bonding.

• Tertiary amines cannot hydrogen bond.

hydrogen bonding. • Tertiary amines cannot hydrogen bond.   =>   Chapter 19 14   Basicity
 

=>

 

Chapter 19

14

cannot hydrogen bond.   =>   Chapter 19 14   Basicity of Amines • Lone pair
 

Basicity of Amines

  Basicity of Amines

• Lone pair of electrons on nitrogen can accept a proton from an acid

• Aqueous solutions are basic to litmus.

• Ammonia pK b = 4.74

• Alkyl amines are usually stronger bases than ammonia. Increasing the number of alkyl groups decreases solvation of ion, so 2° and 3° amines are similar to 1° amines

in basicity.

=>

Chapter 19

16

Energy Diagram

Energy Diagram

Energy Diagram

Alkyl groups are electron-donating and stabilize the cation.

=>
=>
 

Chapter 19

17

and stabilize the cation. =>   Chapter 19 17   Hybridization Effects Electrons are held more
 

Hybridization Effects

  Hybridization Effects

Electrons are held more tightly in orbitals with more s character, so those compounds are weaker bases.

tightly in orbitals with more s character, so those compounds are weaker bases.   =>  
 

=>

 

Chapter 19

19

Resonance Effects Any delocalization of the electron pair weakens the base. Chapter 19 => 18

Resonance Effects

Resonance Effects Any delocalization of the electron pair weakens the base. Chapter 19 => 18

Any delocalization of the electron pair weakens the base.

Chapter 19
Chapter 19

=>

18

Amine Salts • Ionic solids with high melting points • Soluble in water • No

Amine Salts

Amine Salts • Ionic solids with high melting points • Soluble in water • No fishy

• Ionic solids with high melting points

• Soluble in water

• No fishy odor

Amine Salts • Ionic solids with high melting points • Soluble in water • No fishy

Chapter 19

=>

20

Purifying an Amine => Chapter 19 21

Purifying an Amine

Purifying an Amine => Chapter 19 21
=>
=>

Chapter 19

21

Reactions with C=O Ammonia and primary amines react with carbonyls to give an imine (Schiff

Reactions with C=O

Reactions with C=O Ammonia and primary amines react with carbonyls to give an imine (Schiff base).

Ammonia and primary amines react with carbonyls to give an imine (Schiff base).

=>
=>

Chapter 19

23

Phase Transfer Catalysts Chapter 19 => 22

Phase Transfer Catalysts

Chapter 19
Chapter 19
Phase Transfer Catalysts Chapter 19 => 22

=>

22

SOLVED PROBLEM 19-5Show how to synthesize the following amines from the indicated starting materials. (a) N -cyclopentylaniline

Show how to synthesize the following amines from the indicated starting materials.

(a) N -cyclopentylaniline from aniline

(b) N -ethylpyrrolidine from pyrrolidine

Solution

aniline (b) N -ethylpyrrolidine from pyrrolidine Solution (a) This synthesis requires adding a cyclopentyl group to

(a) This synthesis requires adding a cyclopentyl group to aniline (primary) to make a secondary amine. Cyclopentanone is the carbonyl compound.

a secondary amine. Cyclopentanone is the carbonyl compound. (b) This synthesis requires adding an ethyl group

(b) This synthesis requires adding an ethyl group to a secondary amine to make a tertiary amine. The carbonyl compound is acetaldehyde. Formation of a tertiary amine by Na(AcO) 3 BH reductive amination involves an iminium intermediate, which is reduced by (sodium triacetoxyborohydride).

reductive amination involves an iminium intermediate, which is reduced by (sodium triacetoxyborohydride). Chapter 19 24

Chapter 19

24

Aniline Substitution
Aniline Substitution
Aniline Substitution

Aniline Substitution

Aniline Substitution
 

Electrophilic Substitution of Aniline

• -NH 2 is strong activator, o-,p-directing.

Chapter 19
Chapter 19

• May trisubstitute with excess reagent.

• H + changes -NH 2 to -NH 3 + , a meta- allowing deactivator.

• Attempt to nitrate aniline may explode.

 

=>

=>

 

Chapter 19

25

26

  => =>   Chapter 19 25 26   Electrophilic Substitution of Pyridine  
  => =>   Chapter 19 25 26   Electrophilic Substitution of Pyridine  
 

Electrophilic Substitution of Pyridine

  Electrophilic Substitution of Pyridine   Mechanism for Electrophilic Substitution
 

Mechanism for Electrophilic Substitution

  Electrophilic Substitution of Pyridine   Mechanism for Electrophilic Substitution

Attack at the 3-position (observed)

• Strongly deactivated by electronegative N.

Attack at the 2-position (not observed)
Attack at the 2-position (not observed)
Chapter 19
Chapter 19

=>

• Substitutes in the 3-position.

• Electrons on N can react with electrophile.

Chapter 19
Chapter 19

=>

27

   

28

Nucleophilic Substitution of Pyridine

Nucleophilic Substitution of Pyridine

Nucleophilic Substitution of Pyridine

• Deactivated toward electrophilic attack.

• Activated toward nucleophilic attack.

• Nucleophile will replace a good leaving group in the 2- or 4-position.

=>

=>

Chapter 19

29

group in the 2- or 4-position. => Chapter 19 29   Alkylation of Amines • Amines
 

Alkylation of Amines

  Alkylation of Amines

• Amines react with 1° alkyl halides via the S N 2 mechanism.

• Mixtures of the mono-, di-, and tri- alkylated products are obtained.

2 mechanism. • Mixtures of the mono-, di-, and tri- alkylated products are obtained.   Chapter
 

Chapter 19

31 =>

Mechanism for Nucleophilic Substitution Attack at the 2-position (observed) Nucleophilic Attack at the 3-position (not

Mechanism for Nucleophilic Substitution

Mechanism for Nucleophilic Substitution Attack at the 2-position (observed) Nucleophilic Attack at the 3-position (not

Attack at the 2-position (observed)

Substitution Attack at the 2-position (observed) Nucleophilic Attack at the 3-position (not observed) =>

Nucleophilic Attack at the 3-position (not observed)

=>
=>

Chapter 19

30

Useful Alkylations • Exhaustive alkylation to form the tetraalkylammonium salt. _ NH 2 + N(CH
Useful Alkylations
• Exhaustive alkylation to form the
tetraalkylammonium salt.
_
NH 2
+
N(CH 3 ) 3
I
3 CH 3 I
CH 3 CH 2 CHCH 2 CH 2 CH 3
CH 3 CH 2 CHCH 2 CH 2 CH 3
NaHCO 3
• Reaction with large excess of NH 3 to
form the primary amine.
NH 3 (xs)
=>
Chapter 19
32

CH 3 CH 2 CH 2 Br

CH 3 CH 2 CH 2 NH 2

+

NH 4 Br

Acylation of Amines by Acid Chlorides • Amine attacks C=O, chloride ion leaves. • Product

Acylation of Amines by Acid Chlorides

Acylation of Amines by Acid Chlorides • Amine attacks C=O, chloride ion leaves. • Product is

• Amine attacks C=O, chloride ion leaves.

• Product is amide, neutral, not basic.

• Useful for decreasing activity of aniline toward electrophilic aromatic substitution.

O

C O NH 2 N H CH 3 C Cl N
C
O
NH 2
N
H
CH 3
C
Cl
N

to remove HClof aniline toward electrophilic aromatic substitution. O C O NH 2 N H CH 3 C

Chapter 19

CH 3

33

=>

SOLVED PROBLEM 19-1 (continued) Solution (continued) We can control the nucleophilicity of aniline’s amino group

SOLVED PROBLEM 19-1 (continued) Solution (continued)

SOLVED PROBLEM 19-1 (continued) Solution (continued) We can control the nucleophilicity of aniline’s amino group by

We can control the nucleophilicity of aniline’s amino group by converting it to an amide, which is still activating and ortho, para directing for the Friedel–Crafts reaction. Acylation, followed by hydrolysis of the amide, gives the desired product.

the Friedel–Cr afts reaction. Acylation, followed by hydrolysis of the amide, gives the desired product. Chapter

Chapter 19

35

SOLVED PROBLEM 19-1Show how you would accomplish the following synthetic conversion in good yield. Solution An attempted

Show how you would accomplish the following synthetic conversion in good yield.

accomplish the following synthetic conversion in good yield. Solution An attempted Friedel–Crafts acylation on aniline

Solution

the following synthetic conversion in good yield. Solution An attempted Friedel–Crafts acylation on aniline would

An attempted Friedel–Crafts acylation on aniline would likely meet with disaster. The free amino group would attack both the acid chloride and the Lewis acid catalyst.

meet with disaster. The free amino group would attack both the acid chloride and the Lewis

Chapter 19

34

Formation of Sulfonamides • Primary or secondary amines react with sulfonyl chloride. O O O

Formation of Sulfonamides

Formation of Sulfonamides • Primary or secondary amines react with sulfonyl chloride. O O O +
• Primary or secondary amines react with sulfonyl chloride. O O O + base R
• Primary or secondary amines react with
sulfonyl chloride.
O
O
O
+
base
R
NH 2
R'
S
Cl
R'
S
NH
R
Cl _
R'
S
NH
R
O
O
H
O
• Sulfa drugs are sulfonamides
that are antibacterial agents.
=>
Chapter 19
36
Hofmann Elimination • A quaternary ammonium salt has a good leaving group - a neutral

Hofmann Elimination

Hofmann Elimination • A quaternary ammonium salt has a good leaving group - a neutral amine.

• A quaternary ammonium salt has a good leaving group - a neutral amine.

• Heating the hydroxide salt produces the least substituted alkene.

_

 

+

_

Ag 2 O

N(CH 3 ) 3

OH

heat

CH 3 CHCH 2 CH 2 CH 3

H 2 O

CH 3 CHCH 2 CH 2 CH 3

 

CH 2 CHCH 2 CH 2 CH 3

Chapter 19

=>

37

SOLVED PROBLEM 19-2Predict the major product(s) formed when the following amine is treated with excess iodomethane, followed

Predict the major product(s) formed when the following amine is treated with excess iodomethane, followed by heating with silver oxide.

Solution

iodomethane, followed by heating with silver oxide. Solution Solving this type of problem requires finding every
iodomethane, followed by heating with silver oxide. Solution Solving this type of problem requires finding every

Solving this type of problem requires finding every possible elimination of the methylated salt. In this case, the salt has the following structure:

every possible elimination of the methylated salt. In this case, the salt has the following structure:

Chapter 19

39

E2 Mechanism Chapter 19 => 38

E2 Mechanism

E2 Mechanism Chapter 19 => 38
E2 Mechanism Chapter 19 => 38

Chapter 19

=>

38

SOLVED PROBLEM 19-2 (continued) Solution (continued)The green, blue, and red arrows show the thre e possible elimination r outes. The

The green, blue, and red arrows show the three possible elimination routes. The corresponding products are

elimination r outes. The corresponding products are The first (green) alkene has a disubstituted double bond.
elimination r outes. The corresponding products are The first (green) alkene has a disubstituted double bond.

The first (green) alkene has a disubstituted double bond. The second (blue) alkene is monosubstituted, and the red alkene (ethylene) has an unsubstituted double bond. We predict that the red products will be favored.

Chapter 19

40

Oxidation of Amines • Amines are easily oxidized, even in air. • Common oxidizing agents:

Oxidation of Amines

Oxidation of Amines • Amines are easily oxidized, even in air. • Common oxidizing agents: H

• Amines are easily oxidized, even in air.

• Common oxidizing agents: H 2 O 2 , MCPBA.

• 2° Amines oxidize to hydroxylamine (-NOH).

• 3° Amines oxidize to amine oxide (-N + -O - ).

Amines oxidize to hydroxylamine (-NOH). • 3 ° Amines oxidize to amine oxide (-N + -O
Chapter 19
Chapter 19

=>

41

SOLVED PROBLEM 19-3Predict the products expected when the following compound is treated with H 2 O 2

Predict the products expected when the following compound is treated with H 2 O 2 and heated.

compound is treated with H 2 O 2 and heated. Solution Oxidation converts the tertiary amine
compound is treated with H 2 O 2 and heated. Solution Oxidation converts the tertiary amine

Solution

Oxidation converts the tertiary amine to an amine oxide. Cope elimination can give either of two alkenes. We expect the less hindered elimination to be favored, giving the Hofmann product.

Chapter 19
Chapter 19

43

Cope Elimination

Cope Elimination

Cope Elimination

Amine oxides undergo elimination to form the least substituted alkene under milder conditions than the Hofmann reaction.

 

_

+ H N(CH 3 ) 2 H N(CH 3 ) 2 CH 2 CHCH 2
+
H
N(CH 3 ) 2
H
N(CH 3 ) 2
CH 2
CHCH 2 CH 2 CH 3
CH 2
CHCH 2 CH 2 CH 3
CH 2

O

O

HO

N(CH 3 ) 2

CHCH 2 CH 2 CH 3

 

=>

 

Chapter 19

42

2 CH 2 CH 3   =>   Chapter 19 42   Nitrous Acid Reagent •
 

Nitrous Acid Reagent

  Nitrous Acid Reagent

• Nitrous acid is produced in situ by mixing sodium nitrite with HCl.

• The nitrous acid is protonated, loses water to form the nitrosonium ion.

HCl. • The nitrous acid is protonated, loses water to form the nitrosonium ion.   =>
 

=>

 

Chapter 19

44

Reaction with Nitrous Acid • 1 ° Amines form diazonium salts, R-N + ≡ N.

Reaction with Nitrous Acid

Reaction with Nitrous Acid • 1 ° Amines form diazonium salts, R-N + ≡ N. •

• 1° Amines form diazonium salts, R-N + N.

• Alkyldiazonium salts are unstable, but arenediazonium salts are widely used for synthesis.

• 2° Amines form N-nitrosoamines, R 2 N-N=O, found to cause cancer in laboratory animals.

Chapter 19

=>

45

SOLVED PROBLEM 19-4Show how you would convert toluene to 3,5-dibromotoluene in good yield. Solution Direct bromination of

Show how you would convert toluene to 3,5-dibromotoluene in good yield.

Solution

toluene to 3,5-dibromotoluene in good yield. Solution Direct bromination of toluene cannot give 3,5-dibr

Direct bromination of toluene cannot give 3,5-dibromotoluene because the methyl group activates the ortho and para positions.

the methyl group activates the ortho and para positions. Starting with p -toluidine ( p -methylaniline),

Starting with p -toluidine (p -methylaniline), however, the strongly activating amino group directs bromination to its ortho positions. Removal of the amino group (deamination) gives the desired product.

bromination to its ortho positions. Removal of the amino group (deamination) gives the desired product. Chapter

Chapter 19

47

Arenediazonium Salts • Stable in solution at 0°–10°C. • The - + N ≡ N

Arenediazonium Salts

Arenediazonium Salts • Stable in solution at 0°–10°C. • The - + N ≡ N group

• Stable in solution at 0°–10°C.

• The - + NN group is easily replaced by many different groups.

• Nitrogen gas, N 2 , is a by-product.

Chapter 19
Chapter 19

=>

46

Synthesis by Reductive Amination • To produce a 1 ° amine, react an aldehyde or

Synthesis by Reductive Amination

Synthesis by Reductive Amination • To produce a 1 ° amine, react an aldehyde or ketone

• To produce a 1° amine, react an aldehyde or ketone with hydroxylamine, then reduce the oxime.

• To produce a 2° amine, react an aldehyde or ketone with a 1° amine, then reduce the imine.

• To produce a 3° amine, react an aldehyde or ketone with a 2° amine, then reduce the imine salt.

=>

Chapter 19

48

Examples primary amine secondary amine H 3 C CH 3 H 3 C CH 3
Examples
primary amine
secondary amine
H 3 C
CH 3
H 3 C
CH 3
N
N
+
O
C
C
HN(CH 3 ) 2
H
Na(CH 3 COO) 3 BH
H
C
H
H
H +
CH 3 COOH
=>
tertiary amine
Chapter 19
49
Examples primary amine tertiary amine Chapter 19 => 51

Examples

Examples primary amine tertiary amine Chapter 19 => 51
Examples primary amine tertiary amine Chapter 19 => 51

primary amine

tertiary amine
tertiary amine

Chapter 19

=>

51

Acylation-Reduction

Acylation-Reduction • An acid chloride reacts with ammonia or a 1 ° amine or a 2

• An acid chloride reacts with ammonia or a 1° amine or a 2° amine to form an amide.

• The C=O of the amide is reduced to CH 2 with lithium aluminum hydride.

• Ammonia yields a 1° amine.

• A 1° amine yields a 2° amine.

• A 2° amine yields a 3° amine.

Chapter 19

=>

50

Direct Alkylation (1°)

Direct Alkylation (1 ° ) • Use a large excess (10:1) of ammonia with a primary

• Use a large excess (10:1) of ammonia with a primary alkyl halide or tosylate.

• Reaction mechanism is S N 2.

NH 3 CH 3 CH 2 CH 2 Chapter 19
NH 3
CH 3 CH 2 CH 2
Chapter 19

52

=>

CH 3 CH 2 CH 2

Br

NH 2

+ NH 4 Br

Gabriel Synthesis (1°)

Gabriel Synthesis (1 ° ) • Use the phthalimide anion as a form of ammonia that

• Use the phthalimide anion as a form of ammonia that can only alkylate once.

• React the anion with a good S N 2 substrate, then heat with hydrazine.

only alkylate once. • React the anion with a good S N 2 substrate, then heat

Chapter 19

=>

53

Nitrile Reduction (1°)

Nitrile Reduction (1 ° ) • Nitrile, -C ≡ N, is a good S N 2

• Nitrile, -CN, is a good S N 2 nucleophile.

• Reduction with H 2 or LiAlH 4 adds -CH 2 NH 2 .

CN 1) LiAlH 4 2) H 2 O Chapter 19
CN
1) LiAlH 4
2) H 2 O
Chapter 19

55

=>

Br NaCN CH 2 NH 2

Br

NaCN

Br NaCN CH 2 NH 2

CH 2 NH 2

Azide Reduction (1 ° ) • Azide ion, N 3 - , is a good

Azide Reduction (1°)

Azide Reduction (1 ° ) • Azide ion, N 3 - , is a good nucleophile.

• Azide ion, N 3 - , is a good nucleophile.

• React azide with unhindered 1° or 2° halide or tosylate (S N 2).

• Alkyl azides are explosive! Do not isolate.

1 ° or 2 ° halide or tosylate (S N 2). • Alkyl azides are explosive!
Chapter 19
Chapter 19

=>

54

Reduction of Nitro Compounds (1 ° ) • -NO 2 is reduced to -NH 2

Reduction of Nitro Compounds (1°)

Reduction of Nitro Compounds (1 ° ) • -NO 2 is reduced to -NH 2 by

• -NO 2 is reduced to -NH 2 by catalytic hydrogenation, or active metal with acid.

• Commonly used to synthesize anilines.

by catalytic hydrogenation, or active metal with acid. • Commonly used to synthesize anilines. Chapter 19

Chapter 19

=>

56

Hofmann Rearrangement of Amides (1 ° )

Hofmann Rearrangement of Amides (1°)

Hofmann Rearrangement of Amides (1 ° )

In the presence of a strong base, primary amides react with chlorine or bromine to form amines with one less C.

 
O C
O
C
 

Br 2 , OH _

  O C   Br 2 , OH _  
 

NH 2

N H 2 NH 2

NH 2

H 2 O

 

=>

 

Chapter 19

57

2 NH 2 H 2 O   =>   Chapter 19 57   Hofmann Mechanism (2)
 

Hofmann Mechanism (2)

  Hofmann Mechanism (2)

Isocyanate reacts with water to form carbamic acid, which loses CO 2 .

=>
=>
 

Chapter 19

59

Hofmann Mechanism (1) • N-H protons of amide are abstracted. • Rearrangement forms an isocyanate.

Hofmann Mechanism (1)

• N-H protons of amide are abstracted.

• Rearrangement forms an isocyanate.

Hofmann Mechanism (1) • N-H protons of amide are abstracted. • Rearrangement forms an isocyanate. =>
=>
=>

Chapter 19

58

End of Chapter 19 Chapter 19 60

End of Chapter 19

Chapter 19

60