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Chapter 21 Amines. 21.1 Amine Nomenclature. Classification of Amines. Alkylamine N attached to alkyl group Arylamine N attached to aryl group Primary, secondary, or tertiary determined by number of carbon atoms directly attached to nitrogen. Nomenclature of Primary Alkylamines (RNH 2 ).

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classification of amines
Classification of Amines
  • Alkylamine
    • N attached to alkyl group
  • Arylamine
    • N attached to aryl group
  • Primary, secondary, or tertiary
    • determined by number of carbon atoms directly attached to nitrogen
nomenclature of primary alkylamines rnh 2
Nomenclature of Primary Alkylamines (RNH2)
  • Two IUPAC styles
  • 1) Analogous to alcohols: replace -e ending with -amine
  • 2) Name alkyl group and attach -amine as a suffix
examples some primary alkylamines

NH2

CH3CHCH2CH2CH3

NH2

Examples: some primary alkylamines

(RNH2: one carbon directly attached to N)

ethylamine or ethanamine

CH3CH2NH2

cyclohexylamine orcyclohexanamine

1-methylbutylamine or2-pentanamine or

pentan-2-amine

nomenclature of primary arylamines arnh 2

NH2

Br

CH2CH3

F

NH2

Nomenclature of Primary Arylamines (ArNH2)
  • Name as derivatives of aniline.

p-fluoroaniline or

4-fluoroaniline

5-bromo-2-ethylaniline

amino groups as substituents

O

HC

NH2

Amino Groups as Substituents
  • Amino groups rank below OH groups and higher oxidation states of carbon.
  • In such cases name the amino group as a substituent.

HOCH2CH2NH2

2-aminoethanol

p-aminobenzaldehyde

secondary and tertiary amines
Secondary and Tertiary Amines
  • Name as N-substituted derivatives of parent primary amine.
  • (N is a locant-it is not alphabetized, but is treated the same way as a numerical locant)
  • Parent amine is one with longest carbon chain.
examples

NHCH2CH3

NO2

Cl

CH3

N

CH3

Examples

CH3NHCH2CH3

N-methylethylamine

4-chloro-N-ethyl-3-nitroaniline

N,N-dimethylcycloheptylamine

ammonium salts

CH3

+

Cl

N

CF3CO2

CH2CH3

H

Ammonium Salts
  • A nitrogen with four substituents is positivelycharged and is named as a derivative of ammonium ion (NH4+).

+

CH3NH3

methylammoniumchloride

N-ethyl-N-methylcyclopentylammoniumtrifluoroacetate

ammonium salts1

CH3

+

CH3

CH2

I

N

CH3

Ammonium Salts
  • When all four atoms attached to N are carbon,the ion is called a quaternary ammonium ion andsalts that contain it are called quaternaryammonium salts.

benzyltrimethylammonium iodide

alkylamines
Alkylamines

147 pm

112°

106°

alkylamines1
Alkylamines

Most prominent feature is high electrostaticpotential at nitrogen. Reactivity of nitrogen lonepair dominates properties of amines.

geometry at n
Geometry at N

Compare geometry at N of methylamine, aniline,and formamide.

  • Pyramidal geometry at sp3-hybridized N in methylamine.
  • Planar geometry at sp2-hybridized N in formamide.

H

H

H

sp3

sp2

NH2

C

NH2

C

O

H

geometry at n1
Geometry at N

Compare geometry at N of methylamine, aniline,and formamide.

  • Pyramidal geometry at sp3-hybridized N in methylamine.
  • Planar geometry at sp2-hybridized N in formamide.

sp2

sp3

geometry at n2
Geometry at N

Angle that the C—N bond makes with bisector ofH—N—H angle is a measure of geometry at N.

  • Note: This is not the same as the H—N—H bond angle.

sp2

sp3

180°

~125°

geometry at n3
Geometry at N

Angle that the C—N bond makes with bisector ofH—N—H angle is a measure of geometry at N.

sp2

sp3

180°

~125°

142.5°

geometry at n4
Geometry at N

Geometry at N in aniline is pyramidal; closer tomethylamine than to formamide.

142.5°

geometry at n5
Geometry at N
  • Hybridization of N in aniline lies between sp3 and sp2.
  • Lone pair of N can be delocalized into ring best if N is sp2 and lone pair is in a p orbital.
  • Lone pair bound most strongly by N if pair is in an sp3 orbital of N, rather than p.
  • Actual hybridization is a compromise that maximizesbinding of lone pair.

142.5°

electrostatic potential maps of aniline
Electrostatic Potential Maps of Aniline

Nonplanar geometry at N. Region of highestnegative potential is at N.

Planar geometry at N. High negative potential shared by N and ring.

Figure 21.2 (page 934)

physical properties
Physical Properties
  • Amines are more polar and have higher boiling points than alkanes; but are less polar andhave lower boiling points than alcohols.

CH3CH2CH3

CH3CH2NH2

CH3CH2OH

dipolemoment ():

0 D

1.2 D

1.7 D

boiling point:

-42°C

17°C

78°C

physical properties1
Physical Properties

CH3CH2CH2NH2

CH3CH2NHCH3

(CH3)3N

boilingpoint:

50°C

34°C

3°C

  • Boiling points of isomeric amines decrease ingoing from primary to secondary to tertiary amines.
  • Primary amines have two hydrogens on N capable of being involved in intermolecular hydrogen bonding. Secondary amines have one. Tertiary amines cannot be involved in intermolecular hydrogen bonds.
effect of structure on basicity
Effect of Structure on Basicity
  • 1. Alkylamines are slightly stronger bases than ammonia.
table 21 1 basicity of amines in aqueous solution
Table 21.1Basicity of Amines in Aqueous Solution
  • Amine Conj. Acid pKa
  • NH3 NH4+ 9.3
  • CH3CH2NH2 CH3CH2NH3+ 10.8

CH3CH2NH3+ is a weaker acid than NH4+;therefore, CH3CH2NH2 is a stronger base than NH3.

effect of structure on basicity1
Effect of Structure on Basicity
  • 1. Alkylamines are slightly stronger bases than ammonia.
  • 2. Alkylamines differ very little in basicity.
table 21 1 basicity of amines in aqueous solution1
Table 21.1Basicity of Amines in Aqueous Solution
  • Amine Conj. Acid pKa
  • NH3 NH4+ 9.3
  • CH3CH2NH2 CH3CH2NH3+ 10.8
  • (CH3CH2)2NH (CH3CH2)2NH2+ 11.1
  • (CH3CH2)3N (CH3CH2)3NH+ 10.8

Notice that the difference separating a primary,secondary, and tertiary amine is only 0.3 pK units.

effect of structure on basicity2
Effect of Structure on Basicity
  • 1. Alkylamines are slightly stronger bases than ammonia.
  • 2. Alkylamines differ very little in basicity.
  • 3. Arylamines are much weaker bases than ammonia.
table 21 1 basicity of amines in aqueous solution2
Table 21.1Basicity of Amines in Aqueous Solution
  • Amine Conj. Acid pKa
  • NH3 NH4+ 9.3
  • CH3CH2NH2 CH3CH2NH3+ 10.8
  • (CH3CH2)2NH (CH3CH2)2NH2+ 11.1
  • (CH3CH2)3N (CH3CH2)3NH+ 10.8
  • C6H5NH2 C6H5NH3+ 4.6
decreased basicity of arylamines

H

••

+

N

H

+

H2N

Strongeracid

Strongerbase

pKa = 4.6

H

+

H3N

••

+

NH2

Weakerbase

Weakeracid

pKa =10.6

Decreased Basicity of Arylamines

K = 106

decreased basicity of arylamines1

H

N

H

H

+

H3N

••

+

NH2

Decreased Basicity of Arylamines

••

+

+

H2N

Strongeracid

When anilinium ion loses a proton, theresulting lone pair is delocalized into the ring.

Weakeracid

decreased basicity of arylamines2

H

N

H

Strongerbase

H

+

H3N

••

+

NH2

Weakerbase

Decreased Basicity of Arylamines

••

+

+

H2N

Aniline is a weaker base because its lone pair is more strongly held.

decreased basicity of arylamines3

pKa of conjugate acid:

4.6

0.8

~-5

Decreased Basicity of Arylamines
  • Increasing delocalization makes diphenylamine a weaker base than aniline, and triphenylamine a weaker base than diphenylamine.

C6H5NH2

(C6H5)2NH

(C6H5)3N

effect of substituents on basicity of arylamines

X

NH2

Effect of Substituents on Basicity of Arylamines
  • 1. Alkyl groups on the ring increase basicity, but only slightly (less than 1 pK unit).

X pKa of conjugate acid

H 4.6

CH3 5.3

effect of substituents on basicity of arylamines1

X

NH2

Effect of Substituents on Basicity of Arylamines
  • 2. Electron withdrawing groups, especially ortho and/or para to amine group, decrease basicity and can have a large effect.

X pKa of conjugate acid

H 4.6

CF3 3.5O2N 1.0

p nitroaniline

••

••

O

O

••

••

••

+

+

+

••

N

NH2

N

NH2

O

O

••

••

••

••

••

••

p-Nitroaniline
  • Lone pair on amine nitrogen is conjugated with p-nitro group—more delocalized than in aniline itself. Delocalization is lost on protonation.
effect is cumulative
Effect is Cumulative
  • Aniline is 3800 times more basic thanp-nitroaniline.
  • Aniline is ~1,000,000,000 times more basic than 2,4-dinitroaniline.
heterocyclic amines

••

N

N

••

H

piperidine

pyridine

pKa of conjugate acid:

11.2

pKa of conjugate acid:

5.2

(resembles anarylamine inbasicity)

(an alkylamine)

Heterocyclic Amines

is more basic than

heterocyclic amines1

N

H

••

N

••

N

••

Heterocyclic Amines

is more basic than

imidazole

pyridine

pKa of conjugate acid:

7.0

pKa of conjugate acid:

5.2

imidazole

N

H

••

N

••

+

H

H

N

H

N

••

N

N

••

H

Imidazole
  • Which nitrogen is protonated in imidazole?

H+

H+

+

imidazole1

N

H

••

N

••

+

H

H

N

H

N

H

N

N

••

Imidazole
  • Protonation in the direction shown gives a stabilized ion.

H+

+

••

phase transfer catalysis
Phase-Transfer Catalysis
  • Phase-transfer agents promote the solubility ofionic substances in nonpolar solvents. Theytransfer the ionic substance from an aqueousphase to a non-aqueous one.
  • Phase-transfer agents increase the rates ofreactions involving anions. The anion is relativelyunsolvated and very reactive in nonpolar mediacompared to water or alcohols.
phase transfer catalysis1

CH2CH2CH2CH2CH2CH2CH2CH3

CH2CH2CH2CH2CH2CH2CH2CH3

H3C

N

CH2CH2CH2CH2CH2CH2CH2CH3

Phase-Transfer Catalysis

Quaternary ammonium salts are phase-transfercatalysts. They are soluble in nonpolar solvents.

+

Cl–

Methyltrioctylammonium chloride

phase transfer catalysis2

CH2CH3

+

CH2CH3

N

CH2CH3

Phase-Transfer Catalysis

Quaternary ammonium salts are phase-transfercatalysts. They are soluble in nonpolar solvents.

Cl–

Benzyltriethylammonium chloride

example
Example

The SN2 reaction of sodium cyanide with butylbromide occurs much faster when benzyl-triethylammonium chloride is present than whenit is not.

+

CH3CH2CH2CH2Br

NaCN

benzyltriethylammonium chloride

+

CH3CH2CH2CH2CN

NaBr

mechanism

CH2CH3

+

CH2CH3

N

CH2CH3

CH2CH3

+

+

Cl–

CN–

CH2CH3

N

(aqueous)

CH2CH3

(aqueous)

Mechanism

+

CN–

Cl–

(aqueous)

(aqueous)

mechanism1

CH2CH3

+

CH2CH3

CN–

N

CH2CH3

(in butyl bromide)

CH2CH3

+

CH2CH3

N

CH2CH3

Mechanism

CN–

(aqueous)

mechanism2

CH2CH3

+

CH2CH3

N

CH2CH3

CH2CH3

+

+

Br–

CH2CH3

CH3CH2CH2CH2CN

N

CH2CH3

(in butyl bromide)

Mechanism

+

CH3CH2CH2CH2Br

CN–

(in butyl bromide)

preparation of amines
Preparation of Amines
  • Two questions to answer:
    • 1) How is the C—N bond to be formed?
    • 2) How do we obtain the correct oxidation state of nitrogen (and carbon)?
methods for c n bond formation
Methods for C—N Bond Formation
  • Nucleophilic substitution by azide ion (N3–) (Section 8.1, 8.11)
  • Nitration of arenes (Section 12.3)
  • Nucleophilic ring opening of epoxides by ammonia (Section 16.12)
  • Nucleophilic addition of amines to aldehydes and ketones (Sections 17.10, 17.11)
  • Nucleophilic substitution by ammonia on a-halo acids (Section 20.15)
  • Nucleophilic acyl substitution (Sections 19.4, 19.5, and 19.11)
alkylation of ammonia

via:

+

••

••

+

+

R

R

X

X

H3N

H3N

••

••

••

••

••

••

H

H

then:

+

+

+

R

H

+

N

H3N

H

R

H3N

N

••

••

H

H

Alkylation of Ammonia

Desired reaction is:

+

2 NH3

+

R—X

R—NH2

NH4X

alkylation of ammonia1

+

X

R4N

Alkylation of Ammonia

But the method doesn't work well in practice.Usually gives a mixture of primary, secondary,and tertiary amines, plus the quaternary salt.

RX

RX

NH3

RNH2

R2NH

RX

RX

R3N

example1

+

CH3(CH2)6CH2NHCH2(CH2)6CH3

(43%)

Example

NH3

CH3(CH2)6CH2Br

CH3(CH2)6CH2NH2

  • As octylamine is formed, it competes with ammonia for the remaining 1-bromooctane. Reaction of octylamine with 1-bromooctane gives N,N-dioctylamine.

(45%)

gabriel synthesis
Gabriel Synthesis
  • Gives primary amines without formation ofsecondary, etc. amines as byproducts.
  • Uses an SN2 reaction on an alkyl halide to formthe C—N bond.
  • The nitrogen-containing nucleophileis N-potassiophthalimide.
gabriel synthesis1

O

+

K

N

••

••

O

Gabriel Synthesis
  • Gives primary amines without formation ofsecondary, etc. amines as byproducts.
  • Uses an SN2 reaction on an alkyl halide to formthe C—N bond.
  • The nitrogen-containing nucleophileis N-potassiophthalimide.

n potassiophthalimide

O

+

K

N

NH

••

••

O

N-Potassiophthalimide
  • The pKa of phthalimide is 8.3.
  • N-potassiophthalimide is easily prepared bythe reaction of phthalimide with KOH.

O

KOH

••

O

n potassiophthalimide as a nucleophile

O

••

R

X

N

R

••

••

••

O

••

+

X

••

••

••

N-Potassiophthalimide as a Nucleophile

O

SN2

+

N

••

••

O

cleavage of alkylated phthalimide

O

+

H2O

N

R

••

O

CO2H

H2N

R

CO2H

Cleavage of Alkylated Phthalimide
  • Imide hydrolysis is nucleophilic acyl substitution.

acid or base

+

cleavage of alkylated phthalimide1

O

O

H2NNH2

NH

N

R

••

NH

O

O

H2N

R

Cleavage of Alkylated Phthalimide
  • Hydrazinolysis is an alternative method of releasing the amine from its phthalimide derivative.

+

example2

+

K

O

(74%)

N

CH2C6H5

••

O

Example

O

+

C6H5CH2Cl

N

••

••

DMF

O

example3

O

NH

NH

O

O

N

CH2C6H5

••

O

Example

(97%)

+

C6H5CH2NH2

H2NNH2

preparation of amines by reduction
Preparation of Amines by Reduction
  • Almost any nitrogen-containing compound canbe reduced to an amine, including:
  • azides nitriles nitro-substituted benzene derivatives amides
synthesis of amines via azides

CH2CH2Br

CH2CH2N3

1. LiAlH4

2. H2O

CH2CH2NH2

(89%)

Synthesis of Amines via Azides
  • SN2 reaction, followed by reduction, gives a primary alkylamine.

NaN3

(74%)

Azides may also bereduced by catalytichydrogenation.

synthesis of amines via nitriles

H2 (100 atm), Ni

CH3CH2CH2CH2CH2NH2

(56%)

Synthesis of Amines via Nitriles
  • SN2 reaction, followed by reduction, gives a primary alkylamine.

NaCN

CH3CH2CH2CH2Br

CH3CH2CH2CH2CN

(69%)

Nitriles may also bereduced by lithiumaluminum hydride.

synthesis of amines via nitriles1

H2 (100 atm), Ni

CH3CH2CH2CH2CH2NH2

(56%)

Synthesis of Amines via Nitriles
  • SN2 reaction, followed by reduction, gives a primary alkylamine.

NaCN

CH3CH2CH2CH2Br

CH3CH2CH2CH2CN

(69%)

The reduction alsoworks with cyanohydrins.

synthesis of amines via nitroarenes

NO2

Cl

1. Fe, HCl

2. NaOH

NH2

Cl

(95%)

Synthesis of Amines via Nitroarenes

HNO3

Cl

H2SO4

Nitro groups may alsobe reduced with tin (Sn)+ HCl or by catalytichydrogenation.

(88-95%)

synthesis of amines via amides

O

O

COH

CN(CH3)2

1. LiAlH4

2. H2O

CH2N(CH3)2

(88%)

Synthesis of Amines via Amides

1. SOCl2

2. (CH3)2NH

(86-89%)

Only LiAlH4 is anappropriate reducingagent for this reaction.

synthesis of amines via reductive amination

R

R

O

NH

C

C

R'

R'

Synthesis of Amines via Reductive Amination

In reductive amination, an aldehyde or ketoneis subjected to catalytic hydrogenation in thepresence of ammonia or an amine.

  • The aldehyde or ketone equilibrates with theimine faster than hydrogenation occurs.

fast

+

+

NH3

H2O

synthesis of amines via reductive amination1

R

R

O

NH

C

C

R'

R'

R

H2, Ni

R'

NH2

C

H

Synthesis of Amines via Reductive Amination

The imine undergoes hydrogenation fasterthan the aldehyde or ketone. An amine is the product.

fast

+

+

NH3

H2O

example ammonia gives a primary amine

H

O

NH2

via:

NH

Example: Ammonia Gives a Primary Amine

H2, Ni

+

NH3

ethanol

(80%)

example primary amines give secondary amines

O

+

CH3(CH2)5CH

H2N

CH3(CH2)5CH2NH

via:

CH3(CH2)5CH

N

Example: Primary Amines Give Secondary Amines

H2, Ni

ethanol

(65%)

example secondary amines give tertiary amines

O

CH3CH2CH2CH

N

H

N

CH2CH2CH2CH3

Example: Secondary Amines Give Tertiary Amines

+

H2, Ni, ethanol

(93%)

example secondary amines give tertiary amines1

+

N

N

CHCH2CH2CH3

HO

CHCH2CH2CH3

N

CH

CHCH2CH3

Example: Secondary Amines Give Tertiary Amines

Possible intermediates include:

slide83

N

as a base:

H

X

••

as a nucleophile:

N

C

O

••

Reactions of Amines

Reactions of amines almost always involve thenitrogen lone pair.

slide84

Reactions of Amines

Reactions already discussed

  • basicity (Section 21.4)
  • reaction with aldehydes and ketones (Sections17.10, 17.11)
  • reaction with acyl chlorides (Section 19.4),anhydrides (Section 19.5), and esters (Section 19.11)
reaction with alkyl halides

+

••

+

N

N

R

X

R

••

••

••

H

H

+

+

N

R

H

••

Reaction with Alkyl Halides

Amines act as nucleophiles toward alkyl halides.

••

+

X

••

••

••

example excess amine

NH2

ClCH2

NHCH2

Example: excess amine

+

(4 mol)

(1 mol)

NaHCO3

90°C

(85-87%)

example excess alkyl halide

CH2NH2

CH2N(CH3)3

I

Example: excess alkyl halide

+

3CH3I

methanol

heat

+

(99%)

slide90

The Hofmann Elimination

  • A quaternary ammonium hydroxide is the reactantand an alkene is the product.
  • It is an anti elimination.
  • The leaving group is a trialkylamine.
  • The regioselectivity is opposite to the Zaitsev rule.
quaternary ammonium hydroxides

CH2N(CH3)3

I

Ag2O

H2O, CH3OH

+

CH2N(CH3)3

HO

Quaternary Ammonium Hydroxides

are prepared by treating quaternary ammmoniumhalides with moist silver oxide

the hofmann elimination

+

+

H2O

CH2

N(CH3)3

(69%)

CH2N(CH3)3

The Hofmann Elimination

on being heated, quaternary ammonium hydroxides undergo elimination

160°C

+

HO

mechanism3

••

••

H

H

O

O

••

••

••

H

CH2

CH2

N(CH3)3

+

N(CH3)3

••

Mechanism

H

regioselectivity

(95%)

H2C

CHCH2CH3

CH3CHCH2CH3

heat

+

N(CH3)3

+

CH3CH

CHCH3

(5%)

HO

Regioselectivity

Elimination occurs in the direction that gives the less-substituted double bond. This is called the Hofmann rule.

regioselectivity1
Regioselectivity

Steric factors seem to control the regioselectivity.The transition state that leads to 1-butene isless crowded than the one leading to cisor trans-2-butene.

regioselectivity2

H

H

H

CH3CH2

H

C

C

H

H

H

CH3CH2

+N(CH3)3

major product

Regioselectivity

largest group is between two H atoms

regioselectivity3

H

CH3

C

C

H

CH3

minor product

Regioselectivity

H

CH3

H

CH3

H

+N(CH3)3

largest group is between anH atom and a methyl group

nitration of aniline
Nitration of Aniline
  • NH2 is a very strongly activating group.
  • NH2 not only activates the ring toward electrophilic aromatic substitution, it also makes it more easily oxidized.
  • Attemped nitration of aniline fails because nitric acid oxidizes aniline to a black tar.
nitration of aniline1

O

NH2

NHCCH3

O

O

CH3COCCH3

(98%)

CH(CH3)2

CH(CH3)2

(acetyl chloride may be used instead of acetic anhydride)

Nitration of Aniline
  • Strategy: decrease the reactivity of aniline by converting the NH2 group to an amide
nitration of aniline2

O

O

NHCCH3

NHCCH3

NO2

HNO3

CH(CH3)2

CH(CH3)2

(94%)

Nitration of Aniline
  • Strategy: nitrate the amide formed in the first step
nitration of aniline3

O

NHCCH3

NH2

NO2

NO2

KOH

ethanol,heat

CH(CH3)2

CH(CH3)2

(100%)

Nitration of Aniline
  • Strategy: remove the acyl group from the amide by hydrolysis
halogenation of arylamines

NH2

NH2

Br

Br

Br2

acetic acid

CO2H

CO2H

Halogenation of Arylamines
  • occurs readily without necessity of protecting amino group, but difficult to limit it to monohalogenation

(82%)

monohalogenation of arylamines

O

O

NHCCH3

NHCCH3

CH3

CH3

Cl2

acetic acid

Cl

Monohalogenation of Arylamines
  • Decreasing the reactivity of the arylamine by converting the NH2 group to an amide allows halogenation to be limited to monosubstitution.

(74%)

friedel crafts reactions

O

NHCCH3

O

CH2CH3

CH3CCl

AlCl3

O

CCH3

Friedel-Crafts Reactions
  • The amino group of an arylamine must be protected as an amide when carrying out a Friedel-Crafts reaction.

O

NHCCH3

CH2CH3

(57%)

nitrite ion nitrous acid and nitrosyl cation

+

H

••

••

••

••

••

••

O

O

N

O

N

O

H

••

••

••

••

••

+

H

H

H

+

••

••

••

••

+

O

N

O

O

N

O

••

••

••

••

••

+

H

H

Nitrite Ion, Nitrous Acid, and Nitrosyl Cation
nitrosyl cation and nitrosation1

+

••

••

N

N

O

••

••

••

N

N

O

••

••

+

Nitrosyl Cation and Nitrosation

+

nitrosation of secondary alkylamines

+

••

••

••

••

N

N

N

O

N

O

••

••

••

+

H

+

H

••

••

+

N

N

O

••

••

+

H

Nitrosation of Secondary Alkylamines
  • Nitrosation of secondary amines gives an N-nitroso amine.
example4

••

••

••

N

O

(CH3)2NH

(CH3)2N

••

Example

NaNO2, HCl

••

H2O

(88-90%)

some n nitroso amines

N-nitrosodimethylamine(leather tanning)

N

O

(CH3)2N

N

N

N

N

N

O

O

N-nitrosopyrrolidine(nitrite-cured bacon)

N-nitrosonornicotine(tobacco smoke)

Some N-Nitroso Amines
nitrosation of primary alkylamines

R

R

H

+

••

••

••

••

N

N

N

O

N

O

••

••

••

+

H

H

+

H

R

H

••

••

N

N

O

••

••

+

H

Nitrosation of Primary Alkylamines
  • Analogous to nitrosation of secondary amines to this point.

+

nitrosation of primary alkylamines1

R

+

H

••

••

••

••

+

N

N

N

O

N

O

••

••

••

H

H

R

R

H

+

H

••

••

••

N

N

N

O

N

O

••

••

••

••

+

H

H

+

H

Nitrosation of Primary Alkylamines

R

  • This species reacts further.

H

nitrosation of primary alkylamines2

H

+

+

O

N

N

R

••

••

••

H

R

H

••

N

N

O

••

••

+

H

Nitrosation of Primary Alkylamines
  • Nitrosation of a primary alkylamine gives an alkyl diazonium ion.
  • Process is called diazotization.
alkyl diazonium ions

+

+

N

N

N

R

R

N

••

••

••

Alkyl Diazonium Ions
  • Alkyl diazonium ions readily lose N2 to give carbocations.

+

example nitrosation of 1 1 dimethylpropylamine

+

HONO

N

N

NH2

– N2

OH

H2O

+

(80%)

+

(3%)

(2%)

Example: Nitrosation of 1,1-Dimethylpropylamine

Mechanism 21.2

nitrosation of tertiary alkylamines

R

R

R

R

+

••

••

N

N

N

O

••

••

R

R

Nitrosation of Tertiary Alkylamines
  • There is no useful chemistry associated with the nitrosation of tertiary alkylamines.
nitrosation of tertiary arylamines

N(CH2CH3)2

N(CH2CH3)2

1. NaNO2, HCl, H2O, 8°C

2. HO–

N

O

(95%)

Nitrosation of Tertiary Arylamines
  • Reaction that occurs is electrophilic aromatic substitution.
nitrosation of n alkylarylamines

N

O

NHCH3

NCH3

(87-93%)

Nitrosation of N-Alkylarylamines
  • Similar to secondary alkylamines;
  • Gives N-nitroso amines

NaNO2, HCl,H2O, 10°C

nitrosation of primary arylamines

+

fast

+

+

R

N2

RN

N

+

slow

+

+

N

ArN

Ar

N2

Nitrosation of Primary Arylamines
  • Gives aryl diazonium ions.
  • Aryl diazonium ions are much more stable thanalkyl diazonium ions.
  • Most aryl diazonium ions are stable under the conditions of their formation (0-10°C).
example5

NH2

(CH3)2CH

NaNO2, H2SO4

H2O, 0-5°C

+

N

(CH3)2CH

N

Example:

HSO4–

transformations of aryl diazonium salts

Cl

Br

Ar

Ar

F

Ar

CN

Ar

+

N

N

Ar

H

I

Ar

Ar

OH

Ar

Transformations of Aryl Diazonium Salts
preparation of phenols

+

N

N

Ar

OH

Ar

Preparation of Phenols

H2O, heat

example6

NH2

(CH3)2CH

OH

(CH3)2CH

Example

1. NaNO2, H2SO4

H2O, 0-5°C

2. H2O, heat

(73%)

transformations of aryl diazonium salts1

Cl

Br

Ar

Ar

F

Ar

CN

Ar

+

N

N

Ar

H

I

Ar

Ar

OH

Ar

Transformations of Aryl Diazonium Salts
preparation of aryl iodides

+

N

N

Ar

I

Ar

Preparation of Aryl Iodides
  • Reaction of an aryl diazonium salt with potassium iodide:

KI

example7

NH2

Br

Example

I

1. NaNO2, HCl

H2O, 0-5°C

Br

2. KI, room temp.

(72-83%)

transformations of aryl diazonium salts2

Cl

Br

Ar

Ar

F

Ar

CN

Ar

+

N

N

Ar

H

I

Ar

Ar

OH

Ar

Transformations of Aryl Diazonium Salts
preparation of aryl fluorides

F

Ar

+

N

N

Ar

Preparation of Aryl Fluorides
  • Heat the tetrafluoroborate salt of a diazonium ion;
  • process is called the Schiemann reaction.
example8

NH2

F

CCH2CH3

CCH2CH3

O

O

Example

1. NaNO2, HCl,

H2O, 0-5°C

2. HBF4

3. heat

(68%)

transformations of aryl diazonium salts3

Cl

Br

Ar

Ar

F

Ar

CN

Ar

+

N

N

Ar

H

I

Ar

Ar

OH

Ar

Transformations of Aryl Diazonium Salts
preparation of aryl chlorides and bromides

Cl

Br

Ar

Ar

+

N

N

Ar

Preparation of Aryl Chlorides and Bromides
  • Aryl chlorides and aryl bromides are prepared by heating a diazonium salt with copper(I) chloride or bromide.
  • Substitutions of diazonium salts that use copper(I) halides are called Sandmeyerreactions.
example9
Example

NH2

Cl

1. NaNO2, HCl,

H2O, 0-5°C

2. CuCl, heat

NO2

NO2

(68-71%)

example10

NH2

Cl

Example

1. NaNO2, HBr,

H2O, 0-10°C

Br

Cl

2. CuBr, heat

(89-95%)

transformations of aryl diazonium salts4

Cl

Br

Ar

Ar

F

Ar

CN

Ar

+

N

N

Ar

H

I

Ar

Ar

OH

Ar

Transformations of Aryl Diazonium Salts
preparation of aryl nitriles

CN

Ar

+

N

N

Ar

Preparation of Aryl Nitriles
  • Aryl nitriles are prepared by heating a diazonium salt with copper(I) cyanide.
  • This is another type of Sandmeyer reaction.
example11

NH2

CH3

Example

1. NaNO2, HCl,

H2O, 0°C

CN

CH3

2. CuCN, heat

(64-70%)

transformations of aryl diazonium salts5

Cl

Br

Ar

Ar

F

Ar

CN

Ar

+

N

N

Ar

H

I

Ar

Ar

OH

Ar

Transformations of Aryl Diazonium Salts
transformations of aryl diazonium salts6

+

N

N

Ar

H

Ar

Transformations of Aryl Diazonium Salts
  • Hypophosphorous acid (H3PO2) reduces diazonium salts; ethanol does the same thing.
  • This is called reductive deamination.
example12

NH2

CH3

CH3

Example

NaNO2, H2SO4,

H3PO2

or NaNO2, HCl,

CH3CH2OH

(70-75%)

value of diazonium salts
Value of Diazonium Salts
  • 1) Allows introduction of substituents such as OH, F, I, and CN on the ring.
  • 2) Allows preparation of otherwise difficultly accessible substitution patterns.
example13

NH2

NH2

NaNO2, H2SO4,H2O, CH3CH2OH

Br

Br

Br2

H2O

Br

Br

Br

(100%)

Br

(74-77%)

Example
azo coupling

+

+

H

N

N

N

N

Ar'

Ar

Ar

Ar'

an azo compound

Ar' must bear a strongly electron-releasing group such as OH, OR, or NR2.

Azo Coupling
  • Diazonium salts are weak electrophiles.
  • React with strongly activated aromatic compounds by electrophilic aromatic substitution.
example14

OH

+

N

C6H5N

OH

N

NC6H5

Example

+

Cl–

infrared spectroscopy

H

H

N

N

R

R

H

H

symmetric

antisymmetric

Infrared Spectroscopy

The N—H stretching band appears in the range3000-3500 cm-1.

Primary amines give two peaks in this region, onefor a symmetrical stretching vibration, the other foran antisymmetrical stretch.

infrared spectroscopy1
Infrared Spectroscopy

Primary amines give two N—H stretching peaks, secondary amines give one (Figure 21.8).

1 h nmr

H3C

H3C

CH2NH2

CH2OH

 3.9 ppm

 4.7 ppm

N

O

C

is more shielded than

C

H

H

1H NMR

Compare chemical shifts in:

13 c nmr

 26.9 ppm

 48.0 ppm

13C NMR

Carbons bonded to N are more shielded than those bonded to O.

CH3NH2

CH3OH

uv vis

+

NH2

NH3

UV-VIS

An amino group on a benzene ring shifts maxto longer wavelength. Protonation of N causesUV spectrum to resemble that of benzene.

max204 nm256 nm

max230 nm280 nm

max203 nm254 nm

mass spectrometry
Mass Spectrometry

Compounds that contain only C, H, and O have even molecular weights. If an odd number of N atoms is present, the molecular weight is odd.

A molecular-ion peak with an odd m/z value suggests that the sample being analyzed contains N.

mass spectrometry1

••

(CH3)2NCH2CH2CH2CH3

•+

(CH3)2NCH2CH2CH2CH3

+

+

•CH2CH2CH3

(CH3)2N

CH2

Mass Spectrometry

Nitrogen stabilizes carbocations, which drives the fragmentation pathways.

e–

mass spectrometry2

••

CH3NHCH2CH2CH(CH3)2

•+

CH3NHCH2CH2CH(CH3)2

+

+

•CH2CH(CH3)2

CH3NH

CH2

Mass Spectrometry

Nitrogen stabilizes carbocations, which drives the fragmentation pathways.

e–