Chapter 21 Amines Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction...

Chapter 21Chapter 21AminesAmines

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

21.121.1Amine NomenclatureAmine Nomenclature


Alkylamine:

N attached to alkyl group.

Arylamine:

N attached to aryl group.

Primary, secondary, or tertiary:

is determined by number of carbon atoms directly attached to nitrogen.

Classification of Amines

Two IUPAC styles:

1) Analogous to alcohols: replace -e ending with –amine. E.g. pentanamine

2) Name alkyl group and attach -amine as a suffix. E.g. isopropylamine

Nomenclature of Primary Alkylamines (RNH2)

Examples: Some Primary Alkylamines

CH3CHCH2CH2CH3

NH2

(RNH2: one carbon directly attached to N)

CH3CH2NH2 NH2

ethylamine or ethanamine

cyclohexylamine orcyclohexanamine

1-methylbutylamine or2-pentanamine orpentan-2-amine

Name as derivatives of aniline.

Nomenclature of Primary Arylamines (ArNH2)

p-fluoroaniline or4-fluoroaniline

5-bromo-2-ethylaniline

NH2F

NH2

Br CH2CH3

Amino Groups as Substituents

p-aminobenzaldehyde

Amino groups rank below OH groups and higher oxidation states of carbon.

In such cases name the amino group as a substituent.

See list of functional group priorities, Ch 17. NH2HC

O

HOCH2CH2NH2

2-aminoethanol

Name as N-substituted derivatives of the parent primary amine.

(N is a locant and is not alphabetized. It is treated the same way as a numericallocant).

The parent amine is one with longest carbon chain.

Secondary and Tertiary Amines

Examples

CH3NHCH2CH3 N-methylethylamine NHCH2CH3

NO2

Cl

4-chloro-N-ethyl-3-nitroaniline

CH3

N

CH3

N,N-dimethylcycloheptylamine

From a primary From a tertiary amine. amine.

Ammonium Salts

CH3NH3

+Cl

–

methylammoniumchloride

+

N

CH3

H

CH2CH3 CF3CO2–

N-ethyl-N-methylcyclopentylammoniumtrifluoroacetate

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

+

CH2 N

CH3

CH3

CH3 I–

benzyltrimethylammonium iodide

Ammonium Salts

21.221.2Structure and BondingStructure and Bonding


147 pm

106°112°

Alkylamines

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

Compare geometry at N of: aniline (next slide), methylamine and formamide.

sp3 sp2

Geometry at N

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

CO

NH2

H

C NH2

H

H

H

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

sp3 sp2

Geometry at N

~125°180°

142.5°Note: This angle is not the same as the

H—N—H bond angle.

aniline

Geometry at N

142.5°

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

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)

21.321.3Physical PropertiesPhysical Properties


Amines are more polar and have higher boiling points than alkanes; but are less polar andhave lower boiling points than alcohols.

Physical Properties

CH3CH2CH3 CH3CH2NH2 CH3CH2OH

dipolemoment ():

boiling point:

0 D 1.2 D 1.7 D

-42°C 17°C 78°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.

Physical Properties

CH3CH2NHCH3CH3CH2CH2NH2 (CH3)3N

b.p.

less H-bonding and more branching

50°C 34°C 3°C

21.421.4Basicity of AminesBasicity of Amines


Amine Conj. Acid pKa

NH3 NH4+ 9.3

CH3CH2NH2 CH3CH2NH3+ 10.8

Table 21.1Basicity of Amines in Aqueous Solution

CH3CH2NH3+ is a weaker acid than NH4

+; therefore, CH3CH2NH2 is a stronger base than NH3.

1. Alkylamines are slightly stronger bases than ammonia (alkyl is weakly e-donating).


NH3 NH4+ 9.3


(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.


2. Alkylamines differ very little in basicity.


NH3 NH4+ 9.3


(CH3CH2)2NH (CH3CH2)2NH2+ 11.1

(CH3CH2)3N (CH3CH2)3NH+ 10.8

C6H5NH2 C6H5NH3+ 4.6

3. Arylamines are much weaker bases thanammonia or alkyl amines. (Aryl is an EWG.)


Summary: Effects 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 thanammonia.

H2N•• Decreased Basicity of Arylamines

++H

N

H

H NH2 +•• +

H3N

pKa = 4.6

pKa =10.6

Strongeracid

Weakeracid

Strongerbase

Weakerbase

K = 106

Comparison of aryl and alkyl amine basicity.

aniline

cyclohexylamine

+ H2N••

+

H

H

N

H NH2 +•• +

H3N

Strongeracid

Weakeracid

When anilinium ion loses a proton, the resulting lone pair is delocalized into the ring through resonance. Thus, aniline is a weaker base since the electrons are less available.

Decreased Basicity of Arylamines

Weakerbase

Strongerbase

C6H5NH2 (C6H5)2NH (C6H5)3N

pKa of

conj. acid: 4.6 0.8 ~-5

Increasing delocalization (more possible resonance structures) makes diphenylamine a weaker base than aniline, and triphenylamine a weaker base than diphenylamine.

Decreased Basicity of Arylamines

Effect of Substituents on Basicity of Arylamines

1. Alkyl groups (EDG) on the ring increase basicity, but only slightly (less than 1 pK unit).

X NH2

X pKa of conjugate acidH 4.6CH3 5.3

Effect of Substituents on Basicity of Arylamines

2. Electron withdrawing groups (EWG), especially ortho and/or para to amine group, decrease basicity and can have a large effect.

X NH2

X pKa of conjugate acidH 4.6CF3 3.5

NO2 1.0

p-Nitroaniline NH2

O

N

O

– ••••••

••

+

••

••

N

O

O

– ••••••

•• ••••–

NH2

+ +

The lone pair on -NH2 is conjugated with the p-nitro group (more delocalization than in aniline). This delocalization is lost on protonation of -NH2.

Aniline is 3800 times more basic thanp-nitroaniline.

Aniline is ~1,000,000,000 times more basic than 2,4-dinitroaniline.

Heterocyclic Amines N

H

••

N••

is more basic than

piperidine pyridinepKa of conjugate acid:

11.2

pKa of conjugate acid:

5.2

(an alkylamine)(resembles anarylamine in

basicity)

Heterocyclic Amines N••

is more basic than

imidazole pyridinepKa of conjugate acid:

7.0

pKa of conjugate acid:

5.2

N HN••

••

Imidazole N HN••

••

Which nitrogen is protonated in imidazole ?

H+ H+ N HN ••H

+ +

N HN••

H

loss of aromaticity

Imidazole N HN••

••

Protonation in the direction shown gives a resonance stabilized cation.

H+ N HNH

+ ••

N HNH

••+ resonance

stabilizedcation

21.521.5Tetraalkylammonium SaltsTetraalkylammonium Salts

as Phase-Transfer Catalystsas Phase-Transfer Catalysts

Phase-Transfer Catalysis

Phase-transfer agents promote the solubility ofionic substances in nonpolar solvents. Theyare able to transfer the ionic substance from an aqueous phase to a non-aqueous one.

Phase-transfer agents increase the rates ofreactions involving anions. The anion when in nonpolar media is relatively unsolvated and very reactive compared to media like water or alcohols.

+


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

NH3C

CH2CH2CH2CH2CH2CH2CH2CH3

CH2CH2CH2CH2CH2CH2CH2CH3

CH2CH2CH2CH2CH2CH2CH2CH3Cl–

Methyltrioctylammonium chloride


The substituents on N are nonpolar thus enhance the solubility of the ion in nonpolar solvents.

Benzyltriethylammonium chloride

Cl–

+N

CH2CH3

CH2CH3

CH2CH3

CH2

Example

The SN2 reaction of sodium cyanide with butyl

bromide occurs much faster when benzyl-triethylammonium chloride is present than whenit is not.

CH3CH2CH2CH2Br + NaCN

CH3CH2CH2CH2CN + NaBr

benzyltriethylammonium chloride

Cl–

(aqueous)

(aqueous)

CN–+

Cl–+CN–

(aqueous)

(aqueous)

Anion exchange in the aqueous phase

+N

CH2CH3

CH2CH3

CH2CH3

CH2

+N

CH2CH3

CH2CH3

CH2CH3

CH2

Mechanism

CN–

(aqueoussolvent)

(butyl bromide used as solvent)

CN–

Mechanism

Transfer to the organic phase

+N

CH2CH3

CH2CH3

CH2CH3

CH2

+N

CH2CH3

CH2CH3

CH2CH3

CH2

CN–

CH3CH2CH2CH2Br+

Br–

CH3CH2CH2CH2CN+

Mechanism

SN2 reaction in the organic phase

+N

CH2CH3

CH2CH3

CH2CH3

CH2

+N

CH2CH3

CH2CH3

CH2CH3

CH2

(butyl bromide solvent)

(butyl bromide solvent)

21.621.6Reactions That Lead to Amines:Reactions That Lead to Amines:

A Review and a PreviewA Review and a Preview

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

1. Nucleophilic substitution by azide ion (N3–)

(Section 8.1, 8.11)

2. Nitration of arenes (Section 12.3)

3. Nucleophilic ring opening of epoxides by ammonia or amines (Section 16.12)

4. Nucleophilic addition of amines to aldehydes and ketones (Sections 17.10, 17.11)

5. Nucleophilic substitution by ammonia on -halo acids (Section 20.15)

6. Nucleophilic acyl substitution (Sections 19.4, 19.5, and 19.11)

21.721.7Preparation of Amines by Preparation of Amines by

Alkylation of AmmoniaAlkylation of Ammonia

Alkylation of Ammonia

Desired reaction is:

2 NH3 + R—X R—NH2 + NH4X

via:

H3N •••• ••R X••

H3N R+ •• ••X

••••

–+ +

then:

H3N •• +

+

H N

H

H

R H3N H+

+ N

H

H

R••

Alkylation of Ammonia

The method doesn't work well in practice becauseit usually gives mixtures of primary, secondary,and tertiary amines, plus the quaternary salt due to multiple alkylation.

NH3

RXRNH2

RXR2NH

RX

R3NRX

R4N+

X–

(mixtures)

Example

CH3(CH2)6CH2BrNH3 CH3(CH2)6CH2NH2

(45%)

+

CH3(CH2)6CH2NHCH2(CH2)6CH3

(43%)

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

21.821.8The Gabriel Synthesis The Gabriel Synthesis

of Primary Alkyl Aminesof Primary Alkyl Amines

This method yields primary amines without formation of secondary or other amines as byproducts.It uses an SN2 reaction on an alkyl halide to form the C—N bond.

The nitrogen-containing nucleophileis N-potassiophthalimide.

Gabriel Synthesis

O

O

N•• •• K+–

The pKa of phthalimide is 8.3.

N-potassiophthalimide is easily prepared bythe reaction of phthalimide with KOH. O

O

N•• ••–

K+

O

O

NH••

KOH

N-Potassiophthalimide

••–

N-Potassiophthalimide as a Nucleophile O

O

N•••• ••R X••

+

O

O

N R••

+ •• ••X••

••–

SN2

The N of phthaIimide becomes the N in the primary amine.

Cleavage of Alkylated Phthalimide

O

O

N R•• + H2O

H2N R+

CO2H

CO2H

acid or base

Imide hydrolysis is nucleophilic acyl substitution.

primary amine

Cleavage of Alkylated Phthalimide

Hydrazinolysis is an alternative method of releasing the amine from its phthalimide derivative.

O

O

N R••

H2N R+

O

O

NH

NH

H2NNH2

–

O

O

K+

N + C6H5CH2Cl

DMF

O

O

N CH2C6H5

•• (74%)

•• ••

Example

Example

+ C6H5CH2NH2

O

O

N CH2C6H5

••

H2NNH2

(97%)

O

O

NH

NH

21.921.9Preparation of AminesPreparation of Amines

by Reductionby Reduction

Almost any nitrogen-containing compound canbe reduced to an amine, including:

azides,nitriles,nitro-substituted benzene derivatives, andamides.

Preparation of Amines by Reduction

SN2 reaction, followed by reduction, gives a

primary alkylamine.

Synthesis of Amines via Azides CH2CH2Br

CH2CH2N3

NaN3

(74%) CH2CH2NH2

(89%)

1. LiAlH4

2. H2O

Azides may also bereduced by catalytichydrogenation.

Synthesis of Amines via Nitriles

CH3CH2CH2CH2BrNaCN

(69%)

CH3CH2CH2CH2CN

CH3CH2CH2CH2CH2NH2 (56%)

H2 (100 atm), Ni

Nitriles may also bereduced by lithiumaluminum hydride.

SN2 reaction, followed by reduction, gives a

primary alkylamine.

The reduction also works with cyanohydrins.

Synthesis of Amines via Nitroarenes

HNO3

(88-95%)

Cl

Cl NO2

H2SO4

(95%)

1. Fe, HCl

2. NaOH Cl NH2

Aryl nitro groups may be reduced with Sn or Fe+ HCl or by catalytichydrogenation.

Synthesis of Amines via Amides

(86-89%)

COH

O1. SOCl2

2. (CH3)2NH

CN(CH3)2

O

(88%)

1. LiAlH4

2. H2O CH2N(CH3)2

Only LiAlH4 is an

appropriate reducingagent for this reaction.

21.1021.10Reductive AminationReductive Amination

The aldehyde or ketone equilibrates with theimine faster than hydrogenation of C=O occurs.

Synthesis of Amines via Reductive Amination

+ NH3

fast+ H2O

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

OC

R

R'

NHC

R

R'

Synthesis of Amines via Reductive Amination

OC

R

R'

+ NH3

fastNHC

R

R'

+ H2O

H2, Ni

NH2

R

R' C

H

And the imine undergoes hydrogenation faster than the aldehyde or ketone, so an amine is the product.

Example: Ammonia Gives a Primary Amine O + NH3

H

NH2

H2, Ni

ethanol

(80%)

via:

NH

Sodium triacetoxyborohyride, Na(CH3CO2)3BH, is a useful chemical reagent for this reduction. It is readily available and non-toxic. Catalytic reduction is shown below.

Example: Primary Amines Give Secondary Amines

H2, Ni ethanol

(65%)

CH3(CH2)5CH2NH

+ H2N

CH3(CH2)5CH

O

via: N

CH3(CH2)5CH

Example: Secondary Amines Give Tertiary Amines

H2, Ni, ethanol

(93%)

+CH3CH2CH2CH

O

N

H N

CH2CH2CH2CH3

CHCH2CH2CH3

N+

Possible intermediates for the prevoius reaction include:

N

CH CHCH2CH3

CHCH2CH2CH3

N

HO

Example: Secondary Amines Give Tertiary Amines

21.1121.11Reactions of Amines:Reactions of Amines:

A Review and a PreviewA Review and a Preview

Reactions of Amines

Reactions of amines almost always involve the nitrogen lone pair, either:

••N H X

as a base:

••N

C Oas a nucleophile:

or Attacks H

Attacks C

Reactions of Amines

1. Basicity (Section 21.4).

2. Reaction with aldehydes and ketones (Sections 17.10, 17.11).

3. Reaction with acyl chlorides (Section 19.4),anhydrides (Section 19.5), and esters

(Section 19.11).

Reactions already discussed

21.1221.12Reaction of Amines with Alkyl HalidesReaction of Amines with Alkyl Halides

Amines act as nucleophiles toward alkyl halides.

•• X+ ••••

••••N R

H

+ X ••••

••N R

H

+ –

+N R••

H+

Reaction with Alkyl Halides

NH2 + ClCH2

NHCH2

(85-87%)

NaHCO3 90°C

(4 mol) (1 mol)

Example: Excess amine

+ CH3I

(99%)

methanol heat

CH2N(CH3)3

CH2NH2

+

I–

Example: Excess alkyl halide

(3 mol)(1 mol)

This is referred to as exhaustive methylation.

21.1421.14Electrophilic Aromatic SubstitutionElectrophilic Aromatic Substitution

in Aryl Aminesin Aryl Amines

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.

Attempted nitration of aniline fails because nitric acid oxidizes aniline to a black tar.

Strategy for Nitration of Aniline

Step 1: Decrease the reactivity of aniline by converting the NH2 group to an amide.

CH(CH3)2

NH2

CH(CH3)2

NHCCH3

O

O

CH3COCCH3

O

(98%)

(acetyl chloride may be used instead of acetic anhydride)

Step 2: Nitrate the amide formed in the first step.

CH(CH3)2

NHCCH3

O

HNO3

CH(CH3)2

NHCCH3

O NO2

(94%)


Step 3: Remove the acyl group from the amide by hydrolysis.

CH(CH3)2

NHCCH3

O NO2

KOH

ethanol,heat

CH(CH3)2

NH2 NO2

(100%)


This occurs readily without necessity of protecting amino group, but difficult to limit it to monohalogenation.

Halogenation of Arylamines CO2H

NH2

Br2

acetic acid

(82%)

CO2H

NH2

Br Br

Monohalogenation of Arylamines

Cl

NHCCH3

O CH3

(74%)

Cl2

acetic acid

NHCCH3

O

CH3

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

Friedel-Crafts Reactions

The amino group of an arylamine must be protected as an amide when carrying out a Friedel-Crafts reaction3 NHCCH3

O

CH2CH3 CH3CCl

O

AlCl3

(57%)

NHCCH3

O CH2CH3

CCH3OOtherwise –NH2 will complex with the AlCl3.

21.1521.15Nitrosation of AlkylaminesNitrosation of Alkylamines

Nitrite Ion, Nitrous Acid, and Nitrosyl Cation

H+–

O••••

••N O

•• ••••

O•• ••

N O•• ••

••H

H+

O••N O

•• ••

H

H

+••+

••N O

•• ••+O ••

H

H

•• nitrite ion

nitrous acid

nitrosyl cation

Nitrosyl Cation and Nitrosation

+

••N O

•• ••+••N N••N O

•• ••+

The nitrosation reaction.

Nitrosation of Secondary Alkylamines

+

••N O

•• ••

+H + N

••N O

•• ••••

N••N O

•• ••+

H

Nitrosation of secondary amines gives an N-nitroso amine.

••N

H

RR

RR

R

R

Example

(CH3)2NH•• NaNO2, HCl

H2O(88-90%)

••(CH3)2N

••N O

•• ••

N-nitrosodimethylamine(leather tanning)

Some N-Nitroso Amines

N-nitrosopyrrolidine(nitrite-cured bacon)

N

NO

N-nitrosonornicotine(tobacco smoke)

N

NON

Nitrosation of Primary Alkylamines

+

Analogous to nitrosation of secondary amines to this point.

+

••N O

•• ••••N

H

HR

N••N O

•• ••+

H

HR

+H + N

••N O

•• ••••

R

H


H+

N••N O

••••

R

H H

+

This species reacts further.

••N

••N O

••••

R

H

H+

H+

+

H

••N••N O••

R

H

+

N••N O

•• ••••

R

H


H

••O

H

••+

Nitrosation of a primary alkylamine gives an alkyl diazonium ion.

Process is called diazotization.

+

H

••N••N O••

R

H

+N N ••R

Primary Alkyl Diazonium Ions

+N N ••R

Primary alkyl diazonium ions are unstable and readily lose N2 to give carbocations.

R+ + N N ••••

Example: Nitrosation of 1,1-Dimethylpropylamine NH2

N N+

HONO

H2O

OH

(80%) +

(2%)(3%)

+

– N2

Mechanism 21.2

There is no useful chemistry associated with the nitrosation of tertiary alkylamines.

Nitrosation of Tertiary Alkylamines

••NR

R

R

N••N O

•• ••+R

R

R

21.1621.16Nitrosation of ArylaminesNitrosation of Arylamines

Reaction that occurs is electrophilic aromatic substitution.

Nitrosation of Tertiary Arylamines N(CH2CH3)2

(95%)

1. NaNO2, HCl, H2O, 8°C

2. HO–

N(CH2CH3)2

NO

Similar to secondary alkylamines;

Gives N-nitroso amines

Nitrosation of N-Alkylarylamines

NaNO2, HCl,H2O, 10°C

NHCH3

(87-93%)

NCH3

N O

Nitrosation of Primary Arylamines

Gives aryl diazonium ions.

Aryl diazonium ions are much more stable than alkyl diazonium ions.

Most aryl diazonium ions are stable under the conditions of their formation (0-10°C).

ArN N+

RN N+ fast

slow

R+ + N2

Ar+ + N2

Alkyl:

Aryl:

Example: (CH3)2CH NH2

NaNO2, H2SO4

H2O, 0-5°C (CH3)2CH N N

+HSO4

–

Synthetic Origin of Aryl Diazonium Salts

Ar H

Ar NO2

Ar NH2

Ar N N+

21.1721.17Synthetic Transformations ofSynthetic Transformations of

Aryl Diazonium SaltsAryl Diazonium Salts

Transformations of Aryl Diazonium Salts

Ar N N+

Ar H

Ar OH

Ar I

Ar F

Ar BrAr Cl

Ar CN

Preparation of Phenols

Ar OH

H2O, heat

Ar N N+

Example

2. H2O, heat

(CH3)2CH NH2

1. NaNO2, H2SO4

H2O, 0-5°C (CH3)2CH OH

(73%)

Preparation of Aryl Iodides

Ar I

Reaction of an aryl diazonium salt with potassium iodide:

KIAr N N

+

Example

2. KI, room temp.

1. NaNO2, HCl

H2O, 0-5°C

(72-83%)

NH2

Br

I Br

Preparation of Aryl Fluorides

Ar F

Heat the tetrafluoroborate salt of a diazonium ion;

process is called the Schiemann reaction.

Ar N N+

Example

(68%)

NH2 CCH2CH3

O

2. HBF4

1. NaNO2, HCl,

H2O, 0-5°C

3. heat

F CCH2CH3

O

Preparation of Aryl Chlorides and Bromides

Ar BrAr Cl

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 Sandmeyer reactions.

Ar N N+

Example

(68-71%)

NH2 NO2

2. CuCl, heat

1. NaNO2, HCl,

H2O, 0-5°C

Cl NO2

Example

(89-95%)

2. CuBr, heat

1. NaNO2, HBr,

H2O, 0-10°C

NH2

Cl

Br Cl

Preparation of Aryl Nitriles

Ar CN

Aryl nitriles are prepared by heating a diazonium salt with copper(I) cyanide.

This is another type of Sandmeyer reaction.

Ar N N+

Example

(64-70%)

2. CuCN, heat

1. NaNO2, HCl,

H2O, 0°C

NH2

CH3

CN CH3

Transformations of Aryl Diazonium Salts

Ar N N+

Ar H

Hypophosphorous acid (H3PO2) reduces diazonium salts; ethanol does the same thing.

This is called reductive deamination.

Example

(70-75%)

NaNO2, H2SO4,

H3PO2

NH2

CH3 CH3

or NaNO2, HCl,

CH3CH2OH

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.

Example Br

BrBr

NH2

Br

Br

Br

(74-77%)

NaNO2, H2SO4,H2O, CH3CH2OH

NH2 Br2

H2O

(100%)

21.1821.18Azo CouplingAzo Coupling

Azo Coupling

Diazonium salts are weak electrophiles.

React with strongly activated aromatic compounds by electrophilic aromatic substitution.

Ar N N+

Ar' H+ Ar N N Ar'

an azo compound

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

Example OH

+ C6H5N N+ OH

N NC6H5

Cl–

21.1321.13The Hofmann EliminationThe Hofmann Elimination

The Hofmann Elimination

This is an elimination reaction involving a quaternary ammonium hydroxide as the reactant and an alkene is the product.

It is an anti elimination.

The leaving group is a trialkylamine.

The regioselectivity is opposite to the Zaitsev rule.

Ag2O H2O, CH3OH

CH2N(CH3)3

+

HO–

These are prepared by treating quaternary ammmonium halides with moist silver oxide.HO replaces I and AgI precipitates.

CH2N(CH3)3

I–+

Quaternary Ammonium Hydroxides

+ AgI ↓

– –

160°C

CH2N(CH3)3

+

HO–

When heated, quaternary ammonium hydroxides undergo elimination.

CH2

(69%)

+ N(CH3)3 + H2O


H

CH2

+N(CH3)3

–O•••• H••

O••

H••

H

N(CH3)3••

CH2


+

+

heat

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

N(CH3)3+

HO–

CH3CHCH2CH3H2C CHCH2CH3

CH3CH CHCH3

+

(95%)

(5%)

Regioselectivity

1 2 3

4

Steric factors are important in the determining the regioselectivity of this elimination.

The transition state that leads to 1-butene isless crowded than the one leading to cisor trans-2-butene.

Regioselectivity

+N(CH3)3

H

H

H H

CH3CH2

largest group is between two H atoms.

C

HC

HH

CH3CH2

major product

Regioselectivity

Looking down the 1-2 bond

+N(CH3)3

H

H

H

CH3

largest group is between anH atom and a methyl group.

C

HC

CH3 H

CH3

minor product

CH3

Regioselectivity

Looking down the 2-3 bond

21.1921.19Spectroscopic Analysis of AminesSpectroscopic Analysis of Amines

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 Spectroscopy

R N

H

H

symmetric

R N

H

H

antisymmetric

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

Infrared Spectroscopy

Compare chemical shifts in:

1H NMR H3C CH2NH2

H3C CH2OH

N C H is more shielded than

3.9 ppm 4.7 ppm

O C H

13C NMR

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

CH3NH2 CH3OH

26.9 ppm 48.0 ppm

max

204 nm256 nm

max

230 nm280 nm

max

203 nm254 nm

An amino group on a benzene ring shifts max

to longer wavelength. Protonation of N causesUV spectrum to resemble that of benzene.

UV-VIS NH2

NH3

+

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.

In fragmentation, a primary amine generates an M/Z of 30 and the (+) fragment is a monosubstituted N. (CH2NH2)+

(CH3)2NCH2CH2CH2CH3

••

e–

(CH3)2NCH2CH2CH2CH3

•+

•CH2CH2CH3+(CH3)2N CH2

+

Mass Spectrometry

Nitrogen stabilizes carbocations, which drives the fragmentation pathways.

With a 3o amine, the (+) fragment is a trisubstituted N.

CH3NHCH2CH2CH(CH3)2

••

e–

CH3NHCH2CH2CH(CH3)2

•+

•CH2CH(CH3)2+CH3NH CH2

+

Mass Spectrometry

And with a 2o amine, the (+) fragment is a disubstituted N.

End of Chapter 21End of Chapter 21AminesAmines

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