Amines

Reference: Organic Chemistry, Seventh Edition, Francis A. Carey, 2008, McGraw Hill

Primary y Alkylamines y
(RN (R ( NH2: one carbon directly y attached to N) CH3CH2NH2 NH2 ethylamine ethyl amine

cyclohexylamine cyclohexyl amine

CH3CHCH2CH2CH3 NH2

1-methylbutyl methylbutylamine amine

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Primary Arylamines (ArNH2)

N Name as d derivatives i ti of f aniline. ili
NH2 F NH2 Br CH2CH3

p-fluoro fluoroaniline aniline or 4-fluoro fluoroaniline aniline

5-bromo bromo-2-ethyl ethylaniline aniline

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Amino Groups p as Substituents

Amino g groups p rank below OH g groups p and higher oxidation states of carbon. In such cases name the amino group as a substituent.
O HOCH2CH2NH2 2-amino aminoethanol ethanol HC NH2

p-amino aminobenzaldehyde benzaldehyde y

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Secondary and Tertiary Amines

CH3NHCH2CH3 NHCH2CH3 N-methylethyl methylethylamine amine

4-chloro chloro-N-ethyl ethyly -3-nitro nitroaniline aniline NO2 Cl CH3 N CH3 N,N-dimethylcycloheptyl dimethylcycloheptylamine amine
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Ammonium Salts
A nitrogen g with four substituents is p positively y charged and is named as a derivative of ammonium ion (NH4+).
+ CH3NH3 Cl CH3 + N CH2CH3 CF3CO2 H
methylammonium methylammonium chloride N-ethyl ethyl-N-methylcyclopentylammonium methylcyclopentylammonium trifluoroacetate
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Ammonium Salts
When all four atoms attached to N are carbon, th i the ion i is called ll d a quaternary t ammonium i i and ion d salts that contain it are called quaternary ammonium salts.
CH3 CH2 + N CH3 benzyltrimethylammonium benzyltrimethyl ammonium iodide
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CH3 I

Physical Properties
CH3CH2CH2NH2 CH3CH2NHCH3 boiling point: 50 C 34 C (CH3)3N 3 C

Boiling points of isomeric amines decrease in going 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 8 hydrogen bonds.

Basicity y of Amines
It is more useful to describe the basicity of amines in terms of the pKas of their conjugate j g acids than as basicity constants Kb. The more basic the amine, the weaker its conjugate j g acid. The more basic the amine, the larger g the pKa of its conjugate acid.
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Citing amine basicity according to the pKa of the conjugate acid makes it possible to analyze acid-base acid base reactions of amines according to the usual Brnsted relationships. relationships

Amines are converted to ammonium ions by acetic acid.

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Adding sodium hydroxide to an ammonium salt coverts it to the free amine.

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Effect of Structure on Basicity

(1) Alkylamines are slightly stronger bases than ammonia. i Amine NH3 CH3CH2NH2 Conj Acid Conj. NH4+ CH3CH2NH3+ pKa 9.3 10.8

CH3CH2NH3+ is a weaker acid than NH4+; therefore, CH3CH2NH2 is a stronger base than NH3.
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Effect of Structure on Basicity

(2) Arylamines are much weaker bases than ammonia. Amine NH3 CH3CH2NH2 (CH3CH2)2NH (CH3CH2)3N C6H5NH2 Conj Acid Conj. NH4+ CH3CH2NH3+ (CH3CH2)2NH2+ (CH3CH2)3NH+ C6H5NH3+ pKa 9.3 10.8 11.1 10.8 4.6
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Decreased Basicity of Arylamines

The electron pair on nitrogen of aniline is strongly held by delocalization into the system of the aromatic ring.

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Decreased Basicity of Arylamines

Increasing delocalization makes diphenylamine a weaker base than aniline, and d triphenylamine ti h l i a weaker k base b th than diphenylamine.
C6H5NH2 pKa of conjugate acid: 4.6 (C6H5)2NH (C6H5)3N

0.8

-5
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Effect of Substituents on B i it of Basicity f Arylamines A l i

(1) Alkyl Alk l groups on the th ring i increase i b basicity, i it but b t only slightly (less than 1 pK unit).

NH2 pKa of conjugate acid 4.6 53 5.3

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X H CH3

Effect of Substituents on B i it of Basicity f Arylamines A l i

(2) Electron withdrawing groups groups, especially ortho and/or para to amine group, decrease basicity and d can h have a large l effect. ff t
X X H CF3 C O2N NH2 pKa of conjugate acid 4.6 3.5 3 5 1.0

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p-Nitroaniline
O

+ N

O NH2

+ N

+ NH2

Lone p pair on amine nitrogen g is conjugated j g with p-nitro groupmore delocalized than in aniline itself itself.
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Heterocyclic Amines

Why? y
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The nitrogen lone pair occupies an sp3-hybridized orbital in p piperidine p verus an sp p2-hybridized y one in pyridine. Electrons in orbitals with more s character are more strongl strongly held than those with ith less s character. Thus, , nitrogen g holds on to its unshared p pair more strongly in pyridine than in piperidine and is less basic basic.
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Alkylation of Ammonia
Desired reaction is: 2 NH3 via: H3N + R then: H3N + H X

RX

RNH2 +

NH4X

+ H3N + H3N

R +

H + N R H

H H + N H R
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Alkylation of Ammonia

But the method doesn doesn't t work well in practice!

Usually gives a mixture of primary, primary secondary, secondary and tertiary amines, plus the quaternary salt. NH3 RX RNH2 RX R2NH RX + R4N X RX R3N
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Example p
CH3(CH2)6CH2Br B NH3 CH3(CH2)6CH2NH2 (45%) ( ) + CH3(CH2)6CH2NHCH2(CH2)6CH3 (43%) As octylamine A t l i is i f formed, d it competes t with ith ammonia for the remaining 1-bromooctane. R Reaction ti of f octylamine t l i with ith 1 1-bromooctane b t gives N,N-dioctylamine.

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Preparation p of Amines by y Reduction

Almost any nitrogen-containing nitrogen containing compound can be reduced to an amine, including: azides nitriles nitro-substituted benzene derivatives amides

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Synthesis of Amines via Azides

SN2 reaction, followed by reduction, gives a primary alkylamine. alkylamine
CH2CH2Br Azides may also be reduced by catalytic hydrogenation. N N3 NaN Na CH2CH2N3 (74%) 1. 1 LiAlH4 2. H2O CH2CH2NH2 (89%)

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Synthesis of Amines via Nitriles

SN2 reaction, followed by reduction, gives a primary alkylamine. alkylamine
N CN NaCN Na CH3CH2CH2CH2Br Nitriles may also be reduced by lithium aluminum hydride. CH3CH2CH2CH2CN (69%) H2 (100 atm), Ni

CH3CH2CH2CH2CH2NH2 (56%)
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Synthesis of Amines via Nitroarenes

Nitro groups may also be reduced with tin (Sn) + HCl or by catalytic hydrogenation.

Cl (88(88 -95%) 1. Fe, , HCl 2. NaOH

NO2

Cl (95%)

NH2
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Synthesis y of Amines via Amides

O COH 1. SOCl2 2. 2 (CH3)2NH O CN(CH3)2 (86(86 -89%) 1. LiAlH4 2. H2O

Only LiAlH4 is an appropriate reducing agent t for f this thi reaction. ti CH2N(CH3)2 (88%)

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Synthesis of Amines via Reductive Amination

In reductive amination, an aldehyde or ketone is subjected to catalytic hydrogenation in the presence of ammonia or an amine amine.

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Mechanism of Reductive Amination

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Ammonia Gives a Pi Primary Amine A i

H2, Ni O + NH3 ethanol H (80%)

NH2

Synthesis of amphetamine () (a central nervous system stimulant)

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Primary Amines Give Secondary Amines

O CH3(CH2)5CH + H2N ethanol

H2, Ni

CH3(CH2)5CH2NH (65%)
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Secondary Amines Give Tertiary Amines

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Synthesis of
Using Reductive Amination!

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