Lecture 22- Amines

General

Organic Chemistry Two credits Second Semester 2009

King Saud bin Abdulaziz University for Health Science

Reference Book: Organic Chemistry: A Brief Course, by Robert C. Atkins and Francis A. Carey Third Edition

Instructor: Rabih O. Al-Kaysi, PhD.

Lecture 22

Chapter 14

Amines

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 (RNH2) Two IUPAC styles 1)

analogous to alcohols: replace -e ending by -anamine

2)

name alkyl group and attach -amine as a suffix

Examples: some primary alkylamines (RNH2: one carbon directly attached to N) CH3CH2NH2

ethylamine or ethanamine NH2

CH3CHCH2CH2CH3 NH2

cyclohexylamine or cyclohexanamine 1-methylbutylamine or 2-pentanamine

Nomenclature of Primary Arylamines (ArNH2) Name as derivatives of aniline. NH2 F

NH2

p-fluoroaniline

Br

CH2CH3

5-bromo-2-ethylaniline

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

O HOCH2CH2NH2

HC

2-aminoethanol

p-aminobenzaldehyde

NH2

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 CH3NHCH2CH3

N-methylethylamine

NHCH2CH3 4-chloro-N-ethyl-3-nitroaniline NO2 Cl

CH3 N

CH3

N,N-dimethylcycloheptylamine

Ammonium Salts A nitrogen with four substituents is positively charged and is named as a derivative of ammonium ion (NH4+). + CH3NH3 Cl– methylammonium chloride

CH3 + – CF CO CH CH N 3 2 2 3 H

N-ethyl-N-methylcyclopentylammonium trifluoroacetate Just for general knowledge, will not be tested on

Ammonium Salts When all four atoms attached to N are carbon, the ion is called a quaternary ammonium ion and salts that contain it are called quaternary ammonium salts. CH3 + CH2 N

CH3 I –

CH3 benzyltrimethylammonium iodide Just for general knowledge, will not be tested on

Structure and Bonding

Alkylamines 147 pm

112°

106°

Geometry at N Compare geometry at N of methylamine, aniline, and formamide. H H H sp3 sp2 NH2 NH2 C C O H Pyramidal geometry at sp3-hybridized N in methylamine. Planar geometry at sp2-hybridized N in formamide. Just for general knowledge, will not be tested on

Geometry at N Compare geometry at N of methylamine, aniline, and formamide. sp3

sp2

Pyramidal geometry at sp3-hybridized N in methylamine. Planar geometry at sp2-hybridized N in formamide. Just for general knowledge, will not be tested on

Physical Properties

Physical Properties Amines are more polar and have higher boiling points than alkanes; but are less polar and have lower boiling points than alcohols. CH3CH2CH3 CH3CH2NH2 CH3CH2OH dipole moment (µ ):

0D

1.2 D

1.7 D

boiling point:

-42°C

17°C

78°C

Physical Properties

boiling point:

CH3CH2CH2NH2

CH3CH2NHCH3

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 hydrogen bonds.

Basicity of Amines

Effect of Structure on Basicity

1. Alkylamines are slightly stronger bases than ammonia.

Table 22.1 (page 920) Basicity 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 Basicity

1. Alkylamines are slightly stronger bases than ammonia. 2. Alkylamines differ very little in basicity.

Table 22.1 (page 920) Basicity 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 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 22.1 (page 920) Basicity 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 Increasing delocalization makes diphenylamine a weaker base than aniline, and triphenylamine a weaker base than diphenylamine.

C6H5NH2

(C6H5)2NH

(C6H5)3N

0.8

~-5

pKa of conjugate acid: 4.6

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

X X H CH3

NH2

pKa of conjugate acid 4.6 5.3

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 X H CF3 O2N

NH2 pKa of conjugate acid 4.6 3.5 1.0

p-Nitroaniline

–• •• • •O•

•• • O•

+ N

•• O •• – ••

••

NH2

+ N

•• O •• – ••

Lone pair on amine nitrogen is conjugated with p-nitro group—more delocalized than in aniline itself. Delocalization lost on protonation.

+ NH2

Effect is Cumulative

Aniline is 3800 times more basic than p-nitroaniline. Aniline is ~1,000,000,000 times more basic than 2,4-dinitroaniline.

Reactions of Amines: A 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 Nucleophilic substitution by azide ion (N3–) Nitration of arenes Nucleophilic ring opening of epoxides by ammonia Nucleophilic addition of amines to aldehydes and ketones Nucleophilic substitution by ammonia on α -halo acids Nucleophilic acyl substitution

Preparation of Amines by Alkylation of Ammonia

Alkylation of Ammonia Desired reaction is: 2 NH3

+ R—X

R—NH2 +

NH4X

+ H3N

•• – •• •• X ••

via: H3N •• + R then: H3N •• + H

•• • X• ••

H + N R H

R +

H + H3N

H + •• N H

R

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.

NH3

RX

RNH2

RX

R2NH RX

– + R4N X

RX

R3N

Example CH3(CH2)6CH2Br

NH3

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.

The Gabriel Synthesis of Primary Alkylamines

Just for general knowledge, will not be tested on

Gabriel Synthesis gives primary amines without formation of secondary, etc. amines as byproducts uses an SN2 reaction on an alkyl halide to form the C—N bond the nitrogen-containing nucleophile is N-potassiophthalimide

Gabriel Synthesis gives primary amines without formation of secondary, etc. amines as byproducts uses an SN2 reaction on an alkyl halide to form the C—N bond the nitrogen-containing nucleophile is N-potassiophthalimide

O –

•• N–• •

O

K

+

N-Potassiophthalimide the pKa of phthalimide is 8.3 N-potassiophthalimide is easily prepared by the reaction of phthalimide with KOH O

O •• NH

O

KOH

– •• N • • O

K

+

N-Potassiophthalimide as a nucleophile

O

O –

•• N–• •

+ R

•• • X• ••

SN2

•• N

O

O +

– •• • •• X • ••

R

Cleavage of Alkylated Phthalimide O •• N

R + H2O

O

imide hydrolysis is nucleophilic acyl substitution

acid or base CO2H + CO2H

H2N

R

Example O –

•• N–• •

K

+

+

C6H5CH2Cl DMF

O O •• N

O

CH2C6H5

(74%)