chapter 9 amine

AMINESNURUL’ AIN BINTI JAMION

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ORGANIC CHEMISTRY II CHM301

INTRODUCTION Amines are similar to ammonia (base) with

one or more alkyl groups bonded to the nitrogen atom.

The classification: 1o, 2o, or 3o corresponding to the number of

hydrogen atoms or alkyl replaced. General structure:

NH

H

H Ammonia

NR

H

HN

R

R'

HN

R

R'

R''

2

Identify whether the amino group shown by the arrow is primary, secondary or tertiary.

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N

Cl

NH

CH3

N

OH

CH3

Hydroxychloroquine

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NOMENCLATURE OF AMINES

Count the carbons in the longest chain containing the amine

Drop the –e ending for the parent name and add –amine

For a secondary amine an N prefixes the compound giving the shorter carbon chain its side chain prefix name

For a tertiary amine an N,N prefixes the compound giving the two shorter carbon chains their side chain prefix names

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Structural Formula

Condensed Structural Formula

CH3NH2 CH3CH2NHCH3 CH3CH2N(CH3)2

CA format methanamine

N-methylethanamine

N,N-dimethylethanamine

N HC

H

H

H

H

N CH3C

H

C

H

H

H

H

H

N CH3C

CH3

C

H

H

H

H

H

Aromatic amines belong to specific families, which act as parent molecules.

For example, an amino group (—NH2) attached to benzene produces the parent compound aniline.

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NOMENCLATURE OF AMINES

phenylamine

The prefix ‘amino’ is used to indicate the presence of an –NH2 group in a molecule containing more than one functional group.

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NOMENCLATURE OF AMINES

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Compounds with two –NH2 groups are named by adding the suffix ‘diamine’ to the name of the corresponding alkane or aromatic compounds.

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H2N (CH2)6 NH2NH2H2N

hexane-1,6-diamine(1,6-hexanediamine)

benzene-1,4-diamine(1,4-benzenediamine)

NOMENCLATURE OF AMINES

PREPARATION OF AMINES

1. Reduction of nitro compounds2. Reduction of halides with

ammonia3. Reduction of amides4. Reduction of nitriles5. Hoffmann degradation of amides

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1. Reduction of nitro compounds – gives 1o amines Aromatic amines are normally prepared by reduction of

the corresponding aromatic nitro compound. Aniline is prepared from nitrobenzene.

Reducing agents: Fe/H+, Sn/H+ or catalytic hydrogenation (example, H2/Pd or Pt or Ni).

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PREPARATION OF AMINES

Another example:

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PREPARATION OF AMINES

2. Reduction of halides with ammonia The reaction of ammonia with an alkyl halide leads

to the formation of a primary amine.

The primary amine that is formed can also react with the alkyl halide, which leads to a disubstituted amine.(2o amine)

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PREPARATION OF AMINES

Further reaction can form a trisubstituted amine.(3o amine).

In general:

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PREPARATION OF AMINES

3. Reduction of amides Amides yield primary amines on reduction by lithium aluminum hydride, LiAlH4. The oxygen atom is replaced by two hydrogen atoms. 2o and 3o amides produce 2o and 3o amines, respectively. Reaction occurs via nucleophilic acyl substitution then nucleophilic addition.

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PREPARATION OF AMINES

4. Reduction of nitriles Nitriles can be reduced by strong reducing agent

like H2 with catalyst (example Ni) or LiAlH4 to yield primary amines via nucleophilic addition reaction.

Example:

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PREPARATION OF AMINES

R CN 2H2, catalyst

or LiAlH4, ether R CH2NH2

5. Hoffmann degradation of amides Heating the amides with a mixture of bromine

and KOH or NaOH. amides will change to amines. is used to shorten the chain by one carbon.

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PREPARATION OF AMINES

∆

REACTION OF AMINES

1. Formation of amides2. Amine alkylation: formation of

quarternary salts3. With nitrous acid4. Isocyanides (nitrile compound)5. Benzenediazonium salts

1. Preparation of Benzenediazonium chloride

2. Reaction of Benzenediazonium chloride 17

1. Formation of amidesa. From acyl chlorides

Addition of 1o , 2o (or ammonia) to acid chlorides results in amides.

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REACTION OF AMINES

Example:

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REACTION OF AMINES

1. Formation of amidesa. From acid anhydride

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REACTION OF AMINES

2RNH2 R C

O

NHR

2R2NH R C

O

NR2

R C

O

O C

O

R

R C

O

O C

O

R

R C

O

O RNH3+

R C

O

O R2NH2+

acid anhydride amine amide

1. Formation of amidesa. From ester

Esters reacts with ammonia, primary and secondary amines to produce amides and alcohols.

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REACTION OF AMINES

R C

O

O Rester

N R C

O

NH R OHH

H

R

R

R C

O

O Rester

N R C

O

N R OHH

R

R

R

R

secondary amide

tertiary amide

EXAMPLE

H3C C

O

O CH2CH3 N H3C C

O

NH2 CH3CH2 OH

H

HH0-5OC

primary amine

secondary amine

2. Amine alkylation: formation of quarternary salts

Reaction of amines and acid will give amine salt (an ammonium ion).

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REACTION OF AMINES

CH3CH2NH2 + HCl CH3CH2NH3+ + Cl -

n-propylamine n-propylammonium chloride

NH2CH3CH2CH2 HCl NH3ClCH3CH2CH2

N(CH3CH2)3 HCl

triethylamine triethylammonium chloride

NH Cl(CH3CH2)3

Amine alkylation: formation of quarternary salts Examples:

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REACTION OF AMINES

n-propylamine n-propylammonium chloride

NH2CH3CH2CH2 HCl NH3ClCH3CH2CH2

N(CH3CH2)3 HCl

triethylamine triethylammonium chloride

NH Cl(CH3CH2)3

3. With nitrous acid Nitrous acid is unstable and must be prepared in the

reaction solution by mixing sodium nitrite with acid.

Primary amines react with nitrous acid to yield a diazonium salt, which is highly unstable and degradates into a carbocation that is capable of reaction with any nucleophile in solution. Therefore, reacting primary amines with nitrous acid leads to a mixture of alcohol, alkenes, and alkyl halides.

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REACTION OF AMINES

With nitrous acid Primary aromatic amines form stable diazonium

salts at zero degrees.

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REACTION OF AMINES

With nitrous acid Secondary aliphatic and aromatic amines form

nitrosoamine (yellow oils) with nitrous acid.

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REACTION OF AMINES

With nitrous acid Tertiary amines react with nitrous acid to form N-

nitrosoammonium compounds (ammonium salts).

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REACTION OF AMINES

Reaction of nitrous acid with aliphatic amines in cold acidic solution can be used to distinguish between primary, secondary and tertiary amines.

RNH2 + HNO2 → N2 gas evolution from a clear solution.

(1° amines)

R2NH + HNO2 → An insoluble yellow oil formed (N-nitrosoamine) (2° amines)

R3N + HNO2 → A clear solution (ammonium salt formation)

(3° amines) 28

REACTION OF AMINES

4. Isocyanides (nitrile compound)• Primary amines heated with trichloromethane

(CHCl3) and alcoholic KOH solution will produce a foul odor of isocyanide, RNC.

• Isocyanide: - an organic compound with functional group

- The CN functionality is connected to the organic fragment via the nitrogen atom, not via carbon atom.

- a zwitterion (nitrogen atom carries positive charge, carbon atom carries negative charge).

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REACTION OF AMINES

R N C

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REACTION OF AMINES4. Isocyanides (nitrile compound)

examples:

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5. Benzenediazonium salts1. Preparation of Benzenediazonium

chlorideStructure• has the formula C6H5N2+Cl¯• a diazonium group is attached to the benzene ring

• the aromatic ring helps stabilise the ion

REACTION OF AMINES

5. Benzenediazonium salts1.Preparation of Benzenediazonium chlorideFrom phenylamine (which can be made by

reduction of nitrobenzene)Reagents: nitrous acid and hydrochloric acidConditions: keep below 10°CEquation:

C6H5NH2 + HNO2 + HCl C6H5N2 + Cl¯+ 2H2O

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REACTION OF AMINES

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REACTION OF AMINES5. Benzenediazonium salts

2. Reaction of Benzenediazonium chloride Diazonium salts of aromatic amines are very

useful as intermediates to other compounds. Aromatic diazonium salts are only stable at

very low temperatures (zero degrees and below), warming these salts initiates decomposition into highly reactive cations.

These cations can react with any anion present in solution to form a variety of compounds. Figure illustrates the diversity of the reactions.

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REACTION OF AMINES5. Benzenediazonium salts

2. Reaction of Benzenediazonium chloride

• The nitrogen gas is released.