Amines, nomenclature,chemical properties,physical properties, pharmaceutical applications

2. AMINES…
Presented by
 ABDULLAH IFTIKHAR
 HAMMAD AHMAD
 MOIZ AHMAD
 SABBAR
 ISMAIL KHAN
 SALMAN

3. INTODUCTION
Amines are derivatives of ammonia (NH3) that contains basic nitrogen
atom with a lone pair & which one or more hydrogen atoms have been
replaced by alkyl groups OR Aryl groups
These can be:
 ALIPHATIC AMINES
 AROMATIC AMINES

4. STRUCTURE
 Nitrogen present in amines is sp3 hybridized
 Nitrogen has a pair of non bonded electrons
 Due to presence of lone pair , it is pyramidal instead
Of tetrahedral shape
Trimethylamine
 C-N-H angle in amines is less than 109
degrees

5. NOMENCLATURE
 Named by naming the alkyl group attached with nitrogen atom ,followed
By the ending -amine
 CH3-NH2
Methylamine
 CH3CH2-NH2
Ethylamine
 Prefix di- or tri- is added to the name ,when identical alkyl
groups are attached to nitrogen
Dimethylamine
Trimethylamine

6.  If alkyl groups are different ,they are named in alphabetical order
NOMENCLATURE
Ethylmethylamine Methylpropylamine
A > E > M > P > S > …

7. IUPAC Nomenclature
 If the amine is too complex, the IUPAC system is used .
 In this system ,the amino group (NH2) is considered as a substituent
And its position on the chain is indicated by the lowest possible number.
2-Amino-2-methylpropane 2-Aminopropanoic acid

8. CLASSIFICATON OF AMINES
According to number of alkyl groups attached to the nitrogen atom
Amines are classified as:
1. Primary amines
2. Secondary amines
3. Tertiary amines
Primary amines:
Primary amine has only one alkyl group directly attached to
the nitrogen.
Example;
Methylamine

9.  Secondary amines
CLASSIFICATION
Secondary amine has two alkyl groups directly attached to the nitrogen
 Tertiary amines
Tertiary amine has three alkyl groups directly attached to the nitrogen
Example;
Dimethylamine
Example;
Triethylamine

10. PREPARATION OF AMINES
 Methods for primary amines
1. Reduction of nitroalkanes
2. Reduction of nitriles
3. Reduction of oximes
4. Reduction of amides
5. Hofmann,s degradation of amides
6. Gabriel pthalimide Method
 Methods for secondary amines
1. Reaction of primary amine with alkyl halides
2. Reduction of N-SUBSTITUTED AMIDES
3. Reduction of isonitriles
4. Reductive amination of aldehydes and ketones
 Methods for tertiary amines
1. Reaction of alkyl halides with ammonia
2. Reduction of N,N-Disubstituted amides
3. Decomposition of tetraalkylammonium hydroxides
 Methods yielding mixture of amines
1. Reaction of alkyl halides with ammonia
2. Reactions of alcohols with ammonia

11. Preparation of PRIMARY AMINES
1- REDUCTION OF NITROALKANES:
Primary amines can be obtained by reduction of nitroalkanes with
H2 + Pt OR lithium aluminium hydride
R.NO2 + 3H2 → R.NH2 + 2H2O

12. 2- Reduction of nitriles:
 PREPARATION
Primary amines can be preapared by reduction of nitriles ( alkyl cyanides)
with H2 + Ni OR lithium aluminium hydride
3- Reduction of oximes:
Primary amines obtained by reduction of oximes of aldehydes and ketones with
Lithium aluminium hydride.Reducing Agents like H2 + Ni & Na + C2H5OH can also used.

13.  PREPARATION
4- HOFMANN’S Degradation of Amides:
This is a good laboratory method for the conversion of an amide to a pure primary amine.
The amide is warmed with bromine and concentrated aqueous NaOH solution.
This reaction is called Hofmann’s Rearrangement.Notice that the overall result is the removal of
the carbonyl group from the amide. The product contains one carbon less than the original
amides.The method provides a useful technique for the descent of a homologous series
MECHANISM:

14. This involves the treatment of phthalimide with potassium hydroxide to form the potassium salt
The salt is then heated with an alkyl halide to give N-alkylphthalimide ,which in turn reacts
with potassium hydroxide to form a potassium phthalate salt and a pure primary amine
5-Gabriel phthalimide method:

15.  PREPARATION OF SECONDARY AMINES
1- REACTION OF PRIMARY AMINES WITH ALKYL HALIDES:
When a primary amine is heated with an alkyl halide ,a dialkylammonium salt is formed.
This when treated with NaOH solution yields the free secondary amine.
2- Reduction of N-SUBSTITUTED AMIDES:
Secondary amines can be obtained by reduction of N-SUBSTITUTED amides with
Lithium aluminium hydride

16. 3- Reduction of isonitriles:
Secondary amines may obtained by reduction of isonitriles with H2 + Pt.
Amines produced by this method will always have one –CH3 group
4- Reductive amination of
aldehydes and ketones:
Secondary amines obtained by passing aldehyde or ketone ,hydrogen ,
And RNH2(1-amine) over nickel catalyst at high temperature

17.  PREPARATION OF TERTIARY AMINES
1- REACTION OF ALKYL HALIDE WITH AMMONIA
When an alcoholic ammonia solution is heated with an excess of alkyl halide ,
a trialkylammonium halide is formed.This when treated with NaOH solution gives
Free tertiary amine
2- Reduction of N,N-Disubstituted amides:
Tertiary amines may be obtained by reduction of N,N-Disubstituted amides
with lithium aluminium hydride

18. 3- Decomposition of
tetraalkylammonium hydroxides:
Tertiary amines may be obtained by strongly heating tetraalkylammonium hydroxides.
The hydroxides are prepared by treating the corresponding tetraalkylammonium iodide
With moist silver oxide .

19.  METHODS YIELDING MIXTURE OF AMINES
1- Reaction of alkyl halides with ammonia
Amines can be prepared by heating an alkyl halide with alcoholic ammonia in a sealed tube.
A mixture of primary ,secondary ,tertiary amines and quaternary ammonium salt is obtained

20. 2- Reaction of alcohols with ammonia :
Amines can be prepared by passing the vapors of alcohol and ammonia over heated
Alumina at 400 C . A mixture of peimary , secondary , and tertiary amines is produced

21.  SEPARATION OF MIXTURE OF AMINES
Amines are separated by the following methods:
 Hofmann Method
 Hinsberg Method
 Fractional Distillation
1. Hofmann’s Method:
 The mixture is treated with Diethyl Oxalate and the
result is as follows:
o Primary amines react to form Oxamide (A solid
compound).
o Sec. reacts to forms Oxamic Ester (liquid
compound).
o Tertiary amines do not react with Dieth yl Oxalate.

23. 2. Hinsberg Method:
 It is used for separation as well as identification of amines.
 Mixture of amines is treated with benzenesulfonyl
chloride (Hinsberg reagent) in the presence of aqueous
KOH.
 1° reacts to give sulphonamide which forms a water-
soluble salt on treatment with aq.KOH
 2° also forms sulphonamide but remains as an insoluble
derivative on treatment with aq.KOH
 3° does not react with benzenesulfonyl chloride.

25. . Fractional Distillation:
The mixture of primary, secondary and tertiary amines may be separated by
fractional distillation because their boiling points are quite different. This method is
extensively used in industry.

26. Physical Properties:
1- Lower amines are gases or low boiling liquids and
posses a characteristic ammonia like smell
2- Hydrogen bonding
• Primary and secondary amines are capable of forming hydrogen bonds with each
other
• Tertiary amines can not form hydrogen bonds with each other.

27. 3- Boiling point
THE Ability to form hydrogen bonds gives primary and secondary amines relatively high
Boiling points for their molecular weights

28. 4- SOLUBILITY
All amines ,including tertiary amines are capable of forming hydrogen bonds
with water molecules ,so low molecular weight amines are highly soluble in water
5- IR Spectrum
The infrared spectrum of amines show N-H stretching at 3330 to 3570 cm-1.
Primary amines have two sharp peaks in this region
Secondary amines only one and
Tertiary amines none ( no N-H bond).
The N-H bending frequency occurs at 150 to 1650 cm-1

29. CHEMICAL REACTIONS
OF AMINES
 Amines give reactions due to the presence of lone
pair of electrons on Nitrogen
 This lone pair of electrons is available for
donation to electron-seeking reagents.
 Amines are nucleophilic reagents
 Amines are basic in nature due to nitrogen that
has capacity to donate unshared pair of electrons

30. 1. SALT Formation
2. Reaction with alkyl halides
3. Reaction with acid chlorides (ACYLATION)
4. Reaction with nitrous acid
5. Reaction with benzenesulfonyl chloride(SULFONYLATION)
6. Carbylamine reaction
7. Reaction with carbon disulfide
Reactions list:

31. 1- SALT FORMATION
 As amines are basic, they form salts on reaction with
mineral acids.
 Parent amines are liberated on treating with NaOH
2- Reaction with alkyl halides
 They react with alkyl halide to form 2° and 3° amines.
 The amines formed react with HX (one of the products) to
form salts.

32. 3- REACTION WITH ACID CHLORIDES
Mechanism:
The mechanism involves the nucleophilic attack by the amine
on the electrophilic carbon
A- Primary amines:
Primary amines react with acid chlorides or acid anhydride to form
N-substituted amides. For example
B- Secondary amines:
They react with acid chlorides to form N,N-Disubstituted amides
C- Tertiary amines: They do not react since they not have replaceable hydrogen

33. 4- Reaction with nitrous acid:
Nitrous acid HONO is an unstable substance and is therefore prepared in situ by the reaction
Of sodium nitrite with dilute HCL at 0C
A- Primary amines:
They react with nitrous acid to form alcohols and nitrogen gas
B- Secondary amines:
They react with nitrous acid to form N-nitrosoamines which are water-insoluble
Yellow oils

34. C- Tertiary amines:
They react with nitrous acid to form trialkylammonium nitrite salts which are soluble in water
5- Reaction with benzenesulfonyl chloride
Benzenesulfonyl chloride is obtained by the reaction of benzenesulfonic acid with PCL5 OR SOCl2
A- Primary amines:
They react with benzenesulfonyl chloride to form N-alkylbenzenesulfoamide

35. B- Secondary amines:
They react with benzenesulfonyl chloride to form N,N-Dialkylbenzenesulfonamide
C- Tertiary amines:
They do not react since they do not possess a replaceable hydrogen
NOTE;
the sulfonamide from primary amines still have a replaceable H on the N .
This H ia acidic ,so this sulfonamides dissolve in bases to form soluble salts

36. 6- Carbylamine reaction
• Primary amines react with chloroform and a solution of KOH in ethanol to form isocyanides
(carbylamines).
• Secondary and tertiary amines do not give this reaction
7- Reaction with carbon disulfide:
Primary amines react with carbon disulfide to form a dithiocarbamic acid,this acid undergo
Decomposition with mercuric chloride to give the corresponding alkyl isothiocyanate

37. Amines have wide range of applications in the following:
Dyes:
 Primary aromatic amines are used as a starting
material for the manufacture of azo dyes.
 Azo-compounds are highly colored, they are widely
used in dyeing industries, such as:
o Methyl orange
o Direct brown 138
o Sunset yellow FCF
o Ponceau
 Applications of Amines

38.  Chlorpheniramine is an antihistamine that helps to relieve allergic disorders
due to cold, hay fever, itchy skin, insect bites and stings.
 Chlorpromazine is a tranquilizer that sedates without inducing sleep. It is used
to relieve anxiety, excitement, restlessness or even mental disorder.
 Ephedrine and phenylephrine, as amine hydrochlorides, are used as
decongestants.
 Amitriptyline, imipramine, lofepramine and clomipramine are tricyclic
antidepressants and tertiary amines.
 Nortriptyline, desipramine, and amoxapine are tricyclic antidepressants and
secondary amines. (The tricyclics are grouped by the nature of the final amine
group on the side chain.)
Pharmaceutical Applications (Drugs):

39. • Amines are used in making azo-dyes and nylon apart from medicines and
drugs. They are widely used in developing chemicals for crop protection,
medication and water purification. They also find use in products of
personal care.
 Substituted tryptamines and phenethylamines are key
basic structures for a large variety of psychedelic
drugs.
 Opiate analgesics such as morphine, codeine,
and heroin are tertiary amines.
Some amines, such as methamphetamines and
amphetamines, are popular recreational drugs