AMINES, AMIDE AND

DERIVATIVES
EDIT AND COMPILED BY:
HAFIZ ABDUL RAFAY LATIF
KAYANI
Participants are:

• Hafiz Rafay Abdul Latif Kayani

• Osama Ali Khan
• Usama Ali
• Mehboob Elahi
• Shehryar Afridi
• Yasir Anwar
• Ahsan Ali Bajwa

Submitted to: Miss Sabeen Tariq

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 Amines
Amines are the derivatives of ammonia  wherein one or more hydrogen atoms
have been replaced by a substituent such as an alkyl or aryl group.
They may be naturally occurring or synthesized.
 Functional group:

Classification of amines:

Primary amine, Secondary amine and Tertiary amine

• Primary amine: one alkyl or aryl group attached to the nitrogen atom.
• Secondary amine: two alkyl or aryl group attached to the nitrogen atom.
• Tertiary amine: three alkyl or aryl group attached to the nitrogen atom.

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 Preparation of Amines

Amines can be prepared by following methods:

• Substitution of ammonia.

• Reduction of nitriles.

• Reduction of amide.

• Hoffman rearrangement & Curtius rearrangement.

• Gabriel phthalmide synthesis

• reductive amination

• Arylamines.
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 1.
Nucleophilic Substitution Of Ammonia
Alkyl halides react via SN2 with ammonia (NH3) and amines as the attacking nucleophile. Many organic halogen
compounds are converted into amines by treatment with aqueous (or) alcoholic solution of ammonia. This reaction is
generally carried out either by allowing the reactants to stand together at room temperature (or) by heating them
under pressure. Displacement of halogen by NH3 yields the amine.

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 2.
Reduction Of Nitriles
Nitriles can be reduced to primary amines with lithium aluminum hydride (LiAlH ).
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 3.
Reduction Of Amide
Amides can directly be converted into their corresponding amines. This reaction is carried
out by treating the amide with a mixture of base and bromine (KOH + Br 2). This reaction is
called as Hofmann Bromamide reaction.
  
 

RCONH  + Br  + 4KOH → RNH  + K CO  + 2KBr + 2H O

2 2 2 2 3 2

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 4.
Hoffman And Curtius Rearrangement
There are two rearrangement reactions which can be used to convert carboxylic acid derivatives into primary
amines where the carbon chain in the product has been shortened by one carbon unit. These are known as the
Hofmann and the Curtius rearrangements.
• The Hofmann rearrangement involves the treatment of a primary amide with bromine under basic conditions.
• While the Curtius rearrangement involves heating an acyl azide. The end result is the same – a primary amine
with loss of the original carbonyl group.

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 5.
Gabriel Phthalmide Synthesis
This method is  used for the preparation of primary amines. Phthalimide on treatment with ethanolic potassium
hydroxide forms potassium salt of phthalimide which on heating with alkyl halide followed by alkaline hydrolysis
produces the corresponding primary amine.

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 6.
Reductive Amination
Aldehydes and ketones can be converted into 1 o, 2o and 3o amines using reductive amination.  The
reaction takes place in two parts.  The first step is the nucleophilic addition of the carbonyl group to
form an imine.  The second step is the reduction of the imine to an amine using an reducing agent. A
reducing agent commonly used for this reaction is sodium cyanoborohydride (NaBH 3CN).

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 7.
Arylamines
The direct introduction of an amino group to an aromatic ring is not possible. However, nitro groups can be added
directly by electrophilic substitution and then reduced to the amine.The reduction is carried out under acidic
conditions resulting in an arylaminium ion as product. The free base can be isolated by basifying the solution with
sodium hydroxide to precipitate the arylamine. Once an amino group has been introduced to an aromatic ring, it
can be alkylated with an alkyl halide, acylated with an acid chloride or converted to a higher amine by reductive
animation as described for an alkyl amine.

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 Properties Of Amines
• STRUCTURE:
Amines consist of an sp3 hybridized nitrogen linked to three substituents by σ bonds. The functional
group is pyramidal in shape with bond angles of approximately 109.
If the substituents are alkyl groups, the amine is aliphatic or an alkyl amine. If one or more of the
substituents is aromatic, the amine is aromatic or an arylamine. If the amine has only one alkyl or aryl
substituent, it is defined as primary. If there are two such substituents, the amine is secondary, and if
there are three such groups, the amine is tertiary.
• BASICITY:
Amines are weak bases but they are more basic than alcohols, ethers, or water. Asa result, amines act
as bases when they are dissolved in water.

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 Properties Of Amines
• REACTIVITY:
Amines react as nucleophiles or bases since they have a readily available lone pair of electrons which
can participate in bonding. Primary and secondary amines can act as weak electrophiles or acids with
a strong base, by losing an N–H proton to form an amide anion (R2N).
• PHYSICAL PROPERTIES:
• Amines are polar compounds with higher boiling points than comparable
• alkanes.
• They have similar water solubilities to alcohols due to hydrogen bonding,
• and low molecular weight amines are completely miscible with water.
• Low molecular weight amines have an offensive fishy smell.

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 Identificaition Test For Amines

Amines are easily detected by the fact that they contain nitrogen, give basic reactions, and are soluble
in acidic solutions.
Following are test for the identification of amines:
• Tetra phenyl borate test.
• Copper ion test.
• Fluorescein chloride test.
• Quinhydrone test.
• N-halosuccinimide test.
• Hinsberg test.
• Diazonium salt test.
• Lignin test.
 Identificaition Test For Amines
• TETRA PHENYL BORATE TEST:
When a slightly acidic aqueous solution of ammonia or an amine is added to an aqueous solution of
sodium tetraphenylborate, an immediate, thick, white precipitate is formed.
• COPPER ION TEST:
Low molecular weight amines that Are soluble in water including amino alcohols, may be detected by
10 percent copper sulphate solution. formation of a blue or blue-green coloration or precipitate with
the reagent indicates the presence of an amine.
• FLUORESCEIN CHLORIDE TEST.
When amine salt is fused with fluorescein chloride reagent. at 250-260°c in presence of anhydrous
zinc chloride, it forms red water soluble rhodamine dye. Hydrazo compounds and some N-aryl
amides also give positive test with the reagent.

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 Identificaition Test For Amines
• QUINHYDRONE TEST:
Quinhydrone has been found to be an excellent reagent for the detection of certain amines.
Quinhydrone reacts with aliphatic and aryl amine in aqueous or in ethanolic medium to give different
colors depending upon the nature of amine i.e. primary, secondary or tertiary. Nitro substituted
amines can not be detected by the reagent while phenylenediamine gives false colors.
• N-HALOSUCCINIMIDE TEST:
N-Bromosuccinimide and N-iodosuccinimide are good detecting and differentiating reagents for
amines. Primary and tertiary amines react with N-iodo succinimide to give brown colors that do not
fade on heating. Secondary amines produce brown colors that fade to yellow or colorless within few
minutes. Tertiary amines give an orange precipitate with N-bromo succinimide.

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 Identificaition Test For Amines
• HINSBERG TEST:
This test is based on the fact that primary and secondary amines react with benzenesulfonyl halides to
form N-substituted sulfonamides, whereas tertiary amines do not react with the reagent. further, the
sulfonamides of primary amines are soluble in alkaline solution may be differentiated from the
sulfonamides of secondary amines which are insoluble in alkali.
• DIAZONIUM SALT TEST:
Most of the aryl amine and phenols undergo coupling reactions with diazonium salts to form colored
azo .compounds. Alkyl amine gives less intense yellow color than that of aryl amines.
• LIGNIN TEST.
Webster has proposed e very simple test for primary and secondary aryl am~nes. The test depends on
the action of lignin in newspri~t paper. Ethanolic solution of amines applied on newsprint paper and
treated with 6N hydrochloric acid. Primary and secondary aryl aminesproduce immediate yellow or
orange color, whilealkyl and alicyclic amine require hot solution for color development.

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 Pharmaceutical Applications Of Amines
Amines Are Largely Used In Pharmaceutical Industry.

• Morphine And Demerol Are Used As Analgesic That Are Pain Killers.

•  Novocain Is Used As Anesthetic.

• Ephedra Is A Very Common Decongestant

• Tetramethyl Ammonium Iodide For Disinfecting Drinking Water.

• Choline Is One Of These Salts Which Plays A Significant Role In The Production Of
Neurotransmitters In Human Body To Make The Brain Function Properly.
• Chlorpromazine Is A Tranquilizer That Sedates Without Inducing Sleep. It Is Used To Relieve
Anxiety, Excitement, Restlessness Or Even Mental Disorder.

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•
Amides
Amides are molecules that contain nitrogen atoms connected to the carbon atom of a
carbonyl group.
• Amides are derivatives of carboxylic acids, derived by combining carboxylic acids
with amines.
• Structure:

• They can be classified same as amine to aliphatic and aromatic, and aliphatic
• amides can be classified to Primary, Secondary and Tertiary. According to the
number of substituents (non-hydrogen-like groups) connected to the nitrogen of the
amide group.

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 Preparation Of Amides
Highlighted below are the most common strategies by which amides are prepared.
The amides are commonly prepared from the reaction of carboxylic acids, acid chlorides and
acid anhydrides with amines.
 Preparation Of Amides
• Reaction of Carboxylic Acids with Amines in Presence of DCC:
Primary and secondary amines react with carboxylic acids in the presence of DCC to form
amides.

• Reaction of Acid Chlorides with an Amine:

Acid chlorides, with a good leaving group attached to the carbonyl group, react with ammonia
and amines through a nucleophilic acyl substitution to provide amides.

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 Preparation Of Amides
• Reaction of Acid Anhydrides with an Amine:
Just like acid chlorides, acid anhydrides also react with ammonia and amines through a
nucleophilic acyl substitution to provide amides.

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 Propeties Of Amides
• The simplest amides (methanamide, N-methyl, and N,N-dimethyl

derivatives) are liquids at room temperature, and all unbranched amides having 2 or

more carbons on their C-chain side are solids.

• amide have very high boiling points.

• Simple amides are soluble in water.

• Amides do not behave like bases.

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 Identification Test Of Amides
• Sodium Hydroxide Solution Test:
If you add sodium hydroxide solution to an unknown organic compound, and it
gives off ammonia on heating (but not immediately in the cold), then it is an
amide.
You can recognize the ammonia by smell and because it turns red litmus paper
blue.

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 Pharmaceutical Applications Of
Amides
• Acetaminophen is used to reduce fever and pain.
• Some amides such as phenobarbital, Nembutal and Seconal are barbiturates.
• Diazepam (Valium) A benzodiazepene tranquilizer; acts by enhancing the
inhibitory neurotransmitter GABA.
• Thalidomide a very popular, safe sedative.
• Phenobarbitol Anti-seizure medication, sedative.
• Amobarbital (Amytal) Used in the treatment of insomnia

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THANKS!

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