Ammonolysis Reaction: Hoffmann’s Ammonolysis Methode, Physical Properties of Amines, Practice Problems, FAQs

Imagine there’s a sports day going on in your school and you were asked to keep a first aid box with you. You started collecting the contents of a first aid box. You saw a common drug - paracetamol, that is prescribed as a pain killer and antipyretic to contain fever as an important content of the box.

.

Do you know what the base composition of this drug is?

Well, amines are generally used to prepare paracetamol. Let’s understand how amines can be prepared by the ammonolysis method.

Table of Contents

• Definition of Amine
• Classification of Amines
• Definition of Ammonolysis
• Hoffmann's Ammonolysis Method
• Physical Properties of Amines
• Practice problems
• Frequently Asked Questions

Definition of Amine

Chemically speaking, amine is a product of ammonia (NH3). In other terms, amines are derived from ammonia. A nitrogen atom with a lone pair is present in amines, which are organic nitrogen molecules. Aryl or alkyl groups often replace the hydrogen atoms of ammonia in amines.

Classification of Amines

Classification of amines is based on the two factors that is

• Based on the types of group attached to N
• Based on the number of groups attached to N

Amines are further classified into three categories based on the types of groups attached to N

• Alkylamines
• Arylamines
• Heterocyclic amines

Alkyl Amines

An alkyl amine is a substance in which the nitrogen atom of an amine is joined to an alkyl group. Alkyl amines are created when one of the ammonia's three hydrogen atoms is changed for an alkyl.

For example: Methylamine and Ethylmethylamine

Aryl Amines

Any of a category of amines in which aromatic groups are used in place of one or more of the hydrogen atoms in ammonia.

Heterocyclic Amines

These are formed during the high-temperature cooking of meat, poultry, or fish, such as when frying, broiling, or grilling. Carcinogens include heterocyclic amines (substances that may cause cancer). also known as HCA.

Amines are classified into three groups: primary (10), secondary (20), and tertiary depending on how many hydrogen atoms in ammonia are changed for an alkyl or aryl group (30). When one hydrogen atom is replaced, amines with the formula R-NH2 or primary amines (10) are created. Alkyl/aryl groups can replace two of the three hydrogen atoms to form secondary amines. If an alkyl or aryl group is substituted for all three hydrogen atoms, tertiary amines are created.

Primary Amines

When an alkyl or aromatic group replaces one of the hydrogen atoms in ammonia, a primary amine is created. Amino acids and methylamine are examples of primary alkyl amines, whereas aniline is an example of a primary aromatic amine.

Secondary Amine

An amine in which the amino group has a direct link to two carbons of any hybridization, which takes place when an organic molecule with two amine groups. Secondary amines are also called as enamine.

Simple Secondary Amine

An amine where all alkyl or aryl groups attached to the nitrogen atom are same then it is called as simple secondary amine.

Mixed Secondary Amine

An amine where all alkyl or aryl groups attached to the nitrogen atom are not same then it is called as simple secondary amine.

Tertiary Amine

An amine in which three carbons of any hybridization—but not carbonyl group carbons—directly link to the nitrogen atom. tertiary amine structure in general. C is equal to any carbon group besides carbonyl.

Simple Tertiary Amine

An amine, where all alkyl/aryl groups​ attached to N are the same​ then it is called as simple tertiary amine.

Mixed Tertiary Amine

An amine, where all alkyl/aryl groups​ attached to N are not the same​ then it is called as mixed tertiary amine.

Definition of Ammonolysis

Ammonolysis is the process of forming arious amines using ammonia or primary and secondary amines as amminating agents. Hydro Ammonolysis, in which amines are formed directly from carbonyl compounds using an ammonia-hydrogen mixture and a hydrogenation catalyst, is also one of this process.

Hoffmann's Ammonolysis Method

(From alkyl or benzyl halides and ammonia or amines)

• Amines are produced when an alcoholic solution of ammonia (or an amine) and an alkyl or a benzyl halide is heated in a sealed tube at 373 K.
• Breaking up of the carbon halogen bond with ammonia or an amine is referred as ammonolysis.
• This reaction is a typical example of a nucleophilic substitution reaction in which the nucleophile ammonia (or the amine) displaces the halogen atom.
• The ammonolysis reaction is also mentioned as Hoffmann’s ammonolysis
• Depending on the relative amount of halides and ammonia or amines peasant primary, secondary or tertiary, simple or mixed amines will be produced as a mixture.

R-X + NH₃ ———> R-NH₂ + HX - Formation of a primary amine

R-NH₂ + R-X——-> R₂NH + HX - Formation of a secondary amine

R₂NH + R-X ——-> R₃N + HX - Formation of a tertiary amine

R₃N + R-X——-> R₄NX - Formation of a quaternary salt.

Limitations of Hoffmann’s method:

1. Product of Hoffman's ammonolysis is always a mixture of primary, secondary, tertiary and quaternary amine compounds. Hence preparation of any pure amine is not possible.
2. Aryl halides do not undergo Hoffman's ammonolysis to produce aryl amines. Aryl halides have a strong -C-X double bond, that cannot be easily broken by the nucleophile.

Physical Properties of Amines

Some important physical properties of amines are discussed below:

Colour and odour

• Pure amines are almost colourless but develop colour on keeping in air for long time. This is due to the reason that amines, especially aromatic amines, are readily oxidized in air to form coloured oxidation products.
• Lower aliphatic amines are gasses and smell very much like ammonia. Primary amines with three or more carbon atoms are liquids with fishy odours. Lower aromatic amines are liquids having characteristic unpleasant odours but the higher ones are low melting solids which are almost odourless Aromatic amines, in general, are toxic.

Boiling points

• Comparable to the parent hydrocarbons, the primary and secondary substituted amines exhibit higher boiling points. Highly electronegative nitrogen in the amines, lead to the formation of intermolecular hydrogen bonds (R-N-H------NH ) in primary and secondary amines. Tertiary amines do not have any nitrogen attached hydrogen and hence cannot form both intra and intermolecular hydrogen bonding.

• The intermolecular hydrogen bonding keeps the molecules in an associated state. The strength and extent of association directly reated to the polarity of the molecules and number of such positive hydrogen atoms present in the molecule. Primary amines, secondary and tertiary amines have 2, 1 and 0 hydrogen atoms attached to the electronegative nitrogen of amines. Hence the number of associated amine molecules and the increased boiling point of isomeric amines will be in the order of primary > secondary . tertiary amines.

• Electronegativity of nitrogen beng lower than that of oxygen, amines are less polar than hydroxyl groups. Hence, Hydrogen bond formation and strength will be in the order of acids > alcohols . amines. So, the boiling points of amines are lower than those of alcohols and carboxylic acids of comparable molecular masses. For example, ethylamine (mol. mass 45) boils at 292 K while ethyl alcohol (mol. mass 46) and formic acid (mol. mass 46) boil at 351 K and 374 K respectively.

Solubility

• All the three classes of aliphatic amines (1°, 2° and 3°) form H-bonds with water. As a result, lower aliphatic amines are soluble in water.
• Methylamine and ethylamine are gasses but they are -H highly soluble in water. That is why they are sold in the market as their 34% aqueous solutions. However, as the size of the alkyl group increases (with increase in molecular mass), the solubility decreases due to a corresponding increase in the hydrocarbon part (hydrophobic part) of the molecule. The borderline solubility is reached with amines of about six carbon atoms in the molecule. However, amines are quite soluble in organic solvents such as benzene, ether, alcohol, etc.

• Aromatic amines, on the other hand, are insoluble in water. This is due to the larger hydrocarbon part which tends to retard the formation of H-bonds. Thus, aniline is almost insoluble in water. However, it is quite soluble in organic solvents such as benzene, ether, alcohol, etc.

Practice problems

Q1. Select the method that can be used for preparing a primary amine which is lesser by a carbon atom.

1. Hoffmann bromamide degradation reaction
2. Catalytic reduction of isonitrile
3. Gabriel phthalimide synthesis with alkyl halide
4. Aldehyde reduction with ammonia

Answer: (A)
The Hofmann bromamide reaction is the most effective way to get amine having a carbon atom less. When a primary amide is treated with an aqueous or ethanolic solution of potassium hydroxide and bromine (or potassium hypobromite, KOBr), it gives a primary amine that has one carbon atom less than the original amide.

Q2. Amine that cannot be prepared by Gabriel phthalimide synthesis is

1. Aniline
2. methyl amine
3. Benzylamine
4. iso-butylamine

Answer: (A)
Gabriel phthlimide synthesis is a preparative method of primary alkyl amines. Aryl halides are not capable of undergoing nucleophilic substitution reactions. Aniline and benzylamine are aryl amines and cannot be prepared by Gabriel synthesis. Iso-butyl amine though a primary amine is sterically hindered for substitution reaction. So, the correct answer is methyl amine.

Q3. Which of the following amides will give ethanamine on reaction with Br2 and NaOH ?

1. Butanamide
2. Acetamide
3. Propanamide
4. Benzamide

Answer: (C)
When propanamide is heated in presence of Br2 and NaOH it gives rise to ethanamine.

Q4. Reduction of aromatic nitro compounds using HCl gives

1. aromatic primary amines
2. aromatic secondary amines
3. aromatic tertiary amines
4. aromatic amides.

Answer:(A)
Aromatic primary amines are produced when nitro aryl compounds are reduced in the presence of Fe and HCl.

Frequently Asked Questions (FAQs)

Q1. Why secondary and tertiary amines can’t be prepared from isocyanides (Carbylamine reaction)?
Answer: According to the mechanism, this is among the best examples of an Alpha elimination reaction, in which carbanion is formed first, then the chloride ion is lost to form highly reactive dichlorocarbene. The remaining two chlorine atoms are now removed as HCl. The nitrogen in amine provides the necessary hydrogen.

When the secondary and tertiary amines react, nitrogen does not have nearly as many hydrogen atoms as it does in primary amines, and a sterically highly unstable product is expected. Furthermore, alkyl isocyanides have an unpleasant odour. As a result, we only use this test to detect primary amines.

Q2. Why can’t we use conc. HCl instead of conc. Sulphuric acid during the reduction of nitro compounds?
Answer: Sulphuric acid, unlike hydrochloric acid, is an oxidizing agent. As a result, instead of conc. sulphuric acid, conc. HCl is used to reduce nitro compounds.

Q3. Why do we get primary amine when alkyl cyanide is reduced?
Answer: The carbon-nitrogen triple bond of nitriles can be completely reduced to yield primary amines. The reduction is done using H2in presence of Ni or Pt as catalyst or using LiAlH4

Q4. Do we frequently use ammonolysis method for the production of amine?
Answer: Ammonolysis produces a mixture of quaternary salts and primary secondary tertiary amines. This amines must be separated, which is a very challenging process. As a result, producing pure amines through ammonolysis of alkyl halides is challenging. Hence, we don’t use it frequently.

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