Methods of Preparation of Amines: Amine is a chemical substance generated from ammonia (NH3). We can simply state that amines are ammonia derivatives. Which is the most common antihistamine in the doctor’s prescription? Its Benadryl – a drug that contains the tertiary amino groups. An important class of organic molecules is the amino group, also known as Amines, which can be created by substituting one or more hydrogen atoms in an ammonia molecule with an alkyl/aryl group.

Alkaloids present in certain plants; catecholamine neurotransmitters (dopamine and adrenaline); and histamine, a particular chemical mediator found in most animal tissues, are just a few examples of naturally occurring amines. Amines are found naturally in hormones, vitamins, proteins, and other substances. They can also be made synthetically through preparation methods of amines. Read the entire article to know the preparation methods of amines.

Study Classification of Amines Here

What are Amines?

Amines are the organic compounds that are broadly considered derivatives of ammonia. These nitrogen-based organic compounds are obtained by replacing one, two, or all the three hydrogen atoms of an ammonia molecule with alkyl and/or aryl groups.

For example,

The nitrogen orbitals in amines are \({\rm{s}}{{\rm{p}}^3}\) hybridised with a pyramidal geometry. Each of the three \({\rm{s}}{{\rm{p}}^3}\) hybridised orbitals of nitrogen overlap with orbitals of carbon or hydrogen as per the composition of the amines. The fourth orbital of nitrogen contains an unshared pair of electrons which is common in all amines. This unshared pair of electrons reduces the \({\rm{C}} – {\rm{N}} – {\rm{E}}\) (where \({\rm{E}}\) is \({\rm{C}}\) or \({\rm{H}}\)) bond angle from \({109.5^{\rm{o}}}\) to \({108^{\rm{o}}}.\)

Based on the number of hydrogen atoms replaced by alkyl or aryl groups in ammonia molecules, the amines are broadly classified as primary \(\left( {{1^{\rm{o}}}} \right),\) secondary \(\left( {{2^{\rm{o}}}} \right),\) and tertiary \(\left( {{3^{\rm{o}}}} \right).\)

If one hydrogen atom of ammonia is replaced by \({\rm{R}}\) or \({\rm{Ar}},\) we get a primary amine \(\left( {{1^{\rm{o}}}} \right)\) \({\rm{ – RN}}{{\rm{H}}_2}\) and \({\rm{ArN}}{{\rm{H}}_2}.\)

If two hydrogen atoms of ammonia or one hydrogen atom of \({\rm{RN}}{{\rm{H}}_2}\) are replaced by another alkyl/aryl\(\left( {{\rm{R}}’} \right)\) group, we get secondary amine \(\left( {{2^{\rm{o}}}} \right){\rm{R}} – {\rm{NHR}}’.\) The second alkyl/aryl group may be the same or different.

If all the three hydrogen atoms of ammonia or the remaining hydrogen atom of \({\rm{RN}}{{\rm{H}}_2}\) is replaced by the alkyl/aryl group, then we get a tertiary amine \(\left( {{3^{\rm{o}}}} \right).\)

When all the alkyl or aryl groups are the same, then the amine is said to be simple, and when they are different, ‘mixed’ amines are formed.

Methods of Preparation of Amines Class 12

Amines are prepared by the following methods:

1. Reduction of Nitro Compounds

When hydrogen gas is passed over nitro compounds in the presence of finely divided nickel, palladium, or platinum, these are reduced to corresponding amines. Also, nitro compounds can be reduced metals in an acidic environment to generate amines.

This reaction takes place for aliphatic nitro compounds, also where they are reduced to their corresponding alkanamines. Reduction of nitro compounds with iron scrap and hydrochloric acid is preferred. This is because \({\rm{FeC}}{{\rm{l}}_2}\) formed gets hydrolysed to release hydrochloric acid during the reaction. Hence, only a small amount of hydrochloric acid is required to initiate the reaction.

2. Ammonolysis of Alkyl Halides

An alkyl or benzyl halide undergoes a nucleophilic substitution reaction on reaction with an ethanolic solution of ammonia. In this reaction, the halogen atom of the halide is replaced by an amino \(\left( { – {\rm{N}}{{\rm{H}}_2}} \right)\) group. This process involves the cleavage of the \({\rm{C}} – {\rm{X}}\) bond by the ammonia molecule, known as ammonolysis.

The ammonolysis process is carried out in a sealed tube at \(373\,{\rm{K}}.\) The primary amine thus obtained behaves as a nucleophile and keeps on reacting with the alkyl halide until all of the hydrogen atoms of amine are replaced with alkyl groups. Hence, secondary and tertiary amines, and finally quaternary ammonium salt, are also formed in this reaction.

Amine is obtained from the substituted ammonium salt by treating it with a strong base:

Ammonolysis produces a mixture of primary, secondary, and tertiary amines, as well as a quaternary ammonium salt. Primary amine, on the other hand, is a main result of ammonia. Halides react with amines in the following order: \({\rm{RI}} > {\rm{RBr}} > {\rm{RCI}}.\)

3. Reduction of Nitriles

Primary amines are produced by reducing nitriles with lithium aluminium hydride \(\left( {{\rm{LiAI}}{{\rm{H}}_4}} \right).\) The nitriles can also be catalytically hydrogenated to produce primary amines. This reaction is used to ascend in the amine series, i.e., for the preparation of amines containing one carbon atom more than the initial amine.

4. Reduction of Amides

Amides are reduced to their corresponding amines by lithium aluminium hydride. It is possible to synthesise secondary amines by substituting \({\rm{N}}\) and \({\rm{N}},\) \({\rm{N}}\) amides.

5. Gabriel Phthalimide Synthesis

Gabriel phthalimide synthesis is used for the preparation of primary amines only. On treating phthalimide with ethanolic potassium hydroxide solution, the potassium salt of phthalimide is formed. On heating, this potassium salt with alkyl halide followed by alkaline hydrolysis produces the corresponding primary amine. This synthesis process is used only to prepare primary aliphatic amines and is not used to prepare primary aromatic amines. This is due to the fact that aryl halides do not undergo nucleophilic substitution with the phthalimide anion.

6. Hoffmann Bromamide Degradation

Amides can be directly converted into their corresponding amines. This reaction is carried out by treating the amide with a mixture of a base and bromine \(\left( {{\rm{KOH}} + {\rm{B}}{{\rm{r}}_2}} \right).\) Primary amines are prepared by treating an amide with bromine in an ethanolic or aqueous sodium hydroxide solution. In this degradation reaction, the migration of an alkyl or aryl group takes place from the carbonyl carbon of the amide group to the nitrogen atom. The amine so formed contains one carbon less than that is present in the amide group.

Apart from this reaction, amides can also be dehydrated by \({{\rm{P}}_2}{{\rm{O}}_5}\) to their corresponding nitriles that can be further reduced to amines.

By this method, the number of carbon atoms in both amide and the amine is maintained.

7. Reductive Amination Of Aldehydes And Ketones

Carbonyl compounds such as Aldehydes or ketones can be catalytically reduced in the presence of ammonia to produce primary, secondary, or tertiary amines.

The reaction of a ketone with ammonia, followed by catalytic reduction by sodium cyanoborohydride, produces a \({1^{\rm{o}}}\) amine.

The reaction of a ketone with primary amines, followed by catalytic reduction by sodium cyanoborohydride, produces \({\rm{N}}\)‐substituted amines.

The reaction of a ketone with secondary amines, followed by catalytic reduction by sodium cyanoborohydride, produces \({\rm{N,}}\,{\rm{N}}\)‐disubstituted amines.

8. Curtius Reaction

Amines are also prepared by treating acid chloride with sodium azides—the reaction results in the isocyanate formation, which is further hydrolysed to amines.

9. Schmidt Reaction 

Carboxylic acids, ketones, and alkenes react with hydrazoic acid to give corresponding amines.

10. Action of Ammonia on Alcohol

A mixture of \({{\rm{1}}^{\rm{o}}},\,{2^{\rm{o}}},\,{3^{\rm{o}}}\) amines, and \({4^{\rm{o}}}\) salts is obtained in this reaction that is separated by means of the Hinsberg method, Hofmann method, and fractional distillation. However, amines can be prepared in good yield by using an excess of ammonia.

Preparation Methods of Amines Summary

Proteins, vitamins, alkaloids, and hormones are naturally occurring amines. Synthetic amines include drugs, polymers, and dyes. Biologically active compounds such as adrenaline and ephedrine that increase blood pressure contain secondary amino groups. And the very common antihistamine Benadryl has a tertiary amino group. Hence, it is essential to learn their structure and preparation. In this article, we learned the various methods through which we can prepare amines. We also learned some important name reactions such as Gabriel phthalimide synthesis, Hoffmann Bromamide degradation, and Schmidt reaction.

FAQs on Methods of Preparation of Amines

Read the most frequently asked question about methods of preparation of Amines below.

Q.1. Which method is used for the preparation of aromatic amines?
Ans: Aromatic amines can be prepared by:
1. Reduction of nitro compounds
2. Reduction of nitriles
3. Reduction of amides
4. Amination of aldehydes and ketones
5. Hoffmann bromamide degradation

Q.2. How are amines prepared from nitro compounds?
Ans: Amines are prepared from nitro compounds by passing hydrogen gas over nitro compounds in the presence of finely divided nickel, palladium, or platinum. This reaction involves the reduction of nitro compounds to amines. Amines are also formed by the reduction of nitro compounds with metals in an acidic medium.

This reaction takes place for aliphatic nitro compounds, also where they are reduced to their corresponding alkanamines. Reduction of nitro compounds with iron scrap and hydrochloric acid is preferred. This is because \({\rm{FeC}}{{\rm{l}}_2}\) formed gets hydrolysed to release hydrochloric acid during the reaction. Hence, only a small amount of hydrochloric acid is required to initiate the reaction.

Q.3. How do you make a secondary amine?
Ans: By reduction of alkyl isocyanide with sodium and ethanol.

 \({\rm{C}}{{\rm{H}}_3}{\rm{NC}} + 4{\rm{H}} \to {\rm{C}}{{\rm{H}}_3}{\rm{NHC}}{{\rm{H}}_3}\)

 By heating an alcoholic solution \({1^{\rm{o}}}\) amine with alkyl halide.

 \({{\rm{C}}_2}{{\rm{H}}_5}{\rm{N}}{{\rm{H}}_2} + {\rm{I}}{{\rm{C}}_2}{{\rm{H}}_5} \to {\left( {{{\rm{C}}_2}{{\rm{H}}_5}} \right)_2}{\rm{NH}}\)

Q.4. Which method is not used for the preparation of aromatic amines?
Ans: Gabriel phthalimide synthesis is not used for the preparation of aromatic amines. The reaction involves the formation of a phthalimide anion. The aryl halides required for the formation of aromatic amines do not undergo nucleophilic substitution reaction with the anion formed by phthalimide.

Q.5. What are the two types of aromatic amines?
Ans: Aromatic amines are classified into:

 Aryl amine: The amines in which the nitrogen atom is directly bonded to one or more aromatic rings or aryl groups are called arylamines. 

 Example: Aniline \({{\rm{C}}_6}{{\rm{H}}_5}{\rm{N}}{{\rm{H}}_2},\) Diphenylamine \({\left( {{{\rm{C}}_6}{{\rm{H}}_5}} \right)_2}{\rm{NH}},\) Triphenylamine\({\left( {{{\rm{C}}_6}{{\rm{H}}_5}} \right)_3}{\rm{N}}{\rm{.}}\) 

 Aryl-alkyl amine: The amines in which the nitrogen atom is bonded to the side chain of the aromatic ring are called aryl-alkyl amines. 

 Example: Phenylmethanamine 

 (benzylamine) \({{\rm{C}}_6}{{\rm{H}}_5}{\rm{C}}{{\rm{H}}_2}{\rm{N}}{{\rm{H}}_2},\) Dibenzylamine \({\left( {{{\rm{C}}_6}{{\rm{H}}_5}{\rm{C}}{{\rm{H}}_2}} \right)_2}{\rm{NH}}{\rm{.}}\)

Q.6. What is the formula of primary amine?
Ans: When one hydrogen atom of ammonia is replaced by an alkyl \(\left( {\rm{R}} \right)\) and/or aryl group \(\left( {{\rm{Ar}}} \right),\) we get a primary amine \(\left( {{1^{\rm{o}}}} \right).\) The general structural formula of primary amine is \({\rm{RN}}{{\rm{H}}_2}\) or \({\rm{ArN}}{{\rm{H}}_2}.\)

Study Structures of Amines Here

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