Preparation of Amine

 

Table of the Content

Ammonolysis of Alkyl Halides Reduction of Nitro Compounds Reduction of Nitriles Reduction of Amides Action of Ammonia on Alcohol From Carbonyl Compounds Curtius Reaction Schmidt Reaction Gabriel Phthalimide Synthesis Methods yielding primary amine only Methods giving secondary amines only Methods giving tertiary amine only Related Sources

Ammonolysis of Alkyl Halides

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 salt, from which free amine can be liberated with hydroxide ion.

CH₃Cl + NH₃ → CH₃NH₃Cl CH₃NH₂ + Cl^– + H₂O

The above reaction is a class of substitution reaction, which we know as nucleophilic substitution.

Ammonia can act as a nucelophile and it can also act as a base. If ammonia acts a nucleophile substitution takes place, CH₃CH₂CH₂Br + NH₃ →  CH₃CH₂CH₂NH₂  + HBr

And, if ammonia acts as a base, elimination takes place. (CH₃)₃CCl + NH₃ → (CH₃)₂C=CH₂

It is very evident that primary alkyl halides under go substitution very easily than tertiary alkyl halides, which undergo elimination very easily. Reaction with alkyl halide, yield a mixture of primary, secondary and tertiary amines and also a quaternary ammonium salt( which caannot be considered as amine)   

     

This is because the primary amine formed again acts as a base and keep on reacting with the alkyl halide untill off the hydrogen atoms of amine gets replaced with alkyl groups. However, primary amine is obtained as a major product by taking large excess of ammonia.

Reduction of Nitro Compounds

Nitro alkanes can be reduced quantitatively to their corresponding amines

Nitro compound can be reduced in two general ways: (A) by catalytic hydrogenation using molecular hydrogen, or (B) by chemical reduction, usually by a metal and acid.

This method cannot be used when the molecule also contains some other easily hydrogenated group, such as a Carbon carbon double bond. Chemical reduction is most often carried out by adding hydrochloric acid to a mixture of the nitro compound and metal, usually granulated tin or iron. 

Reduction of Nitriles

Alkyl and aryl cyanides (nitriles)  can be reduced to their corresponding primary amines using lithium aluminium hydride (LiAlH₄) or catalytic hydrogenation.

This reaction is used for ascent of amine series, i.e. for preparation of amines containing one carbon atom more than the starting nitrile.
 

Reduction of Amides

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 + Br₂). This reaction is called as Hofmann Bromamide reaction.

The reaction is as follows,

     RCONH₂ + Br₂ + 4KOH → RNH₂ + K₂CO₃ + 2KBr + 2H₂O

Here we can see that the amine formed has one carbon less than that of the corresponding amide. Due to the loss of carbon atom, this reaction is also called as Hofmann degradation of amides.

The mechanism of the reaction is as follows:

Apart from this, amides can be dehydrated by P₂O₅ to their corresponding nitriles and nitriles can then be reduced.

          

By this method you are retaining the number of carbon atoms in both amide and the amine
 

Action of Ammonia on Alcohol

              

This method yields a mixture of 1^o, 2^o, 3^o amines and 4^o salts which are separated from each other by means of Hinsberg method, Hofmann method and fractional distillation. However, amines can be prepared in good yield by using excess of ammonia.   

                                ZnCl₃
                ROH + NH₃ ———> RNH₂ + H₂O
                               300^oC
 

From Carbonyl Compounds

While studying carbonyl compounds we have seen that carbonyl compounds can be converted into any other functional group. How are we converting carbonyl group into amino group?

See, the following sequence,

The reactions are clear and simple so that, we can get an amine from carbonyl compound just by reductive amination (amination and reduction).

Using this reductive amination we can go from 1° amine to 2° amines. How? Look at  the following reaction.

Curtius Reaction

?Amines can be prepared by treating acid chloride with sodium azides the isocyanate thus formed is decomposed with treatment of water and amines are obtained.

Schmidt Reaction 

?Hydrozoic acid reacts with carboxylic acid in presence of a mineral acid to give  amines.

RCOOH +NH3 RNH₂ + CO₂
 

 Gabriel Phthalimide 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.  

Aromatic primary amines cannot be prepared by this method because aryl halides do not undergo nucleophilic substitution with the anion formed by phthalimide.
 

Methods yielding primary amine only

1. By reduction of nitroalkanes: 

C₂H₅NO₂ + 6[H]    C₂H₅NH₂ + 2H₂O 

                             

C₆H₅NO₂ + 6[H]  C₆H₅NH₂ + 2H₂O 

2. Mendius reduction of alkyl cyanides:                                                  

 CH₃CN + 4H  CH₃CH₂NH₂

 Reduction of alkyl isocyanides with Na/C₂H₅OH gives 2^o amines eg.

      CH₃NC CH₃CHCH₃      

3. By reduction of amides and oximes:

ROCONH₂ RCH₂NH₂  

 

 Cyclohexanone          Cyclohexanoxime       Cyclohexylamine     

4.   By Hofmann bromamide reaction:

CH₃CONH₂ + Br₂ + 4KOH ——> CH₃NH₂ + 2KBr + K₂CO₃ + 2H₂O 

C₆H₅CONH₂ + Br₂ + 4KOH ——> C₆H₅NH₂ + 2KBr + K₂CO₃ + 2H₂O 

5.   By Gabriel phthalimide reaction:  

Potassium phthalimide formed after reaction of phthalimide with KOH, on heating with alkyl halide gives N – alkyl phthalimide. This on hydrolysis with 20% hydrochloric acid under pressure gives 1° amine.  

  

6.   By action of chloramine on Grignard’s reagent:         

  

7.   By decarboxylation of amino acids:    

H₂NCH₂COOHH₂NCH_{3
Glycine                                  Methylamine}

8.   By Wurtz method:

  

CH₃ – N = C = O + 2KOH ———> CH₃NH₂ + K₂CO₃

Methyl isocyanate

9.   Schmidt reaction:

CH₃COOH + HN₃ CH₃NH₂ + CO₂ + N₂
Hydrazoic acid                       Methylamine
 

Methods giving secondary amines only 

1.   By reduction of alkyl isocyanide with sodium and ethanol

CH₃NC + 4H ? CH₃NHCH₃                                      

2.   By heating an alcoholic solution of 1^o amine with alkyl halide

 C₂H₅NH₂ + lC₂H₅ ————> (C₂H₅)₂ NH

                                           Dimethylamine

3.   By hydrolysis of p – nitroso dialkyl aniline with boiling alkali              

Methods giving tertiary amine only 

1. By heating alcoholic solution of NH₃ with excess of alkyl halide -  

      3CH₃l + NH₃ →  (CH₃)₃ N + 3Hl

                                Trimethylamine  

2. By decomposition of tetra – alkyl ammonium hydroxide  

                                    

      (CH₃)₄ N⁺ OH^–  (CH₃)₃ N + CH₃OH
 

Related Sources

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