Amines

After studying this Unit, you will be able to · describe amines as derivatives of ammonia having a pyramidal structure; · classify amines as primary, secondary and tertiary; · name amines by common names and IUPAC system; · describe some of the important methods of preparation of amines; · explain the properties of amines; · distinguish between primary, secondary and tertiary amines; · describe the method of preparation of diazonium salts and their importance in the synthesis of a series of aromatic compounds including azo dyes.

“The chief commercial use of amines is as intermediates in the synthesis of medicines and fibres”.

Amines constitute an important class of organic compounds derived by replacing one or more hydrogen atoms of ammonia molecule by alkyl/aryl group(s). In nature, they occur among proteins, vitamins, alkaloids and hormones. Synthetic examples include polymers, dye stuffs and drugs. Two biologically active compounds, namely adrenaline and ephedrine, both containing secondary amino group, are used to increase blood pressure. Novocain, a synthetic amino compound, is used as an anaesthetic in dentistry. Benadryl, a well known antihistaminic drug also contains tertiary amino group. Quaternary ammonium salts are used as surfactants. Diazonium salts are intermediates in the preparation of a variety of aromatic compounds including dyes. In this Unit, you will learn about amines and diazonium salts.

I. AMINES Amines can be considered as derivatives of ammonia, obtained by replacement of one, two or all the three hydrogen atoms by alkyl and/or aryl groups. For example:

Like ammonia, nitrogen atom of amines is trivalent and carries an unshared pair of electrons. Nitrogen orbitals in amines are therefore, $s{p}^3$ hybridised and the geometry of amines is pyramidal. Each of the three $s{p}^3$ hybridised orbitals of nitrogen overlap with orbitals of hydrogen or carbon depending upon the composition of the amines. The fourth orbital of nitrogen in all amines contains an unshared pair of electrons. Due to the presence of unshared pair of electrons, the angle C–N–E, (where E is

C or H) is less than $109.5^{\circ }$; for instance, it is $108^{\circ }$ in case of trimethylamine as shown in Fig. 9.1.

Amines are classified as primary ($1^{\circ }$), secondary ($2^{\circ }$) and tertiary ($3^{\circ }$) depending upon the number of hydrogen atoms replaced by alkyl or aryl groups in ammonia molecule. If one hydrogen atom of ammonia is replaced by R or Ar , we get \ce{RNH2} or \ce{ArNH2}, a primary amine ($1^{\circ }$). If two hydrogen atoms of ammonia or one hydrogen atom of \ce{R-NH2} are replaced by another alkyl/aryl(R’) group, what would you get? You get \ce{R-NHR'}, secondary amine. The second alkyl/aryl group may be same or different. Replacement of another hydrogen atom by alkyl/aryl group leads to the formation of tertiary amine. Amines are said to be ‘simple’ when all the alkyl or aryl groups are the same, and ‘mixed’ when they are different.

In common system, an aliphatic amine is named by prefixing alkyl group to amine, i.e., alkylamine as one word (e.g., methylamine). In secondary and tertiary amines, when two or more groups are the same, the prefix di or tri is appended before the name of alkyl group. In IUPAC system, primary amines are named as alkanamines. The name is derived by replacement of ‘e’ of alkane by the word amine. For example, \ce{CH3NH2} is named as methanamine. In case, more than one amino group is present at different positions in the parent chain, their positions are specified by giving numbers to the carbon atoms bearing \ce{-NH2} groups and suitable prefix such as di, tri, etc. is attached to the amine. The letter ‘e’ of the suffix of the hydrocarbon part is retained. For example, \ce{H2N-CH2-CH2-NH2} is named as ethane-1, 2-diamine. To name secondary and tertiary amines, we use locant N to designate substituent attached to a nitrogen atom. For example, \ce{CH3NHCH2CH3} is

named as N-methylethanamine and \ce{(CH3CH2)3N} is named as N, N-diethylethanamine. More examples are given in Table 9.1. In arylamines, \ce{-NH2} group is directly attached to the benzene ring. \ce{C6H5NH2} is the simplest example of arylamine. In common system, it is known as aniline. It is also an accepted IUPAC name. While naming arylamines according to IUPAC system, suffix ‘e’ of arene is replaced by ‘amine’. Thus in IUPAC system, \ce{C6H5-NH2} is named as benzenamine. Common and IUPAC names of some alkylamines and arylamines are given in Table 9.1.

Amine Common name IUPAC name

\ce{CH3-CH2-NH2} Ethylamine Ethanamine

n-Propylamine \ce{CH3-CH2-CH2-NH2} Propan-1-amine

Amines are prepared by the following methods:

1. Reduction of nitro compounds

Nitro compounds are reduced to amines by passing hydrogen gas in the presence of finely divided nickel, palladium or platinum and also by reduction with metals in acidic medium. Nitroalkanes can also be similarly reduced to the corresponding alkanamines.

Reduction with iron scrap and hydrochloric acid is preferred because \ce{FeCl2} formed gets hydrolysed to release hydrochloric acid during the reaction. Thus, only a small amount of hydrochloric acid is required to initiate the reaction.

2. Ammonolysis of alkyl halides

You have read (Unit 6, Class XII) that the carbon - halogen bond in alkyl or benzyl halides can be easily cleaved by a nucleophile. Hence, an alkyl or benzyl halide on reaction with an ethanolic solution of ammonia undergoes nucleophilic substitution reaction in which the halogen atom is replaced by an amino (\ce{-NH2}) group. This process of cleavage of the C\ce{-}X bond by ammonia molecule is known as ammonolysis. The reaction is carried out in a sealed tube at 373 K. The primary amine thus obtained behaves as a nucleophile and can further react with alkyl halide to form secondary and tertiary amines, and finally quaternary ammonium salt.

The free amine can be obtained from the ammonium salt by treatment with a strong base:

Ammonolysis has the disadvantage of yielding a mixture of primary, secondary and tertiary amines and also a quaternary ammonium salt. However, primary amine is obtained as a major product by taking large excess of ammonia. The order of reactivity of halides with amines is \ce{RI > RBr > RCl}.

Write chemical equations for the following reactions: (i) Reaction of ethanolic \ce{NH3} with \ce{C2H5Cl}. (ii) Ammonolysis of benzyl chloride and reaction of amine so formed with two moles of \ce{CH3Cl}.

3. Reduction of nitriles

4. Reduction of amides

The amides on reduction with lithium aluminium hydride yield amines.

5. Gabriel phthalimide synthesis

Gabriel synthesis 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.

6. Hoffmann bromamide degradation reaction