Organic Compounds with Amino Group

ORGANIC COMPOUNDS WITH AMINO GROUPS

Amines are the organic compounds derived from ammonia (NH3) by replacing its one or more hydrogen atoms by alkyl or aryl group.

For example:

 CH3NH2                              C2H5NH2                            C6H5NH2

Methyl Amine                         Ethyl Amine                           Aniline

 

Structure of amines

Nitrogen atom of amines carries an unshared pair of electrons and is sp3  hybridised with pyramidal shape. 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°.

 

In aromatic amines, the C‒N bond is slightly stronger due to the partial double bond character which arises as a result of delocalisation of lone pair of N with the benzene ring.

Classification of amines

On the basis of number of hydrogen atoms replaced in NH3 molecule, amines are categorized into three types:

•     1° amine: One hydrogen atom of NHis replaced by an alkyl or aryl group.

For example:

CH3NH2

Methyl Amine

•     2° amine: Two hydrogen atoms of NHare replaced by alkyl or aryl groups.

For example:

CH3NHCH3

Dimethyl Amine

•     3° amine: All three hydrogen atoms of NHare replaced by alkyl or aryl groups.

For example:

Nomenclature of amines

Common naming system:

•     Aliphatic amines are named by prefixing an alkyl group to a mine, i.e., alkylamine.

For example:

 

•     Secondary and tertiary amines, having two or more similar groups are named by adding prefix ‘di’ or ‘tri’ before the name of alkyl group.

For example:

 

•     Aromatic amines are named as derivatives of the parent member, aniline (C6H5NH2).

For example:

 

IUPAC naming system:

•     Aliphatic or aromatic amines are named by replacing ‘e’ in the end of the parent hydrocarbon by ‘amine’.

For example:

    CH3NH2                              C6H5NH2

Methanamine                        Benzenamine

•     Amines containing more than one amino groups at different positions in the parent chain, are named by specifying numbers to the carbon atoms bearing –NHgroups along with attaching a suitable prefix such as di, tri, etc. to the amine. The ending ‘e’ of the hydrocarbon is retained.

For example:

H2N ‒ CH‒ CH‒ NH2

Ethane-1, 2-diamine

ALIPHATIC AMINES

Aliphatic amines are organic compounds that contain an amino group (-NH2) attached to an aliphatic carbon chain. Aliphatic carbon chains are straight or branched chains of carbon atoms that are not part of an aromatic ring. Aliphatic amines are classified based on the number of alkyl groups attached to the nitrogen atom. Primary amines have one alkyl group attached to the nitrogen atom, secondary amines have two alkyl groups attached, and tertiary amines have three alkyl groups attached.

Aliphatic amines can be synthesized by the reaction of ammonia or primary amines with alkyl halides or by the reduction of nitriles. They are commonly used in the production of dyes, rubber chemicals, pharmaceuticals, and pesticides. Aliphatic amines are also used as solvents, corrosion inhibitors, and surfactants.

The properties of aliphatic amines, such as solubility, boiling point, and reactivity, depend on the size and nature of the carbon chain and the number of alkyl groups attached to the nitrogen atom. Primary amines are more reactive than secondary and tertiary amines because the nitrogen atom is more basic and can form stronger bonds with electrophiles.

Aliphatic amines have many important applications in industry and are used in a variety of products. However, exposure to high levels of aliphatic amines can be harmful to human health and the environment. Therefore, it is important to handle and dispose of these compounds properly and to follow safety guidelines to minimize any potential risks.

 

Synthesis of amine

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 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.

Ammonolysis of alkyl halides

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 (–NH2) group. This process of cleavage of the C–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 RI > RBr >RCl.

 

Reduction of nitriles

Nitriles on reduction with lithium aluminium hydride (LiAlH4) or catalytic hydrogenation produce primary amines. This reaction is used for ascent of amine series, i.e., for preparation of amines containing one carbon atom more than the starting amine.

Reduction of amides

The amides on reduction with lithium aluminium hydride yield amines.

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.

 

Hoffmann bromamide degradation reaction

Hoffmann developed a method for preparation of primary amines by treating an amide with bromine in an aqueous or ethanolic solution of sodium hydroxide. In this degradation reaction, migration of an alkyl or aryl group takes place from carbonyl carbon of the amide to the nitrogen atom. The amine so formed contains one carbon less than that present in the amide.

 

Physical properties of amine

•    The lower aliphatic amines are gases with fishy smell.

•    Primary amines wit three or more carbon atoms are liquid and higher members are all solids.

•    Lower amines are soluble in water as they can form hydrogen bonds with water, however the solubility decreases with increase in hydrophobic alkyl group.

•    Amines have a higher boiling point than the hydrocarbon of comparable molecular mass. This is due to their ability to associate via intermolecular hydrogen bonding.

 

•    Boiling points order of various isomeric amines is:
1o > 2o > 3o

 

Chemical Reactions of amines

Difference in electronegativity between nitrogen and hydrogen atoms and the presence of unshared pair of electrons over the nitrogen atom makes amines reactive. The number of hydrogen atoms attached to nitrogen atom also decides the course of reaction of amines; that is why primary (–NH2), secondary and tertiary amines differ in many reactions. Moreover, amines behave as nucleophiles due to the presence of unshared electron pair. Some of the reactions of amines are described below:

 

Basicity of amine

Amines have an unshared pair of electrons on nitrogen atom due to which they behave as Lewis base. Basic character of amines can be better understood in terms of their Kb and pKb values

Or


Greater Kb value or smaller pKb indicates base is strong.

(b) Comparison of basic strength of aliphatic amines and ammonia: Aliphatic amines are stronger bases than ammonia due to +I effect of alkyl groups leading to high electron density on the nitrogen atom.

(c) Comparison of basic strength of primary, secondary and tertiary amines

(i) The order of basicity of amines in the gaseous phase follows the expected order on the basis of +I effect: tertiary amine > secondary amine > primary amine > NH3

(ii) In aqueous solution it is observed that tertiary amines are less basic than either primary or secondary amines. This can be explained on basis of following factors:

a) Solvation effect: Greater is the stability of the substituted ammonium cation formed, stronger is the corresponding amine as a base. Tertiary ammonium ion is less hydrated than secondary ammonium ion which is less hydrated than primary amine. Thus tertiary amines have fewer tendencies to form ammonium ion and consequently are least basic.
On the basis of solvation effect order of basicity of aliphatic amines should be primary amine>secondary amine>tertiary amine.

b) Steric factor: As the crowding of alkyl group increases from primary to tertiary amine hinderance to hydrogen bonding increases which eventually decreases the basic strength. Thus there is a subtle interplay of the inductive effect, solvation effect and steric hinderance of the alkyl group which decides the basic strength of alkyl amines in the aqueous state.
When the alkyl group is small like CH3 there is no steric hindrance to hydrogen bonding. In this case order of basicity in the aqueous medium is

When alkyl group is ethyl group order of basicity in aqueous medium is

 

 

Alkylation of amines

Alkylation of 1o amine generates 2o amine, 3o amine and finally the quaternary salts.

 

Acylation of amine

Reaction with acid chlorides, anhydrides and esters by nucleophilic substitution reaction is known as acylation. The reaction is proceeded by the replacement of hydrogen atom of –NH2 or >N–H group by the acyl group (RCOX).

 

Tertiary (3o) amine cannot be acylated as there is no H bonded to nitrogen.

Carbylamine reaction

Only aliphatic and aromatic primary amines on heating with chloroform and ethanolic potassium hydroxide form isocyanides or carbylamines.

Secondary and tertiary amines do not give the above test.

 Amine Reaction with nitrous acid

 

(i) Primary aliphatic amine on reaction with nitrous acid (HNO2) forms aliphatic diazonium salt which decomposes to form alcohol and evolve nitrogen.

 

(ii) Primary aromatic amines react with nitrous acid (HNO2) in cold (273-278 K) to form diazonium salt.

 

Reaction with arylsulphonyl chloride

Hinsberg’s reagent-Benzenesulphonyl chloride (C6H5SO2Cl) reacts with primary and secondary amines to form sulphonamides.

The hydrogen attached to nitrogen in sulphonamide formed by primary amine is strongly acidic due to the presence of strong electron withdrawing sulphonyl group. Hence, it is soluble in alkali.

Since sulphonamide formed by secondary amine does not contain any hydrogen atom attached to nitrogen atom, so it is not acidic. Hence it is insoluble in alkali.

Stereochemistry of amine

Alkyl amines have structure quite similar to ammonia. The geometry of the sp3 hybridized nitrogen atom bonded to three atoms or groups is trigonal pyramidal (or approximately tetrahedral) with nitrogen at the apex of the pyramid. Depending upon the composition of the amine, the three sp3 hybridized orbitals form sigma bond with the hydrogen atom or the carbon atom of the alkyl group that are directed downwards to form the triangular base of the pyramid. Since the lone pair of electron on nitrogen is considered the fourth group, which makes the arrangement of “groups” around nitrogen to be approximately tetrahedral.

 

Due to the presence of lone pair of electron there is repulsion between lone pair and bond pair, as a result the bond angle between the two adjacent hydrogen atoms or alkyl groups in primary and secondary amines decreases from tetrahedral angle of 109.5 to 107o . But in case of tertiary amine the C-N-C bond angle is 108o . The C-N bond distance in all types of aliphatic amines is 1.47Ao .

 

Arylamines also have a pyramidal arrangement of bonds around nitrogen, but the pyramid as in the case of aniline is somewhat shallower.

 

As a consequence of the tetrahedral geometry of the tertiary amines, in which all the alkyl groups bonded to the nitrogen are different, as in the case of ethylmethyl amine. Then this molecule is chiral and can exist in a pair of enantiomers

 

It has been observed that though these tertiary amines are chiral but they optically inactive because the enantiomers cannot be resolved as they undergo rapid interconversion by a process called pyramidal inversion. During the process there is rapid oscillation of nitrogen atom from one side of the plane to another. In the transition state of this inversion process there is rehybridization of the nitrogen to planar sp2 geometry with the lone pair of electron lying in the unhybridized 2p orbital. Nitrogen completes the inversion process and becomes sp3 hybridized again.

 

 

AROMATIC AMINES

Aromatic amines are organic compounds that contain an amine group (-NH2) attached to an aromatic ring, such as benzene or naphthalene. They are also known as arylamines. Aromatic amines can be synthesized by the reduction of nitro compounds or by the reaction of primary amines with aromatic compounds.

Aromatic amines have a wide range of applications in various industries, including dyes, pharmaceuticals, pesticides, and rubber chemicals. However, many aromatic amines have been identified as carcinogenic and mutagenic. Exposure to aromatic amines has been linked to an increased risk of bladder cancer, lung cancer, and other types of cancer.

Some common examples of aromatic amines include aniline, toluidine, and naphthylamine. These compounds are often used as intermediates in the synthesis of dyes and other organic compounds. It is important to handle aromatic amines with care and to follow proper safety protocols to minimize the risk of exposure.

 

Hoffmann bromamide degradation reaction for aromatic amines

 

Gabriel Synthesis Reaction

 

 

Basicity of aromatic amine

 Comparison of basic strength of aryl amines and alkylamines: Generally aryl amines are considerably less basic than alkyl amines .Taking an example of aniline and ethylamine it is observed that ethyl amine is more basic than aniline. In aniline –NH2 group is directly attached to benzene ring. Hence unshared pair of electron on nitrogen is less available for protonation because of resonance. Below mentioned are resonating structures of aniline.

In the above resonating structures there is a positive charge on nitrogen atom making the lone pair less available for protonation. Hence aniline is less basic than ethyl amine which has no resonating structures. Less basicity of aniline can also be explained by comparing the relative stability of aniline and anilinium ion obtained by accepting a proton. Greater the number of resonating structures, greater is the stability of that species.
Aniline is resonance hybrid of five resonating structures whereas anilinium ion has only two resonating structures.

Thus aniline has less tendency to accept a proton to form anilinium ion.

 

Effect of substituent on basic character of amines: Electron donating or electron releasing group/groups (EDG) increases basic strength while electron withdrawing (EWG) decreases basic strength.

 

Chemical reactions of aromatic amines

Electrophilic substitution of aromatic amine

Aniline, due to high electron density at ortho and para-positions, is ortho and para directing towards electrophilic substitution reaction.

Bromination of aniline

Aniline reacts with bromine water at room temperature to give a white precipitate of 2, 4, 6-tribromoaniline

In order to stop reaction at monosubstitution activating effect of –NH2 group is reduced by acetylation. This prevents di and tri substituted products. Acetyl group is removed by hydrolysis.

Nitration of aniline

(a) Under strongly acidic medium aniline gets protonated to form anilinium ion, which is deactivating group and is meta directing. Hence minitroaniline is also formed in 47% along with ortho and para products.

Aromatic amines cannot be nitrated directly because HNO3 being a strong oxidising agent oxidises it forming black mass.

(b) Nitration by protecting the –NH2 group by acetylation reaction with acetic anhydride:

Sulphonation of aniline

Aniline reacts with conc. H2SO4 to form aniliniumhydrogensulphate which on heating with sulphuric acid at 453-473K produces p-amino benzene sulphonic acid, commonly known as sulphanilic acid, as the major product.