Unit 13 Amines
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:
13.1 Structure of Amines
Like ammonia, nitrogen atom of amines is trivalent and carries an unshared pair of electrons. Nitrogen orbitals in amines are therefore,
13.2 Classification
Amines are classified as primary
13.3 Nomenclature
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 ’
To name secondary and tertiary amines, we use locant
In arylamines,
13.4 Preparation of Amines
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
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
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.
3. Reduction of nitriles
Nitriles on reduction with lithium aluminium hydride
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
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.
13.5 Physical Properties
The lower aliphatic amines are gases with fishy odour. Primary amines with three or more carbon atoms are liquid and still higher ones are solid. Aniline and other arylamines are usually colourless but get coloured on storage due to atmospheric oxidation.
Lower aliphatic amines are soluble in water because they can form hydrogen bonds with water molecules. However, solubility decreases with increase in molar mass of amines due to increase in size of the hydrophobic alkyl part. Higher amines are essentially insoluble in water. Considering the electronegativity of nitrogen of amine and oxygen of alcohol as 3.0 and 3.5 respectively, you can predict the pattern of solubility of amines and alcohols in water. Out of butan-1-ol and butan-1-amine, which will be more soluble in water and why? Amines are soluble in organic solvents like alcohol, ether and benzene. You may remember that alcohols are more polar than amines and form stronger intermolecular hydrogen bonds than amines.
Primary and secondary amines are engaged in intermolecular association due to hydrogen bonding between nitrogen of one and hydrogen of another molecule. This intermolecular association is more in primary amines than in secondary amines as there are two hydrogen atoms available for hydrogen bond formation in it. Tertiary amines do not have intermolecular association due to the absence of hydrogen atom available for hydrogen bond formation. Therefore, the order of boiling points of isomeric amines is as follows:
Primary > Secondary > Tertiary Intermolecular hydrogen bonding in primary amines is shown in Fig. 13.2.
13.6 Chemical Reactions
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
1. Basic character of amines
Amines, being basic in nature, react with acids to form salts.
Amine salts on treatment with a base like
Amine salts are soluble in water but insoluble in organic solvents like ether. This reaction is the basis for the separation of amines from the non basic organic compounds insoluble in water.
The reaction of amines with mineral acids to form ammonium salts shows that these are basic in nature. 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
Larger the value of
You may find some discrepancies while trying to interpret the
Structure-basicity relationship of amines
Basicity of amines is related to their structure. Basic character of an amine depends upon the ease of formation of the cation by accepting a proton from the acid. The more stable the cation is relative to the amine, more basic is the amine.
(a) Alkanamines versus ammonia
Let us consider the reaction of an alkanamine and ammonia with a proton to compare their basicity.
Due to the electron releasing nature of alkyl group, it
Greater is the stability of the substituted ammonium cation, stronger should be the corresponding amine as a base. Thus, the order of basicity of aliphatic amines should be: primary
(b) Arylamines versus ammonia
On the other hand, anilinium ion obtained by accepting a proton can have only two resonating structures (kekule).
We know that greater the number of resonating structures, greater is the stability. Thus you can infer that aniline (five resonating structures) is more stable than anilinium ion. Hence, the proton acceptability or the basic nature of aniline or other aromatic amines would be less than that of ammonia. In case of substituted aniline, it is observed that electron releasing groups like
2. Alkylation
Amines undergo alkylation on reaction with alkyl halides (refer Unit 10, Class XII).
3. Acylation
Aliphatic and aromatic primary and secondary amines react with acid chlorides, anhydrides and esters by nucleophilic substitution reaction. This reaction is known as acylation. You can consider this reaction as the replacement of hydrogen atom of
Amines also react with benzoyl chloride
What do you think is the product of the reaction of amines with carboxylic acids ? They form salts with amines at room temperature.
4. Carbylamine reaction
Aliphatic and aromatic primary amines on heating with chloroform and ethanolic potassium hydroxide form isocyanides or carbylamines which are foul smelling substances. Secondary and tertiary amines do not show this reaction. This reaction is known as carbylamine reaction or isocyanide test and is used as a test for primary amines.
5. Reaction with nitrous acid
Three classes of amines react differently with nitrous acid which is prepared in situ from a mineral acid and sodium nitrite.
(a) Primary aliphatic amines react with nitrous acid to form aliphatic diazonium salts which being unstable, liberate nitrogen gas quantitatively and alcohols. Quantitative evolution of nitrogen is used in estimation of amino acids and proteins.
(b) Aromatic amines react with nitrous acid at low temperatures (273-278 K) to form diazonium salts, a very important class of compounds used for synthesis of a variety of aromatic compounds discussed in Section 13.7.
6. Reaction with arylsulphonyl chloride
Benzenesulphonyl chloride
(a) The reaction of benzenesulphonyl chloride with primary amine yields
The hydrogen attached to nitrogen in sulphonamide is strongly acidic due to the presence of strong electron withdrawing sulphonyl group. Hence, it is soluble in alkali.
(b) In the reaction with secondary amine,
Since N, N-diethylbenzene sulphonamide does not contain any hydrogen atom attached to nitrogen atom, it is not acidic and hence insoluble in alkali.
(c) Tertiary amines do not react with benzenesulphonyl chloride. This property of amines reacting with benzenesulphonyl chloride in a different manner is used for the distinction of primary, secondary and tertiary amines and also for the separation of a mixture of amines. However, these days benzenesulphonyl chloride is replaced by p-toluenesulphonyl chloride.
7. Electrophilic substitution
You have read earlier that aniline is a resonance hybrid of five structures. Where do you find the maximum electron density in these structures? Ortho- and para-positions to the
(a) Bromination: Aniline reacts with bromine water at room temperature to give a white precipitate of 2,4,6-tribromoaniline.
The main problem encountered during electrophilic substitution reactions of aromatic amines is that of their very high reactivity. Substitution tends to occur at ortho- and para-positions. If we have to prepare monosubstituted aniline derivative, how can the activating effect of
The lone pair of electrons on nitrogen of acetanilide interacts with oxygen atom due to resonance as shown below:
Hence, the lone pair of electrons on nitrogen is less available for donation to benzene ring by resonance. Therefore, activating effect of
(b) Nitration: Direct nitration of aniline yields tarry oxidation products in addition to the nitro derivatives. Moreover, in the strongly acidic medium, aniline is protonated to form the anilinium ion which is meta directing. That is why besides the ortho and para derivatives, significant amount of meta derivative is also formed.
However, by protecting the
(c) Sulphonation: Aniline reacts with concentrated sulphuric acid to form anilinium hydrogensulphate which on heating with sulphuric acid at
Aniline does not undergo Friedel-Crafts reaction (alkylation and acetylation) due to salt formation with aluminium chloride, the Lewis acid, which is used as a catalyst. Due to this, nitrogen of aniline acquires positive charge and hence acts as a strong deactivating group for further reaction.
II. DIAZONIUM SALTS
The diazonium salts have the general formula
Primary aliphatic amines form highly unstable alkyldiazonium salts (refer to Section 13.6). Primary aromatic amines form arenediazonium salts which are stable for a short time in solution at low temperatures (273-278 K). The stability of arenediazonium ion is explained on the basis of resonance.
13.7 Method of Preparation of Diazoniun Salts
Benzenediazonium chloride is prepared by the reaction of aniline with nitrous acid at
13.8 Physical Properties
Benzenediazonium chloride is a colourless crystalline solid. It is readily soluble in water and is stable in cold but reacts with water when warmed. It decomposes easily in the dry state. Benzenediazonium fluoroborate is water insoluble and stable at room temperature.
13.9 Chemical Reactions
The reactions of diazonium salts can be broadly divided into two categories, namely (A) reactions involving displacement of nitrogen and (B) reactions involving retention of diazo group.
A. Reactions involving displacement of nitrogen Diazonium group being a very good leaving group, is substituted by other groups such as
1. Replacement by halide or cyanide ion: The
Alternatively, chlorine or bromine can also be introduced in the benzene ring by treating the diazonium salt solution with corresponding halogen acid in the presence of copper powder. This is referred as Gatterman reaction.
The yield in Sandmeyer reaction is found to be better than Gattermann reaction.
2. Replacement by iodide ion: Iodine is not easily introduced into the benzene ring directly, but, when the diazonium salt solution is treated with potassium iodide, iodobenzene is formed.
3. Replacement by fluoride ion: When arenediazonium chloride is treated with fluoroboric acid, arene diazonium fluoroborate is precipitated which on heating decomposes to yield aryl fluoride.
4. Replacement by H: Certain mild reducing agents like hypophosphorous acid (phosphinic acid) or ethanol reduce diazonium salts to arenes and themselves get oxidised to phosphorous acid and ethanal, respectively.
5. Replacement by hydroxyl group: If the temperature of the diazonium salt solution is allowed to rise upto 283 K, the salt gets hydrolysed to phenol.
6. Replacement by –NO2 group: When diazonium fluoroborate is heated with aqueous sodium nitrite solution in the presence of copper, the diazonium group is replaced by –NO2 group.
B. Reactions involving retention of diazo group coupling reactions
The azo products obtained have an extended conjugate system having both the aromatic rings joined through the
13.10 Importance of Diazonium Salts in Synthesis of Aromatic Compounds
From the above reactions, it is clear that the diazonium salts are very good intermediates for the introduction of
Aryl fluorides and iodides cannot be prepared by direct halogenation. The cyano group cannot be introduced by nucleophilic substitution of chlorine in chlorobenzene but cyanobenzene can be easily obtained from diazonium salt.
Thus, the replacement of diazo group by other groups is helpful in preparing those substituted aromatic compounds which cannot be prepared by direct substitution in benzene or substituted benzene.
Summary
Amines can be considered as derivatives of ammonia obtained by replacement of hydrogen atoms with alkyl or aryl groups. Replacement of one hydrogen atom of ammonia gives rise to structure of the type
Amines are usually formed from nitro compounds, halides, amides, imides, etc. They exhibit hydrogen bonding which influence their physical properties. In alkylamines, a combination of electron releasing, steric and
Aryldiazonium salts, usually obtained from arylamines, undergo replacement of the diazonium group with a variety of nucleophiles to provide advantageous methods for producing aryl halides, cyanides, phenols and arenes by reductive removal of the diazo group. Coupling reaction of aryldiazonium salts with phenols or arylamines give rise to the formation of azo dyes.