Amines Preparation and Physical Properties

Chapter 22 

Amines I. Preparation and Physical Properties

Structure

• Nearly all the organic compounds that we have studied so far are bases, although very weak ones. Much of the chemistry of alcohols, ethers, esters, and even of alkenes and aromatic hydrocarbons is understandable in terms of the basicity of these compounds. Of the organic compounds that show appreciable basicity (for example, those strong enough to turn litmus blue), by far the most important are the amines. An amine has the general formula RNH2, R2NH, or R3N, where R is any alkyl or aryl group. For example:

Classification

• Amines are classified as primary, secondary, or tertiary, according to the number of groups attached to the nitrogen.

•  In their fundamental properties basicity and the accompanying nucleophilicity amines of different classes are very much the same. In many of their reactions, however, the final products depend upon the number of hydrogen atoms attached to the nitrogen atom, and hence are different for amines of different classes.

Nomenclature

• Aliphatic amines are named by naming the alkyl group or groups attached to nitrogen and following these by the word -amine. More complicated ones are often named by prefixing amino- (or N-methylamina-, N, N-diethylamino-> etc.) to the name of the parent chain. For example:

• Aromatic amines those in which nitrogen is attached directly to an aromatic ring are generally named as derivatives of the simplest aromatic amine, aniline. An amino toluene is given the special name of toluidine. For example:

Physical properties of amine

• Like ammonia, amines are polar compounds and, except for tertiary amines, can form intermolecular hydrogen bonds. Amines have higher boiling points.

• than non-polar compounds of the same molecular weight, but lower boiling points than alcohols or carboxylic acids.

• Amines of all three classes are capable of forming hydrogen bonds with water. As a result, smaller amines are quite soluble in water, with borderline solubility.

• being reached at about six carbon atoms. Amines are soluble in less polar solvents like ether, alcohol, benzene, etc. The methylamines and ethylamine's smell very much like ammonia; the higher alkylamines have decidedly "fishy" odors. Aromatic amines are generally very toxic; they are readily absorbed through the skin, often with fatal results. Aromatic amines are very easily oxidized by air, and although most are colorless when pure, they are often encountered discolored by oxidation prod.

Salts of amines

• Aliphatic amines are about as basic as ammonia; aromatic amines are considerably less basic. Although amines are much weaker bases than hydroxide ion or ethoxide ion, they are much stronger bases than alcohols, ethers, esters, etc. ; they are much stronger bases than water. Aqueous mineral acids or carboxylic acids readily convert amines into their salts; aqueous hydroxide ion readily converts the salts basic into the free amines. As with the carboxylic acids, we can

• do little with amines without encountering this conversion into and from their salts; it is therefore worthwhile to look at the properties of these salts. In Sec. 18.4 we contrasted physical properties of carboxylic acids with those of their salts; amines and their salts show the same contrast. Amine salts are typical ionic compounds. They are non-volatile solids, and when heated generally decompose before the high temperature required for melting is reached. The halides, nitrates, and sulfates are soluble in water but are insoluble in non-polar solvents.

• The difference in solubility behavior between amines and their salts can be used both to detect amines and to separate them from non-basic compounds. A water-insoluble organic compound that dissolves in cold, dilute aqueous hydrochloric acid must be appreciably basic, which means almost certainly that it is an amine. An amine can be separated from non-basic compounds by its solubility in acid; once separated, the amine can be regenerated by making the aqueous solution alkaline. (See Sec. 18.4 for a comparable situation for carboxylic acids.

Stereochemistry of nitrogen

• So far in our study of organic chemistry, we have devoted considerable time to the spatial arrangement of atoms and groups attached to carbon atoms, that is, to the stereochemistry of carbon. Now let us look briefly at the stereochemistry of nitrogen. Amines are simply ammonia in which one or more hydrogen atoms have been replaced by organic groups. Nitrogen uses s/> 3 orbitals, which are directed to the corners of a tetrahedron. Three of these orbitals overlap s orbitals of hydrogen or carbon; the fourth contains an unshared pair of electrons. Amines, then, are like ammonia, pyramidal, and with very nearly the same bond angles (108 in trimethylamine, for example). 

• From an examination of models, we can see that a molecule in which nitrogen carries three different groups is not superimposable on its mirror image; it is chiral and should exist in two enantiomeric forms (I and 11) each of which

 

• But such enantiomers have not yet been isolated for simple amines and spectroscopic studies have shown why: the energy barrier between the two pyramidal arrangements about nitrogen is ordinarily so low that they are rapidly interconverted. Just as rapid rotation about carbon-carbon single bonds prevents isolation of conformational enantiomers so rapid inversion about nitrogen prevents isolation of enantiomers like I and II. Evidently, an unshared pair of electrons of nitrogen cannot ordinarily serve as a fourth group to maintain configuration.

Industrial source

• Some of the simplest and most important amines are prepared on an industrial scale by processes that are not practicable as laboratory methods. The most important of all amines, aniline, is prepared in several ways: (a) reduction of nitrobenzene by the cheap reagents, iron and dilute hydrochloric acid (or by catalytic hydrogenation, Sec. 22.9); (b) treatment of chlorobenzen&with

• ammonia at high temperatures and high pressures in the presence of a catalyst. Process (b), we shall see (Chap. 25), involves nucleophilic aromatic substitution.

Preparation

• Some of the many methods that are used to prepare amines in the laboratory are outlined on the following pages.

• Reduction of aromatic nitro compounds is by far the most useful method of preparing amines, since it uses readily available starting materials, and yields the most important kind of amines, primary aromatic amines. These amines can be converted into aromatic diazonium salts, which are among the most versatile class of organic compounds known.

• The sequence nitro compound > amine > diazonium salt 

• provides the best possible route to dozens of kinds of aromatic compounds. Reduction of aliphatic nitro compounds is limited by the availability of the starting materials.

• Ammonolysis of halides is usually limited to the aliphatic series, because of the generally low reactivity of aryl halides toward nucleophilic substitution. (However, see Chap. 25.) Ammonolysis has the disadvantage of yielding a mixture of different classes of amines. It is important to us as one of the most general methods of introducing the amino (NH2) group into molecules of all kinds; it can be used, for example, to convert bromoacyls into amino acids. The exactly analogous reaction of halides with amines permits the preparation of every class of amine (as well as quaternary ammonium salts, R4N + X~).

• Reductive animation, the catalytic or chemical reduction of aldehydes (RCHO) and ketones (Raco) in the presence of ammonia or an amine, accomplishes much the same purpose as the reaction of halides. tt too can be used to prepare any class of amine and has certain advantages over the halide reaction. The formation of mixtures is more readily controlled in reductive amination than in ammonolysis of halides. Reductive amination of ketones yields amines containing a sec-alky! group; these amines are difficult to prepare by ammonolysis because of the tendency of Jii-alkyl halides to undergo elimination rather than substitution. 

• Synthesis via reduction of nitrites has the special feature of increasing the length Ofa carbon chain, producing a primary amine that has one more carbon atom than the alkyl halide from which the nitrile was made. The Hofmann degradation of amides has the feature of decreasing the length of a carbon chain by one carbon atom; it is also of interest as an example of an important class of reactions involving rearrangement.

Reduction of nitro compounds

• Like many organic compounds, nitro compounds 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. Hydrogenation of a nitro compound to an amine takes place smoothly when a solution of the nitro compound in alcohol is shaken with finely divided nickel or platinum under hydrogen gas. For example:

• This method cannot be used when the molecule also contains some other easily hydrogenated group, such as a carbon-carbon double bond* Chemical reduction in the laboratory is most often carried out by adding hydrochloric acid to a mixture of the nitro compound and a metal, usually granulated tin. In the acidic solution, the amine is obtained as its salt; the free amine is liberated by the addition of base and is steam-distilled from the reaction.

Ammonolysis of halides

• Many organic halogen compounds are converted into amines by treatment with aqueous or alcoholic solutions of ammonia. The 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 the free amine can be liberated by treatment with hydroxide ion.

•  Ammonolysis of halides belongs to the class of reactions that we have called nucleophilic substitution. The organic halide is attacked by the nucleophilic ammonia molecule in the same way that it is attacked by hydroxide ion, alkoxide ion, cyanide ion, acetylide ion, and water:

•  Like these other nucleophilic substitution reactions, ammonolysis is limited chiefly to alkyl halides or substituted alkyl halides. As with other reactions of this kind, elimination tends to compete hydrogen to form alkene as well as attack carbon to form a mine. Ammonolysis thus gives the highest yields with primary halides (where substitution predominates) and is virtually worthless with tertiary halides (where elimination predominates).

• Because of their generally low reactivity, aryl halides are converted into amines only (a) if the ring carries NO2 g r opus, or other strongly electron-withdrawing groups, at positions ortho and para to the halogen, or (b) if a high temperature or a strongly basic reagent is used. Some examples of the application of ammonolysis to synthesis are:

Hofmann degradation of amides

• As a method of synthesis of amines, the Hofmann degradation of amides has the special feature of yielding a product containing one less carbon than the starting material. As we can see, reaction involves migration of a group from carbonyl

• carbon to the adjacent nitrogen atom, and thus is an example of a molecular rearrangement. We shall return to the Hofmann degradation and discuss its mechanism in detail.

Synthesis of secondary and tertiary amines

• So far we have been chiefly concerned with the synthesis of primary amines. Secondary and tertiary amines are prepared by adaptations of one of the processes already described: ammonolysis of halides or reductive animation. For example

• Where ammonia has been used to produce a primary amine, a primary amine can be used to produce a secondary amine, or a secondary amine can be used to produce a tertiary amine. In each of these syntheses there is a tendency for reaction to proceed beyond the first stage and to yield an amine of a higher class than the one that is wanted.