Aliphatic amines are a type of organic compound belonging to the class of amines , which differs in the content of aliphatic substituents at the nitrogen atom. For the first time, the simplest aliphatic amines (methylamines and ethylamines) were synthesized by Charles Wurz in 1849. To obtain them, he hydrolyzed the corresponding alkyl isocyanates , trialkyl cyanurates and alkyl ureas . The fundamental study of the properties, structure and methods of the synthesis of aliphatic amines was carried out by August Wilhelm Hoffmann . He proposed the terms "primary", "secondary", "tertiary" to denote their structure [1] .
Natural amines are usually quite complex substances, but among natural amines there are also aliphatic amines, for example, putrescine and cadaverine , which are products of the decomposition of proteins [2] .
In 2000, the total global production of aliphatic amines amounted to about 100,000 tons. Thus, they are one of the most important industrial chemical intermediates with a very wide range of uses. Among other things, this is the production of agrochemicals (especially herbicides ), dyes , drugs , surfactants , plastics , etc. [1]
Industrial Production Methods
Alcohol production
The most common method for industrial production of lower aliphatic amines is based on the reaction of the corresponding alcohol with ammonia in the presence of a suitable catalyst . In this case, a mixture of primary, secondary and tertiary amines is always obtained, since the resulting primary amine can react with two more alcohol molecules . This is due to the greater nucleophilicity of the product compared to ammonia, and also to the fact that the reactions of the formation of the secondary and tertiary amine are exothermic and more energetically favorable, and the reaction of the formation of the primary amine is approximately thermoneutral. The ratio of products can be controlled by controlling the reaction conditions. Also, products that do not have commercial value can be recycled. Due to these techniques, the yield of the target amine can be increased to 90% and higher [3] .
Previously, the synthesis of amines from alcohols was carried out under the action of dehydration catalysts ( alumina , silica gel , titanium oxide, thorium oxide , mixed oxides, clays and zeolites ) at a temperature of 500 Β° C. Currently, these catalysts are used only for the synthesis of methylamines. Hydrogenation and dehydrogenation catalysts based on nickel , cobalt , copper and iron , as well as, to a lesser extent, platinum and palladium, are now used for the synthesis of older homologues. In this process, alcohol, ammonia, and hydrogen are passed over a catalyst deposited on an inert support at a pressure of 0.5β25 MPa and a temperature of 100β250 Β° Π‘. To shift the equilibrium towards the primary amine, an excess of ammonia (from 2 to 8 equivalents) is used [3] .
It was found that in the first stage of the process, alcohol is dehydrogenated to a carbonyl compound , which then reacts with ammonia to form an imine or enamine . The latter are then hydrogenated to amine [3] .
Production from carbonyl compounds
In the case of economic feasibility, the starting compound may be not alcohol, but a carbonyl compound . First of all, this approach is used for lower aldehydes , which are obtained in industry by the reaction of oxosynthesis and for acetone , which is formed in the cumene synthesis of phenol [4] .
As in the synthesis of amines from alcohols, the formation of an amine occurs through an imine, which is obtained by the reaction of ammonia with a carbonyl compound. Then it is hydrogenated to the corresponding amine. A mixture consisting of a carbonyl compound, ammonia and hydrogen is passed over the catalyst. A significant difference of this process is that hydrogen is used here as a stoichiometric reagent, and therefore a completely different reactor device is required [4] .
Nitrile production
Aliphatic amines can be synthesized from nitriles by catalytic hydrogenation. Typically, noble metals (palladium, platinum, rhodium ), nickel, cobalt, and iron are used as catalysts. Moreover, noble metals allow the reaction to be carried out under mild conditions: 20β100 Β° Π‘, 0.1β0.5 MPa, while nickel and cobalt catalysts require temperatures up to 180 Β° Π‘ and pressures of 25 MPa [5] .
Other methods
The reaction of alkyl halides with ammonia or amines gives ammonium salts , which release a free amine under the action of alkali . This approach, traditional for preparative chemistry, has not found wide application in industry. Currently, only ethylenediamine , homologous polyamines, allylamine and some small-tonnage drugs are obtained this way. The reason for this limited use is the lack of suitable starting materials, corrosion , as well as problems with product quality control [6] .
The reduction of nitro compounds has also received only limited use, since the starting nitroalkanes are not very widely available as starting materials. Currently, this method is used for the synthesis of 2-aminobutanol-1, the precursor of the anti-tuberculosis drug ethambutol [6] .
Amines with a tertiary hydrocarbon substituent, for example tert-butylamine, are very difficult to obtain by conventional methods. They are synthesized by the Ritter reaction , attaching hydrogen cyanide to an alkene in an acidic environment. The process is carried out at 30-60 Β° C, and the resulting intermediate is hydrolyzed at 100 Β° C. The use of the Ritter reaction is very limited, since it involves the use of toxic cyanide hydrogen, which causes corrosion, as well as the formation of a significant amount of side salts (3.3 kg per 1 kg of tert-butylamine ) and the need for their disposal [6] .
General chemical properties
The chemical properties of aliphatic amines are determined by the presence of an unshared electron pair at the nitrogen atom, as well as by the mobility of hydrogen atoms in the amino group [7] .
Salt Formation
Like ammonia , aliphatic amines form salts with acids. Since amines contain alkyl substituents having electron-donating properties, they are stronger bases than ammonia. The resulting salts are well soluble in water, but poorly soluble in organic solvents, that is, their solubility is opposite to that for the starting amines. With this property in mind, aliphatic amines are often used in chemical reactions as acid acceptors. They also find application as solvents for gas purification and in some extraction processes [7] .
Amide Formation
In the reaction with carboxylic acids and their derivatives ( esters , anhydrides and halides ), aliphatic amines form the corresponding substituted amides in very good yield. The yield for reactions with acid chlorides is especially high, since the reaction is very exothermic. On the contrary, the reaction of amines with carboxylic acids often reaches only the formation of an ammonium salt [7] .
Similarly, the reaction of amines with sulfonyl chlorides (sulfonic acid chlorides) leads to the formation of sulfamides . For example, a reaction with benzenesulfonyl chloride serves to distinguish between primary, secondary and tertiary amines ( Hinsberg reaction ). Primary amines form sulfamides soluble in alkalis. Secondary amines produce sulfamides, which do not dissolve in the alkali. Tertiary amines do not react under these conditions [7] .
Reactions with carbonyl compounds
Depending on the reaction conditions and specific compounds, amines react with carbonyl compounds to form imines (in the case of primary amines) or enamines (in the case of primary or secondary amines). Tertiary amines do not enter into such reactions, and aldehydes react faster than ketones. Intermediates β semi - amines β are usually unstable and cannot be isolated. The resulting imines and enamines are industrially important compounds, since after hydrogenation they lead to new amines containing a larger number of substituents [7] .
As a special case of such reactions, we can consider the interaction of amines with carbon dioxide , leading to the formation of carbamic acid [7] .
Alkylation Reactions
Aliphatic amines react with alkyl halides and dialkyl sulfates to give amines with a higher degree of substitution. Thus, the primary amines during alkylation form a mixture of secondary, tertiary amines and quaternary ammonium salt. This non-selectivity of the reaction is explained by the fact that the reaction products are stronger bases than the starting amine and easily enter into further alkylation reactions. Nevertheless, such a method can be used for the synthesis of tertiary amines [7] .
Aliphatic amines are also alkylated by reaction with epoxides . In the case of primary amines, a mixture of mono- and dialkylation products is also formed, secondary amines give only the monoalkylation product, and tertiary amines form quaternary ammonium compounds [7] .
Formation of Isocyanates and Ureas
In the reaction of amines with phosgene, the corresponding carbamic acid chloride is first formed, from which hydrogen chloride is further cleaved, which leads to the formation of isocyanate . If there is an excess of amine in the reaction mixture, a further reaction occurs with the formation of substituted urea . This reaction is characteristic of primary and secondary amines. Often it is used in the industrial synthesis of herbicides, as well as for the production of polyurethanes [7] .
Oxidation
Unlike its salts, free amines are very sensitive to oxidation and undergo a series of reactions under the influence of various oxidizing agents . Tertiary amines are oxidized by hydrogen peroxide to amine oxides , while primary and secondary amines give hydroxylamines and aldoximes [7] .
Nitric acid oxidation is used to distinguish between primary, secondary and tertiary amines. Primary amines under these conditions are diazotized and converted to alcohols with the release of gaseous nitrogen. Secondary amines give yellow N- nitrosamines . Tertiary amines usually do not enter into this reaction [7] .
Storage and Transportation
Aliphatic amines are stored in carbon or stainless steel containers. Relatively small quantities can be stored in glass or ceramic containers. Aqueous solutions of amines have an alkaline reaction and gradually etch the glass. Ethylamine must be stored under pressure since it is gaseous at room temperature. Isopropylamine (boiling point 32.4 Β° C) is stored under cooling or under pressure. For reasons of convenience during transportation, these amines are produced in the form of aqueous solutions (40% or 70%). Despite the fact that aliphatic amines have an almost unlimited shelf life, they must be protected from contact with carbon dioxide and atmospheric moisture [8] .
Lower aliphatic amines are flammable. Some of them form explosive mixtures with air [8] .
Economic Aspects
The total production of aliphatic amines, including fatty amines (with substituents C7 and higher), but excluding methylamines, is estimated at 500,000 tons annually, of which 40% is received in the USA and 30% in Western Europe. The main manufacturers and suppliers of amines in the USA are Air Products , Hoechst Celanese and Elf Atochem ; in Western Europe, BASF , Elf Atochem, Hoechst Celanese, and ICI [9] .
Notes
- β 1 2 Ullmann, 2000 , p. 647.
- β Ullmann, 2000 , p. 648.
- β 1 2 3 Ullmann, 2000 , p. 651-652.
- β 1 2 Ullmann, 2000 , p. 652-653.
- β Ullmann, 2000 , p. 653.
- β 1 2 3 Ullmann, 2000 , p. 654-655.
- β 1 2 3 4 5 6 7 8 9 10 11 Ullmann, 2000 , p. 648-651.
- β 1 2 Ullmann, 2000 , p. 655β656.
- β Ullmann, 2000 , p. 659
Literature
- Eller K., Henkes E., Rossbacher R., HΓΆke H. Amines, Aliphatic (English) // Ullmann's Encyclopedia of Industrial Chemistry. - 2000. - DOI : 10.1002 / 14356007.a02_001 .