In chemistry, amines (, ) are organic compounds that contain carbon–nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of electrons. Amines can also exist as heterocyclic compounds. Aniline is the simplest aromatic amine, consisting of a benzene ring bonded to an amino group.
Amines are classified into three types: primary (1°), secondary (2°), and tertiary (3°) amines. Primary amines (1°) contain one alkyl or aryl substituent and have the general formula RNH2. Secondary amines (2°) have two alkyl or aryl groups attached to the nitrogen atom, with the general formula R2NH. Tertiary amines (3°) contain three substituent groups bonded to the nitrogen atom, and are represented by the formula R3N.
The functional group present in primary amines is called the amino group.
Classification of amines Amines can be classified according to the nature and number of substituents on nitrogen. Aliphatic amines contain only H and alkyl substituents. Aromatic amines have the nitrogen atom connected to an aromatic ring.
Primary (1°) amine Secondary (2°) amine Tertiary (3°) amine Amines, alkyl and aryl alike, are organized into three subcategories (see table) based on the number of carbon atoms adjacent to the nitrogen (how many hydrogen atoms of the ammonia molecule are replaced by hydrocarbon groups):
Primary (1°) amines—Primary amines arise when one of three hydrogen atoms in ammonia is replaced by an alkyl or aromatic group. Important primary alkyl amines include methylamine, most amino acids, and the buffering agent tris, while primary aromatic amines include aniline. Secondary (2°) amines—Secondary amines have two organic substituents (alkyl, aryl or both) bound to the nitrogen together with one hydrogen. Important representatives include dimethylamine, while an example of an aromatic amine would be diphenylamine. Tertiary (3°) amines—In tertiary amines, nitrogen has three organic substituents. Examples include trimethylamine, which has a distinctively fishy smell, and EDTA.
A fourth subcategory is determined by the connectivity of the substituents attached to the nitrogen:
Cyclic amines—Cyclic amines are either secondary or tertiary amines. Examples of cyclic amines include the 3-membered ring aziridine and the six-membered ring piperidine. N-methylpiperidine and N-phenylpiperidine are examples of cyclic tertiary amines.
Related compounds
Compounds where the nitrogen atom is attached to a carbonyl group, thus having the structure , are called amides. Compounds containing four organic substituents on the nitrogen, thus having the structure , are quaternary ammonium salts. Many kinds of anions are found in such compounds.
Naming conventions Amines are named in several ways. Typically, the compound is given the prefix "amino-" or the suffix "-amine". The prefix "N-" shows substitution on the nitrogen atom. An organic compound with multiple amino groups is called a diamine, triamine, tetraamine and so forth.
Lower amines are named with the suffix -amine.
Higher amines have the prefix amino as a functional group. IUPAC however does not recommend this convention, but prefers the alkanamine form, e.g. butan-2-amine.
Physical properties Hydrogen bonding significantly influences the properties of primary and secondary amines. For example, methyl and ethyl amines are gases under standard conditions, whereas the corresponding methyl and ethyl alcohols are liquids. Amines possess a characteristic ammonia smell, liquid amines have a distinctive "fishy" and foul smell.
The nitrogen atom features a lone electron pair that can bind H+ to form an ammonium ion R3NH+. The lone electron pair is represented in this article by two dots above or next to the N. The water solubility of simple amines is enhanced by hydrogen bonding involving these lone electron pairs. Typically salts of ammonium compounds exhibit the following order of solubility in water: primary ammonium () > secondary ammonium () > tertiary ammonium (R3NH+). Small aliphatic amines display significant solubility in many solvents, whereas those with large substituents are lipophilic. Aromatic amines, such as aniline, have their lone pair electrons conjugated into the benzene ring, thus their tendency to engage in hydrogen bonding is diminished. Their boiling points are high and their solubility in water is low.
Spectroscopic identification Typically the presence of an amine functional group is deduced by a combination of techniques, including mass spectrometry as well as NMR and IR spectroscopies. 1H NMR signals for amines disappear upon treatment of the sample with D2O. In their infrared spectrum primary amines exhibit two N–H bands, whereas secondary amines exhibit only one. In their IR spectra, primary and secondary amines exhibit distinctive N–H stretching bands near 3300 cm−1. Somewhat less distinctive are the bands appearing below 1600 cm−1, which are weaker and overlap with C–C and C–H modes. For the case of propylamine, the H–N–H scissor mode appears near 1600 cm−1, the C–N stretch near 1000 cm−1, and the R2N–H bend near 810 cm−1.
Structure Alkyl amines
Alkyl amines characteristically feature tetrahedral nitrogen centers. C-N-C and C-N-H angles are near 109°. C-N distances are slightly shorter than C-C distances. The energy barrier for the nitrogen inversion of the stereocenter is about 7 kcal/mol for a trialkylamine. The interconversion has been compared to the inversion of an open umbrella into a strong wind.
Amines of the type NHRR' and NRR′R″ are chiral: the nitrogen center bears four substituents counting the lone pair. Because of the low barrier to inversion, amines of the type NHRR' cannot be obtained in optical purity. For chiral tertiary amines, NRR′R″ can only be resolved when the R, R', and R″ groups are constrained in cyclic structures such as N-substituted aziridines (quaternary ammonium salts are resolvable).
Aromatic amines In aromatic amines ("anilines"), nitrogen is often nearly planar owing to conjugation of the lone pair with the aryl substituent. The C-N distance is correspondingly shorter. In aniline, the C–N distance is the same as the C–C distances.G. M. Wójcik "Structural Chemistry of Anilines" in Anilines (Patai's Chemistry of Functional Groups), S. Patai, ed. 2007, Wiley-VCH, Weinheim. .
Basicity Like ammonia, amines are bases. Compared to alkali metal hydroxides, amines are weaker.
Alkylamine or aniline pKa of protonated amine Kb Methylamine (MeNH2) 10.62 Dimethylamine (Me2NH) 10.64 Trimethylamine (Me3N) 9.76 Ethylamine (EtNH2) 10.63 Aniline (PhNH2) 4.62 4-Methoxyaniline (4-MeOC6H4NH2) 5.36 N,N-Dimethylaniline (PhNMe2) 5.07 3-Nitroaniline (3-NO2-C6H4NH2) 2.46 4-Nitroaniline (4-NO2-C6H4NH2) 1.00 4-Trifluoromethylaniline (CF3C6H4NH2) 2.75
The basicity of amines depends on: The electronic properties of the substituents (alkyl groups enhance the basicity, aryl groups diminish it). The degree of solvation of the protonated amine, which includes steric hindrance by the groups on nitrogen.
Electronic effects Owing to inductive effects, the basicity of an amine might be expected to increase with the number of alkyl groups on the amine. Correlations are complicated owing to the effects of solvation which are opposite the trends for inductive effects. Solvation effects also dominate the basicity of aromatic amines (anilines). For anilines, the lone pair of electrons on nitrogen delocalizes into the ring, resulting in decreased basicity. Substituents on the aromatic ring, and their positions relative to the amino group, also affect basicity as seen in the table.
Solvation effects Solvation significantly affects the basicity of amines. N−H groups strongly interact with water, especially in ammonium ions. Consequently, the basicity of ammonia is enhanced by 1011 by solvation. The intrinsic basicity of amines, i.e. the situation where solvation is unimportant, has been evaluated in the gas phase. In the gas phase, amines exhibit the basicities predicted from the electron-releasing effects of the organic substituents. Thus tertiary amines are more basic than secondary amines, which are more basic than primary amines, and finally ammonia is least basic. The order of pKb values (basicities in water) does not follow this order. Similarly, aniline is more basic than ammonia in the gas phase, but ten thousand times less so in aqueous solution..
In aprotic polar solvents such as DMSO, DMF, and acetonitrile the energy of solvation is not as high as in protic polar solvents like water and methanol. For this reason, the basicity of amines in these aprotic solvents is almost solely governed by the electronic effects.
Synthesis
From alcohols Industrially significant alkyl amines are prepared from ammonia by alkylation with alcohols: ROH + NH3 -> RNH2 + H2O
From alkyl and aryl halides Unlike the reaction of amines with alcohols the reaction of amines and ammonia with alkyl halides is used for synthesis in the laboratory: RX + 2 R'NH2 -> RR'NH + [RR'NH2]X In such reactions, which are more useful for alkyl iodides and bromides, the degree of alkylation is difficult to control such that one obtains mixtures of primary, secondary, and tertiary amines, as well as quaternary ammonium salts.
Selectivity can be improved via the Delépine reaction, although this is rarely employed on an industrial scale. Selectivity is also assured in the Gabriel synthesis, which involves organohalide reacting with potassium phthalimide.
Aryl halides are much less reactive toward amines and for that reason are more controllable. A popular way to prepare aryl amines is the Buchwald-Hartwig reaction.
From alkenes Disubstituted alkenes react with HCN in the presence of strong acids to give formamides, which can be decarbonylated. This method, the Ritter reaction, is used industrially to produce tertiary amines such as tert-octylamine.
Hydroamination of alkenes is also widely practiced. The reaction is catalyzed by zeolite-based solid acids.
Reductive routes A nickel catalyst can hydrogenate unsaturated N-containing functional groups to amines. Suitable groups include nitriles, imines (including oximes), amides, azides, and nitro groups. Many amines are produced from aldehydes and ketones via reductive amination, reduction of an imine formed in situ or a two-step process.
is more commonly employed to reduce these groups at laboratory scale. In the case of nitriles, reactions are sensitive to acidic or alkaline conditions, which can hydrolyze the group.
Aniline () and derivatives are prepared by reduction of the corresponding nitroaromatics. In industry, hydrogen is the preferred reductant, whereas tin and iron are often employed in the laboratory.
Specialized methods Many methods exist for the preparation of amines, many of these methods being rather specialized. Reaction name Substrate Comment Staudinger reductionOrganic azide This reaction also takes place with a reducing agent such as lithium aluminium hydride. Schmidt reactionCarboxylic acid Aza-Baylis–Hillman reactionImine Synthesis of allylic amines Birch reduction Imine Useful for reactions that trap unstable imine intermediates, such as Grignard reactions with nitriles. Hofmann degradationAmide This reaction is valid for preparation of primary amines only. Gives good yields of primary amines uncontaminated with other amines. Hofmann elimination Quaternary ammonium saltUpon treatment with strong base Leuckart reaction Ketones and aldehydes Reductive amination with formic acid and ammonia via an imine intermediate Hofmann–Löffler reaction Haloamine Eschweiler–Clarke reaction Amine Reductive amination with formic acid and formaldehyde via an imine intermediate
Reactions
Alkylation, acylation, and sulfonation, etc.