The chemical notation for amines contains the letter "R", where "R" is not an element, but an "R-group", which in amines could be a single hydrogen or carbon atom, or could be a hydrocarbon chain.
Compounds with anitrogen atom attached to acarbonyl group, thus having the structureR−C(=O)−NR′R″, are calledamides and have different chemical properties from amines.
Amines can be classified according to the nature and number of substituents onnitrogen.Aliphatic amines contain only H and alkyl substituents.Aromatic amines have the nitrogen atom connected to anaromatic 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 ofcarbon atoms adjacent to the nitrogen (how many hydrogen atoms of theammonia molecule are replaced byhydrocarbon groups):[6][7]
Secondary (2°) amines—Secondary amines have two organic substituents (alkyl, aryl or both) bound to the nitrogen together with one hydrogen. Important representatives includedimethylamine, while an example of anaromatic amine would bediphenylamine.
Tertiary (3°) amines—In tertiary amines, nitrogen has three organic substituents. Examples includetrimethylamine, which has a distinctively fishy smell, andEDTA.
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 ringaziridine and the six-membered ringpiperidine.N-methylpiperidine andN-phenylpiperidine are examples of cyclic tertiary amines.
It is also possible to have four organic substituents on the nitrogen. These species are not amines but arequaternary ammonium cations and have a charged nitrogen center. Quaternary ammonium salts exist with many kinds ofanions.
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 adiamine,triamine,tetraamine and so forth.
Higher amines have the prefixamino as a functional group. IUPAC however does not recommend this convention,[8] but prefers the alkanamine form, e.g. butan-2-amine.
Hydrogen bonding significantly influences the properties of primary and secondary amines. For example,methyl andethyl amines are gases under standard conditions, whereas the correspondingmethyl andethyl alcohols are liquids. Amines possess a characteristic ammonia smell, liquid amines have a distinctive "fishy" and foul smell.
The nitrogen atom features alone electron pair that can bind H+ to form anammonium ion R3NH+. The lone electron pair is represented in this article by two dots above or next to the N. The watersolubility of simple amines is enhanced byhydrogen bonding involving these lone electron pairs. Typically salts of ammonium compounds exhibit the following order of solubility in water: primary ammonium (RNH+ 3) > secondary ammonium (R 2NH+ 2) > tertiary ammonium (R3NH+). Small aliphatic amines display significant solubility in manysolvents, whereas those with large substituents are lipophilic. Aromatic amines, such asaniline, have their lone pair electronsconjugated 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.
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 theirinfrared spectrum primary amines exhibit two N-H bands, whereas secondary amines exhibit only one.[6] 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 ofpropyl amine, 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.[9]
Inversion of an amine spatial configuration: Amine "flip-flop" like an umbrella turned over by the wind. The pair of dots represents the loneelectron pair on the nitrogen atom.
Alkyl amines characteristically feature tetrahedral nitrogen centers. C-N-C and C-N-H angles approach the idealized angle of 109°. C-N distances are slightly shorter than C-C distances. Theenergy barrier for thenitrogen 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″ arechiral: 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 asN-substitutedaziridines (quaternary ammonium salts are resolvable).
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.[10]
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 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's (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.[14]
In aprotic polar solvents such asDMSO,DMF, andacetonitrile 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.
Unlike the reaction of amines with alcohols the reaction of amines and ammonia with alkyl halides is used for synthesis in the laboratory:
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.[5]
Aryl halides are much less reactive toward amines and for that reason are more controllable. A popular way to prepare aryl amines is theBuchwald-Hartwig reaction.
Disubstituted alkenes react with HCN in the presence of strong acids to give formamides, which can be decarbonylated. This method, theRitter reaction, is used industrially to produce tertiary amines such astert-octylamine.[5]
Hydroamination of alkenes is also widely practiced. The reaction is catalyzed by zeolite-basedsolid acids.[5]
Via the process ofhydrogenation, unsaturated N-containing functional groups are reduced to amines using hydrogen in the presence of a nickel catalyst. Suitable groups includenitriles,azides,imines includingoximes, amides, andnitro. In the case of nitriles, reactions are sensitive to acidic or alkaline conditions, which can cause hydrolysis of the−CN group.LiAlH4 is more commonly employed for the reduction of these same groups on the laboratory scale.
Many amines are produced from aldehydes and ketones viareductive amination, which can either proceed catalytically or stoichiometrically.
Aniline (C6H5NH2) and its derivatives are prepared by reduction of the nitroaromatics. In industry, hydrogen is the preferred reductant, whereas, in the laboratory, tin and iron are often employed.
Similarly, with sulfonyl chlorides, one obtainssulfonamides. This transformation, known as theHinsberg reaction, is a chemical test for the presence of amines.
Because amines are basic, they neutralizeacids to form the correspondingammonium saltsR3NH+. When formed from carboxylic acids and primary and secondary amines, these salts thermally dehydrate to form the correspondingamides.
Amines reacts withnitrous acid to give diazonium salts. The alkyl diazonium salts are of little importance because they are too unstable. The most important members are derivatives of aromatic amines such asaniline ("phenylamine") (A = aryl or naphthyl):
Anilines and naphthylamines form more stablediazonium salts, which can be isolated in the crystalline form.[17] Diazonium salts undergo a variety of useful transformations involving replacement of theN2 group with anions. For example,cuprous cyanide gives the corresponding nitriles:
Aryldiazoniums couple with electron-rich aromatic compounds such as aphenol to formazo compounds. Such reactions are widely applied to the production of dyes.[18]
Imine formation is an important reaction. Primary amines react withketones andaldehydes to formimines. In the case offormaldehyde (R' = H), these products typically exist as cyclictrimers: Reduction of these imines gives secondary amines:
Similarly, secondary amines react with ketones and aldehydes to formenamines:
Hormones derived from the modification of amino acids are referred to as amine hormones. Typically, the original structure of the amino acid is modified such that a –COOH, or carboxyl, group is removed, whereas the–NH+ 3, or amine, group remains. Amine hormones are synthesized from the amino acidstryptophan ortyrosine.[23]
Primary aromatic amines are used as a starting material for the manufacture ofazo dyes. It reacts with nitrous acid to form diazonium salt, which can undergo coupling reaction to form an azo compound. As azo-compounds are highly coloured, they are widely used in dyeing industries, such as:
Thioridazine, an antipsychotic drug, is an amine which is believed to exhibit its antipsychotic effects, in part, due to its effects on other amines.[25]
Amines are often used as epoxy resin curing agents.[27][28] These includedimethylethylamine,cyclohexylamine, and a variety of diamines such as 4,4-diaminodicyclohexylmethane.[5] Multifunctional amines such astetraethylenepentamine andtriethylenetetramine are also widely used in this capacity.[29] The reaction proceeds by the lone pair of electrons on the amine nitrogen attacking the outermost carbon on the oxirane ring of the epoxy resin. This relieves ring strain on the epoxide and is the driving force of the reaction.[30] Molecules with tertiary amine functionality are often used to accelerate the epoxy-amine curing reaction and include substances such as2,4,6-Tris(dimethylaminomethyl)phenol. It has been stated that this is the most widely used room temperature accelerator for two-component epoxy resin systems.[31][32]
Low molecular weight simple amines, such asethylamine, are toxic withLD50 between 100 and 1000 mg/kg. They are skin irritants, especially as some are easily absorbed through the skin.[5] Amines are a broad class of compounds, and more complex members of the class can be extremely bioactive, for examplestrychnine.
^Hellwich, K.-H.; Hartshorn, R. M.; Yerin, A.; Damhus, T.; Hutton, A. T. (June 2021)."Brief Guide to the Nomenclature of Organic Chemistry"(PDF).The International Union of Pure and Applied Chemistry (IUPAC). Retrieved7 March 2024.
^G. M. Wójcik "Structural Chemistry of Anilines" in Anilines (Patai's Chemistry of Functional Groups), S. Patai, Ed. 2007, Wiley-VCH, Weinheim.doi:10.1002/9780470682531.pat0385
^Kaljurand, I.; Kütt, A.; Sooväli, L.; Rodima, T.; Mäemets, V.; Leito, I.; Koppel, I. A. (2005). "Extension of the Self-Consistent Spectrophotometric Basicity Scale in Acetonitrile to a Full Span of 28 pKa Units: Unification of Different Basicity Scales".The Journal of Organic Chemistry.70 (3):1019–1028.doi:10.1021/jo048252w.PMID15675863.
^Weiberth, Franz J.; Hall, Stan S. (1986). "Tandem alkylation-reduction of nitriles. Synthesis of branched primary amines".Journal of Organic Chemistry.51 (26):5338–5341.doi:10.1021/jo00376a053.
^March, Jerry (1992).Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (4th ed.). New York: Wiley.ISBN0-471-60180-2.
^ This article incorporatestext available under theCC BY 4.0 license.Betts, J Gordon; Desaix, Peter; Johnson, Eddie; Johnson, Jody E; Korol, Oksana; Kruse, Dean; Poe, Brandon; Wise, James; Womble, Mark D; Young, Kelly A (26 July 2023).Anatomy & Physiology. Houston: OpenStax CNX. 17.2 Hormones.ISBN978-1-947172-04-3.
^Roughley, Stephen D.; Jordan, Allan M. (2011). "The Medicinal Chemist's Toolbox: An Analysis of Reactions Used in the Pursuit of Drug Candidates".Journal of Medicinal Chemistry.54 (10):3451–3479.doi:10.1021/jm200187y.PMID21504168.
^American Society of Health System Pharmacists; AHFS Drug Information 2010. Bethesda, MD. (2010), p. 2510
^Hammer, Georg; Lübcke, Torsten; Kettner, Roland; Davis, Robert N.; Recknagel, Herta; Commichau, Axel; Neumann, Hans-Joachim; Paczynska-Lahme, Barbara (2000). "Natural Gas".Ullmann's Encyclopedia of Industrial Chemistry.doi:10.1002/14356007.a17_073.ISBN3527306730.
^Howarth, Graham (1 January 1995). "The use of water-based epoxies for anti-corrosive primers".Pigment & Resin Technology.24 (6):3–6.doi:10.1108/eb043156.ISSN0369-9420.
^Eller K, Henkes E, Rossbacher R, Höke H (2005). "Amines, Aliphatic".Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH.doi:10.1002/14356007.a02_001.ISBN3527306730.
^Howarth G.A "Synthesis of a legislation compliant corrosion protection coating system based on urethane, oxazolidine and waterborne epoxy technology" pages 12, Chapter 1.3.1 Master of Science Thesis April 1997 Imperial College London
