In organic chemistry, amines (/əˈmiːn, ˈæmiːn/, also UK: /ˈeɪmiːn/) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group (these may respectively be called alkylamines and arylamines; amines in which both types of substituent are attached to one nitrogen atom may be called alkylarylamines). Important amines include amino acids, biogenic amines, trimethylamine, and aniline; see Category:Amines for a list of amines. Inorganic derivatives of ammonia are also called amines, such as chloramine (NClH2); see Category:Inorganic amines. Compounds with a nitrogen atom attached to a carbonyl group, thus having the structure R–CO–NR′R″, are called amides and have different chemical properties from amines.
1 Classification of amines 2 Naming conventions 3 Physical properties 4 Structure
5.1 Electronic effects 5.2 Solvation effects
6.1 Alkylation 6.2 Reductive routes 6.3 Specialized methods
7.1 Alkylation, acylation, and sulfonation 7.2 Diazotization 7.3 Conversion to imines 7.4 Overview
8 Biological activity 9 Application of amines
9.1 Dyes 9.2 Drugs 9.3 Gas treatment
10 Safety 11 See also 12 References 13 External links
Classification of amines
An aliphatic amine has no aromatic ring attached directly to the
Primary amines—Primary amines arise when one of three hydrogen atoms in ammonia is replaced by an alkyl or aromatic. Important primary alkyl amines include, methylamine, most amino acids, and the buffering agent tris, while primary aromatic amines include aniline. Secondary 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 amines—In tertiary amines, nitrogen has three organic substituents. Examples include trimethylamine, which has a distinctively fishy smell, and EDTA. 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.
It is also possible to have four organic substituents on the nitrogen. These species are not amines but are quaternary ammonium cations and have a charged nitrogen center. Quaternary ammonium salts exist with many kinds of anions. 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. Systematic names for some common amines:
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. pentan-2-amine.
2-aminopentane (or sometimes: pent-2-yl-amine or pentan-2-amine)
Inversion of an amine. The pair of dots represents the lone electron pair on the nitrogen atom.
Alkylamine or aniline pKa of protonated amine Kb
methylamine (MeNH2) 10.62 4.17E-04
dimethylamine (Me2NH) 10.64 4.37E-04
trimethylamine (Me3N) 9.76 5.75E-05
ethylamine (EtNH2) 10.63 4.27E-04
aniline (PhNH2) 4.62 4.17E-10
4-methoxyaniline (4-MeOC6H4NH2) 5.36 2.29E-09
4-trifluoromethylaniline (CF3C6H4NH2) 2.75 5.62E-12
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 delocalises into the ring, resulting in decreased basicity. Substituents on the aromatic ring, and their positions relative to the amine 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'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. 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 Alkylation The most industrially significant amines are prepared from ammonia by alkylation with alcohols:
ROH + NH3 → RNH2 + H2O
Unlike the reaction of amines with alkyl halides, the industrial method is green insofar that the coproduct is water. 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
Such reactions, which are most useful for alkyl iodides and bromides,
are rarely employed because the degree of alkylation is difficult to
control. Selectivity can be improved via the Delépine reaction,
although this is rarely employed on an industrial scale.
Via the process of hydrogenation, nitriles are reduced to amines using
hydrogen in the presence of a nickel catalyst. 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
nitriles on the laboratory scale. Similarly, LiAlH4 reduces amides to
amines. Many amines are produced from aldehydes and ketones via
reductive amination, which can either proceed catalytically or
Reaction name Substrate Comment
Gabriel synthesis Organohalide Reagent: potassium phthalimide
Staudinger reduction Azide This reaction also takes place with a reducing agent such as lithium aluminium hydride.
Schmidt reaction Carboxylic acid
Aza-Baylis–Hillman reaction Imine Synthesis of allylic amines
Birch reduction Imine Useful for reactions that trap unstable imine intermediates, such as Grignard reactions with nitriles.
Hofmann degradation Amide This reaction is valid for preparation of primary amines only. Gives good yields of primary amines uncontaminated with other amines.
Hofmann elimination Quaternary ammonium salt Upon treatment with strong base
Reduction of nitro compounds Nitro compounds Can be accomplished with elemental zinc, tin or iron with an acid.
Delepine reaction Organohalide reagent Hexamine
Menshutkin reaction Tertiary amine Reaction product a quaternary ammonium cation
Hydroamination Alkenes and alkynes
Ketones and aldehydes
Hofmann–Löffler reaction Haloamine
Reactions Alkylation, acylation, and sulfonation Aside from their basicity, the dominant reactivity of amines is their nucleophilicity. Most primary amines are good ligands for metal ions to give coordination complexes. Amines are alkylated by alkyl halides. Acyl chlorides and acid anhydrides react with primary and secondary amines to form amides (the "Schotten–Baumann reaction").
Similarly, with sulfonyl chlorides, one obtains sulfonamides. This transformation, known as the Hinsberg reaction, is a chemical test for the presence of amines. Because amines are basic, they neutralize acids to form the corresponding ammonium salts R3NH+. When formed from carboxylic acids and primary and secondary amines, these salts thermally dehydrate to form the corresponding amides.
a m i n e
d e h y d r a t i o n
h e a t
a m i d e
w a t e r
displaystyle underbrace ce H-!! overset displaystyle R1 atop underset atop displaystyle R2 N !!!!: _ amine +underbrace ce R3- overset displaystyle O atop C -OH _ text carboxylic acid -> underbrace ce H- overset displaystyle R1 atop underset atop displaystyle R2 N+ -H +R3-COO^ - _ text substituted-ammonium atop text carboxylate salt ce ->[heat][dehydration] underbrace ce overset displaystyle R1 atop underset atop displaystyle R2 N !!- overset displaystyle O atop C -R3 _ amide +underbrace ce H2O _ water
Diazotization Amines react with nitrous acid to give diazonium salts. The alkyl diazonium salts are of little synthetic importance because they are too unstable. The most important members are derivatives of aromatic amines such as aniline ("phenylamine") (A = aryl or naphthyl):
+ HX ⟶ AN + 2
displaystyle ce ANH2 + HNO2 + HX -> AN + 2X^- + 2 H2O
Anilines and naphthylamines form more stable diazonium salts, which
can be isolated in the crystalline form.
⟶ AY +
displaystyle ce AN2+ + Y^- -> AY + N2
Aryldiazonium couple with electron-rich aromatic compounds such as a
phenol to form azo compounds. Such reactions are widely applied to the
production of dyes.
Conversion to imines
RNH2 + R′2C=O → R′2C=NR + H2O
Reduction of these imines gives secondary amines:
R′2C=NR + H2 → R′2CH–NHR
Similarly, secondary amines react with ketones and aldehydes to form enamines:
R2NH + R′(R″CH2)C=O → R″CH=C(NR2)R′ + H2O
Overview An overview of the reactions of amines is given below:
Reaction name Reaction product Comment
Schotten–Baumann reaction Amide Reagents: acyl chlorides, acid anhydrides
Hinsberg reaction Sulfonamides Reagents: sulfonyl chlorides
Amine–carbonyl condensation Imines
Zincke reaction Zincke aldehyde Reagent: pyridinium salts, with primary and secondary amines
Emde degradation Tertiary amine Reduction of quaternary ammonium cations
Hofmann–Martius rearrangement Aryl-substituted anilines
von Braun reaction Organocyanamide By cleavage (tertiary amines only) with cyanogen bromide
Hofmann elimination Alkene Proceeds by β-elimination of less hindered carbon
Cope reaction Alkene Similar to Hofmann elimination
carbylamine reaction Isonitrile Primary amines only
Hoffmann's mustard oil test Isothiocyanate CS2 and HgCl2 are used. Thiocyanate smells like mustard.
Amines are ubiquitous in biology. The breakdown of amino acids
releases amines, famously in the case of decaying fish which smell of
trimethylamine. Many neurotransmitters are amines, including
epinephrine, norepinephrine, dopamine, serotonin, and histamine.
Protonated amino groups (–NH+
3) are the most common positively charged moieties in proteins,
specifically in the amino acid lysine. The anionic polymer
Direct brown 138
Drugs Many drugs are designed to mimic or to interfere with the action of natural amine neurotransmitters, exemplified by the amine drugs:
Gas treatment Aqueous monoethanolamine (MEA), diglycolamine (DGA), diethanolamine (DEA), diisopropanolamine (DIPA) and methyldiethanolamine (MDEA) are widely used industrially for removing carbon dioxide (CO2) and hydrogen sulfide (H2S) from natural gas and refinery process streams. They may also be used to remove CO2 from combustion gases and flue gases and may have potential for abatement of greenhouse gases. Related processes are known as sweetening. Safety Low molecular weight simple amines, such as ethylamine, are only weakly toxic with LD50 between 100 and 1000 mg/kg. They are skin irritants, especially as some are easily absorbed through the skin. Amines are a broad class of compounds, and more complex members of the class can be extremely bioactive, for example strychnine and heroin. See also
^ "amine". The American Heritage Dictionary of the English Language
(5th ed.). Boston: Houghton Mifflin Harcourt. 2014.
Wikiquote has quotations related to: Amine
Primary amine synthesis: synthetic protocols from organic-reaction.com  Amines have been implicated in migraine headaches; link contains citations, and list of amine containing foods.
v t e
Only carbon, hydrogen and oxygen
Only one element apart from C, H, O
Disulfide Sulfone Sulfonic acid Sulfoxide Thial Thioester Thioether Thioketone Thiol
Selenol Selenonic acid Seleninic acid Selenenic acid
Isothiocyanate Phosphoramide Sulfenyl chloride Sulfonamide Thiocyanate
See also chemical classification, chemical nomenclature (inorganic, organic)
v t e
Hydrides: NH3 NH4+ NH2− MNH2 N3− NH2OH N2H4 N3– Organic: -NH2 -CHR=NHR -CONHR2 HCN CN− C2N2 H2NCN CH2N2 Oxides: N2O NO NO2 N2O3 N2O4 N2O5 HNO2 HNO3 NO2− NO3− NO+ NO2+ Halides: NF3 NCl3 NBr3 NI3 FN3 ClN3 NH2Cl
GND: 4001705-9 N