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chemistry Chemistry is the scientific study of the properties and behavior of matter. It is a natural science that covers the elements that make up matter to the compounds made of atoms, molecules and ions: their composition, structure, proper ...
, amines (, ) are compounds and
functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the r ...
s that contain a
basic BASIC (Beginners' All-purpose Symbolic Instruction Code) is a family of general-purpose, high-level programming languages designed for ease of use. The original version was created by John G. Kemeny and Thomas E. Kurtz at Dartmouth College ...
nitrogen Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...
atom with a
lone pair In chemistry, a lone pair refers to a pair of valence electrons that are not shared with another atom in a covalent bondIUPAC '' Gold Book'' definition''lone (electron) pair''/ref> and is sometimes called an unshared pair or non-bonding pair. L ...
. Amines are formally derivatives of
ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous ...
(), wherein one or more
hydrogen Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-to ...
atoms have been replaced by a
substituent A substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. (In organic chemistry and biochemistry, the terms ''substituent'' and ''functional group'', as well as '' side ...
such as an
alkyl In organic chemistry, an alkyl group is an alkane missing one hydrogen. The term ''alkyl'' is intentionally unspecific to include many possible substitutions. An acyclic alkyl has the general formula of . A cycloalkyl is derived from a cycloa ...
or
aryl In organic chemistry, an aryl is any functional group or substituent derived from an aromatic ring, usually an aromatic hydrocarbon, such as phenyl and naphthyl. "Aryl" is used for the sake of abbreviation or generalization, and "Ar" is used ...
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 acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
s, biogenic amines,
trimethylamine Trimethylamine (TMA) is an organic compound with the formula N(CH3)3. It is a colorless, hygroscopic, and flammable tertiary amine. It is a gas at room temperature but is usually sold as a 40% solution in water. (It is also sold in pressurized ...
, and
aniline Aniline is an organic compound with the formula C6 H5 NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine. It is an industrially significant commodity chemical, as well as a versatile starti ...
;
Inorganic In chemistry, an inorganic compound is typically a chemical compound that lacks carbon–hydrogen bonds, that is, a compound that is not an organic compound. The study of inorganic compounds is a subfield of chemistry known as ''inorganic chemist ...
derivatives of
ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous ...
are also called amines, such as
monochloramine Monochloramine, often called chloramine, is the chemical compound with the formula NH2Cl. Together with dichloramine (NHCl2) and nitrogen trichloride (NCl3), it is one of the three chloramines of ammonia. It is a colorless liquid at its melting p ...
(). The substituent is called an amino group. Compounds with a nitrogen atom attached to a
carbonyl group In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containi ...
, thus having the structure , are called
amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...
s and have different chemical properties from amines.


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 amine In organic chemistry, an aromatic amine is an organic compound consisting of an aromatic ring attached to an amine. It is a broad class of compounds that encompasses aniline Aniline is an organic compound with the formula C6 H5 NH2. Consi ...
s have the nitrogen atom connected to an
aromatic In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...
ring. 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 In organic chemistry, an alkyl group is an alkane missing one hydrogen. The term ''alkyl'' is intentionally unspecific to include many possible substitutions. An acyclic alkyl has the general formula of . A cycloalkyl is derived from a cycloa ...
or
aromatic In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...
group. Important primary alkyl amines include,
methylamine Methylamine is an organic compound with a formula of . This colorless gas is a derivative of ammonia, but with one hydrogen atom being replaced by a methyl group. It is the simplest primary amine. Methylamine is sold as a solution in methanol, ...
, most
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
s, and the
buffering agent A buffer solution (more precisely, pH buffer or hydrogen ion buffer) is an aqueous solution consisting of a mixture of a weak acid and its conjugate base, or vice versa. Its pH changes very little when a small amount of strong acid or base is ...
tris Tris, or tris(hydroxymethyl)aminomethane, or known during medical use as tromethamine or THAM, is an organic compound with the formula (HOCH2)3CNH2, one of the twenty Good's buffers. It is extensively used in biochemistry and molecular biology as ...
, while primary aromatic amines include
aniline Aniline is an organic compound with the formula C6 H5 NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine. It is an industrially significant commodity chemical, as well as a versatile starti ...
. *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 Dimethylamine is an organic compound with the formula (CH3)2NH. This secondary amine is a colorless, flammable gas with an ammonia-like odor. Dimethylamine is commonly encountered commercially as a solution in water at concentrations up to arou ...
, while an example of an aromatic amine would be diphenylamine. *Tertiary (3°) amines—In tertiary amines, nitrogen has three organic substituents. Examples include
trimethylamine Trimethylamine (TMA) is an organic compound with the formula N(CH3)3. It is a colorless, hygroscopic, and flammable tertiary amine. It is a gas at room temperature but is usually sold as a 40% solution in water. (It is also sold in pressurized ...
, which has a distinctively fishy smell, and
EDTA Ethylenediaminetetraacetic acid (EDTA) is an aminopolycarboxylic acid with the formula H2N(CH2CO2H)2sub>2. This white, water-soluble solid is widely used to bind to iron (Fe2+/Fe3+) and calcium ions (Ca2+), forming water-soluble complexes ev ...
. A fourth subcategory is determined by the connectivity of the substituents attached to the nitrogen: *Cyclic amines—
Cyclic Cycle, cycles, or cyclic may refer to: Anthropology and social sciences * Cyclic history, a theory of history * Cyclical theory, a theory of American political history associated with Arthur Schlesinger, Sr. * Social cycle, various cycles in so ...
amines are either secondary or tertiary amines. Examples of cyclic amines include the 3-membered ring
aziridine Aziridine is an organic compound consisting of the three-membered heterocycle . It is a colorless, toxic, volatile liquid that is of significant practical interest. Aziridine was discovered in 1888 by the chemist Siegmund Gabriel. Its derivat ...
and the six-membered ring
piperidine Piperidine is an organic compound with the molecular formula (CH2)5NH. This heterocyclic amine consists of a six-membered ring containing five methylene bridges (–CH2–) and one amine bridge (–NH–). It is a colorless liquid with an odor de ...
. ''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 cation In chemistry, quaternary ammonium cations, also known as quats, are positively charged polyatomic ions of the structure , R being an alkyl group or an aryl group. Unlike the ammonium ion () and the primary, secondary, or tertiary ammonium cation ...
s 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:


Physical properties

Hydrogen bonding In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a l ...
significantly influences the properties of primary and secondary amines. For example,
methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in ...
and ethyl amines are gases under standard conditions, whereas the corresponding
methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in ...
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 In chemistry, a lone pair refers to a pair of valence electrons that are not shared with another atom in a covalent bondIUPAC '' Gold Book'' definition''lone (electron) pair''/ref> and is sometimes called an unshared pair or non-bonding pair. L ...
that can bind H+ to form an
ammonium ion The ammonium cation is a positively-charged polyatomic ion with the chemical formula or . It is formed by the protonation of ammonia (). Ammonium is also a general name for positively charged or protonated substituted amines and quaternary amm ...
R3NH+. The lone electron pair is represented in this article by a two dots above or next to the N. The water
solubility In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution. The extent of the solubi ...
of simple amines is enhanced by
hydrogen bonding In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a l ...
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
solvent A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
s, whereas those with large substituents are lipophilic. Aromatic amines, such as
aniline Aniline is an organic compound with the formula C6 H5 NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine. It is an industrially significant commodity chemical, as well as a versatile starti ...
, 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 Infrared (IR), sometimes called infrared light, is electromagnetic radiation (EMR) with wavelengths longer than those of visible light. It is therefore invisible to the human eye. IR is generally understood to encompass wavelengths from around ...
primary amines exhibit two N-H bands, whereas secondary amines exhibit only one.


Structure


Alkyl amines

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. The
energy barrier In chemistry and physics, activation energy is the minimum amount of energy that must be provided for compounds to result in a chemical reaction. The activation energy (''E''a) of a reaction is measured in joules per mole (J/mol), kilojoules pe ...
for the
nitrogen inversion In chemistry, pyramidal inversion (also umbrella inversion) is a fluxional process in compounds with a pyramidal molecule, such as ammonia (NH3) "turns inside out". It is a rapid oscillation of the atom and substituents, the molecule or ion pass ...
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 Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is distinguishable from i ...
: 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
aziridine Aziridine is an organic compound consisting of the three-membered heterocycle . It is a colorless, toxic, volatile liquid that is of significant practical interest. Aziridine was discovered in 1888 by the chemist Siegmund Gabriel. Its derivat ...
s (
quaternary ammonium salt In chemistry, quaternary ammonium cations, also known as quats, are positively charged polyatomic ions of the structure , R being an alkyl group or an aryl group. Unlike the ammonium ion () and the primary, secondary, or tertiary ammonium cation ...
s 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.


Basicity

Like ammonia, amines are bases. Compared to alkali metal hydroxides, amines are weaker (see table for examples of
conjugate acid A conjugate acid, within the Brønsted–Lowry acid–base theory, is a chemical compound formed when an acid donates a proton () to a base—in other words, it is a base with a hydrogen ion added to it, as in the reverse reaction it loses a ...
''K''a values). 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 Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...
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'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 Acetonitrile, often abbreviated MeCN (methyl cyanide), is the chemical compound with the formula and structure . This colourless liquid is the simplest organic nitrile ( hydrogen cyanide is a simpler nitrile, but the cyanide anion is not clas ...
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 Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effectin ...
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 + R'NH2 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 The Gabriel synthesis is a chemical reaction that transforms primary alkyl halides into primary amines. Traditionally, the reaction uses potassium phthalimide. The reaction is named after the German chemist Siegmund Gabriel. The Gabriel reaction ...
, which involves organohalide reacting with
potassium phthalimide Potassium phthalimide is a chemical compound of formula C8H4KNO2. It is the potassium salt of phthalimide, and usually presents as fluffy, very pale yellow crystals. It can be prepared by adding a hot solution of phthalimide in ethanol to a soluti ...
. 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 a tert-octylamine. Hydroamination of alkenes is also widely practiced. The reaction is catalyzed by zeolite-based
solid acid Solid is one of the four fundamental states of matter (the others being liquid, gas, and plasma). The molecules in a solid are closely packed together and contain the least amount of kinetic energy. A solid is characterized by structural ...
s.


Reductive routes

Via the process of
hydrogenation Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organic ...
, unsaturated N-containing functional groups are reduced to amines using hydrogen in the presence of a nickel catalyst. Suitable groups include
nitrile In organic chemistry, a nitrile is any organic compound that has a functional group. The prefix '' cyano-'' is used interchangeably with the term ''nitrile'' in industrial literature. Nitriles are found in many useful compounds, including me ...
s,
azide In chemistry, azide is a linear, polyatomic anion with the formula and structure . It is the conjugate base of hydrazoic acid . Organic azides are organic compounds with the formula , containing the azide functional group. The dominant appli ...
s, imines including oximes, amides, and nitro. In the case of nitriles, reactions are sensitive to acidic or alkaline conditions, which can cause hydrolysis of the group. is more commonly employed for the reduction of these same groups on the laboratory scale. Many amines are produced from aldehydes and ketones via
reductive amination Reductive amination (also known as reductive alkylation) is a form of amination that involves the conversion of a carbonyl group to an amine via an intermediate imine. The carbonyl group is most commonly a ketone or an aldehyde. It is considered ...
, which can either proceed catalytically or stoichiometrically.
Aniline Aniline is an organic compound with the formula C6 H5 NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine. It is an industrially significant commodity chemical, as well as a versatile starti ...
() 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.


Specialized methods

Many methods exist for the preparation of amines, many of these methods being rather specialized.


Reactions


Alkylation, acylation, and sulfonation, etc.

Aside from their basicity, the dominant reactivity of amines is their
nucleophilicity In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...
. Most primary amines are good
ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elect ...
s for metal ions to give
coordination complex A coordination complex consists of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of bound molecules or ions, that are in turn known as '' ligands'' or complexing agents. M ...
es. Amines are alkylated by alkyl halides.
Acyl chloride In organic chemistry, an acyl chloride (or acid chloride) is an organic compound with the functional group . Their formula is usually written , where R is a side chain. They are reactive derivatives of carboxylic acids (). A specific example o ...
s and
acid anhydride An acid anhydride is a type of chemical compound derived by the removal of water molecules from an acid. In organic chemistry, organic acid anhydrides contain the functional group R(CO)O(CO)R'. Organic acid anhydrides often form when one equivale ...
s react with primary and secondary amines to form
amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...
s (the " Schotten–Baumann reaction"). Similarly, with sulfonyl chlorides, one obtains
sulfonamide In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactive. ...
s. This transformation, known as the Hinsberg reaction, is a chemical test for the presence of amines. Because amines are basic, they neutralize
acid In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a se ...
s to form the corresponding ammonium salts . When formed from carboxylic acids and primary and secondary amines, these salts thermally dehydrate to form the corresponding
amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...
s. : \ \underbrace\ce _ \ce Amines undergo sulfamation upon treatment with
sulfur trioxide Sulfur trioxide (alternative spelling sulphur trioxide, also known as ''nisso sulfan'') is the chemical compound with the formula SO3. It has been described as "unquestionably the most important economically" sulfur oxide. It is prepared on an ind ...
or sources thereof: :R2NH + SO3 -> R2NSO3H


Acid-base reactions

Alkyl amines protonate near pH=7 to give alkylammonium derivative.


Diazotization

Amines reacts with
nitrous acid Nitrous acid (molecular formula ) is a weak and monoprotic acid known only in solution, in the gas phase and in the form of nitrite () salts. Nitrous acid is used to make diazonium salts from amines. The resulting diazonium salts are reagent ...
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 as
aniline Aniline is an organic compound with the formula C6 H5 NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine. It is an industrially significant commodity chemical, as well as a versatile starti ...
("phenylamine") (A = aryl or naphthyl): :ANH2 + HNO2 + HX -> AN2+ + X- + 2 H2O Anilines and naphthylamines form more stable diazonium salts, which can be isolated in the crystalline form. Diazonium salts undergo a variety of useful transformations involving replacement of the group with anions. For example, cuprous cyanide gives the corresponding nitriles: :AN2+ + Y- -> AY + N2 Aryldiazonium couple with electron-rich aromatic compounds such as a
phenol Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it r ...
to form azo compounds. Such reactions are widely applied to the production of dyes.


Conversion to Imines

Imine formation is an important reaction. Primary amines react with
ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double b ...
s and
aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl gro ...
s to form imines. In the case of
formaldehyde Formaldehyde ( , ) ( systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section ...
(R'  H), these products typically exist as cyclic trimers. : 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:


Biological activity

Amines are ubiquitous in biology. The breakdown of
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
s releases amines, famously in the case of decaying fish which smell of
trimethylamine Trimethylamine (TMA) is an organic compound with the formula N(CH3)3. It is a colorless, hygroscopic, and flammable tertiary amine. It is a gas at room temperature but is usually sold as a 40% solution in water. (It is also sold in pressurized ...
. Many
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neu ...
s are amines, including
epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
,
norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...
,
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...
,
serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...
, and
histamine Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discover ...
. Protonated
amino group In chemistry, amines (, ) 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 ...
s () are the most common positively charged moieties in
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s, specifically in the amino acid
lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated − ...
. The anionic polymer DNA is typically bound to various amine-rich proteins. Additionally, the terminal charged primary ammonium on lysine forms salt bridges with
carboxylate In organic chemistry, a carboxylate is the conjugate base of a carboxylic acid, (or ). It is an ion with negative charge. Carboxylate salts are salts that have the general formula , where M is a metal and ''n'' is 1, 2,...; ''carboxylat ...
groups of other amino acids in
polypeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...
s, which is one of the primary influences on the three-dimensional structures of proteins.


Application of amines


Dyes

Primary aromatic amines are used as a starting material for the manufacture of
azo dye Azo dyes are organic compounds bearing the functional group R−N=N−R′, in which R and R′ are usually aryl and substituted aryl groups. They are a commercially important family of azo compounds, i.e. compounds containing the C-N ...
s. 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: *
Methyl orange Methyl orange is a pH indicator frequently used in titration because of its clear and distinct color variance at different pH values. Methyl orange shows red color in acidic medium and yellow color in basic medium. Because it changes color at the ...
* Direct brown 138 *
Sunset yellow Sunset yellow FCF (also known as orange yellow S, or C.I. 15985) is a petroleum-derived orange azo dye with a pH dependent maximum absorption at about 480 nm at pH 1 and 443 nm at pH 13 with a shoulder at 500 nm. When added to f ...
FCF * Ponceau


Drugs

Approximately 42% of drugs and drug candidates contain amine functional groups: *
Chlorpheniramine Chlorphenamine (CP, CPM), also known as chlorpheniramine, is an antihistamine used to treat the symptoms of allergic conditions such as allergic rhinitis (hay fever). It is taken by mouth. The medication takes effect within two hours and lasts ...
is an
antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provide ...
that helps to relieve allergic disorders due to cold, hay fever, itchy skin, insect bites and stings. *
Chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar di ...
is a tranquilizer that sedates without inducing sleep. It is used to relieve anxiety, excitement, restlessness or even mental disorder. *
Ephedrine Ephedrine is a central nervous system (CNS) stimulant that is often used to prevent low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred treatment. It is of unclear benefit in ...
and phenylephrine, as amine hydrochlorides, are used as decongestants. *
Amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
,
methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamp ...
, and methcathinone are psychostimulant amines that are listed as controlled substances by the US DEA. * Thioridazine , an antipsychotic drug, is an amide which is believed to exhibit its antipsychotic effects, in part, due to its effects on other amides. *
Amitriptyline Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat cyclic vomiting syndrome (CVS), major depressive disorder and a variety of pain syndromes from neuropathic pain to fibromyalgi ...
, imipramine, lofepramine and clomipramine are
tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...
s and tertiary amines. *
Nortriptyline Nortriptyline, sold under the brand name Pamelor, among others, is a medication used to treat depression. This medicine is used for: neuropathic pain, attention deficit hyperactivity disorder (ADHD), smoking cessation and anxiety. As with many ...
, desipramine, and
amoxapine Amoxapine, sold under the brand name Asendin among others, is a tricyclic antidepressant (TCAs). It is the N-demethylated metabolite of loxapine. Amoxapine first received marketing approval in the United States in 1992 (approximately 30 to 40 ...
are
tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...
and secondary amines. (The tricyclics are grouped by the nature of the final amino group on the side chain.) *
Substituted tryptamine Substituted tryptamines, or serotonin analogues, are organic compounds which may be thought of as being derived from tryptamine itself. The molecular structures of all tryptamines contain an indole ring, joined to an amino (NH2) group via an et ...
s and
phenethylamine Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace am ...
s are key basic structures for a large variety of
psychedelic drug Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips").Pollan, Michael (2018). ''How to Change Your Mind: What the New Science o ...
s. *
Opiate An opiate, in classical pharmacology, is a substance derived from opium. In more modern usage, the term '' opioid'' is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain (including antagoni ...
analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...
s such as
morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies ('' Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. T ...
,
codeine Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically ...
, and
heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is a potent opioid mainly used as a recreational drug for its euphoric effects. Medical grade diamorphine is used as a pure hydrochloride salt. Various white and bro ...
are
tertiary Tertiary ( ) is a widely used but obsolete term for the geologic period from 66 million to 2.6 million years ago. The period began with the demise of the non-avian dinosaurs in the Cretaceous–Paleogene extinction event, at the start ...
amines.


Gas treatment

Aqueous
monoethanolamine Ethanolamine (2-aminoethanol, monoethanolamine, ETA, or MEA) is an organic chemical compound with the formula or . The molecule is bifunctional, containing both a primary amine and a primary alcohol. Ethanolamine is a colorless, viscous liquid ...
(MEA), diglycolamine (DGA),
diethanolamine Diethanolamine, often abbreviated as DEA or DEOA, is an organic compound with the formula HN(CH2CH2OH)2. Pure diethanolamine is a white solid at room temperature, but its tendencies to absorb water and to supercool meaning that it is often encou ...
(DEA), diisopropanolamine (DIPA) and methyldiethanolamine (MDEA) are widely used industrially for removing
carbon dioxide Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is t ...
(CO2) and
hydrogen sulfide Hydrogen sulfide is a chemical compound with the formula . It is a colorless chalcogen-hydride gas, and is poisonous, corrosive, and flammable, with trace amounts in ambient atmosphere having a characteristic foul odor of rotten eggs. The under ...
(H2S) from natural gas and refinery process streams. They may also be used to remove CO2 from combustion gases and
flue gas Flue gas is the gas exiting to the atmosphere via a flue, which is a pipe or channel for conveying exhaust gases from a fireplace, oven, furnace, boiler or steam generator. Quite often, the flue gas refers to the combustion exhaust gas produc ...
es and may have potential for abatement of
greenhouse gas A greenhouse gas (GHG or GhG) is a gas that absorbs and emits radiant energy within the thermal infrared range, causing the greenhouse effect. The primary greenhouse gases in Earth's atmosphere are water vapor (), carbon dioxide (), methane ...
es. Related processes are known as sweetening.


Epoxy resin curing agents

Amines are often used as epoxy resin curing agents. These include dimethylethylamine,
cyclohexylamine Cyclohexylamine is an organic compound, belonging to the aliphatic amine class. It is a colorless liquid, although, like many amines, samples are often colored due to contaminants. It has a fishy odor and is miscible with water. Like other amine ...
, and a variety of diamines such as 4,4 -diaminodicyclohexylmethane. Multifunctional amines such as
tetraethylenepentamine Tetraethylenepentamine (TEPA) is an organic compound and is in the class of chemicals known as ethyleneamines. It is a slightly viscous liquid and is not colorless but, like many amines, has a yellow color. It is soluble in most polar solvents. Di ...
and
triethylenetetramine Triethylenetetramine (TETA and trien), also known as trientine (INN) when used medically, is an organic compound with the formula H2NHCH2CH2NH2sub>2. The pure freebase is a colorless oily liquid, but, like many amines, older samples assume a ye ...
are also widely used in this capacity. 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.


Safety

Low molecular weight simple amines, such as
ethylamine Ethylamine, also known as ethanamine, is an organic compound with the formula CH3CH2NH2. This colourless gas has a strong ammonia-like odor. It condenses just below room temperature to a liquid miscible with virtually all solvents. It is a nucl ...
, are only weakly toxic with 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 Strychnine (, , US chiefly ) is a highly toxic, colorless, bitter, crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine, when inhaled, swallowed, or absorbed through the e ...
and
heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is a potent opioid mainly used as a recreational drug for its euphoric effects. Medical grade diamorphine is used as a pure hydrochloride salt. Various white and bro ...
.


See also

* Acid-base extraction *
Amine value In chemistry, amines (, ) 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 ...
*
Amine gas treating Amine gas treating, also known as amine scrubbing, gas sweetening and acid gas removal, refers to a group of processes that use aqueous solutions of various alkylamines (commonly referred to simply as amines) to remove hydrogen sulfide (H2S) and c ...
* Ammine * Biogenic amine *
Ligand isomerism In coordination chemistry, ligand isomerism is a type of structural isomerism in coordination complexes which arises from the presence of ligands which can adopt different isomeric forms. 1,2-Diaminopropane and 1,3-Diaminopropane 1,3-Diaminopr ...
* Official naming rules for amines as determined by the International Union of Pure and Applied Chemistry (
IUPAC The International Union of Pure and Applied Chemistry (IUPAC ) is an international federation of National Adhering Organizations working for the advancement of the chemical sciences, especially by developing nomenclature and terminology. It is ...
)


References


Further reading

* *


External links


Synthesis of amines

Factsheet, amines in food
{{Authority control Functional groups