Editing Amine

{{Short description|Chemical compounds and groups containing nitrogen with a lone pair (:N)}}
{{Other uses}}
{{Redirect|Amino}}
{{Distinguish|Amin (disambiguation){{!}}Amin|Anime}}
{{Use dmy dates|date=March 2022}}
[[File:Amine Functional Group.png|thumb|164x164px|Amine]]
In [[chemistry]], '''amines''' ({{IPAc-en|ə|ˈ|m|i:|n|,_|ˈ|æ|m|i:|n}},<ref>{{Cite American Heritage Dictionary|amine}}</ref><ref>{{cite dictionary |url=http://www.collinsdictionary.com/dictionary/english/amine |title=Amine definition and meaning |dictionary=Collins English Dictionary |access-date=2017-03-28 |archive-date=23 February 2015 |archive-url=https://web.archive.org/web/20150223133401/http://www.collinsdictionary.com/dictionary/english/amine |url-status=live }}</ref> {{small|UK also}} {{IPAc-en|ˈ|eɪ|m|iː|n}}<ref>{{cite web |url=http://www.oxforddictionaries.com/us/definition/english/amine |title=amine – definition of amine in English |publisher=Oxford Dictionaries |access-date=2017-03-28 |archive-date=23 February 2015 |archive-url=https://web.archive.org/web/20150223133030/http://www.oxforddictionaries.com/us/definition/english/amine |url-status=dead }}</ref>) are [[chemical compound|compounds]] and [[functional group]]s that contain a [[base (chemistry)|basic]] [[nitrogen]] atom with a [[lone pair]]. Formally, amines are [[derivative (chemistry)|derivatives]] of [[ammonia]] ({{chem2|NH3}} in which the bond angle between the nitrogen and hydrogen is 107°), wherein one or more [[hydrogen]] atoms have been replaced by a [[substituent]] such as an [[alkyl]] or [[aryl]] group<ref>{{McMurray3rd}}</ref> (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]]s, [[biogenic amine]]s, [[trimethylamine]], and [[aniline]]. [[Inorganic compound|Inorganic]] derivatives of [[ammonia]] are also called amines, such as [[monochloramine]] ({{chem2|NClH2}}).<ref name="Ullmann" />

The substituent {{chem2|\sNH2}} is called an amino group.<ref name="OChemSmith3E">{{cite book |last1=Smith |first1=Janice Gorzynski <!--
|editor1-last=Hodge |editor1-first=Tami |editor2-last=Nemmers |editor2-first=Donna |editor3-last=Klein |editor3-first=Jayne
--> |title=Organic chemistry |date=2011 |publisher=McGraw-Hill |location=New York, NY |isbn=978-0-07-337562-5 |pages=949–993 |edition=3rd |chapter-url=http://highered.mheducation.com/sites/007340277x/student_view0/index.html |language=en |chapter-format=Book |chapter=Chapter 25 Amines |access-date=26 June 2018 |archive-date=28 June 2018 |archive-url=https://web.archive.org/web/20180628152511/http://highered.mheducation.com/sites/007340277x/student_view0/index.html |url-status=dead }}</ref>

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 a [[nitrogen]] atom attached to a [[carbonyl group]], thus having the structure {{chem2|R\sC(\dO)\sNR′R″}}, are called [[amide]]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]]s''' have the nitrogen atom connected to an [[aromaticity|aromatic]] ring.

<!-- [[primary amine]] redirects to this section -->
{| class="wikitable"  style="margin:auto 1em auto 1em; float:right; text-align:center;"
|- id="amino_group_connectivity_table"
! Primary (1°) amine !! Secondary (2°) amine !! Tertiary (3°) amine
|-
| [[File:Primary-amine-2D-general.svg|100px|primary amine]]
| [[File:Secondary-amine-2D-general.svg|100px|secondary amine]]
| [[File:Amine-2D-general.svg|100px|tertiary amine]]
|}Amines, alkyl and aryl alike, are organized into three subcategories [[#amino_group_connectivity_table|<small>(see table)</small>]] based on the number of [[carbon]] atoms adjacent to the nitrogen (how many hydrogen atoms of the [[ammonia]] molecule are replaced by [[hydrocarbon]] groups):<ref name=OChemSmith3E/><ref>{{Cite web|date=2015-09-28|title=3.11 Basic properties of amines|url=https://chem.libretexts.org/Courses/Middle_Georgia_State_University/MGA_CHEM_1152K_Survey_of_Chemistry_II/Chapters/Unit_3%3A_More_Reactions_and_Properties/3.11_Basic_properties_of_amines|access-date=2021-05-23|website=Chemistry LibreTexts|language=en|archive-date=23 May 2021|archive-url=https://web.archive.org/web/20210523170747/https://chem.libretexts.org/Courses/Middle_Georgia_State_University/MGA_CHEM_1152K_Survey_of_Chemistry_II/Chapters/Unit_3:_More_Reactions_and_Properties/3.11_Basic_properties_of_amines|url-status=live}}</ref>

*'''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 acid]]s, 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 compound|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 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.

Lower amines are named with the suffix ''-amine''.
[[File:Butan-1-amine.png|center|thumb|[[N-Butylamine|butan-1-amine]]]]
Higher amines have the prefix ''amino'' as a functional group. IUPAC however does not recommend this convention,<ref>{{Cite web |last1=Hellwich |first1=K.-H. |last2=Hartshorn |first2=R. M. |last3=Yerin |first3=A. |last4=Damhus |first4=T. |last5=Hutton |first5=A. T. |date=June 2021 |title=Brief Guide to the Nomenclature of Organic Chemistry |url=https://iupac.org/wp-content/uploads/2021/06/Organic-Brief-Guide-brochure_v1.1_June2021.pdf |access-date=2024-03-07 |website=The International Union of Pure and Applied Chemistry (IUPAC)}}</ref> but prefers the alkanamine form, e.g. butan-2-amine.
[[File:2-aminobutane.png|center|thumb|135x135px|[[Sec-Butylamine|2-aminobutane]] (or butan-2-amine)]]

==Physical properties==
[[Hydrogen bonding]] significantly influences the properties of primary and secondary amines. For example, [[Methylamine|methyl]] and [[Ethylamine|ethyl]] amines are gases under standard conditions, whereas the corresponding [[Methanol|methyl]] and [[Ethanol|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<sup>+</sup> to form an [[ammonium ion]] R<sub>3</sub>NH<sup>+</sup>. 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 ({{chem|RNH|3|+}}) > secondary ammonium ({{chem|R|2|NH|2|+}}) > tertiary ammonium (R<sub>3</sub>NH<sup>+</sup>). Small aliphatic amines display significant solubility in many [[solvent]]s, whereas those with large substituents are lipophilic. Aromatic amines, such as [[aniline]], have their lone pair electrons [[conjugated system|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. <sup>1</sup>H NMR signals for amines disappear upon treatment of the sample with D<sub>2</sub>O.  In their [[infrared spectrum]] primary amines exhibit two N-H bands, whereas secondary amines exhibit only one.<ref name=OChemSmith3E />  In their IR spectra, primary and secondary amines exhibit distinctive N-H stretching bands near 3300&nbsp;cm<sup>−1</sup>.   Somewhat less distinctive are the bands appearing below 1600&nbsp;cm<sup>−1</sup>, which are weaker and overlap with C-C and C-H modes.  For the case of [[propyl amine]], the H-N-H scissor mode appears near 1600&nbsp;cm<sup>−1</sup>, the C-N stretch near 1000&nbsp;cm<sup>−1</sup>, and the R<sub>2</sub>N-H bend near 810&nbsp;cm<sup>−1</sup>.<ref>{{cite journal |last1=Smith |first1=Brian |title=Organic Nitrogen Compounds II: Primary Amines |url=https://www.spectroscopyonline.com/view/organic-nitrogen-compounds-ii-primary-amines |website=Spectroscopy |series=Spectroscopy-03-01-2019 |date=March 2019 |volume=34 |pages=22–25 |access-date=12 February 2024}}</ref>

==Structure==
===Alkyl amines===
[[File:Inversion of amine.svg|thumb|right|Inversion of an amine spatial configuration: Amine "flip-flop" like an umbrella turned over by the wind. The pair of dots represents the lone [[electron 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.  The [[activation energy|energy barrier]] for the [[nitrogen inversion]] of the stereocenter is about 7&nbsp;[[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 [[chirality (chemistry)|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 [[aziridine]]s ([[quaternary ammonium salt]]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.<ref>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}}</ref>

==Basicity==
Like ammonia, amines are [[base (chemistry)|bases]].<ref>{{cite book|chapter=Basicity and complex formation|title= Patai's Chemistry of Functional Groups|pages= 161–204|editor=S. Patai|year=1968|author=J. W. Smith|doi=10.1002/9780470771082.ch4|isbn= 9780470771082}}</ref> Compared to alkali metal hydroxides, amines are weaker.

{| class="wikitable" style="float:center; margin:0 1em;"
|-
!Alkylamine<ref>{{Cite journal | last1 = Hall | first1 = H. K. | title = Correlation of the Base Strengths of Amines | doi = 10.1021/ja01577a030 | journal = Journal of the American Chemical Society | volume = 79 | issue = 20 | pages = 5441–5444 | year = 1957 | bibcode = 1957JAChS..79.5441H }}</ref> or aniline<ref>{{Cite journal | last1 = Kaljurand | first1 = I. | last2 = Kütt | first2 = A. | last3 = Sooväli | first3 = L. | last4 = Rodima | first4 = T. | last5 = Mäemets | first5 = V. | last6 = Leito | first6 = I. | last7 = Koppel | first7 = I. A. | doi = 10.1021/jo048252w | title = Extension of the Self-Consistent Spectrophotometric Basicity Scale in Acetonitrile to a Full Span of 28 pKa Units: Unification of Different Basicity Scales | journal = The Journal of Organic Chemistry | volume = 70 | issue = 3 | pages = 1019–1028 | year = 2005 | pmid =  15675863}}</ref>
! pK<sub>a</sub> of <br />protonated amine
! ''K''<sub>b</sub>{{Clarify|date=April 2022}}
|-
| [[Methylamine]] (MeNH<sub>2</sub>)
| 10.62
| {{val|4.17e-4}}
|-
| [[Dimethylamine]] (Me<sub>2</sub>NH)
| 10.64
| {{val|4.37e-4}}
|-
| [[Trimethylamine]] (Me<sub>3</sub>N)
| {{pad|0.3em}}9.76
| {{val|5.75e-5}}
|-
| [[Ethylamine]] (EtNH<sub>2</sub>)
| 10.63
| {{val|4.27e-4}}
|-
| [[Aniline]] (PhNH<sub>2</sub>)
| {{pad|0.3em}}4.62
| {{val|4.17e-10}}
|-
| [[p-Anisidine|4-Methoxyaniline]] (4-MeOC<sub>6</sub>H<sub>4</sub>NH<sub>2</sub>)
| {{pad|0.3em}}5.36
| {{val|2.29e-9}}
|-
| [[Dimethylaniline|''N'',''N''-Dimethylaniline]] (PhNMe<sub>2</sub>)
| {{pad|0.3em}}5.07
| {{val|1.17e-9}}
|-
| [[3-Nitroaniline]] (3-NO<sub>2</sub>-C<sub>6</sub>H<sub>4</sub>NH<sub>2</sub>)
| {{pad|0.3em}}2.46
| {{val|2.88e-12}}
|-
| [[4-Nitroaniline]] (4-NO<sub>2</sub>-C<sub>6</sub>H<sub>4</sub>NH<sub>2</sub>)
| {{pad|0.3em}}1.00
| {{val|1.00e-13}}
|-
| 4-Trifluoromethylaniline (CF<sub>3</sub>C<sub>6</sub>H<sub>4</sub>NH<sub>2</sub>)
| {{pad|0.3em}}2.75
| {{val|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 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 10<sup>11</sup> 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 pK<sub>b</sub>'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.<ref>{{March6th}}</ref>

In aprotic polar solvents such as [[Dimethyl sulfoxide|DMSO]], [[Dimethylformamide|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 ==
<!-- This section is linked from [[Organic reaction]] -->

===From alcohols===
Industrially significant alkyl amines are prepared from ammonia by [[alkylation]] with alcohols:<ref name=Ullmann/>
:<chem>ROH + NH3 -> RNH2 + H2O</chem>

===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:
:<chem>RX + 2 R'NH2 -> RR'NH + [RR'NH2]X</chem>
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.<ref name=Ullmann>{{Ullmann|doi=10.1002/14356007.a02_001|title=Amines, Aliphatic|year=2000|last1= Eller|first1=Karsten|last2=Henkes|first2=Erhard|last3=Rossbacher|first3=Roland|last4=Höke|first4=Hartmut|isbn=3527306730}}</ref>

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|''tert''-octylamine]].<ref name=Ullmann/>

Hydroamination of alkenes is also widely practiced.  The reaction is catalyzed by zeolite-based [[solid acid]]s.<ref name=Ullmann/>

===Reductive routes===
Via the process of [[hydrogenation]], unsaturated N-containing functional groups are reduced to amines using hydrogen in the presence of a nickel catalyst. Suitable groups include [[nitrile]]s, [[organic azide|azide]]s, [[imine]]s including [[oxime]]s, amides, and [[Nitro compound|nitro]]. In the case of nitriles, reactions are sensitive to acidic or alkaline conditions, which can cause hydrolysis of the {{chem2|\sCN}} group. [[Lithium aluminium hydride|{{chem2|LiAlH4}}]] 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]], which can either proceed catalytically or stoichiometrically.

[[Aniline]] ({{chem2|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.

===Specialized methods===
Many methods exist for the preparation of amines, many of these methods being rather specialized.
{| class="wikitable sortable" style="background:white; float:center; margin:0 1em;"
|-
! style="width:200px;"|Reaction name !! Substrate !! class="unsortable" | Comment
|-
|valign=top| [[Staudinger reduction]]
|[[Organic azide]]
| This reaction also takes place with a reducing agent such as [[lithium aluminium hydride]].
|-
|valign=top| [[Schmidt reaction]]
|valign=top|[[Carboxylic acid]]
|
|-
|valign=top| [[Aza-Baylis–Hillman reaction]]
|valign=top|[[Imine]]
| Synthesis of allylic amines
|-
|valign=top| [[Birch reduction]]
|valign=top| [[Imine]]
| Useful for reactions that trap unstable imine intermediates, such as [[Grignard reaction]]s with [[nitrile]]s.<ref>{{cite journal|last1=Weiberth|first1=Franz J.|last2=Hall|first2=Stan S.|title=Tandem alkylation-reduction of nitriles. Synthesis of branched primary amines|journal=Journal of Organic Chemistry|date=1986|volume=51|issue=26|pages=5338–5341|doi=10.1021/jo00376a053}}</ref>
|-
|valign=top| [[Hofmann rearrangement|Hofmann degradation]]
|valign=top|[[Amide]]
| This reaction is valid for preparation of primary amines only. Gives good yields of primary amines uncontaminated with other amines.
|-
|valign=top| [[Hofmann elimination]]
|valign=top| [[Quaternary ammonium salt]]
|Upon treatment with strong base
|-
|valign=top| [[Leuckart reaction]]
|valign=top| [[Ketone]]s and [[aldehyde]]s
| [[Reductive amination]] with [[formic acid]] and [[ammonia]] via an [[imine]] intermediate
|-
|valign=top| [[Hofmann–Löffler reaction]]
|valign=top| [[Haloamine]]
|
|-
|valign=top| [[Eschweiler–Clarke reaction]]
|valign=top| Amine
| [[Reductive amination]] with [[formic acid]] and [[formaldehyde]] via an [[imine]] intermediate
|}

==Reactions==

===Alkylation, acylation, and sulfonation, etc.===
Aside from their basicity, the dominant reactivity of amines is their [[nucleophilicity]].<ref>{{March4th}}</ref> Most primary amines are good [[ligand]]s for metal ions to give [[coordination complex]]es. Amines are alkylated by alkyl halides. [[Acyl chloride]]s and [[Organic acid anhydride|acid anhydride]]s react with primary and secondary amines to form [[amide]]s (the "[[Schotten–Baumann reaction]]").
[[File:Amide formation from amine.svg|center|Amide formation]]
Similarly, with sulfonyl chlorides, one obtains [[sulfonamide]]s. This transformation, known as the [[Hinsberg reaction]], is a chemical test for the presence of amines.

Because amines are basic, they neutralize [[acid]]s to form the corresponding [[ammonium salt]]s {{chem2|R3NH+}}. When formed from carboxylic acids and primary and secondary amines, these salts thermally dehydrate to form the corresponding [[amide]]s.
:<math chem="" title="Amine reaction with carboxylic acids">
{
  \underbrace\ce{H-\!\!\overset{\displaystyle R1 \atop |}{\underset{| \atop \displaystyle R2}N}\!\!\!\!:}_\text{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{->[\text{heat}][\text{dehydration}]}{
  \underbrace\ce{\overset{\displaystyle R1 \atop |}{\underset{| \atop \displaystyle R2}N}\!\!-\overset{\displaystyle O \atop \|}C-R3}_\text{amide} +
  \underbrace\ce{H2O}_\text{water}
}</math>

Amines undergo [[sulfamation]] upon treatment with [[sulfur trioxide]] or sources thereof: 
:<chem>R2NH  +  SO3  -> R2NSO3H</chem>

===Diazotization===
Amines reacts with [[nitrous 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 as [[aniline]] ("phenylamine") (A = aryl or naphthyl):
:<chem>ANH2 + HNO2 + HX -> AN2+ + X- + 2 H2O</chem>

Anilines and naphthylamines form more stable [[diazonium]] salts, which can be isolated in the crystalline form.<ref>{{OrgSynth | title = β-Naphthylmercuric chloride | author = [[Alexander Nesmeyanov|A. N. Nesmajanow]] | collvol = 2 | collvolpages = 432 | year = 1943 | prep = cv2p0432}}</ref> Diazonium salts undergo a variety of useful transformations involving replacement of the {{chem2|N2}} group with anions. For example, [[Copper(I) cyanide|cuprous cyanide]] gives the corresponding nitriles:

:<chem>AN2+ + Y- -> AY + N2</chem>

Aryldiazoniums couple with electron-rich aromatic compounds such as a [[phenol]] to form [[azo compound]]s. Such reactions are widely applied to the production of dyes.<ref>{{Cite book|doi=10.1002/14356007.a03_245|chapter=Azo Dyes|title=Ullmann's Encyclopedia of Industrial Chemistry|year=2000|last1=Hunger|first1=Klaus|last2=Mischke|first2=Peter|last3=Rieper|first3=Wolfgang|last4=Raue|first4=Roderich|last5=Kunde|first5=Klaus|last6=Engel|first6=Aloys|isbn=3527306730}}</ref>

===Conversion to imines===
[[Alkylimino-de-oxo-bisubstitution|Imine formation]] is an important reaction. Primary amines react with [[ketone]]s and [[aldehyde]]s to form [[imine]]s. In the case of [[formaldehyde]] (R'&nbsp;{{=}}&nbsp;H), these products typically exist as cyclic [[trimer (chemistry)|trimers]]: <chem display=block>RNH2 + R'_2C=O -> R'_2C=NR + H2O</chem> Reduction of these imines gives secondary amines: <chem display=block>R'_2C=NR + H2 -> R'_2CH-NHR</chem>

Similarly, secondary amines react with ketones and aldehydes to form [[enamine]]s: <chem display=block> R2NH + R'(R''CH2)C=O -> R''CH=C(NR2)R' + H2O</chem>

[[Mercuric]] ions reversibly oxidize [[tertiary amine]]s with an [[locant|&alpha;]] hydrogen to [[iminium]] ions:<ref>{{cite book|title=Nitrosation|first=D.&nbsp;L.&nbsp;H.|last=Williams|publisher=[[Cambridge University Press|Cambridge University]]|location=Cambridge, UK|year=1988|isbn=0-521-26796-X|url=https://archive.org/details/nitrosation0000will|url-access=registration|page=195}}</ref> <chem display=block>Hg^2+ + R2NCH2R' <=> Hg + [R2N=CHR']+ + H+</chem>

===Overview===
An overview of the reactions of amines is given below:
{| class="wikitable sortable" style="background:white; float:center; margin:0 1em;"
|-
! style="width:200px;"|Reaction name !! Reaction product !! class="unsortable" | Comment
|-
|valign=top | [[Amine alkylation]]
|valign=top|Amines
| Degree of substitution increases
|-
|valign=top | [[Schotten–Baumann reaction]]
|valign=top|[[Amide]]
| Reagents: [[acyl chloride]]s, [[acid anhydride]]s
|-
|valign=top | [[Hinsberg reaction]]
|valign=top|[[Sulfonamide]]s
| Reagents: [[sulfonyl chloride]]s
|-
|valign=top | [[Amine-carbonyl condensation|Amine–carbonyl condensation]]
|valign=top|[[Imines]]
|-
|valign=top | [[Organic oxidation]]
|valign=top|[[Nitroso]] compounds
| Reagent: [[peroxymonosulfuric acid]]
|-
|valign=top | [[Organic oxidation]]
|valign=top| [[Diazonium salt]]
| Reagent: [[nitrous acid]]
|-
|valign=top| [[Zincke reaction]]
|[[Zincke aldehyde]]
| Reagent: [[pyridinium]] salts, with primary and secondary amines
|-
|valign=top| [[Emde degradation]]
|valign=top|[[Tertiary amine]]
| Reduction of [[quaternary ammonium cation]]s
|-
|valign=top| [[Hofmann–Martius rearrangement]]
|valign=top|Aryl-substituted [[aniline]]s
|-
|valign=top| [[von Braun reaction]]
|valign=top| [[Nitrile#Organic cyanamides|Organic cyanamide]]
|By cleavage (tertiary amines only) with cyanogen bromide
|-
|valign=top| [[Hofmann elimination]]
|valign=top| [[Alkene]]
|Proceeds by β-elimination of less hindered carbon
|-
|valign=top| [[Cope reaction]]
|valign=top| [[Alkene]]
|Similar to [[Hofmann elimination]]
|-
|valign=top| [[Carbylamine reaction]]
|valign=top| [[Isonitrile]]
|Primary amines only
|-
|valign=top| Hofmann's mustard oil test
|valign=top| [[Isothiocyanate]]
|[[Carbon disulfide]] {{chem2|CS2}} and [[mercury(II) chloride]] {{chem2|HgCl2}} are used. Thiocyanate smells like mustard.
|}

==Biological activity==
Amines are ubiquitous in biology. The breakdown of [[amino acid]]s releases amines, famously in the case of decaying fish which smell of [[trimethylamine]]. Many [[neurotransmitter]]s are amines, including [[epinephrine]], [[norepinephrine]], [[dopamine]], [[serotonin]], and [[histamine]]. [[Protonated]] [[amino group]]s ({{chem|–NH|3|+}}) are the most common positively charged moieties in [[protein]]s, specifically in the amino acid [[lysine]].<ref>{{Cite journal|doi=10.1006/jmbi.1997.1498|title=Adaptation of protein surfaces to subcellular location|year=1998|last1=Andrade|first1=Miguel A.|last2=O'Donoghue|first2=Seán I.|last3=Rost|first3=Burkhard|journal=Journal of Molecular Biology|volume=276|issue=2|pages=517–25|pmid=9512720|citeseerx=10.1.1.32.3499}}</ref> The anionic polymer [[DNA]] is typically bound to various amine-rich proteins.<ref>{{Cite book|last1= Nelson|first1= D. L.|last2= Cox|first2= M. M.|title= Lehninger, Principles of Biochemistry|edition= 3rd|publisher= Worth Publishing|location= New York|year= 2000|isbn= 1-57259-153-6|url-access= registration|url= https://archive.org/details/lehningerprincip01lehn}}</ref> Additionally, the terminal charged primary ammonium on lysine forms [[Salt bridge (protein and supramolecular)|salt bridges]] with [[carboxylate]] groups of other amino acids in [[polypeptide]]s, which is one of the primary influences on the three-dimensional structures of proteins.<ref>{{Cite journal|doi=10.1021/bi00483a001|title=Dominant forces in protein folding|year=1990|last1=Dill|first1=Ken A.|journal=Biochemistry|volume=29|issue=31|pages=7133–55|pmid=2207096|s2cid=30690389 }}</ref>

===Amine hormones===
[[Hormone]]s 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 {{chem|–NH|3|+}}, or amine, group remains. Amine hormones are synthesized from the amino acids [[tryptophan]] or [[tyrosine]].<ref name="Openstax Anatomy & Physiology attribution">{{CC-notice|cc=by4|url=https://openstax.org/books/anatomy-and-physiology/pages/17-2-hormones}} {{cite book|last1=Betts|first1=J Gordon|last2=Desaix|first2=Peter|last3=Johnson|first3=Eddie|last4=Johnson|first4=Jody E|last5=Korol|first5=Oksana|last6=Kruse|first6=Dean|last7=Poe|first7=Brandon|last8=Wise|first8=James|last9=Womble|first9=Mark D|last10=Young|first10=Kelly A|title=Anatomy & Physiology|location=Houston|publisher=OpenStax CNX|isbn=978-1-947172-04-3|date=July 26, 2023|at=17.2 Hormones}}</ref>

==Application of amines==

===Dyes===
Primary aromatic amines are used as a starting material for the manufacture of [[azo dye]]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]]
* Direct brown 138
* [[Sunset yellow]] FCF
* [[Ponceau 4R|Ponceau]]

===Drugs===
Most drugs and drug candidates contain amine functional groups:<ref>{{cite journal |doi=10.1021/jm200187y|title=The Medicinal Chemist's Toolbox: An Analysis of Reactions Used in the Pursuit of Drug Candidates|year=2011|last1=Roughley|first1=Stephen D.|last2=Jordan|first2=Allan M.|journal=Journal of Medicinal Chemistry|volume=54|issue=10|pages=3451–3479|pmid=21504168}}</ref>
* [[Chlorpheniramine]] is an [[antihistamine]] that helps to relieve allergic disorders due to cold, hay fever, itchy skin, insect bites and stings.
* [[Chlorpromazine]] is a tranquilizer that sedates without inducing sleep. It is used to relieve anxiety, excitement, restlessness or even mental disorder.
* [[Ephedrine]] and [[phenylephrine]], as amine hydrochlorides, are used as decongestants.
* [[Amphetamine]], [[methamphetamine]], and [[methcathinone]] are psychostimulant amines that are listed as controlled substances by the US [[Drug Enforcement Administration|DEA]].
* [[Thioridazine]], an antipsychotic drug, is an amine which is believed to exhibit its antipsychotic effects, in part, due to its effects on other amines.<ref>American Society of Health System Pharmacists; AHFS Drug Information 2010. Bethesda, MD. (2010), p. 2510</ref>
* [[Amitriptyline]], [[imipramine]], [[lofepramine]] and [[clomipramine]] are [[tricyclic antidepressant]]s and tertiary amines.
* [[Nortriptyline]], [[desipramine]], and [[amoxapine]] are [[tricyclic antidepressants]] and secondary amines. (The tricyclics are grouped by the nature of the final amino group on the side chain.)
* [[Substituted tryptamine]]s and [[substituted phenethylamine|phenethylamine]]s are key basic structures for a large variety of [[psychedelic drug]]s.
* [[Opiate]] [[analgesic]]s such as [[morphine]], [[codeine]], and [[heroin]] are [[Tertiary (chemistry)|tertiary]] amines.

===Gas treatment===
Aqueous [[monoethanolamine]] (MEA), [[diglycolamine]] (DGA), [[diethanolamine]] (DEA), [[diisopropanolamine]] (DIPA) and [[N-methyl-diethanolamine|methyldiethanolamine]] (MDEA) are widely used industrially for removing [[carbon dioxide]] (CO<sub>2</sub>) and [[hydrogen sulfide]] (H<sub>2</sub>S) from natural gas and refinery process streams. They may also be used to remove CO<sub>2</sub> from combustion gases and [[flue gas]]es and may have potential for abatement of [[greenhouse gas]]es. Related processes are known as [[Amine gas treating|sweetening]].<ref>{{Cite book|doi=10.1002/14356007.a17_073|chapter=Natural Gas|title=Ullmann's Encyclopedia of Industrial Chemistry|year=2000|last1=Hammer|first1=Georg|last2=Lübcke|first2=Torsten|last3=Kettner|first3=Roland|last4=Davis|first4=Robert N.|last5=Recknagel|first5=Herta|last6=Commichau|first6=Axel|last7=Neumann|first7=Hans-Joachim|last8=Paczynska-Lahme|first8=Barbara|isbn=3527306730}}</ref>

===Epoxy resin curing agents===
Amines are often used as epoxy resin curing agents.<ref>{{Cite web |title=amine curing agent: Topics by Science.gov |url=https://www.science.gov/topicpages/a/amine+curing+agent |access-date=2022-03-01 |website=science.gov |language=en}}</ref><ref>{{Cite journal|last=Howarth|first=Graham|title=The use of water-based epoxies for anti-corrosive primers|journal=Pigment & Resin Technology|volume=24|issue=6|pages=3–6|date=1995-01-01|doi=10.1108/eb043156|issn=0369-9420}}</ref> These include [[dimethylethylamine]], [[cyclohexylamine]], and a variety of diamines such as 4,4-diaminodicyclohexylmethane.<ref name=Ullmann/> Multifunctional amines such as [[tetraethylenepentamine]] and [[triethylenetetramine]] are also widely used in this capacity.<ref>{{cite encyclopedia | vauthors = Eller K, Henkes E, Rossbacher R, Höke H | chapter = Amines, Aliphatic | encyclopedia = Ullmann's Encyclopedia of Industrial Chemistry | year = 2005 | publisher = Wiley-VCH | location = Weinheim | doi = 10.1002/14356007.a02_001 |isbn=3527306730 }}</ref> 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.<ref>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</ref> Molecules with tertiary amine functionality are often used to accelerate the epoxy-amine curing reaction and include substances such as [[2,4,6-Tris(dimethylaminomethyl)phenol]]. It has been stated that this is the most widely used room temperature accelerator for two-component epoxy resin systems.<ref>{{Cite journal |last1=Seo |first1=Jiae |last2=Yui |first2=Nobuhiko |last3=Seo |first3=Ji-Hun |date=January 2019 |title=Development of a supramolecular accelerator simultaneously to increase the cross-linking density and ductility of an epoxy resin |url=https://doi.org/10.1016/j.cej.2018.09.020 |journal=Chemical Engineering Journal |volume=356 |pages=303–311 |doi=10.1016/j.cej.2018.09.020 |bibcode=2019ChEnJ.356..303S |issn=1385-8947}}</ref><ref>{{Cite journal |last1=Chen |first1=Fengjun |last2=Liu |first2=Fan |last3=Du |first3=Xiaogang |date=2023-01-10 |title=Molecular dynamics simulation of crosslinking process and mechanical properties of epoxy under the accelerator |url=https://onlinelibrary.wiley.com/doi/10.1002/app.53302 |journal=Journal of Applied Polymer Science |language=en |volume=140 |issue=2 |doi=10.1002/app.53302 |issn=0021-8995}}</ref>

==Safety==
Low molecular weight simple amines, such as [[ethylamine]], are toxic with {{LD50}} between 100 and 1000&nbsp;mg/kg. They are skin irritants, especially as some are easily absorbed through the skin.<ref name=Ullmann/> Amines are a broad class of compounds, and more complex members of the class can be extremely bioactive, for example [[strychnine]].

==See also==
* [[Acid–base extraction]]
* [[Amine value]]
* [[Amine gas treating]]
* [[Ammine]]
* [[Biogenic amine]]
* [[Ligand isomerism]]
* [[IUPAC nomenclature of organic chemistry#Amines|Official naming rules for amines]] as determined by the International Union of Pure and Applied Chemistry ([[IUPAC]])

==References==
{{Reflist}}

== Further reading ==
* {{Cite web|title=Amines {{!}} Introduction to Chemistry|url=https://courses.lumenlearning.com/introchem/chapter/amines/#:~:text=The%20amine%20functional%20group%20contains,by%20a%20carbon-containing%20substituent.&text=Amine%20groups%20bonded%20to%20an,are%20known%20as%20aromatic%20amines.|access-date=2021-07-22|website=courses.lumenlearning.com}}
* {{Cite book|last=Flick|first=Ernest W.|url=https://www.worldcat.org/oclc/915134542|title=Epoxy Resins, Curing Agents, Compounds, and Modifiers: An Industrial Guide |publisher=Noyes Publications |date=1993|isbn=978-0-8155-1708-5|location=Park Ridge, NJ|oclc=915134542}}

==External links==
{{wikiquote}}
* [https://www.organic-chemistry.org/synthesis/C1N/amines/primaryamines.shtm Synthesis of amines]
* [http://www.millhousemedical.co.nz/files/docs/factsheet_7_amines_in_foods.pdf Factsheet, amines in food] {{Webarchive|url=https://web.archive.org/web/20180219074057/http://www.millhousemedical.co.nz/files/docs/factsheet_7_amines_in_foods.pdf |date=19 February 2018 }}

{{Functional group}}
{{nitrogen compounds}}
{{Authority control}}

[[Category:Amines| ]]
[[Category:Functional groups]]