Benzylamine: Difference between revisions

| = changed

|Watchedfields = changed

|verifiedrevid = 443418509

| = Benzylamine

|ImageFile = Benzylamine2DCSD.svg

|ImageSize = 160

|ImageAlt = Skeletal formula of benzylamine

|ImageFile1 = Benzylamine-from-xtal-3D-bs-17.png

|ImageSize1 = 150

|ImageAlt1 = Space-filling model of the benzylamine molecule

|PIN = Phenylmethanamine

|OtherNames = α-Aminotoluene<br>Benzyl amine<br>Phenylmethylamine

|Section1={{Chembox Identifiers

|DrugBank_Ref = {{drugbankcite|correct|drugbank}}

|DrugBank = DB02464

|UNII_Ref = {{fdacite|correct|FDA}}

|UNII = A1O31ROR09

|ChEBI_Ref = {{ebicite|correct|EBI}}

|ChEBI = 40538

|SMILES = c1ccc(cc1)CN

| = {{|correct|chemspider}}

|ChemSpiderID = 7223

| = {{|correct|}}

|ChEMBL = 522

| = {{|correct|}}

| =

|InChI = 1/C7H9N/c8-6-7-4-2-1-3-5-7/h1-5H,6,8H2

|InChIKey = WGQKYBSKWIADBV-UHFFFAOYAL

|StdInChI_Ref = {{stdinchicite|correct|chemspider}}

|StdInChI = 1S/C7H9N/c8-6-7-4-2-1-3-5-7/h1-5H,6,8H2

|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

|StdInChIKey = WGQKYBSKWIADBV-UHFFFAOYSA-N

|CASNo_Ref = {{cascite|correct|CAS}}

|CASNo = 100-46-9

|RTECS = DP1488500

|PubChem = 7504

|EC_number = 202-854-1

|UNNumber = 2735

| =

|Beilstein = 741984

}}

|Section2={{Chembox Properties

|C=7 | H=9 | N=1

|Appearance = Colorless liquid

|Odor = weak, [[ammonia]]-like

|Solubility = Miscible<ref name=GESTIS>{{GESTIS|ZVG=16550}}</ref>

|SolubleOther = miscible in [[ethanol]], [[diethyl ether]] <br> very soluble in [[acetone]] <br> soluble in [[benzene]], [[chloroform]]

|Density = 0.981 g/mL<ref name=Aldrich>{{cite web|url = http://www.sigmaaldrich.com/catalog/product/sial/13180?lang=en|title = Benzylamine|publisher = [[Sigma-Aldrich]]|access-date = 28 December 2015}}</ref>

| =

|MeltingPt_ref = <ref name=GESTIS/>

|BoilingPtC = 185

| = <ref name=GESTIS/>

|pKa = 9.34<ref>{{cite journal | author = Hall, H. K. | journal = [[J. Am. Chem. Soc.]] | year = 1957 | volume = 79 | pages = 5441–5444 | doi = 10.1021/ja01577a030 | issue = 20 | title = Correlation of the Base Strengths of Amines}}</ref>

|pKb = 4.66

|RefractIndex = 1.543

|MagSus = -75.26·10⁻⁶ cm³/mol

}}

|Section3={{Chembox Structure

|Dipole = 1.38 [[Debye|D]]

}}

|Section4={{Chembox Hazards

|ExternalSDS = [https://fscimage.fishersci.com/msds/97226.htm Fischer Scientific]

|MainHazards = Flammable and corrosive

|NFPA-H = 3

|NFPA-F = 2

|NFPA-R = 0

|FlashPtC =65

|FlashPt_ref = <ref name=GESTIS/><ref name=Aldrich/>

|GHSPictograms = {{GHS05}}{{GHS07}}

|GHSSignalWord = Danger

|HPhrases = {{H-phrases|302|312|314}}

|PPhrases = {{P-phrases|260|264|270|280|301+312|301+330+331|302+352|303+361+353|304+340|305+351+338|310|312|321|322|330|363|405|501}}

}}

|Section5={{Chembox Related

|OtherFunction_label = [[amine]]s

|OtherFunction = [[aniline]]

}}

'''Benzylamine''' is [[chemical compound]] with the [[ formula|formula]] C₆H₅CH₂NH₂. It consists of a [[benzyl]] group, C₆H₅CH₂ attached to an amine [[functional group]]. This colorless liquid is a common precursor in [[organic ]].

==Manufacturing==

Benzylamine can be produced by several methods, the main industrial route being the reaction of [[benzyl chloride]] and [[ammonia]]. It is also produced by the reduction of [[benzonitrile]] and [[reductive amination]] of [[benzaldehyde]], both done over [[Raney nickel]].<ref name=Ullmann>{{cite book |last= Heuer |first= L. |date= 2006|chapter= Benzylamines |title= Ullmann's Encyclopedia of Industrial Chemistry |publisher= [[Wiley-VCH]] |doi= 10.1002/14356007.a04_009.pub2 |isbn= 3527306730 }}</ref>

It was first produced accidentally by [[Rudolf Leuckart]] in the reaction of benzaldehyde with [[formamide]] in a process now known as the [[Leuckart reaction]],<ref>{{cite journal|last1 = Crossley|first1 = F. S.|first2 = M. L.|last2 = Moore|title = Studies on the Leuckart Reaction|journal = [[J. Org. Chem.]]|year = 1944|volume = 9|issue = 6|pages = 529–536|doi = 10.1021/jo01188a006}}</ref> a general process in which reductive amination of [[aldehyde]]s or [[ketone]]s yields the corresponding [[amine]].<ref>{{cite journal|last1 = Webers|first1 = V. J.|last2 = Bruce|first2 = W. F.|title = The Leuckart Reaction: A study of the Mechanism|journal = [[J. Am. Chem. Soc.]]|year = 1948|volume = 70|issue = 4|pages = 1422–1424|doi = 10.1021/ja01184a038|pmid = 18915755}}</ref><ref>{{cite journal|last1 = Pollard|first1 = C. B.|last2 = Young|first2 = D. C.|title = The Mechanism of the Leuckart Reaction|journal = [[J. Org. Chem.]]|year = 1951|volume = 16|issue = 5|pages = 661–672|doi = 10.1021/jo01145a001}}</ref>

==Biochemistry==

Benzylamine occurs biologically from the action of the [[N-substituted formamide deformylase|''N''-substituted formamide deformylase]] enzyme, which is produced by ''[[Arthrobacter pascens]]'' bacteria.<ref>{{cite book|chapter-url = https://books.google.com/books?id=hN38HsVK5HgC&q=benzylformamide&pg=PA376|chapter = 3.5.1.91 ''N''-substituted formamide deformylase|pages = 376–378|title = Class 3 Hydrolases: EC 3.4.22–3.13|series = Springer Handbook of Enzymes|editor1-first = D.|editor1-last = Schomburg|editor2-first = I.|editor2-last = Schomburg|editor3-last = Chang|editor3-first = A.|edition = 2nd|publisher = [[Springer Science & Business Media]]|year = 2009|isbn = 9783540857051}}</ref> This [[hydrolase]] catalyses the conversion of [[N-benzylformamide|''N''-benzylformamide]] into benzylamine with [[formate]] as a by-product.<ref>{{cite journal|last1 = Fukatsu|first1 = H.|last2 = Hashimoto|first2 = Y.|last3 = Goda|first3 = M.|last4 = Higashibata|first4 = H.|last5 = Kobayashi|first5 = M.|year = 2004|title = Amine-synthesizing enzyme ''N''-substituted formamide deformylase: screening, purification, characterization, and gene cloning|journal = [[Proc. Natl. Acad. Sci.]]|volume = 101|pages = 13726–13731|pmid = 15358859|doi = 10.1073/pnas.0405082101|issue = 38|pmc=518824|bibcode = 2004PNAS..10113726F|doi-access = free}}</ref> Benzylamine is degraded biologically by the action of the [[monoamine oxidase B]] [[enzyme]],<ref>{{cite web|title = MAOB: Monoamine oxidase B – Homo sapiens|url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=4129|publisher = [[National Center for Biotechnology Information]]|access-date = 29 December 2015|date = 6 December 2015}}</ref> resulting in benzaldehyde.<ref>{{cite journal|last1 = Tipton|first1 = K. F.|last2 = Boyce|first2 = S.|last3 = O'Sullivan|first3 = J.|last4 = Davey|first4 = G. P.|last5 = Healy|first5 = J.|year = 2004|title = Monoamine oxidases: Certainties and uncertainties|journal = [[Curr. Med. Chem.]]|volume = 11|issue = 15|pages = 1965–1982|doi = 10.2174/0929867043364810|pmid = 15279561}}</ref>

==Uses==

Benzylamine is used as a masked source of [[ammonia]], since after ''N''-[[alkylation]], the benzyl group can be removed by [[hydrogenolysis]]:<ref>{{OrgSynth | author = Gatto, V. J. |author2=Miller, S. R. |author3=Gokel, G. W. | title = 4,13-Diaza-18-Crown-6 | collvol = 8 | collvolpages = 152 | year = 1993 | prep = cv8p0152}} (example of alklylation of benzylamine followed by hydrogenolysis).</ref>

Benzylamine reacts with [[acetyl chloride]] to form ''N''-benzylacetamide.

Isoquinolines can be prepared from benzylamine and [[glyoxal]] [[acetal]] by an analogous approach known as the Schlittler-Müller modification to the Pomeranz–Fritsch reaction. This modification can also be used for preparing substituted isoquinolines.<ref>{{cite book|last = Li|first = J. J.|title = Name Reactions: A Collection of Detailed Mechanisms and Synthetic Applications|year = 2014|chapter = Schlittler–Müller modification|publisher = [[Springer Science+Business Media|Springer]]|isbn = 9783319039794|pages = 492|edition = 5th|url = https://books.google.com/books?id=HoXBBAAAQBAJ&q=Name+reactions:+A+collection+of+detailed+reaction+mechanisms}}</ref>

:[[File:Synthesis CL20.svg|left|thumb|upright=1.33|Synthesis of HNIW from benzylamine]]

Benzylamine is used in the manufacture of other pharmaceuticals, including [[alniditan]],<ref>{{Cite journal|title = The discovery of a series of new non-indole 5HT_1D agonists|year = 1995|last1 = Lommen| first1 = G.|last2 = De Bruyn|first2 = M.|last3 = Schroven|first3 = M.|last4 = Verschueren|first4 = W.|last5 = Janssens|first5 = W.|last6 = Verrelst|first6 = J.|last7 = Leysen|first7 = J.|journal = [[Bioorg. Med. Chem. Lett.]]|volume = 5|issue = 22|pages = 2649–2654|doi = 10.1016/0960-894X(95)00473-7}}</ref> [[lacosamide]],<ref>{{cite journal|last1 = Choi|first1 = D.|last2 = Stables|first2 = J. P.|last3 = Kohn|first3 = H.|title = Synthesis and anticonvulsant activities of ''N''-Benzyl-2-acetamidopropionamide derivatives|journal = [[J. Med. Chem.]]|year = 1996|volume = 39|issue = 9|pages = 1907–1916|pmid = 8627614|doi = 10.1021/jm9508705}}</ref><ref>{{cite journal|last1 = Morieux|first1 = P.|last2 = Stables|first2 = J. P.|last3 = Kohn|first3 = H.|title = Synthesis and anticonvulsant activities of ''N''-benzyl-(2''R'')-2-acetamido-3-oxysubstituted propionamide derivatives|journal = [[Bioorg. Med. Chem.]]|year = 2008|volume = 16|issue = 19|pages = 8968–8975|pmid = 18789868|doi = 10.1016/j.bmc.2008.08.055|pmc = 2701728}}</ref> [[moxifloxacin]],<ref>{{cite book|chapter-url = https://books.google.com/books?id=FjKfqkaKkAAC&q=discovery+benzylamine&pg=PA338|pages = 338–342|chapter = Quinolone Antibiotics: The Development of Moxifloxacin|title = Analogue-based Drug Discovery|editor1 = IUPAC|editor-link = IUPAC|editor2-first = J.|editor2-last = Fischer|editor3-first = C. R.|editor3-last = Ganellin|publisher = [[John Wiley & Sons]]|isbn = 9783527607495|year = 2006|first = U.|last = Peterson}}</ref> and [[nebivolol]].<ref>{{cite patent|country = US|number = 4654362|status = patent|title = Derivatives of 2,2'-iminobisethanol|pubdate = 1987-03-31|fdate = 1984-10-12|pridate = 1983-12-05|invent1 = Van Lommen, G. R. E.|invent2 = De Bruyn, M. F. L.|invent3 = Schroven, M. F. J.|assign1 = [[Janssen Pharmaceutica|Janssen Pharmaceutica, N.V.]]|class = <!-- ECLA classification -->}}. {{US patent|4654362|Full text}}</ref>

Benzylamine is also used to manufacture the military explosive [[hexanitrohexaazaisowurtzitane]] (HNIW), which is superior to older [[nitroamine]] [[high explosive]]s like [[HMX]] and [[RDX]]. Illustrating the debenzylation tendency of benzylamines, four of the benzyl groups are removed from hexabenzylhexaazaisowurtzitane by hydrogenolysis catalysed by [[palladium on carbon]].<ref name = HNIW>{{cite journal|journal = [[Combust. Explos. Shock Waves]]|year = 2005|volume = 41|issue = 2|pages = 121–132|title = Hexanitrohexaazaisowurtzitane (CL-20) and CL-20-based formulations (review)|first1 = U. R.|last1 = Nair|first2 = R.|last2 = Sivabalan|first3 = G. M.|last3 = Gore|first4 = M.|last4 = Geetha|first5 = S. N.|last5 = Asthana|first6 = H.|last6 = Singh|doi = 10.1007/s10573-005-0014-2|s2cid = 95545484}}</ref>

==Salts==

The [[hydrochloride]] [[salt (chemistry)|salt]] of benzylamine, C₆H₅CH₂NH₃Cl or C₆H₅CH₂NH₂·HCl,<ref>{{cite web|url = http://www.sigmaaldrich.com/catalog/product/aldrich/b5136?lang=en|title = Benzylamine hydrochloride|publisher = [[Sigma-Aldrich]]|access-date = 28 December 2015}}</ref> is prepared by reacting benzylamine with [[hydrochloric acid]], and can be used in treating [[motion sickness]]. [[NASA]] astronaut [[John Glenn]] was issued with benzylamine hydrochloride for this purpose for the [[Mercury-Atlas 6]] mission.<ref>{{cite book|chapter-url = https://history.nasa.gov/SP-4201/ch13-2.htm|title = This New Ocean: A History of Project Mercury|last1 = Swenson|first1 = L. S.|first2 = J. M.|last2 = Grimwood|first3 = C. C.|last3 = Alexander|chapter = 13: Mercury Mission Accomplished (13.1 Preparing a Man to Orbit)|pages = 413–418|publisher = [[NASA|nasa.gov]]}}</ref> The cation in this salt is called benzylammonium and is a moiety found in pharmaceuticals such as the [[anthelmintic]] agent [[bephenium hydroxynaphthoate]], used in treating [[ascariasis]].<ref>{{cite book|chapter-url = https://books.google.com/books?id=DYc7bY-egLEC&q=Bephenium&pg=PA35|pages = 33–35|title = Handbook of Drugs for Tropical Parasitic Infections|first1 = U.|last1 = Hellgren|first2 = Ö.|last2 = Ericsson|first3 = Y.|last3 = Aden Abdi|first4 = L. L.|last4 = Gustafsson|chapter = Bephenium hydroxynaphthoate|edition = 2nd|year = 2003|publisher = [[CRC Press]]|isbn = 9780203211519}}</ref>

Other derivatives of benzylamine and its salts have been shown to have [[anti-emetic]] properties, including those with the ''N''-(3,4,5-trimethoxybenzoyl)benzylamine moiety.<ref>{{cite patent|country = US|number = 2879293|status = patent|title = Benzylamine derivatives|pubdate = 1959-03-24|gdate = 1959-03-24|fdate = 1957-02-19|pridate = 1957-02-19|invent1 = Sidney, T.|invent2 = [[Moses Wolf Goldberg|Goldberg, M. W.]]|assign1 = [[Hoffmann La Roche]]|class = <!-- ECLA classification -->}}. {{US patent|2879293|Full text}}</ref> Commercially available motion-sickness agents including [[cinnarizine]] and [[meclizine]] are derivatives of benzylamine.

==Other benzylamines==

[[1-Phenylethylamine]] is a [[methylated]] benzylamine derivative that is [[chiral]]; [[enantiopure]] forms are obtained by [[chiral resolution|resolving]] [[racemic mixture|racemates]]. Its racemic form is sometimes known as (±)-α-methylbenzylamine.<ref>{{cite web|url = https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=7408|title = 1-Phenylethylamine|author = PubChem Public Chemical Database|publisher = [[National Center for Biotechnology Information]]|access-date = 29 December 2015|date = 26 December 2015|author-link = PubChem}}</ref> Both benzylamine and 1-phenylethylamine form stable ammonium salts and imines due to their relatively high [[basicity]].

==Safety and environment==

Benzylamine exhibits modest oral toxicity in rats with [[LD50|LD₅₀]] of 1130&nbsp;mg/kg. It is readily biodegraded.<ref name=Ullmann/>

{{Reflist|30em}}

[[Category:Aldehyde dehydrogenase inhibitors]]

[[Category: compounds]]

[[Category:Human drug metabolites]]