Isocyanide: Difference between revisions
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{{Short description|Chemical compound with isocyanide group (-N+≡C-)}} |
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{{Distinguish|Isocyanate}} |
{{Distinguish|Isocyanate}} |
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{{Image frame|content=<math chem>\left[\ce{R}-\overset{\oplus}\ce{N}\ce{#}\overset{\ominus}\ce{C}\ce{:\, <-> R-\ddot{N}=C{:}}\right]</math>|caption=General [[Resonance (chemistry)|resonance]] structure of an isocyanide}} |
{{Image frame|content=<math chem>\left[\ce{R}-\overset{\oplus}\ce{N}\ce{#}\overset{\ominus}\ce{C}\ce{:\, <-> R-\ddot{N}=C{:}}\right]</math>|caption=General [[Resonance (chemistry)|resonance]] structure of an isocyanide}} |
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An '''isocyanide''' (also called '''isonitrile''' or '''carbylamine''') is an [[organic compound]] with the [[functional group]] - |
An '''isocyanide''' (also called '''isonitrile''' or '''carbylamine''') is an [[organic compound]] with the [[functional group]] –{{chem2|N+\tC-}}. It is the [[isomer]] of the related [[nitrile]] (–C≡N), hence the prefix is ''isocyano''.<ref name=isocyanides>IUPAC Goldbook [http://goldbook.iupac.org/I03270.html ''isocyanides'']</ref> The organic fragment is connected to the isocyanide group through the [[nitrogen]] atom, not via the [[carbon]]. They are used as building blocks for the synthesis of other compounds.<ref name=Patil>{{Cite journal|last1=Patil|first1=Pravin|last2=Ahmadian-Moghaddam|first2=Maryam|last3=Dömling|first3=Alexander|date=2020-09-29|title= Isocyanide 2.0|journal= Green Chemistry|volume=22|issue=20|pages=6902–6911|language=en|doi=10.1039/D0GC02722G|issn=1463-9270|doi-access=free}}</ref> |
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==Properties== |
==Properties== |
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===Structure and bonding=== |
===Structure and bonding=== |
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The C-N distance in isocyanides is 115.8 pm in [[methyl isocyanide]]. The C-N-C angles are near 180°.<ref name="Kessler1950">{{cite journal| last = Kessler | first = M. |author2=Ring, H. |author3=Trambarulo, R. |author4=Gordy, W. | title = |
The C-N distance in isocyanides is 115.8 pm in [[methyl isocyanide]]. The C-N-C angles are near 180°.<ref name="Kessler1950">{{cite journal| last = Kessler | first = M. |author2=Ring, H. |author3=Trambarulo, R. |author4=Gordy, W. | title = Microwave Spectra and Molecular Structures of Methyl Cyanide and Methyl Isocyanide| journal = Physical Review | year = 1950 | volume = 79 | issue = 1 | pages = 54–56 | doi = 10.1103/PhysRev.79.54|bibcode=1950PhRv...79...54K }}</ref> |
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Akin to [[carbon monoxide]], isocyanides are described by two [[Resonance (chemistry)|resonance structures]], one with a [[triple bond]] between the nitrogen and the carbon and one with a [[double bond]] between. The π lone pair of the nitrogen stabilizes the structure and is responsible of the linearity of isocyanides, although the reactivity of isocyanides reflects some carbene character, at least in a formal sense. Thus, both resonance structures are useful representations.<ref name="Ramozzi2012"/> They are susceptible to [[polymerization]].<ref name="Ramozzi2012">{{cite journal | last = Ramozzi | first = R. |author2=Chéron, N. |author3=Braïda, B. |author4=Hiberty, P. C. |author5=Fleurat-Lessard, P. | title = A Valence Bond View of Isocyanides' Electronic Structure | journal = New Journal of Chemistry | year = 2012 | volume = 36 | issue = 5 | pages = 1137–1340 | doi = 10.1039/C2NJ40050B}}</ref> |
Akin to [[carbon monoxide]], isocyanides are described by two [[Resonance (chemistry)|resonance structures]], one with a [[triple bond]] between the nitrogen and the carbon and one with a [[double bond]] between. The π lone pair of the nitrogen stabilizes the structure and is responsible of the linearity of isocyanides, although the reactivity of isocyanides reflects some carbene character, at least in a formal sense. Thus, both resonance structures are useful representations.<ref name="Ramozzi2012"/> They are susceptible to [[polymerization]].<ref name="Ramozzi2012">{{cite journal | last = Ramozzi | first = R. |author2=Chéron, N. |author3=Braïda, B. |author4=Hiberty, P. C. |author5=Fleurat-Lessard, P. | title = A Valence Bond View of Isocyanides' Electronic Structure | journal = New Journal of Chemistry | year = 2012 | volume = 36 | issue = 5 | pages = 1137–1340 | doi = 10.1039/C2NJ40050B}}</ref> |
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===Odour=== |
===Odour=== |
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Isocyanides have a very disagreeable odour. To quote from Lieke, "''Es besitzt einen penetranten, höchst unangenehmen Geruch; das Oeffnen eines Gefässes mit Cyanallyl reicht hin, die Luft eines Zimmers mehrere Tage lang zu verpesten, ...''" (It has a penetrating, extremely unpleasant odour; the opening of a flask of allyl [iso]cyanide is enough to foul up the air in a room for several days). Note that in Lieke's day, the difference between isocyanide and nitrile was not fully appreciated.{{quote without source}} |
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[[Ivar Karl Ugi]] states that "''The development of the chemistry of isocyanides has probably suffered only little delay through the characteristic odor of volatile isonitriles, which has been described by Hofmann and Gautier as 'highly specific, almost overpowering', 'horrible', and 'extremely distressing'. It is true that many potential workers in this field have been turned away by the odour, but this is heavily outweighed by the fact that isonitriles can be detected even in traces, and that most of the routes leading to the formation of isonitriles were discovered through the odor of these compounds."''<ref name="Ugi1965">{{cite journal | last = Ugi | first = I. |author2=Fetzer, U. |author3=Eholzer, U. |author4=Knupfer, H. |author5=Offermann, K. | title = Isonitrile Syntheses | journal = Angewandte Chemie International Edition | year = 1965 | volume = 4 | issue = 6 | pages = 472–484 | doi = 10.1002/anie.196504721 }}</ref> Isocyanides have been investigated as potential [[non-lethal weapon]]s.<ref>{{cite journal | last = Pirrung | first = M. C. |author2=Ghorai, S. |author3=Ibarra-Rivera, T. R. | title = Multicomponent Reactions of Convertible Isonitriles | journal = The Journal of Organic Chemistry | year = 2009 | volume = 74 | issue = 11 | pages = 4110–4117 | doi = 10.1021/jo900414n | pmid = 19408909 }}</ref> |
[[Ivar Karl Ugi]] states that "''The development of the chemistry of isocyanides has probably suffered only little delay through the characteristic odor of volatile isonitriles, which has been described by Hofmann and Gautier as 'highly specific, almost overpowering', 'horrible', and 'extremely distressing'. It is true that many potential workers in this field have been turned away by the odour, but this is heavily outweighed by the fact that isonitriles can be detected even in traces, and that most of the routes leading to the formation of isonitriles were discovered through the odor of these compounds."''<ref name="Ugi1965">{{cite journal | last = Ugi | first = I. |author2=Fetzer, U. |author3=Eholzer, U. |author4=Knupfer, H. |author5=Offermann, K. | title = Isonitrile Syntheses | journal = Angewandte Chemie International Edition | year = 1965 | volume = 4 | issue = 6 | pages = 472–484 | doi = 10.1002/anie.196504721 }}</ref> Isocyanides have been investigated as potential [[non-lethal weapon]]s.<ref>{{cite journal | last = Pirrung | first = M. C. |author2=Ghorai, S. |author3=Ibarra-Rivera, T. R. | title = Multicomponent Reactions of Convertible Isonitriles | journal = The Journal of Organic Chemistry | year = 2009 | volume = 74 | issue = 11 | pages = 4110–4117 | doi = 10.1021/jo900414n | pmid = 19408909 }}</ref> |
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===From formamides=== |
===From formamides=== |
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Commonly, isocyanides are synthesized by [[dehydration reaction|dehydration]] of [[formamide]]s. The formamide can be dehydrated with [[toluenesulfonyl chloride]], [[phosphorus oxychloride]], [[phosgene]], [[diphosgene]], or the [[Burgess reagent]] in the presence of a base such as pyridine or triethylamine.<ref>{{cite journal |author=R. E. Schuster |author2=J. E. Scott | title = Methyl isocyanide |journal=Organic Syntheses | year = 1966 | volume = 46 | pages = 75 | doi = 10.15227/orgsyn.046.0075|title-link=Methyl isocyanide}}</ref><ref>{{cite journal | author1 =Ivar Karl Ugi | author-link =Ivar Karl Ugi |author2 =R. Meyr| title = Neue Darstellungsmethode für Isonitrile | journal = [[Angewandte Chemie]] | year = 1958 | volume = 70 | issue = 22–23 | pages = 702–703 | doi = 10.1002/ange.19580702213}}</ref><ref>{{cite journal | author1 =Siobhan Creedon| author2 =H. Kevin Crowley| author3 =Daniel G. McCarthy| title = Dehydration of formamides using the Burgess Reagent: a new route to isocyanides| journal = [[J. Chem. Soc., Perkin Trans. 1]] | year = 1998 | issue = 6 | pages = 1015–1018 | doi = 10.1039/a708081f}}</ref> |
Commonly, isocyanides are synthesized by [[dehydration reaction|dehydration]] of [[formamide]]s. The formamide can be dehydrated with [[toluenesulfonyl chloride]], [[phosphorus oxychloride]], [[phosgene]], [[diphosgene]], or the [[Burgess reagent]] in the presence of a base such as pyridine or triethylamine.<ref>{{cite journal |author=R. E. Schuster |author2=J. E. Scott | title = Methyl isocyanide |journal=Organic Syntheses | year = 1966 | volume = 46 | pages = 75 | doi = 10.15227/orgsyn.046.0075|title-link=Methyl isocyanide}}</ref><ref>{{cite journal | author1 =Ivar Karl Ugi | author-link =Ivar Karl Ugi |author2 =R. Meyr| title = Neue Darstellungsmethode für Isonitrile | journal = [[Angewandte Chemie]] | year = 1958 | volume = 70 | issue = 22–23 | pages = 702–703 | doi = 10.1002/ange.19580702213| bibcode =1958AngCh..70..702U }}</ref><ref>{{cite journal | author1 =Siobhan Creedon| author2 =H. Kevin Crowley| author3 =Daniel G. McCarthy| title = Dehydration of formamides using the Burgess Reagent: a new route to isocyanides| journal = [[J. Chem. Soc., Perkin Trans. 1]] | year = 1998 | issue = 6 | pages = 1015–1018 | doi = 10.1039/a708081f}}</ref><ref>{{cite journal |last1=Basoccu |first1=Francesco |last2=Cuccu |first2=Federico |last3=Casti |first3=Federico |last4=Mocci |first4=Rita |last5=Fattuoni |first5=Claudia |last6=Porcheddu |first6=Andrea |title=A trustworthy mechanochemical route to isocyanides |journal=Beilstein Journal of Organic Chemistry |date=22 June 2022 |volume=18 |pages=732–737 |doi=10.3762/bjoc.18.73|pmid=35821692 |pmc=9235834 |doi-access=free }}</ref> |
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:{{chem2|RNHC(O)H + ArSO2Cl + 2 C5H5N -> RNC + [C5H5NH]+[ArSO3]– + [C5H5NH]+Cl-}} |
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:RNHC(O)H + ArSO<sub>2</sub>Cl + 2C<sub>5</sub>H<sub>5</sub>N → RNC + [C<sub>5</sub>H<sub>5</sub>NH]<sup>+</sup>[ArSO<sub>3</sub>]<sup>–</sup> + [C<sub>5</sub>H<sub>5</sub>NH]<sup>+</sup>Cl<sup>–</sup> |
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The formamide precursors are, in turn, prepared from amines by formylation with formic acid or formyl acetyl anhydride<ref>{{Cite journal| |
The formamide precursors are, in turn, prepared from amines by formylation with formic acid or formyl acetyl anhydride<ref>{{Cite journal|last1=정선호|last2=안진희|last3=Park, Sang-Kyu|last4=최중권|date=2002-01-20|title=A Practical and Convenient Procedure for the N-Formylation of Amines Using Formic Acid|journal=Bulletin of the Korean Chemical Society|volume=23|issue=1|pages=149–150|doi=10.5012/BKCS.2002.23.1.149|doi-access=free}}</ref>.or from the Ritter reaction of alkenes (and other sources of carbocations) and hydrogen cyanide.<ref>{{Cite journal|date=1964|title=a,b-DIMETHYL-b-PHENETHYLAMINE|url=http://orgsyn.org/demo.aspx?prep=CV5P0471|journal=Organic Syntheses|volume=44|pages=44|doi=10.15227/orgsyn.044.0044}}</ref> |
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===From dichlorocarbene=== |
===From dichlorocarbene=== |
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In the [[carbylamine reaction]] (also known as the Hofmann isocyanide synthesis) alkali base reacts with [[chloroform]] to produce [[dichlorocarbene]]. The carbene then converts primary [[amine]]s to isocyanides. Illustrative is the synthesis of ''tert''-butyl isocyanide from [[Tert-Butylamine|''tert''-butylamine]] in the presence of [[catalytic]] amount of the [[phase transfer catalyst]] |
In the [[carbylamine reaction]] (also known as the Hofmann isocyanide synthesis) alkali base reacts with [[chloroform]] to produce [[dichlorocarbene]]. The carbene then converts primary [[amine]]s to isocyanides. Illustrative is the synthesis of ''tert''-butyl isocyanide from [[Tert-Butylamine|''tert''-butylamine]] in the presence of [[catalytic]] amount of the [[phase transfer catalyst]] benzyltriethylammonium chloride.<ref>{{cite journal|author1=G. W. Gokel|author2=R. P. Widera|author3=W. P. Weber| title = Phase-transfer Hofmann Carbylamine Reaction: tert-Butyl Isocyanide| journal = Organic Syntheses| volume=55|doi=10.15227/orgsyn.055.0096| pages = 232| year = 1988}}</ref> |
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:{{chem2|Me3CNH2 + CHCl3 + 3 NaOH → Me3CNC + 3 NaCl + 3 H2O}} |
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As it is only effective for primary amines this reaction can be used as a [[chemical test]] for their presence. |
As it is only effective for primary amines this reaction can be used as a [[chemical test]] for their presence. |
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===Other methods=== |
===Other methods=== |
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Another route to isocyanides entails deprotonation of [[oxazole]]s and [[benzoxazole]]s in the 2-position.<ref name="pirrung2006">{{cite journal |author1=Pirrung, M. C. |author2=Ghorai, S. | title = Versatile, Fragrant, Convertible Isonitriles | journal = [[Journal of the American Chemical Society]] | year = 2006 | volume = 128 | issue = 36 | pages = 11772–11773 | doi = 10.1021/ja0644374 | pmid = |
Another route to isocyanides entails deprotonation of [[oxazole]]s and [[benzoxazole]]s in the 2-position.<ref name="pirrung2006">{{cite journal |author1=Pirrung, M. C. |author2=Ghorai, S. | title = Versatile, Fragrant, Convertible Isonitriles | journal = [[Journal of the American Chemical Society]] | year = 2006 | volume = 128 | issue = 36 | pages = 11772–11773 | doi = 10.1021/ja0644374 | pmid = 16953613}}</ref> The resulting organolithium compound exists in [[chemical equilibrium]] with the ''2-isocyanophenolate'', which can be captured by an [[electrophile]] such as an [[acid chloride]]. |
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[[File:Benzoxazole-isocyanide synth.png|center|frameless|400x400px]] |
[[File:Benzoxazole-isocyanide synth.png|center|frameless|400x400px]] |
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Isocyanides are stable to strong base (they are often made under strongly basic conditions), but they are sensitive to acid. In the presence of aqueous acid, isocyanides hydrolyse to the corresponding [[formamides]]: |
Isocyanides are stable to strong base (they are often made under strongly basic conditions), but they are sensitive to acid. In the presence of aqueous acid, isocyanides hydrolyse to the corresponding [[formamides]]: |
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:RNC + |
:{{chem2|RNC + H2O → RNHC(O)H}} |
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This reaction is used to destroy odorous isocyanide mixtures. Some isocyanides can polymerize in the presence of Lewis and Bronsted acids.<ref>{{cite journal | last1 = Deming | first1 = T. J. | last2 = Novak | first2 = B. M. | year = 1993 | title = Mechanistic Studies on the Nickel Catalyzed Polymerization of Isocyanides | journal = J. Am. Chem. Soc. | volume = 115 | issue = 20 | page = 9101 | doi = 10.1021/ja00073a028 }}</ref> |
This reaction is used to destroy odorous isocyanide mixtures. Some isocyanides can polymerize in the presence of Lewis and Bronsted acids.<ref>{{cite journal | last1 = Deming | first1 = T. J. | last2 = Novak | first2 = B. M. | year = 1993 | title = Mechanistic Studies on the Nickel Catalyzed Polymerization of Isocyanides | journal = J. Am. Chem. Soc. | volume = 115 | issue = 20 | page = 9101 | doi = 10.1021/ja00073a028 }}</ref> |
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Isocyanides have also been shown to be a useful reagent in palladium catalysed reactions with a wide variety of compounds being formed using this method.<ref>{{cite journal | author = Lang, S. | title = Unravelling the labyrinth of palladium catalysed reactions involving isocyanides | journal = [[Chemical Society Reviews]] | year = 2013 | volume = 42 | issue = 12 | pages = 4867–4880 | doi = 10.1039/C3CS60022J | pmid = 23443313}}</ref> |
Isocyanides have also been shown to be a useful reagent in palladium catalysed reactions with a wide variety of compounds being formed using this method.<ref>{{cite journal | author = Lang, S. | title = Unravelling the labyrinth of palladium catalysed reactions involving isocyanides | journal = [[Chemical Society Reviews]] | year = 2013 | volume = 42 | issue = 12 | pages = 4867–4880 | doi = 10.1039/C3CS60022J | pmid = 23443313}}</ref> |
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The α position of isocyanides have substantial acidity. For example, benzyl isocyanide has a p''K''<sub>a</sub> of 27.4. In comparison, benzyl cyanide has a p''K''<sub>a</sub> of 21.9.<ref>{{Cite web|url=https://www.chem.wisc.edu/areas/reich/pkatable/|title=Bordwell pKa Table (Acidity in DMSO)|website=www.chem.wisc.edu|access-date=2018-12-20}}</ref> In the gas phase, |
The α position of isocyanides have substantial acidity. For example, benzyl isocyanide has a p''K''<sub>a</sub> of 27.4. In comparison, benzyl cyanide has a p''K''<sub>a</sub> of 21.9.<ref>{{Cite web|url=https://www.chem.wisc.edu/areas/reich/pkatable/|title=Bordwell pKa Table (Acidity in DMSO)|website=www.chem.wisc.edu|access-date=2018-12-20}}</ref> In the gas phase, {{chem2|CH3NC}} is 1.8 kcal/mol less acidic than {{chem2|CH3CN}}.<ref>{{Cite journal|last1=Filley|first1=Jonathan|last2=DePuy|first2=Charles H.|last3=Bierbaum|first3=Veronica M.|date=1987-09-01|title=Gas-phase negative-ion chemistry of methyl isocyanide|journal=Journal of the American Chemical Society|volume=109|issue=20|pages=5992–5995|doi=10.1021/ja00254a017|issn=0002-7863}}</ref> |
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Chlorination of isocyanides gives [[isocyanide dichloride]]s. |
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===Ligands in coordination chemistry=== |
===Ligands in coordination chemistry=== |
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{{main|Transition metal isocyanide complexes}} |
{{main|Transition metal isocyanide complexes}} |
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[[File:Tc CNCH2CMe2(OMe) 6Cation.png|thumb|left|220px|[[Technetium sestamibi]] is a commercial isocyanide complex that is used in medicine for imaging.]] |
[[File:Tc CNCH2CMe2(OMe) 6Cation.png|thumb|left|220px|[[Technetium sestamibi]] is a commercial isocyanide complex that is used in medicine for imaging.]] |
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Isocyanides form [[coordination complex]]es with most transition metals.<ref>{{cite journal | last1 = Singleton | first1 = Eric | last2 = Oosthuizen | first2 = Hester E. | year = 1983 | title = Metal Isocyanide Complexes | journal = Advances in Organometallic Chemistry | volume = 22 | pages = 209–310 | doi = 10.1016/S0065-3055(08)60404-9 | isbn = 9780120311224 }}</ref> They behave as electron-rich analogues of carbon monoxide. For example [[tert-butyl isocyanide]] forms |
Isocyanides form [[coordination complex]]es with most transition metals.<ref>{{cite journal | last1 = Singleton | first1 = Eric | last2 = Oosthuizen | first2 = Hester E. | year = 1983 | title = Metal Isocyanide Complexes | journal = Advances in Organometallic Chemistry | volume = 22 | pages = 209–310 | doi = 10.1016/S0065-3055(08)60404-9 | isbn = 9780120311224 }}</ref> They behave as electron-rich analogues of carbon monoxide. For example [[tert-butyl isocyanide]] forms {{chem2|Fe2(tBuNC)9}}, which is analogous to {{chem2|Fe2(CO)9}}.<ref>{{cite journal | last1 = Bassett | first1 = J.M. | last2 = Barker | first2 = G.K. | last3 = Green | first3 = M. | last4 = Howard | first4 = J.A. | last5 = Stone | first5 = G.A. | last6 = Wolsey | first6 = W.C. | title = Chemistry of low-valent metal isocyanide complexes | journal = Journal of the Chemical Society, Dalton Transactions | volume = 1981 | pages = 219–227 }}</ref> Although structurally similar, the analogous carbonyls differ in several ways, mainly because ''t''-BuNC is a better donor ligand than CO. Thus, {{chem2|Fe(tBuNC)5}} is easily protonated, whereas its counterpart {{chem2|Fe(CO)5}} is not.<ref>{{cite journal | last1 = Bassett | first1 = J.-M. | author-link3 = F.G.A. Stone | last2 = Farrugia | first2 = L. J. | last3 = Stone | first3 = F.G.A. | year = 1980| title = Notes. Protonation of pentakis(t-butyl isocyanide)iron| journal = Journal of the Chemical Society, Dalton Transactions| volume = 1980 | issue = 9 | pages = 1789–1790 | doi = 10.1039/DT9800001789 }}</ref> |
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==Naturally occurring isocyanides== |
==Naturally occurring isocyanides== |
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Only few naturally occurring compounds exhibit the isocyanide functionality. The first was discovered in 1957 in an extract of the mold ''[[Penicillium notatum]]''. The compound [[xanthocillin]] later was used as an [[antibiotic]]. Since then numerous other isocyanides have been isolated. Most of the marine isocyanides are terpenoid, while some of the terrestrial isocyanides originate from α-aminoacids.<ref>{{cite journal | author = Scheuer, P. J. | title = Isocyanides and Cyanides as Natural Products | journal = [[Accounts of Chemical Research]] | year = 1992 | volume = 25 | issue = 10 | pages = 433–439 | doi = 10.1021/ar00022a001}}</ref> |
Only few naturally occurring compounds exhibit the isocyanide functionality. The first was discovered in 1957 in an extract of the mold ''[[Penicillium notatum]]''. The compound [[xanthocillin]] later was used as an [[antibiotic]]. Since then numerous other isocyanides have been isolated. Most of the marine isocyanides are terpenoid, while some of the terrestrial isocyanides originate from α-aminoacids.<ref>{{cite journal | author = Scheuer, P. J. | title = Isocyanides and Cyanides as Natural Products | journal = [[Accounts of Chemical Research]] | year = 1992 | volume = 25 | issue = 10 | pages = 433–439 | doi = 10.1021/ar00022a001}}</ref> |
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:[[File:Xantocillin.svg|thumb|220px|[[Xanthocillin]] is a rare [[natural product]] that contains |
:[[File:Xantocillin.svg|thumb|220px|[[Xanthocillin]] is a rare [[natural product]] that contains two isocyanide groups.]] |
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== Nomenclature == |
== Nomenclature == |
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⚫ | |||
Whereas in [[IUPAC nomenclature]] in most cases the [[suffix]] "isonitrile" or "carbylamine" is used for organic [[cyanide]]s (R-C≡N),<ref>[http://www.acdlabs.com/iupac/nomenclature/93/r93_557.htm IUPAC Nomenclature of Organic Compounds (Recommendations 1993)]</ref> |
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⚫ | |||
The sometimes used term "carbylamine" conflicts with systematic nomenclature. An [[amine]] always has three single bonds,<ref>[http://www.acdlabs.com/iupac/nomenclature/79/r79_510.htm IUPAC Nomenclature of Organic Compounds (Recommendations 1993)]</ref> whereas an isocyanide has only one single and one multiple bond. |
The sometimes used old term "carbylamine" conflicts with systematic nomenclature. An [[amine]] always has three single bonds,<ref>[http://www.acdlabs.com/iupac/nomenclature/79/r79_510.htm IUPAC Nomenclature of Organic Compounds (Recommendations 1993)]</ref> whereas an isocyanide has only one single and one multiple bond. |
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The [[Isodiazomethane|isocyanamide]] functional group consists of a amino group attached to an isocyano moiety. |
The [[Isodiazomethane|isocyanamide]] functional group consists of a amino group attached to an isocyano moiety. |
Latest revision as of 20:09, 4 February 2024
An isocyanide (also called isonitrile or carbylamine) is an organic compound with the functional group –N+≡C−. It is the isomer of the related nitrile (–C≡N), hence the prefix is isocyano.[1] The organic fragment is connected to the isocyanide group through the nitrogen atom, not via the carbon. They are used as building blocks for the synthesis of other compounds.[2]
Properties
[edit]Structure and bonding
[edit]The C-N distance in isocyanides is 115.8 pm in methyl isocyanide. The C-N-C angles are near 180°.[3]
Akin to carbon monoxide, isocyanides are described by two resonance structures, one with a triple bond between the nitrogen and the carbon and one with a double bond between. The π lone pair of the nitrogen stabilizes the structure and is responsible of the linearity of isocyanides, although the reactivity of isocyanides reflects some carbene character, at least in a formal sense. Thus, both resonance structures are useful representations.[4] They are susceptible to polymerization.[4]
Spectroscopy
[edit]Isocyanides exhibit a strong absorption in their IR spectra in the range of 2165–2110 cm−1.[5]
The electronic symmetry about the isocyanide 14N nucleus results in a slow quadrupolar relaxation so that 13C-14N nuclear spin coupling can be observed, with coupling constants of ca. 5 Hz for the isocyanide 13C nucleus and 5–14 Hz for the 13C nucleus which the isocyanide group is attached to.[5]
Odour
[edit]Isocyanides have a very disagreeable odour. To quote from Lieke, "Es besitzt einen penetranten, höchst unangenehmen Geruch; das Oeffnen eines Gefässes mit Cyanallyl reicht hin, die Luft eines Zimmers mehrere Tage lang zu verpesten, ..." (It has a penetrating, extremely unpleasant odour; the opening of a flask of allyl [iso]cyanide is enough to foul up the air in a room for several days). Note that in Lieke's day, the difference between isocyanide and nitrile was not fully appreciated.[This quote needs a citation]
Ivar Karl Ugi states that "The development of the chemistry of isocyanides has probably suffered only little delay through the characteristic odor of volatile isonitriles, which has been described by Hofmann and Gautier as 'highly specific, almost overpowering', 'horrible', and 'extremely distressing'. It is true that many potential workers in this field have been turned away by the odour, but this is heavily outweighed by the fact that isonitriles can be detected even in traces, and that most of the routes leading to the formation of isonitriles were discovered through the odor of these compounds."[6] Isocyanides have been investigated as potential non-lethal weapons.[7]
Some isocyanides convey less offensive odours such as malt, natural rubber, creosote, cherry or old wood.[8] Non-volatile derivatives such as tosylmethyl isocyanide do not have an odor.[9]
Toxicity
[edit]While some isocyanides (e.g., cyclohexyl isocyanide) are toxic, others "exhibit no appreciable toxicity for mammals". Referring to ethyl isocyanide, toxicological studies in the 1960s at Bayer showed that "oral and subcutaneous doses of 500-5000 mg/kg can be tolerated by mice".[6]
Synthesis
[edit]Many routes to isocyanides have been developed.[2]
From formamides
[edit]Commonly, isocyanides are synthesized by dehydration of formamides. The formamide can be dehydrated with toluenesulfonyl chloride, phosphorus oxychloride, phosgene, diphosgene, or the Burgess reagent in the presence of a base such as pyridine or triethylamine.[10][11][12][13]
- RNHC(O)H + ArSO2Cl + 2 C5H5N → RNC + [C5H5NH]+[ArSO3]− + [C5H5NH]+Cl−
The formamide precursors are, in turn, prepared from amines by formylation with formic acid or formyl acetyl anhydride[14].or from the Ritter reaction of alkenes (and other sources of carbocations) and hydrogen cyanide.[15]
From dichlorocarbene
[edit]In the carbylamine reaction (also known as the Hofmann isocyanide synthesis) alkali base reacts with chloroform to produce dichlorocarbene. The carbene then converts primary amines to isocyanides. Illustrative is the synthesis of tert-butyl isocyanide from tert-butylamine in the presence of catalytic amount of the phase transfer catalyst benzyltriethylammonium chloride.[16]
- Me3CNH2 + CHCl3 + 3 NaOH → Me3CNC + 3 NaCl + 3 H2O
As it is only effective for primary amines this reaction can be used as a chemical test for their presence.
Silver cyanide route
[edit]Of historical interest but not often of practical value, the first isocyanide, allyl isocyanide, was prepared by the reaction of allyl iodide and silver cyanide.[17]
- RI + AgCN → RNC + AgI
Other methods
[edit]Another route to isocyanides entails deprotonation of oxazoles and benzoxazoles in the 2-position.[8] The resulting organolithium compound exists in chemical equilibrium with the 2-isocyanophenolate, which can be captured by an electrophile such as an acid chloride.
Reactions
[edit]Isocyanides have diverse reactivity.[2]
Isocyanides are stable to strong base (they are often made under strongly basic conditions), but they are sensitive to acid. In the presence of aqueous acid, isocyanides hydrolyse to the corresponding formamides:
- RNC + H2O → RNHC(O)H
This reaction is used to destroy odorous isocyanide mixtures. Some isocyanides can polymerize in the presence of Lewis and Bronsted acids.[18]
Isocyanides participate in many multicomponent reactions of interest in organic synthesis, two of which are: the Ugi reaction and the Passerini reaction.
Isocyanides also participate in cycloaddition reactions, such as the [4+1] cycloaddition with tetrazines.[19] Depending on the degree of substitution of the isocyanide, this reaction converts isocyanides into carbonyls or gives stable cycloadducts.[20] They also undergo insertion into the C–Cl bonds of acyl chlorides in the Nef isocyanide reaction, a process that is believed to be concerted and illustrates their carbene character.
Isocyanides have also been shown to be a useful reagent in palladium catalysed reactions with a wide variety of compounds being formed using this method.[21]
The α position of isocyanides have substantial acidity. For example, benzyl isocyanide has a pKa of 27.4. In comparison, benzyl cyanide has a pKa of 21.9.[22] In the gas phase, CH3NC is 1.8 kcal/mol less acidic than CH3CN.[23]
Chlorination of isocyanides gives isocyanide dichlorides.
Ligands in coordination chemistry
[edit]Isocyanides form coordination complexes with most transition metals.[24] They behave as electron-rich analogues of carbon monoxide. For example tert-butyl isocyanide forms Fe2(tBuNC)9, which is analogous to Fe2(CO)9.[25] Although structurally similar, the analogous carbonyls differ in several ways, mainly because t-BuNC is a better donor ligand than CO. Thus, Fe(tBuNC)5 is easily protonated, whereas its counterpart Fe(CO)5 is not.[26]
Naturally occurring isocyanides
[edit]Only few naturally occurring compounds exhibit the isocyanide functionality. The first was discovered in 1957 in an extract of the mold Penicillium notatum. The compound xanthocillin later was used as an antibiotic. Since then numerous other isocyanides have been isolated. Most of the marine isocyanides are terpenoid, while some of the terrestrial isocyanides originate from α-aminoacids.[27]
Xanthocillin is a rare natural product that contains two isocyanide groups.
Nomenclature
[edit]IUPAC uses the prefix "isocyano" for the systematic nomenclature of isocyanides: isocyanomethane, isocyanoethane, isocyanopropane, etc.
The sometimes used old term "carbylamine" conflicts with systematic nomenclature. An amine always has three single bonds,[28] whereas an isocyanide has only one single and one multiple bond.
The isocyanamide functional group consists of a amino group attached to an isocyano moiety. for nomenclature as suffix of isonitrile or prefix of isocyano is used depending upon priority table.
References
[edit]- ^ IUPAC Goldbook isocyanides
- ^ a b c Patil, Pravin; Ahmadian-Moghaddam, Maryam; Dömling, Alexander (2020-09-29). "Isocyanide 2.0". Green Chemistry. 22 (20): 6902–6911. doi:10.1039/D0GC02722G. ISSN 1463-9270.
- ^ Kessler, M.; Ring, H.; Trambarulo, R.; Gordy, W. (1950). "Microwave Spectra and Molecular Structures of Methyl Cyanide and Methyl Isocyanide". Physical Review. 79 (1): 54–56. Bibcode:1950PhRv...79...54K. doi:10.1103/PhysRev.79.54.
- ^ a b Ramozzi, R.; Chéron, N.; Braïda, B.; Hiberty, P. C.; Fleurat-Lessard, P. (2012). "A Valence Bond View of Isocyanides' Electronic Structure". New Journal of Chemistry. 36 (5): 1137–1340. doi:10.1039/C2NJ40050B.
- ^ a b Stephany, R. W.; de Bie, M. J. A.; Drenth, W. (1974). "A 13C-NMR and IR study of isocyanides and some of their complexes". Organic Magnetic Resonance. 6 (1): 45–47. doi:10.1002/mrc.1270060112.
- ^ a b Ugi, I.; Fetzer, U.; Eholzer, U.; Knupfer, H.; Offermann, K. (1965). "Isonitrile Syntheses". Angewandte Chemie International Edition. 4 (6): 472–484. doi:10.1002/anie.196504721.
- ^ Pirrung, M. C.; Ghorai, S.; Ibarra-Rivera, T. R. (2009). "Multicomponent Reactions of Convertible Isonitriles". The Journal of Organic Chemistry. 74 (11): 4110–4117. doi:10.1021/jo900414n. PMID 19408909.
- ^ a b Pirrung, M. C.; Ghorai, S. (2006). "Versatile, Fragrant, Convertible Isonitriles". Journal of the American Chemical Society. 128 (36): 11772–11773. doi:10.1021/ja0644374. PMID 16953613.
- ^ B. E. Hoogenboom, O. H. Oldenziel, and A. M. van Leusen "Toluenesulfonylmethyl isocyanide" Organic Syntheses, Coll. Vol. 6, p.987 (1988).
- ^ R. E. Schuster; J. E. Scott (1966). "Methyl isocyanide". Organic Syntheses. 46: 75. doi:10.15227/orgsyn.046.0075.
- ^ Ivar Karl Ugi; R. Meyr (1958). "Neue Darstellungsmethode für Isonitrile". Angewandte Chemie. 70 (22–23): 702–703. Bibcode:1958AngCh..70..702U. doi:10.1002/ange.19580702213.
- ^ Siobhan Creedon; H. Kevin Crowley; Daniel G. McCarthy (1998). "Dehydration of formamides using the Burgess Reagent: a new route to isocyanides". J. Chem. Soc., Perkin Trans. 1 (6): 1015–1018. doi:10.1039/a708081f.
- ^ Basoccu, Francesco; Cuccu, Federico; Casti, Federico; Mocci, Rita; Fattuoni, Claudia; Porcheddu, Andrea (22 June 2022). "A trustworthy mechanochemical route to isocyanides". Beilstein Journal of Organic Chemistry. 18: 732–737. doi:10.3762/bjoc.18.73. PMC 9235834. PMID 35821692.
- ^ 정선호; 안진희; Park, Sang-Kyu; 최중권 (2002-01-20). "A Practical and Convenient Procedure for the N-Formylation of Amines Using Formic Acid". Bulletin of the Korean Chemical Society. 23 (1): 149–150. doi:10.5012/BKCS.2002.23.1.149.
- ^ "a,b-DIMETHYL-b-PHENETHYLAMINE". Organic Syntheses. 44: 44. 1964. doi:10.15227/orgsyn.044.0044.
- ^ G. W. Gokel; R. P. Widera; W. P. Weber (1988). "Phase-transfer Hofmann Carbylamine Reaction: tert-Butyl Isocyanide". Organic Syntheses. 55: 232. doi:10.15227/orgsyn.055.0096.
- ^ W. Lieke (1859). "Über das Cyanallyl". Annalen der Chemie und Pharmacie. 112 (3): 316–321. doi:10.1002/jlac.18591120307.
- ^ Deming, T. J.; Novak, B. M. (1993). "Mechanistic Studies on the Nickel Catalyzed Polymerization of Isocyanides". J. Am. Chem. Soc. 115 (20): 9101. doi:10.1021/ja00073a028.
- ^ Imming, P.; R. Mohr; E. Müller; W. Overheu; G. Seitz (1982). "[4 + 1]Cycloaddition of Isocyanides to 1,2,4,5-Tetrazines: A Novel Synthesis of Pyrazole". Angewandte Chemie International Edition. 21 (4): 284. doi:10.1002/anie.198202841.
- ^ Stöckmann, H.; A. Neves; S. Stairs; K. Brindle; F. Leeper (2011). "Exploring Isonitrile-Based Click Chemistry for Ligation with Biomolecules". Organic & Biomolecular Chemistry. 9 (21): 7303–7305. doi:10.1039/C1OB06424J. PMID 21915395.
- ^ Lang, S. (2013). "Unravelling the labyrinth of palladium catalysed reactions involving isocyanides". Chemical Society Reviews. 42 (12): 4867–4880. doi:10.1039/C3CS60022J. PMID 23443313.
- ^ "Bordwell pKa Table (Acidity in DMSO)". www.chem.wisc.edu. Retrieved 2018-12-20.
- ^ Filley, Jonathan; DePuy, Charles H.; Bierbaum, Veronica M. (1987-09-01). "Gas-phase negative-ion chemistry of methyl isocyanide". Journal of the American Chemical Society. 109 (20): 5992–5995. doi:10.1021/ja00254a017. ISSN 0002-7863.
- ^ Singleton, Eric; Oosthuizen, Hester E. (1983). "Metal Isocyanide Complexes". Advances in Organometallic Chemistry. 22: 209–310. doi:10.1016/S0065-3055(08)60404-9. ISBN 9780120311224.
- ^ Bassett, J.M.; Barker, G.K.; Green, M.; Howard, J.A.; Stone, G.A.; Wolsey, W.C. "Chemistry of low-valent metal isocyanide complexes". Journal of the Chemical Society, Dalton Transactions. 1981: 219–227.
- ^ Bassett, J.-M.; Farrugia, L. J.; Stone, F.G.A. (1980). "Notes. Protonation of pentakis(t-butyl isocyanide)iron". Journal of the Chemical Society, Dalton Transactions. 1980 (9): 1789–1790. doi:10.1039/DT9800001789.
- ^ Scheuer, P. J. (1992). "Isocyanides and Cyanides as Natural Products". Accounts of Chemical Research. 25 (10): 433–439. doi:10.1021/ar00022a001.
- ^ IUPAC Nomenclature of Organic Compounds (Recommendations 1993)