Isocyanide

An isocyanide (also called an isonitrile [According to IUPAC's meaning of nitrile and cyanide the only correct name for R-N≡C is isocyanide. The term "nitrile" denotes the triply bound N atom, not the carbon atom attached to it and cyanide denotes the whole group -C≡N, including the carbon. Thus, CH₃CN can be called ethanenitrile, where both carbons are included in the suffix "eth", or methyl cyanide, where one carbon is included in the term cyanide. Its isomer CH₃NC can only be methyl isocyanide and never ethaneisonitrile, which would be CH₃CH₂N≡ http://www.acdlabs.com/iupac/nomenclature/93/r93_557.htm.] ) is an organic compound with the functional group R-N≡C. The CN functionality is connected to the organic fragment via the nitrogen atom, not via carbon as is found in the isomeric nitriles, which have the connectivity R-C≡N. Hence the prefix "iso". Nitrogen and carbon are connected through a triple bond with a positive charge on nitrogen and a negative charge on carbon.

Physical properties

Isocyanides are conventional organic compounds in terms of their physical properties. They are susceptible to polymerization.

In terms of bonding, isocyanides are isoelectronic with CO. Thus the C-N-CR₃ (R = hydrogen or an organic group) is linear.

Odour of isocyanides

Their disagreeable odour is legendary. 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.

Ugi of Ugi reaction fame states that "The development of the chemistry of isocyanides has probably suffered ... 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 odor.”" [Ugi, I.; Fetzer, U.; Eholzer, U.; Knupfer, H.; Offermann, K. Angew. Chem.,Int. Ed. Eng. 1965, 4, 472-484.] Isocyanides have been investigated as potential non-lethal weapons.

Tosylmethyl isocyanide (TOSMIC) is a notable exception (it doesn't smell as bad).

ynthesis of isocyanides

The first isocyanide, allyl isocyanide was prepared in 1859 by the chemist Lieke from the reaction of
allyl iodide and silver cyanide. [cite journal
author = Lieke, W.
title = Über das Cyannllyl
journal = Annalen der Chemie und Pharmacie
volume = 112
year = 1859
pages = 316–321
url = http://books.google.com/books?id=NYs8AAAAIAAJ&pg=RA1-PA319&dq=Cyanallyl++%22Es+besitzt+einen+penetranten%22&ie=ISO-8859-1
doi = 10.1002/jlac.18591120307] Normally the alkylation of an alkali metal cyanide gives a nitrile, but the silver ion protects the carbon end of the cyanide. Commonly, isocyanides are synthesized by the reaction of primary amines with dichlorocarbene or by dehydration of a formamide with phosphorus oxychloride. [cite journal
author = I. Ugi, R. Meyr
title = Neue Darstellungsmethode für Isonitrile
journal = Angewandte Chemie
volume = 70
year = 1958
issue = 22-23
pages = 702–703
doi = 10.1002/ange.1760702213
doi_brokendate = 2008-06-23]

:RNH₂ + CCl₂ + 2 NaOH → RNC + 2 NaCl + 2 H₂O:RNHC(O)H + POCl₃ → RNC + "PO₂Cl" + 2 HCl

The Hofmann isocyanide synthesis is a chemical test for primary amines based on their reaction with potassium hydroxide and chloroform as dichlorocarbene precursors to foul smelling isocyanides.

Another route to isocyanides is by reaction of organolithium compounds with oxazoles and benzoxazoles [cite journal
author = Michael C. Pirrung, Subir Ghorai
title = Versatile, Fragrant, Convertible Isonitriles
journal = Journal of the American Chemical Society
volume = 128
year = 2006
issue = 36
pages = 11772–11773
doi = 10.1021/ja0644374] :

The benzoxazole gets deprotonated at the 2-position by "n"-butyllithium. The lithium compound is in chemical equilibrium with the "2-isocyanophenolate" which can be captured by an electrophile such as an acid chloride. Being an ester the formed isocyanate in the example above behaves uncharacteristically with reportedly a mild cherry smell.

Another synthetic route towards an isocyanide is 1) condensation of an amine with formic acid, yielding a formamide, and 2) dehydrating this formamide. Phosgene can be used in combination with formamide to yield isocyanides. [http://en.wikipedia.org/wiki/Diphosgene]

Reactions

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. However, some isocyanides can polymerize in the presence of acids. Acid-hydrolysis is a convenient method for removing the obnoxiously odiferous isocyanides.

Isocyanides are reactants in two multicomponent reactions of interest in organic synthesis: the Ugi reaction and the Passerini reaction.

Naturally occurring isocyanides

Several organic molecules extracted from living organisms contain the isocyanide functionality. The first was discovered in 1957 in an extract of the mold "Penicillium notatum" Westling. The compound xanthocillin later was used as the antibiotic. Since then numerous other isocyanides have been isolated. Most of the marine isocyanides are terpenes, while some of the terrestrial isocyanides originate from α-aminoacids. [cite journal
author = Paul J. Scheuer
title = Isocyanides and cyanides as natural products
journal = Accounts of Chemical Research
volume = 25
year = 1992
issue = 10
pages = 433–439
doi = 10.1021/ar00022a001]

References