Isocyanide

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An isocyanide, also called an isonitrile, 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.

1 Physical properties
2 Organic synthesis
3 Organic reactions
4 Natural products
5 References

[edit] Physical properties

Isocyanides are isoelectronic with CO yet are only moderately toxic. 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 [iso]cyanoallyl 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 ^[1]The development of the chemistry of isonitriles 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.”. Isonitriles have been investigated as potential non-lethal weapons.

Tosylmethyl isocyanide (TOSMIC) is a notable exception.

[edit] Organic synthesis

The first isocyanide, allyl isocyanide was prepared in 1859 by the chemist Lieke from the reaction of allyl iodide and silver cyanide.^[2] Normally the alkylation of an alkali metal cyanide gives the 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.^[3]

RNH₂ + CCl₂ + 2 NaOH → RNC + 2 NaCl + 2 H₂O

RNHC(O)H + POCl₃ → RNC + "PO₂Cl" + 2 HCl

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

Another route to isonitriles is by reaction of organolithium compounds with oxazoles and benzoxazoles^[4]:

The benzoxazole gets deprotonated at the 2-position by n-butyllithium. The lithium compound is in chemical equilibrium with the r-isocyano enolate 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.

[edit] Organic reactions

Isocyanides are reactants in two multicomponent reactions: the Ugi reaction and the Passerini reaction.

[edit] Natural products

There are several organic molecules extracted from living organisms containing isocyanides. The first was discovered in 1957 in an extract of a Penicillium notatum Westling. The compound xanthocillin later was used as the antibiotic. Since than numerous other isocyanides have been isolated. Most of the marine isocyanides are terpenes, while some of the terrestrial isocyanides originate from α-aminoacids.^[5]

[edit] References

^ Ugi, I.; Fetzer, U.; Eholzer, U.; Knupfer, H.; Offermann, K. Angew. Chem.,Int. Ed. Eng. 1965, 4, 472-484.
^ Lieke, W. (1859). "Über das Cyannllyl". Annalen der Chemie und Pharmacie 112: 316-321.
^ I. Ugi, R. Meyr (1958). "Neue Darstellungsmethode für Isonitrile". Angewandte Chemie 70 (22-23): 702 - 703. DOI:10.1002/ange.1760702213.
^ Michael C. Pirrung, Subir Ghorai (2006). "Versatile, Fragrant, Convertible Isonitriles". Journal of the American Chemical Society 128 (36): 11772 - 11773. DOI:10.1021/ja0644374.
^ Paul J. Scheuer (1992). "Isocyanides and cyanides as natural products". Accounts of Chemical Research 25 (10): 433 - 439. DOI:10.1021/ar00022a001.