Isocyanide

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An isocyanide (also called an isonitrile^[1]) 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.”^[1] Isocyanides have been investigated as potential non-lethal weapons.

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

Synthesis of isocyanides

The first isocyanide, allyl isocyanide was prepared in 1859 by the chemist Lieke from the reaction of allyl iodide and silver cyanide.^[1] 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.^[1]

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^[1]:

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 rout towards an isocyanide is 1) condensation of an amine with formic acid, yielding a formamide, and 2) dehydrating this formamide.

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 than numerous other isocyanides have been isolated. Most of the marine isocyanides are terpenes, while some of the terrestrial isocyanides originate from α-aminoacids.^[1]

References

v • d • e Functional groups

Chemical class: Alcohol • Aldehyde • Alkane • Alkene • Alkyne • Amide • Amine • Azo compound • Benzene derivative • Carboxylic acid • Cyanate • Disulfide • Ester • Ether • Haloalkane • Hydrazone • Imine • Isocyanide • Isocyanate • Ketone • Oxime • Nitrile • Nitro compound • Nitroso compound • Peroxide • Phosphoric acid • Pyridine derivative • Sulfone • Sulfonic acid • Sulfoxide • Thioester • Thioether • Thiol

de:Isonitrile

ja:イソニトリル