Isocyanide
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.
Encyclopedia
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.
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 Cyanally reicht hin, die Luft eines Zimmers mehrere Tage lang zu verpesten, ..." . Note that in Leike'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 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 is a notable exception.
Organic synthesis
The first isocyanide,
allyl isocyanide was prepared in 1859 by the chemist Lieke from the reaction of
allyl iodide and
silver cyanide. 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.
- RNH2 + CCl2 + 2 NaOH → RNC + 2 NaCl + 2 H2O
- RNHCH + 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 :
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.
Organic reactions
Isocyanides are reactants in two multicomponent reactions: the
Ugi reaction and the
Passerini reaction.
References
