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. 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.
Properties
Structure and bonding The C-N distance in isocyanides is 115.8 pm in methyl isocyanide. The C-N-C angles are near 180°. 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 them. 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. They are susceptible to polymerization.
Spectroscopy Isocyanides exhibit a strong absorption in their IR spectra in the range of 2165–2110 cm−1. 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.
Odour Volatile isocyanides frequently have very disagreeable odours. Lieke remarked that "Es besitzt einen penetranten, höchst unangenehmen Geruch; das Oeffnen eines Gefässes mit Cyanallyl [sic] 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 cyanide [sic] 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. 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." Isocyanides have been investigated as potential non-lethal weapons. Some isocyanides convey less offensive odours such as malt, natural rubber, creosote, cherry or old wood. Non-volatile derivatives such as tosylmethyl isocyanide do not have an odor.
Toxicity 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".
Synthesis Many routes to isocyanides have been developed.
From formamides 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. Modern synthesis also employ the use of triphenylphosphine with iodine.
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, or from the Ritter reaction of alkenes (and other sources of carbocations) and hydrogen cyanide.
From dichlorocarbene 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.
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
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.
RI + AgCN → RNC + AgI
Other methods Another route to isocyanides entails deprotonation of oxazoles and benzoxazoles in the 2-position. The resulting organolithium compound exists in chemical equilibrium with the 2-isocyanophenolate, which can be captured by an electrophile such as an acid chloride.
In some cases, a phosphonite ester-amide can desulfurize isothiocyanates to isocyanides. Likewise triphenylphosphine reduces isocyanide dichlorides to isocyanides.
Reactions Isocyanides have diverse reactivity. 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:
… excerpt ends here. Continue reading the full article.
