Tolyl Isocyanide

Toluenesulfonylhydrazide, 40, 93 o-Toluidine, conversion to N-o-tolyl-formamide, 41, 102 N-o-Tolylformamide, 41, 102 dehydration to o-tolyl isocyanide, 41, 102... 

Isocyanides, which are better candidates to react with dienes in a 1,4-fashion, were shown to cycloadd to 1-azadienes. Thus, the formation of isoindole derivative 15 as the major product (ca. 28% yield), upon treatment of benzoquinone 13 with two equivalents of p-tolyl isocyanide [81AG(E)982] was reported the reaction involves the insertion of the isocyanide carbon atom into the C—H bond of 13 leading to the 1-azadiene derivative 14, which in turn undergoes a [4 + 1] cycloaddition with a second isocyanide molecule (Scheme 4). 

N-o-Tolylformamide (135 g., 1.00 mole) (Note 2) is added to the hot stirred suspension, which becomes a clear solution within a few minutes. The solution is cooled to 10-20° by means of an ice bath and maintained at this temperature while 92 g. (0.60 mole) of phosphorus oxychloride is added to it with stirring over the course of 30-40 minutes. The reaction mixture is stirred at 30-35° for 1 hour and poured into an ice-cold stirred solution of 50 g. of sodium bicarbonate in 5 1. of water (Note 3). o-Tolyl isocyanide precipitates as an oil. It is taken up in 300 ml. of petroleum ether (b.p. 40-60°), and the organic phase is separated in a separatory funnel. The aqueous phase is extracted with three 200-ml. portions of petroleum ether. The combined extracts are washed with 50 ml. of 5% sodium bicarbonate solution, dried over 50 g. of powdered potassium hydroxide, and distilled through a 30-cm. vacuum-jacketed Vigreux column, o-Tolyl isocyanide is collected as a colorless, vile-smelling liquid at 61-63°/10 mm. 1.5212-1.5222 weight 74-85 g. (63-73%) (Note 4). 

The equipment used in this preparation can be freed of the disagreeable odor of o-tolyl isocyanide by being washed with 5% methanolic sulfuric acid. 

Among the features of Volume 41 is the smallest-scale synthesis yet published in Organic Syntheses, namely, the preparation of 0.0005 mole of cholestanyl methyl ether by a generally useful methylation procedure that employs diazomethane and fluoboric acid (p. 9). Two preparations of isocyanides by dehydration of formamides are included. One of these, illustrated by cyclohexyl isocyanide (p. 13), is most suitable for aliphatic isocyanides while the other, illustrated by o-tolyl isocyanide (p. 101), is most suitable for aromatic isocyanides. 

A p-tolyl isocyanide complex of stoichiometry [Re02(PPh3)2(CNR)2]I has been reported312 but remains incompletely characterized. Other isocyanide-containing derivatives are unknown. 

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