[10468-64-1] · C8H7N · o-Tolyl Isocyanide · (MW 117.16)
(synthesis of N-heterocycles and azomethines)
Physical Data: bp 75 °C/16 mmHg; d 0.97 g cm-3.
Solubility: sol most organic solvents, e.g. methanol, ethanol, ether, toluene, dichloromethane.
Analysis of Reagent Purity: by gas chromatography.
Preparative Method: see Ugi and Meyr.3
Handling, Storage, and Precautions: should be freshly distilled before use. Foul smelling liquid; store and use in a fume hood. Contaminated equipment should be washed with 5% methanolic sulfuric acid.
o-Tolyl isocyanide can be used to synthesize a great variety of compounds.1,2 The aromatic o-methyl group can be lithiated to create a bifunctional isocyanide reagent (eq 1).4
Reaction of o-tolyl isocyanide with Lithium Diisopropylamide followed by alkylation5,6 or acylation7-9 and then cyclization gives 3-substituted indoles (eqs 2-4).
b,g-Butenolide imines can be made in reasonable yields by Lewis acid-catalyzed [4 + 1] cycloaddition (eq 5).10 The azetidine ring system, otherwise very difficult to obtain, results in reasonable yield in a one-step [2 + 2 + 2] cycloaddition using o-tolyl isocyanide (eq 6).11
Nucleophilic attack of organozinc compounds on the isocyanide carbon leads to the corresponding Schiff bases (eq 7).12 Similarly, Pd0 catalysis effects insertion of o-tolyl isocyanide into the Si-Si bond of bis-silyl compounds (eq 8).13
Heiner Eckert, Alfons Nestl & Ivar Ugi
Technische Universität München, Garching, Germany