TosMIC

Technical Specifications

Product Description & Scientific Applications

TosMIC (p-toluenesulfonylmethyl isocyanide; (p-tolylsulfonyl)methyl isocyanide), the van Leusen reagent, is a densely functionalised isocyanide and one of the most versatile isocyanide reagents in synthesis. It delivers a C–N–C unit in azole ring synthesis and a single carbon in the homologation of carbonyl compounds to nitriles.

Reactivity basis. Its behaviour follows from three groups on one short framework: a strongly acidic methylene (pKa ≈ 14), flanked by the sulfonyl and isocyanide groups, that bases from potassium carbonate to n-butyllithium deprotonate; the p-toluenesulfonyl (tosyl) group, which departs as a sulfinate; and the isocyanide carbon, incorporated as the new ring or nitrile carbon.

Handling. Unusually for an isocyanide, TosMIC is an odourless, bench-stable white solid.

Applications and Reactions

• Oxazoles — van Leusen oxazole synthesis: deprotonated TosMIC adds to an aldehyde; cyclisation and elimination of toluenesulfinic acid deliver a 5-substituted oxazole. Under milder base the 4,5-dihydrooxazole (oxazoline) intermediate can be isolated.
• Imidazoles — van Leusen imidazole synthesis: with an aldimine — or with an aldehyde and a primary amine forming the imine in situ (three-component) — TosMIC undergoes base-induced [3+2] cycloaddition to 1,5-disubstituted and 1,4,5-trisubstituted imidazoles.
• Pyrroles — van Leusen pyrrole synthesis: TosMIC reacts with electron-deficient alkenes (Michael acceptors bearing ester, ketone, nitro, cyano or aryl groups) by [3+2] cycloaddition to give substituted pyrroles.
• Thiazoles: under phase-transfer conditions TosMIC reacts with carbon disulfide, giving a thiazole salt that is converted to the thiazole.
• 1,2,4-Triazoles: TosMIC condenses with aryldiazonium salts to give 1,2,4-triazoles.
• Carbonyls to nitriles — reductive cyanation: with potassium tert-butoxide in a non-protic solvent (DME, DMSO), TosMIC converts ketones directly into the one-carbon-homologated nitriles, without an α-hydroxy (cyanohydrin) intermediate; the same reductive cyanation extends to aldehydes. The reaction spans a broad range of substrates.
• Connective C1 reagent: as a formaldehyde equivalent of reversed polarity, the acidic methylene is mono- or dialkylated and the isocyanide then hydrolysed, coupling alkyl halides through a carbonyl carbon to give aldehydes and symmetrical or unsymmetrical ketones — an umpolung of formaldehyde.
• Catalytic asymmetric addition: a dimethylzinc-mediated catalytic, enantio- and diastereoselective addition of TosMIC to ketones gives enantioenriched oxazolines.

Shipping Destinations

• EU & UK only: Priority delivery, 2–5 business days. Classified as dangerous goods — shipping restrictions apply outside the EU/UK.