p-Tolylthiomethyl Isocyanide

[41514-80-1]  · C9H9NS  · p-Tolylthiomethyl Isocyanide  · (MW 163.26)

(synthesis of imidazoles from cyanides;1 conversion of aldehydes and ketones to ketene N,S-acetals2)

Physical Data: bp 60 °C/0.001 mmHg.

Form Supplied in: ill-smelling colorless liquid, which solidifies at -10 °C; turns yellow on standing.

Analysis of Reagent Purity: IR (neat) 2150 cm-1; 1H NMR (CDCl3) d 4.4 (s, CH2).

Preparative Method: prepared by dehydration of N-(p-tolylthiomethyl)formamide in 89% yield.2

Handling, Storage, and Precautions: should be stored at -20 °C. Use in a fume hood.

Introduction.

p-Tolylthiomethyl isocyanide (1) is one of the (hetero) substituted derivatives of methyl isocyanide, and thus belongs to a class of reagents which includes p-Tolylsulfonylmethyl Isocyanide (TosMIC), Diethyl Isocyanomethylphosphonate, Methyl N-(p-Tolylsulfonylmethyl)thiobenzimidate (a TosMIC derivative), and Ethyl Isocyanoacetate. TosMIC is a multipurpose synthesis reagent which, for example, forms imidazoles in a base-induced cycloaddition of its C-N-C unit across the C=N bond of imines.3 p-Tolylthiomethyl isocyanide (1) has been developed as an alternative for TosMIC on the assumption that the anion of (1) is a stronger nucleophile than the anion of TosMIC.4 Indeed, (1) is able to convert cyanides into imidazoles with greater efficiency than TosMIC (eqs 1-3).1,4 Several analogs of (1) have been prepared, among which are (2-naphthylthio)methyl isocyanide (2) (mp 76-78 °C) and (p-chlorophenylthio)methyl isocyanide (3) (mp 76-77 °C).2 Reagent (2) should replace (1) in future applications, because: (1) it does not have the characteristic (bad) smell of isocyanides; and (2) being a solid, it is more stable and can be stored for long periods at room temperature.2

Synthesis of Imidazoles and Oxazoles.

Imidazoles are formed in one operation by a base-induced cycloaddition of (1) to the triple bond of cyanides (eqs 1-3).1,4 The p-tolylthio group remains part of the product, unlike imidazoles prepared from imines and TosMIC where the tosyl group is eliminated.3 The formation of oxazoles from (1) and Acetic Anhydride5 or Methyl Formate6 has also been reported.

Synthesis of Ketene N,S-Acetals.

The Peterson alkenation of (2) with ketones and aldehydes provides 1-(2-naphthylthio)alkenyl isocyanides, which form a new class of ketene N,S-acetals (eqs 4 and 5).2 The trimethylsilyl derivative of (2) is formed in situ.


1. van Leusen, A. M.; Schut, J. TL 1976, 285.
2. van Leusen, A. M.; Wildeman, J.; Moskal, J.; van Hemert, A. W. RTC 1985, 104, 177.
3. van Leusen, A. M.; Wildeman, J.; Oldenziel, O. H. JOC 1977, 42, 1153.
4. Compare: van Nispen, S. P. J. M.; Mensink, C.; van Leusen, A. M. TL 1980, 21, 3723.
5. van Leusen, A. M.; van Gennep, H. E. TL 1973, 627.
6. Schöllkopf, U.; Blume, E. TL 1973, 629.

Albert M. van Leusen & Daan van Leusen

Groningen University, The Netherlands



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