Methyl N-(p-Tolylsulfonylmethyl)thiobenzimidate

(E)

[80224-81-3]  · C16H17NO2S2  · Methyl N-(p-Tolylsulfonylmethyl)thiobenzimidate  · (MW 319.48) (Z)

[80224-48-2]

(reagent for the synthesis of 2,3,4-trisubstituted pyrroles1 from Michael acceptors, and of 2,5-disubstituted oxazoles2 from aldehydes)

Physical Data: mp 98.5-100.5 °C (E,Z-mixture).

Form Supplied in: colorless crystalline, shelf-stable material.

Analysis of Reagent Purity: IR (Nujol) 1600 (C=N), 1320 and 1135 cm-1 (SO2); 1H NMR (CDCl3; E/Z mixture) d 2.0 (s), 2.3 (s), 2.4 (s), and 2.5 (s) (2 × Me), 4.7 (s) and 5.0 (s) (CH2); 13C NMR (CDCl3) d 74.1 and 74.6 (CH2).

Preparative Methods: prepared by S-methylation of N-(p-tolylsulfonylmethyl)thiobenzamide in 74% yield using methyl fluorosulfonate,1a and in 91% yield using Iodomethane.1b

Introduction.

Methyl N-(p-tolylsulfonylmethyl)thiobenzimidate (1) has been designed as a derivative of p-Tolylsulfonylmethyl Isocyanide (TosMIC). TosMIC is a multipurpose synthesis reagent. One of the major applications of TosMIC is the base-induced cycloaddition of the C-N-C unit of TosMIC across the C=C double bond of Michael acceptors to form 3,4-disubstituted pyrroles, which inherently do not carry substituents at the ring positions 1, 2, and 5. Modified reagents such as (1) bearing two substituents on the isocyano carbon of TosMIC may react with Michael acceptors to give 2,3,4-trisubstituted pyrroles, in much the same way as TosMIC does. Thus reagent (1) would provide the product pyrroles with a phenyl substituent at position 2 (next to the ring carbon carrying the electron-withdrawing group of the former Michael acceptor molecule) (eq 1).1 The second substituent at the isocyano carbon of TosMIC (MeS in 1) needs to be a leaving group.

Synthesis of Pyrroles.

Reaction of (1) with Michael acceptors produces 2,3,4-trisubstituted pyrroles in one operation (eq 1),1 with a phenyl substituent at C-2. Substituents in (1) other than Ph and MeS have also been used.1

Synthesis of Oxazoles and Imidazoles.

The reaction of (1) with aromatic aldehydes provides 2,5-disubstituted oxazoles (eq 2).2 2-Methoxyoxazoles have been prepared by a similar process using dimethyl N-(p-tolylsulfonylmethyl)iminocarbonate (2), instead of (1) (eq 3).2 1,2,5-Trisubstituted imidazoles are formed accordingly by reaction of (1) with imino compounds.3

Related Reagents.

Diethyl Isocyanomethylphosphonate; Ethyl Isocyanoacetate; Methyl Isocyanide; p-Tolylthiomethyl Isocyanide.


1. (a) Houwing, H. A.; van Leusen, A. M. JHC 1981, 18, 1127. (b) Methyl fluorosulfonate (Magic Methyl, a dangerous methylating agent) is no longer commercially available. However, F. R. Leusink of this laboratory has shown that MeI is an excellent replacement when the procedure of Walter and Saha is followed, using acetonitrile (20 °C, 10 min) instead of acetone. See: Walter, W.; Saha, C. R. PS 1983, 17, 367.
2. Houwing, H. A.; Wildeman, J.; van Leusen, A. M. JHC 1981, 18, 1133.
3. Houwing, H. A.; Wildeman, J.; van Leusen, A. M. TL 1976, 143.

Albert M. van Leusen & Daan van Leusen

Groningen University, The Netherlands



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