N-Methyl-N-tosylpyrrolidinium Perchlorate

[39830-53-0]  · C12H18ClNOS  · N-Methyl-N-tosylpyrrolidinium Perchlorate  · (MW 339.84)

(selective tosylating reagent for amines)

Physical Data: mp 148-150 °C.

Solubility: usually used in CH2Cl2.

Form Supplied in: not commercially available.

Analysis of Reagent Purity: sharp mp and satisfactory elemental analysis are reported.1

Preparative Method: N-methylpyrrolidine is reacted with p-Toluenesulfonyl Chloride in CH2Cl2, in the dark, in the presence of Silver(I) Perchlorate, to yield the required production in 67.7 % yield.1-3

Handling, Storage, and Precautions: N-methyl-N-tosylpyrrolidinium perchlorate can be stored for six months without significant decomposition. It is reasonably stable in water, with approximately 50% remaining unchanged after 60 min.

Introduction.

N-Methyl-N-tosylpyrrolidinium perchlorate is used as a selective tosylating reagent for amines in the presence of alcohols.1 The use of ClO4- as counterion avoids a possible side reaction that occurs when SbCl6- is used as counterion, namely attack of Cl- liberated from SbCl6- on the S atom of the sulfonamide. This yields TsCl.

Protection of Primary and Secondary Amines.

The protection of amines is easily achieved by reacting the amine and tosylating agent in CH2Cl2 at 0 °C. The hindered amine 1,3-Dicyclohexylcarbodiimide is tosylated in better yield than by previous methods4 which have used TsCl. However, when the weakly basic diphenylamine is used, slow and forcing conditions are required and tosylation is only achieved in moderate yield (Table 1).

Alcohols are not tosylated by N-methyl-N-tosylpyrrolidinium perchlorate, as exemplified by stirring cholesterol in CH2Cl2 with the tosylating reagent, at room temperature for 7 h. No reaction occurs.

Selective Tosylation of Amines in the Presence of Alcohols.

The attempted N-tosylation of amino alcohol (1), an intermediate in the synthesis of b,b-disubstituted indoline alkaloids, using 10% NaOH and TsCl resulted in 20-40% of the required product, plus a significant amount of the N-Ts/O-Ts compound.4 However, using N-methyl-N-tosylpyrrolidinium perchlorate, yields of the required N-Ts compound are improved to 75% (eq 1).

Similarly, amino alcohol (2) is N-tosylated in 80% yield with only 5% of the N-tosyl-O-tosyl compound being formed (eq 2).

N-Methyl-N-tosylpyrrolidinium perchlorate is stable in water (approximately 50% remaining unchanged after 60 min). The authors1 therefore suggest that it may be applicable to protein modification. However, no reports on this application have been forthcoming.


1. Oishi, M.; Kamata, K.; Kosuda, S.; Ban, Y. CC 1972, 1148.
2. Klages, F.; Hoheisel, K. CB 1963, 96, 2057.
3. Klages, F.; Malecki, F. E. LA 1966, 691, 15.
4. Klamann, D.; Bertsch, H. CB 1956, 89, 2007.

Helen Osborn

University of Bristol, UK



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.