Abstract
A new, simple method has been developed for the methylation of cyclodextrins. The reaction proceeds in the heterogeneous phase with dimethyl sulphate, using a solvent in which the original cyclodextrins and the bases used are poorly soluble or insoluble. However, in the presence of phase transfer catalysts, methylation proceeds with good yields. The products are mixtures of randomly methylated cyclodextrins (RAMEB), containing 60–70% of heptakis(2,6-di-O-methyl)-β-cyclodextrin (DIMEB), 10–15% of heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TRIMEB) and some monomethylated isomers. These methylated products have proved to be excellent detergents; e.g., they are able to significantly increase the water solubility of hydrocortisone, methyltesterone, etc. On repeating methylation twice, the amount of TRIMEB increases, and a pure product (28% yield) can be obtained by crystallisation.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
J. C. Irvine, H. Pringsheim and J. MacDonald:J. Chem. Soc. 125, 942 (1942).
I. Muskat:J. Am. Chem. Soc. 56, 693 (1934);ibid. 56, 2449 (1934).
K. Freudenberg and M. Meyer-Delius:Ber. 71, 1596 (1938).
B. Casu, M. Reggiani, G. G. Gallo and A. Viegevani:Tetrahedron 24, 803 (1968).
R. Kuhn, H. Trischmann and I. Löw:Angew. Chem. 67, 32 (1955).
R. Kuhn, H. H. Baen and A. Seelinger:Ann. 611, 236 (1988).
A. Lipták, P. Fügedi, J. Szurmai, P. Imre, P. Nánási and J. Szejtli:Int. Symp. on Cyclodextrins, Budapest, p. 275 (1981).
J. Szejtli, A. Lipt'ak, I. Yodál, P. Fügedi, P. Nánási and A. Neszményi:Starke 32, 165 (1980).
J. Boger, R. J. Concoran and J. M. Lehn:Helv. Chim. Acta. 61, 2190 (1978).
J. Szejtli:J. Incl. Phenom. 1, 153 (1984).
Hungarian Patent 185.580 (1980).
S. Hakamori:J. Biochem. (Tokyo) 55, 205 (1964).
J. S. Brimacombe, B. D. Jones, M. Stacey and J. J. Willard:Carbohydr. Res. 2, 167 (1966).
J. Szejtli:Cyclodextrins and Their Inclusion Complexes, Akadémia Kiadó, Budapest (1982).
J. Szejtli (Ed.):Proceedings of the 1st International Symposium on Cyclodextrins, Akadémia Kiadó, Budapest (1982).
W. P. Weber and G. W. Gokel:Phase Transfer Catalysis in Organic Synthesis, Springer-Verlag, Berlin-Heidelberg-New York (1980).
Ch. M. Starks and Ch. Liotta:Phase Transfer Catalysis, Academic Press, New York-San Francisco-London (1978).
E. V. Dehmlow and S. S. Dehmlow:Phase Transfer Catalysis, Monographs in Modern Chemistry, Vol. 11, Verlag Chemie, Weinheim (1980).
P. Di Cesare and B. Gross,Carbohydrate Res. 48, 271 (1976).
P. Di Cesare and B. Gross:Synth. Commun., 458 (1978).
J.-P. Joly and B. Gross:Tetrahedron Lett. 30, 4231 (1989).
L. Töke, L. Fenichel, P. Bakó and J. Szejtli:Acta Chim. Acad. Sci. Hung. 98, 357 (1978).
P. Bakó, L. Fenichel, L. Töke and M. Czugler:Liebigs Ann. Chem., 1163 (1981).
M. Bessodes, I. Shamsazar and K. Antonakis:Synthesis, 560 (1988).
J. Szejtli, L. Szente, P. Bakó, L. Fenichel and L. Töke:Hungarian Patent 194.917 (1987).
A. Steyermark:Quantitative Organic Microanalysis, 2nd Ed., Academic Press, New York, p. 751 (1961).
W. A. König, D. Icheln, T. Runge, I. Pforr and A. Krebs:High Res. Chromatogr. 13, 702 (1990).
W. A. König, S. Lutz and G. Wenz:Angew. Chem. 100, 989 (1988).
W. A. König, R. Krebber and G. Wenz:High Res. Chromatogr. 12, 790 (1989).
K. Takeo, H. Mitoh and K. Uemura:Carbohydr. Res. 187, 203 (1989).
Author information
Authors and Affiliations
Additional information
Dedicated to Professor Szejtli.
Proceedings of the Fourth International Symposium on Cyclodextrins (Ed. O. Huber and J. Szejtli), Munich 1988, p. 113. Kluwer Academic Publishers.
Rights and permissions
About this article
Cite this article
Bakó, P., Fenichel, L., Töke, L. et al. Methylation of cyclodextrins by phase-transfer catalysis. J Incl Phenom Macrocycl Chem 18, 307–314 (1994). https://doi.org/10.1007/BF00708737
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00708737