An efficient approach towards syntheses of ethers and esters using CsF-Celite as a solid base

Article abstract of DOI:10.1016/S0040-4039(02)02060-9

The coupling reactions of a number of alcohols and phenols with alkyl, acyl or benzoyl halides in acetonitrile with cesium fluoride-Celite are described. It has been found that CsF-Celite combinations provide an efficient, convenient and practical method for syntheses of both, ethers and esters.

Full text of DOI:10.1016/S0040-4039(02)02060-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 8603–8606
An efficient approach towards syntheses of ethers and esters
using CsF–Celite as a solid base
Syed Tasadaque A. Shah,a Khalid M. Khan,b Angelica M. Heinrich,a M. Iqbal Choudharyb and
W. Voeltera,*
aAbteilung fu¨r Physikalische Biochemie des Physiologisch-chemischen Instituts der Universita¨t Tu¨bingen, Hoppe-Seyler Straße 4,
D-72076 Tu¨bingen, Germany
bHEJ Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi 75270,
Pakistan
Received 17 July 2002; accepted 6 September 2002
Abstract—The coupling reactions of a number of alcohols and phenols with alkyl, acyl or benzoyl halides in acetonitrile with
cesium fluoride–Celite are described. It has been found that CsF–Celite combinations provide an efficient, convenient and
practical method for syntheses of both, ethers and esters. © 2002 Elsevier Science Ltd. All rights reserved.
Hydroxyl groups are present in a number of com-
pounds of biological and synthetic interest, including
nucleosides, carbohydrates, steroids and alkaloids, etc.
During oxidation, acylation, halogenation with phos-
phorus or hydrogen halides, or dehydration reactions
of these compounds, a hydroxyl group must be pro-
tected. Ethers and esters are among the most used
protective groups in organic synthesis which were
formed and removed under a wide variety of condi-
tions.1 However, these methods suffer serious limita-
tions, when the substrates have acid or base labile
moieties in their skeletons.
phine as a catalyst for acylation of alcohols.6 However,
there is still a demand for base catalysts to generate
ethers and esters via an environmentally friendly pro-
cess. We wish to report a practical and convenient
method for the preparation of ethers and esters using
cesium fluoride–Celite as a solid base which can over-
come such types of limitations. We also demonstrate
herewith the utility of CsF–Celite/CH3CN for the syn-
theses of ethers and esters using the reaction conditions,
presented below.
The importance of the fluoride ion as a catalyst for the
promotion of various types of base-catalyzed reactions
in organic synthesis has been previously recognized.7
The work of Clark and Miller, in particular, revealed
that the fluoride ion has an effect on coupling reactions
because of its high capability of hydrogen-bond forma-
tion.8 As reagents for generating the fluoride ion in
these reactions, potassium, cesium and tetra-
alkylammonium fluorides were generally used so far.
However, it is not easy to handle these hygroscopic
reagents and the reproducibility of these reactions are
invariably poor. Previously, poorly hygroscopic reagent
generating fluoride ions were designed by allowing
cesium fluoride to be absorbed on Celite.9 The effect of
cesium fluoride–Celite might be twofold: (a) activation
of the hydroxyl group by the fluoride ion, whose ionic
character is increased owing to the low charge/surface
Yin et al.,2 reported protection of hydroxyl groups as
ethers using allyl bromide- and potassium fluoride-
impregnated alumina. Hijfte and Little reported3 O-
alkylation of primary alcohols with benzyl bromide and
Ag2O in DMF, however, use of benzyl and benzoyl
halides for the protection of primary and secondary
alcohols is more often used in carbohydrate synthesis.4
Although acylation of alcohols and phenols is routinely
carried out using acid anhydrides or acyl halides in the
presence of tertiary amines such as triethylamine and
pyridine.5 Vedejs and co-workers reported tributylphos-
* Corresponding
authors.
E-mail:
tasadaque@hotmail.com;
wolfgang.voelter@uni-tuebingen.de
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02060-9

8604
S. T. A. Shah et al. / Tetrahedron Letters 43 (2002) 8603–8606
Table 1. O-Acylation of hydroxyl groups using CsF–Celite
area ratio of the cesium cation and (b) activation of
the alkyl or acyl halide groups by a Lewis acid type
effect.10
In a typical reaction, a mixture of alcohol (1.0 mol),
CsF–Celite (1.5 mol) and alkyl or acyl halide (2.0
mol) in acetonitrile is stirred at room temperature or
under reflux (Scheme 1). The completion of the reac-
tion was monitored by TLC. After completion of
reaction, the reaction mixture was filtered and the
filtrate was evaporated to afford the pure product.
The reactions catalyzed by cesium fluoride–Celite are
usually carried out under mild conditions with good
yields and simple workup of these reactions; only
filtration is required to remove the catalyst and often
evaporation of the filtrate afforded pure products.
Previously in a short communication,9b esters of acids
were prepared from carboxylic acids and alkyl halides
via CsF–Celite catalysis, however, this report is lim-
ited only to the formation of esters from acids,
whereas they have also used the alcoholic moieties in
their reactions, but they overlooked the utility of this
solid base under the same reaction conditions for the
protection of an alcohol as an ether or ester. We
explored further utility of the CsF–Celite system as
an efficient, inexpensive, non-corrosive and an envi-
ronmentally friendly reagent for the protection of a
hydroxy function to an ether or ester depending upon
the substrate used.
Scheme 1.
Acknowledgements
We express our gratitude to Deutscher Akademischer
Several examples of CsF–Celite-assisted couplings of
aromatic hydroxyl groups with various alkyl or acyl
halides, resulting in alkylation, acylation benzylation
and benzoylation are presented in Tables 1 and 2.
Austauschdienst (DAAD, Bonn, Germany) for
a
sandwich-type scholarship, granted to Syed
Tasadaque Ali Shah and a short term scholarship,
granted to Dr. Khalid Mohammed Khan.

S. T. A. Shah et al. / Tetrahedron Letters 43 (2002) 8603–8606
8605
Table 2. O-Alkylation of hydroxyl groups using CsF–Celite
References
Diver, S. T.; Gingrass, M.; Lin, S.; Oliver, P. A.; Peter-
son, M. J. J. Org. Chem. 1993, 48, 7286–7288.
7. Miller, J. M.; So, K.-H.; Clark, J. H. J. Chem. Soc.,
Chem. Commun. 1978, 466–467.
8. Clark, J. H. J. Chem. Soc., Chem. Commun. 1978, 789–
791 and references cited therein.
1. Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis; John Wiley: New York, 1991.
2. Yin, H.; Frank, R. W.; Chen, S.-Le; Quigley, G. J.;
Todaro, L. J. Org. Chem. 1992, 57, 644–651.
3. Hijfte, L. V.; Little, R. D. J. Org. Chem. 1985, 50,
3940–3942.
9. (a) Hayat, S.; Atta-ur-Rahman; Choudhary, M. I.; Khan,
K. M.; Schumann, W.; Bayer, E. Tetrahedron 2001, 57,
9951; (b) Lee, J. C.; Choi, Y. Synth. Commun. 1998, 28,
2021–2026.
10. (a) Yamada, M.; Yahiro, S.; Yamano, T.; Nakatani, Y.;
Ourisson, G. Bull. Soc. Chim. Fr. 1990, 127, 824–829; (b)
Kruizinga, W. H.; Kellogg, R. M. J. Am. Chem. Soc.
1981, 103, 5183–5189; (c) Kruizinga, W. H.; Kellogg, R.
M. Bull. 1959, 7, 146–148.
4. (a) Wold, F. J. Org. Chem. 1961, 26, 197–199; (b) In
Vogel’s Textbook of Practical Organic Chemistry, 5th ed.;
Addison Wesley Longman: London, 1994; p. 646.
5. (a) Zhdanov, R. I.; Zhenodarova, S. M. Synthesis 1975,
222–229; (b) Horton, D. Org. Synth. Coll. 1973, 5, 1–5.
6. (a) Vedejs, E.; Diver, S. T. J. Am. Chem. Soc. 1993, 115,
3358–3359; (b) eedejs, E.; Bennett, N. S.; Conn, L. M.;

8606
S. T. A. Shah et al. / Tetrahedron Letters 43 (2002) 8603–8606
11. de la Mare, P. B. D.; Isaacs, N. S.; McGlone, M. J. J.
Chem. Soc., Perkin Trans. 1 1976, 784–786.
12. Cilento, G. J. Am. Chem. Soc. 1953, 75, 3748–3750.
13. Menger, F. M.; Smith, J. H. J. Am. Chem. Soc. 1972, 94,
8324–8325.
1801–1807.
22. Maslak, P.; Guthrie, R. D. J. Am. Chem. Soc. 1986, 108,
2628–2636.
23. Huang, R. L.; Lee, K. H. J. Am. Chem. Soc. 1964, 86,
5963–5969.
24. Rao, A. V. R.; Gaitonde, A. S.; Parkash, K. R. C.; Rao,
S. P. Tetrahedron Lett. 1994, 35, 6347–6350.
25. Raman, K.; Singh, H. K.; Salzman, S. K.; Parmar, S. S.
J. Pharm. Sci. 1993, 82, 167–169.
14. Williams, K.; Halpern, B. Synthesis 1974, 727–728.
15. Tarbell, D. S.; Price, J. A. J. Org. Chem. 1957, 22,
245–248.
16. Chem. Abstr. 1965, 63, 17909c.
26. Buu-Hoi; Hiong-ki-wie; Royer, R. Bull. Soc. Chim. Fr.
17. Kataoka, H. Chem. Abstr. 1966, 64, 8058.
18. Reckhow, W. A.; Tarbell, D. S. J. Am. Chem. Soc. 1952,
14, 4968–4969.
19. Hurd, C. D.; Kreuz, K. L. J. Am. Chem. Soc. 1950, 27,
5543–5546.
20. Baciocchi, E.; Piermattei, A.; Rol, C.; Ruzziconi, R.;
Sebastiani, G. V. Tetrahedron 1989, 45, 7049.
21. Brown, H. C.; Cope, O. J. J. Am. Chem. Soc. 1964, 86,
1945, 12, 866–869.
27. Lyman, J. A.; Reid, E. E. J. Am. Chem. Soc. 1920, 42,
615.
28. Coleman, R. S.; Chen, W. Org. Lett. 2001, 3, 1141–1144.
29. Maatschappij, N. V. Chem. Abstr. 1963, 59, 2721.
30. Hayashi, E.; Yamanaka, H.; Shimizu, K. Chem. Pharm.
Bull. 1959, 7, 146–148.