An Ether Synthesis Using Phase Transfer Catalysis Phase-transfer catalysis has become an important technique in synthetic organic chemistry. An extensive search of current laboratory manuals, however, shows that the method still is not widely used in sophomore organic chemistry laboratories. Only two of the manuals that we searched have experiments that make use of PTC (1.2). An experiment similar to that in reference (I) has been described in this Journal (3). Gokel and Weber ( 4 ) have provided an excellent review of the subject and Vsrughese (5) has included some phase-transfer reactions in his review of the use of quaternary ammonium salts in organic syntheses. PTC has also been reviewed in two excellent commercial publications (6,7). This paper describes an ether synthesis using PTC. In the usual Williamson synthesis of an ether, a primaryalkyl halide is reacted with an alkoride. The conditions must he rigorous, with special attention to avoiding contamination by water. Williamson syntheses may be carried out under milder conditions by employing a phase-transfer catalyst. Most notably, anhydrous solvents are not needed. As the name implies, phw-transfer catalysis is w r i e d out in a two-phase system; one phase is aqueous, the other organic. An increase in reaction rate is obtained by adding catalytic amounts of an organic salt which transfers the water soluble reagent into the organic phase for reaction. The phase-transfer catalyst Q+X-, far example, transfers the water soluble nucleophile, 2-, into the organic phase as an ion-pair [QCZ-1. There the nucleophile reacts with the alkyl halide, RX, to give RZ. The cation of the catalyst migrates hack to the aqueous phase and the reaction continues. The process may be summarized by the schematic shown below at left. The procedure described here is adapted from that of Freedman and Dubois (8). The phase-transfer catalyst is tetrabutylammonium hydrogen sulfate (9),the alkyl halide is benzyl chloride, and the nucleophile is the alkaxide of l-butanol (shown below a t right). aqueous phase Q+X-
+ Z-
e [Q+Z-] + X-
organic phase [Q+X-]
+ RZ
-
-------If -------------- i t ------[Q+Z-]
+ RX
aqueous phase Bu4N+HS04-
+ BuO- e [B4NCBuO-] + HS04-
organic phase [BurNCHS04-]
+ BzOBu
--------------- It -------------- i t --------------
Procedure
-
[BurNtBuO-]
+ BzCl
In a round-bottom flask, make a 50% solution of sodium hydroxide by dissolving 20 g of NaOH (0.5 mole) in 20 ml of water. Cool to room temperature and add 7.4 g (9.2 ml, 0.1 mole) of 1-butanol. A thick, white slurry is obtained. Now add 15.2 g (13.8 ml, 0.12 mole) of benzyl chloride (CAUTION: Lachrymator) and 1.7 g (0.005 mole) of tetrabutylammonium hvdroeen sulfate. Fit with s reflux candenser and stir on a water bath at 75 OC for 15 min. Stm the stirring and extract with diethd ether. Dry the ether extract over anhydrous calcium chloride. Remove the diethyl ether bysimple distillation. When all the diethyl ether has been distilled, disconnect the condenser water and heat strongly to distill the benzyl butyl ether through the air-cooled condenser. Benzyl butyl ether boils a t 200 'C. The product was obtained in good yield (50-9090, average 67%). A high degree of product purity was demonstrated by gas chromatography and by infrared and NMR spectra. Helpful suggestions were made by Professors Michael Keenan, Milan Webking, Joseph Conrad, and an anonymous referee. They are gratefully acknowledged.
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Literature Cited (1) Fieser, Lo& F.. and WiUiamron, Kenneth L., "OlganicExperiments." 4th d, D, C. Heath, Lcxinglon. MA, 1919. (2) Dunf H. D., and Gakel. G. W.,"Erperimsntal Organic Chemistry." MeGraw-Hill, New York, 1980. (3) A u k A.. and Wright, 8..J. CHEM. EDUC., 53.489 (1976). (4) Gokel, G. W.. and Wehr, W. P.. J. CHEM. EDUC., 55.350.429 (1976). (5) Varugheac, P.,J. CHEM. EDUC., 54,666 (1977). (6) Eosf&n Organic Chemical Bulletin. 48.[1]. 1-3 (1976). (7) Jones, R. Alan, Aldriehimieo Act., 9. f3135-45 (19%). (8) Freedman, H. H., and Dub& R.A.. Tetrahedron Lett., 3251 (1975). (9) Availeble from Aldrieh Chemical Co., 940 W. St. Paul Avc., Milwaukee, WI 53233, catalog no. 15.583-1.
'T o whom correspondence should be addressed.
Present addresa: Centro Nacional Investigaciones Agropecuarias, Carimagua, A. A. 6713, Cali, Columbia University of Wisconsin J o h n W. Hill' River Falls, Wisconsin 54022 a n d J o r g e CorredoZ
822 1 Journal of Chemical Education
