The Synthesis of Substituted Benzyl Phenyl Ethers An Undergraduate Organic Chemistry Experiment Klrnberly Dilts and Marc Durand West Chester Univ'ersity. West Chester, PA 19383 The experiment below presents a convenient and safe procedure for the semimicro S N Williamson ~ synthesis of henzyl phenyl ethers. The SN2 reaction normally used to synthesize alkyl ethers involves the reaction of sodium metal and a n alcohol with the generation of an alkoxide ion. As a rule, for safety reasons, such a reagent is avoided in a beginning organic chemistry laboratory; thus, ether synthesis via this method is usually not performed. On the other hand, benzyl phenyl ethers can be easily prepared from the phenoxide ions geuerated by reaction of phenols with alcoholic sodium hydroxide. The resulting nucleophiles can then be reacted with benzyl chloride to produce the ethers. The experimental section descrihes the procedure used to produce generally good yields of a variety of substituted ethers via this pathway.
Since the procedure involves the use of an indicator (an acid-base titration), no excess sodium hydroxide remains as a competing nucleophile. of the reaction is monitored by thin-layer ~ h d chromatography (TLC) on silica gel, providing an additional annlication of this imoortant techniaue in the undergraduate' organic lab. In addition, spec&oscopic analysis (IR, NMR. and mass s~ectrometerv)are performed on the final produet. Since a wide variety bf different substituted phenols are commerciallv available, individual studentscan prepare a variety of ethkrs requiring different recrystalliz$ion solvents or solvent pairs. The results can be discussed in a group session. Table 1 summarizes the yields and melting points of various ethers, while Rf values from TLC analysis are presented in Table 2.
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Journal of Chemical Education
TeMe 1. Yields and MeHlng Points ol Subotnuted Benzyl Phevl Fthars
R
TeMe 2.
Mailing Point Ex~erimemal Literalwe
% Yield
R,Valuea tor Selected Sub.tltuted Benzyl Phenyl Ethers n
a.
Experimental Athree-necked,250-mL round-bottomed flask is equipped with a thermarneter,areflux condenser, and a septum. The flask is charged with the appropriate phenol (2 g), which is dissolved in 20 mL of 0.25 M ethanolicsodium hydroxide. Several drops of thymal blue indicator (1%in ethanol) are added, and the phenol is titrated to the end point with 0.25 M ethanol sodium hydroxide. The phenoxide solution is stirred for 15 min, after which time a stoichiometric amount of benzyl chloride is added. A 1-mL aliquot of the mixture is removed by pipet at this time and subjected to TLC analysis. The mixture is refluxed for 2 h, during which time sodium chloride precipitates. Aliquota of the mixture are removed at 15-min intervals, spotted on silicagel-F fluorescentplates, and developed in 982 toluenelethanolsolvent. Detection is accomplished via fluorescence. After this time, the mixture is cooled and vacuum filtered to remove the salt. The solution is then poured into 100mL of water, whereupon the solid ether precipitates. The ether is collected by vacuum filtration and is recrystallized from a mixed solvent system of ethanol and water. Hazardous Warning Both phenol and benzyl chloride are toxic. Benzyl chloride is an irritant to the eyes, mucous membranes and skin, thus the reagents should be mixed in a hood.
