WILLIAMSON ETHERIFICATION SYNTHESIS OF PHENYL ETHYL ETHER

DANA REVENCU-s1057552

ABSTRACT
Ethers are an essential class of compounds which find their applicability in medicine as anesthetics, in
agriculture as insecticides and as solvents for oils, waxes, perfumes. Williamson etherification synthesis
is one route for synthesizing ethers. The aim of this experiment was to synthesize phenyl ethyl ether by
reacting phenol with ethyl bromide in the presence of a catalyst-potassium iodide. The synthesis was
done heating to reflux in an oil-bath and the progress was monitored by TLC. Further on, the extraction
was done and the product was purified and analyzed by means of fractional distillation, refractive index,
GC-MS and 1H-NMR. The refractive index was 1,507. The Rf value of phenyl ethyl ether – 0.63. The gas
chromatogram showed a retention time of 2.105 with an area of 248153577. The mass spectra showed
the molecular ion with a m/z of 122-the product. The 1H-NMR spectra showed 5 signals: 1.53-0.76 ppm
corresponds to the 5 H of the ethyl group, 4.14-3.23 ppm and 7.46-6.20 ppm correspond to the protons
attached to the benzyl ring. As the fractional distillation never happened, the yield was not calculated.

In conclusion, the experiment went as expected and the synthesis of phenyl ethyl ether was achieved,
although the fractional distillation did not take place due to low yield, thus low pressure.

INTRODUCTION

Ethers represent an important class of compounds which are extremely useful as solvents for fats, oils,
waxes, perfumes, dyes and a lot more. It plays an exceptionally important role in medicine, as well.
Codeine, for example, a potent pain-relieving drug is the methyl ether of morphine. Williamson
etherification synthesis is a simple way to generate an ether. The process involves an organic chemistry
SN2 reaction where a halide is displaced from an alkyl halide by an alkoxide ion to produce an ether.
(Figure 1) The alkoxide ion acts as a nucleophile, attacking the electrophilic carbon with the leaving
group. This method allows the formation of both symmetrical and asymmetrical ethers (two different alkyl
groups).

According to literature, a typical Williamson reaction is conducted at 50-100C and is completed in 1 to 8

hours. [2] In most of the cases, the completion of the reaction is not achieved, as the starting material is
still present in the solution. Side reactions are also common during this process. Catalysis is not usually
used in the lab, but if the alkylating agent is unreactive, iodide salt is utilized as a catalyst in order to lower
the rate of the reaction. [2]

This experiment was aimed at converting phenol into phenyl ethyl ether using n-ethyl bromide and
ethanol as solvent. The reaction mixture was heated to reflux in an oil-bath, as the reaction does not
occur quickly at room temperature and require a period of heating. In order to speed up the reaction,
potassium iodide was used as a catalyst, as the ethyl bromide was unreactive. The resulting yellow oil
was extracted with diethyl ether and further washed with water and brine to isolate the desired compound.

After the synthesis and isolation step, it was important to identify and analyze the targeted compound.
The purification and analysis were done using fractional distillation, GC-MS and 1H-NMR spectrometry,
keeping in mind that some limitations of the Williamson reaction might have had occurred. Alkoxides may
undergo C-alkylation alongside to the expected ether formation. On top of that, secondary alkyl halides, in
our case ethyl bromide may undergo E2 elimination in the presence of the alkoxide. Thus, an alkene may
be produced due to this reaction. [2]

To help mitigate the issues stated above, most organic chemists use microwave-enhanced technology in
order to speed up the reaction time. This technique decreases the amount of time needed for refluxing up
to minutes and is run at 130C. According to some data acquired from several different labs using the
technology, the yield has increased from a range of 6-29% to 20-55%. [3] When considering minimizing
the side reactions, it is best to use a primary alkyl halide which is basic and not sterically hindered. [4]
 To sum it up, the aim of the experiment was to synthesize and identify phenyl ethyl ether (yellow oil) by
means of Williamson etherification reaction. (Figure 1)

Figure 1. The mechanism of reacting phenol with sodium alkoxide- Williamson etherification synthesis.
Drawn by Chemdraw

EXPERIMENTAL

A solution of sodium ethoxide was prepared in a round bottom flask by dissolving small pieces of 5,7 g of
Na (250 mmol) in 75 mL of absolute ethanol. The solution was stirred continuously until all the sodium
was dissolved (1 hour). 18 g of phenol (200 mmol) were dissolved in approximately 10 mL of ethanol. The
solution was added to the reaction mixture, as well as 16 mL of n-ethyl bromide and a scoop of potassium
iodide. The reaction mixture was heated up to reflux at 300C. When the thermometer showed +83C, the
temperature was lowered and was kept at 140C. The progress of the reaction was monitored by TLC
(silica, ethyl acetate/heptane, 50:50). The TLC plates were examined under UV light. Removed the
solvent under reduced pressure. The crude product was washed with 100 mL of NaOH (1 mol dm-3). 3
extraction were carried out and the organic layer was collected: diethyl ether (3x50 mL), water (3x50 mL)
and brine (3x50 mL). The organic layer was dried over calcium chloride and filtered. The solvent was
removed under reduced pressure. Fractional distillation was performed. The process was stopped as the
temperature did not increase above 26C. The product was analyzed with TLC. As the fractional distillation
never happened, the yield was not calculated.

Yellow oil; Refractive index: 1,507. Rf values: phenol- 0.72, phenyl ethyl ether- 0.63. GC: retention time:
2.105 min., area- 248153577 (split injection in a 25.0 split ratio, temp.: 250C, carrier gas: H2). MS:
calculated for (C8H10O) m/z 122.17; found 122.05 (C8H10O+, 36.20%), base peak m/z=94 (C6H5O+, 100%).
1H-NMR (300MHz, CDCl3, ppm) δ 7.46 – 6.20 (m, 5H), 4.14 – 3.23 (m, 2H), 2.25 – 1.61 (m, 1H), 1.53 –
0.76 (m, 3H).
RESULTS AND DISCUSSION

After conducting the purification and analysis of the generated phenyl ethyl ether, the following results
were obtained. Fractional distillation was started but the temperature never increased above 26C, so the
process was stopped after 1-2 hours of monitoring and increasing the temperature of the heating mantle.
This might have happened due to a low presence of the compound in the flask, thus not enough pressure
to raise the temperature. TLC was done in order to verify the presence of the product. Rf value of 0. 63
was obtained. Phenol was still present in the reaction and the Rf value:0 72. The yield could not be
calculated due to the presence of the starting material. The refractive index indicated a value of 1.507,
which represents a value within the expected range [1], thus the presence of impurities was probably very
low, as well as that of phenol.
The GC-MS analysis was conducted using a split injection in a 25.0 split ratio at 250C. The gas
chromatogram (Figure 3) showed one peak with an area of 248153577 and a retention time of 2.105 min.
Furthermore, the mass spectrum of the compound was derived (Figure 4). The molecular ion with a m/z
of 122.05 with an abundance of 36.20% was detected which corresponds to the molecular weight of
phenyl ethyl ether: 122.17. The peak m/z at 123 might have had represented the presence of an isotope
A base peak at m/z of 94 corresponds to the phenolate ion, it is attributed to the loss of the ethyl radical
from the molecular ion. The phenolate ion showed the highest abundance (100%). A peak at m/z of 107
was observed due to a loss of methyl radical from the molecular ion. Signals at 39. 51 and 66 Da
correspond to the splitting of the phenol group.

After performing 1H-NMR spectrometry (300 MHz, CDCl3, ppm), 5 signals were present, each
representing a proton environment. (Figure 5)

Figure 2. Structure of phenyl ethyl ether

One signal was observed at 0.76-1.53 ppm which corresponds to 3H of the methyl group (HD-Figure 2).
The signal at 3.23-4.14 ppm corresponds to the 2 protons bonded to the secondary carbon (HA) On the
left side of the spectrum, at 6.20-746 ppm, the signals correspond to the hydrogens of the benzyl ring (HB,
HC). Moreover, two additional signals were observed representing possible impurities. One signal at 1.61-
2.25 ppm corresponds to the water present in the solution. The shift at 7.72 ppm represents the solvent
used: CDCl3.

Due to time limit, the refluxing had to be stopped after 3h, even though the reaction didn’t go to
completion. The TLC showed small traces of phenol in the solution and a big, pronounced spot of the
product. This might have influenced the yield as not all the phenol reacted with sodium alkoxide.

The data from GC-MS and NMR are consistent and both respond to the final product: phenyl ethyl ether,
incorporating at the same time the presence of phenol- starting material. The product was relatively pure,
with small traces of water and d-chloroform (solvent).

Overall, the experiment went as expected and the product was formed and purified, although some
improvements may have been done such as: using a microwave-enhanced technique to speed up the
reaction and completing the reaction. Despite the outcome of the fractional distillation, the product was
pure, with no traces of impurities other than water and d-chloroform.
 REFERENCES:

1. Francesconi, Romolo; Bigi, Adriana; Comelli, Fabio[Journal of Chemical and Engineering

Data, 2005, vol. 50, # 4, p. 1404 - 1408]

2. Libretexts. 15.3: The Williamson Ether Synthesis [Internet]. Chemistry LibreTexts. Libretexts;
2016 [cited 2022 Mar 9]. Available from:
https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Map
%3A_Organic_Chemistry_(Wade)/15%3A_Ethers_Epoxides_and_Thioethers/
15.03%3A_The_Williamson_Ether_Synthesis
3. Baar, Marsha R.; Falcone, Danielle; Gordon, Christopher (2010). "Microwave-Enhanced
Organic Syntheses for the Undergraduate Laboratory: Diels−Alder Cycloaddition, Wittig
Reaction, and Williamson Ether Synthesis". Journal of Chemical Education. 87 (1): 84–
86. Bibcode:2010JChEd..87...84B. doi:10.1021/ed800001x
4. Dhaneeshwor. Williamson Reaction - Mechanism, Conditions & Applications | ProtonsTalk
[Internet]. ProtonsTalk. 2021 [cited 2022 Mar 5]. Available from:
https://protonstalk.com/alcohols-phenols-ethers/williamson-ether-synthesis-reaction/

APPENDIX:

Figure 3. Gas chromatogram of phenyl ethyl ether

Figure 4. Mass spectra of phenyl ethyl ether

Figure 5. 1H-NMR spectra of phenyl ethyl ether (300 MHz, CDCl3, ppm)