Williamson ether synthesis of 2-octadecyloxy-naphthalene

Abstract
The Williamson etherification method is commonly used to synthesize an ether with the
use of an alkoxide intermediate and an alkyl halide. In this experiment,
2-octadecyloxy-naphthalene crystals were synthesized in a 2 step reaction; involving
the deprotonation of 2-naphthol (using cesium carbonate) to form an alkoxide
intermediate, followed by an Sn2 substitution reaction with 1-bromooctadecane to
ultimately form crystals of the desired product. However, impurities were still present
within the product; so by employing various methods, these impurities were extracted
and filtered, and the product recrystallized to retain pure 2-octadecyloxy-naphthalene
crystals.

Introduction
Seeing how it was the first lab done within the first year of our Chemistry course, the
Williamson ether synthesis provided a good (and challenging) foundation to start our lab
work with. The specific method necessary to successfully create pure crystals of the
2-octadecyloxy-naphthalene introduced us to a new skillset and mindset as the
approach towards lab-work needs to include accuracy, as well as encompass safety
standards. Therefore a lot of safety regulations had to already be addressed within the
preparation. Seeing as most resources were given to us concerning the experiment
itself, the research question should focus more on how to properly carry out the
experiment. Therefore, the research question addressed in this report is as follows: How
does Williamson etherification yield pure ether crystals?

Theory
The synthesis of 2-octadecyloxy-naphthalene follows 2 mechanisms[1] that create the
crystals of the product. Firstly, certain quantities of 2-naphthol, 1-bromooctadecane, and
cesium carbonate were dissolved in acetonitrile by heating the mixture under reflux
conditions. Here the first mechanism presents itself, whereby the cesium carbonate
allows for the deprotonation of 2-naphthol. As seen in Figure 1, the oxygen on the
cesium carbonate is able to attack the proton on the 2-naphthol, leaving the oxygen with
a negative charge. The deprotonation of 2-naphthol leads to the production of the
alkoxide intermediate.

Figure 1: The mechanism showing the formation of the alkoxide by deprotonation of the 2-naphthol

This mechanism also indicates that an impurity will be present in the final mixture of
compounds, namely the protonated cesium carbonate. Next, the alkoxide capable of
acting as a nucleophile, allowing for a Sn2 substitution to take place with the
1-bromooctadecane. In this reaction, the alkoxide intermediate substitutes the Bromine

atom, whereby Br- is left present in the mixture. (another impurity within the mixture) The
mechanism for the substitution is seen in Figure 2.

Figure 2: the mechanism showing the Sn2 substitution of the Br-- with the alkoxide intermediate, whereby
an ether bond (R-O-R) is formed.

While the reaction mixture is undergoing reflux, Thin Layer Chromatography (TLC)
needs to be used to confirm whether all of the reactants have been converted to
products. TLC is accomplished by putting a spot of starting mixture, (2-naphthol
dissolved in acetonitrile) and a spot of the mixture engaging in reflux, next to each other
on on a layer of silica (SiO2) on an aluminium foil. The bottom part of this plate is then
put in a mixture of heptane and ethyl acetate which act as the eluent (with correct
polarity) for the mobile phase. As the eluent moves vertically up the plate (stationary
phase) it interacts with the compounds present in the mixture to reveal whether all the
reactants have been formed into their products. If a lot of product has been formed, the
compound will move farther up the stationary phase with the eluent, while the reactants
tend to not move up as much as the product does.
Once it is confirmed that the majority of reactants have formed products, the final
product needs to be separated from its impurities and solvents. This is done through
various methods, the first of which is the use of a rotary evaporator to evaporate the
acetonitrile (solvent) at a reduced pressure*. The acetonitrile then condensates into
another round bottom flask.
This procedure is then followed by extraction, whereby the solution is mixed with
quantities of diethyl ether and water, and thusly washed. This washing is done by
shaking a separatory funnel and releasing pressure that is created by the mixing of
layers. The organic layer (product) will dissolve within the layer of diethyl ether, while
impurities (cesium carbonate and Br-) will be washed away with the H2O(which is more
dense than the diethyl ether layer, thus forming the bottom layer within the funnel. This

process is repeated 3 times with H2O as added solvent, followed by another trial with
brine(saturated salt solution), to separate and filter out residue water molecules. Next,
the solution is stirred with MgSO4 and filtered using Buchner funnel attached to a flask
with vacuum a pump. Here, the MgSO4 is used to dehydrate the solution completely,
leaving only the desired product dissolved in diethyl ether.
Using the rotary evaporator once more, the diethyl ether is evaporated and separated,
leaving only the desired product in its solid form. The 2-naphthyl ether solid is then
heated with ethanol as solvent under reflux conditions to allow for crystallization. The
reflux condenser is used to ensure that all the product can dissolve within the ethanol
without ethanol evaporating too quickly. As a last step for the formation of crystals, the
solution needs to cool down while attached to a CaCl tube, this in order to filter any CO2
created during the combustion of the ethanol. Lastly, the crystals are filtered over a
Buchner funnel to create the final pure product.

Experimental
0.5g or 2-naphthol was dissolved in 25 ml of acetonitrile in a 3-necked flask. The flask
was attached to a reflux condenser and magnetic stirrer(and hot plate), whereby a
temperature of 100 degrees celsius was chosen as it is well above the boiling point for
acetonitrile[2]. The magnetic stirrer was put up to around 400 rpm to allow for steady
stirring. While the solution started to heat up, approximately 1.15g of C2CO3 and 1.18g
C18H27 were added to the solution. This process was left alone for approximately 50
minutes before a first trial of TLC was used to check the progress of the reaction.
Seeing the resulting Rf value, it was concluded that the reaction still needed to go to
completion. After approximately 2 hours since the start of the reflux, another TLC check
confirmed that a majority of the reactants had formed product.
The solution was then transferred into a 250 ml round bottom flask and into the
rotary evaporator, whereby the acetonitrile was evaporated at a reduced pressure of
approximately 226 mBar at 40 degrees Celsius. After condensation of acetonitrile
stopped occurring, it was concluded that it had been fully separated from the solution.
Next, approximately 200 ml of diethyl ether was added to the residue of the
solution, and was thoroughly washed 3 times with H2O in a separatory funnel, followed
by an addition trial with Brine to dehydrate the solution. Here it was observed that the
organic layer dissolved within the diethyl ether, while impurities mixed with the water, as
the H2O layer in the first and second trial of washing had a faint yellow hue to it due to
these impurities.
Following this, the resulting solution was placed in an Erlenmeyer flask and
stirred with a magnetic stirrer while adding an arbitrary amount of solid MgSO4 to it as a

final dehydration process of the water molecules still present within the solution. The
MgSO4 was then filtered using a Buchner funnel attached to a vacuum pump. The first
trial of filtration did fail due to the filter paper not being stuck properly to the Buchner
funnel. After successful filtration, the solution presumed completely dehydrated, (despite
an arbitrary amount of MgSO4 was used) and transferred into a clean 250 ml round
bottom flask and placed into the rotary evaporator to separate the diethyl ether. The
diethyl ether was evaporated at a reduced pressure of approximately 800 mBar at 40
degrees celsius.
Now being left with solid product in the round bottom flask, the product was
dissolved using a small amount of technical grade ethanol and transferred to a clean 3
necked flask. Then the 3 necked flask was attached to a reflux condenser and magnetic
stirrer and heated to 100 degrees celsius to account for the boiling point of ethanol[3].
(stirring happened at 400 rpm) More ethanol was added in the process to ensure that all
the product would dissolve. After leaving this process to occur for approx. 35 to 40
minutes, the flask was attached to a CaCl tube and left to cool down. However, after 20
minutes of naturally cooling down, the scarcity of time in the lab became apparent when
the flask containing the solution had to be transferred to an ice-bath to artificially cool
down the solution. This resulted in some errors when it came to checking the purity of
the crystals. After the solution had cooled down, a Buchner funnel attached to a flask
with vacuum pump were used to filter the crystals from the ethanol; leaving the
presumed pure crystals.
Afterwards, a small sample of the crystals were used to determine their melting
point.

Results
The following table shows the calculation for the Rf values for both trials done at
separate time intervals. The units for the movement of both the mobile phase and
the movement of the compound vertical across the stationary phase is in cm.
The calculation for Rf values is

Rf =

movement of compound
movement of eluent

Mobile phase

Compound

Trial 1 (cm)

4.5

3.0

0.625

Trial 2 (cm)

4.0

2.9

0.725

The weight of the petridish was 142.0 grams exactly, while the petri dish with the
crystals had a weight of 144.5 grams. Therefore the yield of crystals was about

actual yield

2.5 grams. The equation for percentage yield is %yield = theoretical yield 100 ,
where the theoretical yield equals the Molar weight of 2-naphthyl ether
(396.65g/mol) times the amount of moles that should be theoretically produced
(3.5mmol). So (396.5g/mol x 0.0035)= ~1.39g theoretical yield.
Based on this equations, the percentage yield of this experiment is about 180%,
which is very inaccurate, yet possible due to the solution with ethanol being
artificially cooled, so there are still impurities within the crystals.
The melting point for the crystals was measured to be 64.5 degrees celsius,
which is narrowly within the literary values of 64~68 degrees celsius.

Discussion
It should definitely be mentioned that the weighted value for the 1-bromooctadecane
was slightly inaccurate to a value of 1.184 instead of the initially calculated value of
1.179, (which was then rounded up) this probably caused a small error concerning the
percentage yield of the crystals.
Secondly, discussing the Rf values for the TLC trials, the second trial is closer to
the theoretical value of all reactants having been formed to product (approximately 0.9),
although not by much. Seeing as the Rf calculations have been done after the
experiment was finished, this might explain the lowered value for percentage yield,
whereby when the reflux process was stopped, not all the reagents formed product.
Thirdly, since the cooling of the flask containing the product crystals and ethanol
was artificially sped up through use an ice bath, the ethanol was not completely dried,
causing the product to be very impure. This would explain its absurdly high mass of
2.5g compared to the theoretical value of 1.39g. This would also explain its low melting
point of 64.5 degrees compared to the literary value ranging between 64 and 68
degrees. Although the crystals were within the range of the literary values, the melting
point was narrowly on the edge, thus it is being presumed that there were impurities left
within the solution.

Conclusion
Despite the errors in following the exact methodology of the experiment, 2-naphthyl
ether was still successfully produced. However, the last step of cooling down the
solution containing the product and the ethanol accounts for a large error concerning
the percentage yield. Therefore it is concluded that the resulting crystals were far from
pure. To answer my research question, a lot more efficiency and patience would lead to
better results with a more pure yield. This experiment will have to be referenced in
future endeavours to create a yield that is more pure with accurate numbers so the
percentage yield can be found without any errors.

Bibliography
[1] Williamson Ether Synthesis. ~ Name-Reaction.com,
http://www.name-reaction.com/williamson-ether-synthesis.

[2] Acetonitrile MSDS. Sciencelab, http://www.sciencelab.com/msds.php?msdsid=9927335.

[3] Ethanol MSDS. Nafaa.org, http://www.nafaa.org/ethanol.pdf