Department of Chemistry

Virginia Commonwealth University

CHEZ 302 – Organic Chemistry II Lab

Experiment #8: Synthesis of an Ester

Submitted by: Joseph Thomas Morrison ___________________________

Start date: March 28th, 2013 Signature

Completion date: March 28th, 2013

Submission date: April 4th, 2013

Pages in lab notebook: 21-23

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Table of Contents

1. Title Page…………………………...……………………………………

2. Table of Contents………………………………………………………...

3. Objective……………………………………………………………........

4. Synthetic Equations…………………………………………..………….

5. Physical Properties……………………………………...……………….

6. Experimental Procedure…………………...…………………………….

7. Calculations……………………………………………………………...

8. Results…………………………………………………………………...

9. Discussion……………………………………………………………….

10. References…………………………………...…………………………..

11. Attachments

IR Spectrum of Product (Methyl Salicylate)

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Objective

The objective of this experiment was to form methyl salicylate from salicylic acid and

methanol in the presence of an acid catalyst through a facilitated esterfication chemical reaction

using the techniques of heating under reflux, separation, gravity filtration, and rotary evaporation

while driving the reaction equilibrium toward the products by using an excess of methanol. An

additional objective of this experiment was to validate the product (methyl salicylate) using the

techniques of percent yield calculation and IR (infrared spectroscopy).

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Synthetic Equations

Theoretical Yield of Methyl Salicylate

(mols of Limiting Reagent )( molsof Methl Salicylatemols of Limiting Reagent )( gramsof Methyl Salicylatemol of Methyl Salicylate )=TheoreticalYield of Methyl Salicylate

Percent Yield of Methyl Salicylate

[ Actual Yield of Methyl SalicylateTheoreticalYield of Methyl Salicylate ]×100 %=Percent Yield of Methyl Salicylate

Overall Reaction of Salicylic Acid and Methanol to Methyl Salicylate

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Physical Properties

Note: All physical properties of liquids and solids from this experiment were obtained from

Sigma Aldrich. [1]

Liquids

Name: Methanol

Molecular Weight: 32.04 g/mol

Boiling Point: 64.7 °C

Density: 0.7918 g/mL

Hazards: Flammable and toxic.

Structure:

Name: Sulfuric Acid

Molecular Weight: 98.08 g/mol

Boiling Point: 337 °C

Density: 1.84 g/mL

Hazards: Corrosive and toxic.

Structure:

Name: Methylene Chloride

Molecular Weight: 84.93 g/mol

Boiling Point: 39.6 °C

1[] Sigma-Aldrich. N.p., n.d. Web. 13 Mar. 2013. <.http://www.sigmaaldrich.com>.

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Density: 1.33 g/mL

Hazards: Carcinogen.

Structure:

Name: Sodium Bicarbonate

Molecular Weight: 84.01 g/mol

Boiling Point: 851 °C

Density: 2.20 g/mL

Hazards: Irritant.

Structure:

Name: Methyl Salicylate

Molecular Weight: 152.15 g/mol

Boiling Point: 220-224 °C

Density: 1.174 g/mL

Hazards: Toxic by ingestion.

Structure:

Solids

Name: Salicylic Acid

Molecular Weight: 138.12 g/mol

Melting Point: 159 °C

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Hazards: Toxic by ingestion.

Structure:

Name: Sodium Sulfate (Anhydrous)

Molecular Weight: 142.04 g/mol

Melting Point: 884 °C

Hazards: Irritant.

Structure:

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Experimental Procedure

To a 50 mL round-bottom flask, 4.9 grams of salicylic acid (4.9 grams, 0.035 mols) was

added. 12.5 mL of methanol (9.9 grams, 0.309 mols) was added to the flask, and the flask was

swirled to dissolve the solid. When the solid was dissolved, 5.0 mL of concentrated sulfuric

acid (9.2 grams, 0.094 mols) was slowly added with swirling. A white solid formed in the

flask. A reflux condenser was attached and the mixture was heated at reflux for 45 minutes. A

layer of oil formed on the top of the refluxing mixture. The mixture was swirled occasionally

during the reflux period. The reaction mixture was allowed to cool to room temperature. 10

mL of ICE water was added to the mixture and the contents of the flask were transferred to a

separatory funnel. The product (methyl salicylate) was extracted into two 15 mL portions of

methylene chloride (19.9 grams, 0.235 mols). The mixture was shaken gently during the

extractions and washings. The combined methylene chloride extracts were washed with 15

mL of water, followed by 15 mL of 5 % aqueous sodium bicarbonate solution (33.3 grams,

0.393 mols). The organic layer was dried over sodium sulfate and then gravity filtered into a

pre-weighed 100 mL round-bottom flask (39.5 grams) and the solvent was evaporated using a

rotary evaporator. The product was an oil – and care was taken not to evaporate past the point

where the solvent was gone, or evaporation (and, therefore, loss) of the product occurred. The

product was weighed and the percent yield was determined. An IR and an NMR were run on

the product.

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Calculations

Theoretical Yield of Methyl Salicylate

( 4.9 gSalicylic Acid

( 138.12g Salicylic Acid1mol Salicylic Acid ) )(

1molMethyl Salicylate1mol Salicylic Acid )( 152.15 gMethyl Salicylate

1molMethyl Salicylate )=5.40gMethyl Salicylate

Percent Yield of Methyl Salicylate

[ 5.03 gMethyl Salicylate5.40 gMethyl Salicylate ]×100%=93.15 %

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Results

IR Results

The IR spectrum showed peaks at 3100 cm-1, 1640 cm-1, 1500 cm-1, and 1050 cm-1, which

represented a C=CH aromatic stretch, C=O amide, C=C aromatic, and a C-O ether respectively.

NMR Results

The NMR spectrum showed a 2H doublet at7.4 ppm, 2H doublet at 6.8 ppm, 2H quartet at 4.0

ppm, 3H singlet at 2.1 ppm, and a 3H triplet at 1.4 quartet at 1.4 ppm, which represented

hydrogen(s) attached to a aromatic group (CH), aromatic group (CH), OC6H5 group (CH2),

CONR2 group (CH3), and a CH2R group (CH3) respectively.

Percent Yield

The percent yield of phenacetin from the experiment was determined to be 35.39 %

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Discussion

The objective of this experiment was to form phenacetin from acetaminophen through a

facilitated Williamson ether synthesis chemical reaction using the techniques of heating under

reflux, vacuum filtration and recrystallization incorporating a mixed-solvent system. An

additional objective of this experiment was to validate the product (phenacetin) using the

techniques of melting point determination, percent yield calculation, IR (infrared spectroscopy),

and NMR (nuclear magnetic resonance). The melting point of the product was determined to be

109-110 °C which was significantly lower than the literature melting point of phenacetin (134-

136 °C) which supported the hypothesis that impurities were present in the product. Phenacetin

was successfully formed during this experiment with a determined percent yield of 35.39 %. As

stated earlier in this report, the IR spectrum showed peaks at 3100 cm-1, 1640 cm-1, 1500 cm-1,

and 1050 cm-1, which represented a C=CH aromatic stretch, C=O amide, C=C aromatic, and a

C-O ether respectively. These results were representative of the results expected from the IR

spectrum of pure phenacetin. As stated earlier in this report, the NMR spectrum showed a 2H

doublet at7.4 ppm, 2H doublet at 6.8 ppm, 2H quartet at 4.0 ppm, 3H singlet at 2.1 ppm, and a

3H triplet at 1.4 quartet at 1.4 ppm, which represented hydrogen(s) attached to a aromatic group

(CH), aromatic group (CH), OC6H5 group (CH2), CONR2 group (CH3), and a CH2R group (CH3)

respectively. These results were representative of the results expected from the NMR spectrum

of pure phenacetin with one exception. It was expected that there would be a 1H singlet at 8 from

the amide N-H, however this peak was not observed in the NMR spectrum which indicated that

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human error or equipment error was a possible factor in the non-existent peak. In this

experiment, p-acetamidophenol (acetaminophen), a phenol, was be de-protonated by sodium

methoxide. The resulting phenoxide ion then reacted with bromoethane (ethyl bromide) to give

phenacetin (p-ethoxyacetanilide). Because of the nature of a Williamson ether synthesis, adding

equimolar amounts of acetaminophen and sodium methoxide was crucial in preventing unwanted

side reactions and to obtain the pure phenacetin product. The results of the Williamson ether

synthesis showed that human error was probable due to the significantly low melting point (109-

110 °C) and the significantly low percent yield of phenacetin (35.39 %). Of which, human error

in the form of the addition of non-equimolar amounts of acetaminophen and sodium methoxide

mistakenly was probable. The results of the Williamson ether synthesis also showed that

equipment error was probable due to the missing peak in the NMR spectrum (amide N-H) but the

represented C=O amide peak in the IR spectrum. Overall, phenacetin was obtained from the

experiment using the techniques of heating under reflux, vacuum filtration and recrystallization

incorporating a mixed-solvent system. The product was also validated using the techniques of

melting point determination, percent yield calculation, IR (infrared spectroscopy), and NMR

(nuclear magnetic resonance). Therefore, the experiment’s objectives were successfully

completed.

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References

[] Sigma-Aldrich. N.p., n.d. Web. 13 Mar. 2013. <.http://www.sigmaaldrich.com>.

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