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 Completion date: March 28th, 2013 Submission date: April 4th, 2013 Pages in lab notebook: 21-23

___________________________ Signature

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)

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).

Synthetic Equations Theoretical Yield of Methyl Salicylate

( )( )( )

Percent Yield of Methyl Salicylate

[ ]

Overall Reaction of Salicylic Acid and Methanol to Methyl Salicylate

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 Density: 1.33 g/mL

[1]

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

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 Hazards: Toxic by ingestion.

Structure:

Name: Sodium Sulfate (Anhydrous) Molecular Weight: 142.04 g/mol Melting Point: 884 C Hazards: Irritant. Structure:

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.

Calculations Theoretical Yield of Methyl Salicylate

( (

)( )

)(

Percent Yield of Methyl Salicylate

[ ]

10

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 %

11

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 (134136 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 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

12

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 (109110 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 experiments objectives were successfully completed.

13

References
[]

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