Experiment 32: Multi-Step Synthesis

Morgan Lepley (Lab partner: Lauren Mullinax Johnson)

Organic Chemistry Lab, CHEM 369 The University of Tennessee, Knoxville TA: Bo Meng Instructor: Dr. Laureta Smith Date Performed: 4 August 2011 Due Date: 8 August 2011

Introduction: The purpose of this experiment is to convert benzaldehyde to benzilic acid with a three-step set of reactions. With the use of a thiamine-catalyzed reaction, two equivalents of benzaldehyde react to form benzoin. Step two oxidizes benzoin to form benzil by using nitric acid. Finally, benzil rearranges to form benzilic acid by reactions with KOH and then H3O+. The full experiment can be found in Introduction to Organic Laboratory Techniques: A Small Scale Approach as Experiment 32. Thiamine hydrochloride is used as a green reagent as opposed to thiamine pyrophosphate (TPP) to catalyze the benzoin condensation. In the reaction, the proton at carbon two is removed with a weak base to form the ylide, which acts as a nucleophile and adds to the carbonyl group of benzaldehyde. Then another proton is removed with a base to form a double bond, which then reacts with another equivalent of benzaldehyde to form another intermediate. The base then removes another proton to yield benzoin and the ylide, which can hen react with more molecules of benzaldehyde. Next, the benzoin produced in the first step is oxidized with nitric acid to prepare benzil in the final reaction, the benzil produces is rearranged with potassium hydroxide and then an acid reaction, the benzil produced is rearranged with potassium hydroxide and then an acid (hydrochloric acid). The addition of potassium hydroxide to benzil yields a carboxylate salt, potassium benzilate, which then reacts with an acid to produce the final product< benzilic acid.

Equation 1: Thiamine Catalysis of Benzoin

Equation 2:Oxidation of Benzil

Equation 3: Rearrangement of Benzil to Benzilic Acid

Infrared Spectroscopy (IR) is performed after each step to determine if the desired product is formed. The 1H and 13C Nuclear Magnetic Resonance Spectroscopy (NMR) of the final product is also determined to ensure the correct product is created. These spectra can be found in the attached appendix. Procedures On the first session of the experiment, 1.5 g of thiamine hydrochloride was added to a 50-mL Erlenmeyer flask. The solid was then dissolved by swirling in 2mL of H2O. 15-mL of 95% ethanol was then added to the flask and the solution was swirled until homogeneous. Next, 4.5-mL of aqueous NaOH solution was added and

swirled until the color changed from a bright yellow to a pale yellow. 4.5-mL of pure benzaldehyde was added to the flask and swirled until homogenous. This flask containing the solution was then closed with a stopper and placed in the lab drawer to crystallize until the next lab period. For the second lab session, the crystals were broken up with a metal spatula and the solution was rapidly swirled and quickly transferred to a Buchner funnel to be vacuum filtered. The benzoin crystals were washed with two 5-mL portions of ice-cold and allowed to dry for 5 minutes in the funnel. After drying, the percent yield and melting point of the crystals were determined. The crystals were then recrystallized and vacuum filtered while washed with 95% ethanol. The percent yield and melting point were then recalculated. The crystals then went into a drying oven fro 20 minutes before being placed in the lab drawer to air-dry until the next week. The third session of the experiment began the synthesis of benzil. 2.50g of benzoin were placed in a 25-mL round bottom flask and then 12-mL of concentrated HNO3 was carefully added along with a magnetic stir bar. A condenser was attached and the whole apparatus was placed under the hood where it was heated in a hot water bath (~70C but not above) for one hr with stirring. The solution was then poured into a 40-mL of cool H2O and stirred vigorously until the oil crystallized completely as a yellow solid. The crystals were then vacuum filtered, washed with cold water, and allowed to dry in the funnel. The crystals were then weighed and the percent yield was calculated. They were then dissolved in hot 95% ethanol in an Erlenmeyer flask on a hot plate with a 10mL/g ratio. Once dissolved it was allowed

to cool slowly until crystals formed and was then placed in an ice bath. The crystals were vacuum filtered, rinsed with ice-cold ethanol, and allowed to sit until the next lab period. On the final week of the experiment the percent yield and melting point of benzil were determined and then the synthesis of benzilic acid was started. 2.0 g of benzil and 6-mL of 95% ethanol were added to a 25-mL round bottom flask with a boiling stone and attached to a condenser. The apparatus was the heated with a heating mantle until the solid dissolved. 5-mL of aq. KOH was added drop-wise and the mixture was gently boiled and swirled for 15minutes. The condenser was detached when the mixture cooled and was then transferred to a small beaker to cool to room temperature. It was then placed in an ice bath for 15 minutes for crystallization and then was vacuum filtered and rinsed with 4-mL portions of icecold ethanol and then transferred to a 100-mL Erlenmeyer flask containing 60-mL of 70 C H2O. The solution was stirred until the solid dissolved. Unfortunately, the solution did not undergo gravity filtration after the solid was most dissolved. 1.4-mL of concentrated HCI was then carefully added drop-wise while swirling until a precipitate formed and a pH of 2 was recorded. Once at room temperature, the solution was placed in an ice bath for 26 minutes and then vacuum filtered, rinsed with 30-mL portions of ice-cold water, and placed in a drying oven for 20 minutes. The product was then weighed, the percent yield and melting point were determined, and an IR was obtained.

Data
Compound Thiamine Hydrochloride Ethanol Role in Experiment Used in Exp. 32A to make the reaction mixture Used in all three parts of the experiment; used to wash the crystals in the Buchner funnel. Used in Exp. 32A to make the reaction mixture Used in Exp. 32A to make the reaction mixture Used in the preparation of Benzil Used in Exp. 32B to make the reaction mixture Used in Exp. 32C for the preparation of Benzilic Acid Used in Exp. 32C to prepare Benzilic Acid. Used in Exp. 32C to prepare Mol wt (g/mol) 337.27 Amount used 1.5g m. p. (C) 248-260 b. p. (C) Density (g/cm3) Hazard Low toxicity, may cause burning sensation

46.07

21-mL

-114.3

78.4

.789

Volatile and Flammable

Aqueous Sodium Hydroxide Benzaldehyde

39.997

4.5-mL

318

1388

2.13

Causes burns

106.12

4.5-mL

-26

178.1

1.0415

Fire hazard May cause irritation to skin and eyes Corrosive Cause eye and skin irritation

Benzoin

212.24

2.5 g

137

344

1.31

Nitric Acid

63.012

12-mL

-42

83

1.5129

Benzil

210.23

2.0 g

94.4395.08

346- 348

1.23

Potassium Hydroxide

56.105 6

5-mL

360

1327

2.044

Reacts violently with acids. Corrosive

Hydrochloric Acid

36.46

1.3-mL

-27.32

110

118

Benzilic Acid

OH

Benzoin IR refers to Figure 1. IR Cm -1 3416.34 2922.50 1678.52 1050-1150 1450, 1500, 1580, 1600 Stretch R-OH Ar-C-H C=O C-O alcohol C=C within Aromatic

Benzil IR refers to Figure 2. IR Cm -1 2921.6 1680 1591.70, 1452.21 1173.51 Stretch H-C-C-H C-C=O-R C=C within an Aromatic C=O

O
1 6

OH
3 2 5 4

OH

Benzilic Acid IR refers to Figure 3. IR Cm -1 3399.06 2904.71 1247.95 1175.74 Stretch Ar-C-H H-C-C-H C=C within Aromatic C=O

Chemical shift 12.3 --7.5 7.4 7.3 2.84 Calculations

1H-NMR refers to Figure 4. 13C-NMR refers to Figure 5. 1H-NMR 13C-NMR Integration Splitting Chemical Splitting Assigned Shift (if given) 1H Singlet -----176.12 Singlet 1 --141.06 Singlet 2 4H Multiplet 128.48 Doublet 3 2H Multiplet 128.33 Doublet 4 4H Multiplet 127.30 Doublet 5 1H Singlet 81.2 Singlet 6

Benzoin: 3.18g crude was recovered and 4.68 was the theoretical. 3.18/4.68*100=67.9% Melting point was 130-132 C 3.12g pure was recovered and 3.18 was the theoretical. 3.12/4.18*100=98% Melting point was 134-135 C Benzil: 2.33g crude was recovered and 2.49g was the theoretical. 2.33g/2.49g * 100= 93.6%

1.40g pure was recovered after crystallization and 2.33 was the theoretical. 1.40/2.33*100 = 60.1% Melting Point: 90-92 C Benzilic Acid: 1.72g was recovered and 2.17g was the theoretical. 1.72g/2.17g * 100= 79.3% Melting Point: 147-149 C Mechanisms 1. Benzaldehyde Benzoin through Thiamine Catalyzed Reaction

2. Benzoin (HNO3) Benzil

3. Benzil (1. KOH in Alcohol 2. H3O+) Benzilic Acid

Results and Discussion The experiment began with benzaldehyde and thiamine hydrochloride, which reacted to form a pale-yellow homogenous mix. After sitting and crystallizing

in the dark for one week, a mass of yellow-white crystals was produced and seeding was not necessary. After drying in the Buchner funnel and being washed with icecold water, the mass of the benzoin crystals was calculated to be 3.18g (70% yield) and the melting point was 130 C-132 C. the crystals were the recrystallized again and dried in the Buchner funnel wile washed with 95% ethanol. The second recrystalliztion of the first session yielded a mass of 3.12g (98% yield) of benzoin and a melting point of 134 C-135 C. For the third session of the experiment, benzoin was used to synthesize benzil. 2.5g of the previously synthesized benzoin was used. When mixed with nitric acid and heated for a little over an hour, the mixture turned yellow-orange and a rust colored gas was emitted. When poured into cool water the mixture turned pale yellow and after scratching and seed, crystals formed. After vacuum filtering, 2.33 g of benzil crystals were recovered, which was calculated to be an 94% yield. Dissolving in 20-mL of hot 95% ethanol then purified these crystals. After re-crystallizing, the crystals were again vacuum filtered, rinsed with ice-cold ethanol. The benzil crystals were found to be 1.40 g for a 60.1% yield and have a melting point of 90-92 C off of pure benzils melting point, 95 C. Finally, in the fourth session, the synthesis of benzilic acid was started, 2.00g of benzil was combined with 6-mL of 95% ethanol and reflux condenser was attached. While heating on a heating mantle, 5.0-mL of aqueous potassium hydroxide was added drop=wise with a Pasteur pipet through the condenser. As it was added, a color change occurred and the mixture was dark brown. Once the solution cooled, the condenser was detached and the liquid was transferred to a small beaker and allowed to cool to room temperature. It was then placed into an ice

bath and took about 30 minutes to crystallize instead of 15 minutes, but once the crystals started forming, the entire solution turned into sludgy, brown mass. These crystals were the vacuum filtered and rinsed with 4-mL portions of ethanol, which removed some of the brown tint and the crystals now had more of a tan appearance. Once dried, the crystals were transferred to a 100-mL Erlenmeyer flask with 60-mL of hot water and were stirred until the solid dissolved. Some solid particles remained, but unfortunately, these particles were not filtered out by use of gravity filtration. However, while the solution still warm, 1.3-mL of concentrated HCI was added drop wise while swirling until a precipitant was consistent. The pH was then monitored with litmus paper to determined if the pH value was 2, which produced a dark red color on the litmus paper, the solution as allowed to cool as the benzilic acid crystals formed and were again vacuum filtered and rinsed with 30-mL portions of water and then allowed to dry in the funnel before they were placed in a drying oven for 15 minutes. The final crystals were found to weigh 1.72 g, which gave a high percent yield of 79.3%. The melting point was calculated as 147 C-149 C, slightly off from the pure melting point of benzilic acid, 150 C. After each product was made (benzoin, benzil, and benzilic acid), and IR spectrum was conducted. For the benzoin, the major peaks appear at ~3416, 3060, 2922, ad 1678 cm-1. The large peak at 3416 represent the R-OH group, the peaks at 3060 and 2922 represent the Ar-H groups, and the tall peak at 1678 represents the R2C=O group of benzoin. For the benzil, the major peaks present were at ~3063 and 1667 cm-1. The 3063 peak is the Ar-H stretch and the 1667 peak is the RcC=O stretch of benzil. The peaks for the final product, benzilic acid were present at ~3399 (as a

broad mass) and 1719 cm-1, representing the COOH stretch and RcC=O stretch, respectively. A peak around 3000 is also present on benzilic acid, which would correspond to the Ar-H stretch. H-NMR and C-NMR wee also run for benzilic acid.
1H

and 13 C NRM spectra were also obtained from the final product, benzilic

acid. In the 1H-NMR, the broad singlet and 2.84 ppm corresponds to a O-H group, and the extremely small peak around 13 ppm represent the O-H bond of the carboxylic acid group. The 7.35 ppm and 7.48 ppm peaks correspond to the aromatic Hs in the molecule in the 13C-NMR of benzilic acid the small peak and 81.2 ppm represents the R3C-OH bond, the peaks from 127.3 ppm to 141.1 ppm correspond to the C bonds on the aromatic rings with different shifts due to meta, para, or ortho positioning, and the peak at 176.1 corresponds to the C bond on the carboxylic acid group. Conclusion The final product from the multistep reaction sequence conversion of benzaldehyde to benzilic acid yielded 81% of the theoretical yield. However, this product may not be entirely pure based on the percent yields of the other sections. Mass could have been added by not fully washing the crystals, errors in weighing the mass throughout the experiment, or most likely, not gravity filtering the solutions before adding HCl during the last week. Regardless, the IR, H-NMR, and CNMR of the final product all correspond to the expected spectra of benzilic acid; all major peaks are represented in each spectrum. Therefore, the processes of this experiment proved to be effective in converting benzaldehyde to benzilic acid through the steps and reactions discussed.

References Pavia, Donald L., Gary M. Lampman, George S. Kriz, and Randall G. Engel. A SmallScale Approach to Organic Laboratory Techniques. 3rd ed. Belmont, CA: Brooks/Cole; Cengage Learning, 2001. Print. Appendices Figure 1: IR spectrum of benzoin from session one and two. Figure 2: IR spectrum of benzil from session three. Figure 3: IR spectrum of benzilic acid from the final session. Final Product. Figure 4: 1H-NMR of benzilic acid from the final session. Final Product. Figure 5: 13C-NMR of benzilic acid from the final session. Final Product.