Experiment 32: Multi-Step Synthesis

Morgan Lepley

(Lab partner: Lauren Mullinax Johnson)

Organic Chemistry Lab, CHEM 369The University of Tennessee, Knoxville

TA: Bo MengInstructor: Dr. Laureta SmithDate 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 2-

mL 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 (~70°C 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 ice-

cold 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

CompoundRole in

ExperimentMol wt (g/mol)

Amount used

m. p. (°C) b. p. (°C)Density (g/cm3)

Hazard

Thiamine Hydrochloride

Used in Exp. 32A to make the reaction

mixture

337.27 1.5g 248-260

Low toxicity, may cause

burning sensation

Ethanol Used in all three parts

of the experiment;

used to wash the

crystals in the Buchner

funnel.

46.07 21-mL -114.3 78.4 .789Volatile and Flammable

Aqueous Sodium

Hydroxide

Used in Exp. 32A to make the reaction

mixture

39.997 4.5-mL 318 1388 2.13Causes burns

Benzaldehyde Used in Exp. 32A to make the reaction

mixture

106.12 4.5-mL -26 178.1 1.0415 Fire hazard

BenzoinUsed in the preparation

of Benzil212.24 2.5 g 137 344 1.31

May cause irritation to

skin and eyes

Nitric Acid Used in Exp. 32B to make the reaction

mixture

63.012 12-mL -42 83 1.5129 Corrosive

Benzil Used in Exp. 32C for the preparation of Benzilic

Acid

210.23 2.0 g94.43-95.08

346- 348 1.23

Cause eye and skin irritation

Potassium Hydroxide

Used in Exp. 32C to

prepare Benzilic

Acid.

56.1056

5-mL 360 1327 2.044Reacts

violently with acids.

Hydrochloric Acid

Used in Exp. 32C to

prepare

36.46 1.3-mL -27.32 110 118 Corrosive

Benzilic Acid

O

OH

Benzoin

IR refers to Figure 1.

IRCm -1 Stretch

3416.34 R-OH2922.50 Ar-C-H1678.52 C=O

1050-1150 C-O alcohol1450, 1500, 1580, 1600 C=C within Aromatic

O

O

Benzil

IR refers to Figure 2.

IRCm -1 Stretch2921.6 H-C-C-H1680 C-C=O-R

1591.70, 1452.21 C=C within an Aromatic1173.51 C=O

5

4

3

26

1OHO

OHBenzilic Acid

IR refers to Figure 3.IR

Cm -1 Stretch3399.06 Ar-C-H2904.71 H-C-C-H1247.95 C=C within Aromatic1175.74 C=O

1H-NMR refers to Figure 4. 13C-NMR refers to Figure 5.1H-NMR 13C-NMR

Chemical shift

Integration Splitting Chemical Shift

Splitting (if given)

Assigned

12.3 1H Singlet -- -- ---- -- -- 176.12 Singlet 1-- -- -- 141.06 Singlet 27.5 4H Multiplet 128.48 Doublet 37.4 2H Multiplet 128.33 Doublet 47.3 4H Multiplet 127.30 Doublet 52.84 1H Singlet 81.2 Singlet 6

Calculations

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

Mechanisms1. 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 ice-

cold 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 benzil’s 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 H’s 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 C-

NMR 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 Small-

Scale 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.