03/01/2023

A MULTI STEP SYNTHETIC SEQUENCE: SYNTHESIS OF DIMETHYL 3,4,5,6-

TETRAPHENYLPHTHALATE

Objective:

3,4,5,6 DimethylTetraphenylphthalate was the end product of this four-step experiment. To

create benzoin, two benzaldehyde(aldehydes) molecules were combined in step 1 through a

condensation reaction. Nitric acid, an oxidizing agent, changed benzoin and benzil in step two,

resulting in the production of benzil. Tetraphenylcyclopentadienone was produced in Step 3

from an aldol condensation. In Step 4, 3,4,5,6 Dimethyl Tetraphenylphthalate was created from

a diene (tetraphenylcyclopentadienone) and a dienophile (dimethyl acetylenedicarboxylate)

containing electron withdrawing groups through a Diels Alder reaction (a cycloaddition reaction).

This reaction produced carbon monoxide as a byproduct and the aromatic compound 3,4,5,6

dimethyl tetraphenylphthalate.
Physical Constant Data Table:

SDS:

Compound Name Safety Hazard

Potassium Cyanide Nose Bleed and sores in the nose

 Ethanol Liver or Kidney Disease

Methanol Highly flammable and toxic

Benzaldehyde Irritate nose and cause coughing

Dinitrogen Tetroxide Poison Brown vapors can rupture

Nitric Acid Irritation to eyes, skin and mucous membrane

Benzil Skin irritation, organ toxicity

Benzoin Irritation to eyes, skin and mucous membrane

Dibenzyl Ketone Irritate eyes, skin and respiratory tract

Triethylene Glycol Toxic to kidneys and nervous system

Benzyl Trimethyl Ammonium Hydroxide Toxic if inhaled and swallowed

Tetraphenylcyclopentadienone Cause eye irritation

O-dichlorobenzene Irritate and burn skin

Dimethyl Acetylenedicarboxylate Combustible

Introduction:

The experiment was aimed at synthesizing dimethyl 3, 4, 5, 6-tetraphenylphthalate, which has

several applications in organic chemistry. The starting material for the synthesis was

benzaldehyde, a widely available and inexpensive compound.

The synthesis process involved four steps, each of which had specific challenges and required

careful attention to ensure the desired product was obtained. The first step was the benzoin

condensation, which involved the condensation of benzaldehyde to form benzoin. The reaction

was catalyzed by thiamine hydrochloride and required the use of methanol as a solvent. The

reaction proceeded smoothly, and benzoin was obtained in good yield.

The second step involved the oxidation of benzoin to benzil. This step was crucial to the

synthesis process as benzil was required for the subsequent steps. Nitric acid was used as the

oxidizing agent, and the reaction was carried out under a fume hood as hazardous NO2 gas

was released during the reaction. The reaction was monitored closely, and the progress was

checked using TLC.

The third step was the synthesis of tetraphenyl cyclopentadiene using aldol condensation. This

step involved the reaction of benzil with dibenzyl ketone to produce an intermediate, which was

then deprotonated by trimethyl ammonium hydroxide to form an ion that acted as a nucleophile.

The ion attacked the carbonyl group of benzil, leading to the elimination of the alcohol group.

The base was then deprotonated again to create an ion that attacked a ketone to form a ring.

The reaction was carried out in an outdoor condensation reaction, and the product was obtained

in good yield.

The final step of the synthesis process involved a 1,4-cycloaddition reaction, which resulted in

the formation of an adduct and the creation of a ring to produce dimethyl 3, 4, 5, 6-

tetraphenylphthalate. This step required careful control of temperature and reaction conditions

to ensure the desired product was obtained. The product was characterized using NMR

spectroscopy and other analytical techniques to confirm its identity.

Overall, the synthesis process required careful attention to detail, knowledge of various reaction

mechanisms, and the use of specific reagents and reaction conditions. The successful synthesis

of dimethyl 3, 4, 5, 6-tetraphenylphthalate demonstrates the effectiveness of the synthesis

process and the importance of organic chemistry in the development of new materials and

compounds with various applications.

Chemicals and Equipment:

● KCN
● Distilled Water
● 95% ethanol
● Benzaldehyde
● Boiling chips
● Heating Mantle
● Benzoin
● Nitric acid
● Ice
● Benzil
● Dibenzyl ketone
● Triethylene glycol
● Melting point apparatus
● RBF
● Methanol
● O-dichlorobenzene
● Dimethyl Acetylenedicarboxylate
● Watch glasses
● Graduated cylinder
● Measuring scale

Methods and Procedure:

Part 1:

1. Dissolve 1 gram KCN in 20 mL distilled water in a 250 mL round bottom flask

2. Add 40 mL 95% ethanol, 20 mL pure benzaldehyde, and boiling chips
3. Reflux gently over a heating mantle for 45 minutes and then allow the reaction to cool
4. Collect the product and wash of the rest of the product with a 1:1 mixture of ethanol-
water

Part 2:

1. Place 10 grams of Benzoin in a small flask, add 34 mL of conc. HNO3 and heat the flask
while stirring occasionally for 30-40 minutes
2. Cool the flask in an ice bath then pour out the contents ino 250 mL of cold water
containing ice chunks.
3. Break up the lumps and filter through a vacuum filter.
4. Wash benzil with an ice cold 95% ethanol. Make sure to press down with a glass stopper
and finally spread out onto a watch glass.
5. Perform recrystallization on the product.

Part 3:
 1. Place 2.10 grams of benzil and 2.103 grams of dibenzyl ketone and 10 mL of triethylene
glycol into a 50 mL flask.
2. Swirl mixture on a hot plate until benzil is dissolved
3. Ready a test tube with 40% solution of benzyl trimethyl ammonium hydroxide
4. Adjust temperature of mixture to 100oC and then add base
5. Swirl the mixture and remove from the heat
6. Let the temperature drop to 800C then cool in a bath and add 10 mL of ethanol.
7. Swirl and then collect the product and wash with cold ethanol until the filtrate is a purple
color.

Part 4:

1. Add 0.5 grams of tetraphenylcyclopentadienone, 2.5 mL of O-dichlorobenzene and 0.25

mL of dimethyl acetylenedicarboxylate and boiling chips to a round bottom flask.
2. Attach the air condenser and boil gently until there is no more color change.
3. Cool to 100oC, stir slowly in 15 mL of methanol and let crystallization proceed.
4. Cool and collect the product. Wash with cold methanol.

Results and Observations:

Step 1: Benzoin Condensation

Weight of Watch Glass 154.02 grams

Weight of Watch Glass with Product 164.83 grams

Experimental Melting Point 133.5oC-136oC

Literature Melting Point 134oC-135oC

Step 2: Oxidation of Benzoin to Benzil

Weight of Watch Glass 152.78 grams

Weight of Watch Glass with Product 165.51 grams

Experimental Melting Point 85oC-95oC

Literature Melting Point 94oC-95oC

Step 3: Tetraphenylcyclopentadienone
 Weight of Watch Glass 35.34 grams

Weight of Watch Glass with Product 38.54 grams

Experimental Melting Point 200oC-213oC

Literature Melting Point 219oC-221oC

Step 4: Dimethyl 3,4,5,6-Tetraphenylphthalate

Weight of Watch Glass 27.95 grams

Weight of Watch Glass with Product 28.26 grams

Experimental Melting Point 257.1oC

Literature Melting Point 258oC-260oC

Treatment of Results:

Step 1: Benzoin Condensation

2C7H6O ⟶ C14H12O2

Experimental Yield: 10.81 grams

Theoretical Yield: 20 mL benzaldehyde * (1.04 g/mL)= 20.8 g benzaldehyde

20.8 g benzaldehyde * (1 mol/106.12 grams) = 0.196 mol benzaldehyde

0.196 mol benzaldehyde * (1 mol benzoin/2 mol benzaldehyde) = 0.098mol benzoin

0.098 mol benzoin * (212.24 g/1 mol benzoin) = 20.8 g benzoin

Percent Yield: (10.81 grams / 20.8 grams) * 100 = 52%

Step 2: Oxidation of Benzoin to Benzil

C14H12O2 + 2HNO3 → 2NO3 + C14H10O2 + 2H2O

Experimental Yield: 12.73 grams

Theoretical Yield: 12.73 g benzoin * (1 mol / 212.24 g) = 0.050 mol benzoin

0.050 mol benzoin (1 mol benzil / 1 mol benzoin) = 0.050 mol benzil

0.050 mol benzil * (210.23 g / 1 mol benzil) = 10.71 g benzil

Percent Yield: (12.73 grams / 10.71 grams) * 100 = 118%

Step 3: Tetraphenylcyclopentadienone

C14H10O2 + C15H14O → 2 H2O + C29H20O

Experimental Yield: 3.2 grams

Theoretical Yield: 0.01 mol benzil * (1 mol tetraphenylcyclopentadienone/ 1 mol benzil) = 0.01
mol tetraphenylcyclopentadienone

0.01 mol tetraphenylcyclopentadienone * (384.48 g/ 1 mol tetraphenylcyclopentadienone) =

3.845 g tetraphenylcyclopentadienone

Percent Yield: (3.2 grams / 3.845 grams) * 100 = 83%

Step 4: Dimethyl 3,4,5,6-Tetraphenylphthalate

C29H20O + C6H6O4 → CO + C34H226O4

Experimental Yield: 0.31 grams

Theoretical Yield: 0.50 g tetraphenylcyclopentadienone * (384.48 g / 1 mol

tetraphenylcyclopentadienone) = 0.0013 mol tetraphenylcyclopentadienone

0.0013 mol tetraphenylcyclopentadienone * (1 mol 3,4,5,6-DimethylTetraphenylphthalate / 1 mol

tetraphenylcyclopentadienone) = .0013 mol 3,4,5,6-Dimethyl Tetraphenylphthalate

.0013 mol 3,4,5,6-Dimethyl Tetraphenylphthalate * (498.568 g / 1 mol 3,4,5,6-Dimethyl

Tetraphenylphthalate) = 0.648 g 3,4,5,6-DimethylTetraphenylphthalate

Percent Yield: (0.31 grams / 0.648 grams) * 100 = 48%

1
H NMR:
a)
b)
c)
d)
e)
13
C NMR:

a)
b)
c)
d)
e)
Discussion:

The above reaction mechanism depicts Step 4 of the multi-step synthesis which is the synthesis

of Dimethyl Tetraphenylphthalate. In this step of the lab, when boiling gently with the air

condenser attached, we overheated the solution in the round bottom flask. Color change had

stopped around 5-10 minutes before we took the RBF off of its heat source. I think this caused

us to lose some yield due to the heat vaporizing the rest of the intended product after the color

change had stopped. Furthermore, once we took it off of its heat source, we didn’t exactly wait

for the mixture to cool to 100oC and added our methanol. This may have also caused some

error in our yield. In our next steps, we should closely monitor a reaction's color change

because once color change has stopped occurring there is no reason for the mixture to go

through more heat. Adding on we should also always closely monitor the temperature of our

mixtures when heat is involved in the synthesis.

Conclusion:

The use of multi-step reactions in science is essential because it emphasizes precision

and control in the procedures carried out to have the best yield and pure product. Because each

step depends on the previous one, the experimenters are guaranteed to have the knowledge

and recognition necessary to recognize significant results without having many errors hold them

back. Even though there will always be some degree of human error, sequential multi-step

reactions keep the pressure on for meticulousness. As a result of the experiment's numerous

steps requiring purification, it also highlights the importance of having knowledge of these

techniques. The use of toxic chemicals was also likely to present a number of risks that needed

to be taken into consideration.

A multi-step reaction experiment is crucial because it enables researchers to show that

they have a firm grasp on the procedures needed to carry out and produce reliable results.

Assigned Question:
1.

2. The generation of the stable compound carbon monoxide serves as a catalyst for the

reaction in step 4. How else could stability be used to account for the simplicity of the

reaction? Because there is a withdrawing group on the dienophile in this reaction, a

Diels-Alder reaction, which is thermodynamically advantageous, will occur

spontaneously. This helps stabilize the product as well because the dienophile used in

step 4—dimethyl acetylenedicarboxylate—has two withdrawing groups (CO2Me). The

fact that the diene, tetraphenylcyclopentadienone, was in s-cis conformation made it

suitable for the reaction as well. A stable aromatic ring is also created during this

reaction.
3. Since the exo product rather than the endo product, which would form under kinetic

control, is produced, the reaction is under thermodynamic control. Although the exo

product's overall energy is lower than that of the endo product, the energy of the

endoproduct's transition state is lower than that of the exo product.

4. As an endo product is kinetically preferred, maleic anhydride will react with furan to

produce one. Due to its higher melting point, the Exo product has greater

thermodynamic stability. The Exo product uses a retro Diels-Alder process to recreate

the maleic anhydride and furan.