Friedel-Crafts Alkylation Reaction

Friedel-Crafts Alkylation Reaction Preparation of 1, 4-Di-t-butyl-2, 5-dimethoxybenzene

Microscale Experiment

Leah Monroe

April 8, 2003

Organic Chemistry Lab II

Experiment performed on March 20 and 25, 2003

Lab Partners (NMR only): Shannon Land and Jamie Yeadon

Abstract:

In this experiment, 1,4-dimethoxybenzene reacted with t-butyl alcohol to form 1, 4-Di-t-butyl-2, 5 – dimethoxybenzene via a Friedel-Crafts Alkylation mechanism. A small amount of 1,4-dimethoxybenzene was dissolved in acetic acid and t-butyl alcohol, along with H2SO4. The reaction was then allowed to go to completion at room temperature, and the crystals were washed with water and methanol. The percent yield of the product was 57.48%. This was lower due to the fact that many of the crystals were stuck in the reaction tube and could not be removed for weighing. Also, when a Pasteur pipet was used to remove the solvent from the reaction tube, many crystals were lost. The observed melting point of the product was 96 - 98°C, which is considerably lower than the literature value of 104 – 105°C. This may be due to impurities in the product or the sample may still have been wet. An NMR spectrum of the sample indicated that the sample was 1, 4-Di-t-butyl-2, 5 – dimethoxybenzene and that the reaction was successful.

Friedel-Crafts Alkylation Reaction

Introduction: The purpose of this experiment is to synthesize 1, 4-Di-t-butyl-2, 5 – dimethoxybenzene by reacting 1, 4 – dimethoxybenzene with tertiary-butyl alcohol in the presence of sulfuric acid as a Lewis acid catalyst. The reaction will occur via the Friedel-Crafts alkylation mechanism, and involves the attack of the aryl group at the electrophilic trimethylcarbocation. The resulting product will be recrystallized using methanol and characterized using IR spectroscopy and melting point analysis.

Materials Used:

1 beaker, 400-mL sand bath ice for ice bath Erlenmeyer flask, 25-mL several Pasteur pipets, 1.0-mL 10 x 100 mm reaction tube glass stirring rod rubber bulb

Substances Formula Weight, g/mol

Amount Used

Moles Used

Mole Ratio

Melting Point °C

Boiling Point °C

Density g/mL

1, 4-dimethoxybenzene

138.16 0.120 g 8.69 x 10-4 1 to 1 58 - 60 N/A 1.053

Acetic acid 60 0.4 mL N/A N/A N/A 118 1.049 t-butyl alcohol 74.12 200 µL 0.00213 2 to 1 N/A 83 0.7856 Concentrated

H2SO4 98.06 2.0 mL N/A N/A N/A 327 1.84

Methanol 32.0 1.0 mL N/A N/A N/A 64.7 0.7914 Water 18.0 2.5 mL N/A N/A N/A 212 1.0

1, 4-Di-t-butyl-2, 5 – dimethoxybenzene

250.17 product product 1 to 1 104 - 105 N/A N/A

Reaction and its Mechanism:

The limiting reagent for this reaction is 1, 4 – dimethoxybenzene. See calculations section for explanation. Overall Reaction: C8H10O2 + 2C4H10O C16H26O2 + 2H2O

1,4-di-t-butyl-2,5-dimethoxybenzene

H2SO4

1, 4-dimethoxybenzene

OCH3

OCH3

+ OH CH3

CH3

CH3

Tert-butyl alcohol

OCH3

OCH3

H2O +

Mechanism:

H

H

H O SO3H

Sulfuric Acid

OH CH3

CH3

CH3

O CH3

CH3

CH3

+

+ CH3

CH3

CH3

C

Friedel-Crafts Alkylation Reaction Mechanism (con’t)

+ CH3

CH3

CH3

C

OCH3

OCH3

+

OCH3

OCH3

H

+

OCH3

OCH3

H

+

OCH3

OCH3

H

-OSO3H OCH3

OCH3

+

H

OCH3

OCH3

+

+ CH3

CH3

CH3

C

OCH3

OCH3

-OSO3H H

OCH3

OCH3

+

H

OCH3

OCH3

OCH3

OCH3

H2SO4 +

1,4-di-t-butyl-2,5-dimethoxybenzene

Procedure:

Dissolve 120 mg 1,4-dimethoxybenzene in a 10 x 100 mm reaction tube with 0.4 mL acetic acid. Add to it 0.2 mL t-butyl alcohol and heat gently until the mixture is in solution. Once it’s in solution, cool the mixture in ice. Then, add 0.4 mL concentrated H2SO4 (18 M) to the tube dropwise with a Pasteur pipet. After each drop is added, mix the solution thoroughly with a glass stirring rod.

After all the H2SO4 has been added, remove the reaction tube from the ice and allow it to warm to room temperature. Allow the tube to remain at 20-25°C for approximately 10 minutes in order to complete the reaction. Then cool the mixture in ice so that crystallization will occur. Very carefully, add a drop of water to the mixture. Stir with a glass stirring rod, then continue to add water dropwise with both cooling and mixing until 2.5 mL of water have been added to the reaction tube. Remove the solvent (liquid) layer using a glass Pasteur pipet with a

Friedel-Crafts Alkylation Reaction rubber bulb on the end. Be sure to expel all the air out of the pipet before you lower it into the reaction mixture. Remove all the solvent from the cold solution. Now, add approximately 0.5 mL methanol to the reaction tube. Heat the tube until everything is in solution. Then, allow the tube to cool to room temperature. Once the tube is at room temperature, allow the tube to sit in ice until crystals form. If necessary, scratch the inside of the reaction tube with a glass stirring rod to induce crystallization. Once the crystals have formed, again, carefully, remove the solvent from the reaction tube with a glass Pasteur pipet and rubber bulb. Once most the solvent has been removed, place the reaction tube in a 25-mL Erlenmeyer flask, label it with your name, and place it under the fume hood for a few days. This will evaporate any left-over methanol. Then, weigh your product. Characterize it by taking a melting point. Also, take an NMR spectrum of the product. In order to prepare a sample for NMR, place approximately 40 mg of the sample in an NMR tube. Add 0.9 mL of carbon tetrachloride (CCL4). TMS is used as a reference to perform the NMR. Be sure to integrate your peaks after you perform the spectrum. Place all waste materials in their appropriate containers. Data: Mass 1,4-dimethoxybenzene used: 0.118 g Mass of product: 0.123 g Theoretical Yield: 0.214 g 1,4-di-t-butyl-2,5-dimethoxybenzene Percent Yield: 57.48% Observed melting point: 96 - 98°C Literature value: 104 - 105°C Calculations: Finding Limiting Reagent

1,4-dimethoxybenzene (DMOB) (0.118 g DMOB) (1 mol DMOB) (1 mol product) (250.17 g product) (138.16 g DMOB) (1 mol DMOB) (1 mol product) = 0.214 g product t-Butyl Alcohol (TBA) (0.2 mL TBA) (0.7856 g TBA) (1 mol TBA) (1 mol product) (250.17 g product) (1 mL TBA) (74.12 g TBA) (2 mol TBA) (1 mol product) = 0.265 g product The limiting reagent for this Friedel-Crafts alkylation reaction is 1,4-dimethoxybenzene. The 1,4-dimethoxybenzene yields less product than the t-Butyl Alcohol does, and therefore, the 1,4-dimethoxybenzene will be completely used up in the reaction and is the limiting reagent. Theoretical Yield 1,4-dimethoxybenzene (DMOB) (0.118 g DMOB) (1 mol DMOB) (1 mol product) (250.17 g product) (138.16 g DMOB) (1 mol DMOB) (1 mol product) = 0.214 g product (1, 4-Di-t-butyl-2, 5 – dimethoxybenzene)

Friedel-Crafts Alkylation Reaction P

ercent Yield

For recrystallized prod uct (mass of recrystallized product) (0.123 g) x (100) = 57.48%

(theoretical yield) (0.214 g) NMR Data and Interpretation: My lab partners and I used one person’s product and ran an NMR spectrum on it. We then analyzed the product, and that analysis indicated that the product was 1, 4-Di-t-butyl-2, 5 – dimethoxybenzene as expected. A singlet at 6.7 ppm with 1 hydrogen indicated the presence of a hydrogen on a benzene ring. The singlet at 3.8 ppm with 3 hydrogens indicated a –OCH3 group. The third singlet 1.3 ppm with 9 hydrogens was a tertiary butyl group. It consists of a central carbon with three methyl groups attached to it. When all these pieces were put together, the structure was that of 1, 4-Di-t-butyl-2, 5 – dimethoxybenzene, the product obtained in the Friedel-Crafts reaction performed in this experiment. Another singlet peak was also located downfield from the benzene ring peak at 6.7 ppm. This peak is due to the hydrogens on the aromatic ring. Results and Conclusions: In this experiment, 1,4-dimethoxybenzene reacted with t-butyl alcohol to form 1, 4-Di-t-butyl-2, 5 – dimethoxybenzene via a Friedel-Crafts Alkylation mechanism. The percent yield of the product was 57.48%. This was lower due to the fact that many of the crystals were stuck in the reaction tube and could not be removed for weighing. In addition, when a Pasteur pipet was used to remove the solvent from the reaction tube, many crystals were lost. They stayed in the solvent and came up the Pasteur pipet, where they remained stuck and thus, were not weighed with the rest of the product. The observed melting point of the product was 96 - 98°C, which is considerably lower than the literature value of 104 – 105°C. This may be a result of the product still being wet when the melting point was taken. It may also be due to impurities in the product. Most likely, there is still some solvent present in the product that didn’t evaporate. Although we let the product sit in a fume hood for a couple days, it was still in the reaction tube and may not have dried out completely before the melting point was taken. As a result, some of the solvent, even trace amounts of it, may still have been present in the product and this would have caused the observed melting point to be lower than the literature value, as was observed. An NMR spectrum of the sample indicated that the sample was 1, 4-Di-t-butyl-2, 5 – dimethoxybenzene and that the reaction was successful. Please see the NMR Data and Interpretations section for a detailed interpretation of the spectrum. Overall, the Friedel-Crafts alkylation reaction and the experiment were successful.

Reference:

Class Handout. Taken from Williamson’s manual, 2nd edition. D.C. Heath, p. 440 Weast, Robert C., ed. CRC Handbook of Chemistry and Physics. 70th ed. Boca Raton, FL: CRC Press, Inc., 1990.

Friedel-Crafts Alkylation Reaction Post-Lab Questions: 1. Please see above lab report for detailed mechanism, including resonance structures of the intermediates. 2. In place of t-butyl alcohol, one could use t-butyl chloride. However, this reaction is not convenient to do in the

lab. You could also use 2-methylpropene. Both of these yield the same carbocations as the reaction that was performed in the experiment, and thus yield the same product when reacted with 1,4-dimethoxybenzene.

H+

H O SO3H

Sulfuric Acid

Cl CH3

CH3

CH3

+ CH3

CH3

CH3

C + HCl + -OSO3H

+ CH3

CH3

CH3

C CH3 C

CH3

CH2