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Friedel-Crafts Acylation of Toluene

Objective: The purpose of this experiment is to perform Elecrtophilic Aromatic Substitution reaction (Friedel-Crafts
acylation) of toluene. The product will be isolated and analyzed by IR and TLC. The substitution pattern will be verified. Reaction yield and percent recovery will be discussed.

Chemicals: toluene, anhydrous aluminum chloride, acetyl chloride, methylene chloride, conc. HCl, 5% NaHCO3,
brine, anhydrous MgSO4 or Na2SO4.

Glassware and equipment: 50 and 100 mL RBF, air condenser, Claisen adaptor, addition funnel, short stem glass
funnel, 60 and125 mL separatory funnels, 150 mL beaker, 50 mL Erlenmeyer flasks, 10 mL graduated cylinder, lab jack, crystallizing dish, magnetic stir bar.

Techniques: reflux, extraction, rotary evaporation, IR spectroscopy. Introduction

O Cl AlCl3 CH3

O 1. CH3 H3C

+ CH3 CH3 O

CH3

2. H3O+, H2O

Electrophilic aromatic substitution reactions (EAS) take place between the nucleophilic a- electrons of an aromatic ring and an enhanced electrophile. The intermediate carbocation rapidly goes through elimination of proton to restore the aromatic system. In the case of Friedel-Crafts acylation, the electrophile is an acylium ion, formed by the reaction of an acyl chloride with aluminum chloride. The mechanism is shown in Fig. 1.
O H3C Cl + Cl Al Cl Cl Cl O H3C CH3 H O + -AlCl3/HCl CH3 CH3 CH3 O CH3 CH3 O CH3 Cl

Cl Al Cl +

O CH3

O H3C

Fig. 1. Reaction mechanism

major

minor

Experimental Procedure:
Caution: anhydrous aluminum chloride is moisture sensitive and will irritate your skin producing HCl. Wear gloves and handle this chemical carefully. Close the bottle as soon as you obtain the amount needed. Acetyl chloride is an eye and lung irritant: do not remove from the hood and close tightly after measuring the amount needed. Wash the glassware after this experiment in the hood with some acetone before moving it to your bench top.

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First Class Period:

1. Assemble apparatus shown below. Weigh carefully anhydrous aluminum chloride (0.0275 mol, MW=133.34 g/mol) and add it to the dry 50 mL round bottom flask using glass funnel. Wash the catalyst off the funnel with 8 mL of methylene chloride into the same flask. Equip the RBF with a magnetic stir bar. Place a Claisen adaptor on top of the RBF and attach a 60 or 125 mL addition funnel and air condenser. Lightly grease the joints. 2. Cool the mixture on an ice bath to 0oC. 3. Measure carefully in the hood 0.0275 mol acetyl chloride (MW=78.5 g/mol, d=1.104 g/mL) using a dry graduated cylinder. Transfer the reagent into a clean addition funnel and add to it 5 mL methylene chloride (use the same graduated cylinder). 4. Start adding the mixture to the suspension of aluminum chloride in RBF. The addition should be done over 10 min. As you add acyl chloride solution to the mixture in the round bottom flask, the solution should become homogeneous and turn bright yellow. If you form a cloudy off-white mixture, the chances are your reaction absorbed moisture and the catalyst was deactivated. Show the setup to your instructor: you might have to start over. 5. Once the electrophile is activated, add a solution of 0.025 mol of toluene (MW=92.13 g/mol, d=0.87 g/mL) mixed with 5 mL methylene chloride into the same addition funnel. Adjust the rate of addition so the solution does not boil excessively. The solution at this point turns amber color. 6. After the addition is complete, remove the ice bath and let the mixture to come to room temperature. Stir for additional 15 min at room temperature. 7. Now pour the reaction mixture carefully and slowly with stirring into 25 g of ice and 10 mL of conc. HCl in a beaker. The color will change to off-white. Transfer the mixture into clean 125 mL separatory funnel and extract the bottom organic layer. Collect the bottom layer in a clean Erlenmeyer flask and extract the aqueous layer one more time with additional 10 mL methylene chloride. Combine organic layers, wash them with 10 mL deionized water, 15 mL sodium bicarbonate, 15 mL brine, and dry the organic layer over anhydrous Na2SO4 in a dry 50mL Erlenmeyer flask. Cork and parafilm the product; label it and save until next class period.

125 mL separatory funnel

air condenser: do not cork

keck clamps

Claisen head

50 mL RBF water-ice bath

Fig. 2. Reaction setup

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Second Class Period:

1. 2. 3. 4. Decant the dried solution into a clean, dry pre-weighed 100 mL RBF. Rotovap the solution. Report actual yield and percent yield. Analyze the product by IR (you might have to run a background with methylene chloride to eliminate the residual peak from the remaining solvent in your product). 5. Run TLC of the product in 20:80 EtOAC/Hexanes mixture.

Guidelines for Formal Report: (20 pt)

Note: Attach all spectra and label the important peaks (Draw the structures, label the functional groups or H, C, and match them with the spectra). Severe point deduction will follow if spectral data is missing. Abstract (2 pt) Target molecule and the reactions with mechanisms (2 pt) Tabulated results: Product Yields (grams /%) Color/Texture Purity (from TLC) Rf values

Crude product

Purified product

Discussion: Yield (5 pt): Explain what could affect the yield of reaction. Be specific and refer to your notebook. TLC (3 pt): compare the TLC of the products and comment on the presence of possible products. IR and NMR (6 pt): when reporting IR and NMR of the products, please do not just list the chemical shifts and the wavenumbers on NMR and IR but rather comment on the changes from one compound to another in terms of reporter peaks. The NMRs of the starting material and the major possible products are presented below: Conclusion (2 pt): comment on any disadvantages or failures of this experiment and propose modifications/improvements for the synthetic procedure. Please be specific and note that general comments such as use a different solvent, different glassware, etc. are not valid to make your point!

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!"#$%&'#$()*+%,-./0) H NMR of Toluene:

CH3

13C

NMR of Toluene:
CH3

4 PPM

150

140

130

120

110

100

90

80 PPM

70

60

50

40

30

20

10

IR of Toluene:

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!"#$%&'#$()*+%,-./0) H NMR of p-product:

CH3

CH3

13C

NMR of p-product:

4 PPM

CH3

O
200 180

CH3
160 140 120 100 80 60 40 20 0

PPM

IR of p-product:

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!"#$%&'#$()*+%,-./0) H NMR of o-product:

CH3 O CH3

4 PPM

13C

NMR of o-product:

CH3

O CH3

220

200

180

160

140

120

PPM

100

80

60

40

20

IR of o-product:

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