Chemistry 340 at Winona State University – Professor Thomas Nalli
Experiment #4. Electrophilic Aromatic Substitution. Part 1 – Running the Reaction
You will be assigned an electrophilic substitution reaction to carry out on a mono-substituted benzene. Crude product mixtures will be analyzed by 1H NMR and GC/MS. The crude products will then be purified by recrystallization (procedures will be provided later in a separate handout) and once again analyzed by 1H NMR and GC/MS. The goal is to determine o:m:p ratios formed in the reactions (i.e., what is the directing effect of the substituent).
1. Nitration of bromobenzene2. Nitration of iodobenzene
3. Nitration of methyl benzoate
4. Butylation of phenol
5. Butylation of tert-butylbenzene
6. Propylation of p-xylene
7. Bromination of toluene / Overview – This is a 3-week lab:
Week 1 – run reaction obtain crude product
Week 2 – analyze crude samples and recrystallize
Week 3 – analyze pure samples
Reaction Procedures
General. Run the reaction using the apparatus indicated in each procedure. Begin by placing the stir bar in the r.b. flask and clamping the flask to the ring stand.
References for Techniques. (Look at the Macroscale sections in the Lehman textbook)
Vacuum Filtration. pp 65-68 operation 13.
Magnetic Stirring. pp 55-57 operation 10.
Addition of reactants, pp 57-59 operation 11
Assembling glassware with standard-taper joints, pp 22-24 operation 2
General References. Chapter 5 in McMurry’s Fundamental of Organic Chemistry
Nitration of bromobenzene/iodobenzene. Add 4.0 mL of HNO3(conc) and 4.0 mL of H2SO4(conc) to the reaction flask. Now assemble the rest of the apparatus shown in Figure 1, cooling the mixture with stirring on a cold water bath to approx 30ºC. Add 4.5 mL of the assigned halobenzene (iodobenzene or brombenzene) or in small portions (~0.5 mL) through the top of the condenser to the stirring solution. The rate of addition should be adjusted so that the temperature does not exceed 55ºC. After all of the bromobenzene has been added and the temperature has begun to decrease gently heat the solution using a hot water bath for 15 minutes (keep the temperature below 60ºC). After cooling to room temperature pour the mixture into 40 mL of crushed ice in a beaker. After the ice has melted, carry out vacuum filtration with a Buchner funnel to isolate the precipitate crude product mixture. Wash the filter cake thoroughly with cold distilled water until the filtrate is no longer acidic as indicated by pHydrion paper. Store the crude solid in your drawer until next week. Safety: Nitric acid and sulfuric acid are extremely corrosive and cause severe burns. Wear gloves and rinse any skin exposure immediately with lots of water. Do not dispose of excess of either of the acids down the drain.
Nitration of methyl benzoate. Add 6.0 mL of H2SO4(conc) to the reaction flask, cool to 3-4 ºC on an ice bath, and then add 5.5 mL of methyl benzoate. Now assemble the rest of the apparatus shown in Figure 1, cooling the mixture with stirring on an ice bath to at least 10ºC. While this solution is cooling and the apparatus is being assembled, one team member should prepare a mixture of 4 mL HNO3(conc) and 4 mL H2SO4(conc) in a small Erlenmeyer flask and cool it on ice. The cooled nitric acid/sulfuric acid solution is then added dropwise to the cooled and stirring methyl benzoate solution. (Use a Pasteur pipet to add the solution drop by drop through the top of the condenser.) The rate of addition should be adjusted so that the temperature does not exceed 15ºC. After the addition is complete allow the mixture to warm to room temperature, let stand for 15 min and then pour it into 50 mL of crushed ice in a beaker. After the ice has melted, carry out vacuum filtration with a Buchner funnel to isolate the precipitate crude product mixture. Wash the filter cake thoroughly with cold distilled water until the filtrate is no longer acidic as indicated by pHydrion paper. Finally, wash with two 5-mL portions of cold methanol. Store the crude solid in your drawer until next week. Safety: Nitric acid and sulfuric acid are extremely corrosive and cause severe burns. Wear gloves and rinse any skin exposure immediately with lots of water. Do not dispose of excess of either of the acids down the drain.
Butylation of phenol. Run this reaction in a fume hood. Add 6.5 mL of tert-butyl chloride to the reaction flask and then add 4.7 g of phenol. Assemble the rest of the apparatus shown in Figure 1, stirring the mixture so that the phenol eventually dissolves before going on. In the meantime, weigh 0.5 g of AlCl3 into a dry screw-cap vial and immediately cap the vial. Remove the thermometer and thermometer adapter and add 0.5 g AlCl3 a little at a time to the stirring solution. HCl gas evolution should begin immediately. Replace the thermometer and monitor the temperature. If it begins to warm up much (above 30-35ºC) then cool briefly on a cold water bath. Allow 20-30 min for the reaction to go to completion. Add 25 mL water and break up the solid that forms with a spatula as much as you can. Carry out vacuum filtration with a Buchner funnel to isolate the crude product mixture. Wash with a few mL of cold water. Store the crude solid in your drawer until next week. Safety: phenol is corrosive to the eyes and skin and may cause dermatitis. Wear gloves and rinse any skin exposure immediately with lots of water. Aluminum chloride dust is extremely hygroscopic and reacts rapidly with water, even the moisture on your hands, producing fumes of HCl. Do not allow AlCl3 to come in contact with your skin. If it does rinse the affected area with lots of water. This reaction evolves HCl gas, therefore it is essential that it be run in a functioning fume hood.
Butylation of tert-butylbenzene. Run this reaction in a fume hood. Add 6.5 mL of tert-butyl chloride to the reaction flask and then add 7.7 mL of tert-butylbenzene. Now assemble the rest of the apparatus shown in Figure 1, cooling the mixture with stirring on an ice bath to at least 3ºC. In the meantime, weigh 0.5 g of AlCl3 into a dry screw-cap vial and immediately cap the vial. Remove the thermometer and thermometer adapter and add approximately ¼ of the AlCl3 to the stirring cold solution. HCl gas evolution should begin immediately. Replace the thermometer and monitor the temperature. When it has once again cooled to near 3º add a second ¼ of the AlCl3. Continue like this until all of the catalyst has been added. When a solid begins to form remove the reaction from the ice bath and let stand for 5 min. Add 25 mL water and then pour the contents into approx 15 mL of crushed ice. After the ice has melted, carry out vacuum filtration with a Buchner funnel to isolate the crude product mixture. Wash the filer cake with cold water. Store the crude solid in your drawer until next week. Safety: Aluminum chloride dust is extremely hygroscopic and reacts rapidly with water, even the moisture on your hands, producing fumes of HCl. Do not allow AlCl3 to come in contact with your skin. If it does rinse the affected area with lots of water. This reaction evolves HCl gas, therefore it is essential that it be run in a functioning fume hood.
Propylation of p-xylene. Run this reaction in a fume hood. Add 7.5 mL of p-xylene to the reaction flask and then assemble a simple distillation apparatus (see Figure E7 on p 152 in Lehman). Use a heating mantle and Variac as the heat source and clip together the joints with the yellow Keck clips in your drawer. Distill the p-xylene until the distillate is no longer cloudy (no more than 1.5 mL should have to be distilled). While the distillation is proceeding weigh 0.35 g of AlCl3 into a dry screw-cap vial and immediately cap the vial. Allow the undistilled xylene to cool to room temperature and assemble the rest of the apparatus shown in Figure 2. Remove the addition funnel, add the AlCl3 to the stirring solution, then replace the funnel. Add 4.3 mL of 1-bromopropane into the addition funnel (stopcock closed!). Have an ice bath ready just in case it is needed. Add the 1-bromopropane dropwise to the stirring reaction mixture. If gas evolution becomes too violent then slow down the addition process and cool on ice if necessary. The addition should take about ten minutes. After the addition is complete continue stirring for 30 min. Pour the mixture into 5 mL of crushed ice in a beaker. Stir until all the ice has melted then pour it into a separatory funnel and drain off the lower aqueous layer. Pour the top layer (the crude product) out through the top of the funnel into an Erlenmeyer flask containing approx 1-2 g of anhydrous sodium sulfate. Cork the flask and store in your drawer until next week. Safety: Aluminum chloride dust is extremely hygroscopic and reacts rapidly with water, even the moisture on your hands, producing fumes of HCl. Do not allow AlCl3 to come in contact with your skin. If it does rinse the affected area with lots of water. This reaction evolves HCl gas, therefore it is essential that it be run in a functioning fume hood.
Bromination of toluene. Run this reaction in a fume hood. Use a 250-mL round bottom flask (instead of a 50-mL flask) for this reaction. Add 85 mL of distilled water to the flask, then carefully add 13.5 mL of HNO3(conc). Begin stirring the solution. Carefully add 1.0 mL of bromine to this nitric acid solution. . Continue stirring until the bromine has dissolved completely (5-10 minutes). Wrap the flask with aluminium foil to exclude light assemble the reast of the apparatus shown in figure 2. Add 3.7 mL of toluene to the addition funnel (stopcock closed!). Add the toluene drop by drop to the stirring reaction mixture and once the addition is complete allow the reaction to continue for another 15 min. Uncover the flask and add 0.5 g of sodium sulfite to destroy any unreacted bromine. Pour the reaction mixture into a separatory funnel, and extract the mixture (See pp 55-57 in Lehman.) with two 30-mL portions of diethyl ether. Wash the separated ether extracts with aqueous sodium carbonate to remove any residual nitric acid. Transfer the organic upper layer to an Erlenmeyer flask containing approx 1-2 g of anhydrous sodium sulfate. Cork the flask and store in your drawer until next week. Safety: Due to the toxicity and volatility of bromine this reaction must be carried out in a fume hood.
Figure 1. Reaction apparatus which allows temperature monitoring.
Figure 2. Reaction apparatus which facilitates dropwise addition.