Chem 241 Lab Manual - Lab 4 - Selectivity of Aromatic Bromination

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CHEMISTRY 241 Organic Chemistry Laboratory 1 Lab Manual Lab 4 Selectivity of Aromatic Bromination Professor Lawrence Goldman Professor Tomi Sasaki Department of Chemistry University of Washington
Chemistry 241 Lab 4: Selectivity of Aromatic Bromination 2023-2024 2 L AB 4: S ELECTIVITY OF A ROMATIC B ROMINATION Scenario: Seeing that the two ketones in diacetylferrocene could either be added on the same ring or opposite rings has made you curious about how someone could predict the selectivity of aromatic bromination. When a monosubstituted benzene reacts one time, which isomer will form? You decide to test this on a series of benzene derivatives. Your first task will be to determine what benzene derivatives to use. Benzene is known to cause leukemia, and it doesn’t matter where the bromination occurs so that’s out. You heard from a colleague that when she tried to brominate nitrobenzene and benzaldehyde, the reaction took several days. You don’t want to wait that long, so you decide to limit yourself to more reactive benzene derivatives. You think back to Chem 238 and different activated and deactivated benzene derivatives. Based on what you learn in class, you decide to study N,N-dimethylaniline, acetanilide, and phenol. Then you look up how harmful and corrosive phenol is, so you decide to replace it with anisole. Now that you have your candidate molecules, your task is to react them with bromine to see what product forms ortho, meta, or para. But there’s another catch, liquid bromine is itself fairly hazardous. So instead of using bromine directly, you’ll instead use N -bromosuccinimide, a reagent that is safer and generates Br 2 over time. Hopefully the isomer(s) you make will match up with what you learned in lecture, you’d hate to think that your instructor lied to you. Once you get a product, you’ll also need to use the right purification method to make sure you only have 1 brominated product. And you’ll need the right analytical tool to make sure you can tell the difference between the ortho, meta, and para isomers. Theory: The classic method of brominating an aromatic compound is to use Br 2 with a Lewis acid catalyst, such as FeBr 3 . The first step is the reaction between bromine and the Lewis acid: The positively-charged bromine ion then reacts with the aromatic ring in an electrophilic aromatic substitution reaction: When substituted benzenes undergo electrophilic aromatic substitution reactions, both the reactivity and the orientation of the electrophilic attack are affected by the nature of the substituent(s) on the benzene ring. Generally the meta position is relatively unaffected by the substituent, while the ortho and para positions may either be stabilized or destabilized. A catalyst (such as a Lewis acid) may or may not be necessary depending on how reactive the substrate is.
Chemistry 241 Lab 4: Selectivity of Aromatic Bromination 2023-2024 3 Purpose: The purpose of this experiment is to determine the relative selectivity of several substituent groups - the acetamido group ( NHCOCH 3 ), the amino group ( NH 2 ), and the methoxy group ( OCH 3 ). You will experiment, you will study the relative reactivities of acetanilide, N,N-dimethylaniline , and anisole in an electrophilic aromatic bromination reaction. Each student will carry out the bromination of one of the compounds shown above. Melting points and NMR spectroscopy will be used to identify products. By sharing your data, you will have information on the products of reactions of each of the starting materials. You will also compare the selectivity you observe with what you learn in lecture. Note that some of the products are liquids, For these compounds you will still be able Pre-lab Information: There is 1 pre-lab quiz for this experiment. Reading: PLKE Experiment 44 and Loudon 6th 16.4-16.5 or McMurry 5.1, 5.4, 5.7, and 5.8. Melting points of possible brominated products: Reactant Ortho mp (C) Meta mp (C) Para mp (C) N,N-dimethylaniline < 0 (liquid) 11 (liquid) 53 Anisole 3 (liquid) 2 (liquid) 13 (liquid) Acetanilide 99 87 168
Chemistry 241 Lab 4: Selectivity of Aromatic Bromination 2023-2024 4 Safety Information: In this experiment, you will be using dilute hydrochloric acid, which is toxic and an irritant to the eye, skin, and digestive and respiratory tracts. NOTE Using alternative reagents. Liquid bromine has several safety hazards that make it undesirable to use in the lab. Instead, you will be using N -bromosuccinimide (NBS). This reagent has fewer health hazards than liquid bromine, though it is still an irritant to the eyes, skin, and respiratory tract. Notebook Notes: While you should include safety and chemical/physical properties for ALL 3 reactants, you only need to include yield calculations and safety information for 1 of the 9 potential products. You can assume that all possible brominated products have the same safety hazards. Additionally, make sure to note any and all color changes that occur during the reaction. P ROCEDURE : The procedure for the reaction is the same for all starting materials. However, the work-up (extraction and purification) is different, depending on which substrate on which the reaction was performed. Reaction: Into a 1 dram vial, add 0.95-1.05 mmol of anisole, acetanilide, or N,N-dimethylaniline. (For liquids, assume that 1 drop is equal to 0.015 g.) Then, add 2 mL of reagent-grade acetone and0.95-1.05 mmol of NBS. Make sure that you use at least as many mmol of NBS as aromatic reactant. Add one drop of 1 M HCl. The solution should turn a deeper/brighter yellow upon this last addition. At room temperature, lightly agitate the solution by shaking it until it becomes colorless. If there is no color change after 5 minutes, continue on to the next step anyway. Transfer the solution to a small beaker, using as little excess reagent-grade acetone as necessary to completely transfer it, and evaporate the solvent using the air line. Once the solid is dry, add 5 mL of hexanes, then put the beaker in an ice bath for 5 minutes to precipitate as much solid as possible. From here, follow the procedure corresponding to your starting material. Anisole and N,N-dimethylaniline Work-Up: Pre-weigh a beaker that you will use to collect your final product. The solid that was precipitated is reacted succinimide (NBS without its bromine). Decant the hexanes off and put it in a separate container. Remember: The hexanes now contains your product. Do not throw it away! Place the beaker with the hexanes solution into a hot water bath to evaporate off the solvent. What is left should be your product. Note that for anisole, it will be a liquid. For N,N- dimethylaniline it may be a solid or liquid. If it is a waxy solid, you might not be able to get a melting point. If your product is a solid, take a melting point. Acetanilide Work-Up: The brominated product will precipitates along with succinimide, so you will need to separate them. Succinimide is soluble in water while your brominated product is not. Decant off the hexanes. Add 5 mL of room temperature DI water to the solid to dissolve succinimde. Filter the mixture via vacuum filtration with water aspiration and collect the solid. Wash the crystals on the filter with a few milliliters of DI water, then allow it to dry on the filter. This solid should be your product. Take a melting point. Solid products with melting points less than 60C may be isolated as liquids/oils if they have significant amounts of impurities.
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