Experiment 15: SUBSTITUENT EFFECTS ON THE RATE OF ELECTROPHILIC AROMATIC SUBSTITUTION Objectives: To perform electrophilic aromatic substitution reactions on various monosubstituted aromatic compounds using elemental bromine. To determine the rate of the substitution reaction based on a color change in order to explore how different substituent groups on an aromatic ring affect the reaction rate. To purify the acetanilide product using liquid extraction, then analyze the product using TLC analysis to explore how the acetamide group affects the orientation of the reaction. Before coming to lab… Review these techniques: TLC Analysis Acid-base Extraction CHEMICAL EQUATION • The progress of the bromination of an aromatic ring can be followed easily by a color change. • The more reactive the aromatic ring is, the faster the color will disappear. G G + Br2 (red) colorless + HBr Br colorless colorless MECHANISM CH2CH2CH3 + Br H CH2CH2CH3 CH2CH2CH3 Br Br An electron pair from the aromatic ring attacks Br2, forming a new C-Br bond… HBr H H H + H Br …and leaving a nonaromatic, carbocation intermediate. Br The carbocation intermediate loses H+, and the neutral substitution product forms as two electrons from the C-H bond move to regenerate the aromatic ring. HBr forms as a byproduct. REACTIVITY OF AROMATIC RINGS The substituent ALREADY ON the aromatic ring determines the position and rate of substitution of the second (INCOMING) electrophile. We use the reactivity of BENZENE (no substituent) as a reference point. REACTIVITY OF AROMATIC RINGS If we use the reactivity of benzene (substituent = H) as a reference point, activating substituents are all electron donating groups, and their relative activation strengths are: H < Phenyl < CH3 < NHCOCH3 < OCH3 < OH < NH2 Deactivating groups are electron withdrawing groups and their activities relative to hydrogen are: NO2 < COR < CHO < I < Br < Cl < F < H SUBSTITUENT EFFECTS GENERALIZATIONS Substituents in which the atom bonded to the ring has an unshared pair of electrons, with the exception of alkyl and phenyl groups, are ortho-para directing. All other substituents are meta directing. All ortho/para directors are activators, with the exception of halogens. Halogens are ortho-para deactivators. All meta directors are deactivators. Alkyl and Phenyl groups are also ortho-para directing. OVERVIEW React bromine solution with six monosubstituted aromatic compounds. Rank reactivity of aromatic compounds using the rate of reaction based on color change. Neutralize and extract acetanilide product to purify compound for further analysis. To analyze the bromoacetanilide product by TLC analysis to identify product substitution. SYNTHESIS Place small amount of monosubstituted aromatic compound in small test tube. Place test tubes in water bath. Add Bromine solution to each. Record the approximate amount of time it takes for the solution to lose color. Place in hot water bath if necessary to complete reaction. After 1 hour, estimate the reaction order based on the relative amount of color lost. Table 15.1: Reactivity Rates of Aromatic Compounds * The substituents can be completed by hand once the table has been copied into your POST LAB document! Compound Structure OPA, OPD, or MD Reaction Order ethyl benzene anisole acetanilide phenol benzaldehyde nitrobenzene ***Aromatic ring is given for each compound…remember to complete structure with appropriate substituent!*** ***Identify each substituent as an ortho/para activator (OPA), ortho/para deactivator (OPD), or a meta deactivator (MD).*** ***Simply record the order that the reactions occurred. Actual reaction times are not required. 1=fastest 6=slowest! *** PURIFICATION/ISOLATION Once pale yellow, remove acetanilide tube. Add deionized water to tube. Add 5 drops of NaOH. Stir with glass rod. Continue adding 5 drops at a time until visible precipitate forms. Add ethyl acetate. Place small cork in top of test tube, and shake to mix. Allow layers to separate. ANALYSIS • Prepare TLC plate and chamber. • Apply provided standards to TLC plate. • Apply TOP layer from test tube to TLC plate ( sample solution). A B U C D • Develop plate and visualize spots using UV lamp. filter paper • Calculate Rf value of all spots and identify product in sample solution. A B U C D Table 15.2: TLC Results TLC Diagram Name of Compound Rf Values Standard Sample Solvent Front= _________cm o-bromoacetanilide TLC developing solvent used: m-bromoacetanilide _______________________ p-bromoacetanilide * The TLC diagram can be completed by hand once the table has been copied into your POST LAB document! HINTS… Be sure that your test tubes do NOT contain any acetone. It reacts very quickly with bromine and can give inaccurate test results. If after the one hour period of heating in the water bath the solutions have not completely lost their color, estimate by the relative amount of color lost. SAFETY CONCERNS CAUTION: In this experiment you are using bromine, which is poisonous and can cause severe burns! All aromatic solutions are prepared in glacial acetic acid which can cause severe burns! WASTE MANAGEMENT Place ALL liquid waste in container labeled “LIQUID ORGANIC WASTE”. Place used TLC plates and filter papers in yellow trash can. Place used TLC spotters broken glass box (NOT TRASHCAN!!!!!!!!!!!). CLEANING UP… TEST TUBES: clean all test tubes with soap/water/brush and rinse with wash acetone. Leave inverted in test tube rack to dry. TLC CHAMBER: remove filter paper and leave in drawer with cap off. BEAKER: if only used for water, simply dry out with a paper towel. GRADUATED CYLINDER: rinse any excess bromine solution into wash acetone container. Clean with soap/water/brush and rinse with wash acetone. IN LAB QUESTIONS… (The following questions should be answered in laboratory notebook.) Rate the relative reactivity toward electrophilic aromatic substitution of benzene substituted with the following: (1 = most reactive, 6 = least reactive) CH3 C N F CH2CH2CH3 O OCH 2CH3 OH H3C N CH3 IN LAB QUESTIONS… (The following questions should be answered in laboratory notebook.) Draw the structure of the major product, and a complete mechanism for its formation, for the bromination of acetanilide which took place in this experiment.