Experiment [28] Electrophilic Bromination of Acetanilide This experiment demonstrates the substitution of hydrogen on a benzene. ting by molecular bromine. Please answer the following prelab questions. (1) If cack molecule of acetanilide produces one molecule of hydrogen ‘bromide, what volume of HBr gas should be evolved from the reaction? @) Draw all the possible ring-monobrominated derivatives of acetanilide. Prior Reading Technique 5: Ceystallization Use of the Hirsch funnel (see pp. 93-95). Craig Tube Crystallization (see pp. 95-96). E49 REACTION Aromatic compounds may be brominated by treatment with bromine in DISCUSSION the presence of a Lewis acid catalyst, such as ferric chloride. For very electron-rich aromatic rings, such as arylamines, the reaction may proceed in the absence of a catalyst. With amines or phenols, in many cases, it is difficult to stop the bromination at monosubstitution, and all open ortho and para positions are brominated. For this reason, primary aromatic amines are often converted to a corresponding amide derivative, ifa mono- brominated product is desired. This strategy is demonstrated in the present experiment. The —NHCOCH; group is a less powerful ,p direct- ing group than —NIH; due to the presence of the electron-withdrawing, carbonyl group, which renders the ring less nucleophilic. Electrophilic sub- stitution by bromine is still, however, effectively directed electronically to ‘the ortho. and pera positions on the ring. The_acetamidg_group, =NHCOCH:, effectively blocks the ortho positions by steric hindrance. For these reasons, only para substitution is observed. The acetanilide use in this experiment may be prepared using the procedure described in Fx periment (23A}. ‘The mechanism of the bromination reaction is a classic lustration of an electrophilic substitution on an aromatic ring. The mechanism shown below is presented as proceeding without the aid of a catalyst.E50 6 Microscale Organic Laboratory Experiments. EXPERIMENTAL PROCEDURE HOOD HOOD Estimated time for completion of the experiment: 1.5 hours. Physical Properties of Reactants Physical Properties of Reactant Compound MW Amount —mmot_— mp) _—_beC) Acetanilide 135.17 25mg 0.19 us Glacial acetic acid 05 drops ns Bromine-acetic aid 3 drops solution SBS eeeseeceeceE ee Reagents and Equipment Weigh and place 25 mg (0.19 mmol) of acetanilide in a 3.0-mL. conical vial fitied with a cap. Add 4 drops of glacial acetic acid using a medicine dropper. Stirring with a glass rod may be necessary to help dissolve the acetanilide. Now add to the clear solution three drops of the bromine~ acetic acid solution (HOODI Cap the vial immediately. ee WARNING: Bromine is a severe irritant. It is suggested that plastic gloves be wom since bromine burns can be severe and require extended periods of time to heal. Dispense bromine only in the hood. Prepare the bromine-acetic acid reagent by mixing 2.5 mL of bromine with 5.0 ml. of glacial acetic acid. Ee mere rere sce eee ee eee Reaction Conditions [Allow the reddish-brown solution to stand at room temperature for 10 min. with intermittent shaking. During this period, yellow-orange calored crys- tals precipitate from the solution. Isolation of Product ‘Add 0.5 ml. of water (calibrated Pasteur pipet) to the reaction mixture with ‘swirling, followed by 5 drops of aqueous sodium bisulfite solution (33%) ‘This treatment destroys the unreacted bromine (and its residual color), anc results in white crystals. Cool the reaction mixture in an ice bath for 10 min to maximize the yield of product. ‘Collect the white crystals of 4-bromoacetanilide by vacuum filtration ‘using Hirsch funnel. (Hl) Wash the filter cake with three 0.25-mL portions of cold water (calibrated Pasteur pipet) and partially dry by drawing air through the crystals under reduced pressure for approximately 5 min. A sheet of plastic food wrap over the funnel mouth aids this process (see Prior Reading). Purification and Characterization Purify the crude 4-bromoacetanilide by recrystallization from 95% ethanol using the Craig tube. Weigh the dried product and calcwate the percent yield. Determine the melting point and compare your result to the value given in the literature.