Chemistry 263 Laboratory Experiment 3: The Cannizzaro Disproportionation of Benzaldehyde to Benzoic Acid and Benzyl Alcohol 1 4/19/18, 4/20/18

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1 Chemistry 263 Laboratory Experiment 3: The Cannizzaro Disproportionation of Benzaldehyde to Benzoic Acid and Benzyl Alcohol 1 4/19/18, 4/20/18 Introduction If an aldehyde has no -hydrogens that can be removed in a strongly basic environment, the aldehyde can undergo a self-disproportionation reaction leaving one molecule at a 2 electron higher oxidation state (benzoic acid in the case of benzaldehyde) and one at a 2 electron lower oxidation state. In lab session 6, we will juxtapose this reaction against a similar environment that contains acetone and which rapidly leads to dibenzalacetone, demonstrating the preference for removal of the -H of acetone when compared to the slower disproportionation process, which typically is left overnight. Purpose While the insights gained concerning intermolecular hydride transfer are reason enough to carry out this reaction, we will ultimately be transforming almond essence (benzaldehyde) to a principal flavoring component of cranberries (benzyl benzoate) when we condense our disproportionated products together. Notice the molar mass of benzaldehyde is 106.1, and the molar mass of benzyl benzoate is The hydroxide that initially attacks the aldehyde carbonyl is lost as water when we condense the alcohol and aldehyde together to form the final benzyl benzoate ester in week 2 from an atom economy standpoint this reaction is perfect! Week 1: 2PhCHO KOH PhCH 2 OH + PhCOOH Week 2: H + H2O 1 This lab is a modification of The Cannizzaro Reaction with 4-chlorobenzaldehyde, as found in Microscale Organic Laboratory with Multistep and Multiscale Syntheses, 5 th ed., D.W. Mayo, R.M. Pike, and D.C. Forbes, (2011, Wiley)

2 Pre-lab Questions 1. Occasionally, a crossed Cannizzaro reaction is carried out to reduce benzaldehyde derivatives to the corresponding benzyl alcohol, utilizing formaldehyde as the reducing agent. a. Please show the mechanism by which this occurs (you may wish to consult the post-lab questions prior to doing this). b. Why is this method effective? That is, why are the principal products benzyl alcohol and formic acid and not benzoic acid and methanol? 2. What is the principal reason benzophenone does not undergo a Cannizzaro reaction? What does this imply about migratory aptitude? Procedure for the Removal of Benzoic Acid As you will recall, aldehydes are very easily oxidized to carboxylic acids, and benzaldehyde with an aldehyde functional group at the benzylic position even more so (please keep the benzaldehyde closed when not in use to limit exposure to oxygen). As a result, we need to remove any benzoic acid which has previously formed from our benzaldehyde, so we can investigate the efficiency of the Cannizzaro reaction and determine if, in fact, we end up with an equal ratio of benzaldehyde to benzoic acid. We will need approximately 100 mmol for the formation of dibenzalacetone (lab session 5), trans-cinnamaldehyde (lab session 5 bonus), and for the formation of benzyl benzoate here C 7 H 6 O MW = mol(106.1 g/mol) = 10.6 g d 20 = g/ml 10.6 g(ml/1.046 g) = 10.1 ml Assuming a 25 % loss due to contamination and workup losses, 10.1 ml (10.1 ml) = 12.7 ml crude benzaldehyde

3 Wash the benzaldehyde 2 x 5 ml with 10 % NaOH, erring on the side of losing a little benzaldehyde, Follow by drying the benzaldehyde briefly over anh. MgSO 4 o o You can be quick (ca min) with the drying since the wash was very much in keeping with the reaction conditions to come. Really, the only reason you are drying the benzaldehyde at all is to get an accurate determination of the amount you will add by displacement pipette As a test of your lab skills, determine the % contamination of the benzaldehyde by benzoic acid. Clearly state how you will go about doing this in your lab book, and provide readily identifiable places for necessary data 2 Reaction Procedure Using a displacement pipette, place 22 mmol benzaldehyde in a 50 ml Erlenmeyer flask equipped with a spin bar atop a magnetic stirrer o MW = mg/mmol or 2.33 g o d 20 = g/ml 2.33 g(ml/1.046 g) = 2.23 ml Add 8.0 ml MeOH via 10 ml graduated cylinder Begin stirring gently, then carefully add 11 ml of 11 M aqueous KOH, in 2 divided portions using the same 10 ml graduated cylinder Cover the Erlenmeyer with Parafilm, label appropriately (including several Jolly Rogers that s Rogers, not Ranchers) and place out of the way until the next lab session Bear in mind that our reaction mixture is highly corrosive so avoid contact with it. If contact occurs, immediately wash with ample cold water 2 If you are really good, the mass of recovered benzoic acid + benzaldehyle will equal the initial mass you treated with 10 % NaOH

4 Purification Procedure Given the high ionic strength of the aqueous environment, there is some likelihood we will have exceeded the solubility limit for the potassium benzoate. If this is in fact the case, add a minimal amount of room temperature water until the crystals redissolve Transfer the reaction mixture to a small separatory funnel and extract 3 x 10 ml with CH 2 Cl 2, using the first 10 ml portion to rinse the Erlenmeyer reaction flask. Retain both layers (why?). Extract the combined DCM layer with 2 x 5 ml saturated NaHCO 3 (be careful for pressure buildup), followed by 10 ml cold H 2 O. These may be combined with the initial aqueous layer. Dry the organic layer over approximately 0.5 g anhydrous Na 2 SO 4 while you proceed to isolation of the benzoic acid Place 10 g of crushed ice in a 100 ml beaker followed by 8 ml conc. HCl. Slowly add the aqueous layer, and I do mean slowly to the HCl/ice mixture (what did your momma tell you about adding strong acids and bases together?). Test with ph paper to ensure the solution is acidic, then retrieve the crude benzoic acid using a small Büchner funnel/vacuum filtration apparatus Record the crude weight, and then recrystallize from hot water. Vacuum filter, oven dry at 60 o C. Record the weight and mmol recovered for comparison to benzyl alcohol recovery Evaporate the solvent, heating gently under a stream of air and record the resulting mass of the crude product (pre-weighing the container is probably a good idea, eh?) If analysis indicates a significant contribution of benzaldehyde, we will give it the old NaBH 4 treatment why remove it as an impurity when you can add it to your product total? Besides, benzaldehyde can form a gem-diol hydrate and so has properties close to the benzyl alcohol the best way to get rid of it is to react it!

5 Compare the mmol outcome of the benzoic acid to benzyl alcohol products isolated to see how close you came to a 1 to 1 ratio. This of course is prior to reduction by NaBH 4, and you may need to use comparative GC/MS peak heights to estimate the % contamination by benzaldehyde Save your final products in an appropriately labeled vial for the synthesis of benzyl benzoate Analysis The reactants and products formed lend themselves to analysis by IR. First, get a sense of purity by GC/MS, then either run as a neat liquid (benzaldehyde, benzyl alcohol) or as a cast film (benzoic acid) At your discretion, or as time allows, you may run an NMR on the reactants and products though they are pretty much snoozerville spectra if pure Post-Lab Questions When the Cannizzaro disproportionation of benzaldehyde is carried out in D 2 O/KOD, there is no deuterium bonded to carbon in either the resulting benzoic acid or benzyl alcohol, strongly suggesting hydride transfer after initial hydroxide attack. Imagine for a moment that 2 H had been incorporated in the benzyl alcohol. Propose a mechanism by which this could occur. -ketoaldehydes give the corresponding -hydroxyacids in an internal Cannizarro reaction. Using this knowledge, please synthesize lactic acid from the highly toxic former riot control agent (lachrymator) bromoacetone. Hint: S N 2 reactions of 1 o haloketones work well, with a considerably enhanced rate owing to the presence of an adjacent carbonyl