Chemistry 263 Laboratory Experiment 5: Dibenzalacetone 5/10/18. Introduction

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1 Chemistry 263 Laboratory Experiment 5: Dibenzalacetone 5/10/18 Introduction We have been examining the electrophilic nature of the carbonyl of late. In particular, we have been trying to determine how leaving group capacity influences the reactivity of the carbonyl where ester formation is concerned clearly, an acyl chloride is a much more reactive electrophile than a carboxylic acid, to such an extent great care must be taken in preparation and handling of these compounds. Clearly then, the carbonyl is subject to nucleophilic attack, so long as a good leaving group is present to allow a net reaction. In the Cannizzaro reaction we saw the curious case of a hydride transfer subsequent to the addition of hydroxide resulting in the disproportionation of benzaldehyde to benzoic acid and benzyl alcohol. Recall, however, this is a system with limited alternative options, and was slow, requiring we wait a lab session between setting up the reaction and working up the product. Generally, aldehydes and ketones do not directly provide a good leaving group (readily rationalized by the base strength of hydride or a carbanion). In order for aldehyde and ketone carbonyls to react multiple steps are required, resulting in the loss of the carbonyl oxygen. Such is the case with acetal (from aldehydes) and ketal (from ketones) formation, such as when ethylene glycol is reacted with acetone in an acidic environment The mechanism involves first protonating the carbonyl, then attacking with an alcohol oxygen. This is followed by deprotonating the attacking alcohol oxygen and protonating the newly formed alcohol (oxygen-18 labelled in the scheme above). This allows the 2 nd alcohol to attack, kicking out the carbonyl oxygen as water 1

2 Carbonyls also have the ability to profoundly influence reactivity at the carbon immediately adjacent the carbon. As you recall, the pk a at this position is in the range, which makes the carbon susceptible to deprotonation in a strong base environment. This leaves an enolate ion, so named since it is the deprotonated version of what is termed an enol part alkene and part alcohol a tautomer of a carbonyl containing compound. Such an interconversion can be carried out in an acidic environment + Tautomers - rapidly interconvertable constitutional isomers differing by the location of a proton + + When carried out in base, the resulting enolate is a good nucleophile and allows for the making of C to C bonds The condensing of an aldehyde (with only one C and thus limiting the number of product outcomes) with another is referred to as an aldol condensation, since the initial product is an aldehyde and an alcohol. eating the resulting aldol product eliminates water, driven by the formation of an alkene conjugated to the carbonyl. This is how we will turn benzaldehyde, the compound principally responsible for the scent of almonds, into trans-cinnamaldehyde, the compound which gives cinnamon its well-known flavoring properties next week 2

3 - D As the aldol condensation may be carried out at room temperature, it is little wonder that the reaction figures prominently in biochemistry (see for example fatty acid biosynthesis). ur lab for this Thursday will also feature benzaldehyde, but instead of the acetaldehyde shown above, we will use acetone as our nucleophile. By using a 2.2:1 ratio of benzaldehyde to acetone, we will make the aldol condensation product on either side of the acetone carbonyl, and with subsequent elimination of water the sunscreen dibenzalacetone. Please follow the scanned procedure below, using the benzaldehyde you liberated from the oxidation product benzoic acid in the Cannizzaro reaction. As you carry out the reaction, watch how rapidly the product develops, and think back to the Cannizzaro reaction removal of an - from acetone (or other carbonyl containing species) is a much more energetically facile process, and the formation of benzyl alcohol and benzoic acid in a K environment only occurs owing to the absence of such a hydrogen in benzaldehyde 3

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7 Tips and Suggestions The lab procedure is fairly clear I believe. The only problem one can really run into is not having the benzaldehyde available to react when the enolate is generated; i.e. it must be in the reaction flask with the Na prior to the addition of acetone, otherwise the acetone will self-condense. This normally isn t a problem, since aldehydes are more susceptible to nucleophilic attack, especially benzaldehyde with the electron withdrawing benzene ring next to the carbonyl, but if there are no other options The solvent/catalytic solution being called for is a 1:1 ratio of 95 % Et: 3.0 M Na (25 ml each) Product Analysis As stated in the handout, you will want to take both a crude melting point and a melting point after recrystallization from ethanol. Determine the mass recovered and report the percent yield. Submit your sample in an appropriately labeled vial Check the purity of your product both crude and purified - by PLC, then run an NMR o As we have a very nice chromophore, I anticipate a 0.5 mg/ml solution should be plenty for your PLC determination 5 mg dissolved into 10 ml using a 10 ml volumetric flask, and fill the autosampler vial fairly full. If you find 5 mg difficult to measure effectively, measure 50 mg and dissolve it into 10 ml using a 10 ml volumetric flask, then carry out a 1 in 10 serial dilution using C1V1 = C2V2 for dilution (5 mg/ml)v1 = (0.5 mg/ml)(10 ml) again using a 10 ml volumetric flask for the final serial dilution, and again filling the autosampler vial fairly full once you have done so Given the conjugation in dibenzalacetone, time permitting we will run a UV/Vis spectrum 7

8 Post-Lab Questions 1. Please answer the questions in the scanned procedure 2. What would the principal product be if you forgot to add the benzaldehyde 1 st and the acetone self-condensed? 3. ow many isomers are possible for the reaction? Why is the principal product the one shown in the mechanism? 4. If acetone is reacted with butanone under similar conditions (2.2:1 butanone to acetone) what are the structures for the principal product outcomes? Bearing in mind stoichiometric ratios, and considering only fully dehydrated products, I am seeing 10 extra credit point for every plausible isomer you can identify I may have missed 8

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