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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

+ +

H+

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 2nd alcohol to attack, kicking out the

carbonyl oxygen as water

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Carbonyls also have the ability to profoundly influence reactivity at the carbon

immediately adjacent – the carbon. As you recall, the pKa at this position is in

the 19-20 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

OOHH+

OHO

H

O+

H

H

H

H

O

H

H+

When carried out in base, the resulting enolate is a good nucleophile and allows

for the making of C to C bonds

OH-

O-

O O

-

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. Heating 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

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O

O-

OH O

OOH O

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).

Our 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 -H 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 KOH environment only occurs

owing to the absence of such a hydrogen in benzaldehyde

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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 NaOH 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 % EtOH:

3.0 M NaOH (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 HPLC, 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 HPLC 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

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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

1st and the acetone self-condensed?

3. How 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

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