Niels stergaard Hammer Kristian Mark Jacobsen

20103576 20107504

Synthesis Report #41 - Part 1

- A Claisen-Schmidt Condensation
The purpose of experiment #41 part 1 was to synthesize E-4-phenylbut-3-en-2-one (benzylideneacetone) by using the Claisen-Schmidt Condensation reaction. The reaction scheme in part 1 of the exercise can be seen below:

Figure 1: Reaction scheme

Experimental procedure
Table 1: Amounts and equivalents used in Ex. 41

c (mol/L) Benzaldehyde Acetone NaOH 2,5 -

V (mL) 2,0

m (g) 8,40 12,7

M (g/mol) 106,12 58,08 39,997

n (mol)

Eq. 1 2,77 0,063

Initially benzaldehyde (8,40 g, 1 eq., 79,2 mmol) and acetone (12,7 g, 2,77 eq., 5 mmol) were weighed into a 100 mL round-bottomed flask. The solution was made basic by adding NaOH (2 mL, 2,5 M) using a syringe. The reaction mixture was left on a magnetic stirrer and heated to C with an oil bath. The

reaction mixture were left on the stirrer for 90 minutes. After 25 minutes the solution had changed color to clear yellow. A division of the solution in a yellow oil phase and a water phase is observed after 1 hour. A TLC analysis was performed to examine how the reactions progress. This was done with 9:1 pentane/diethyl ether as eluent due to the products nonpolar nature. The amount of benzaldehyde used as a reference sample was too high, so the results were inconclusive. After a total reaction time of 120 Page 1 of 7

Niels stergaard Hammer Kristian Mark Jacobsen

20103576 20107504

minutes another TLC analysis was performed, with the exact same eluent. For reasons just described benzaldehyde was diluted in pentane but nevertheless the concentration was still too high. Even though, the TLC showed rather conclusive results, showing that the reaction was done (see figure 2).

Figure 2: TLC performed after 120 minutes

The still yellow solution was devided in an oil phase and a water phase as before. To remove the remaining alkaline residues diluted hydrochloric acid (1M, 5 mL) was now added to the solution, until it was just acidic on pH-paper. On addition of HCl the solution changed color into a lighter yellow. At this point the next step would be to separate the two phases in a separatory funnel. During this process, the separatory funnel broke in half and the solution was spilled. In an attempt to recover the wanted oil phase everything was collected with tissues. The oil phase was now extracted from the tissues with large amounts of diethyl ether. The diethyl ether was removed on the rotary evaporator. The solution was dried over MgSO4 to remove any remaining water and then filtered with suction to obtain the anhydrous solution. The water phase is now believed to be of minimal size in spite of the accident. The solvent is removed on the rotary evaporator. A distillation under vacuum was performed to obtain the fraction distilling at 130-145C. The wanted fraction was transferred to a beaker with a known mass. Crystallization was achieved by scratching the walls of the beaker with a glass rod, while cooling with ice water. After measuring the mass of the dried crystals an analysis of its melting point was performed (see results). A small portion (approx. 1,6g) was recrystallized in which the suspected impure product is dissolved in as little solvent (pentane) as possible during reflux. The recrystallized product was washed in cold pentane under suction filtration. This resulted in harder but still light yellow crystals. The crystals were left on filter paper to dry and later used for melting point analysis, IR spectroscopy and NMR analysis. The final yield was 3,29 g.

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Niels stergaard Hammer Kristian Mark Jacobsen

20103576 20107504

Reaction mechanism
A Claisen-Schmidt condensation reaction is a nucleophilic attack onto a carbonyl without a -Hydrogen with an enolate derived from deprotonation of a ketone, in this case acetone. This is followed by an E1cB elimination of water where the leaving group (atypically eliminations) can be a hydroxide-ion, creating a conjugated carbonyl group.

Figure 3: Reaction mechanism

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Niels stergaard Hammer Kristian Mark Jacobsen

20103576 20107504

Possible side reactions

A possible side reaction is the reaction between benzylideneacetone and an additional benzaldehyde molecule. This reaction is statistically unfavorable due to the equivalents chosen in table 1. The possibility of a benzylideneacetone molecule reacting with benzaldehyde is very low but not unrealistic.

Figure 4: Side reaction (benzylideneacetone with benzaldehyde)

A plausible side reaction is the self-condensation of acetone to mesityl oxide. Mesityl oxide is in a liquid state between -53 to 129 and is nonpolar, but since the product is isolated through fraction distilling

at 130-145C, the pollution is very likely to be boiled off into the waste-fraction. Being nonpolar the remaining pollution will decrease when washed in cold pentane under suction filtration.

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Niels stergaard Hammer Kristian Mark Jacobsen

20103576 20107504

Overall these two side reactions both seem possible. As mentioned above the first reaction is statistically unrealistic due to the reagent equivalents chosen. The latter reaction hasnt happened because it statistically is more plausible that an additional acetone will enolize, because acetone is in large excess compared to benzylideneacetone.

Results
Yield: The product was placed in a beaker with known mass (41,0 g) and the mass of the beaker and product was measured to 44,3 g. This results in a yield of 3,29 g. The theoretical yield is 11,6 g. This corresponds to a mass% of 28,4 %. The low yield is due to the accident with the separatory funnel, where a large amount of the product was lost. Melting point The results from the analysis of the melting point are shown in the table below:
Table 2: Melting points

Target temperature1 Before recrystallization After recrystallization

1

Melting point interval 35-37 35-37,9 34,2-37

T. Ken, S. Takeaki, H. Masao, Eur.J.Org.Chem., 2007, 16, 2687

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Niels stergaard Hammer Kristian Mark Jacobsen

20103576 20107504

IR-spectroscopy The IR-spectrum was analyzed in the following manner: IR, (neat), 3062 (weak/medium, C-H stretch Aryl-H or alkene-H). 3001 (weak/medium, C-H stretch -unsaturated ketone), 1602 + 1574+ 1495 (strong, C=C

Aryl-H or alkene-H), 1678 (strong, C=O stretch -

stretch Aryl), 982 (strong, C-H bending trans R-HC=CH-R) cm-1.

1

H-NMR spectroscopy

Figure 5: Benzylideneacetone with atom numbers

-NMR (400 MHz,

(ppm) 2,39 (s, 3H, ), 7,55 (m, 2H,

), 6,72 (d, 1H, J=16,3 Hz, ).

), 7,40 (m, 3H,

), 7,52 (d, 1H, J=16,1 Hz, The doublet at

7,52 ppm is disturbed by the multiplet from

7,55 ppm. The most intense peak in the

multiplet is chosen as the second peak in the doublet. The coupling constant J=16,3 Hz and J=16,1 Hz corresponds to a trans configuration of the hydrogens at the C=C double bond. The sum of the integrals are 9,59 (10 when normalized), which matches the 10 hydrogen atoms in benzylideneacetone.

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Niels stergaard Hammer Kristian Mark Jacobsen

20103576 20107504

Conclusion
The IR-spectrum shows the expected main groups of the target molecule, and the 1H-NMR-spectrum was able to support this result. The melting point of the recrystallized product is quite close to the reference. Therefore it can be concluded that the synthesized product is indeed benzylideneacetone in a satisfyingly pure form.

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