Selective propynylation of cinnamaldehyde

Experiment 17
Bogdan Stefan
Demonstrator: Xinkai Qiu
20.09.2013

Summary
Organolitium compounds can be used in nucleophilic addition reactions to attack electrophilic
centers.
Introduction
The purpose of this experiment is to make an alkyl lithium reagent from n-BuLi and 1-bromo-1propene and use it react with cinnamaldehyde at the desired electrophilic center.
Theory
Due to lithiums electropositivity, the carbon atom bonded to it will generate a partially negative
charge, making it possible to attack a proton from 1-bromo-1-propene and generate an electronic
movement through the molecule, forming a new pi bond and break the bond with the bromine. In
the next step, the carbo anion takes the proton form the alkyne, making that carbon to bond with
the lithium atom.

The partially positive charged carbon from the carbonyl group is attacked by the alkyne anion
because it has a big reactivity. The added ammonium chloride will be deprotonated by the
oxygen atom while the chlorine will bond with the loose lithium atoms.

Experimental
(Z/E)-1-bromo-1-propene (1.86 g) and tetrahydrofuran (THF) (10 mL) were added in a flask
equipped with a dropping funnel flushed with nitrogen gas. The mixture was cooled in a 1:1
solution of methanol and ethanol and liquid nitrogen. n-BuLI (14 mL) was added dropwise and
after that, the funnel was rinsed with THF (2 mL). The solution was stirred for 2 hours at -78 oC
before adding cinnamaldehyde (1.32 g) in THF (5 mL) drop-wise. The funnel was rinsed again
with THF (2 mL) and the mixture was stirred for 30 min. The solution was quenched with
ammonium chloride (5 mL) and warmed to room temperature. The mixture was diluted with
water (20 mL) and ether (20 mL) and extracted with ether (3x20 mL). The combined organic
layers were washed with brine (2x20 mL) and then dried with sodium sulfate afterwards, the
solution was filtered, and the solvent was removed in vacuo. The product was purified by column
chromatography while monitored by TLC and send for UV, IR and 1H-NMR analysis.
Name
Quantity
Boiling point (C) Melting point (C) Density (g/mL)
1-bromo-1-propene
1.86 g
-116
1.423
THF
19 mL
66
-108.4
0.889
n-BuLi
14 mL
-76
0.68
Ammonium chloride 5 mL
520
338
1.527
Cinnamaldehyde
1.32 g
248
-7.5
1.049
Results and discussion
During the column chromatography, the reaction was followed by 5 TLCs (figure 1). Tube #1
was used to test tube 6 which had 2 products. The next one was used for 4 showing the presence
of one of the products. Plate #3 measured tubes 2;3 and 5 only to reveal that tube 5 had some
product. Tubes 9 and 11 were tested and after 10 and 12 on the next plate, showing that the other
product was isolated only in tube 11.

Figure 1- TLC plates (Blank + 5 samples)

The UV spectra (figure 2) doesnt tell much about the product, only some slight absorption peaks
around between 400-300 nm that might be the conjugated system in the benzene ring.

Figure 2- UV-vis spetra

The IR analysis (figure 3) shows 3 peaks that confirm the presence of the same functional groups
as the desired product has. The first one at 1650 cm -1 corresponds to a carbon-carbon double
bond stretch, the second one at 2225 cm-1 represents the carbon-carbon triple bond stretch which
is a weak stretch and the third one at 3350 cm -1 is the oxygen-hydrogen stretch from the hydroxyl
group.

Figure 3- IR spectra
The NMR spectra shows the presence of other impurities in the final product. There are 10
signals: triplet at =1, a complex signal at =1.25, singlet at 1.8 and 2.1, quartet at 3.5, singlet at
3.75 and 5, doublet of doublets at 6.3, doublet at 6.75 and another complex signal at 7.4. Some of
these peaks can be seen also on a simulated spectrum: the benzene ring (complex at 7.4), the
proton from the hydroxyl group (singlet at 5 ppm) and the protons from the methyl group (singlet
at 2 ppm). The reason why the final product was so impure is because of human error: tubes 4
and 5, which contained a product, were mixed with tube 11, containing another product, before
removing the solvent.

Figure 4- 1H-NMR spectra of the product

Conclusion
Cinnamaldehyde was attacked at the stronger electrophilic center by the organolithium reagent,
synthesizing the final product, but in an impure from as it can be seen for the NMR spectra.
Questions and answers
1.Describe three different ways of preparing alkyl lithium reagents.
One method is metalation, is a simple lithium-hydrogen exchange. Similar to this is the lithiumhalogen exchange between an organohalide and organolithium species. A third method is the
Shapiro reaction which consists two equivalents of strong alkyl lithium base react with ptosylhydrazone compounds to produce the vinyl lithium.
2.Why is it important to exclude water from your reaction?
n-BuLi reacts violently with water, resulting normal butane and lithium hydroxide which have a
very low reactivity.
3.What is the role of BuLi in this reaction?
Its acts as initiator to deprotonate 1-bromo-propene and form the organolithium reagent.
5

4. Cinnamaldehyde has 2 electrophilic centers. Reaction with alkyl lithium is selective for one.
What reactants can you use if you want to achieve reaction at the other electrophilic center? Do
you know what causes this difference?
One of the centers is at the double bond with the oxygen (most electrophilic center) and other
connecting to benzene. Because strong nucleophiles with react with strong electrophilic centers,
so will weak nucleophiles will react with weak nucleophiles (e.g water).
References
https://en.wikipedia.org/wiki/Organolithium_reagent#Preparation