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Multi-Step Synthesis: Insect Pheromones
The synthesis of the German cockroach (Blattella germanica) sex pheromone,
Blattellaquionone1, and the ant (tapinoma nigerimum/simruthi) alarm pheromone,
2-methyl-4-heptanone2, were chosen for the multi-step project. Each project is
composed of a two-step synthesis to arrive at the final product. NMR, IR, and
melting point analysis were used to determine the identity of the final product.
Blattellaquinone (Fig.1) features a 6 membered carbon ring, 2 conjugated
ketone groups, an ester group, and alkyl groups. The structure was first elucidated
as the pheromone in 20053. It took over 10 years and about 10,000 cockroaches
using specialized gas chromatography techniques to do so, as the compound is
thermally unstable and produced in very small amounts. The specific cockroach is
good at transferring human pathogens, so a viable application includes use of the
pheromone as a more efficient cockroach trapping method.
Figure 1: Blattellaquinone
2-methyl-4-heptanone (Fig. 2) is composed of a 7 carbon aliphatic chain, a
ketone group, and a methyl group. A search reveals no available history, nor
applications.
1
Feist, P. L. J. Chem. Educ. 2008, 85, 1548-1549.
De Jong, E. A., Feringa, B. L. J. Chem. Educ. 1991, 68, 71-72.
3 Science, 307, 1104 (2005)
2
Figure 2: 2-methyl-4-heptanone
The synthesis of Blattellaquinone (Fig. 3) begins with 2,5-dimethoxybenzyl
alcohol and isovaleryl chloride, which react by a nucleophilic acyl substitution
(Fig.4). Then the resulting product, 2,5-dimethoxy 3-methylbutanoate is oxidized by
ceric ammonium nitrate (CAN) to generate the final product Blattellaquinone
(Figure. 5). CAN is used because it is inexpensive, non-hygroscopic, relatively nontoxic, and easy to handle.
Figure 3: Blattellaquinone Reaction Scheme
Figure 4: Step One Mechanism
Figure 5: Step Two Mechanism
A percent yield was calculated at the end of step one and at the end of step
two. The theoretical yield was 2.52 g and 2.22 g and the experimental yield was 1.44
g and 1.07g, respectively. Thus, the percent yield after step one was 57.14% and the
final percent yield was 48.19%.
A melting point of 53.2 °C was recorded for the generated final product. The
literature provides a value of 56.5 °C. Although the melting points values are not
spot on, as they differ by about 3 °C, the literature also states that most students
received similar values.
IR was performed on the final product. Literature and experimental spectra
are attached for reference. As noted earlier in the structure of Blattellaquinone, the
structure features alkyl, ketone, and ester groups, all of which are present in the IR.
The alkyl peaking is found in the 2850-3000 cm-1 range, and the ester and ketone
are found in the 1670-1820 cm-1 range. The peak at 1737.33 cm-1 is the ester and
the peak at 1653.32 cm-1 is the ketone. Besides evidence of the correct functional
groups being present, the literature and experimental spectra match up quite well.
Thus far, the data indicates that Blattellaquinone was generated.
NMR was also performed on the intermediate, 2,5-dimethoxybenzyl 3methybutanoate, and the final product, Blattellaquinone. NMR of experimental and
literature spectra are attached for reference as well. A thorough analysis of
experimental spectra is provided on the respective spectra, specifically involving
key hydrogen peaks. Integration ratios match up as well from experimental to
literature.
2-methyl-4-heptanone is synthesized (Fig. 6) from 1-chloro-2methylpropane and butanal to produce 2-methyl-4-heptanol by Grignard reaction
(Fig. 7), which is followed up by an oxidation by sodium hypochlorite (Fig. 8).
Figure 6: Reaction Scheme 2-methyl-4-heptanone
Figure 7: Grignard Mechanism
Figure 8: Oxidation by Sodium Hypochlorite
A Grignard reaction calls for the absence of H2O and CO2, due to side reactions, to
have a successful yield. Thus, a nitrogen atmosphere is employed during step one of
the reaction scheme. A three-necked flask was fitted with a glass stopper, nitrogen
tubing, and an addition funnel. The flask was filled with nitrogen, and then addition
of the specific reagents was allowed to proceed.
A yield and melting point were not performed, as the intermediate and
product were liquid and quite impure.
The NMR spectra, which are attached, of 2-methyl-4-heptanol and 2-methyl4-heptanone were extremely messy. This mess represented solvent and other
impurities from Grignard reaction. Although the spectra improves greatly from the
intermediate to the supposed final product, it still is not pretty, nor is it likely to be
the final product.
The cockroach pheromone synthesis went well, and the data indicates that
the final product, Blattellaquinone, was indeed generated. The ant pheromone
synthesis on the other hand did not turn out as well. The only form of indentification
used, NMR, indicates a wild mess. Important peaks are present, however the
spectrum is simply too unreliable to come to any conclusions. However, the lab was
important as I was able to experience more advanced laboratory techniques. In
conclusion, both projects were valuable experiences and very enjoyable.
NMR Spectra for Blatellaquinone
NMR Spectra for 2-Methyl-4-heptanone