1. The synthesis of julolidine was attempted using the Discover LabMate
Microwave for heating. Optimizations included the amount of starting
material, the temperature of the solution, the power of the
microwave, and the reaction time to determine the best route to
improve the synthesis of julolidines and its derivatives. The main focus
is to reduce the reaction time and produce better yields of the
solution.
1. Abd El-Aal, H.; Khalaf, A.; El-Khawaga, A., J. Heterocyclic Chem.
2014, 51, 262
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2014 <http://cem.com/discover-sp.html>.
3. Gavvala, K.; Sasikala, W.; Segupta, A.; Dalvi, S.; Mukherjee, A.;
Hazra P., Phys. Chem. Chem. Phy. 2013, 15, 330-340.
4. Goh, W.; Lee, M.; Joseph, T.; Quah, S.; Brown, C.; Verma, C., J. Am.
Chem. Soc. 2014, 136, 6159-6162.
INTRODUCTION DISCUSSION
The reactions for the synthesis of julolidines were optimized
using the control panel on the Microwave Synthesizer shown in
Figure 1. The control panel allows methods to be formulated with
different reaction times, temperature, power, and cooling time.
Based on the results for previous trials, the determination for the
methods for the next trials was made. Table 1 shows the trials
performed for the synthesis of julolidines. Equation 1 shows the
steps used to complete the synthesis involving a mixture of
aniline, 1-bromo-3-chloropropane, and DMF shown in Figure 2.
Figure 3 is the crude product from this reaction which is a result
of a lower reaction time with a high power and temperature.
Figure 4 shows the product once the workup was done. Results
shown in Table 1 were compared to the standard julolidine 1H-
NMR spectrum in Figure 6. It shows that the synthesis produces
more product at a temperature of 200 ˚C and a power of 300
Watts. As you can see the product for Trial 10 has very similar
peaks to the 1H-NMR spectrum in julolidine. The spectrum has
the same number of signals with the integration and chemical
shift. The 1H-NMR spectrum for Trial 9 indicates that a by-product
or intermediate is the major product. It only has trace amounts
of the final product. This trial was conducted at a low reaction
time and temperature thus supporting the results from Figure 7
where a higher temperature and power are used.
METHODS/ RESULTS
Thanks to the Department of Chemistry and Biochemistry Research
Initiation Award and Corning for the support of this project .
ACKNOWLEDGEMENTS
REFERENCES
ABSTRACT
Julolidines are heterocyclic aromatic compounds with one ring junction nitrogen atom, classified as molecular rotors. molecular rotors have
been used as sensors, with the capability of measuring the viscosity in cell membranes to detect diseases such as Parkinson’s and Alzheimer’s.
The possibility of julolidine and its derivatives being used for photoconductivity, as anesthetics, dyes, as potential antidepressants and
tranquilizers, and used to refine the color strength in photography has induced an interest to research the substance and its properties. The
development of valuable and efficient tactics for the structure of these ring systems remains a significant task. Few synthesis methods for the
synthesis of julolidine and its derivatives have been reported. One method of conducting the reaction that has not been reported in the
literature is using a microwave synthesizer. The microwave synthesizer is known to reduce reaction times, about 10-1000 times faster and
produce better yields than conventional heating. This device provides monitoring and control of temperature, pressure, and stirring to ensure
maximum safety and reproducibility in the lab. The microwave synthesizer could make the reaction more energy and time efficient, produce
better yields, reduce the amount of hazardous solvents, and enhance safety. Using the microwave synthesizer, optimizations for the trials will
include the amount of starting material, the temperature of the solution, the power of the microwave, and the reaction time to determine
the best route to improve the synthesis of julolidines and its derivatives. The microwave will allow more ability to control the experiment by
introducing new variables into the experiment to produce better results.
Julolidines consist of electron donating and electron
withdrawing units, which are conjugated in the planar ground
state. When light hits the compound it becomes excited and
takes on a twisted structure, which disrupts the conjugation. It
then relaxes through fluorescence emission or a non-
fluorescent relaxation pathway.4 These molecular rotors can be
highly sensitive to the environment. The compound will
undergo fluorescence in a viscous environment; the non-
fluorescent relaxation pathway is prevented. This allows
compounds in the molecular rotor family to be used as
fluorescent dyes and sensors in biological systems. Further
analysis of this family of compounds is needed to analyze their
potential as sensors in applications relevant to biological and
energy fields. However, in order to study these compounds an
efficient synthesis strategy is needed to produce a variety of
substituted julolidines. Varying substituents can be on the
piperidines ring, aromatic ring, and the vinyl carbon.3 The aim of
this project is to provide more efficient synthesis routes to form
a variety of julolidines. The current synthesis for julolidines is
limited by the harsh reaction conditions. The least expensive
method of making these compounds is from aniline derivatives.
The general procedure involves refluxing the reactions in
dimethylformamide for 14 hours. The average yield reported is
about 50 percent. Another route involves alkylation of a 1,2,3,4-
tetrahydroquiline with 3-chloro-1-bromopropane.1 However,
tetrahydroquinolines are very expensive and not practical
starting materials. Instead of tetrahydroquinoline, aniline will be
used to produce the julolidine derivatives reducing the
preparation cost. Various reaction conditions will be tested to
synthesize the juloliodines using the microwave to improve the
results. The microwave will allow more ability to control the
experiment by introducing new variables, such as the
temperature of the mixture, the power of the microwave, the
cooling time, the pressure applied, and the reaction time. The
microwave synthesizer is known to reduce reaction times, about
10-1000 times faster than current methods.2 Instead of waiting
12 hours for the reaction to completely reflux, the microwave
synthesizer may allow shorter heating periods or a combination
of heating and cooling periods.
Equation 1: Current Synthesis of Julolidine from Aniline
Figure 1: Microwave Control Panel Figure 2: Starting
Material
RESULTS
Table 1: Trials for Julolidine Synthesis
Trials Time
(mins)
Temperature
(°C)
Power
(Watts)
Increments NMR Results -
major peaks
1 60 200 150 1 Product
2 30 150 300 1 Product
3 20 200 150 1 Product
4 60 200 300 3 Product
5 60 150 150 3 Intermediate
6 60 150 300 3 Intermediate
7 30 150 300 1 Intermediate
8 20 150 300 1 Intermediate
9 60 150 300 1 Intermediate
10 60 200 300 1 Product
FUTURE PLANS
The next steps include checking the yields of the product from the best
trials. Once the reaction is optimized other aniline derivatives, shown
in Figure 5, can be screened in the reaction to test the scope.
Figure 3: Crude
Product
Figure 4: Product
Figure 6: Julolidine 1H-NMR Spectrum
Figure 7: Julolidine 1H-NMR Spectrum of Trials
Trial 10: 60 minutes, 200 °C, 300 W (Crude Product)
Trial 10: 60 minutes, 200 °C, 300 W (Clean Product)
Trial 8: 20 minutes, 150 °C, 300 W (Crude Product)
Figure 5: Selected Aniline Derivatives for Julolidine Synthesis