RESEARCH FRONT
Fischer Indole Synthesis over Hydrous Zirconia-Supported Niobium Oxide
1033
measurements, the samples were degassed for 4 h under a flow
of nitrogen at temperatures of 100–300◦C. Thermogravimetric
analysis (Dupont SDT 2960) was carried out using a heating
ramp of 20◦C min−1 in 100 mL min−1 of air. To remove any
physically adsorbed water, the sample was held isothermally
at 100◦C for 30 min before increasing the temperature. Ele-
mental analysis of the samples was carried out using ICP-AES
after dissolution of the solid in HF. The density of acid sites
was determined by titrating 0.05 g of the sample with 0.04 N
n-butylamine in benzene, using 0.1% methyl red as the indica-
tor. Infrared adsorption spectroscopy of pyridine adsorbed on the
samples was used to determine the type of acid sites present on
the samples. Self-supporting wafers (6–8 mg) were mounted in
an evacuable Pyrex IR cell with NaCl windows. After degassing
the sample at 300◦C in vacuum (0.1013 Pa) for 2 h, the sam-
ple was cooled to room temperature and pyridine at 2.2 kPa was
introduced into the cell.The cell was again evacuated for another
hour before making an IR measurement.A Bio-Rad FTS 165 FT-
IR spectrometer was used with a resolution of 2 cm−1. Further
measurements were done after the sample had been heated at
100◦C and 200◦C for 1 h at each temperature.
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Catalytic Activity Testing
The Fischer indole reaction of phenylhydrazine and 3-heptanone
was carried out in a two-necked 25 mL round-bottomed flask
equipped with a condenser. The reaction mixture consisted of
0.202 mL (2 mmol) of phenylhydrazine, 0.279 mL (2 mmol) of
3-heptanone, and 1 mmol dodecane as internal standard in 5 mL
of p-xylene as solvent. The flask was flushed with nitrogen and
the stirred reaction mixture was heated up to 140◦C under nitro-
gen. Once the complete condensation of phenylhydrazine with
3-heptanone to form phenylhydrazone was confirmed by gas
chromatography (Agilent GC 6890 equipped with a HP-5 cap-
illary column and an FID detector), 0.25 g of the catalyst was
introduced. Aliquots were removed at regular time intervals and
analyzed by GC. The temperature program used for separation
of the products was as follows: 80◦C for 2 min, 10◦C min−1 to
230◦C, then 20◦C min−1 to 300◦C. The identity of the products
was verified by comparison with the retention times of authentic
samples and by GC-MS (Shimadzu GCMS QP5000, DB5MS
column). The Fischer indole reaction of phenylhydrazine and
cyclohexanone was carried out in a similar way using 2 mmol
cyclohexanone instead of 3-heptanone. To test for reusability, a
25 wt-% Nb2O5/Zr(OH)4 was recovered after reaction, washed
with p-xylene and immersed in 30% H2O2 at 40◦C for 5 h. After
drying overnight at 100◦C, the sample was tested for its activ-
ity in another batch reaction. Leaching of the catalyst into the
solution phase was tested by filtering the catalyst from the hot
reaction mixture and monitoring the progress of the reaction in
the filtered solution.
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Acknowledgements
Financial support from National University of Singapore under grant number
R-143–000–329–112 is gratefully acknowledged.
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