A Practical Synthesis of Indole-2-carboxylic Acid
477
It is noteworthy that in this procedure RS001 is immobilized and used as a catalyst
which can be easily reused. The process is environmentally benign, easy to work up and
leads to product of excellent purity in 56% yield.
Experimental Section
Mp of product was uncorrected. The HPLC purity of product was established on an Agilent
1260. 1H NMR spectra were recorded in DMSO-d6 on a Bruker 400 (400 MHz) instrument
with TMS as internal standard. All chemicals were reagent grade and available commercially.
Pd-loaded Al-MCM-41 Mesoporous Catalyst (RS001)
One g of PdCl2 was dissolved in a mixture of 2 mL hydrochloric acid (37%) and 15 mL
of deionized water. Ten g of Al-MCM-41 mesoporous molecular sieve was poured into
the solution with rigorous stirring at 75ꢀC for 30 min. Then 8 mL of 0.7 M sodium for-
mate was added. The mixture was kept under stirring at the same temperature for another
2 h and then filtered at the pump. The filter cake was washed with 15 mL water,
collected, dried in vacuo at 100ꢀC for 4 h, then calcined at 500ꢀC for 3 h with a heat rate
1.5ꢀC/min in air to afford the Pd-loaded Al-MCM-41 mesoporous catalyst, RS001.
Indole-2-carboxylic acid (4)
In a 150 mL round-bottomed flask was placed of a solution of 5.94 g (0.11 mol) sodium
methylate in 20 mL methyl alcohol, and a mixture of 13.7 g (0.10 mol) nitrotoluene (1)
and 14.6 g (0.10 mol) of diethyl oxalate (2) was added. The mixture was kept stirring at
65ꢀC for 2 h and then poured into 500 mL ice water. The aqueous solution was purified
through steam distillation until no emulsion dropped out. Then the mother liquor was
decolorized with 10 g actived carbon and concentrated to a solution (70 g) of 3-(2-nitro-
phenyl)-2-oxopropanoic sodium salt (3), directly used in the next step. In a 250 mL pres-
sure reactor was placed the above sodium salt (3) and 70 g methyl alcohol. Then 1.5 g
RS001 was added while the pH of the mixture was adjusted to 7.5 with ammonium
hydroxide. Under a hydrogen pressure of 1.5 Mpa, the mixture was stirred at 70ꢀC for
4 h. Then the mixture was cooled and filtered at the pump. The filtrate was acidified with
4 M hydrochloric acid to pH 3 which led to precipitation. The precipitated solid was col-
1
lected and dried in vacuo to afford 9.05 g (56%) product (4) (HPLC >97%), H NMR
(DMSO-d6): d 12.93 (1 H, s), 11.76 (1 H, s), 7.65 (1 H, d, J D 8.0 Hz,), 7.48–7.42 (1 H,
m), 7.28–7.20 (1 H, m), 7.13–7.03 (2 H, m). An analytical sample was prepared by
recrystallization from methanol, mp 204–205ꢀC, lit mp 204ꢀC.9
Acknowledgments
We thank the Science and Technology Foundation of Hangzhou (20170533B02) and the
Program for Changjiang Scholars and Innovative Research Team in Chinese University
(IRT 1231).
References
1. S. Narsimha, N. S. Kumar, K. S. Battula, V. R. Nagavelli, S. K. A. Hussain and M. S. Rao,
Bioorg. Med. Chem. Lett., 26, 1639 (2016).
Jiang, Ting
