Chinese Chemical Letters
Original article
Convenient synthesis of bis(indolyl)alkanes by dithiocarbohydrazone
Schiff base/Zn(ClO4)2ꢀ6H2O catalyzed Friedel–Crafts reaction of
indoles with imines
*
Yong-Hai Hui, Yong-Cheng Chen, Hai-Wei Gong, Zheng-Feng Xie
Key Laboratory of Oil & Gas Fine Chemicals, Ministry of Education & Xinjiang Uyghur Autonomous Region, College of Chemistry and Chemical Engineering,
Xinjiang University, Urumqi 830046, China
A R T I C L E I N F O
A B S T R A C T
Article history:
A new, convenient and excellent yield procedure for the preparation of bis(indolyl)methanes (BIMs) by
Friedel–Crafts reaction of indoles with imines in the presence of dithiocarbohydrazone Schiff base/
Zn(ClO4)2ꢀ6H2O as a highly stable, effective and readily available catalyst is described. Moderate to good
yields (up to 99% yield) were obtained with both substrates for imine derivatives. This procedure is
simple, practical and economic.
Received 20 May 2013
Received in revised form 22 July 2013
Accepted 30 August 2013
Available online 28 October 2013
ß 2013 Zheng-Feng Xie. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights
reserved.
Keywords:
Friedel–Crafts reaction
Indoles
Imines
BIMs
1. Introduction
catalysts are promising, there is still the need to develop a new
type of effective catalyst for the synthesis of BIMs.
Since first being reported by Gomberg in 1900, triaryls and
triheteroarylmethanes have gained attention from synthetic,
medicinal and industrial chemists [1,2]. Indole fragments exist
in a wide variety of pharmacologically and biologically active
compounds [3]. For example, bis(indolyl)methanes (BIMs) and
their derivatives are found in terrestrial and marine metabolites
[4], and they have varied biological activities, including antioxi-
dant, antibacterial, and insecticidal properties [5]. In recent years,
people have found that they are useful in the treatment of
fibromyalgia, chronic fatigue, and irritable bowel syndrome [6]; as
dietary supplements for promoting healthy estrogen metabolism
in humans [7]; as effective cancer preventors [8]; and in inducing
apoptosis in human cancer cells [9].
Friedel–Crafts reactions, an immensely powerful tool for
carbon–carbon bond-formations, have been used extensively in
synthetic chemistry [10]. Among F–C alkylations, reports about the
synthesis of BIMs and their derivatives have been described in the
literature. Generally, BIMs are prepared by the condensation of
indoles with various aldehydes or ketones in the presence of either
Protic acids [11] or Lewis acids [12]. Although some of these
Previously, dithiocarbohydrazone Schiff base catalysts have
been applied to some organic reactions in our group (Scheme 1)
[13]. Herein, we report a highly efficient Friedel–Crafts reaction of
indoles to imines using dithiocarbohydrazone Schiff base/
Zn(ClO4)2ꢀ6H2O complexes as a catalyst.
2. Experimental
Analytical thin-layer chromatography (TLC) was performed on
silica gel GF254 (Qingdao, China) with petroleum ether (60–90 8C)
and ethyl acetate and detected by UV light or iodine vapor. Melting
points were recorded on an elemental digital melting point
apparatus and were uncorrected. The 1H NMR and 13C NMR spectra
were recorded on an INOVA 400 MHz FT-NMR spectrometer. The
IR spectrum was recorded on
a Bruker Equinox 55 FT-IR
spectrophotometer. X-ray diffraction data were obtained with
an XRD, MAC18XHF22-SRA.
2.1. General procedure for preparation of Schiff bases
The Schiff base ligand L3 was synthesized from the reaction
with 1 mmol diamino thiourea and 2 mmol 5-chloro-3-methyl-1-
phenyl-1H-pyrazole-4-carbaldehyde in 15 mL anhydrous ethanol
in the presence of glacial acetic acid under reflux for 3–5 h. The
mixture was cooled to room temperature and filtered to give the
*
Corresponding author.
1001-8417/$ – see front matter ß 2013 Zheng-Feng Xie. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.