Synthesis of bis(indolyl) methanes in catalyst- and solvent-free reaction

Article abstract of DOI:10.1080/00397911003642690

Efficient synthesis of bis(indolyl) methanes by the reaction of indoles with various carbonyl compounds in the absence of catalyst and solvent afforded the corresponding bis(indolyl) methanes in excellent yields.

Full text of DOI:10.1080/00397911003642690

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Synthesis of Bis(indolyl) Methanes in
Catalyst- and Solvent-Free Reaction
Vishvanath D. Patil a , Ganesh B. Dere a , Priyanka A. Rege a
Jaymala J. Patil a
&
a Organic Chemistry Research Laboratory, Department of Chemistry,
C. K. Thakur College, Raigad, Maharashtra, India
Version of record first published: 31 Jan 2011.
To cite this article: Vishvanath D. Patil , Ganesh B. Dere , Priyanka A. Rege & Jaymala J. Patil (2011):
Synthesis of Bis(indolyl) Methanes in Catalyst- and Solvent-Free Reaction, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 41:5, 736-747
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Synthetic Communications1, 41: 736–747, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911003642690
SYNTHESIS OF BIS(INDOLYL) METHANES IN
CATALYST- AND SOLVENT-FREE REACTION
Vishvanath D. Patil, Ganesh B. Dere, Priyanka A. Rege, and
Jaymala J. Patil
Organic Chemistry Research Laboratory, Department of Chemistry,
C. K. Thakur College, Raigad, Maharashtra, India
Abstract Efficient synthesis of bis(indolyl) methanes by the reaction of indoles with various
carbonyl compounds in the absence of catalyst and solvent afforded the corresponding
bis(indolyl) methanes in excellent yields.
Keywords Aldehydes; bis(indolyl) methanes; indole; solvent-free
INTRODUCTION
Simple, efficient, environmentally benign, and economically viable chemical
processes or methodologies for widely used organic compounds are in great demand.
Bis(indolyl) alkanes are a biologically useful class of organic compounds, and a large
number of these indolyl methanes have been isolated from terrestrial and marine
natural sources such as tunicates and sponges.[1] For example, vibrindole A
(3,30-diindolyl ethane) exhibits antibacterial activity, and 3,30-diindolyl methane
has potent carcinogenic properties.[2] Because of their wide occurrence as natural
products and various biological activities, synthesis of these bis(indolyl) methanes
have attracted attention. Recently, oxidized bis(indolyl) methanes containing a con-
jugated bis(indolyl) skeleton have acted as colorimetric sensors and chromogenic
sensors.[3] In addition, 1,1-bis(30-indolyl)-1-(p-substituted phenyl) methanes
Received December 7, 2009.
Address correspondence to Vishvanath D. Patil, Organic Chemistry Research Laboratory,
Department of Chemistry, C. K. Thakur College, New Panvel, Raigad, Maharashtra, India. E-mail:
patilvd148@yahoo.in
736

SYNTHESIS OF BIS(INDOLYL) METHANES
737
containing p-trifluoromethyl (DIM-C-p-CF3Ph), p-t-butyl (DIM-C-p-tBuPh), and
p-phenyl (DIMC-p-C6H5Ph) substituents have been identified as belonging to a
new class of peroxisome proliferator-activated receptors (PPAR) agonists that
exhibit antitumorigenic activity.[4] Various methods have been developed for their
synthesis using Lewis acid catalysts such as LiClO4,[5] In(OTf)3,[6] Dy(OTf)3,[7]
Sc(OTf)3,[8,9] ceric ammonium nitrate (CAN),[10] ZrOCl2,[11] InCl3,[12] and
AlPW12O40,[13] ionic liquids,[14] trichloro-1,3,5-triazine,[15] potassium hydrogen
sulfate,[16] La(NO3)3 ꢀ 6H2O,[17] and Fe(DS)3.[18] However, many of these reported
methods suffer from one or more disadvantages such as harsh experimental pro-
cedure and reagents that are expensive, moisture sensitive, or highly toxic in nature.
A mild and efficient catalyst for the synthesis of bis(indolyl) methanes is highly
desirable. Consequently, there is an opportunity for further development of mild
conditions, increased variation of the components, and better yields. In this com-
munication, we report a green protocol for the synthesis of bis(indolyl) methanes
in the absence of catalyst.
RESULTS AND DISCUSSION
A wide variety of compounds were applied to the optimal reaction conditions
to prepare a wide range of bis(indolyl) methanes (Scheme 1).
The results are summarized in Table 1. The reaction proceeded efficiently and
smoothly at 80 ꢁC in the absence of catalyst and absence of solvent, and the products
were obtained in excellent yields. Furthermore, the reaction conditions are very mild,
and no by-products were observed. Aromatic aldehydes reacted more rapidly than
aliphatic aldehyde. The effect of electron deficiency and nature of the substituents
on the aromatic ring showed some effect on this conversion. The nitro substituted
aryl aldehydes required slightly longer reaction times than those of their simple
and electron-rich counterparts to produce comparable yields (Table 1, entries
1–14). Electron-rich aldehydes such as anisaldehyde, piperonal, and veratraldehyde
reacted rapidly with indole to give corresponding products in excellent yields within
40 min (Table 1, entries 3, 4, and 15). Aliphatic aldehydes such as n-hexanal,
n-heptanal, and cyclohexane carboxaldehyd showed somewhat less reactivity
(Table 1, entries 16–18). Substituted indoles reacted rapidly with aryl aldehydes with
considerable yields (Table 1, entries 19, 20, and 21). Further, the reaction of ketones
proceeded with more reaction time under the same reaction conditions, and the
corresponding products were obtained in moderate yields (Table 1, entries 22–25).
Scheme 1. R: phenyl, alkyl; R0: H, phenyl, alkyl.

738

739

740

741

742

743

744

SYNTHESIS OF BIS(INDOLYL) METHANES
745
GENERAL EXPERIMENTAL PROCEDURE FOR BIS(INDOLYL) METHANES
A mixture of benzaldehyde (2 mmol) and indole (4 mmol) was stirred magneti-
cally at 80 ꢁC in the absence of solvent and the progress of the reaction was moni-
tored by thin-layer chromatography (TLC). The completion of reaction confirmed
with TLC. The product was dried over anhydrous Na2SO4 and then evaporated
under vacuum to afford the crude product, which was further purified by column
chromatography. In all the cases, the product obtained after the usual workup gave
satisfactory spectral data.
SPECTRAL DATA FOR SELECTED COMPOUNDS
3,3’-Bisindolyl Phenylmethane (1b)
Pale red solid, yield 92%, mp 123–125; IR (KBr): 735, 1094, 1342, 1458, 1483,
1
2927, 2956, 3045, 3387 cmꢂ1; H NMR (300 MHz, CDCl3): d ¼ 7.78 (br s, 2H), 7.36
(d, J ¼ 8.1 Hz, 2H), 7.10–7.36 (m, 9H), 6.95 (t, J ¼ 7.5 Hz, 2H), 6.46 (d, J ¼ 1.8 Hz,
2H), 5.82 (s, 1H); 13C NMR (CDCl3): 143.0, 136.2, 128.5, 128.6, 127.3, 126.5,
123.4, 121.3, 119.4, 119.0, 118.9, 111.3, 40.6.
3,3’-Bisindolyl-4-methoxylphenylmethane (3b)
Brown needles, yield 89%, mp 193–195; IR (KBr): 740, 780, 1015, 1090, 1132,
1341, 1450, 1607, 2922, 3052, 3386, 3422 cmꢂ1 1H NMR (300 MHz, CDCl3):
;
d ¼ 7.90 (br s, 2H), 6.9–7.9 (m, 12H), 6.4 (s, 2H), 6.1 (s, 1H), 3.95 (s, 3H), 13C
NMR (CDCl3): 39.4, 55.6, 102.3, 111.3, 119.7, 122, 123.8, 128.2, 129.9, 135.8,
136.8, 157.8; EIMS: m=z 352.
3,3’-Bisindolyl-4-dimethylaminophenylmethane (7b)
Pink solid, yield 91%, mp 168–170; IR (KBr): 740, 760, 1015, 1095, 1222, 1350,
1
1456, 1512, 2920, 3062, 3342, 3418, 3520 cmꢂ1; H NMR (300 MHz, DMSO): 11.30
(br s, 2H), 8.30 (d, J ¼ 2.0 Hz, 2H), 8.02 (dd, J ¼ 8.8, 2.0 Hz, 2H), 7.50 (dd, J ¼ 9.2,
1.6 Hz, 2H), 7.43 (d, J ¼ 7.6 Hz, 2H), 7.36 (t, J ¼ 7.6 Hz, 2H), 7.25 (d, J ¼ 7.2 Hz,
1H), 7.20 (s, 2H), 6.23(s, 1H); 13C NMR (DMSO): 148.6, 145.2, 144.2, 133.1,
133.5, 132.6, 131.7, 130.2, 125.8, 121.4, 121.5, 117.3, 43.7; MS (ESI) m=z: 411.34.
3,3’-Bisindolyl-4-methylphenylmethane (8b)
Pale red solid, yield 90%, mp 95–98; IR (KBr): 742, 788, 999, 1090, 1225, 1340,
1
1457, 1508, 2925, 3056, 3386, 3420 cmꢂ1; H NMR (300 MHz, CDCl3): 7.84 (br s,
2H), 7.42 (d, J ¼ 8.0 Hz, 2H), 7.30 (d, J ¼ 8.3 Hz, 2H), 7.26 (d, J ¼ 8.0 Hz, 2H),
7.15 (dd, J ¼ 7.6 Hz, 2H), 7.03 (d, J ¼ 8.0 Hz, 2H), 7.00 (t, J ¼ 7.2 Hz, 2H), 6.64 (s,
2H), 5.83 (s, 1H), 2.33 (s, 3H); 13C NMR (CDCl3): 141.2, 136.5, 136.5, 129.2,
128.5,127.3, 123.4, 122.1, 120.2, 119.5, 119.2, 111.2, 40.2, 21.3.

746
V. D. PATIL ET AL.
3,3’-Bisindolyl-4-chlorophenylmethane (11b)
Pale solid, yield 86%, mp 74–76; IR (KBr): 743, 787, 1010, 1100, 1130, 1325,
1
1456, 1603, 2920, 3050, 3382, 3420 cmꢂ1; H NMR (300 MHz, CDCl3): d ¼ 7.7 (br
s, 2H), 7.3 (d, 2H, J ¼ 7.8), 7.01–7.15 (m, 8H), 6.86–6.97 (m, 2H), 6.35 (s, 2H),
5.73 (s, 1H); 13C NMR (CDCl3): 44.4, 111.1, 112.2, 119.1, 120.4, 121.6, 122.8,
128.8, 130.7, 131.5, 135.9, 136.6.
ACKNOWLEDGMENT
The authors acknowledge partial support of this work by Prof. B. P. Bandgar,
vice chancellor, University of Solapur, India.
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