An efficient method for synthesis of bis(indolyl)methane and di-bis(indolyl)methane derivatives in environmentally benign conditions using TBAHS

Figures & data

Scheme 1. TBAHS efficiently catalyzed synthesis of bisindolylmethanes.

Scheme 2. Optimization of reaction condition.

Table 1. Optimization of reaction condition for synthesis of 3,3′-bis-indolyl phenylmethane^a

Entry	Catalyst (mmol)	Solvent	Temperature (°C)	Time (h)	Yield (%)^b
1	Bu4NHSO4 (0.1)	EtOH	r.t.	24	80
2	Bu4NHSO4 (0.1)	EtOH/H2O (3:1)	r.t	24	0
3	Bu4NHSO4 (0.1)	CH3CN	r.t	24	75
4	Bu4NHSO4 (0.1)	EtOAc	r.t	11	90
5	Bu4NHSO4 (0.1)	EtOAc	60	1	95
6	Bu4NHSO4 (0.1)	–	60	4	91
7	–	–	60	12	36
8	Bu4NHSO4 (0.1)	–	r.t	12	87
9	Bu4NHSO4 (0.15)	–	r.t	12	85
10	Bu4NHSO4 (0.2)	–	r.t	12	86
11	–	–	r.t	22	10

^a Benzaldehyde (1 mmol), indole (2 mmol).

^b Isolated yields.

Table 2. Synthesis of bisindolylmethanes catalyzed by TBAHS

Entry	Aldehyde or ketone	Product	A^a		B^b		Reference
			Time (h)	Yield (%)^c	Time (h)	Yield (%)^c
1	C6H5CHO	3a	1	95	4	91	Hojati et al. (2013)
2	4-Me-C6H4CHO	3b	1.5	93	5	95	Hojati et al. (2013)
3	4-Cl-C6H4CHO	3c	1	94	3	95	Hojati et al. (2013)
4	4-OMe-C6H4CHO	3d	1	90	4	88	Hojati et al. (2013)
5	3-NO2-C6H4CHO	3e	1	91	4	92	Hojati et al. (2013)
6	4-NO2-C6H4CHO	3f	1	90	4	91	Hojati et al. (2013)
7	2,4-Cl2-C6H3CHO	3g	1	93	3	94	Veisi et al. (2009)
8	2-Cl-C6H4CHO	3h	1.2	89	5	91	Hojati et al. (2013)
9	Isophthaldehyde	3i	1.5	88	5	91	–^d
10	Terphthaldehyde	3j	1.5	90	5	90	Veisi et al. (2009)
11	Acetone	3k	12	45	24	40	Veisi et al. (2009)
12	Cyclohexanone	3l	10	90	24	93	Hojati et al. (2013)
13	4-Me-cyclohexanone	3m	10	87	24	92	–^d
14	Acetophenone	3n	12	60	24	50	Veisi et al. (2009)
15	Isatin	3o	2	93	6	96	Haghighi and Nikoofar (2014)

^a Method A: Bu₄NHSO₄ (0.1 mmol), 60°C, EtOAc (1 mL).

^b Method B: Bu₄NHSO₄ (0.1 mmol), 60°C.

^c Isolated yields.

^d Novel product.

Hojati, S. F., Zeinali, T., & Nematdoust, Z. (2013). A novel method for synthesis of bis(indolyl)methanes using 1,3-dibromo-5,5-dimethylhydantoin as a highly efficient catalyst under solvent-free conditions. Bulletin of the Korean Chemical Society, 34, 117–120.10.5012/bkcs.2013.34.1.117

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Veisi, H., Hemmati, S., & Veisi, H. (2009). Highly efficient method for synthesis of bis(indolyl)methanes catalyzed by FeCl. Journal of the Chinese Chemical Society, 56, 240–245.10.1002/jccs.v56.2

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Haghighi, M., & Nikoofar, K. J. (2014). Nano TiO2/SiO2: An efficient and reusable catalyst for the synthesis of oxindole derivatives. Journal of Saudi Chemical Society, Retrieved from : https://scholar.google.com/citations?view_op=view_citation&hl=en&user=llpcGOYAAAAJ&citation_for_view=llpcGOYAAAAJ:ufrVoPGSRksC doi:10.1016/j.jscs.2014.09.002

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