WCl₆ as an efficient, heterogeneous and reusable catalyst for the preparation of 14-aryl-14H-dibenzo[a,j]xanthenes with high TOF

Abstract

An efficient solvent-free protocol for the synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes from β-naphthol and arylaldehydes using WCl₆ as a reusable catalyst is reported. The turn over frequency (TOF) value of the catalyst is several times higher than that of the previously reported catalysts. A clean reaction, simple purification, short reaction time and high yield are some other advantages of this work.

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14-Aryl-14H-dibenzo[a,j]xanthene functionality is a key structural element of many biologically active compounds, such as antibacterials,¹ antivirals² and anti-inflammatory agents,³ and in photodynamic therapy.⁴ Xanthene-based compounds have also been investigated for agricultural bactericide activity and some other benzoxanthenes find applications in industry as dyes in laser technology⁵ and fluorescent materials for visualization of biomolecules.⁶ Xanthene dyes are extracted naturally from soil and plants such as Indigofera Longeracemosa.^7,8 Some methods for the synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes have been reported by condensing β-naphthol with aldehydes in the presence of protic or Lewis acid catalysts such as sulfamic acid,⁹ Sc[N(SO₂C₈F₁₇)₂]₃,¹⁰ AcOH–H₂SO₄,¹¹p-TSA,¹² TaCl₅,¹³ Dowex-50W,¹⁴ NH₄H₂PO,¹⁵ I₂,¹⁶ HClO₄–SiO₂,¹⁷ PW acid,¹⁸ cyanuric chloride,¹⁹ Yb(OTf)₃,²⁰ LiBr,²¹ CoPy₂Cl₂,²² Sc[N(SO₂C₈F₁₇)₂]₃,²³ NaHSO₄,²⁴ Al(HSO₄)₃,²⁵ P₂O₅²⁶ and InCl₃.²⁶ However, these catalyst systems suffer from some limitations, such as long reaction times, high catalyst loadings, the use of toxic solvents or special apparatus. The search for milder and more environmentally benign conditions is, therefore, highly demanding for the synthesis of these compounds.

Having the above facts, we would like to introduce tungsten(VI) chloride (WCl₆) as a highly efficient, reusable and heterogeneous catalyst for the preparation of 14-aryl-14H-dibenzo[a,j]xanthene derivatives by the reaction of β-naphthol with aromatic aldehydes under solvent-free conditions (Scheme 1).²⁹

Scheme 1 The synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes catalyzed by WCl₆.

To optimize the reaction conditions, as a model reaction, the solvent-free condensation of β-naphthol with 3-nitrobenzaldehyde was tested in the presence of different amounts of WCl₆ in the range 80–130 °C.²⁹ A higher yield and shorter reaction time were obtained when the reaction was carried out using 1 mol% of WCl₆ at 110 °C.

To assess the efficiency and scope of the catalyst, the reaction of β-naphthol with various arylaldehydes was studied under the optimal conditions.²⁹ The results are summarized in Table 1. As it is shown in Table 1, all aldehydes, including benzaldehyde, as well as aromatic aldehydes possessing electron-releasing substituents, electron-withdrawing substituents, basic groups or halogens on their aromatic rings afforded the desired 14-aryl-14H-dibenzo[a,j]xanthenes in high to excellent yields (78–97%) in very short reaction times (4–60 min).

Table 1 The solvent-free preparation of 14-aryl-14H-dibenzo[a,j]xanthenes using WCl₆ (Scheme 1)

Entry	R	Time (min)/Yield^a (%)	M.p. (°C) (Lit.)
a Isolated yield. b This reaction was performed using 2 mol% of catalyst.
1a ^b	C6H5	5/88	180–182
			(182–183)^8
1b	4-NO2C6H4	4/98	308–310
			(310)^8
1c	3-NO2C6H4	4/94	209–210
			(210–211)^27
1d	2-NO2C6H4	4/87	212–214
			(214)^8
1e	4-ClC6H4	6/97	284–286
			(289–290)^28
1f	3-ClC6H4	5/97	207–209
			(209–211)^27
1g	2-ClC6H4	6/88	211–213
			(215–216)^8
1h	4-BrC6H4	5/91	295–297
			(296)^8
1i	3-BrC6H4	5/93	187–188
			(190–191)^27
1j ^b	4-MeC6H4	7/96	227–229
			(230)^8
1k	4-C6H5CH2OC6H4	30/92	163–165
1l	4-OMeC6H4	60/85	200–202
			(203–205)^28
1m	Me2NC6H4	30/78	290–293

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In the proposed mechanism (Scheme 2), at first, arylaldehyde is activated by WCl₆. Then, β-naphthol attacks the carbonyl group of the activated aldehyde, and affords intermediate I. II is produced by the hydrogen transfer in I, then after removing one molecule of H₂O, orthoquinone methide (o-QM, III) is prepared. Intermediate III is activated by WCl₆ and acts as a Michael acceptor. Afterward, Michael addition of another β-naphthol to intermediate III affords IV. Intermediate IV converts to V by the WCl₆ catalyzed ring closing of IV. Finally, by removing H₂O from V, 14-aryl-14H-dibenzo[a,j]xanthene forms.

Scheme 2 The proposed mechanism for the synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes catalyzed by WCl₆.

By the reaction of WCl₆ with H₂O, WO₃ and HCl could be produced. According to the given mechanism (Scheme 2), two molecules of H₂O were prepared during the condensation reaction. But this reaction was carried out at 110 °C. Due to evaporation of produced water at this temperature; WCl₆ could not be converted to WO₃. Therefore, WCl₆ is the real active species in this condensation, and after the reusable step.

To compare the applicability and efficiency of WCl₆ with reported catalysts in the synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes, we have tabulated the TOF of these catalysts in the condensation reaction of β-naphthol with 3-nitrobenzaldehyde (Table 2). As shown in Table 2, WCl₆, relative to the previously reported catalysts, is superior in terms of TOF.

Table 2 Comparison of the results of the reaction of β-naphthol with 3-nitrobenzaldehyde using WCl₆ with those obtained by reported catalysts

Catalyst/conditions	Catalyst amount (mol%)	Time (min)	Yield (%)	TOF^a (h^−1)	Ref.
a Turn over frequency. b Our work.
WCl6, 110 °C, solvent-free^b	1	4	94	23.5	—
Sulfamic acid, 125 °C, solvent-free	4	12	91	1.89	9
Sc[N(SO2C8F17)2]3, 110 °C, C10F18	1	180	90	0.5	10
TaCl5, reflux conditions, 1,2-dichloroethane	10	60	93	0.155	13
I2, 90 °C, solvent-free	10	180	92	0.051	16
HClO4–SiO2, reflux conditions, 1,2-dichloroethane	1	720	88	0.122	17
HClO4–SiO2, 125 °C, solvent-free	1	10	90	9	17
CyCl, 110 °C, solvent-free	20	45	90	0.1	19
Yb(OTf)3, 110 °C, [BPy]BF4 (IL)	1	180	89	0.49	20
Al(HSO4)3, 125 °C, solvent-free	16	39	91	0.145	25
P2O5, 80 °C, solvent-free	20	52	90	0.086	26
InCl3, 80 °C, solvent-free	30	60	82	0.045	26

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Conclusions

In summary, we have introduced WCl₆ as a heterogeneous catalyst for the synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes by the condensation of β-naphthol with arylaldehydes. Recovery of the catalyst, easy purification, high yields, short reaction times and higher turn over frequency (TOF) of the catalyst in comparison with reported catalysts are some important advantages presented in this work.

Acknowledgements

The authors gratefully acknowledge partial support of this work by the Research Affairs Office of Bu-Ali Sina University (Grant number 32-1716 entitled development of chemical methods, reagents and molecules), and the Center of Excellence in Development of Chemical Method (CEDCM), Hamedan, I. R. Iran.

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29. General procedure for the synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes: a mixture of arylaldehyde (1 mmol), β-naphthol (2 mmol) and WCl₆ (3.9 mg, 0.01 mmol, 1 mol%) was stirred at 110 °C. After completion of the reaction, as monitored by TLC, CHCl₃ (1 mL) was added to the reaction mixture, stirred and refluxed for 3 min, and filtered to separate the catalyst. The solvent of the filtrate was evaporated, and the solid residue (crude product) was recrystallized from hot EtOH (95%) to give the pure product. The recovered catalyst was washed with CHCl₃, dried and reused for the next run. The catalyst was recovered and reused for three times without any significant changes in the yield and the reaction time.

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Footnote

† Electronic Supplementary Information (ESI) available: General experimental details for starting materials and instruments, catalysis measurements, spectral data of all compounds and literature references for compounds. See DOI: 10.1039/c2ra00014h/

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