In(OTf)<sub>3</sub> as a powerful and recyclable catalyst for Pechmann condensation without solvent


扩展功能
	加入收藏夹

	复制引文信息

	加入引用管理器

	Email Alert

	RSS
本文作者相关文章
	Bahador Karami

	Mahtab Kiani

	Mohsen Ahmad Hoseini

In(OTf)₃ as a powerful and recyclable catalyst for Pechmann condensation without solvent

Bahador Karami , Mahtab Kiani, Mohsen Ahmad Hoseini

Department of Chemistry, Yasouj University, Yasouj 75918-74831, Iran

Received: 2013-12-15. Accepted: 2014-3-21. Published: 2014-7-20.

* Corresponding author. Tel: +98‐7412223048;Fax: +98‐7412224167;E‐mail: karami@mail.yu.ac.ir

Abstract: In(OTf)₃ plays the role of a Lewis acid catalyst in the Pechmann condensation of phenols with β-ketoesters under solvent-free conditions to give coumarin derivatives. This novel and inexpensive method has advantages such as short reaction time, excellent product yields, and avoids the use of organic solvents in agreement with green chemistry principles. Catalyst loadings can be as low as 1 mol% to give high yields of the corresponding coumarins at 80℃. The catalyst can be recovered after the reaction, and reused with only a slight decrease in the yield.

Key words: In(OTf)₃ Lewis acid catalyst Pechmann condensation Coumarin Solvent-free condition

In(OTf)₃ as a powerful and recyclable catalyst for Pechmann condensation without solvent

1. Introduction

2H-Chromen-2-ones (coumarins) continue to be investigated owing to their importance to medicinal chemists because of their variety of biological activity ^[1]. They are widely used as additives in food, perfumes, cosmetics ^[2], pharmaceuticals ^[3], optical brighteners ^[4] and dispersed fluorescent and laser dyes ^[5]. Thus, the synthesis of this heterocyclic nucleus is of much interest.

Various methods are known for the synthesis of substituted coumarins, including Pechmann, Perkin, Knoevenagel, Claisen, Reformatsky, and Wittig reactions ^[6]. Some of these reactions have disadvantages such as harsh conditions, long reaction time, low product yields, and the use of expensive and toxic reagents or organic solvents ^[4].

In recent years, Lewis acids such as polyvinylpolypyrrolidone ^[5], nanocrystalline sulfated tin oxide ^[9], Zr-TMS-TFA-25 ^[12], ZrOCl₂·8H₂O/SiO₂ ^[13], and mesoporous zirconium phosphate (m-ZrP) ^[12] have been used to catalyze the Pechmann reaction. This method is suitable and better than the other methods to synthesize coumarins in terms of the amount of the catalyst used, reaction time, and product yields. In this study, continuing our work on catalyzed reactions ^[2], a new application of In(OTf)₃ as a Lewis acid catalyst in the synthesis of coumarins was reported.

2. Experimental

2.1. General

The chemicals were purchased from Aldrich, Fluka, and Merck chemical companies and were freshly used after purification by standard procedures (distillation and recrystallization). The products were isolated and identified by comparing their physical and spectral data with those in the literature. Infrared (IR) spectra were recorded on a JASCO-680 Fourier transform IR spectrometer using KBr disks and the ¹H-NMR spectra were recorded on a Bruker NMR spectrometer (400 MHz model) as CDCl₃ solutions. The chemical shifts are expressed in δ with (CH₃)₄Si (TMS) as the internal standard.

2.2. General procedure for the preparation of coumarin derivatives 1-15a

In a typical experimental procedure, β-ketoester (1 mmol) was added to a mixture of substituted phenol (1 mmol) and In(OTf)₃ (0.056 g, 1 mol%) in a solvent-free tube. The reaction mixture was stirred in a preheated oil bath (80 °C). After completion of the reaction, the solid product was suspended in water (20 mL). The resulting crude product was filtered off and recrystallized from hot ethanol to give a white crystalline solid.

2.3. Preparation of 7-hydroxy-4-methyl-2H-chromen-2-one (1a)

Compound 1a was prepared according to the general procedure using ethyl acetoacetate (0.13 g, 1 mmol), resorcinol (0.11 g, 1 mmol), and In(OTf)₃ (0.056 g, 1 mol%). The reaction progress was monitored by thin-layer chromatography (TLC). After completion of the reaction, the solid product was suspended in water (20 mL). The resulting crude product was filtered off and recrystallized from hot ethanol to give a white crystalline solid.

2.4. Reusability of the catalyst

At the end of the reaction of ethyl acetoacetate (1 mmol), resorcinol (1 mmol), and In(OTf)₃ (1 mol%), the catalyst was filtered, washed with chloroform, and dried at 120 °C for 1 h. The catalyst was used for five times in the model reaction (i.e., recycling four times).

Specific detailed data for each of the compounds are given below.

7-Hydroxy-4-methyl-2H-chromen-2-one (1a). Colorless prisms, mp 183-185 °C; Yield 92%. ¹H-NMR (400 MHz, DMSO-d₆): δ = 10.138 (s, 1H), 7.373 (m, 5H), 6.722 (s, 1H), 6.470 (s, 1H), 5.957 (s, 1H), 2.292 (s, 3H). ¹³C-NMR (100 MHz, DMSO-d₆): δ = 160.09, 156.05, 155.96, 155.51, 143.93, 139.75, 128.34, 127.92, 127.75, 113.88, 112.52, 108.19, 105.44, 21.65. IR (KBr, cm⁻¹): 3050, 2900, 1690, 1615, 1590, 1500, 1080.

7-Hydroxy-4-phenyl-2H-chromen-2-one (2a). Colorless prisms, mp 251-253 °C; Yield 83%. ¹H-NMR (400 MHz, CDCl₃): δ = 5.905 (s, 1H), 6.56 (m, 2H), 7.04 (d, 1H), 7.28 (t, 1H), 7.322 (m, 3H), 10.65 (s, 1H). ¹³C-NMR (100 MHz, CDCl₃): δ = 103.12, 110.10, 111.08, 113.68, 128.54, 128.79, 129.29, 130.07, 135.52, 155.9. IR (KBr, cm⁻¹): 3050, 1690, 1600, 1250, 1150.

5-Hydroxy-4,7-dimethyl-2H-chromen-2-one (4a). Colorless prisms, mp 253-255 °C; Yield 95%. ¹H-NMR (400 MHz, DMSO-d₆): δ = 10.52 (s, 1H), 6.62 (d, 1H, J = 1.2 Hz), 6.57 (d, 1H, J = 1.2 Hz), 6.03 (d, 1H, J = 1.2 Hz), 2.54 (d, 3H, J = 1.2 Hz), 2.27 (s, 3H). ¹³C-NMR (100 MHz, DMSO-d₆): δ = 160.29, 156.90, 155.28, 154.04, 143.18, 112.37, 112.3, 108.15, 106.96, 23.91, 21.56. IR (KBr, cm⁻¹): 3393 (OH), 1655 (C=O).

5-Hydroxy-7-methyl-4-phenyl-2H-chromen-2-one (5a). Colorless prisms, mp 211-213 °C; Yield 80%. ¹H-NMR (400 MHz, DMSO-d₆): δ = 10.14 (s, 1H), 7.35 (m, 5H), 6.72 (s, 1H), 6.47 (s, 1H), 5.96 (s, 1H), 3.01 (s, 3H). ¹³C-NMR (100 MHz, DMSO-d₆): δ = 160.09, 156.05, 155.96, 155.51, 143.93, 139.75, 128.34, 127.92, 127.75, 113.88, 112.52, 108.19, 105.44, 21.65. IR (KBr, cm⁻¹): 3180 (OH), 1680 (C=O).

5,7-Dihydroxy-4-methyl-2H-chromen-2-one (7a). White solid, mp 288-290 °C; Yield 98%. ¹H-NMR (400 MHz, DMSO-d₆): δ = 10.51 (1H, s), 10.28 (1H, s), 6.24 (1H, s), 6.15 (1H, s), 5.83 (1H, s), 2.49 (3H, s). ¹³C-NMR (100 MHz, DMSO-d₆): δ = 16.51, 160.55, 158.39, 156.96, 155.43, 109.22, 102.55, 99.45, 94.98, 23.88. IR (KBr cm⁻¹): 3400, 3070, 2940, 1670, 1600, 1480, 1080.

7-Methoxy-4-methyl-2H-chromen-2-one (10a). Colorless prisms, mp 165-167 °C; Yield 96%. ¹H-NMR (400 MHz, CDCl₃): δ = 7.50 (d, 1H, J = 8.8 Hz), 6.87 (dd, 1H, J = 8.8, 2.4 Hz), 6.83 (d, 1H, J = 2.4 Hz), 6.14 (d, 1H, J = 1.2 Hz), 3.88 (s, 3H), 2.40 (d, 3H, J = 1.2 Hz). ¹³C-NMR (100 MHz, CDCl₃): δ = 162.83, 160.59, 155.24, 153.86, 126.88, 113.56, 112.54, 111.58, 101.16, 56.36, 18.58. IR (KBr, cm⁻¹): 3400 (OH), 1705 (C=O).

7,8-Dihydroxy-4-methyl-2H-chromen-2-one (14a). White solid, mp 239-241 °C; Yield 87%. ¹H-NMR (400 MHz, DMSO-d₆): δ = 10.1 (s, 1H), 9.35(s, 1H), 7.07 (d, 1H, J = 8.8 Hz), 6.81 (d, 1H, J = 8.4 Hz), 6.12 (d, 1H, J = 1.2 Hz), 2.4 (d, 3H, J = 1.2 Hz). ¹³C-NMR (100 MHz, DMSO-d₆): δ = 160.71, 154.35, 149.81, 143.47, 132.60, 115.88, 113.23, 112.56, 110.60, 18.63. IR (KBr, cm⁻¹): 3231 (OH), 1668 (C=O).

7-Amino-4-methyl-2H-chromen-2-one (15a). Light yellow solid, mp 223-225 °C; Yield 98%. ¹H-NMR (400 MHz, DMSO-d₆): δ = 7.4 (d, 1H, J = 8.8 Hz), 6.56 (d, 1H, J = 7.2 Hz), 6.39 (s, 1H), 6.09 (s, 2H), 5.89 (s, 1H), 2.39 (s, 3H). ¹³C-NMR (100 MHz, DMSO-d₆): δ = 160.90, 152.80, 151.00, 148.00, 127.60, 113.00, 112.50, 111.10, 106.70, 21.2. IR (KBr, cm⁻¹): 3439 (N-H), 1684 (C=O).

3. Results and discussion

To study the efficiency of In(OTf)₃ for the Pechmann condensation reaction, the reaction of β-ketoesters and phenol derivatives was selected as the model reaction. The expected coumarins were obtained as pure products in high yield by solvent-free stirring (Scheme 1).

Scheme 1. Synthesis of coumarin derivatives using the In(OTf)₃ catalyst.

To optimize the reaction conditions, we tested both various temperatures and amounts of the catalyst In(OTf)₃ in the model reaction of resorcinol with ethyl acetoacetate to produce 7-hydroxy-4-methyl-2H-chromen-2-one (1a) (Tables 1 and 2). Excellent yields were achieved using only 1 mol% In(OTf)₃ at 80 °C. There was no change in the reaction profile when more than 1 mol% of In(OTf)₃ was used. When similar reactions were carried out in the absence of the catalyst, approximately 5%-10% conversion was observed after 2 d.

Table 1
Optimization of the amount of In(OTf)₃ catalyst under solvent-free conditions at 80 °C for the synthesis of 1a.

Table 2
Optimization of the reaction temperature under solvent-free conditions using In(OTf)₃ catalyst (1 mol%) for the synthesis of 1a.

After optimization of the reaction conditions, to extend the scope of this reaction, various phenols, such as resorcinol, pyrogallol and phloroglucinol, were used for the optimized Pechmann reaction with different β-ketoesters (Table 3). A wide variety of coumarins were obtained through this method in good to excellent yield in short reaction time.

Table 3
Synthesis of coumarins by Pechmann condensation of phenols with β-ketoesters catalyzed by In(OTf)₃.

Coumarin 1a was synthesized in 87% yield in 32 min (CCl₄:ethylacetate = 5:1). Coumarin 1a was characterized by IR, NMR and other spectral data. Similarly, resorcinol was treated with ethyl 4-chloroacetoacetate and ethyl benzoylacetate to give coumarins 2a and 3a (Table 3, entries 2 and 3), respectively.

Encouraged by the above results, other phenolic substrates were subjected to the Pechmann reaction using In(OTf)₃. In all cases, the reactions successfully proceeded to give the corresponding coumarins in good to excellent yield. Electron- donating substituents in the meta position to the phenolic −OH facilitated the cyclization. The reactivity of phloroglucinol (1,3,5- trihydroxybenzene) (Table 3, entry 7) with ethyl acetoacetate was observed to be higher than pyrogallol (Table 3, entry 14) owing to two hydroxyl groups at meta positions in phloroglucinol compared to only one in pyrogallol. The presence of m-hydroxy groups strongly activates the substrates because of the resonance effect. m-Methoxyphenol (Table 3, entry 10) showed no detectable demethylation under the optimized reaction conditions. Similarly, 1-naphthol (Table 3, entry 12) requires a slightly higher temperature and longer reaction time. These results show that besides of the catalyst acidity and the reactivity of phenolic substrates. Finally, the reactions are remarkably clean, and no chromatographic separation is necessary to obtain the spectra-pure compounds.

The suggested mechanism for the Pechmann condensation reaction of phenols with β-ketoesters in the presence of In(OTf)₃ catalyst has been described using condensation as the probe reaction (Scheme 2). The In(OTf)₃ catalyst would cause dehydration and produce an olefinic bond, and simultaneously ethanol would be eliminated with the formation of the coumarin ring.

Scheme 2. Suggested mechanism for the Pechmann condensation of phenols with β-ketoesters in the presence of In(OTf)₃.

Comparing this method with other methods, the synthesis of 7-hydroxy-4-methyl-2H-chromen-2-one (Table 1, entry 1) as the model reaction was performed in the presence of other catalysts. The results are shown in Table 4. It shows that our method is suitable and better than other methods to synthesize coumarins in terms of the catalyst amount, the reaction time, and the product yield.

Table 4
Ocontent and N content of the N-doped samples determined by XPS.

Catalyst	Catalyst amount	Conditions	Time (min)	Yield (%)	Ref.
In(OTf)₃	1 mol%	solvent-free, 80 °C	32	87	this work
ZrPW	0.2 g	solvent-free, 130 °C	480	58	^[5]
Nanocrystalline sulfated tin oxide	25 wt%	solvent-free, 120 °C	240	95	^[9]
Zr-TMS-TFA-25	0.1 g	solvent-free, 100 °C	540	88	^[12]
ZrOCl₂·8H₂O/SiO₂	10 mol%	solvent-free, 80 °C	10	98	^[13]
Mesoporous zirconium phosphate (m-ZrP)	15 wt%	solvent-free, 160 °C	240	94	^[22]
Y(NO₃)₃·6H₂O	10 mol%	solvent-free, 90 °C	45	94	^[23]
H₃PW₁₂O₄₀ supported on nanoparticle tin oxide	30 wt%	solvent-free, 120 °C	120	78	^[yes]

Table 4
Ocontent and N content of the N-doped samples determined by XPS.

The design and synthesis of recoverable catalysts is a highly challenging interdisciplinary field, which combines chemistry, materials science, and engineering from both economic and environmental perspectives. The main disadvantage of many of the reported methods is that the catalysts are destroyed in the procedure and cannot be recovered or reused. In the process described here, as outlined in Fig. 1, the catalyst can be used in up to five times, during which there is negligible loss in the catalytic activity.

Fig. 1. Recyclability of In(OTf)₃ as a catalyst for the synthesis of 1a in the condensation of resorcinol (1 mmol) and ethylacetoacetate (1 mmol) under solvent-free conditions at 80 °C for 32-38 min.

4. Conclusions

We have demonstrated the facile In(OTf)₃-catalyzed synthesis of coumarins by the Pechmann reaction. The important advantages of this method are the short reaction time, high yield, simple workup, the use of an inexpensive and available catalyst, the nonchromatographic purification of the products, and the use of solvent-free conditions instead of organic solvents in accordance with green chemistry principles.

References

[1]	Basanagouda M, Jambagi V B, Barigidad N N, Laxmeshwar S S, Devaru V, Narayanachar. Eur J Med Chem, 2014, 74: 225
[2]	Ghodke S, Chudasama U. Appl Catal A, 2013, 453: 219
[3]	Zhao J Y, Zhou M, Liu Y, Zhang G L, Luo Y G. Fitoterapia, 2011, 82: 767
[4]	Mokhtary M, Najafizadeh F. C R Chim, 2012, 15: 530
[5]	Ahmed A I, El-Hakam S A, Khder A S. Abo El-Yazeed W S. J Mol Catal A, 2013, 366: 99
[6]	Rajitha B, Naveen Kumar V N, Someshwar P, Madhav J V, Reddy P N, Reddy Y T. Arkivoc, 2006, (12): 23
[7]	De S K, Gibbs R A. Synthesis, 2005: 1231
[8]	Goswami P. Synth Commun, 2009, 39: 2271
[9]	Kalita P, Kumar R. Microporous Mesoporous Mater, 2012, 149: 1
[10]	Sheng S R, Huang P G, Wang Q, Huang R, Liu X L. Synth Commun, 2006, 36: 3175
[11]	Kumar V, Tomar S, Patel R, Yousaf A, Parmar V S, Malhotra S V. Synth Commun, 2008, 38: 2646
[12]	Karami B, Kiani M. Catal Commun, 2011, 14: 62
[13]	Sinhamahapatra A, Sutradhar N, Pahari S, Bajaj H C, Panda A B. Appl Catal A, 2011, 394: 93
[14]	Sharma G V M, Reddy J J, Sree Lakshmi P, Krishna P R. Tetrahedron Lett, 2005, 46: 6119
[15]	Zagotto G, Gia O, Baccichetti F, Uriarte E, Palum M. Photochem Photobiol, 1993, 58: 486
[16]	Jung K, Park Y J, Ryu J S. Synth Commun, 2008, 38: 4395
[17]	Goswami P. Synth Commun, 2009, 39: 2271
[18]	Smitha G, Reddy C S. Synth Commun, 2004, 34: 3997
[19]	Bahekar S S, Shinde D B. Tetrahedron Lett, 2004, 45: 7999
[20]	Heravi M M, Khorasani M, Derikvand F, Oskooie H A, Bamoharram F F. Catal Commun, 2007, 8: 1886
[21]	Xie S S, Wang X B, Li J Y, Yang L, Kong L Y. Eur J Med Chem, 2013, 64: 540
[22]	Karami B, Khodabakhshi S, Jamshidi M. J Chin Chem Soc, 2013, 60: 1103
[23]	Ahmed A I, El-Hakam S A, Abd Elghany M A. Abo El-Yazeed W S. Appl Catal A, 2011, 407: 40