One pot ‘click’ reaction: Cu^II–hydrotalcite catalyzed tandem synthesis of β-hydroxy triazoles via regioselective opening of epoxide followed by [3+2] cycloaddition

Abstract

A novel copper (II) hydrotalcite catalyst has been investigated for its use in the cascade synthesis of β-hydroxy triazoles. It is found to be a dynamic catalyst for regioselective organic synthesis in water. The copper (II) hydrotalcite catalyst, in various Cu : Al molar ratios, was prepared by adopting a coprecipitation method and characterized using different techniques. The three component (epoxides, sodium azide and terminal alkynes) reactions under investigation were performed in water at ambient temperature without any additives. The formation of 2-azido alcohol, generated in situ, was observed to be the key step in the [3+2] cycloaddition of the click reaction. The optimized reaction procedures described herein are not only regioenriched and high yielding but also eco-friendly.

---

1. Introduction

Due to increasing concern about the environment, there has been great interest in the development of organic chemical processes that use more environmentally benign alternatives in terms of product selectivity, operational simplicity and environmental safety.¹ Therefore, we have been working on a new class of eco-friendly heterogeneous catalysts that are easy to prepare, handle and recycle. Multicomponent reactions (MCRs) have been attracting considerable attention in recent years as they are convergent, exhibit economy of the steps and often atom economy, since most of the incoming atoms are linked together in a single product. Combining all these aspects in a heterogeneous and eco-friendly catalysis would reinforce the greening of such reactions for the progression of industrial implementation. On those lines, MCRs have emerged as powerful tools in modern synthetic organic chemistry as well as in the field of drug discovery.²

Click chemistry was first introduced by Sharpless and co-investigators³ in 2001. It describes a modular approach to organic synthesis towards the assembly of new molecular entities. Huisgen 1,3-dipolar cycloadditions⁴ unite two unsaturated reactants and provide rapid access to an enormous number of diverse five-membered heterocyclic compounds. In heterocyclic chemistry, triazoles are treated as particularly important scaffolds, which exhibit an ample spectrum of biological activities and are widely employed as pharmaceuticals and agrochemicals.⁵ [3+2] Cycloaddition of azides with alkynes to produce 1,2,3-triazoles has emerged as an extremely helpful leading example of “click chemistry”, and a key step in the first series of click backbone amide linkers.⁶ These motifs (1,2,3-triazoles) generate large numbers of peptides, oligosaccharides,⁷ natural product analogues⁸ and drug-like molecules with significant biological properties including anti-HIV activity⁹ and antimicrobial activity against Gram positive bacteria. They are also useful in bioconjugate chemistry.¹⁰

Many catalysts have been investigated for use in the click reaction, including Zn/C with DMF at 50 °C,¹¹ CuNPs with Et₃N and THF at 65 °C,¹² latent-[(SIPr)CuCl] with DMSO,¹³ and a Cu^I catalyst with TBTA ligand in t-BuOH.¹⁴ However, very few catalysts have been studied for the construction of β-hydroxy triazoles, which typically employs epoxides and a 1,3-dipolar cycloaddition using, for example, halohydrin dehalogenase (HheC), CuSO₄ with a buffer and sodium ascorbate,¹⁵ enzymatic reduction of α-azidoacetophenone,¹⁶ or CuSO₄·5H₂O with a sodium ascorbate additive.¹⁷ Nevertheless, most of these procedures are characterized by various drawbacks such as insignificant reactivity, use of volatile organic solvents, requirement of additives, high reaction temperatures, low yields and the formation of undesired side products such as bistriazole, diacetylenes, etc.¹⁸ Furthermore, most of the above-mentioned approaches are mostly homogeneous in nature. The present investigation was undertaken against the aforesaid background.

2. Experimental section

Preparation of Cu^II–hydrotalcite (Cu^II–HT) catalysts

The Cu^II–HT catalysts under investigation were synthesized by adopting a coprecipitation method. In a typical procedure, solution A containing the requisite quantities of Cu(NO₃)₂·6H₂O and Al(NO₃)₃·9H₂O (Cu/Al mole ratios = 2 : 1, 3 : 1 and 4 : 1; all chemicals are Fluka, AR grade) precursors and solution B containing the base mixture (1 : 1 volume of 2 M NaOH and 1 M Na₂CO₃) were prepared separately in distilled water. Both solutions A and B were added slowly and simultaneously to a beaker containing distilled water with continuous stirring. A constant pH∼9 was maintained throughout the addition. Afterwards, the formed precipitates were filtered off, washed thoroughly with distilled water until the pH reached 7 and dried at 373 K for 12 h.

Catalyst characterization

The X-ray powder diffraction (XRD) patterns were acquired with a Siemens D-5005 diffractometer using a Ni-filtered Cu-Kα radiation (0.15418 nm) source and a Scintillation counter detector. The XRD phases present in the samples were identified with the help of JCPDS data files. The FTIR spectra were recorded on a Nicolet 740 FT-IR spectrometer at ambient conditions, using KBr disks, with a nominal resolution of 4 cm⁻¹ and an average of 100 spectra.

Synthesis of β-hydroxy 1,4-disubstituted 1,2,3-triazoles

All chemicals employed in this study were commercially available and were used without further purification. A mixture of the epoxide (1 mmol), sodium azide (1.2 mmol), the terminal alkyne (1 mmol) and a catalytic amount of Cu^II–HT (20 mg) in water (1.5 mL) was stirred at room temperature for an appropriate time. After completion of the reaction, as confirmed by TLC, the reaction mixture was filtered off and washed with ethyl acetate (3 × 5 mL). The combined layers were dried over anhydrous Na₂SO₄, concentrated under vacuum and purified by column chromatography on 60-120 mesh silica gel, using ethyl acetate and hexane as the eluent (2 : 8) to afford pure 1,4-disubstituted 1,2,3-triazole. All products were identified by comparing their spectral data with the literature.^18,22,24,25 In addition, the solid catalyst was conveniently separated from the reaction mixture by simple filtration and its activity was examined in subsequent experiments. Interestingly, the used Cu^II–HT catalyst did not exhibit any significant loss of activity in terms of product yield, and the catalyst could be recycled successively for five runs (Fig. 1).

Fig. 1 Recycling of Cu^II–HT catalyst for the reaction between styrene oxide, sodium azide and phenylacetylene.

3. Results and discussion

Hydrotalcite type compounds exhibit two-dimensional layered structures consisting of alternating positively charged mixed metal (M²⁺/M³⁺) hydroxide sheets and negatively charged interlayer anions as well as water molecules. The HTs, which have a typical brucite-like structure can be represented by the general formula [M²⁺_1−x M³⁺_x (OH)₂]Aⁿ⁻_x/n·mH₂O, where M²⁺ = Mg²⁺, Ni²⁺, Zn²⁺, etc.; M³⁺ = Al³⁺, Fe³⁺, Ga³⁺, etc.; Aⁿ⁻ = [CO₃]²⁻, NO₃⁻, Cl⁻, etc.¹⁹

As we know, hydrotalcites are extensively used for various applications such as catalysts and catalyst precursors, anion exchangers, pharmaceutics, anion scavengers, adsorbents, filtration beds, electroactive and photoactive materials and polymer stabilizers.²⁰ The Cu^II–HT catalysts being investigated in the present study were characterized by XRD and FTIR techniques. The obtained XRD patterns of the synthesized Cu^II–HT catalysts are shown in Fig. 2. The observed typical reflection peaks at 2θ = 11.7, 23.6, 34.6, 35.6, 37.7, 40.4 and 53.3° are almost identical to the characteristic peaks of the hydrotalcite phase (JCPDC # 460099). The typical FTIR spectra of Cu^II–HT (3 : 1) and Cu^II–HT (2 : 1) catalysts are presented in Fig. 3. The intense absorption bands at around 1 350–1 410 and 800–890 cm⁻¹ are due to symmetric stretching (ν₃) and out-of-plane deformation vibrations (ν₂) of interlayer carbonate anions, respectively. The splitting of the peak at ∼1360 cm⁻¹ into a double band is due to lowering of the carbonate anion symmetry and the disordered nature of the interlayer. This disorder occurs due to electrostatic interaction, either with positively charged layers or with the water molecules. The broad band observed at ∼3450 cm⁻¹ is due to the OH⁻ stretching vibration of the brucite-like layers, caused by the interlayer water molecules and the hydroxyl groups of the layers. The presence of the peak at 1620 cm⁻¹ is due to the OH bending vibration. The absorption band at around 445 cm⁻¹ (δ O–M–O) is ascribed to the lattice vibrations of the octahedral sheets of the hydrotalcites. Water has been considered to be an excellent reaction medium for synthetic organic chemistry in recent years and it has many potential advantages. It is logical that if a reaction proceeds in water, there are several benefits, including the replacement of environmentally unfriendly, potentially dangerous and expensive organic solvents, and the elimination of volatile organic compounds in the atmosphere.^21,22 Recently, we have reported the synthesis of β-amino alcohols from epoxides and amines/indoles, employing water as the reaction medium.^22c Due to their highly strained structure, epoxides are versatile starting materials and active intermediates in synthetic organic chemistry. In the present study, Cu^II–HTs are used in an attempt to explore the feasibility of the MCR with epoxides, sodium azide and terminal alkynes in the presence of water as the solvent (Scheme 1). The one pot, two-step synthesis of β-hydroxy 1,2,3-triazoles by a three-component click reaction proceeds via the formation of 2-azido alcohols from sodium azide and epoxides. In click chemistry, the formation of the organic azide [R–N₃] is the key step, and these azides made a transitory appearance in organic synthesis.²³ During the reaction, the 2-azido alcohols are easily formed with short reaction times (15 min), confirmed by the observation of the characteristic azido stretching frequency at ∼2100 cm⁻¹.¹⁸

Fig. 2 Powder X-ray diffraction patterns of Cu^II–HT catalysts.

Fig. 3 FTIR spectra of Cu^II–HT catalysts.

Scheme 1 Synthesis of β-hydroxy 1,4-disubstituted 1,2,3-triazoles using Cu^II–HT as the catalyst in water.

Initially, we optimized typical reaction parameters including various mole ratios of Cu^II–HTs and solvents, using styrene epoxide (1.0 mmol), sodium azide (1.2 mmol) and phenylacetylene (1.0 mmol) as the model substrates (Table 1). A preliminary reaction was carried out to identify the best catalyst system, with water as the reaction medium and at room temperature. Among the Cu^II–HTs with various mole ratios we screened, the 3 : 1 (Cu : Al) mole ratio catalyst exhibited excellent activity and enriched regioselectivity towards the desired product. The Cu^II–HTs with 4 : 1 and 2.5 : 1 (Cu : Al) mole ratios also showed considerable activity (Table 1, entries 2 and 4), but the yields were lower than that of the 3 : 1 mole ratio catalyst. Trace amounts of the products including some by-products and longer reaction times were noted in the absence of the Cu^II–HT catalyst (Table 1, entry 6). The Cu^II–HT catalyst with carbonate ions as interlayer stabilizing anions, and the Cu^II species present in the clay framework exhibited an impressive activity at room temperature, without the need for an inert atmosphere, and provided the expected adduct as a single regioisomer with good product selectivity.²⁴

Table 1 Optimization of reaction conditions for the synthesis of 1,4-disubstituted 1,2,3-triazoles^a

Entry	Catalyst mole ratio (Cu : Al)	Solvent	Yield (%)^b
a Reagents and reaction conditions: styrene oxide (1 mmol), sodium azide (1.2 mmol), phenylacetylene, catalyst (20 mg) and solvent (1.5 mL); unless otherwise mentioned, stirred at room temperature for 5 h. b Yields of isolated products. c Without catalyst, stirred at room temperature for more than 12 h.
1	Cu^II–HT (1 : 1)	Water	45
2	Cu^II–HT (4 : 1)	Water	79
3	Cu^II–HT (2 : 1)	Water	68
4	Cu^II–HT (2.5 : 1)	Water	76
5	Cu^II–HT (3 : 1)	Water	91
6	—	Water	—^c
7	Cu^II–HT (3 : 1)	Methanol	79
8	Cu^II–HT (3 : 1)	Dichloromethane	72
9	Cu^II–HT (3 : 1)	Acetonitrile	68
10	Cu^II–HT (3 : 1)	Tetrahydrofuran	64
11	Cu^II–HT (3 : 1)	Toluene	61
12	Cu^II–HT (3 : 1)	Benzene	57
13	Cu^II–HT (3 : 1)	Water + MeOH	84

---

After selecting the most efficient catalyst, we screened different solvents in order to optimize reaction conditions (Table 1). Among the various solvents we examined, water was found to be the most appropriate for providing the desired β-hydroxy triazoles with excellent regioselectivity and high yields (Table 1, entry 5).

The enhanced product yields are partly due to the hydrophobic nature of the reactants, since their repulsion from water would enhance the number of collisions between organic molecules and increase their ground-state energies, leading to an increase in reaction rate. The mixture of water and methanol (1 : 1) also afforded considerably high yields of hydroxy triazoles (Table 1, entry 13). Lower catalytic activity and longer reaction times were observed with various organic solvents such as methanol, dichloromethane, acetonitrile, tetrahydrofuran, toluene and benzene at room temperature. This is probably due to interference of the solvents with the surface active sites of the catalysts (Table 1, entries 7–13).

The optimized reaction conditions (catalyst, solvent, ambient temperature and additive-free) have prompted us to extend our studies through a variety of epoxides with sodium azide, followed by cycloaddition with diverse terminal alkynes, and the results are summarized in Table 2. Reaction of cyclohexene oxide with a variety of alkynes (Scheme 2) afforded diastereo-enriched trans-regioisomers, and the resultant racemic 1H, 1,2,3-triazole-1-yl-cyclohexanol products were recognized as the trans-diastereoisomers on the basis of NMR spectral data. Reaction of aliphatic oxiranes (epichlorohydrin, 1,2-butylene oxide and propylene oxide) with various alkynes afforded the major secondary alcohol triazole regioisomer (Table 2, entries 4, 5, 7, 11 and 12) by nucleophilic attack at the less sterically hindered carbon. Whereas in the case of aryl oxiranes (styrene oxide and p-chloro styrene oxide), electronic factors predominate over the steric factors to produce a major primary alcohol triazole regioisomer by nucleophilic attack at the more stable benzylic carbon (Table 2, entries 6, 8–10, and 13–16). The reaction is also regio-enriched (Scheme 3).

Table 2 Regioselective synthesis of β-hydroxy 1,4-disubstituted 1,2,3-triazoles from various epoxides, sodium azide and terminal alkynes^a

Entry	Epoxide	Alkyne	Product	Time (h)	Yield (%)^b
a Reagents and reaction conditions: epoxide (1 mmol), sodium azide (1.2 mmol), terminal alkyne (1 mmol), Cu^II-HT catalyst (20 mg), and water (1.5 mL). b Isolated yield of the products.
1	Cyclohexeneoxide 1a	R 2 = C6H53a	4a	6	85
2	1a	R 2 = n-hexyl 3b	4b	8	78
3	1a	R 2 = 3-MeC6H43c	4c	8	83
4	R 1 = CH2Cl 1b	3a	4d	6	81
5	1b	R 2 = 4-F,3-MeC6H33d	4e	5	85
6	R 1 = C6H51c	3a	4f	5	91
7	R 1 = ethyl 1d	R 2 = propyl 3e	4g	9	61
8	1c	3d	4h	5	93
9	1c	3c	4i	5	83
10	1c	3b	4j	7	81
11	R 1 = methyl 1e	3a	4k	8	79
12	1e	3e	4l	10.5	67
13	R 1 = 4-ClC6H41f	3d	4m	5	87
14	1f	3c	4n	6	84
15	1f	3b	4o	8	73
16	1f	3a	4p	5	85

---

Scheme 2 Regioenriched ring opening of symmetrical epoxide.

Scheme 3 Desired product differentiation by changing the nature of the unsymmetrical epoxide.

We strongly believe that rendering of the nucleophile is governed by the group environment of the oxirane and the stability of the carbonium ion. Generally, opening of unsymmetrical epoxides yields a mixture of two isomers 1A and 1B (Scheme 3). In the case of alkyl substituted epoxides, 1B has been observed as the major product. On the other hand, 1A was the major product in the case of aryl substituted epoxides. Under the investigated reaction conditions, we observed 1A and 1B as the sole products with aryl and alkyl substituted epoxides, respectively (Scheme 3).

Electronic effects are known to influence reaction rates and product yields in most organic synthesis reactions. The terminal alkyne with a fluorine group in the para position, and even in the meta position, enhances the reaction rate as well as the product yield (Table 2, entries 5, 8 and 13). Slightly lower conversion was observed when the styrene oxide and p-chloro styrene oxide were reacted with aliphatic alkynes (1-pentyne, 1-octyne, etc.) (Table 2, entries 10 and 15). In the reaction of simple aliphatic oxiranes (epichlorohydrin, butylene oxide and propylene oxide) with alkynes, the corresponding yields were good to moderate (aromatic to aliphatic) (Table 2, entries 4, 5, 7, 11 and 12). We have conducted this reaction on a large scale (with styrene oxide (2.4 g), sodium azide and phenylacetylene as the model reaction) to further advance the industrial utility of the catalytic formulations; interestingly, we found remarkable regioselectivity and high yields of the desired products.

By analogy with our investigation and earlier reports,²⁵ the plausible mechanistic pathways are shown in Scheme 4. The role of the Cu species in the HT framework is to facilitate the formation of the Cu^II–acetylide complex and the activation of the azide function towards nucleophilic attack by reducing the electron density of the alkyne. Since the chance of having adjacent Cu^II ions in the HT framework is very high, the energy barrier for the addition reaction decreases greatly and thus accelerates the click reaction without any additives.²⁴ Ring contraction from X to Y is supported by DFT calculations.^25b

Scheme 4 Plausible reaction mechanism for synthesis of β-hydroxy 1,4-disubstituted 1,2,3-triazoles with Cu^II–HT as the catalyst.

In conclusion, we report that Cu^II–HT is a dynamic catalyst for regioselective organic synthesis in water. With such a catalyst, we have developed a simple and efficient method for three component (epoxide, sodium azide and terminal alkyne) azide–alkyne cycloaddition as a one-pot, two-step reaction. Furthermore, the Cu^II–HT catalyst can be readily recovered by filtration and recycled for at least five runs without any significant loss of activity, and it has the potential for large scale applications.

Acknowledgements

ANP, BT, GR, and RS thank the Council of Scientific and Industrial Research (CSIR), New Delhi for Senior Research Fellowships. The authors thank the Department of Science and Technology (DST), New Delhi, Govt. of India (SERC Scheme: SR/S1/PC-63/2008) for financial support of this work.

Notes and references

1. (a) P. T. Anastas and J. C. Warner, Green Chemistry: Theory and Practice, Oxford University Press, New York, 1998; (b) M. Eissen, J. O. Metzger, E. Schmidt and V. Schneidewind, Angew. Chem., Int. Ed., 2002, 41, 414; (c) Special Topic Issue on Green Chemistry: Acc. Chem. Res., 2002, 35, 685.
2. (a) Multicomponent Reactions, ed. J. Zhu and H. Bienaymé, Wiley-VCH, Weinheim, 2005; (b) Domino Reactions in Organic Synthesis, ed. L. F. Tietze, G. Brasche and K. Gericke, Wiley-VCH, Weinheim, 2006; (c) A. Dömling and I. Ugi, Angew. Chem., Int. Ed., 2000, 39, 3168; (d) A. Dömling, Chem. Rev., 2006, 106, 17.
3. (a) H. C. Kolb, M. G. Finn and K. B. Sharpless, Angew. Chem., 2001, 113, 2056 ( Angew. Chem., Int. Ed. , 2001 , 40 , 2004 ); (b) H. C. Kolb and K. B. Sharpless, Drug Discovery Today, 2003, 8, 1128; (c) A. Deiters, T. A. Cropp, M. Mukherji, J. W. Chin, J. C. Anderson and P. G. Schultz, J. Am. Chem. Soc., 2003, 125, 11782.
4. (a) R. Huisgen, in 1,3-Dipolar Cycloaddition Chemistry, ed. A. Padwa, Wiley, New York, 1984, pp. 1–176; (b) R. Huisgen, Pure Appl. Chem., 1989, 61, 613.
5. A. Kamal, N. Shankaraiah, V. Devaiah, K. L. Reddy, A. Juvekar, S. Sen, N. Kurian and S. Zingde, Bioorg. Med. Chem. Lett., 2008, 18, 1468.
6. S. Löber, P. Rodriguez-Loaiza and P. Gmeiner, Org. Lett., 2003, 5, 1753.
7. (a) D. P. Temelkoff, M. Zeller and P. Norris, Carbohydr. Res., 2006, 341, 1081; (b) L. Marmuse, S. A. Nepogodiev and R. A. Field, Org. Biomol. Chem., 2005, 3, 2225.
8. (a) J. Yang, D. Hoffmeister, L. Liu, X. Fu and J. S. Thorson, Bioorg. Med. Chem., 2004, 12, 1577; (b) H. Lin and C. T. Walsh, J. Am. Chem. Soc., 2004, 126, 13998.
9. (a) R. Alvarez, S. Valazquez, F. San, S. Aquaro, C. De, C. F. Perno, A. Karlsson, J. Balzarini and M. J. Camarasa, J. Med. Chem., 1994, 37, 4185; (b) S. Velazquez, R. Alvarez, C. Perez, F. Cago, C. De, J. Balzarini and M. J. Camarasa, Antivir. Chem. Chemother., 1998, 9, 481.
10. (a) Q. Wang, T. R. Chan, R. Hilgraf, V. V. Fokin, K. B. Sharpless and M. G. Finn, J. Am. Chem. Soc., 2003, 125, 3192; (b) A. J. Link and D. A. Tirell, J. Am. Chem. Soc., 2003, 125, 11164; (c) V. G. Nenajdenko, A. V. Gulevich, N. V. Sokolova, A. V. Mironov and E. S. Balenkova, Eur. J. Org. Chem., 2010, 1445.
11. X. Meng, X. Xu, T. Gao and B. Chen, Eur. J. Org. Chem., 2010, 5409.
12. F. Alonso, Y. Moglie, G. Radivoy and M. Yus, Tetrahedron Lett., 2009, 50, 2358.
13. S. Díez-González, E. D. Stevens and S. P. Nolan, Chem. Commun., 2008, 4747.
14. T. R. Chan, R. Hilgraf, K. B. Sharpless and V. V. Fokin, Org. Lett., 2004, 6, 2853.
15. L. S. Campbell-Verduyn, W. Szymański, C. P. Postema, R. A. Dierckx, P. H. Elsinga, D. B. Janssen and B. L. Feringa, Chem. Commun., 2010, 46, 898.
16. H. Ankati, Y. Yang, D. Zhu, E. R. Biehl and L. Hua, J. Org. Chem., 2008, 73, 6433.
17. J. S. Yadav, B. V. S. Reddy, G. M. Reddy and D. N. Chary, Tetrahedron Lett., 2007, 48, 8773.
18. H. Sharghi, M. H. Beyzavi, A. Safavi, M. M. Doroodmand and R. Khalifeh, Adv. Synth. Catal., 2009, 351, 2391.
19. J. S. Valente, M. S. Cantu and F. Figueras, Chem. Mater., 2008, 20, 1230.
20. M. R. Othman, Z. Helwani, Martunus and W. J. N. Fernando, Appl. Organometal. Chem., 2009, 23, 335.
21. (a) C.-J. Li and T.-H. Chan, Organic Reactions in Aqueous Media, Wiley, Chichester, UK, 1997; (b) Organic Synthesis in Water, ed. P. A. Grieco, Blake Academic and Professional, London, 1998; (c) R. A. Sheldon, Green Chem., 2005, 7, 267.
22. (a) M. K. Patil and B. M. Reddy, Chem. Rev., 2009, 109, 2185; (b) M. K. Patil, A. N. Prasad and B. M. Reddy, Curr. Org. Chem., 2011, 15, 3961; (c) B. Thirupathi, R. Srinivas, A. N. Prasad, J. K. P. Kumar and B. M. Reddy, Org. Process Res. Dev., 2010, 14, 1457.
23. V. V. Rostovtsev, L. G. Green, V. V. Fokin and K. B. Sharpless, Angew. Chem., 2002, 114, 2708 ( Angew. Chem., Int. Ed. , 2002 , 41 , 2596 ).
24. K. Namitharan, M. Kumarraja and K. Pitchumani, Chem. –Eur. J., 2009, 15, 2755.
25. (a) V. D. Bock, H. Hiemstra and J. H. van Maarseveen, Eur. J. Org. Chem., 2006, 51; (b) F. Himo, T. Lovell, R. Hilgraf, V. V. Rostovtsev, L. Noodleman, K. B. Sharpless and V. V. Fokin, J. Am. Chem. Soc., 2005, 127, 210.

---

Footnote

† Electronic supplementary information (ESI) available: Additional characterization studies supporting the results which include: ¹H NMR, FTIR, and MS data of isolated compounds. See DOI: 10.1039/c2cy20052j

---