4′-(5-Methylfuran-2-yl)-2,2′:6′,2″-terpyridine: A New Ligand Obtained from a Biomass-Derived Aldehyde with Potential Application in Metal-Catalyzed Reactions

Abstract

The new ligand 4′-(5-methylfuran-2-yl)-2,2′:6′,2″-terpyridine (1) was prepared in one step from 2-acetylpyridine and 5-methylfurfural. The latter is an aldehyde that can be readily obtained from biomass. The new terpyridine molecule was characterized by ¹H and ¹³C-NMR spectroscopy as well as by elemental analyses and HR-MS. Owing to its chelating properties, this new terpyridine molecule was tested as a ligand in a metal-catalyzed reaction: The Ni-catalyzed dimerization of benzyl bromide.

1. Introduction

2,2′:6′,2″-Terpyridine molecules (tpy) are a class of heterocyclic compounds that possess three pyridine moieties (Figure 1). These molecules can form complexes with a broad range of metals owing to the chelate effect. Therefore, tpy and their complexes have been widely studied [1]. Terpyridines and their complexes find applications in various fields, such as photovoltaic devices [2], sensors [3], medicinal chemistry [4], and for the construction of MOFs [5] just to name a few.

Many methods are available for the preparation of terpyridine derivatives [6,7,8]. A classical method, the so-called Kröhnke’s method [9,10] involves the reaction of 2-acetylpyridine and an aldehyde. Biomass-derived aldehyde furfural has been already used for the preparation of terpyridines [11]. Apart of providing terpyridines with interesting properties, the use of furfural in tpy preparation allows greener synthetic procedures since furfural is obtained from biomass and therefore renewable [12]. Furthermore, the use of furfural in the preparation of functionalized terpyridine derivatives allows the design of greener synthetic pathways [13].

5-Methylfurfural is another furan derivative that can be easily obtained from biomass [14]. To the best of our knowledge, this aldehyde has not been used for the preparation of a terpyridine molecule. This article describes the preparation of compound 1 (Figure 1) from 5-methylfurfural and its use as a ligand in metal-catalyzed reactions.

2. Results and Discussion

Terpyridine 1 was prepared by simply mixing 2-acetylpyridine and 5-methylfurfural in ethanol in the presence of potassium hydroxide and aqueous ammonia (Scheme 1), according to the method of Wang and Hanan [15].

Since the product precipitates as a light yellow solid, it was easily isolated by filtration in 38% to 43% yield over three experiments. The synthetic protocol is very simple and provided a material that was sufficiently pure (>98% by quantitative ¹H-NMR) to be used without purification. Nevertheless, an analytically pure sample was obtained by recrystallization in ethanol. The identity of the compound was confirmed by ¹H and ¹³C-NMR spectroscopy, as well as by elemental analyses and HR-MS.

Terpyridines can be used as ligands in a vast list of metal-catalyzed reactions [16]. Thus compound 1 was tested in the nickel-catalyzed dimerization of alkyl halides [17,18]. In fact, it has been reported that 4,4′,4″-tritertbutyl-2,2′:6′,2″-terpyridine is an efficient ligand for this reaction [19]. Although 81% yield is obtained in the dimerization of benzyl bromide using 4,4′,4″-tritertbutyl-2,2′:6′,2″-terpyridine, substituting it by compound 1 resulted in a very low yield under the same conditions (Scheme 2,

Table 1. Yields obtained for the Ni-catalyzed dimerization of benzyl bromide with 4,4′,4″-tritertbutyl-2,2′:6′,2″-terpyridine and compound 1 as ligands.

Ligand	Yield (%)
4,4′,4″-tritertbutyl-2,2′:6′,2″-terpyridine	81
1	2

). This can be explained by the effects of the substituents onto the terpyridine, which can have important effects onto the outcome of reactions [20]. For instance, the nature of the substituents can influence the redox properties of the complex formed between the ligand and the metal [18] thus modifying the course of the reaction.

3. Materials and Methods

All reagents were purchased from commercial suppliers and used as received. Flash chromatography was carried out on a Combiflash Rf + Lumen (Teledyne ISCO, Lincoln, NE, USA) using Redisep Rf silica column (Teledyne ISCO, Lincoln, NE, USA). ¹H and ¹³C-NMR spectra were recorded on a Brucker AC 400 (Bruker, Wissembourg, France) at 400 and 100 MHz, respectively using CDCl₃ as a solvent. UV-Vis spectrum was recorded on a Cary 300 (Agilent Technologies, Santa Clara, CA, USA) using acetonitrile (C = 1.15 × 10⁻⁴ M) as solvent. Melting point was recorded with a Stuart SMP 10 melting point apparatus (Bibby Sterilin, Stone, UK) and is uncorrected. Elemental analysis was performed at Service d’Analyses Elementaires, UMR 7565 CNRS, Vandoeuvre-les-Nancy, France. HR-MS was recorded at Welience, Dijon, France.

3.1. Preparation of 4′-(5-Methylfuran-2-yl)-2,2′:6′,2″-terpyridine

4′-(5-Methylfuran-2-yl)-2,2′:6′,2″-terpyridine (1): To a solution of 2-acetylpyridine (4.84 g; 40 mmol) in ethanol (100 mL) are added 5-methylfurfural (2.20 g; 20 mmol), 85% potassium hydroxide pellets (3.08 g; 47 mmol) and 25% aqueous ammonia (58 mL). The reaction mixture was stirred at room temperature for 24 h. The solid was then filtered on a glass-sintered funnel and washed with ice-cold 50% ethanol until washings were colorless. The product was dried under vacuum over phosphorus pentoxide. Compound 1 was obtained as a light yellow solid (2.42 to 2.71 g; 38% to 43%). An analytical sample was obtained by recrystallization in ethanol. Mp = 174 °C. ¹H-NMR (CDCl₃, 400 MHz), δ (ppm): 8.75 (ddd, 2H, H6, 6″, J = 4.8 Hz, J = 1.6 Hz, J = 0.8 Hz), 8.67 (s, 2H, H3′, 5′), 8.65 (d, 2H, H3, 3″, J = 8.0 Hz), 7.87 (dt, 2H, H4, 4″, J = 7.7 Hz, J = 1.8 Hz), 7.35 (ddd, 2H, H5, 5″, J = 7.4 Hz, J = 4.8 Hz, J = 1.1 Hz), 7.03 (d, 1H, H2-furyl, J = 3.3 Hz), 6.17 (dd, 1H, H3-furyl, J = 3.3 Hz, J = 0.9 Hz), 2.44 (s, 3H, CH₃-furyl). ¹³C-NMR (CDCl₃, 100 MHz), δ (ppm): 156.2, 155.7, 154.0, 150.2, 149.0, 139.7, 136.8, 123.7, 121.3, 114.5, 110.4, 108.4, 13.9. Elemental analysis for C₂₀H₁₅N₃O: C, 76.66; H, 4.82; N, 13.41. Found C, 77.00; H, 4.93; N, 13.50. HR-MS: calc. for [C₂₀H₁₅N₃O + H]⁺ 314.12773, found 314.12879. UV-Vis (nm, L·cm⁻¹·mol⁻¹): λ_abs = 229, ε = 24017; λ_abs = 251, ε = 21434; λ_abs = 286, ε = 33678; λ_abs = 312, ε = 28008.

3.2. Nickel-Catalyzed Dimerization of Benzyl Bromide with Compound 1 as a Ligand

In a test tube were successively added NiCl₂·glyme (2.6 mg; 0.01 mmol), compound 1 (3.1 mg; 0.01 mmol), benzyl bromide (238 μL; 2.00 mmol), manganese powder (110.0 mg; 2.00 mmol), and DMF (2 mL). The test tube was stoppered and the mixture was stirred at 40 °C for 24 h. After cooling to room temperature, the crude solution was directly injected onto a 12 g-silica column and the product was purified by flash chromatography using hexane as eluent. The pure product was obtained as a white solid (3.6 mg; 2%). Analytical data match those reported in the literature [19,21].

4. Conclusions

A new member of the terpyridine family has been prepared and characterized. It was prepared from the biomass-derived reagent 5-methylfurfural. Its preparation was easy on the gram-scale. This new terpyridine was assessed for its potential application as a ligand in metal-catalyzed reactions. Although it was not efficient in the nickel-catalyzed dimerization of benzyl bromide, considering the vast number of reactions employing terpyridines as a ligand, 4′-(5-methylfuran-2-yl)-2,2′:6′,2″-terpyridine could be a promising tool in synthetic organic chemistry. Future work will focus on screening other reactions, in which this new terpyridine could be used.