Synthesis and Characterization of Three New Furan-Containing Terpyridine Derivatives

Abstract

Three new terpyridine derivatives which contain a pendant furan heterocycle have been prepared and characterized. The first two, 4′-(4,5-dimethylfuran-2-yl)-2,2′:6′,2″-terpyridine (1) and 4′-((1,3-dioxolan-2-yl)furan-2-yl)-2,2′:6′,2″-terpyridine (2), are obtained through the reaction of 2-acetylpyridine and suitable furaldehydes using the Kröhnke reaction. The last one, 4′-(5-formylfuran-2-yl)-2,2′:6′,2′’-terpyridine (3) is obtained via acidic hydrolysis of the acetal onto terpyridine (2). The structures of these new compounds are confirmed using different analytical techniques such as NMR and infrared spectroscopy (ATR-IR) as well as by High Resolution Mass Spectrometry (HRMS).

1. Introduction

Terpyridine derivatives (abbreviated as terpy or tpy) are heterocyclic ligands which can form a broad range of complexes with many metals. The coordination compounds thus obtained find applications in many fields [1,2], such as sensitizers for photovoltaic applications [3], supramolecular assemblies [4], electrochromic materials [5], or as catalysts [6], just to name a few. In this large family of ligands, terpyridines carrying a furan heterocycle are important members [7]. Indeed, they can be used as synthesis intermediates to prepare terpyridines and their complexes carrying carboxylic acids [8,9], for the construction of Metal–Organic Frameworks and metallopolymers [10,11] or in the biomedical domain [12,13,14] amongst others. Therefore, preparation and characterization of new furan-functionalized tpy is still a subject of interest. This paper describes the synthesis of three new terpy ligands (Figure 1) from 2-furaldehyde derivatives and 2-acetylpyridine. The molecular structures of these compounds are confirmed by different analytical techniques such as NMR, infrared spectroscopy, and mass spectrometry.

2. Results and Discussion

Terpyridines 1 and 2 were prepared in the same way, starting from 2-acetylpyridine and 4,5-dimethylfuran-2-furaldehyde or 5-(1,3-dioxolan-2-yl)-2-furaldehyde, respectively, using a Kröhnke reaction [15,16]. The specific protocol that was used is a one-pot procedure in which the terpyridine precipitates from the reaction mixture [17]. They are recovered by simple filtration, and after washing with ice-cold ethanol, analytically pure (as determined by quantitative ¹H NMR using ethylene carbonate as internal standard) compounds were obtained albeit in moderate yields (Scheme 1).

The last ligand, 4′-(5-formylfuran-2-yl)-2,2′:6′,2″-terpyridine (3), is simply obtained from compound 2 via acidic hydrolysis of acetal moiety (Scheme 2). The reaction was carried out using concentrated hydrochloric acid [18]. By doing so, terpy 3 was obtained in 88% yield. Once again, the product was analytically pure without the need for purification. Attempts to prepare 3 by other synthetic pathways (for instance oxidation of a primary alcohol) have failed so far.

These three new ligands were characterized by different analytical techniques (Supplementary Material). Firstly, ¹H NMR spectra were recorded. They all exhibit the characteristics signals for the terpyridine core and agree with data reported for structurally related furan-functionalized tpy [19,20,21,22]. Nevertheless, it is interesting to note that for compound 3 the signal for protons 3′ and 5′ (singlet at 8.82 ppm) is deshielded when compared to molecules 1 and 2 (singlets at 8.62 and 8.70 ppm respectively). This highlights the effect of the formyl electron withdrawing group. The ¹³C NMR spectra are also in agreement with the molecular structures for compounds 1–3 since they display 14, 14, and 13 signals as expected.

Mass spectra (HR-MS) of these three new ligands agreed with the proposed structures. Indeed, the peaks of molecular ions [M + H]⁺ are observed at m/z = 328.14412 (calc. 328.14444), 372.13380 (calc. 372.13427), and 328.10775 (calc. 328.10805), respectively.

Finally, these three new compounds were characterized by attenuated total reflectance infrared spectroscopy (ATR-IR). Here again, the characteristic peaks of molecules of the terpyridine family are observed [23]. In particular, the C=N stretching vibration, which is characteristic of the pyridine heterocycle [24], is observed in the 1500–1600 cm⁻¹ region. In addition, molecule 3 also presents the characteristic peaks of the carbonyl and C-H stretch of the aldehyde function at 1671 cm⁻¹ and 2829 cm⁻¹, respectively. When combined, all these analytical data confirm the proposed structures for ligands 1–3.

3. Materials and Methods

The starting aldehydes 4,5-dimethylfuran-2-furaldehyde and 5-(1,3-dioxolan-2-yl)-2-furaldehyde were purchased from Thermo Fisher Scientific (Loughborough, UK) and TCI Chemicals Europe (Zwijndrecht, Belgium), respectively. The other reagents were obtained from TCI Chemicals Europe and VWR Chemicals (Rosny-sous-Bois, France) and used as received. ¹H and ¹³C NMR spectra were recorded on a Brucker AC 400 (Bruker, Wissem-bourg, France) at 400 and 100 MHz, respectively, using CDCl₃ as a solvent. Infrared spectra were recorded on a VERTEX 70 spectrometer equipped with an ATR PRO 4X (Bruker, Wissem-bourg, France). The melting point was recorded with a M 565 melting point apparatus (Büchi, Flawil, Switzerland) according to European Pharmacopoeia. HR-MS was recorded at Sayence SATT, Dijon, France.

• 4′-(4,5-Dimethylfuran-2-yl)-2,2′:6′,2″-terpyridine (1): 4,5-dimethylfuran-2-furaldehyde (5.00 g; 40.3 mmol), 85% potassium hydroxide pellets (6.21 g; 94.1 mmol), and 25% aqueous ammonia solution (120 mL) were successively added to a solution of 2-acetylpyridine (9.76 g; 80.6 mmol) in absolute ethanol (200 mL). The reaction mixture was stirred at room temperature for 72 h. The precipitated solid was collected by filtration and washed with ice-cold 50% ethanol until washings were colorless. The crude product was air-dried and 1 is obtained as a yellow solid (6.34 g; 48%) that was analytically pure by ¹H NMR. m.p. = 222.1–223.1 °C. ¹H-NMR (CDCl₃, 400 MHz), δ (ppm): 8.72 (d, 2H, H6, 6″, J = 4.8 Hz), 8.62 (m, 4H, H3, 3″, 3′, 5′), 7.84 (td, 2H, H4, 4″, J = 7.6 Hz, J = 1.8 Hz), 7.32 (ddd, 2H, H5, 5″, J = 7.4 Hz, J = 4.8 Hz, J = 1.1 Hz), 6.90 (s, 1H, H_a), 2.32 (s, 3H, H_b), 2.00 (s, 3H, H_c). ¹³C-NMR (CDCl₃, 100 MHz), δ (ppm): 156.3, 155.7, 149.7, 149.1, 148.9, 139.8, 136.8, 123.7, 121.3, 116.9, 114.5, 112.8, 11.7, 9.9. HR-MS: calc. for [C₂₁H₁₇N₅O + H]⁺ 328.14444, found 328.14412. IR (ATR): ν_max (cm⁻¹): 3052.5, 1583.9, 1396.0, 791.3.
• 4′-((1,3-Dioxolan-2-yl)furan-2-yl)-2,2′:6′,2″-terpyridine (2): 5-(1,3-Dioxolan-2-yl)-2-furaldehyde (1.92 g; 11.4 mmol), 85% potassium hydroxide pellets (1.76 g; 26.7 mmol), and 25% aqueous ammonia solution (34 mL) were successively added to a solution of 2-acetylpyridine (2.76 g; 22.8 mmol) in absolute ethanol (60 mL). The reaction mixture was stirred at room temperature for 72 h. The precipitated solid was collected by filtration and washed with ice-cold 50% ethanol until washings were colorless. The crude product was air-dried and 2 was obtained as a white solid (1.96 g; 46%) that was analytically pure by ¹H NMR. m.p. = 114.4–115.4 °C. ¹H-NMR (CDCl₃, 400 MHz), δ (ppm): 8.72 (dd, 2H, H6, 6″, J = 4.8 Hz, J = 0.8 Hz), 8.70 (s, 2H, H3′, 5′), 8.62 (d, 2H, H3, 3″, J = 8.0 Hz), 7.85 (td, 2H, H4, 4″, J = 7.7 Hz, J = 1.8 Hz), 7.34 (ddd, 2H, H5, 5″, J = 7.4 Hz, J = 4.8 Hz, J = 1.1 Hz), 7.07 (d, 1H, H_b, J = 3.4 Hz), 6.60 (d, 1H, H_a, J = 3.4 Hz), 6.06 (s, 1H, H_c), 4.18 (m, 2H, H_d), 4.06 (m, 2H, H_e). ¹³C-NMR (CDCl₃, 100 MHz), δ (ppm): 156.0, 155.8, 152.7, 152.4, 149.0, 139.3, 137.0, 124.0, 121.4, 115.3, 110.6, 109.7, 97.8, 65.2. HR-MS: calc. for [C₂₂H₁₇N₃O₃ + H]⁺ 372.13427, found 372.13380. IR (ATR): ν_max (cm⁻¹): 2892.3, 1585.7, 1410.0, 1113.5, 785.2.
• 4′-(5-Formylfuran-2-yl)-2,2′:6′,2″-terpyridine (3): To a solution of 2 (1.00 g; 2.7 mmol) in acetone is added conc. hydrochloric acid (3 mL). The obtained suspension is stirred at room temperature for 2 h. The solvent is removed under vacuo and the residue is taken up in water (100 mL). The pH of the solution is adjusted to 9 by the portion-wise addition of solid sodium carbonate. The resulting precipitate is filtered, washed with water and air-dried. Analytically pure 3 is obtained as a white solid (0.78 g; 88%). m.p. = 227.6–229.1 °C. ¹H-NMR (CDCl₃, 400 MHz), δ (ppm): 9.78 (s, 1H, H_c), 8.82 (s, 2H, H3′, 5′), 8.73 (dd, 2H, H6, 6″, J = 4.7 Hz, J = 0.7 Hz), 8.62 (d, 2H, H3, 3″, J = 8.0 Hz), 7.87 (td, 2H, H4, 4″, J = 7.7 Hz, J = 1.8 Hz), 7.36 (m, 3H, H5, 5″, H_b), 7.25 (d, 1H, H_a, J = 1.4 Hz). ¹³C-NMR (CDCl₃, 100 MHz), δ (ppm): 178.1, 156.8, 156.3, 155.5, 153.0, 149.1, 138.0, 137.1, 124.2, 121.9, 121.4, 116.3, 111.2. HR-MS: calc. for [C₂₀H₁₃N₃O₂ + H]⁺ 328.10805, found 328.10775. IR (ATR): ν_max (cm⁻¹): 3063.3, 3021.5, 2829.1, 1671.0, 1587.2, 1513.4, 1404.8, 786.9.

4. Conclusions

Three new furan-containing terpyridine ligands have been prepared and characterized. These compounds were prepared via well-established synthetic methods. Spectroscopic data confirmed the molecular structures of these new compounds. Future work will focus on using these substances for the preparation of new functional materials, especially by exploiting the aldehyde functional group onto 3 (e.g., for the construction of supramolecular assemblies) [25].