Skip to content
BY-NC-ND 3.0 license Open Access Published by De Gruyter July 29, 2015

Synthesis of new 4′-(N-alkylpyrrol-2-yl)-2,2′: 6′,2″-terpyridines via N-alkylation of a pyrrole moiety

  • Jérôme Husson EMAIL logo and Laurent Guyard

Abstract

New 4′-(N-alkylpyrrol-2-yl)-2,2′:6′,2″-terpyridines were synthesized by N-alkylation of a pyrrole substituent with alkyl halides in dimethyl sulfoxide.

Introduction

2,2′:6′,2″-Terpyridines (terpyridines) are ligands that have been widely studied owing to their capability to form complexes with many metals [1, 2]. Alkyl-functionalized terpyridines and their complexes find many applications such as sensitizers for photovoltaic devices [3, 4], as ligands for the removal of actinides from nuclear wastes [5, 6], or as catalysts [7], to name a few. Synthesis of such alkyl-containing terpyridines is of interest in view of the above-mentioned applications. This article describes the preparation of new alkyl-functionalized terpyridines through the N-alkylation of a pyrrole moiety attached to the terpyridine scaffold. This methodology was selected owing to the fact that terpyridines containing five-membered heterocycles are easily prepared [8, 9] and the pyrrole ring can be easily modified at the N-atom [10].

Results and discussion

The synthesis started with the preparation of the pyrrole-functionalized terpyridine 1 [11–13] from 2-acetylpyridine and pyrrole-2-carboxaldehyde. Among the methods available [14, 15], a simple and efficient one-pot two steps method was employed [16] (Scheme 1).

Scheme 1
Scheme 1

With 1 in hand, three different methods were tested for the N-functionalization of the pyrrole ring. The first one (method i) relies on the use of potassium hydroxide as a base in the aprotic polar solvent dimethyl sulfoxide (DMSO) [17] and has been already used in our laboratory [18]. The second one (method ii) is a solvent-less procedure with a phase transfer reagent [19] that has a ‘green’ advantage because solvent is not used. The final method (method iii) uses an ionic liquid as a medium [20]. Ionic liquids are generally considered green solvents because they are non-volatile and recyclable [21]. To determine which method would be the most adequate, a series of experiments were carried out on the alkylation of 1 with hexyl bromide (Scheme 1) to obtain compound 2. Method ii failed in providing the desired pure compound. Thin layer chromatography (TLC) analysis showed that the crude mixture contained many polar compounds that were inseparable by chromatography as well as large amount of the remaining starting material. Method iii provided the desired product but with a low yield. Additionally, recovery of the ionic liquid was not possible, resulting in the loss of the ‘green’ advantage of the method. The best result in the preparation of compound 2 was achieved using the classical method i. Subsequently, this method was successfully used in the preparation of other pyrrole-containing terpyridines 37 and 10 by alkylation of 1 with the corresponding halides. Unfortunately, the attempted alkylation of 1 with isopropyl or t-butyl bromide failed to produce the respective products 8 and 9, apparently for steric reasons. Quite low yields were obtained for 5 and 10 with large amount of starting material remaining. It is nevertheless interesting to note that this protocol tolerates the presence of double bonds. Thus, efforts are in progress to improve the yield of 10 because this ethylenic derivative could be valuable for further functionalization of terpyridines. Although the use of primary alkyl chlorides resulted in the preparation of the corresponding alkylpyrroles in low yields, a notable exception was the alkylation of the polymeric Merrifield resin. The reaction of the chloromethyl groups of the resin with 1 enabled a partial functionalization of the polymer to provide the polymeric material 11 (Scheme 2). Functionalization of the polymer matrix was evidenced by elemental analysis, and the degree of functionalization was estimated to be 0.15 mmol/g of the material.

Scheme 2
Scheme 2

Conclusions

New alkyl-functionalized pyrrolyl-substituted terpyridines were prepared by N-alkylation of the pyrrole ring with primary alkyl halides in the presence of potassium hydroxide in DMSO. The protocol is also suitable for the functionalization of the Merrifield resin.

Future work will focus on integrating these new terpyridines in metal complexes, developing applications for the Merrifield-terpyridine resin, and the synthesis of further functionalized terpyridines.

Experimental

All reagents were obtained from commercial suppliers and used as received. For N-alkylation, potassium hydroxide pellets (85%) were powdered with an IKA A11 analytical mill, and the powder was stored under reduced pressure over P2O5. Anhydrous DMSO and Merrifield polymer resin (2% cross-linked with divinylbenzene, 2.8–3.2 mmol Cl/g, 200–400 mesh) were purchased from Acros Organics. 1H NMR (300 MHz) and 13C NMR (75 MHz) spectra were recorded in CDCl3 on a Bruker Avance 300 spectrometer. Elemental analysis was obtained at Service d’Analyse Elementaire (Vandoeuvre-les-Nancy, France).

4′-(Pyrrol-2-yl)-2,2′:6′,2″-terpyridine (1)

2-Acetylpyridine (13.43 g; 0.11 mol), ethanol (250 mL), pyrrole-2-carboxaldehyde (5.27 g; 0.055 mol), 85% potassium hydroxide pellets (8.56 g; 0.13 mol), and 25% aqueous ammonia (170 mL) were placed in a round-bottom flask, and the mixture was stirred at room temperature for 72 h. The resultant precipitate was filtered, washed with ice-cold 50% aqueous ethanol until washings were colorless, and dried under reduced pressure. Compound 1 was obtained as a light yellow solid and used in the next step without further purification. Physical and spectroscopic properties are in agreement with those reported [10–12].

Preparation of 4′-(N-alkylpyrrol-2-yl)-2,2′:6′, 2″-terpyridines 2–7 and 10

A suspension of powdered potassium hydroxide (0.44 g; 6.7 mmol) in DMSO (35 mL) was stirred at room temperature under argon for 30 min, then treated with compound 1 (1.00 g; 3.35 mmol), and the resultant red solution was stirred at room temperature under argon for 30 min. The appropriate alkyl halide (3.35 mmol) was added, and the mixture was stirred at room temperature under argon for 24 h. It was then poured onto water (100 mL), and a small amount of brine was added for an easy decantation. The aqueous layer was extracted with dichloromethane (4×25 mL). Organic layers were combined, washed with brine (100 mL), dried over sodium sulfate, and concentrated under reduced pressure. The residue was subjected to flash chromatography on neutral alumina (8 g), eluting initially with n-hexane followed by n-hexane/ethyl acetate (4:1).

4′-(N-Hexylpyrrol-2-yl)-2,2′:6′,2″-terpyridine (2)

Light yellow oil; yield 59% from hexyl iodide; 1H NMR: δ 0.81 (t, 3H, J = 7 Hz), 1.27 (m, 6H), 1.77 (t, 2H, J = 7 Hz), 4.15 (t, 2H, J = 7 Hz), 6.28 (t, 1H, J = 3.4 Hz), 6.61 (dd, 1H, J = 1.8 Hz and J′ = 3.4 Hz), 6.87 (t, 1H, J = 1.8 Hz), 7.32 (t, 2H, J = 7 Hz), 7.85 (td, 2H, J = 1.8 Hz and J′ = 8 Hz), 8.56 (s, 2H), 8.66 (d, 2H, J = 8 Hz), 8.71 (d, 2H, J = 3.4 Hz); 13C NMR: δ 14.0, 22.5, 26.3, 31.3, 31.7, 48.0, 108.4, 111.3, 119.5, 121.2, 123.7, 124.7, 131.8, 136.8, 142.9, 149.2, 155.6, 156.3. Anal. Calcd for C25H26N4: C, 78.50; H, 6.85; N, 14.65. Found: C, 78.34; H, 6.74; N, 14.40.

4′-(N-Methylpyrrol-2-yl)-2,2′:6′,2″-terpyridine (3)

White solid; mp 125–127°C; yield 38% from methyl iodide; 1H NMR: δ 3.89 (s, 3H), 6.26 (t, 1H, J = 4 Hz), 6.66 (dd, 1H, J = 1.8 Hz and J′ = 4.0 Hz), 6.81 (m, 1H), 7.34 (t, 2H, J = 6 Hz), 7.86 (td, 2H, J = 1.8 Hz and J′ = 8.0 Hz), 8.55 (s, 2H), 8.65 (d, 2H, J = 8.0 Hz), 8.71 (d, 2H, J = 4 Hz); 13C NMR: δ 35.9, 108.4, 111.3, 119.2, 121.3, 123.7, 126.1, 132.2, 138.8, 142.5, 149.2, 155.6, 156.3. Anal. Calcd for C20H16N4: C, 76.90; H, 5.16; N, 17.94. Found: C, 76.70; H, 5.13; N, 17.56.

4′-(N-Ethylpyrrol-2-yl)-2,2′:6′,2″-terpyridine (4)

White solid; mp 144–146°C; yield 39% from ethyl iodide; 1H NMR: δ 1.41 (t, 3H, J = 7.2 Hz), 4.21 (q, 2H, J = 7.2 Hz), 6.28 (t, 1H, J = 3.3 Hz), 6.58 (dd, 1H, J = 1.5 Hz and J′ = 3.3 Hz), 6.89 (m, 1H), 7.34 (dd, 2H, J = 4.2 Hz and J′ = 7.2 Hz), 7.86 (td, 2H, J = 1.5 Hz and J′ = 8.0 Hz), 8.53 (s, 2H), 8.65 (d, 2H, J = 8.0 Hz), 8.71 (d, 2H, J = 4.2 Hz); 13C NMR: δ 16.8, 42.6, 108.6, 111.3, 119.6, 121.3, 123.7, 123.8, 131.7, 136.8, 142.9, 149.2, 155.6, 156.3. Anal. Calcd for C21H18N4: C, 77.28; H, 5.56; N, 17.17. Found: C, 77.49; H, 5.64; N, 16.80.

4′-(N-Propylpyrrol-2-yl)-2,2′:6′,2″-terpyridine (5)

White solid; mp 109–111°C; yield 9% from propyl iodide, 6% from propyl chloride; 1H NMR: δ 0.85 (t, 3H, J = 7.2 Hz), 1.77 (q, 2H, J = 7.2 Hz), 4.13 (t, 2H, J = 7.2 Hz), 6.26 (s, 1H), 6.59 (m 1H), 6.87 (s, 1H), 7.33 (dd, 2H, J = 5.0 Hz and J′ = 6.3 Hz), 7.86 (t, 2H, J = 7.2 Hz), 8.53 (s, 2H), 8.66 (d, 2H, J = 7.2 Hz), 8.71 (d, 2H, J = 5.0 Hz); 13C NMR: δ 11.1, 24.9, 49.6, 108.4, 111.4, 119.5, 121.2, 123.7, 124.7, 131.8, 136.8, 142.9, 149.2, 155.6, 156.3. Anal. Calcd for C22H20N4: C, 77.62; H, 5.92; N, 16.46. Found: C, 77.34; H, 5.87; N, 16.23.

4′-(N-Butylpyrrol-2-yl)-2,2′:6′,2″-terpyridine (6)

Light yellow oil; yield 37% from butyl iodide, 1.8% from butyl chloride); 1H NMR: δ 0.87 (t, 3H, J = 7.2 Hz), 1.28 (q, 2H, J = 7.5 Hz), 1.75 (q, 2H, J = 7.5 Hz), 4.17 (t, 2H, J = 7.2 Hz), 6.29 (t, 1H, J = 3 Hz), 6.63 (dd, 1H, J = 1.5 Hz and J′ = 3 Hz), 6.88 (s, 1H), 7.31 (dd, 2H, J = 3 Hz and J′ = 7.2 Hz), 7.84 (td, 2H, J = 1.5 Hz and J′ = 7.5 Hz), 8.58 (s, 2H), 8.67 (d, 2H, J = 7.5 Hz), 8.71 (d, 2H, J = 3 Hz); 13C NMR: δ 13.7, 19.8, 33.8, 47.8, 108.5, 111.4, 119.5, 121.2, 123.7, 124.7, 131.8, 136.8, 142.9, 149.2, 155.6, 156.3. Anal. Calcd for C23H22N4: C, 77.94; H, 6.26; N, 15.81. Found: C, 77.68; H, 6.26; N, 15.43.

4′-(N-Undecylpyrrol-2-yl)-2,2′:6′,2″-terpyridine (7)

Light yellow oil; yield 42% from undecyl bromide; 1H NMR: δ 0.87 (t, 3H, J = 6.9 Hz), 1.22 (m, 14H), 1.77 (t, 2H, J = 6.9 Hz), 4.15 (t, 2H, J = 7.5 Hz), 6.28 (t, 1H, J = 4 Hz), 6.61 (dd, 1H, J = 1.5 Hz and J′ = 4 Hz), 6.87 (s, 1H), 7.33 (dd, 2H, J = 5 Hz and J′ = 7.5 Hz), 7.86 (td, 2H, J = 1.5 Hz and J′ = 7.5 Hz), 8.56 (s, 2H), 8.67 (d, 2H, J = 7.5 Hz), 8.71 (d, 2H, J = 4 Hz); 13C NMR: δ 14.1, 22.7, 29.1, 29.3, 29.4, 29.5, 29.5, 29.6, 31.9, 48.0, 108.5, 111.3, 119.5, 121.2, 123.7, 124.6, 131.9, 136.7, 142.9, 149.2, 155.6, 156.3. Anal. Calcd for C29H34N4 C, 79.41; H, 7.81; N, 12.77. Found: C, 80.09; H, 8.09; N, 12.25.

4′-(N-Pent-5-enylpyrrol-2-yl)-2,2′:6′,2″-terpyridine (10)

Light yellow oil; yield 2% from 5-bromo-1-pentene; 1H NMR: δ 1.86 (m, 2H), 2.02 (m, 2H), 4.17 (t, 2H, J = 7.5 Hz), 4.90 (d, 1H, J = 10.2 Hz), 4.96 (dd, 1H, J = 1.5 Hz and J′ = 17.1 Hz), 5.74 (tdd, 1H, J = 6 Hz, J′ = 10.2 Hz and J″ = 17.1 Hz), 6.27 (t, 1H, J = 3 Hz), 6.61 (t, 1H, J = 1.5 Hz), 6.87 (s, 1H), 7.34 (t, 2H, J = 6 Hz), 7.87 (td, 2H, J = 1.5 Hz and J′ = 7.8 Hz), 8.53 (s, 2H), 8.66 (d, 2H, J = 7.8 Hz), 8.71 (d, 2H, J = 3 Hz); 13C NMR: δ 30.6, 30.7, 47.3, 108.5, 111.5, 115.5, 119.4, 121.2, 123.7, 124.7, 131.8, 136.8, 137.4, 142.8, 149.2, 155.6, 156.3. Anal. Calcd for C24H22N4 C, 78.66; H, 6.05; N, 15.29. Found: C, 78.76; H, 6.13; N, 15.22.

Preparation of terpyridine-functionalized Merrifield resin (11)

A suspension of powdered potassium hydroxide (2.09 g) in DMSO (50 mL) was stirred at room temperature under argon for 30 min. Then, 4′-(pyrrol-2-yl)-2,2′:6′,2″-terpyridine (1, 4.78 g) was added, and the resultant red solution was stirred at room temperature under argon for 30 min followed by addition of Merrifield resin (5.00 g). The suspension was stirred at room temperature for 72 h. The resin was filtered, washed with water and ethanol, and then extracted for 24 h in a Soxhlet apparatus with dichloromethane. After drying under a reduced pressure over phosphorus pentoxide, the product was obtained as a dark solid (5.40 g). Elemental analysis (C, 76.01; H, 6.13; N, 0.86) indicates a degree of functionalization of 0.15 mmol/g.


Corresponding author: Jérôme Husson, Institut UTINAM UMR CNRS 6213, Université de Franche-Comté, 16 Route de Gray, 25030 Besançon cedex, France, e-mail:

Acknowledgments

This work was supported by Université de Franche-Comté (BQR Rebiocell).

References

[1] Schubert, U. S.; Hofmeier, H.; Newkome, G. R. Modern Terpyridine Chemistry; Wiley-VCH: Weinheim, 2006.10.1002/3527608486Search in Google Scholar

[2] Schubert, U. S.; Winter, A.; Newkome, G. R. Terpyridine-Based Materials; Wiley-VCH: Weinheim, 2011.10.1002/9783527639625Search in Google Scholar

[3] Ozawa, H.; Yamamoto, Y.; Fukushima, K.; Yamashita, S.; Arakawa, H. Synthesis and characterization of a novel ruthenium sensitizer with a hexylthiophene-functionalized terpyridine ligand for dye-sensitized solar cells. Chem. Lett. 2013, 42, 897–899.Search in Google Scholar

[4] Ozawa, H.; Yamamoto, Y.; Kawaguchi, H.; Shimizu, R.; Arakawa, H. Ruthenium sensitizers with a hexylthiophene-modified terpyridine ligand for dye-sensitized solar cells: synthesis, photo- and electrochemical properties, and adsorption behavior to the TiO2 surface. ACS Appl. Mater. Interfaces 2015, 7, 3152–3161.Search in Google Scholar

[5] Hudson, M. J.; Harwood, L. M.; Laventine, D. M.; Lewis, F. W. Use of soft heterocyclic N-donor ligands to separate actinides and lanthanides. Inorg. Chem. 2013, 52, 3414–3428.Search in Google Scholar

[6] Lewis, F. W.; Hudson, M. J.; Harwood, L. M. Development of highly selective ligands for separation of actinides from lanthanides in the nuclear fuel cycle. Synlett. 2011, 18, 2609–2632.Search in Google Scholar

[7] Prinsell, M. R.; Everson, D. A.; Weix, D. J. Nickel-catalyzed, sodium iodide-promoted reductive dimerization of alkyl halides, alkyl pseudohalides, and allylic acetates. Chem. Commun. 2010, 46, 5743–5745.Search in Google Scholar

[8] Husson, J.; Knorr, M. Syntheses and applications of furanyl-functionalized 2,2′:6′,2″-terpyridines. Beilstein J. Org. Chem. 2012, 8, 379–389.Search in Google Scholar

[9] Husson, J.; Knorr, M. 2,2′:6′,2″-Terpyridines functionalized with thienyl substituents: synthesis and applications. J. Heterocycl. Chem. 2012, 49, 453–478.Search in Google Scholar

[10] Jolicoeur, B.; Chapman, E. E.; Thompson, A.; Lubell, W. D. Pyrrole protection. Tetrahedron 2006, 62, 11531–11563.Search in Google Scholar

[11] Abboud, M.; Kalinina, D.; Potvin, P. G. Pyrrole-substituted tridentate complexes of Ru(II): Spectroscopy, electrochemistry, photosensitization and the role of orbital mixing. Inorg. Chim. Acta 2009, 362, 4953–4959.Search in Google Scholar

[12] Beley, M.; Delabouglise, D.; Houppy, G.; Husson, J.; Petit, J.-P. Preparation and properties of ruthenium (II) complexes of 2,2′:6′,2″-terpyridines substituted at the 4′-position with heterocyclic groups. Inorg. Chim. Acta 2005, 358, 3075–3083.Search in Google Scholar

[13] Husson, J.; Migianu, E.; Beley, M.; Kirsch, G. Synthesis of new terpyridines under solventless conditions using alumina. Synthesis 2004, 2, 267–270.Search in Google Scholar

[14] Fallahpour, R. A. Synthesis of 4′-substituted-2,2′: 6′,2″-terpyridines. Synthesis 2003, 2, 155–184.10.1055/s-2003-36811Search in Google Scholar

[15] Heller, M.; Schubert, U. S. Syntheses of functionalized 2,2′:6′,2″-terpyridines. Eur. J. Org. Chem. 2003, 6, 947–961.Search in Google Scholar

[16] Wang, J.; Hanan, G. S. A facile route to sterically hindered and non-hindered 4′-aryl–2,2′:6′,2″-terpyridines. Synlett. 2005, 8, 1251–1254.Search in Google Scholar

[17] Dhanabalan, A.; Van Dongen, J. L. J.; Van Duren, J. K. J.; Janssen, H. M.; Van Hal, P. A.; Janssen, R. A. J. Synthesis, characterization, and electrooptical properties of a new alternating N-dodecylpyrrole-benzothiadiazole copolymer. Macromolecules 2001, 34, 2495–2501.Search in Google Scholar

[18] Taouil, A. E.; Lallemand, F.; Melot, J.-M.; Husson, J.; Hihn, J.-Y.; Lakard, B. Effects of polypyrrole modified electrode functionalization on potentiometric pH response. Synth. Met. 2010, 160, 1073–1080.Search in Google Scholar

[19] Diez-Barra, E.; De la Hoz, A.; Loupy, A.; Sanchez-Migallon, A. Selective Alkylation of pyrrole by phase-transfer catalysis in the absence of solvent. J. Heterocycl. Chem. 1994, 31, 1715–1717.Search in Google Scholar

[20] Jorapur, Y. R.; Jeong, J. M.; Chi, D. Y. Potassium carbonate as a base for the N-alkylation of indole and pyrrole in ionic liquids. Tetrahedron Lett. 2006, 47, 2435–2438.Search in Google Scholar

[21] Suresh; Sandhu, J. S. Recent advances in ionic liquids: green unconventional solvents of this century: part I. Green Chem. Lett. Rev. 2011, 4, 289–310.Search in Google Scholar

Received: 2015-4-8
Accepted: 2015-4-28
Published Online: 2015-7-29
Published in Print: 2015-8-1

©2015 by De Gruyter

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Downloaded on 28.3.2024 from https://www.degruyter.com/document/doi/10.1515/hc-2015-0058/html
Scroll to top button