rac-2-(2′-Ferrocenyl-2′-hydroxy-n-propyl)-1,3-benzothiazole

Abstract

The synthesis and characterisation (UV-Vis, IR, HRESI-MS, ¹H and ¹³C NMR spectroscopies, electrochemistry) is reported of the novel title material (1: alternatively named rac-1-(2′-benzothiazolyl)-2-ferrocenyl-2-propanol): a rare example of a ferrocenyl-benzothiazole hybrid species. Compound 1 is produced by the low temperature reaction of acetylferrocene (3) with a solution of the methyl anion derived via the deprotonation of 2-methyl-1,3-benzothiazole. The yield of 1 is moderate (34%) after purification and is an air and thermally stable solid under ambient conditions. Attempts to sublime 1, however, result in decomposition with one of the products being identified (NMR) as 3. The spectroscopic features of 1 are presented. Attempts to obtain suitable crystalline material of 1 for a single crystal X-ray diffraction study were unfortunately unsuccessful. Compound 1 also does not form stable coordination complexes with various metal salts (e.g., Ni[2+], Co[2+], etc.) under the conditions tested.

1. Introduction

Ferrocene and its many known derivatives have played a pivotal role in our understanding of organometallics [1,2] and the ferrocenyl functionality is routinely explored for its unique aspects and their influence on applications such as catalysis, ligand design, medicinal chemistry and materials science [3,4,5,6,7,8]. Benzothiazoles, a subclass of the azole heterocycles [9], have likewise found widespread use in drug development, and in novel organic and materials syntheses [10,11,12,13,14,15,16]. As part of our broader interest in both ferrocene [17,18] and azole-derivatives [19,20,21,22], we report herein the synthesis and characterisation of a rare hybrid example: that of rac-2-(2′-ferrocenyl-2′-hydroxy-n-propyl)-1,3-benzothiazole (i.e., 1). This material may also alternatively be named as rac-1-(2′-benzothiazolyl)-2-ferrocenyl-2-propanol.

2. Results and Discussion

The synthesis of the title material (i.e., 1) was carried out by the initial in situ formation of the methyl anion derived from 2-methyl-1,3-benzothiazole (2) using n-BuLi at low temperature (Scheme 1). The treatment of the solution of the resulting anion with acetylferrocene (3) at low temperature, followed by slow warming to room temperature (RT) afforded crude 1, which was thereafter isolated via extraction and subsequent recrystallization (see: Materials and Methods; Section 3.2).

Compound 1 is an air-stable dark-orange coloured solid under ambient conditions; however, 1 is unstable over extended time periods when dissolved in chlorinated solvents (e.g., CHCl₃, CH₂Cl₂) as these mixtures change colour to black and become opaque in nature. Sublimation of 1 in air also results in the decomposition of the compound [16]; one of the products of this process is identified (¹H NMR) as acetylferrocene 3 (Scheme 1). Compound 1 is only slightly soluble in aromatic solvents and insoluble in saturated hydrocarbons.

Despite the many crystallographically characterised examples of CpFeCp–R (R ≠ H; Cp = η⁵-cyclopentadienyl) derivatives that have been previously reported (e.g., [17,18,23,24,25]), our attempts to obtain a material suitable for X-ray crystallographic characterisation of 1 were never forthcoming, despite a wide variety of methods employed [26,27,28]. Macroscopic crystals of 1 were invariably found to be multi-twinned species and hence did not yield crystallographic datasets of acceptable quality [29]. The spectroscopic and analytical (NMR, MS, m.p., etc.) features of 1, (found in Section 3.2 and in the Supplementary Materials associated with this manuscript) are, however, all fully consistent with the surmised formation of 1 as depicted in Scheme 1. The NMR characteristics, from both a ¹H and ¹³C perspective, are perhaps best classified as routine and unsurprising [23,24,25]. The UV-Vis spectrum of 1 contains several absorbances that can be assigned to that of the benzothiazolyl unit [30,31,32,33,34] with a weaker d-d type transition in the visible region which is likely associated with the ferrocenyl moiety as previously described [35]. Infrared examination of 1 likewise reveals absorbances typical of this class of compounds [36,37,38,39]. Examination of 1 by cyclic voltammetry (CV) reveals two reversible redox processes with E_½ values of 0.54 and 0.83 V (Figure S10); again these can be assigned to redox chemistry occurring in a localised fashion at the azoyl and ferrocenyl groups [23,24,25].

As we have a long-standing interest in the coordination chemistry of azoles (e.g., [19,20,21,22]), we have also investigated the potential of 1 to act as a ligand to transition metal centres. Benzothiazoles are well-known to form complexes, via N-atom binding interactions, to a variety of electrophilic centres such as Ni(2+), Pd(2+), U(6+), etc. [40,41,42,43,44,45,46]. We further envisioned that de-protonation of the –OH group of 1, followed by the addition of such metal centres, would allow for possible κ²-N,O-chelation as has been observed for related species [19,20,21,22]. Disappointingly, the treatment of solutions of 1 with t-BuOK, followed by the addition of metal salts (i.e., CoBr₂·6H₂O; Zn(OAc)₂; Cu(NO₃)₂·2.5H₂O; NiBr₂·3H₂O), did not yield any isolable metal complexes and only extensive decomposition, or partial recovery of 1, were the results.

3. Materials and Methods

3.1. General Information

All reagents, solvents and deuterated solvents were obtained from commercially available sources. Dry solvents were dispensed from an Mbraun solvent purification system (MBraun, Stratham, NH, USA) immediately before use. Nuclear magnetic resonance spectroscopic measurements (¹H: 400 MHz; ¹³C{¹H}: 101 MHz) were carried out using a Bruker Avance II AC-400 MHz spectrometer (Bruker, Billerica, MA, USA) operating at 300K in the specified deuterated solvent as described. Abbreviations used in the ¹H NMR line listings are as follows: ABq = AB quartet, ArH = aryl H-atom, br-s = broad singlet, CpH = H-atom on the mono-substituted cyclopentadienyl group, d = doublet, m = multiplet, q = quartet, s = singlet and t = triplet. Infrared spectroscopy was performed on an Agilent Cary 630 FTIR Spectrometer (Agilent Technologies, Inc., Santa Clara, CA, USA) in open air. The CV data were collected using a MetrOhm Autolab Type II potentiostat/galvanostat (Metrohm AUTOLAB BV, Utrecht, The Netherlands). The solvent (CH₂Cl₂) was degassed prior to analysis by CV. UV-Vis absorption profiles were collected using an Agilent Cary 60 UV-vis spectrometer (cuvette path length = 1 cm). Molar extinction coefficients were calculated using the Beer-Lambert law. Melting point measurements were determined with a BUCHI 565 melting point apparatus (Büchi Labortechnik AG, Flawil, Switzerland) in triplicate under ambient conditions. High resolution ESI mass spectrometry (HRESI-MS) was performed at the University of Toronto at the AIMS facility using electrospray ionization with positive polarity.

3.2. Synthesis of rac-2-(2′-Ferrocenyl-2′-hydroxy-n-propyl)-1,3-benzothiazole (1)

A three-neck round-bottomed flask containing dry THF (20 mL) and 2 (1.5 mL; 1.76 g: 11.8 mmol) was cooled to −84 °C (EtOAc/N₂ [l] bath). Once appropriately chilled, n-BuLi (11 mL; 1.0 M in hexanes: 11 mmol) was added dropwise over a period of 10 min. The mixture was then stirred for 30 min. Then, 3 (2.82 g: 12.4 mmol), dissolved in dry THF (20 mL), was added dropwise over a period of 10 min. The contents of the reaction flask were then stirred at −84 °C for 1 h and left to warm slowly to RT; it was thereafter stirred for an additional hour. The resulting mixture was then poured into ice water (~100 mL) and the liquids added into a separatory funnel. The organic constituents were extracted with diethyl ether (50 mL × 2) and the combined organic phase was dried (MgSO₄), filtered and evaporated via rotary evaporation. The resulting waxy solid was recrystallised with a 1:4 solvent mixture of toluene and hexanes. A dark orange coloured air-stable powder was thereafter recovered by vacuum filtration (Yield 1.39 g: 34%). The m.p. (uncorrected) of this solid was found to be 98.0 ± 0.1 °C. HRESI-MS calcd for C₂₀H₂₀NOSFe⁺: 378.0610; found 378.0600. UV-Vis (nm, [log ε]: MeCN): 207 [5.06], 214 [5.05], 259 [4.20], 269 [4.05], 438 [2.24]. Selected FT-IR ν (cm⁻¹): 3403, 3089, 2978, 1632, 1438, 1315, 1170, 1103, 998, 760, 693. ¹H NMR (C₆D₆), δ: 1.56 (s, 3H, –CH₃), 3.30 (ABq, ²J_H-H = 14.5 Hz, 2H, –CH₂–), 3.84-3.86 (m, 1H, CpH), 3.87-3.89 (m, 1H, CpH), 3.91-3.92 (m, 1H, CpH), 3.93 (br-s, 1H, –OH), 4.04 (s, 5H, C₅H₅), 4.08-4.09 (m, 1H, CpH), 6.97-7.01 (m, 1H, ArH), 7.11-7.15 (m, 1H, ArH), 7.41-7.43 (m, 1H, ArH), 7.97-8.00 (m, 1H, ArH). ¹H NMR (dmso-d₆), δ: 1.49 (s, 3H, –CH₃), 3.42 (m, 2H, –CH₂–), 4.10 (t, ³J_H-H = 1.9 Hz, 1H, CpH), 4.14 (q, ³J_H-H = 1.9 Hz, 1H, CpH), 4.21 (s, 5H, C₅H₅), 4.23-4.24 (m, 1H, CpH), 5.05 (s, 1H, –OH), 7.36-7.40 (m, 1H, ArH), 7.43-7.47 (m, 1H, ArH), 7.92-7.94 (m, 1H, ArH), 8.01-8.03 (m, 1H, ArH). ¹³C NMR (dmso-d₆), δ: 27.8, 48.6, 65.5, 65.8, 67.0, 67.1, 68.4, 69.7, 98.2, 121.8, 122.1, 124.7, 125.7, 135.7, 152.0, 168.1.