Perfluoro-3-ethyl-1,2,3,10b-tetrahydrofluoranthene

Abstract

The title compound was synthesized from perfluoro-1-ethyltetralin and 1,2,3,4-tetrafluorobenzene under the action of antimony pentafluoride as a mixture of cis- and trans-isomers in a 71% isolated yield. The structure and cis-/trans-configuration of the isomers were determined by NMR (¹⁹F, ¹³C), ¹⁹F–¹⁹F COSY, and ¹⁹F–¹⁹F NOESY 2D NMR spectroscopy.

1. Introduction

Organofluorine compounds are receiving increasing attention in terms of basic research in organic chemistry as well as finding application in materials science, biomedicine, and agriculture [1,2,3,4,5,6,7,8,9]. In particular, fluorine-containing fluorenes are regarded as promising objects for optoelectronics [10,11,12,13], catalysis [14,15,16], and have even found success as drugs approved for medical use [17]. With the polyfluorinated species of this class of compounds being represented by only a handful of examples [11,18,19,20], further research on their useful properties and application is still impeded.

Previously, we studied the reactions of perfluoroalkylbenzenes with polyfluorobenzenes leading to polyfluorinated 9-alkylfluorenes [21,22,23]. Then, we showed that perfluorotetralin—a cyclic analog of perfluoroalkylbenzenes—reacted with 1,2,3,4-tetrafluorobenzene in the presence of antimony pentafluoride to produce perfluoro-1,2,3,10b-tetrahydrofluoranthene containing a fluorene motif in the molecule [24]. The present study focuses on the synthesis of a 3-ethyl derivative of perfluoro-1,2,3,10b-tetrahydrofluoranthene and its unambiguous characterization.

2. Results and Discussion

The interaction of perfluoro-1-ethyltetralin (1) with 1,2,3,4-tetrafluorobenzene (2) in the presence of antimony pentafluoride at 50 °C for 30 h, followed by treating the reaction mixture with HF–Py and then with water, yielded perfluoro-3-ethyl-1,2,3,10b-tetrahydrofluoranthene (3) as a mixture of cis- and trans-isomers in an approximately equal ratio (Scheme 1). The separation of the individual isomers proved to be a difficult task. After the reaction mixture was subjected to column chromatography, only small amounts of individual isomers were isolated, with the major fraction being a mixture of the isomers. The total isolated yield was 71%.

Similar to the formation of parent perfluoro-1,2,3,10b-tetrahydrofluoranthene [24], the formation of compound 3 seems to proceed as follows. Tetralin 1 reacts with tetrafluorobenzene 2 in the presence of SbF₅ to form an intermediate compound A. The latter, under the action of antimony pentafluoride, generates cation A⁺, which undergoes intramolecular cyclization, with the loss of a proton, to yield intermediate B. In the SbF₅ medium, compound B transforms into cation B⁺. The subsequent addition of a fluorine anion to cation B⁺ during HF–Py work-up results in product 3 as a mixture of two stereoisomers (Scheme 2).

The structure of compound 3 was established by ¹⁹F, ¹³C, and 2D NMR spectroscopy and HRMS. In the ¹⁹F NMR spectra, the isomers have close chemical shifts for respective nuclei, the most profound difference being in the shifts of F³. The chemical shifts and splitting of the signals are in conformity with the patterns observed for the parent perfluoro-1,2,3,10b-tetrahydrofluoranthene [24]. Nevertheless, these data were not enough to establish the cis-/trans-configurations of the two isomers and resolve the ambiguity in assigning the signals of tertiary F³ and F^10b. For that, a series of additional 2D NMR spectra (¹⁹F–¹⁹F COSY and ¹⁹F–¹⁹F NOESY) were obtained. In the COSY spectrum of trans-3 (Figure 1), we observed correlations between F³ and F⁴ as well as between F³ and CF₃. We also observed a weak correlation between F^10b and F¹⁰ alongside a strong cross peak of F^10b with CF₂-1. These findings validate the assignment of the tertiary fluorine atoms F³ and F^10b. Both the COSY and NOESY spectra of trans-3 (Figure 1) showed a significant correlation between F^10b and the CF₂ moiety of the CF₂CF₃ group that can only be if trans-3 indeed has trans-configuration. The other correlations observed in both spectra corresponded with the assignment of all the signals.

In the case of cis-3, a similar analysis was performed to assign the tertiary fluorine atoms. The COSY spectrum did not seem to have cross peaks of the tertiary fluorine atoms with the aromatic F⁴ and F¹⁰, instead showing a correlation between F³ and the CF₂CF₃ group, whereas F^10b had a cross peak with CF₂-1. The COSY and NOESY spectra of the isomer showed no cross peaks between F^10b and the CF₂ moiety of the CF₂CF₃ group, thereby clearly indicating the cis-arrangement of the tertiary fluorine atoms. Both spectra also showed F³–F^10b cross peaks (Figure 2).

It is noteworthy that the signals of the tertiary fluorine atoms in cis-3 were unresolved and rather broadened, arguably because of the conformational transitions of the alicyclic moiety. Therefore, a series of variable-temperature ¹⁹F NMR experiments were conducted. In a CDCl₃ solution, the signals had a chemical shift difference of ca. 1 ppm at 298 K. With increasing temperature, the signals started to appear as doublets of an AB system (J_AB ≈ 40 Hz) and shift toward each other, degrading into what appeared like a single peak at 325 K. To obtain a better picture, we switched to another solvent. In a DMSO-d₆ solution, the difference in the tertiary fluorine chemical shifts exceeded 4 ppm at the ambient temperature, and the AB system became more obvious. With increasing temperature, the signals also shifted toward each other, became narrower, and splitting patterns emerged (Figure 3). This ⁵J_FF ≈ 40 Hz constant between F³ and F^10b confirmed their cis-arrangement because it can only arise from through-space fluorine–fluorine coupling.

The ¹³C spectra of the individual isomers revealed seven aromatic carbons along with two tertiary C, five quaternary C, and a CF₃ group; the signals due to CF₂ carbons are located in the δ_C 108–113 region, have rather complex splitting patterns, and, with the signal components overlapping, their further analysis appeared to be superfluous since it yields little additional information on the structural characteristics.

3. Materials and Methods

3.1. General Information

¹⁹F spectra were recorded on a Bruker AV 400 (Bruker Corporation, Billerica, MA, USA) instrument (376.5 MHz), variable-temperature ¹⁹F NMR experiments were conducted on a Bruker AV 300 instrument (282.4 MHz), and ¹³C NMR spectra were recorded on a Bruker AV 600 (150.92 MHz) instrument. Chemical shifts (δ) are reported in ppm relative to CCl₃F (¹⁹F, upfield negative) and TMS (¹³C); C₆F₆ (δ_F = −162.9 ppm) and CDCl₃ (δ_C = 76.9 ppm) served as internal standards. Coupling constants (J) are reported in Hz and rounded to the nearest 0.5 Hz. The following abbreviations were used to designate multiplicities: d = doublet, t = triplet, q = quartet, and m = multiplet.

2D NMR experiments were performed on a Bruker AV400 spectrometer, equipped with a 5 mm z-axis field-gradient probehead. Bruker programs for pulse sequence were used. Typical parameters for 2D NMR experiments were as follows. FID data were processed with zero-filling and sine-bell function weighting applied prior to Fourier transformation in order for the resolution to be optimized appropriately.

¹⁹F–¹⁹F COSY: cosygpqf—pulse program, gradient pulses for selection were used, 8K x 1024 time-domain data matrix, 1 scan for each FID with a relaxation time of 3 s.

¹⁹F–¹⁹F NOESY: noesygpph—pulse program, States-TPPI (time-proportional phase incrementation) acquisition mode, 800 ms mixing time, 8K × 512 time-domain data matrix, 2 scans for each FID with a relaxation time of 2 s.

Molecular masses of the compounds were determined by HRMS with a Thermo Electron Corporation DFS (Thermo Fisher Scientific, Waltham, MA, USA) instrument (EI 70 eV). Column chromatography was carried out on Silica gel 60 (Merck KGaA, Darmstadt, Germany, particle size 0.063–0.200 mm).

Contents of products in the reaction mixture were determined by ¹⁹F NMR integration versus pentafluorobenzoic acid. For that, a ¹⁹F NMR spectrum was acquired using zgflqn pulse program. The relaxation delay (D1) was 10 s to take into account differential relaxation times. The FID was multiplied by an exponential weighting (lb  =  0.5 Hz) and zero-filled to 256k data points before Fourier transformation; phase and baseline correction were performed manually prior to integration.

Antimony pentafluoride was distilled under atmospheric pressure (bp 142–143 °C). 1,2,3,4-Tetrafluorobenzene was purchased from commercial sources (>98% purity) and used as received. Perfluoro-1-ethyltettralin was synthesized according to the literature procedure [25].

3.2. Synthesis of Perfluoro-3-ethyl-1,2,3,10b-tetrahydrofluoranthene

Into a nickel container, SbF₅ (5.27 g, 24.31 mmol) and compound 1 (1.82 g, 4.06 mmol) were placed, then tetrafluorobenzene 2 (0.61 g, 4.07 mmol) was added dropwise at 0 °C. The mixture was properly stirred and heated at 50 °C for 30 h. The resultant mixture was treated with HF–Py (6.0 mL) at −15 °C and kept for 4 h with occasional shaking, then cooled down to −15 °C and poured onto ice, extracted with CHCl₃, and the extract was dried over MgSO₄. After filtration, the solvent was removed under reduced pressure to afford 2.29 g of a crude reaction mixture containing 76% of compound 3 as a mixture of cis- and trans-isomers in a 51 : 49 molar ratio (¹⁹F NMR). Column chromatography (hexane as the eluent) yielded 50 mg of compound trans-3, 40 mg of compound cis-3, and 1.52 g of a mixture of isomers in an approximately 1:1 ratio (71% total isolated yield).

Perfluoro-3-ethyl-1,2,3,10b-tetrahydrofluoranthene (Figure 4)

Trans-isomer. Colorless liquid. ¹⁹F NMR (376.5 MHz, CDCl₃): δ −79.0 (m, 3F, CF₃), −110.9 (dm, 1F_A2, CF₂-2) and −121.5 (dm, 1F_B2, CF₂-2), −115.6 (dm, 1F_A3, CF₂CF₃) and −116.7 (dm, 1F_B3, CF₂CF₃), −120.3 (dm, 1F_A1, CF₂-1) and −131.5 (ddm, 1F_B1, CF₂-1), −120.8 (ddd, 1F, F-6), −124.1 (m, 1F, F-4), −132.9 (dddd, 1F, F-7), −133.5 (dddd, 1F, F-10), −145.5 (dddd, 1F, F-8), −146.7 (ddd, 1F, F-5), −149.7 (ddd, 1F, F-9), −157.9 (m, 1F, F-10b), −168.6 (m, 1F, F-3); J_A1,B1 = 261, J_A2,B2 = 278, J_A3,B3 = 290, J_B1,10 = 42, J_4,5 = 17, J_4,6 = 16, J_5,6 = 19, J_5,10b = 4, J_6,7 = 59, J_7,8 = 20, J_7,9 = 5, J_7,10 = 15, J_8,9 = 18, J_8,10 = 8, J_8,10b = 4, J_9,10 = 21.

¹³C NMR (150.92 MHz, CDCl₃): δ 151.4 (dd, ¹J_CF = 273, ²J_CF = 13.5) and 148.5 (dd, ¹J_CF = 272, ²J_CF = 13, C-4, C-10), 145.9 (dd, ¹J_CF = 262, ²J_CF = 12.5) and 142.7 (dd, ¹J_CF = 261, ²J_CF = 13, C-6, C-7), 144.9 (dt, ¹J_CF = 262, ²J_CF = 15.5) and 144.7 (dt, ¹J_CF = 261, ²J_CF = 14.5, C-5, C-8), 142.1 (dt, ¹J_CF = 262, ²J_CF = 14.5, C-9), 131.0 (dm, ²J_CF ~ 15, C-3a¹), 120.5 (d, ²J_CF = 14.5) and 119.7 (d, ²J_CF = 15.5, C-6a, C-6b), 117.9 (qt, ¹J_CF = 288, ²J_CF = 34, CF₃), 117.0 (t, ²J_CF = 18, C-10a), ~112.6 (m, C-3a), ~108.7–113.5 (m, C-1, C-2, CF₂CF₃), 92.6 (dtdd, ¹J_CF = 218, ²J_CF = 29, ²J_CF = 29, ²J_CF = 22, C-3), 92.4 (ddd, ¹J_CF = 200, ²J_CF = 35, ²J_CF = 25, C-10b).

HRMS (EI) m/z: calcd. for C₁₈F₁₈ 557.9707; found 557.9712.

Cis-isomer. Colorless liquid. ¹⁹F NMR (376.5 MHz, CDCl₃): δ −79.4 (m, 3F, CF₃), −112.9 (dm, 1F_A, CF₂-2) and −121.7 (dm, 1F_B, CF₂-2), −114.0 (dm, 1F_A, CF₂CF₃) and −117.4 (dm, 1F_B, CF₂CF₃), −118.8 (dm, 1F_A, CF₂-1) and −124.2 (ddm, 1F_B, CF₂-1), −120.0 (m, 1F, F-4), −120.2 (ddd, 1F, F-6), −132.7 (dddd, 1F, F-7), −134.0 (dddd, 1F, F-10), −145.9 (dddd, 1F, F-8), −146.1 (ddd, 1F, F-5), −149.7 (ddd, 1F, F-9), −152.3 (m, 1F, F-3), −153.5 (m, 1F, F-10b); J_A1,B1 = 259, J_A2,B2 = 275, J_A,B(CF2CF3) = 293, J_B1,10 = 39, J_4,5 = 16.5, J_4,6 = 17, J_5,6 = 20, J_5,10b = 4, J_6,7 = 59, J_7,8 = 21, J_7,9 = 5, J_7,10 = 15, J_8,9 = 17, J_8,10 = 8, J_8,10b = 4, J_9,10 = 20.5.

¹³C NMR (150.92 MHz, CDCl₃): δ 150.4 (dd, ¹J_CF = 274, ²J_CF = 14) and 148.6 (dd, ¹J_CF = 273, ²J_CF = 12.5, C-4, C-10), 145.5 (dd, ¹J_CF = 262, ²J_CF = 13) and 142.7 (dd, ¹J_CF = 261, ²J_CF = 13.5, C-6, C-7), 144.9 (dt, ¹J_CF = 262, ²J_CF = 16.5) and 144.6 (dt, ¹J_CF = 261, ²J_CF = 15, C-5, C-8), 142.2 (dt, ¹J_CF = 261, ²J_CF = 14.5, C-9), 132.8 (d, ²J_CF = 16, C-3a¹), 121.5 (d, ²J_CF = 14.5) and 119.4 (d, ²J_CF = 15.5, C-6a, C-6b), 118.0 (qt, ¹J_CF = 289, ²J_CF = 34, CF₃), 117.4 (t, ²J_CF = 17.5, C-10a), ~108.5–114.3 (m, C-1, C-2, CF₂CF₃), ~112.3 (m, C-3a), 92.9 (ddd, ¹J_CF = 200, ²J_CF = 35.5, ²J_CF = 25.5, C-10b), 90.7 (dtt, ¹J_CF = 215, ²J_CF ~ 27, ²J_CF ~ 27, C-3).

HRMS (EI) m/z: calcd. for C₁₈F₁₈ 557.9707; found 557.9706.