Received: August 2017
Synthesis of Sterically Hindered Fluorous Aryl Perfluoroalkyl Sulfides
Antal Harsányi, Gitta Schlosser and József Rábai*
Institute of Chemistry, Eötvös Loránd University, Pázmány Péter sétány 1-A, Budapest, H-1117, Hungary
Abstract: The sodium salt of 2,6-dimethyl-4-tert-butyl-benzenethiol was reacted in dimethyl formamide with a series of perfluoroalkyl iodides and 1,8-diiodoperfluorooctane to afford the corresponding perfluoroalkyl sulfides and 1,8-bis(arylthio)perfluorooctane in good yields.
Keywords: fluorous sulfides, perfluoroalkyl iodides, perfluoroalkylation
Inspired by the introduction of FluoleadTM by Umemoto et al.  as a novel fluorinating reagent and with the early publication on the preparation of some aryl(trifluoromethyl)difluorosulfuranes by Yagupolskii et al.  we aimed at to synthesize ArSF2Rfn type sulfuranes (4) (Scheme 1).
Such perfluoroalkyl substituted reagents are expected to have unique physical-chemical properties similar to that of fluorocarbons and allowing easy separation of used reagents from products .
Here we disclose the optimized synthesis of precursor aryl perfluoroalkyl sulfides (3a-e) based on spontaneous perfluoroalkylation of thiols without initiators under similar conditions that reported for simple thiols by Feiring and Boiko (Scheme 1).
Scheme 1. Planned synthesis of novel fluorous aryl perfluoroalkyl difluorosulfuranes 4.
Sterically hindered aryl perfluoroalkyl sulfides 3a-e were prepared in good to excellent isolated yields using the reaction of the sodium salt of 1 with a slight excess of 1-iodoperfluoroalkanes (RfnI, 2a-d) or with that of 1,8-diiodoperfluorooctane (2e) in absolute DMF at room temperature for 20 to 40 h. The purified new fluorous sulfides 3a-e were appropriately characterized. It is worth to mention that mass spectrometric measurements by APCI technique were highly facilitated by using a 1:1 vol/vol solvent mixture of CH3CN and CF3CH2OH for sample preparation. The synthesis of the analogue trifluoromethyl sulfide (Rfn = CF3) was effected by using CF3I dissolved in DMF as a perfluoroalkylating reagent and reported earlier by us .
Our attempts for oxidative fluorination of 3 to 4 (Rfn = CF3) with the use of Br2/KF/CH2Cl2 and some other reagent systems however has not succeeded yet .
1H-, 13C- and 19F-NMR spectra were recorded on Bruker Avance 250 instrument using a 5 mm inverse 1H/13C/31P/19F probe head at room temperature. Chemical shifts (δ) are given in parts per million (ppm) units relatively solvent (CDCl3) residual peaks (δ=7.26 for 1H, δ=77.0 for 13C) and to CFCl3 as external standard (δ=0.00 for 19F). Determination of molecular mass was performed by atmospheric pressure chemical ionization mass spectrometry (APCI-MS) on a Bruker Daltonics Esquire 3000 plus (Germany) ion trap mass spectrometer. Samples were dissolved in acetonitrile – trifluoroethanol solvent mixture (50:50, V/V). Mass spectra were acquired in the 50-1500 m/z range yielding singly charged radical cations (M•+). Nebulizer gas pressure was 25 psi, drying gas flow was 5 L/min, the heated capillary temperature was 250 oC and the vaporizer temperature was 450 oC. Samples were injected into the ion source in a flow rate of 10 L/min using a syringe pump. Melting points were determined on a Böetius micro-melting point apparatus and are uncorrected. Gas chromatographic analysis of volatile products was performed using a Hewlett-Packard 5890 Series II instrument with PONA [crosslinked methylsilicone gum] 50 m x 0.2mm x 0.5 mm column, H2 carrier gas, FID detection; Program: 120 °C, 5 min, 10 °C/min, 250 °C, 5 min, Inj.: 250°C, Det.: 280°C.
General Procedure for the Synthesis of Aryl Perfluoroalkyl Sulfides (GP) 
4-(tert-Butyl)-2,6-dimethylbenzenethiol  (1.93 g, 10 mmol) was suspended in absolute DMF (15 mL) and reacted with sodium hydride (11 mmol) in small portions, prepared by washing under an argon atmosphere a 57% w/w sodium hydride – white oil dispersion with pentane (3 x 5 mL). When the evolution of hydrogen ceased the perfluoroalkyl iodide (2a-d, CnF2n+1I, [n=4,6,8,10], 11.0 mmol) or 1,8-diiodoperfluorooctane (2e, I(CF2)8I, 5.50 mmol) was added and the mixture was stirred at room temperature for 20 h (3a-c) or 40 h (3d-e) under an N2 atmosphere. Then the reaction mixture was poured into water (100 mL) and extracted with diethyl ether (3 x 20 mL), the combined organic extracts were washed with water (3 x 20 mL) and saturated aq-NaCl solution (20 mL). The ether phase was separated and dried (Na2SO4), then the ether was removed by distillation and the product was purified by vacuum distillation or crystallization.
Yield: 2.90 g (71 %) colourless liquid, obtained by short path distillation; 20 Hgmm@160°C bath. It solidifies
in the freezer. GC assay: 98%+, tRET: 14.47 min. 1H NMR (250 MHz, CDCl3):
δ 1.33 (s, 9H, C(CH3)3), 2.57 (s, 6H, CH3), 7.22 (s, 2H, Ar CH).
13C NMR (62.5 MHz, CDCl3): δ 22.88, 31.43, 34.97, 118.81, 126.34, 145.98, 154.82.
19F NMR (243 MHz, CDCl3): δ -81,50 (m, 3F, CF3),
-85,96 (m, 2F, CF2), -121,29 (m, 2F, CF2), -126,01 (m, 2F, CF2). MS (APCI, M•+): calcd. for C16H17F9S = 412.1; measured: 412.0.
Yield: 3.50 g (68 %) white waxy solid with mp = 32-34 oC, obtained by short path distillation; 20 Hgmm@170°C bath. GC assay: 98%, tRET: 15.90 min. 1H NMR (250 MHz, CDCl3): δ 1.32 (s, 9H, C(CH3)3), 2.56 (s, 6H, CH3), 7.21 (s, 2H, Ar CH). 13C NMR (62.5 MHz, CDCl3): δ 22.89, 31.44, 34.97, 118.81, 126.34, 145.99, 154.82. 19F NMR (243 MHz, CDCl3): δ -81.33 (m, 3F, CF3), -85.74 (m, 2F, CF2), -120.38 (m, 2F, CF2), -121.85 (m, 2F, CF2), -123.28 (m, 2F, CF2), -126.63 (m, 2F, CF2). MS (APCI, M•+): calcd. for C18H17F13S = 512.1; measured: 511.9.
Yield: 5.30 g (86 %) white crystals with mp = 53-54 oC, obtained by short path distillation; 0.5 Hgmm@120°C bath. GC assay: 98%, tRET: 17.31 min. 1H NMR (250 MHz, CDCl3): δ 1.31 (s, 9H, C(CH3)3), 2.55 (s, 6H, CH3), 7.20 (s, 2H, Ar CH). 13C NMR (62.5 MHz, CDCl3): δ 22.90, 31.45, 34.98, 118.82, 126.34, 145.98, 154.81. 19F NMR (243 MHz, CDCl3): δ -81.28 (m, 3F, CF3), -85.72 (m, 2F, CF2), -120.33 (m, 2F, CF2), -121.65 (m, 2F, CF2), -122.35 (m, 4F, CF2), -123.24 (m, 2F, CF2), -126.62 (m, 2F, CF2). MS (APCI, M•+): calcd. for C20H17F17S = 612.1; measured: 611.8.
Yield: 5.70 g (76 %) white crystals with mp = 72-75 oC, obtained by short path distillation; 0.5 Hgmm@140°C bath. 1H NMR (250 MHz, CDCl3): δ 1.31 (s, 9H, C(CH3)3), 2.55 (s, 6H, CH3), 7.20 (s, 2H, Ar CH). 13C NMR (62,5 MHz, CDCl3): δ 22.90, 31.46, 34.98, 118.82, 126.33, 145.97, 154.81. 19F NMR (243 MHz, CDCl3): δ -81.26 (m, 3F, CF3), -85.72 (m, 2F, CF2), -120.33 (m, 2F, CF2), -121.64 (m, 2F, CF2), -122.24 (m, 8F, CF2), -123.20 (m, 2F, CF2), -126.58 (m, 2F, CF2). MS (APCI, M•+): calcd. for C22H17F21S = 712.1; measured: 711.8.
The crude product was recrystallization from acetone (15 mL). Yield: 2.80 g (50 %) white crystals with mp = 100-101 oC. 1H NMR (250 MHz, CDCl3): δ = 1.32 (s, 9H, C(CH3)3), 2.56 (s, 6H, CH3), 7.21 (s, 2H, Ar CH). 13C NMR (62.5 MHz, CDCl3): δ = 22.90; 31.45; 34.98; 118.82; 126.34; 145.98; 154.81. 19F NMR (243 MHz, CDCl3): δ = -85.67 (m, 4F, CF2), 120.31 (m, 4F, CF2), -121.62 (m, 4F, CF2), -122.22 (m, 4F, CF2). MS (APCI, M•+): calcd. for C32H34F16S2 = 786.2; measured: 786.0.
We thank the National Research, Development and Innovation Office for the financial support of the M-ERA.Net COR_ID program (NKFIH NN117633). G. S. acknowledges the support by the MTA János Bolyai Research Scholarship and by the MTA Premium Post-Doctorate Research Program of the Hungarian Academy of Sciences (HAS, MTA).
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- Unpublished results of PhD student Mr. Bálint Menczinger, Institute of Chemistry, Eötvös Loránd University, Budapest.
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Recommended for publication by Prof. József Rábai