Synthesis of Polyfluorinated Thia- and Oxathiacalixarenes Based on Perfluoro-m-xylene

Abstract

Perfluorinated tetrathiacalix[4]arene was obtained by heating perfluoro-m-xylene with thiourea or 2,5-difluoro-4,6-bis(trifluoromethyl)benzene-1,3-dithiol at 90 °C. Interaction of perfluoro-m-xylene with resorcinol or orcinol under mild conditions and subsequent heating of the mixture with 2,5-difluoro-4,6-bis(trifluoromethyl)benzene-1,3-dithiol leads to polyfluorinated dioxadithiacalix[4]arenes. Triphenyl and pentaphenyl ethers formed by the interaction of perfluoro-m-xylene with resorcinol under heating with thiourea gives polyfluorinated oxathiacalixarenes containing six and five aromatic nuclei, respectively.

1. Introduction

Thiacalixarenes are one of the widely used platforms in supramolecular chemistry; this is due to their unique ability for complex formation with various metal cations [1,2]. Thiacalixarenes are used to create sensors [1,3,4], catalysts [5,6], molecular magnets [7], and luminescent materials [1,8]. This widespread usage of thiacalixarenes is due to a fairly simple synthesis method based on the interaction of phenols with sulfur in the presence of NaOH [1,9]. Other synthesis methods are based on the aromatic nucleophilic substitution reactions in 1,3-dihalogenarenes or hetarenes [10,11,12,13,14,15]. Sodium sulphide [10] or sodium hydrosulphide [11], plus dithioresorcinol [12,13,14,15], can be used as the S-nucleophile in these reactions, which leads to the formation of thiacalixarenes containing several (n ≥ 3) identical aromatic (heteroaromatic) rings, as well as macrocycles with alternating acceptor and donor arenes.

We have previously shown that the interaction of polyfluoroaromatic compounds (perfluoro-m-xylene, pentafluorobenzonitrile and pentafluoronitrobenzene) with various resorcins and bisphenols leads to the formation of polyfluorinated tetraoxacalixarenes with a good yield [16,17,18,19]. Interest in fluorinated tetraoxacalixarenes is associated with a fairly high electron-deficiency of polyfluorinated aromatic nuclei in these compounds, which may increase their ability with regard to host–guest intermolecular interactions.

In this paper, the possibility of polyfluorinated thia- and oxathiacalixarenes synthesis based on the reactions of perfluoro-m-xylene with thiourea and 2,5-difluoro-4,6-bis(trifluoromethyl)benzene-1,3-dithiol was investigated. This is of interest for studying the possibility of the polyfluorinated thia- and oxathiacalixarenes complexation with various metal cations, since the bridged sulfur atoms in thiacalixarenes can directly coordinate with metal ions [1].

2. Results and Discussion

Earlier in the work of Tatlow [20], it has been shown that the interaction of polyfluorinated aromatic compounds with thiourea, under mild conditions, is a convenient method for the synthesis of diaryl sulphides, but in the case of perfluoro-m-xylene, polymerization of the latter was observed. It should be noted that the composition of the oligomeric mixture in this reaction has not been studied. It may be assumed that linear oligomers with a low polymerization depth will form predominantly in this reaction under mild conditions with a sufficiently high concentration of the initial perfluoro-m-xylene. We performed this reaction under conditions favored by cyclo-oligomerization. Indeed, when a mixture of perfluoro-m-xylene with an excess of thiourea is heated at 80–90 °C in a diluted (c~0.08 mol/L) DMF solution, perfluorinated tetrathiacalix[4]arene 1 is formed as the main product (Scheme 1).

It is assumed that the interaction of polyfluoroaromatic compounds with thiourea proceeds through the intermediate formation of an isothiouronium derivative of type 2, which then acts as an ArS⁻ equivalent in the reaction with polyfluoroarene, giving diaryl sulphides or linear oligomers as the products [20,21]. Subsequent oligomerization in the case of perfluoro-m-xylene leads to the intermediate formation of isothiouronium 3 macrocyclization of which gives tetrathiacalixarene 1 (Scheme 1).

We also obtained tetrathiacalix[4]arene 1 by interaction of perfluoro-m-xylene with dithiol 4 (Scheme 1). The latter was synthesized by us from perfluoro-m-xylene via intermediate formation of bis(benzylthio)benzene 5 according to Scheme 2. The standard deprotection method [22] in compound 5, due to the presence of acceptor substituents, does not lead to the formation of dithiol 4. Therefore, based on studies of the reactivity of polyfluorinated arenthiols [23], for deprotection of the thiobenzyl group in compound 5, it was proposed to use chlorination by SO₂Cl₂, hydrolysis and subsequent reduction by Zn of the resulting product mixture.

We have previously shown that the reaction of perfluoro-m-xylene with resorcinol under mild conditions led to the formation of a mixture of polyphenyl ethers with a predominant content of triphenyl ether [17]. Further heating of this mixture with resorcinol or tetrafluororesorcinol gave polyfluorinated oxacalixarenes of the ABAB or ABAC type. The same approach was used in the reactions of pentafluorobenzonitrile and pentafluoronitrobenzene with various resorcinoles [18,19], and the synthesis was also performed without intermediate isolation of triphenyl ethers. We used this approach for the synthesis of dioxadithiacalix[4]arenes. Thus, the interaction of two equivalents of perfluoro-m-xylene with the equivalent of resorcinol or orcinol under mild conditions and subsequent heating of the reaction mixtures with the equivalent of dithioresorcinol 4 leads to the formation of polyfluorinated dioxadithiacalix[4]arenes 8, 9 with a good yield (Scheme 3).

At the same time, the interaction of triphenyl ether 6 with thiourea leads to tetraoxadithiacalix[6]arene 12 and dioxadithiacalix[4]arene 8 as the main and minor products, respectively (Scheme 4). The intermediate isothiouronium derivative 10 formed in this reaction then reacts successively with another equivalent of triphenyl ether 6 and thiourea giving another isothiouronium derivative 11. Macrocyclization of derivative 11 can take place both on the terminal (main pathway a) and the internal (minor pathway b) perfluoro-m-xylene fragments to form tetraoxadithiacalix[6]arene 12 and dioxadithiacalix[4]arene 8, respectively. Intramolecular cyclization of isothiouronium derivative 10 with the formation of dioxatiacalix[3]arene is unlikely, which can be explained in terms of strain of the intended cycle.

In contrast, the reaction of pentaphenyl ether 13 with thiourea intramolecular macrocyclization of isothiouronium derivative 14 leads to the formation of tetraoxatiacalix[5]arene 15, which is due to a decrease in transannular strain in the cycle (Scheme 5).

The structure of thia- and oxathiacalixarenes 1, 8, 9, 12, 15 was determined based on analytical and ¹H, ¹⁹F, ¹³C NMR data (Supplementary Material Figures S1_F–S13_C). The structure of tetrathiacalixarene 1 was also confirmed by X-ray data.

According to X-ray analysis of the single crystal obtained from CH₂Cl₂, tetrathiacalixarene 1 is in the 1,3-alternate conformation, which is typical for tetrathiacalixarenes that do not have substituents in the inner cycle [13,15,24] (Figure 1a). The sulphur atoms are located in the same plane practically without deviation. The C–S bond length 1.78 Å corresponds to the literature data for tetrathiacalixarenes [15,24]. The C–S–C angles are 100.6–100.7°, and the torsion angles around the C–S bonds are 57.8–60.3°. The sulphur atoms are slightly displaced outside from the planes of the aromatic nucleus, the deviation is 0.12–0.21 Å. The opposite aromatic nuclei are located almost parallel to each other, and the dihedral angles are 2.44° and 4.69°, respectively. It should be noted that the difference in the dihedral angles for the tetrathiacalixarenes described in the literature is significantly higher (2–130°) [15,24]. Crystallization of tetrathiacalixarene 1 from acetone or acetonitrile leads to the formation of complexes including 1 or 2 solvent molecules (Figure 1b). In this case, the dihedral angles between the opposite aromatic nuclei increase to 19.2° and 20.1° (1*2CH₃CN).

One set of three signals in the ¹⁹F NMR spectra (Supplementary Material Figure S3_F) of tetrathiacalixarene 1 without significant broadening in the signal structure at room temperature can indicate both the realization of one symmetric conformation and a very fast conformational interconversion in the NMR time scale. It can be assumed that the presence of fairly large eight-CF₃ groups in the tetrathiacalixarene 1 molecule should shift the equilibrium towards the least sterically hindered 1,3-alternate conformation similar to that determined by the X-ray method for the crystal state. A similar 1,3-alternate conformation was proposed earlier in the analysis of ¹H NMR spectra for solutions of tetrathiacalixarene without substituents in the internal macrocycle [14]. When four volume substituents (OC₂H₅) are introduced, the interconversion becomes difficult, and the equilibrium between all four possible conformations of tetrathiacalixarene according to NMR spectra is fixed [25].

We have previously observed a noticeable upfield shift of the inner-rim hydrogen and fluorine atoms of the resorcinol fragments in the ¹H and ¹⁹F NMR spectra of polyfluorinated tetraoxacalixarenes, which is characteristic for this class of compounds [16,17,18,19]. The value of this upfield shift is solvent dependent, which may be due to implementation of some equilibrium 1,3-alternate conformations characterized by different degrees of magnetic shielding of the inner-rim protons and fluorines of the resorcinol fragments by the neighboring aromatic rings [19].

In the ¹H NMR spectra of dioxadithiacalix[4]arenes 8–9, an upfield shift of the inner-rim protons (H-28) of the resorcinol fragment is also observed, and the value of this shift depends on the solvent (Supplementary Material Figure S5_H). So, the chemical shift of the hydrogen atom H-28 in CDCl₃ is 5.45 ppm for 8 and 5.08 ppm for 9, and in (CD₃)₂CO 6.25 ppm for 8 (Figure 2a) and 6.00 ppm for 9. The presence of an upfield shift of the inner-rim protons in the ¹H NMR spectra indicates that dioxadithiacalix[4]arenes 8–9, as well as tetraoxacalixarenes [26], have a 1,3-alternate conformation in solution. In the ¹H NMR spectra of tetraoxadithiacalix[6]arene 12, a noticeable upfield shift of the inner-rim protons (H-39,42; δ 6.14 ppm in acetone-d₆, Figure 2b) of the resorcinol fragment is also observed, and it is practically absent in the ¹H NMR spectra of tetraoxathiacalixarene 15 (H-33,35; δ 6.92 ppm in acetone-d₆, Figure 2c). For comparison, the chemical shift of the hydrogen atom, located between two perfluorinated phenoxy fragments, in triphenyl ether 6 (H-2; δ 7.10 ppm in acetone-d₆) and pentaphenyl ether 13 (H-2′; δ 7.13 ppm in acetone-d₆, Figure 2d) can be used as reference points. It should be noted that, in contrast to tetraoxadithiacalix[6]arene 12, the ¹H NMR spectra of closely related polyfluorinated hexaoxacalix[6]arenes are lacking for an upfield shift of the inner-rim hydrogen atoms signals [17].

3. Materials and Methods

3.1. General Methods

Thiourea, resorcinol and orcinol monohydrate were obtained from Aldrich (Milwaukee, WI, USA), AppliChem (Darmstadt, Germany) and FluoroChem (Hadfield, UK), respectively, and used directly without further purification. Dimethylformamide and triethylamine were held over NaOH during a week and distilled immediately before use. Perfluoro-m-xylene was a ~3:1 mixture with its para-isomer (according to the ¹⁹F NMR data) which is considerably less reactive [27]. This mixture is a byproduct in the synthesis of octafluorotoluene by interaction of hexafluorobenzene with Teflon chips [28,29].

The ¹⁹F and ¹H NMR spectra were recorded for solutions in CDCl₃ and OC(CD₃)₂ on a Bruker AV300 spectrometer at 282.36 MHz and 300 MHz, respectively, ¹³C NMR spectra were recorded on a Bruker AV-400 instrument (100.6 MHz). Chemical shifts are given in δ ppm from CCl₃F (¹⁹F) and TMS (¹H, ¹³C), J values in Hz; C₆F₆ (−162.9 ppm from CCl₃F), CHCl₃ (7.24 ppm from TMS), OC(CD₃)₂ (2.05 ppm from TMS), OC(CD₃)₂ (29.8 ppm from TMS) were used as internal standards.

The X-ray diffraction experiments for 1 and 1*2CH₃CN were carried out on a Bruker KAPPA APEX II diffractometer with graphite monochromated MoKα (λ = 0.71073 Å) radiation at 296 K. Experimental data reduction was performed using APEX2 suite [30]. The structures were solved by direct methods and refined by the full-matrix least-squares technique against F² in the anisotropic-isotropic approximation. The H atom positions in 1*2CH₃CN were calculated with the riding model. All calculations were performed using SHELXL-2018/3 [31]. All CF₃ groups in crystal 1 are disordered over two positions with SOF 0.21–0.74 and some restrictions were applied.

Gas chromatographic–mass spectrometric analysis (GC–MS) was performed on a Hewlett Packard HP 5890 Series II chromatograph coupled with an HP 5971 mass-selective detector (HP-5MS capillary column, 30 m × 0.25 mm, film thickness 0.25 μm; carrier gas helium, flow rate 1 mL/min; oven temperature programming from 50 °C (2 min) to 280 °C at a rate of 10 °/min and finally 5 min at 280 °C; injector temperature 280 °C; ion source temperature 175 °C; electron impact, 70 eV; 1.2 scan/s, a.m.u. range 30–650). HPLC analysis was performed on a Milichrome-A-02 (Econova, Novosibirsk, Russia). Column—2.0 × 75 mm with ProntoSIL-120-5-C18 (BISCHOFF Analysentechnik U.—GERÄTE GMBH, Leonberg, Germany). Temperature of column 30 °C. Eluent: methanole/water, gradient from 4:1 to pure methanole (1500 mcl) and then methanole (1500 mcl). The reference wavelength—260 nm.

The elemental compositions of thiacalixarene 1 and oxathiacalixarenes 8, 9, 12, 15, were determined by classical methods and their molecular weights were determined in acetone solution at 40 °C using a Knauer K-7000 osmometer. The elemental compositions of compounds 4, 5, were determined from the high-resolution mass spectra which were recorded on a Thermo Scientific DFS instrument (electron impact, 70 eV).

The progress of reactions was monitored by TLC on Silica gel 60 F254 plates (Merck, Darmstadt, Germany). Silica gel (0.063–0.200 mm; Merck, Darmstadt, Germany) was used for column chromatography.

3.2. Synthesis of 2,5-difluoro-4,6-bis(trifluoromethyl)benzene-1,3-dithiol 4

3.2.1. 1,3-Bis(benzylthio)-2,5-difluoro-4,6-bis(trifluoromethyl)benzene 5

Na₂CO₃ (3.11 g, 10.9 mmol) and 18.82 g (58.3 mmol) benzyl mercaptan was added successively to a stirred solution of 10.04 g of a mixture of perfluorinated m- and p-xylenes (~26.3 mmol of the meta-isomer) in 80 mL of dimethylformamide. The solution was stirred for 18 h at 5–10 °C, and then poured into 160 mL of 10% aqueous HCl solution. The precipitate was filtered out and dried over CaCl₂. Solid product (12.51 g) contained 85% of dithiol 4, according to HPLC data. Analytical sample was obtained by crystallization from hexane. Mp 62.3–63.7 °C. ¹⁹F NMR (CDCl₃): δ −116.0 (septet d, 1F, J = 36 Hz, J = 15 Hz, F-5), −93.6 (d, 1F, J = 15 Hz, F-2), −55.5 (d, 6F, J = 36 Hz, 2CF₃). ¹H NMR (CDCl₃): δ 4.10 (s, 2H, CH₂), 7.15–7.28 (m, 5H, C₆H₅). Anal. Calcd for C₂₂H₁₄F₈S₂: C 53.44; H 2.85; F 30.74; S 12.97%. Found: C 53.85; H 2.79; F 31.18; S 12.80. HRMS m/z: 494.0403 (M⁺). Calculated: M = 494.0404.

3.2.2. 2,5-Difluoro-4,6-bis(trifluoromethyl)benzene-1,3-dithiol 4

Compound 5 (11.12 g, 19.1 mmol, technical product with an 85% content) and SO₂Cl₂ (7.52 g, 55.7 mmol) were placed in a glass ampoule. The ampoule was sealed and heated in a metal casing for 16 h at 100–110 °C. The reaction mixture was cooled and poured into 200 mL of water, then 10 mL EtOAc, 40 mL CHCl₃ and 9.41 g (88.8 mmol) Na₂SO₃ were added. After stirring, the organic layer was washed with water (2 × 200 mL) and the solvents were evaporated. The oily product was dissolved in 70 mL of glacial acetic acid, and then Zn (12.62 g, 192.9 mmol) was added by small portions and stirred for 24 h at 20 °C. The reaction mixture was treated by 60 mL of 10% aqueous HCl solution, and the product was extracted with CHCl₃ (3 × 25mL) and additionally with EtOAc (3 × 15 mL). The solvents were evaporated, and the product was distilled with steam. Two fractions were obtained: solid (3.51 g) and liquid (1.18 g) with a dithiol 4 content of 87% and 52%, respectively (GC–MS). Pure dithiol 4 (1.86 g, 51% with 98% content according to GC–MS) was obtained by crystallization of solid fraction from hexane. Mp 66.4–67.2 °C. ¹⁹F NMR (CDCl₃): δ −115.7 (septet d, 1F, J = 27 Hz, J = 15 Hz, F-5), −103.6 (m, 1F, F-2), −57.1 (dd, 6F, J = 27 Hz, J = 8 Hz, 2CF₃). ¹H NMR (CDCl₃): δ 4.36 (quintet, 2H, J = 9.7 Hz, SH). ¹³C NMR (CDCl₃): δ 113.5 (qdd, ²J_CF = 33.6 Hz, ²J_CF = 15.8 Hz, J_CF = 1.7 Hz, C–CF₃), 122.2 (qdd, ¹J_CF= 275.6 Hz, J_CF = 2.3 Hz, J_CF = 1.5 Hz, CF₃), 127.8 (dd, ²J_CF = 28.1 Hz, J_CF = 3.2 Hz C-SH), 147.9 (dd, ¹J_CF= 231.0 Hz, J_CF = 3.7 Hz C-F), 155.4 (dm, ¹J_CF= 266.9 Hz, C–F). Anal. Calcd for C₈H₂F₈S₂: C 30.58; H 0.64; F 48.37; S 20.41%. Found: C 30.16; H 0.51; F 48.33; S 20.05. HRMS m/z: 313.9472 (M⁺). Calculated M = 313.9465.

3.3. Synthesis of Polyfluorinated Triphenyl and Pentaphenyl Ethers 6, 13

Solution of trimethylamine (1.60 g, 16 mmol) and resorcinol (0.36 g, 3.3 mmol) in 10 mL of acetone was added dropwise to a stirred solution of 2.20 g of a mixture of perfluorinated m- and p-xylenes (~6 mmol of the meta-isomer) in 15 mL of acetone. The solution was stirred for 20 h at 20 °C, and solvent was evaporated. Column chromatography (eluents petroleum ether (40–70 °C)/CCl₄ 1:2, 1:3, 1:5) on silica gel gave 1.16 g (1.8 mmol, 60%) of triphenyl ether 6, 0.45 g (0.45 mmol, 27%) of pentaphenyl ether 13 and 0.17 g of polyphenyl ethers.

3.3.1. 1,3-Bis[3,5,6-trifluoro-2,4-bis(trifluoromethyl)phenoxy]benzene 6:

Viscous oil ¹⁹F NMR (OC(CD₃)₂): δ −149.8 (dd, 2F, F-6′), −126.6 (qd, 2F, F-5′), −115.7 (m, 2F, F-3′), −55.4 (t, 6F, 2CF₃), −55.3 (d, 6F, 2CF₃). ¹H NMR (OC(CD₃)₂): δ 6.97 (dd, 2H, H-4,6), 7.10 (t, H, H-2), 7.41 (t, H, H-5). GC–MS, m/z: 642 (M⁺).

The ¹H and ¹⁹F NMR spectra and the mass spectrum of triphenyl ether 6 coincide with the product data obtained from [17].

3.3.2. 1,3-Bis{3-[3,5,6-trifluoro-2,4-bis(trifluoromethyl)phenoxy]phenoxy}-2,5-difluoro-4,6-bis(trifluoromethyl)benzene 13:

Viscous oil ¹⁹F NMR (OC(CD₃)₂): δ −149.6 (dd, 2F, J = 20 Hz, J = 11 Hz, F-6′), −138.9 (d, 1F, J = 12 Hz, F-2), −126.6 (qd, 2F, J = 23 Hz, J = 20 Hz, F-5′), −115.6 (qqd, 2F, J = 28 Hz, J = 23 Hz, J = 11 Hz, F-3′), −115.2 (septet d, 1F, J = 28 Hz, J = 12 Hz, F-5), −55.5 (t, 6F, J = 23 Hz, 2CF₃), −55.4 (d, 6F, J = 28 Hz, 2CF₃), −55.3 (d, 6F, J = 28 Hz, 2CF₃). ¹H NMR (OC(CD₃)₂): δ 6.94 (dd, 2H, J = 8.2 Hz, J = 2.1 Hz, H-4′), 7.01 (dd, 2H, J = 8.4 Hz, J = 2.1 Hz, H-6′), 7.13 (t, 2H, J = 2.1 Hz, H-2′), 7.39 (t, 2H, J = 8.3 Hz, H-5′). GC–MS, m/z: 499 (M⁺⁺, M 998).

3.4. Synthesis of Tetrathiacalixarene 1

Method A: Thiourea (0.60 g, 8 mmol) was added to a stirred solution of 1.60 g of a mixture of perfluorinated m- and p-xylenes (~4.1 mmol of the meta-isomer) in 50 mL of dimethylformamide. The solution was stirred for 3 h at 20 °C and 5 h at 90 °C, and then the solvent was evaporated in vacuum. By column chromatography on silica gel using mixture (3:1) CCl₄ and CHCl₃ as eluent 1.20 g of the solid product was isolated, double-play crystallization of which from CCl₄ gave 0.64 g of tetrathiacalixarene 1.

Method B: Triethylamine (0.80 g, 8 mmol) was added to a stirred solution of 0.35 g (1.1 mmol) of dithioresorcinol 4 and 0.80 g of a mixture of perfluorinated m- and p-xylenes (~2 mmol of the meta-isomer) in 70 mL of dimethylformamide. The mixture was stirred for 17 h at room temperature and 30 min at 90 °C then 0.30 g (1 mmol) of dithioresorcinol 4 was introduced and stirred for 20 h at 90 °C. The mixture after evaporation of solvent was treated with 80 mL of ~5% aqueous HCl and then with methylene chloride (3 × 50 mL). The extract was dried over Na₂SO₄, and evaporation gave 2.30 g of a viscous material. By column chromatography on silica gel using CCl₄ and CHCl₃ as eluents, 0.68 g of the solid product containing (GC–MS) 93% tetrathiacalixarene 1 was isolated.

5,11,17,23,25,26,27,28-Octafluoro-4,6,10,12,16,18,22,24-octakis(trifluoromethyl)-2,8,14,20-tetrathiapentacyclo[19.3.1.1^3,7.1^9,13.1^15,19]octacosa-1(25),3(28),4,6,9(27),10,12,15(26),16,18,21,23-dodecaene 1:

White solid (0.64 g, 57%). mp 304.6–304.9 °C. ¹⁹F NMR ((CD₃)₂CO): δ −112.1 (septet d, 4F, J_{F(5)-2CF3(4,6)} = 33 Hz, J_F(5)-F(28) = 15 Hz, F-5,11,17,23), −91.6 (m, 4F, F-25,26,27,28), −53.5 (dd, 24F, J_CF3(4)-F(5) = 33 Hz, J_CF3(4)-F(28) = 7 Hz, CF₃(4,6,10,12,16,18,22,24)). ¹³C NMR ((CD₃)₂CO): δ 122.3 (qd, ²J_CF = 32.5 Hz, ²J_CF = 14.0 Hz, C–CF₃), 122.5 (q, ¹J_CF = 276.0 Hz, CF₃), 127.7 (d, ²J_CF = 25.9 Hz, C–S), 155.3 (d, ¹J_CF = 269.8 Hz, C–F), 158.5 (dd, ¹J_CF = 244.2 Hz, J_CF = 3.0 Hz, C–F). Anal. Calcd for C₃₂F₃₂S₄: C, 34.30; F, 54.25; S, 11.44%; M 1120. Found: C, 34.00; F, 54.37; S, 11.48%; M 1120.

Crystal data of 1: C₃₂F₃₂S₄, M = 1120.56, monoclinic, space group P2₁/c, a = 12.5563(14), b = 15.9119(18), c = 18.7987(18) Å, β = 96.635(4)°, V = 3730.7(7) ų, Z = 4, d_calc = 1.995 g·cm⁻³, μ = 0.444 mm⁻¹, a total of 67,724 (θ_max = 27.58°), 8648 unique (R_int = 0.0541), 6093 [I > 2σ(I)], 837 parameters. GooF = 1.02, R₁ = 0.0399, wR₂ = 0.0938 [I > 2σ(I)], R₁ = 0.0680, wR₂ = 0.1136 (all data), max/min diff. peak 0.280/−0.233 e Å⁻³.

Crystal data of 1*2CH₃CN: C₃₂F₃₂S₄+2(CH₃CN), M = 1202.67, triclinic, space group P-1, a = 10.1087(6), b = 10.1752(6), c = 20.9515(10) Å, α = 82.318(2), β = 81.616(2), γ = 82.275(3)°, V = 2098.3(2) ų, Z = 2, d_calc = 1.904 g·cm⁻³, μ = 0.403 mm⁻¹, a total of 67,731 (θ_max = 28.01°), 10,126 unique (R_int = 0.0435), 7405 [I > 2σ(I)], 669 parameters. GooF = 1.04, R₁ = 0.0550, wR₂ = 0.1488 [I > 2σ(I)], R₁ = 0.0784, wR₂ = 0.1726 (all data), max/min diff. peak 0.810/−0.447 e·Å⁻³.

3.5. General Procedure for the Synthesis of Dioxadithiacalixarenes 8, 9

Solution of trimethylamine (1.20 g, 12 mmol) and resorcinol (orcinol monohydrate) (2 mmol) in 10 mL of dimethylformamide was added dropwise to a stirred solution of 1.50 g of a mixture of perfluorinated m- and p-xylenes (~4 mmol of the meta-isomer) in 40 mL of dimethylformamide. The solution was stirred for 3 h at 20 °C and 30 min at 90 °C, then 0.63 g (2 mmol) of dithioresorcinol 4 was introduced and the mixture was stirred for 3 h at 90 °C. The solvent was evaporated in vacuum, and by column chromatography on silica gel using CCl₄ as eluent, the solid product was isolated. Pure dioxadithiacalixarenes 8, 9, were obtained by crystallization of the solid product from CCl₄.

3.5.1. 11,17,23,25,26,27-Hexafluoro-10,12,16,18,22,24-hexakis(trifluoromethyl)-2,8-dioxa-14,20-dithiapentacyclo[19.3.1.1^3,7.1^9,13.1^15,19]octacosa-1(25),3(28),4,6,9(27),10,12,15(26),16,18,21,23-dodecaene 8:

White solid (1.17 g), containing according ¹⁹F NMR data dioxadithiacalixarene 8 and tetrathiacalixarene 1 (94:6). mp 225–231 °C. ¹⁹F NMR (CDCl₃): δ −119.5 (dq, 2F, J_F(25)-F(23) = 14 Hz, J_{F(25)-CF3(22)} = 6 Hz, F-25,27), −112.8 (qqd, 2F, J_{F(11)-CF3(12)} = 35 Hz, J_{F(11)-CF3(10)} = 28 Hz, J_F(11)-F(27) = 14 Hz, F-11,23), −112.2 (septet d, 1F, J_{F(17)-2CF3(16,18)} = 36 Hz, J_F(17)-F(26) = 15 Hz, F-11,23), −96.6 (dm, 1F, J_F(26)-F(17) = 15 Hz, F-26), −58.0 (d, 6F, J_{CF3(10)-F(11)} = 28 Hz, CF₃(10,24)), −55.3 (dd, 6F, J_{CF3(12)-F(11)} = 36 Hz, J_{CF3(12)-F(27)} = 6 Hz, CF₃(12,22)), −55.1 (dd, 6F, J_{CF3(16)-F(17)} = 36 Hz, J_{CF3(16)-F(26)} = 4 Hz, CF₃(16,18)). ¹⁹F NMR (OC(CD₃)₂): δ −118.5 (dq, 2F, F-25,27), −113.9 (qqd, 2F, F-11,23), −111.7 (septet d, 1F, F-11,23), −92.6 (dm, 1F, F-26), −55.6 (d, 6F, CF₃(10,24)), −53.1 (dd, 6F, CF₃(12,22)), −52.7 (dd, 6F, CF₃(16,18)). ¹H NMR (CDCl₃): δ 5.45 (m, 1H, H-28), 7.17 (dd, 2H, J = 8.3 Hz, J = 2.2 Hz, H-4,6), 7.56 (t, 1H, J = 8.3 Hz, H-5). ¹H NMR (OC(CD₃)₂): δ 6.25 (m, 1H, H-28), 7.14 (dd, 2H, H-4,6), 7.55 (t, 1H, H-5). Anal. Calcd for C₃₀H₄F₂₄O₂S₂: C, 39.32; H, 0.44; F, 49.75; S, 7.00%; M 916. Found: C, 38.72; H, 0.41; F, 49.91; S, 6.89%; M 911. GC–MS, m/z: 458 (M⁺⁺, M 916).

3.5.2. 11,17,23,25,26,27-Hexafluoro-5-methyl-10,12,16,18,22,24-hexakis(trifluoromethyl)-2,8-dioxa- 14,20-dithiapentacyclo[19.3.1.1^3,7.1^9,13.1^15,19]octacosa-1(25),3(28),4,6,9(27),10,12,15(26),16,18,21,23- dodecaene 9:

White solid (1.02 g, 55%). mp 161–165 °C. ¹⁹F NMR (CDCl₃): δ −119.5 (dq, 2F, J_F(25)-F(23) = 14 Hz, J_{F(25)-CF3(22)} = 6 Hz, F-25,27), −112.9 (qqd, 2F, J_{F(11)-CF3(12)} = 36 Hz, J_{F(11)-CF3(10)} = 28 Hz, J_F(11)-F(27) = 14 Hz, F-11,23), −112.3 (septet d, 1F, J_{F(17)-2CF3(16,18)} = 36 Hz, J_F(17)-F(26) = 15 Hz, F-11,23), −96.6 (dm, 1F, J_F(26)-F(17) = 15 Hz, F-26), −57.9 (d, 6F, J_{CF3(10)-F(11)} = 28 Hz, CF₃(10,24)), −55.3 (dd, 6F, J_{CF3(12)-F(11)} = 36 Hz, J_{CF3(12)-F(27)} = 6 Hz, CF₃(12,22)), −55.1 (dd, 6F, J_{CF3(16)-F(17)} = 36 Hz, J_{CF3(16)-F(26)} = 4 Hz, CF₃(16,18)). ¹⁹F NMR (OC(CD₃)₂): δ −118.4 (dq, 2F, F-25,27), −113.9 (qqd, 2F, F-11,23), −111.6 (septet d, 1F, F-11,23), −92.6 (dm, 1F, F-26), −55.6 (d, 6F, CF₃(10,24)), −53.1 (dd, 6F, CF₃(12,22)), −52.7 (dd, 6F, CF₃(16,18)). ¹H NMR (CDCl₃): δ 2.38 (s, 3H, CH₃), 5.08 (m, 1H, H-28), 6.82 (d, 2H, J_H(4,6)-H(28) = 4 Hz, H-4,6). ¹H NMR (OC(CD₃)₂): δ 2.40 (s, 3H, CH₃), 6.00 (m, 1H, H-28), 6.95 (d, 2H, H-4,6). ¹³C NMR (OC(CD₃)₂): δ 21.2 (C(5)-CH₃), 97.2 (C-28), 114.1 (C-4,6), 116.3 (qd, ²J_CF = 33.0 Hz, ²J_CF = 14.9 Hz, C-CF₃), 116.5 (qd, ²J_CF = 32.5 Hz, ²J_CF = 13.2 Hz, C-CF₃), 121.9 (qd, ²J_CF = 32.4 Hz, ²J_CF = 13.9 Hz, C–CF₃), 122.0 (q, ¹J_CF = 274.9 Hz, CF₃), 122.6 (q, ¹J_CF = 276.4 Hz, CF₃), 122.8 (q, ¹J_CF = 275.8 Hz, CF₃), 127.3 (d, ²J_CF = 24.9 Hz, C–S), 128.4 (d, ²J_CF = 17.4 Hz, C–S), 144.2 (C-5), 144.9 (dd, ²J_CF = 16.7 Hz, J_CF = 5.0 Hz, C(1,9)-0), 152.4 (dd, ¹J_CF = 249.8 Hz, J_CF = 3.7 Hz, C–F), 155.1 (d, ¹J_CF = 267.8 Hz, C–F), 155.4 (d, ¹J_CF = 271.8 Hz, C–F), 158.4 (d, ¹J_CF = 246.9 Hz, C–F), 159.1 (C(3,7)-0). Anal. Calcd for C₃₁H₆F₂₄O₂S₂: C, 40.02; H, 0.65; F, 49.00; S, 6.89%; M 930. Found: C, 40.30; H, 0.98; F, 48.91; S, 6.88%; M 926.

3.6. Synthesis of Tetraoxadithiacalixarene 12

Thiourea (0.76 g, 10 mmol) was added to a stirred solution of 1.27 g (1.9 mmol) of 1,3-bis(2,4-bis(trifluoromethyl)trifluorophenoxy)benzene 6 in 50 mL of dimethylformamide. The solution was stirred for 15 h at 90 °C, and the solvent was evaporated in vacuum. By column chromatography on silica gel using CCl₄ as eluent, 1.32 g of the viscous material containing (GC–MS) 91% tetraoxadithiacalixarene 12 and 5% dioxadithiacalixarene 8 was isolated. Double-play crystallization of viscous material from CCl₄ gave 0.76 g of tetraoxadithiacalixarene 12*CCl₄.

11,17,29,35,37,38,40,41-Octafluoro-10,12,16,18,28,30,34,36-octakis(trifluoromethyl)-2,8,20,26- tetraoxa-14,32-dithiaheptacyclo[31.3.1.1^3,7.1^9,13.1^15,19.1^21,25.1^27,31]dotetraconta-1(37),3(42),4,6,9(41),10,12,15 (40),16,18,21(39),22,24,27(38),28,30,33,35-octadecaene 12:

White solid (0.76 g, 47%). mp 291 °C (decomp.). ¹⁹F NMR (OC(CD₃)₂): δ −117.0 (m, 4F, F-37,38,40,41), −112.4 (m, 4F, F-11,17,29,35), −55.8 (d, 12F, J_{CF3(10)-F(11)} = 26 Hz, CF₃(10,18,28,36)), −53.1 (d, 12F, J_{CF3(12)-F(11)} = 34 Hz, CF₃(12,16,30,34)). ¹H NMR (OC(CD₃)₂): δ 6.14 (m, 2H, H-39,42), 6.85 (dd, 4H, J_H(4)-H(5) = 8.4 Hz, J_H(4)-H(42) = 2.3 Hz, H-4,6,22,24), 7.38 (t, 2H, J_H(5)-H(4,6) = 8.4 Hz, H-5,23). ¹³C NMR (OC(CD₃)₂): δ 102.7 (C-39,42), 111.8 (C-4,6,22,24), 116.5 (qd, ²J_CF = 33.4 Hz, ²J_CF = 15.6 Hz, C–CF₃), 118.3 (qd, ²J_CF = 32.7 Hz, ²J_CF = 13.2 Hz, C–CF₃), 121.8 (q, ¹J_CF = 275.0 Hz, CF₃), 122.8 (q, ¹J_CF = 276.4 Hz, CF₃), 128,7 (d, ²J_CF = 18.5 Hz, C–S), 132.5 (C-5,23), 144.3 (dd, ²J_CF = 17.8 Hz, J_CF = 4.8 Hz, C(1,9,19,27)-0), 152.8 (d, ¹J_CF = 249.1 Hz, C–F), 155.6 (d, ¹J_CF = 268.9 Hz, C–F), 158.7 (C(3,7,21,25)-0). Anal. Calcd for C₄₄H₈F₃₂O₄S₂*CCl₄: C, 37.89; H, 0.57; F, 42.62; Cl, 9.94; S, 4.50%; M 1272. Found: C, 37.80; H, 0.70; F, 42.68; Cl, 9.96; S, 4.79%; M 1272.

3.7. Synthesis of Tetraoxathiacalixarene 15

Thiourea (0.23 g, 3 mmol) was added to a stirred solution of 1.08 g (1.1 mmol) of pentaphenyl ether 13 in 50 mL of dimethylformamide. The solution was stirred for 15 h at 90 °C, and the solvent was evaporated in vacuum. By column chromatography on silica gel using CCl₄ as eluent, 0.99 g of the viscous material containing (GC–MS) 61% tetraoxathiacalixarene 15, 20% pentaphenylether 13, and 17% dimethylformamide was isolated. Double-play crystallization of viscous material from CCl₄ gave 0.36 g of tetraoxathiacalix[5]arene 15.

11,23,29,31,32,34-Hexafluoro-10,12,22,24,28,30-hexakis(trifluoromethyl)-2,8,14,20-tetraoxa-26- thiahexacyclo[25.3.1.1^3,7.1^9,13.1^15,19.1^21,25]pentatriaconta-1(31),3(35),4,6,9(34),10,12,15(33),16,18,21(32),22,24,27,29-pentadecaene 15:

White solid (0.36 g, 33%). mp 194 ^°C (decomp.). ¹⁹F NMR (OC(CD₃)₂): δ −134.2 (d, 1F, J_F(34)-F(11) = 12 Hz, F-34), −116.4 (septet d, 1F, J_{F(11)-CF3(10,12)} = 29 Hz, J_F(11)-F(34) = 12 Hz, F-11), −116.0 (d, 2F, J_F(31)-F(29) = 10 Hz, F-31,32), −113.3 (unresolved m, 2F, F-23,29), −55.9 (d, 6F, J = 27 Hz, 2CF₃), −55.0 (d, 6F, J = 29 Hz, 2CF₃), −53.2 (d, 6F, J = 30 Hz, 2CF₃). ¹H NMR (OC(CD₃)₂): δ 6.92 (m, 1H, H-33,35), 6.94 (dd, 2H, J_H(4)-H(5) = 8.4 Hz, J_H(4)-H(35) = 1.4 Hz, H-4,18), 7.01 (dd, 2H, J_H(6)-H(5) = 8.1 Hz, J_H(6)-H(35) = 1.5 Hz, H-6,16), 7.38 (dd, 2H, J = 8.4 Hz, J = 8.1 Hz, H-5,17). ¹³C NMR (OC(CD₃)₂): δ 105.7 (C-33,35), 109.0 (qd, ²J_CF = 33.1 Hz, ²J_CF = 14.5 Hz, C–CF₃), 112.9 (C-4,18), 113.4 (C-6,16), 116.5 (qd, ²J_CF = 33.1 Hz, ²J_CF = 15.4 Hz, C–CF₃), 118.1 (qd, ²J_CF = 33.1 Hz, ²J_CF = 13.0 Hz, C–CF₃), 121.7 (q, ¹J_CF = 274.4 Hz, CF₃), 121.8 (q, ¹J_CF = 274.0 Hz, CF₃), 122.0 (q, ¹J_CF = 276.0 Hz, CF₃), 126,7 (d, ²J_CF = 20.9 Hz, C–S), 131.3 (C-5,17), 143.7 (dd, ¹J_CF = 254.9 Hz, J_CF = 4.2 Hz, C–F), 144,6 (d, ²J_CF = 16.3 Hz, C–O), 144,7 (d, ²J_CF = 18.0 Hz, C–O), 153.1 (dd, ¹J_CF = 251.3.1 Hz, J_CF = 2.2 Hz, C–F), 154.3 (d, ¹J_CF = 264.8 Hz, C–F), 154.7 (d, ¹J_CF = 267.9 Hz, C–F),157.7 (C-0), 158.4 (C-0). Anal. Calcd for C₃₆H₈F₂₄O₄S: C, 43.57; H, 0.81; F, 45.94; S, 3.23%; M 992. Found: C, 43.30; H, 0.99; F, 45.82; S, 3.30%; M 994.

4. Conclusions

Thus, it has been shown that perfluoro-m-xylene and 2,5-difluoro-4,6-bis (trifluoromethyl)benzene-1,3-dithiol are convenient building blocks for the synthesis of polyfluorinated thiacalixarenes. Sequential interaction of perfluoro-m-xylene with resorcinols and 2,5-difluoro-4,6-bis (trifluoromethyl)benzene-1,3-dithiol or thiourea leads to the formation of polyfluorinated oxathiacalixarenes containing 4–6 aromatic nuclei in the macrocycle. Based on the analysis of X-ray diffraction data and ¹H and ¹⁹F NMR spectra, it has been shown that polyfluorinated tetratia- and dioxadithiacalix[4]arenes are in the 1,3-alternate conformation in the crystal and in solution.