Synthesis and structure of lower rim-substituted alkynyl derivatives of ...

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A. A. Murav'eva, F. B. Galievab, A. G. Strel'nika, R. I. Nugmanovb, M. Grünerc, S. E. Solov'evaa, ...... Solovieva, S.E., Gruener, M., Omran, A.O., Gubaidul- lin, A.T. ...
ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 9, pp. 1334–1342. © Pleiades Publishing, Ltd., 2015. Original Russian Text © A.A. Murav’ev, F.B. Galieva, A.G. Strel’nik, R.I. Nugmanov, M. Grüner, S.E. Solov’eva, Sh.K. Latypov, I.S. Antipin, A.I. Konovalov, 2015, published in Zhurnal Organicheskoi Khimii, 2015, Vol. 51, No. 9, pp. 1360–1368.

Dedicated to Full Member of the Russian Academy of Sciences N.S. Zefirov on his 80th anniversary

Synthesis and Structure of Lower Rim-Substituted Alkynyl Derivatives of Thiacalix[4]arene A. A. Murav’eva, F. B. Galievab, A. G. Strel’nika, R. I. Nugmanovb, M. Grünerc, S. E. Solov’evaa, Sh. K. Latypova, I. S. Antipina, b, and A. I. Konovalova a

Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, ul. Arbuzova 8, Kazan, 420088 Tatarstan, Russia e-mail: [email protected] b

Butlerov Institute of Chemistry, Ulyanov-Lenin Kazan (Volga Region) Federal University, ul. Kremlevskaya 1/29, Kazan, 420008 Tatarstan, Russia c

Dresden University of Technology, Mommsenstraße 9, Drezden, D-01062 Germany Received January 27, 2015

Abstract—Lower-rim substituted bis- and tetrakis(alkynyloxy)thiacalix[4]arenes in cone and 1,3-alternate configurations were synthesized by the Mitsunobu reaction, and their structure was determined using homoand heteronuclear one- and two-dimensional NMR techniques. Bis(prop-2-yn-1-yloxy)thiacalix[4]arene was found to exist in conformational equilibrium whose position depends on the temperature and reaction conditions.

DOI: 10.1134/S1070428015090213 Introduction of substituents with a terminal C≡C bond to the lower rim of calixarene macrocycle gives rise to valuable intermediate products for the synthesis of a variety of compounds, including biologically active triazoles, photoactive diynes, and aromatic structures, through metal-catalyzed cross-couplings. The number of functional substituents and configuration of the macrocycle determine physicochemical and supramolecular properties of calixarenes [1, 2], in particular their ability to bind charged and neutral species [3–11] in solution [12, 13], on the surface of nanoparticles [14, 15], and in a phase boundary film [16, 17], as well as their nonlinear optical properties [18]. Deviations of the observed properties from the additivity rule may be related to differences in the size of cavity [4, 5, 7], overall dipole moment [18] and aggregation of ligands [9, 12, 14, 15, 19], allosteric effect of the macrocycle [3], different binding modes of lower-rim substituents [6, 17], and cooperative chelate effect of the substituents [10, 13]. Purposeful modification of thiacalix[4]arenes at the lower rim with a view to obtaining derivatives with practically important properties requires chemo- and stereoselec-

tive replacement of the lower-rim hydroxy groups. This is a difficult task, taking into account similarity of the dissociation constants of these hydroxy groups and conformational mobility of the calixarene macrocycle upon introduction of small substituents [6]. The reaction of thiacalix[4]arene with propargyl bromide in the presence of alkali metal carbonates gives only tetrasubstituted derivatives in good yields when the alkylating agent is taken in a large excess [20]. It is impossible to obtain partially substituted thiacalixarenes because in all cases inseparable mixtures of products with different degrees of substitution at the lower rim are formed. A convenient method for the synthesis of di- and tetrasubstituted thiacalixarenes is based on the Mitsunobu reaction [21–24] which requires fairly mild conditions (room temperature and the absence of strong bases). We have studied the reaction of thiacalix[4]arene with terminal acetylenic alcohols in order to elucidate how the reaction conditions affect the selectivity of substitution of the hydroxy groups and the ratio of conformers with propargyl substituents in the reaction mixture (Scheme 1). In the reaction of thiacalix[4]-

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SYNTHESIS AND STRUCTURE OF LOWER RIM-SUBSTITUTED ALKYNYL DERIVATIVES

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Scheme 1. CH ( )n

t-Bu

CH

Bu-t

O

O S

S

S

CH

S

( )n

Bu-t

t-Bu

t-Bu

OH

TPP/DEAD (DIAD) (2.2 equiv) toluene, 40°C

OH

HO

t-Bu

O

Bu-t

S

Bu-t

S

CH

CH

S S HO t-Bu

O

S ( )n

S

S OH

Bu-t

Bu-t

O O

O

2a, 4a–4c

S

S

OH

CH TPP/DEAD (DIAD) (8 equiv) toluene, 40°C

t-Bu

OH

O

1a, 3a–3c

CH

S

S

S

Bu-t

CH

Bu-t

Bu-t

( )n

O O ( )n ( )n t-Bu

t-Bu

t-Bu

S

CH

O O HC OH S S

Bu-t

Bu-t

CH CH

1b

2b

1, 2, n = 1; 3, 4, n = 2 (a), 3 (b), 4 (c).

arene with propargyl alcohol in the presence of 8 equiv of triphenylphosphine/diisopropyl azodicarboxylate (TPP/DIAD) in toluene at 40°C, the yield of tetrasubstituted compounds 1a and 1b was ~56%; i.e., it was lower than in the previously described reaction with halogen derivatives mediated by alkali metal carbonates (77%, 80°C) [20]. Compounds 1a and 1b exist in a dynamic equilibrium (1,3-alternate–partial cone), and the conformer ratios in both reactions were similar (1a/1b 2.5 : 1). This means that the propargyl group is capable of rapidly rotating through the macrocycle. To obtain partially substituted thiacalix[4]arenes, excess TPP/DIAD with respect to thiacalix[4]arene was reduced to ratios of 4 : 1 and 3 : 1. As a result, a mixture of di-, tri-, and tetrasubstituted products was formed. When 1 equiv of TPP/DIAD was used, the product was a mixture of disubstituted derivative 2a/2b with unreacted initial compound (according to the NMR data). The optimal TPP/DIAD-to-thiacalixarene ratio (2.2 : 1) ensured formation of 64–68% of distally disubstituted thiacalixarenes 2a/2b. The mass spectra (electrospray ionization) confirmed the presence of only disubstituted products (m/z 796.5 [M]+).

The multiplicity and intensity of proton signals in the 1 H NMR spectrum indicated formation of two distally substituted products 2a and 2b. As the temperature increased to 363 K (DMF), the population density of the two species changed (2a/2b = 3 : 1). Thus, the interconversion of the conformers is fairly slow on the NMR time scale, i.e., ΔG≠363 > 17 kcal/mol, and the conformers appreciably differ in energy (ΔG 0303 = 0.97 kcal× mol–1). The conformer ratio in the reaction mixture depends on the reaction temperature (3 : 1 at 25°C and ~1 : 1 at 40°C). To exclude rotation of the low-rim substituents through the macrocycle cavity, we have synthesized diand tetrasubstituted derivatives 3a–3c and 4a–4c with C4–C6 chains; it is known that p-tert-butylthiacalix[4]arenes with lower-rim substituents longer than C4 are unable to undergo conformational changes [25]. Compounds 3a–3c (1,3-alternate) and 4a–4c (cone) were isolated in high yields, and their structure was unambiguously determined on the basis of one- and twodimensional NMR experiments. Preliminary analysis of the one-dimensional NMR spectrum of major conformer 2a showed that it also

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 9 2015

MURAV’EV et al.

1336 4b

11b

11b-H 3

10-H

10

4b-H

4b-H* 11b-H*

3-H

2b

8a

8a 5

DMF

8a-H

H2O 7

5-H 2a (distorted cone)

7-H

10-H*

DMF

5-H*

8.0

7.5

7.0

6.5

6.0

5.5

5.0

1

4.5

x

7-H*

4.0

3.5 1

3.0

2.5

2.0

1.5

δ, ppm

13

Fig. 1. H NMR spectrum of conformer mixture 2a/2b (*) in DMF at 303 K; H– C HMBC correlations are shown with solid arrows, and key NOEs, with dotted double-sided arrows.

has cone conformation; the position of signals was similar to those observed in the spectra of thiacalixarenes 4 and was analogous to published data for other distally disubstituted derivatives in the cone conformation [4, 20. 22–24]. A number of NMR experiments were performed at various temperatures in different solvents to get detailed information on the conformer structure and energy parameters of the conformational equilibrium of bis(prop-2-yn-1-yloxy)thiacalix[4]arene 2 in solution. The 1H NMR spectrum of 2 in DMF-d7 at 303 K can be regarded as a superposition of two spectra with an intensity ratio of 5 : 1 (Fig. 1). The structure of both components was analyzed by two-dimensional 1H–1H COSY, 1H–13C HSQC, and 1H–13C HMBC techniques. Major conformer 2a displayed a series of 1 H– 13C HMBC correlations (Fig. 1): 7-H/C6i, 5-H/C1i, 5-H/C6i. The 3-H/C1i correlation indicated that this fragment is attached to the aromatic ring. By moving along the chain of 1H–13C HMBC correlation from C1i to the 3-H aromatic proton, next to C2i and C4i, and then to t-Bu we succeeded in eventually bonding particular atoms in a “bottom-up” manner and determining the structure of one fragment of conformer 2a. Likewise, following 1H–13C HMBC correlations 8a-H/C8i, 8a-H/C9i and 10-H/C8i, 10-H/C9i, 10-H/C4i, we determined the structure of the second fragment of 2a. The NMR data for minor component 2b were analyzed in a similar way (Fig. 1).

The conformations of 2a and 2b were assigned on the basis of the 1H NMR spectra and nuclear Overhauser effects (NOEs). The 1H NMR spectra of both conformers correspond to high-symmetry structures (C2v). The observed spectral patterns may appear due to both really high symmetry and magnetic equivalence of different fragments as a result of fast (on the NMR time scale) intramolecular exchange. There were no difficulties in the identification of major conformer 2a. First, strong “stereospecific” NOEs 11b-H/4b-H, 3-H/10-H, 3-H/11b-H, 10-H/4b-H, and 5-H/8a-H (Fig. 1) indicated that all tert-butyl groups are located at one side of the thiacalixarene rim (cone conformation). Second, the upfield position of signals from the upper-rim protons of the “long arene fragment” (4b-H and 3-H) implies that these protons appear in the area shielded by aromatic fragments. This is possible in the C 2v symmetric structure (pinched cone) due to shielding by the “short arene fragments” or in the Cs symmetric distorted cone structure due to shielding by the opposite fragments [26]. Strong exchange broadening of signals in the 1 H NMR spectra (CD2Cl2) at 193 K suggest slow interconversion of conformers with nonequivalent long arene fragments, i.e., the actual symmetry is lower than C 2v. Thus, major conformer 2a is distorted cone. The “pendulum” distorted cone–distorted cone equilibrium involves alternate formation of two hydrogen bonds with each ether oxygen atom, which favor opposite inclination of the long arene fragment. This

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SYNTHESIS AND STRUCTURE OF LOWER RIM-SUBSTITUTED ALKYNYL DERIVATIVES 11b*

11b*

11b* 7*

7* 3* 10*

10*

O

O S

S

S OH

5*

S

OH

8a*

OH O 5*

3*

8a*

S

S

S

1337

O

10*

3*

5*

S

HO

8a*

7*

4b*

10*

5*

O

5*

3*

S

S

S

O

S

HO OH

8a*

3*

4b*

1,3-alternate

1,2-alternate

interpretation is consistent with the X-ray diffraction data [27] according to which the most favorable structure is cone where the benzene rings with lower-rim substituents are inclined with respect to the macrocycle plane. A more complicated pattern was observed for minor component 2b. The ether groups in distally substituted thiacalixarenes are capable of rotating through the macrocycle cavity, so that 1,3-alternate structure can be formed in addition to cone. This follows from the data for crystalline (allyloxy)thiacalixarenes with nitro groups on the upper rim [28] and classical calix[4]arene with quinazoline fragments on the lower rim [29], as well as from the MMF94 and MM3 molecular mechanics calculations. On the one hand, the 1H NMR

partial cone

spectrum of 2b at room temperature matches C2v symmetry, and there are no indications of slow exchange processes on lowering the temperature to 193 K (CD2Cl2). On the other hand, structure 2b displayed NOEs (e.g., 5-H*/10-H*, 11b-H*/7-H*) corresponding to alternation of structural units, which may be observed for a number of conformers (1,3-alternate, 1,2-alternate, and partial cone, where the propargyl fragments are oriented anti with respect to each other, Fig. 2). However, some less intense specific NOEs (10-H*/3-H*, 10-H*/5-H*, 8a-H*/5-H*, 11b-H*/3-H*) rule out 1,3-alternate conformer. These weak NOEs may be rationalized assuming partial cone or 1,2-alternate structure in rapid exchange with the conjugate conformer.

E, kcal/mol 20

15

10

5 Partial cone

1,2-Alternate

Partial cone*

1,2-Alternate*

Distorted cone Reaction coordinate Fig. 2. Energy profile for the conformational transitions of distally substituted thiacalix[4]arenes. RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 9 2015

MURAV’EV et al.

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Experimental and calculateda 1H chemical shifts of disubstituted thiacalixarenes 2a and 2b Proton

c

*

**

2b (exptl.)

1,2-alternate

DMF CDCl3

partial cone

1,3-alternate

*

**

*

**

**

b

*

**

0.86 1.38

1.32 0.79

1.19 1.29

1.31 0.88

1.36 1.23

1.25 1.31

1.35 1.34

1.24 1.21

1.46 1.39

0.81 1.49

1.16 1.09

1.27 1.44

1.19 1.27

5-H

5.43

5.24

5.20

4.73

4.67

4.50

4.38

4.62

4.70

4.89

4.84

4.70

5.35

3-H

7.16

6.96

7.00

7.16

7.83

7.59

7.57

7.86

7.59

9.52

7.26

7.40

7.37

10-H

7.87

7.66

7.50

7.30

7.51

7.44

7.42

7.36

7.33

7.03

6.29

7.65

7.32

0.00

0.00

0.00

0.70

0.97

0.97

2.00

0.00

2.40

1.90

2.90

8.90

5.60

DMF

0.26

0.48

0.17

0.07

0.17

0.90

0.53

0.25

0.43

CDCl3

0.27

0.30

0.08

0.15

0.14

0.97

0.54

0.17

0.43

MSD

b

DMF CDCl3

distorted cone

4b-H 11b-H

∆E, kcal/mol

a

2a (exptl.)

c

GIAO B3LYP/6-31G(d) (*), GIAO PBE/3z (**). Partial cone with anti orientation of the hydroxy groups. MSD stands for mean-square deviation.

Bhalla et al. [30] postulated mutual transformation of anti forms of disubstituted cyanomethoxy- and aminoethoxy thiacalixarene derivatives in the 1,2-alternate condormation, while Lhoták et al. [31] synthesized distally substituted dimethoxythiacalix[4]arene which formed in crystal molecular channels composed of 1,2-alternate conformers and existed in solution as two symmetric structures, one being the cone conformer (the second structure was not identified). The NOE data did not allow us to unambiguously distinguish between 1,2-alternate and partial cone. Some protons in 2b (5-H, 10-H, 11b-H) resonated in a stronger field than did those in, e.g., cone conformer (Fig. 1). According to the results of quantum chemical calculations [GIAO B3LYP/6-31G(d)//B3LYP/ 6-31G(d) and GIAO PBE/3z] [32, 33] (see table), such upfield shifts are possible for protons of both 1,2-alternate and partial cone conformers, which follows from the lowest mean-square deviation of the calculated chemical shifts from the experimental data. It should be noted that the proton chemical shifts calculated for 1,3-alternate differ substantially from the experimental values. The relative energies of the optimized structures showed a qualitative correlation with the experimental data. The energy minimum corresponds to distorted cone, 1,3-alternate has the highest energy, and the energies of 1,2-alternate and partial cone are fairly similar and appreciably lower than that of 1,3-alternate (see table). These results differ from those obtained by simpler molecular mechanics methods [28, 29] that are not optimized for the calculation of energies of calixarenes [2]. Variation of the solvent (CDCl3, CD2Cl2,

DMF-d 7 , acetone-d 6 ) in NMR experiments did not appreciably change the populations of both conformers at 30°C relative to the calculated value for the gas phase, and the cone conformer remained the major stereoisomer. Thus, the transformations of distally substituted thiacalix[4]arenes may be described as follows (Fig. 2). The major conformer in solution is distorted cone; in addition, there exist several minor conformers characterized by opposite orientations of the lower-rim ether substituents (partial cone, 1,2-alternate, partial cone*, 1,2-alternate*). The latter are interconvertible via stepwise low-barrier (∆G193 17 kcal/mol). Synchronous turnover of the distal benzene rings may be ruled out since it would induce strong distortion of the dihedral angles at the bridging sulfur atoms; no such turnover occurs even in strained thiacalix[4] monocrown-3 in the cone conformation [18]. We do not consider partial cone structure with syn-oriented ether fragments, for the first barrier to the transition cone–partial cone should be very high (insofar as the NMR spectral pattern does not change with rise in temperature, this is possible only for the rotation of long arene fragments). Rotation of phenolic rings has never been observed in disubstituted thiacalix[4]arenes with bulky substituents (no NOE was observed between aromatic and OH protons, in particular for compound 4). By contrast, the barriers for the minor

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SYNTHESIS AND STRUCTURE OF LOWER RIM-SUBSTITUTED ALKYNYL DERIVATIVES

component should be low even at low temperature (the spectrum corresponds to a symmetric structure). This is possible in the case of rotation of the OH groups. EXPERIMENTAL All reactions were carried out under argon. The solvents were purified prior to use according to standard procedures [34]. Commercial reagents (Aldrich, Acros, Alfa Aesar) were used without additional purification. Thiacalix[4]arene was synthesized as described in [35] and was dried for 1 h at 100°C before use. The physical constants of compounds 1a and 1b coincided with those reported in [20]. The NMR spectra were recorded on Bruker Avance 600 [600.13 (1H), 150.92 MHz (13C)] and Avance 400 pulse spectrometers [399.93 (1H), 100.57 MHz (13C)]. The chemical shifts were measured relative to the residual proton and carbon signals of the deuterated solvents (CDCl 3 , δ 7.26, δ C 77.16 ppm; DMF-d 7, δ 2.75, 2.92, 8.03, δ C 29.76, 34.89, 163.15 ppm; CD2Cl2, δ 5.32, δC 54.0 ppm). One- and two-dimensional NMR experiments (COSY, HSQC, HMBC) were carried out by means of standard Bruker software; 1D DPFGROE/DPFGNOE [36]: d1 = 5 s, τm = 0.3 s; the power and duration of Hermite-shaped bandselective radiofrequency pulses were selected individually for each experiment. The temperature was varied from 193 to 363 K and was maintained with an accuracy of ±0.1 K). The atom numbering in molecules 1–4 is analogous to that shown in Fig. 1 for compound 2. The molecular weights were determined by mass spectrometry on Bruker MALDI-TOF Ultraflex III (p-nitroaniline matrix) and Bruker Esquire-LC instruments (methanol containing 0.1% of NH4OAc). The melting points were measured on a Boetius hot stage equipped with a PHMK 05 microscope. The purity of the isolated compounds was checked by TLC [Silufol UV 254, hexan–ethyl acetate (4 : 1), detection under UV light (VL-6.LC lamp, 6 W, λ 254 nm)]. The IR spectra were recorded in KBr on Bruker Vector-22 and Nicolet FT-IR 205 spectrometers. The elemental analyses were obtained on a Euro Vector Hekatech EA 3000 CHNSO analyzer. Quantum chemical calculations. The proton chemical shifts were calculated by the DFT GIAO method [37] using B3LYP functional in combination with 6-31G(d) basis set (Gaussian 98 [38]) and PBE functional in combination with the triple zeta (3z) basis set (PRIRODA 6 [39–42]). The geometric parameters were completely optimized at the B3LYP/6-31G(d)

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level of theory (Gaussian). Conformational analysis was performed (PRIRODA 6) using B3LYP and PBE functionals and 3z basis set. The B3LYP energies (PRIRODA) were better consistent with the experimental data. All chemical shifts (1H and 13C) are given relative to tetramethylsilane. An empirical correction was applied to the chemical shifts calculated by PBE/3z (PRIRODA 6): δ′ = 0.96 δ [33]. Tetrakis(alkynyloxy)thiacalix[4]arenes 1a, 1b, and 3a–3c (general procedure). Thiacalix[4]arene, 1 g (1.39 mmol), and triphenylphosphine (TPP), 2.914 g (11.11 mmol), were dispersed in 40 mL of toluene, and 13.9 mmol of terminal acetylenic alcohol CnH2n – 3OH (n = 3–6) and 2.19 mL (11.11 mmol) of diisopropyl azodicarboxylate (DIAD; in the synthesis of 1a and 1b) or diethyl azodicarboxylate (DEAD; in the synthesis of 3a–3c) were added dropwise. The mixture was stirred under argon for 8 h at room temperature and for 8 h at 40°C, the progress of the reaction being monitored by TLC. The solvent was removed under reduced pressure, the residue was treated with 70 mL of methanol, and the precipitate was filtered off and dried at 100°C in a drying box. 5,11,17,23-Tetra-tert-butyl-25,27,26,28-tetrakis(but-3-yn-1-yloxy)-2,8,14,20-tetrathiacalix[4]arene (3a). Yield 0.780 g (69%), white powder, mp 260°C, Rf 0.87 (hexane–EtOAc, 4 : 1). IR spectrum, ν, cm–1: 3312 (≡C–H), 2960 (C–Harom), 1445 (C=Carom), 1243 (t-Bu). 1H NMR spectrum (CDCl3, 400 MHz, 293 K), δ, ppm: 7.36 s (8H, 3-H), 4.00 t (8H, 5-H, J = 7.6 Hz), 1.90 t (4H, 7-H, J = 2.8 Hz), 1.60 m (8H, 6-H), 1.32 s (36H, t-Bu). Mass spectrum (MALDI TOF), m/z: 930.1 [M + H]+, 952.1 [M + Na]+, 968.2 [M + K]+. Found, %: C 67.60; H 7.49. C56H64O4S4 · 2 H2O · 2 MeOH. Calculated, %: C 67.67; H 7.44. 5,11,17,23-Tetra-tert-butyl-25,27,26,28-tetrakis(pent-4-yn-1-yloxy)-2,8,14,20-tetrathiacalix[4]arene (3b). Yield 1.038 g (76%), white powder, mp 250°C, Rf 0.95 (hexane–EtOAc, 4 : 1). IR spectrum, ν, cm–1: 3292 (≡C–H), 2961 (C–H arom ), 1443 (C–C arom ). 1 H NMR spectrum (CDCl3, 400 MHz, 293 K), δ, ppm: 7.35 s (8H, 3-H), 3.95 t (8H, 5-H, J = 7.2 Hz), 1.89 t (8H, 6-H, J = 7.8 Hz), 1.86 t (4H, 8-H, J = 2.8 Hz), 1.30 s (36H, t-Bu), 1.22 m (8H, 7-H). Mass spectrum (MALDI TOF), m/z: 986.5 [M + H]+, 1008.5 [M + Na]+, 1024.4 [M + K] + . Found, %: C 70.47; H 8.04. C60H72O4S4 · 2 H2O. Calculated, %: C 70.55; H 7.50. 5,11,17,23-Tetra-tert-butyl-25,27,26,28-tetrakis(hex-5-yn-1-yloxy)-2,8,14,20-tetrathiacalix[4]arene (3c). Yield 1.130 g (78%), white powder, mp 150°C,

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Rf 0.90 (hexane–EtOAc, 4 : 1). IR spectrum, ν, cm–1: 3281 (≡C–H), 2957 (C–H arom ), 1442 (C–C arom ). 1 H NMR spectrum (CDCl3, 400 MHz, 293 K), δ, ppm: 7.34 s (8H, 3-H), 3.86 t (8H, 5-H, J = 7.6 Hz), 2.09 m (8H, 6-H), 1.94 t (4H, 10-H, J = 2.8 Hz), 1.40 m (8H, 7-H), 1.28 s (36H, t-Bu). Mass spectrum (MALDI TOF), m/z: 1042.3 [M + H]+, 1064.3 [M + Na]+, 1080.3 [M + K]+. Found, %: C 70.71; H 8.29. C64H80O4S4 · 3 MeOH. Calculated, %: C 70.73; H 8.15. Bis(alkynyloxy)thiacalix[4]arenes 2a, 2b, and 4a–4c (general procedure). Thiacalix[4]arene, 1 g (1.39 mmol), and triphenylphosphine (TPP), 0.801 g (3.06 mmol), were dispersed in 30 mL of toluene, and 6.94 mmol of the corresponding acetylenic alcohol (CnH2n – 3OH, n = 3–6) and 3.06 mmol of DIAD (in the synthesis of 2a and 2b) or DEAD (in the synthesis of 4a–4c) were added dropwise. The mixture was stirred under argon for 8 h at room temperature and for 8 h at 40°C, the progress of the reaction being monitored by TLC. The solvent was removed under reduced pressure, the residue was treated with 70 mL of methanol, and the precipitate was filtered off and dried at 100°C in a drying box. 5,11,17,23-Tetra-tert-butyl-26,28-bis(prop-2-yn1-yloxy)-2,8,14,20-tetrathiacalix[4]arene-25,27-diol (2a/2b). Yield 0.720 g (64%), white powder, mp 185°C (decomp.), Rf 0.87/0.74 (hexane–EtOAc, 4 : 1). IR spectrum, ν, cm–1: 3378 (≡C–H), 3300 (O–H), 2960 (C–Harom), 1452 (C–Carom). Mass spectrum (ESI), m/z: 796.5 [M]+, 814.5 [M + NH4]+. Found, %: C 71.19; H 6.53. C46H52O4S4. Calculated, %: C 69.31; H 6.57. Cone (2a). 1H NMR spectrum, δ, ppm: in CDCl3 (400 MHz, 293 K): 7.66 s (4H, 10-H), 7.63 s (2H, 8a-H), 6.96 s (4H, 3-H), 5.24 d (4H, 5-H, J = 2.4 Hz), 2.64 t (2H, 7-H, J = 2.4 Hz), 1.32 s (18H, 11b-H), 0.79 s (18H, 4b-H); in DMF (600 MHz, 303 K): 8.01 s (2H, 8a-H), 7.87 s (4H, 10-H), 7.16 s (4H, 3-H), 5.43 d (4H, 5-H, J = 2.4 Hz), 3.70 t (2H, 7-H, J = 2.4 Hz), 1.38 s (18H, 11b-H), 0.86 s (18H, 4b-H). 13C NMR spectrum, δC, ppm: in CDCl3 (151 MHz, 293 K): 155.57 (C8i), 154.73 (C1i), 148.52 (C4i), 142.76 (C11i), 134.46 (C10), 132.72 (C3), 129.39 (C2i), 121.90 (C9i), 78.60 (C6i), 76.57 (C7), 62.37 (C5), 34.16 (C11a), 34.03 (C4a), 31.44 (C11b), 30.70 (C4b); in DMF (151 MHz, 303 K): 155.9 (C 8i), 154.7 (C 1i), 148.9 (C 4i), 143.3 (C11i), 135.2 (C10), 132.9 (C3), 129.5 (C2i), 121.9 (C9i), 79.1 (C6i), 78.3 (C7), 62.0 (C5), ~35 (C11a, C4a), 31.0 (C11b), 30.3 (C4b). 1,2-Alternate/partial cone (2b). 1H NMR spectrum, δ, ppm: in CDCl3 (400 MHz, 293 K): 7.59 s (4H, 3-H),

7.44 s (4H, 10-H), 7.26 s (2H, 8a-H), 4.50 d (4H, 5-H, J = 2.4 Hz), 2.18 t (2H, 7-H, J = 2.4 Hz), 1.31 s (18H, 4b-H), 1.25 s (18H, 11b-H); in DMF (600 MHz, 303 K): 7.83 s (4H, 3-H), 7.51 s (4H, 10-H), 4.67 d (4H, 5-H, J = 2.4 Hz), 3.40 t (2H, 7-H, J = 2.4 Hz), 1.36 s (18H, 4b-H), 1.23 s (18H, 11b-H). 13C NMR spectrum (151 MHz, 303 K), δC, ppm: in CDCl3: 155.9 (C8i), 155.3 (C1i), 148.0 (C4i), 142.6 (C11i), 133.4 (C3), 132.4 (C10), 129.1 (C2i), 119.8 (C9i), 78.9 (C6i), 77.9 (C7), 60.0 (C5), ~35 (C4a, C11a), 31.0 (C11b), 30.8 (C4b); in DMF: 155.9 (C1i), 155.3 (C8i), 148.0 (C4i), 142.6 (C11i), 133.4 (C3), 132.4 (C10), 129.1 (C2i), 119.8 (C9i), 78.9 (C6i), 77.9 (C7), 60.0 (C5), ~35 (C4a, C11a), 31.0 (C11b), 30.8 (C4b). 5,11,17,23-Tetra-tert-butyl-26,28-bis(but-3-yn1-yloxy)-2,8,14,20-tetrathiacalix[4]arene-25,27-diol (4a). Yield 0.920 g (80%), white powder, mp 220°C, Rf 0.42 (hexane–EtOAc, 4 : 1). IR spectrum, ν, cm–1: 3312 (≡C–H), 2958 (C–Harom), 1451 (C–Carom), 1244 (t-Bu). 1H NMR spectrum (CDCl3, 400 MHz, 293 K), δ, ppm: 7.79 s (2H, 9a-H), 7.70 s (4H, 11-H), 6.95 s (4H, 3-H), 4.65 t (4H, 5-H, J = 7.2 Hz), 2.99 m (4H, 6-H), 2.10 t (2H, 8-H, J = 2.8 Hz), 1.34 s (18H, 12b-H), 0.80 s (18H, 4b-H). 13 C NMR spectrum (CDCl3, 101 MHz, 303 K), δC, ppm: 20.2 (C6), 30.8 (C4b), 31.5 (C12b), 34.0 (C6a), 34.2 (C12a), 70.3 (C7), 72.8 (C5), 80.4 (C7i), 122.1 (C2i), 128.9 (C10i), 132.8 (C3), 134.4 (C11), 142.7 (C12i), 148.1 (C4i), 155.7 (C1i), 155.9 (C9i). Mass spectrum (MALDI TOF), m/z: 825.6 [M + H]+, 847.7 [M + Na]+, 863.7 [M + K]+. Found, %: C 63.71; H 7.12. C48H56O4S4 · 4 H2O. Calculated, %: C 64.25; H 7.19. 5,11,17,23-Tetra-tert-butyl-26,28-bis(pent-4-yn1-yloxy)-2,8,14,20-tetrathiacalix[4]arene-25,27-diol (4b). Yield 1.016 g (86%), white powder, mp 200°C, Rf 0.8 (hexane–EtOAc, 4 : 1). IR spectrum, ν, cm–1: 3323 (O–H), 2960 (C–Harom), 1447 (C–Carom), 1245 (t-Bu). 1H NMR spectrum (CDCl3, 400 MHz, 293 K), δ, ppm: 7.86 s (2H, 10a-H), 7.66 s (4H, 12-H), 6.99 s (4H, 3-H), 4.55 t (4H, 5-H, J = 6.4 Hz), 2.61 m (4H, 6-H), 2.26 m (4H, 7-H), 2.00 t (2H, 9-H, J = 2.4 Hz), 1.33 s (18H, 13b-H), 0.82 s (18H, 4b-H). 13C NMR spectrum (CDCl3, 101 MHz, 303 K), δC, ppm: 15.9 (C6), 29.6 (C7), 31.1 (C4b), 31.8 (C13b), 34.4 (C4a), 34.5 (C13a), 69.1 (C9), 75.0 (C5), 84.3 (C8i), 122.4 (C2i), 129.2 (C 11i), 133.4 (C 3 ), 134.7 (C 12 ), 143.0 (C 13i), 148.3 (C4i), 156.3 (C1i), 156.7 (C10i). Mass spectrum (MALDI TOF), m/z: 854.9 [M + H]+, 876.0 [M + Na]+, 8 9 2 . 0 [M + K ] + . F o u n d , %: C 6 7 . 2 0 ; H 7 . 4 1. C50H60O4S4 · 2 H2O. Calculated, %: C 67.53; H 7.25.

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SYNTHESIS AND STRUCTURE OF LOWER RIM-SUBSTITUTED ALKYNYL DERIVATIVES

5,11,17,23-Tetra-tert-butyl-26,28-bis(hex-5-yn1-yloxy)-2,8,14,20-tetrathiacalix[4]arene-25,27-diol (4c). Yield 0.971 g (79%), white powder, mp 200°C, Rf 0.88 (hexane–EtOAc, 4 : 1). IR spectrum, ν, cm–1: 3311 (O–H), 2959 (C–Harom), 1449 (C–Carom), 1244 (t-Bu). 1H NMR spectrum (CDCl3, 400 MHz, 293 K), δ, ppm: 7.87 s (2H, 11a-H), 7.66 s (4H, 13-H), 6.95 s (4H, 3-H), 4.53 t (4H, 5-H, J = 6.4 Hz), 2.40 m (4H, 6-H), 2.13 m (4H, 7-H), 1.98 t (2H, 10-H, J = 2.8 Hz), 1.89 t (4H, 8-H, J = 7.2 Hz), 1.34 s (18H, 14b-H), 1.80 s (18H, 4b-H). 13 C NMR spectrum (CDCl 3, 101 MHz, 303 K), δC, ppm: 15.9 (C6), 25.2 (C7), 29.4 (C8), 31.1 (C4b), 31.8 (C14b), 34.4 (C4a), 34.5 (C14a), 69.0 (C 10 ), 75.3 (C 5 ), 84.7 (C 9i), 122.5 (C 2i), 129.3 (C11i), 133.2 (C3), 134.7 (C13), 143.0 (C14i), 148.2 (C4i), 156.2 (C 1i), 156.6 (C 11i). Mass spectrum (MALDI TOF), m/z: 881.9 [M + H]+, 903.8 [M + Na]+, 919.9 [M + K]+. Found, %: C 67.38; H 7.70. C52H64O4S4 · H2O · 2 MeOH. Calculated, %: C 67.32; H 7.74. This study was performed under financial support by the Russian Foundation for Basic Research (project no. 14-03-31 909) and by the Ministry of Education and Science of the Russian Federation. REFERENCES 1. Antipin, I.S. and Konovalov, A.I., Mendeleev Commun., 2008, vol.18, p. 229. 2. Gutsche, C.D., Calixarenes: An Introduction, Stoddart, J.F., Ed., Cambridge: Roy. Soc. Chem., 2008, 2nd ed. 3. Stoikov, I.I., Omran, O.A., Solovieva, S.E., Latypov, Sh.K., Enikeev, K.M., Gubaidullin, A.T., Antipin, I.S., and Konovalov, A.I., Tetrahedron, 2003, vol. 59, p. 1469. 4. Solovieva, S.E., Gruener, M., Omran, A.O., Gubaidullin, A.T., Litvinov, I.A., Habicher, W.D., Antipin, I.S., and Konovalov, A.I., Russ. Chem. Bull., Int. Ed., 2005, vol. 54, p. 2104.. 5. Solovieva, S.E., Kleshnina, S.R., Kozlova, M.N., Galiullina, L.F., Gubaidullin, A.T., Latypov, Sh.K., Antipin, I.S., and Konovalov, A.I., Russ. Chem. Bull., Int. Ed., 2008, vol. 57, p. 1477. 6. Baldini, L., Melegari, M., Bagnacani, V., Casnati, A., Dalcanale, E., Sansone, F., and Ungaro, R., J. Org. Chem., 2011, vol. 76, p. 3720. 7. Ziganshin, M.A., Gorbatchuk, V.V., Sitdikov, R.R., Stoikov, I.I., and Antipin, I.S., Russ. Chem. Bull., Int. Ed., 2014, vol. 63, p. 201. 8. Okunola, O.A., Seganish, J.L., Salimian, K.J., Zavalij, P.Y., and Davis, J.T., Tetrahedron, 2007, vol. 63, p. 10 743.

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