3-(4-Ethynylphenyl)-1,5-diphenylformazan

Abstract

The structure of the “clickable” formazan, 3-(4-ethynylphenyl)-1,5-diphenylformazan, has been determined for the first time in a single crystal. The synthesis of 3-(4-ethynylphenyl)-1,5-diphenylformazan was carried out by coupling 4-(trimethylsilyl)ethynylbenzaldehyde phenylhydrazone with diazotized aniline, followed by desilylation, with a total yield of 54%.

1. Introduction

The interest in formazans is due to the presence of a set of practically important properties, which are rarely manifested simultaneously in representatives of other classes of organic compounds [1,2,3,4,5]. Formazans can exhibit photo- and thermochromic properties, act as effective metal ligands or indicators of redox processes, and also demonstrate various types of biological activity. Their applications include use as dyes, indicators, components of optical recording media and photographic compositions, and catalysts for oxidation–reduction reactions. Formazans are also applied in fine organic synthesis; they are particularly important as starting compounds for the synthesis of tetrazolium salts [6,7,8,9,10], verdazyls [11,12,13,14], and boratetrazines [15,16,17,18,19,20,21] (Figure 1), as well as various heterocycles [22,23].

The structural diversity of formazans is due to the ease of varying the three substituents in the azo-hydrazone chain. Of particular interest are “clickable” formazans, which can be used to synthesis conjugates with various molecules and to functionalize solid matrices. To date, several “clickable” formazans have been described [24,25,26,27,28,29,30] (Figure 2). One of the simplest compounds of this type, containing an ethynyl group in the meso position of the azo-hydrazone chain, is 3-(4-ethynylphenyl)-1,5-diphenylformazan 2, which was recently synthesized for the first time by coupling 4-ethynylbenzaldehyde phenylhydrazone with phenyldiazonium tosylate [27] and used for the synthesis of verdazyls.

The present work describes the synthesis of 3-(4-ethynylphenyl)-1,5-diphenylformazan and its crystal structure.

2. Results and Discussion

As the starting building block, we used the readily available compound 4-(trimethylsilyl)ethynylbenzaldehyde (8) [31], which is also a commercially available reagent ($6.03/1 g Macklin Inc., Rochelle, IL, USA). When compound 8 was reacted with phenylhydrazine in boiling ethanol, 1-phenyl-2-[4-((trimethylsilyl)ethynyl)benzylidene]hydrazine (10) was synthesized, with a yield of 74% (Scheme 1).

For the synthesis of formazan, a classical scheme was chosen involving the condensation of the phenylhydrazone with the diazonium salt in a pyridine medium in the presence of glacial acetic acid. The reaction was carried out at −5 °C (Scheme 2). According to TLC data, the product (12) formed is sufficiently pure and does not require additional purification.

Desilylation of 12 was performed using potassium hydroxide in methanol at room temperature (Scheme 3).

The structure of products 10, 12, and 2 was confirmed by ¹H, ¹³C NMR, IR spectroscopy and mass spectrometry.

The structure of 3-(4-ethynylphenyl)-1,5-diphenylformazan (2) was unambiguously confirmed by single-crystal X-ray analysis (Figure 3). The single crystals of 2 were grown by recrystallization of the title compound in ethanol.

Compound 2 crystallizes in the centrosymmetric orthorhombic space group Pbca. The whole molecule is non-planar, with the aryl rings slightly twisted with respect to the formazan plane N2N1C1N3N4. The dihedral angles between the aromatic planes C2–C7, C10–C15, C16–C21 and the plane N2N1C1N3N4 are 5.8 °, 10.2 °, and 15.4 °, respectively. The formazan system has the syn,s-cis configuration, which is characteristic of some other triaryl substituted formazans [16,17]. The difference between the lengths of the double and single bonds in the formazan moiety is reduced, indicating π-electron density delocalization (e.g., N4 = N3 1.288 (1) Å, N1–N2 1.314 (1) Å). A similar distribution of bond lengths is observed in other triaryl-substituted formazans (e.g., CSD refcodes: PEVWET [16], PUVCOA [17]). Thus, the ethynyl substituent does not affect the structure of the formazan moiety but makes the arrangement of the aryl rings more twisted compared to the PEVWET [16] and PUVCOA [17], probably due to the packing features of the ethynyl compound. The hydrogen atom of the NH group is refined as disordered over two positions with occupancies of 0.69 (2) for H2 and 0.31 (2) for H4A. The syn, s-cis configuration is stabilized by intramolecular hydrogen bonds N2–H2∙∙∙N4 (N2–H2 0.89 (2) Å, H2∙∙∙N4 1.86 (2) Å), and N4–H4A∙∙∙N2 (N4–H4A 0.89 (5) Å, H4A∙∙∙N2 1.87 (6) Å) for the minor disorder component.

In conclusion, 3-(4-ethynylphenyl)-1,5-diphenylformazan was synthesized, and its structure was confirmed by a combination of ¹H, ¹³C NMR, IR spectroscopy, mass spectrometry, and X-ray diffraction data.

3. Materials and Methods

The reactions were monitored by thin-layer chromatography (Sorbfil, Imid Ltd., Krasnodar, Russia). The ¹H-NMR and ¹³C-NMR spectra were acquired on ECA400 (JEOL, Tokyo, Japan) (400 and 100 MHz, respectively) spectrometers in CDCl₃ and (CD₃)₂SO at room temperature. The chemical shifts δ were measured in ppm with reference to the residual solvent resonances (¹H: CDCl₃, δ = 7.25 ppm; ¹³C: CDCl₃, δ = 77.2 ppm; ¹H: (CD₃)₂SO, δ = 2.49 ppm; ¹³C: (CD₃)₂SO, δ = 39.5 ppm) or Me₄Si. The splitting patterns are referred to as s, singlet; d, doublet; t, triplet; m, multiplet. Coupling constants (J) are given in hertz. IR spectra were recorded on an IR Prestige (Shimadzu, Kyoto, Japan), using tablets of samples with KBr. High-resolution and accurate mass measurements were carried out using a Bruker MaXis Impact (electrospray ionization/time of flight) (Bruker, Bremen,_Germany). The melting points were determined on a Stuart SMP30 apparatus and left uncorrected. X-ray diffraction investigation of compound 2 was conducted using an automatic diffractometer Bruker Apex DUO (CuKα radiation, ω- and φ-scanning). Empirical absorption correction and systematic error correction were performed using the SADABS program [32]. The structure was deciphered by direct methods and refined using the least squares method in the anisotropic full-matrix approximation based on F2hkl. The positions of hydrogen atoms bonded to nitrogen atoms and the carbon atom of the acetylene fragment were determined from difference Fourier syntheses of electron density, while the positions of the remaining hydrogen atoms were calculated. All hydrogen atoms, except for the one bonded to the nitrogen atom, were refined in the riding model with Uiso(H) = 1.2Ueq(C). All calculations were performed using the SHELXTL PLUS software package [33].

The commercial reagents employed in the synthesis were 4-(trimethylsilyl)ethynylbenzaldehyde (95%, Manchester Organics Ltd., Runcorn, UK), Phenylhydrazine (for synthesis, ≥97%, Aldrich, St. Louis, MO, USA), and aniline (≥99%, Vekton, Saint Petersburg, Russia).

3.1. 1-Phenyl-2-[4-((trimethylsilyl)ethynyl)benzylidene]hydrazine (10)

In a reflux flask with a condenser, 20 mL of ethanol, 1 g (4.94 mmol) of 4-(trimethylsilyl)ethynylbenzaldehyde, and 485 µL (4.94 mmol) of phenylhydrazine were added and heated for 20 min. The reaction mixture was cooled to 3 °C for crystallization. The precipitate was filtered and washed with a small amount of cold ethanol.

Yield: 1.07 g (74%); beige crystals; mp 132-135 °C. IR (KBr): ν = 3311 (NH), 3078, 3049, 3034 (Csp²-H), 2954, 2897 (Csp³-H), 2154 (Csp-Csp), 1598, 1589, 1523, 1494 (Csp²-Csp²), 1444, 1408, 1355, 1313, 1296, 1261, 1249, 1222, 1134, 1102, 1068, 920, 864, 846, 835 cm⁻¹ (SI, Figure S1). ¹H NMR (CDCl₃, 399.78 MHz): δ = 0.26 (s, 9H, CH₃), 6.86–6.90 (m, 1H, CH), 7.08–7.12 (m, 2H, CH), 7.24–7.30 (m, 2H, CH), 7.43–7.46 (m, 2H, CH), 7.55–7.59 (m, 2H, CH + 1H CH) (SI, Figure S2). ¹³C NMR (CDCl₃, 100.5 MHz): δ = −0.03 (CH₃), 95.4 (Csp), 105.1 (Csp), 112.8 (CH), 120.3 (CH), 122.7 (C), 125.8 (CH), 129.3 (CH), 132.2 (CH), 135.4 (C), 136.2 (CH_imine), 144.3 (C) (SI, Figure S3). UV–VIS λmax, nm (Irel, %): 252 (6671), 372 (11396). HRMS ESI TOF: m/z = 293.1476 [M+H]⁺ (293.1468 calcd. for C₁₈H₂₁N₂Si) (SI, Figure S4).

3.2. 1,5-Diphenyl-3-[4-((trimethylsilyl)ethynyl)phenyl]formazan (12)

To a solution of 0.46 g (1.57 mmol) of 1-phenyl-2-[4-((trimethylsilyl)ethynyl)benzylidene]hydrazine in 15 mL of pyridine and 0.5 mL of glacial acetic acid, a solution of phenyl diazonium chloride, synthesized from 143 µL (1.57 mmol) of aniline, 0.108 g (1.57 mmol) of NaNO₂, and 1.2 mL of 37% HCl in 1 mL of water, was added at −5 °C. The resulting cherry–red reaction mixture with precipitate was maintained for 30 min at −5 °C, and then for 1 h at room temperature. The reaction mixture was then poured into 150 mL of 2M HCl, and the precipitate was filtered and washed with water. Yield: 525 mg (84%); cherry–red powder; mp 193-195 °C. Rf = 0.41 (Hexane–EtOAc 10:1). IR (KBr): ν = 3084, 3064, 3049, 3032 (Csp²-H), 2954 (Csp³-H), 2152 (Csp-Csp), 1597, 1506, 1498 (Csp²-Csp²), 1452, 1404, 1354, 1313, 1249, 1236, 1186, 1074, 1035, 866, 842 cm⁻¹ (SI, Figure S5). ¹H NMR (CDCl₃, 399.78 MHz): δ = 0.28 (s, 9H, CH₃), 7.26–7.30 (m, 2H, CH), 7.43–7.47 (m, 4H, CH), 7.51–7.53 (m, 2H, CH), 7.65–7.67 (m, 4H, CH), 8.06–8.08 (m, 2H, CH), 15.51 (s, 1H, NH) (SI, Figure S6). ¹³C NMR (CDCl₃, 100.5 MHz): δ = 0.06 (CH₃), 94.8 (Csp), 105.5 (Csp), 118.8 (CH), 122.0 (C), 125.3 (CH), 127.7 (CH), 129.4 (CH), 132.1 (CH), 137.5 (C), 140.4 (C), 147.7 (C) (SI, Figure S7). UV-VIS λmax, nm (Irel, %): 252 (6671), 372 (11396). HRMS ESI TOF: exact mass found 397.1842 (397.1842 calcd. for C₂₄H₂₃N₄Si) (SI, Figure S8).

3.3. 3-(4-Ethynylphenyl)-1,5-diphenylformazan (2)

To 300 mg (0.76 mmol) of 1,5-diphenyl-3-[4-((trimethylsilyl)ethynyl)phenyl]formazan in 20 mL of MeOH, 420 mg (3.04 mmol) of finely ground K₂CO₃ was added. The reaction mixture was stirred at room temperature for 4 h. Then, the reaction mixture was poured into 100 mL of 2M HCl, and the precipitate was filtered and washed with water. Yield: 214 mg (87%); purple–black needles; mp 205-207 °C. Rf = 0.41 (Hexane–EtOAc 10:1). IR (KBr): ν = 3278 (Csp-H), 3062, 3045, 3030 (Csp²-H), 2096 (Csp-Csp), 1597, 1500 (Csp²-Csp²), 1450, 1406, 1354, 1313, 1238, 1184, 1163, 1147, 1072, 1033, 1012, 839 cm⁻¹ (SI, Figure S9). ¹H NMR ((CD₃)₂SO, 399.78 MHz): δ = 7.32–7.36 (m, 2H, CH), 7.49–7.57 (m, 6H, CH), 7.85–7.87 (m, 2H, CH), 8.01–8.04 (m, 2H, CH), 14.42 (s, 1H, NH) (SI, Figure S10). ¹³C NMR ((CD₃)₂SO, 100.5 MHz): δ = 81.6 (Csp), 83.6 (Csp), 119.1 (CH), 120.8 (C), 126.0 (CH), 127.8 (CH), 129.5 (CH), 131.9 (CH), 136.5 (C), 140.6 (C), 147.5 (C) (SI, Figure S11). UV-VIS λmax, nm (Irel, %): 252 (6671), 372 (11396). MS (EI, 70 eV), m/z (Irel, %): 324 [M⁺] (100), 247 (4), 219 (41), 92 (31), (SI, Figure S12). HRMS ESI TOF: exact mass found 323.1277 (exact mass calculated for C₂₁H₁₄N₄ 323.1291) (SI, Figure S13).

Crystal data for C₂₁H₁₆N₄ (M = 324.38 g/mol): Orthorhombic, space group Pbca, a = 7.89300(10) Å, b = 18.6508(3) Å, c = 22.6827(3) Å, α = 90°, β = 90°, γ = 90°, V = 3339.14(8) ų, Z = 8, T = 120 K, μ = 6.21 cm⁻¹, Dcalc. = 1.290 Mg/m³. In total, 24,973 reflections were measured, 3221 of which were unique and used in all calculations. The final R₁ was 0.0342, and the wR₂ was 0.0913 (all data) (SI, Tables S1–S7). CCDC 2,410,636 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge at http://www.ccdc.cam.ac.uk/or (accessed on 29 November 2021) from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44-1223-336033; E-mail: deposit@ccdc.cam.ac.uk.