4-[2-(Chlorodiphenylstannyl)phenyl]-4-hydroxybutan-2-one

Abstract

An aldol condensation reaction between [2-(O=CH)C₆H₄]SnPh₂Cl and acetone gave [2-{CH₃C(=O)CH₂(OH)CH}C₆H₄]SnPh₂Cl (1). The compound was characterized in a solution using multinuclear NMR spectroscopy and HR-MS spectrometry and in a solid state using IR spectroscopy and single-crystal X-ray diffraction. The molecular structure revealed the presence of both enantiomers in the crystal.

1. Introduction

[(C,O)-aryl]tin(IV) compounds [1,2,3,4,5,6,7] have raised interest due to their versatility when the pendant arm contains an aldehyde [8,9,10], a ketone [11,12] or an amide [13] functional group, which can be readily transformed into imines by condensation with amines [8,10,14,15], amines by hydrogenation of the previously mentioned imines [16], or hydroxides by hydrogenation [16]. Functionalization of such derivatives can produce compounds with multiple donor atoms in the pendant arm ligand(s), allowing their use in the preparation of hetero- [14,15,16] or homomultimetallic species [15,17]. The (C,O)-aryl ligand supported the formation of an unusual octacoordinated tin(IV) species with four [2-(O=CH)C₆H₄] substituents encumbering the metal center [8]. Some of the designed compounds showed encouraging biological activity toward several carcinoma cells [11], while others demonstrated catalytic properties [5].

Aldol condensation is one of the most resourceful organic reactions [18] resulting in the formation of a new C−C bond. The reaction between an aldehyde or ketone and a compound containing an enolizable hydrogen atom is the usual pathway for aldol condensation and results in the formation of a β-hydroxy carbonyl derivative [19]. The reaction is usually performed in the presence of an acid or base catalyst [20,21], but similar results can be obtained by aldol reaction, which can provide regiospecific generation of novel carbon–carbon bonds [22,23]. The interest in this reaction has grown lately due to its applications in converting small molecules into larger ones [24], transforming biomass into more valuable chemicals [25], or, more recently, building organic functional materials [26]. Here, we report the first example of aldol condensation involving a metal-bearing benzaldehyde.

2. Results and Discussion

We have previously reported the hydrolysis of [2-{(CH₂O)₂CH}C₆H₄]SnPh₂Cl in a water/THF mixture to give [2-(O=CH)C₆H₄]SnPh₂Cl [17]. When the hydrolysis was attempted in a water/acetone mixture, traces of aldol condensation product [2-{CH₃C(=O)CH₂(OH)CH}C₆H₄]SnPh₂Cl (1) were detected. In order to isolate this compound, [2-(O=CH)C₆H₄]SnPh₂Cl [17] was stirred for 1 week at room temperature in acetone with a small quantity of p-TsOH, leading to the isolation of [2-{CH₃C(=O)CH₂(OH)CHC₆H₄]SnPh₂Cl (1) (Scheme 1).

The solution behavior of compound 1 was monitored using multinuclear NMR spectroscopy. The assignment (according to the numbering scheme shown in Figure S1) of the ¹H (Figure S2) and ¹³C NMR (Figure S3) chemical shifts was made using 2D NMR correlation experiments [COSY (Figure S4), HSQC (Figure S5), HMBC (Figure S6)]. Both ¹H and ¹³C NMR spectra of 1 display the predicted number of resonance signals with the characteristic multiplicity pattern corresponding to the organic fragments bonded to tin. The strong O→Sn intramolecular interaction disclosed in the solid state (vide infra) is also conserved in solution. Additionally, the presence of a five-coordinate tin atom in CDCl₃ solution is supported by the calculated C-Sn-C angle based on the ¹J_CSn coupling constants. According to Holeček [27], the magnitude of the calculated C-Sn-C angle observed in CDCl₃ solution for 1 (123.1°) is indicative of a trigonal bipyramidal geometry around the metal center in solution, with the two phenyl substituents located at equatorial sites.

The ¹¹⁹Sn{¹H} NMR spectrum of compound 1 fulfills the solution characterization with a singlet resonance at δ = −145.7 ppm (Figure S7). This magnitude matches well with those found for related triaryltin(IV) halides [2-{(CH₂O)₂CH}C₆H₄]SnPh₂Cl (δ = −116 ppm) [17] or [2-(O=CH)C₆H₄]SnPh₂Cl (δ = −121 ppm) [17] and suggests a five-coordinated metal center in solution.

The HR-MS APCI(+) spectrum of 1 contains a base peak at m/z = 379.01745, and it was assigned to the [{2-(O=CH)C₆H₄}SnPh₂+H]⁺ fragment, while the [M–Cl]⁺ fragment is visible at m/z = 435.05061 (2.85%) (Figure S8).

The IR stretching vibration corresponding to the O–H bond of 1 can be observed as a weak band around 3100 cm⁻¹. The ν_C=O stretching vibration band corresponding to the ketone is found at 1693 cm⁻¹. These wavenumbers fit into the characteristic range of 1775–1650 cm^–1 for a ketone group [28] (Figure S9).

The molecular structures for compound 1 were established by single-crystal X-ray diffraction and are depicted in Figure 1. Suitable crystals for X-ray diffraction studies were obtained through the slow diffusion of hexane into a CHCl₃ solution of 1. The complex crystallized in the monoclinic space group P2₁/c. This is the first structural determination of a compound containing a pendant arm with an OH group coordinated to a tin atom. The unit cell of compound 1 contains the two enantiomers (R_c7-1a and S_C29-1b) generated by the chirality of the aliphatic carbon atom from an aldol fragment directly bonded to the aromatic ring. The metal centers are pentacoordinated with a distorted trigonal bipyramidal geometry, as a result of strong O→Sn intramolecular interactions [2.376(2) Å in R_c7-1a, 2.374(2) Å in S_C29-1b] trans the chlorine [168.91(4)° in R_c7-1a, 168.66(5)° in S_C29-1b]. These tin–oxygen intramolecular contacts within the SnC₃O chelate ring in 1 are the shortest alongside all the related [(C,O)-aryl]tin(IV) derivatives, e.g., [2-{(CH₂O)₂CH)}C₆H₄]SnPh₂Cl [2.487(3) Å], [2-(O=CH)C₆H₄]SnPh₂Cl [2.451(6) Å, 2.462(7) Å, for the two molecules from the unit cell] [17], [2-{(CH₂O)₂CH}C₆H₄]Me₂SnCl [2.486(4) Å], [2-(O=CH)C₆H₄]Me₂SnCl [2.466(5) Å, 2.491(4) Å. for the two molecules from the unit cell] [15].

Each enantiomer forms dimers through strong O−H⋯O=C intermolecular interactions [O1⋯H1O = 1.87(2) Å, O1⋯O2′ = 2.705(2) Å for R_c7-1a and O3⋯H3O = 1.87(2) Å, O3⋯O4″ = 2716(2) Å for S_C29-1b] (Figure 2). Each type of dimer is further connected by C−H⋯Cl interactions in a layer spreading along bc plane, with layers containing R_c7-1a and S_C29-1b enantiomers staked in an alternative fashion (Figure S10).

3. Materials and Methods

All synthetic manipulations were performed in the air. Solvents and chemicals were used as provided without further purification. [2-(O=CH)C₆H₄]SnPh₂Cl was prepared according to the method reported in the literature [17]. Multinuclear NMR spectra (¹H, ¹³C, ¹¹⁹Sn, and 2D experiments) were recorded at room temperature on a Bruker Avance III 400 NMR spectrometer (Bruker BioSpin, Ettlingen, Germany). The ¹H and ¹³C chemical shifts are reported in δ units (ppm) relative to the residual signal of the deuterated solvent (ref. CDCl₃: ¹H 7.26 ppm, ¹³C 77.16 ppm). For the ¹¹⁹Sn NMR spectra, the chemical shifts are reported in ppm relative to SnMe₄. ¹H and ¹³C resonances were assigned using 2D NMR experiments (COSY, HSQC, and HMBC). The NMR spectra were processed using the MestReNova 12 software [29]. Abbreviations used in multiplicities are s, singlet; d, doublet; t, triplet; m, multiplet; and br, broad. The melting point was measured with an Electrothermal 9200 apparatus and was not corrected. Infrared spectra were recorded on a Jasco FT-IR 4100–ATR (JASCO EUROPE s.r.l., Cremella, Italy). The abbreviations w = weak, m = medium, s = strong, vs. = very strong, b = broad, sh = shoulder were used to assign the peak intensities. The APCI(+) mass spectrum was recorded on a Thermo Scientific LTQ Orbitrap XL mass spectrometer (ThermoFisher Scientific, Bremen, Germany) equipped with a standard ESI/APCI source. The sample was introduced by direct infusion with a syringe pump, and CH₃CN was used as the mobile phase.

3.1. Synthesis of 4-[2-(Chlorodiphenylstannyl)phenyl]-4-hydroxybutan-2-one 1

A catalytic amount of p-TsOH was added to a solution of [2-(O=CH)C₆H₄]SnPh₂Cl (0.8 g, 1.94 mmol) in acetone (30 mL) and the reaction mixture was left under stirring for 1 week at room temperature. Slow evaporation of the solvent gave the title compound as a white crystalline solid, 0.25 g (27%).

¹H NMR (400.1 MHz, CDCl₃, 20 °C): δ 1.88s (3H, H10), 2.35dd (1H, H8b, ²J_HH = 18.8 Hz, ³J_HH = 10.9 Hz), 2.80dd (1H, H8a, ²J_HH = 18.8 Hz, ³J_HH = 2.2 Hz), 5.37d (1H, H7, ³J_HH = 10.8 Hz), 5.89d (1H, H11, ³J_HH = 1.5 Hz), 7.11d (1H, H3, ³J_HH = 7.2 Hz), 7.35m 3H, H18, H19), 7.39m (3H, H14, H15), 7.42m (1H, H4), 7.47td (1H, H5, ³J_HH = 7.4 Hz, 4JHH = 1.2 Hz), 7.68m (2H, H17), 7.77m (2H, H13), 8.39dd (1H, H6, ³J_HH = 7.3 Hz, ⁴J_HH = 1.4 Hz, ³J_SnH = 69.9 Hz).

¹³C{¹H} NMR (100.6 MHz, CDCl₃, 20 °C): δ 30.2s (C10), 50.81s (C8), 71.2s (C7, ³J_SnC = 16 Hz), 124.6s (C3, ³J_117/119SnC = 61/64 Hz), 128.4s (C5, ³J_117/119SnC = 66/69 Hz), 128.8s (C14, ³J_117/119SnC = 69/72 Hz), 128.8s (C18, ³J_117/119SnC = 66/70 Hz), 129.4s (C19, ⁴J_SnC = 14 Hz), 129.7s (C15, ⁴J_SnC = 15 Hz), 129.9s (C4, ⁴J_SnC = 14 Hz), 133.8s (C1), 135.8s (C17, ³J_SnC = 49 Hz), 136.2s (C13, ²J_SnC = 51 Hz), 138.0s (C6, ²J_SnC = 41 Hz), 141.2s (C12, ¹J_117/119SnC = 738/769 Hz), 143.8s (C16, ¹J_117/119SnC = 709/742 Hz), 145.8s (C2, ²J_SnC = 40 Hz), 211.1s (C9).

¹¹⁹Sn{¹H} NMR (149.2 MHz, CDCl₃, 20 °C): δ −145.7s.

HR-MS (APCI+, CH₃CN): m/z (%): [R–Cl]⁺, calcd. for C₂₂H₁₉O₂Sn 435.04015; found 435.05061 (3). [{2-(O=CH)C₆H₄}SnPh₂+H⁺], calcd. for C₁₉H₁₅OSn 379.01394; found 379.02260 (100.00). [{2-(O=CH)C₆H₄}SnPh⁺], calcd. for C₁₃H₉OSn 300.96699; found 300.97370 (8).

IR (ATR, υ, cm⁻¹): 3100 (O–H), 1693 m (C=O).

3.2. X-Ray Crystallography

X-ray diffraction data for compound 1 were collected at 101(2) K using a Bruker D8 VENTURE diffractometer (Bruker AXS GmbH – Analytical X-Ray Systems, Karlsruhe, Germany) using Mo radiation (λ = 0.71073 Å) from a IμS 3.0 microfocus source with multilayer optics. The structure was solved by direct method and refined with anisotropic thermal parameters for non-H atoms. Hydrogen atoms were placed in fixed, idealized positions and refined with a riding model and a mutual isotropic thermal parameter, except H10 and H30 from the OH groups, which were found in the electron density difference map and refined with restrained distances of 0.85(2) Å and 0.89(2) Å. For structure solving and refinement, the Bruker APEX5 (version 2023.9-2) software package was used [30]. Visual representations were created with the Diamond program [31].

Crystal data for C₂₂H₂₁ClO₂Sn (M = 471.53 g/mol) are as follows: monoclinic, space group P2₁/c (no. 14), a = 15.5621(5) Å, b = 16.7398(6) Å, c = 15.6454(6) Å, β = 96.5030(10)°, V = 4049.5(2) ų, Z = 8, T = 101(2) K, μ(MoKα) = 0.71073 mm⁻¹, and D_calc = 1.547/cm³, with 143,745 reflections measured (2.13 ≤ 2Θ ≤ 28.30°), 10,076 unique (R_int = 0.0431, R_sigma = 0.0156), which were used in all calculations. The final R₁ was 0.0228 (I > 2σ(I)) and wR₂ was 0.0505 (all data).

4. Conclusions

A novel [(C,O)-aryl]tin(IV) derivative, [2-{CH₃C(=O)CH₂(OH)CH}C₆H₄]SnPh₂Cl, was obtained through an aldol condensation reaction. The structure of the synthesized organotin(IV) compound was established using both nuclear magnetic resonance and X-ray diffraction.