Synthesis and structural characterization of substituted phenols with a m-terphenyl backbone 2,4,6-R₃C₆H₂OH (R=2,4,6-Me₃C₆H₂, Me₅C₆)

1 Introduction

In recent years, molybdenum and tungsten complexes of aryloxo ligands with a m-terphenyl backbone were shown to be active catalysts in Z-selective olefin metathesis [1–6], whereas cationic aluminum aryloxides with these ligands were found to catalyze CO₂ reduction with Et₃SiH to methane [7]. The bulky terphenyloxo ligands were also shown to stabilize rare species such as the carbene analogues of heavy tetrels [8, 9], monomeric two-coordinate cobalt complexes [10], or unsolvated alkali metal aryloxides [11]. The symmetrically substituted phenols 2,6-R₂C₆H₃OH (R=2,4,6-Me₃C₆H₂ [12], 2,6-iPr₂C₆H₃ [11] and 2,4,6-iPr₃C₆H₂ [11]), used as starting materials for the preparation of these terphenolates, were synthesized from m-terphenyl lithium derivatives and nitrobenzene, following the previously reported reaction of phenyl lithium with nitrobenzene [13]. Other methods used for the synthesis of similar substituted phenols are the ortho-arylation of phenol [14, 15], Suzuki cross-coupling reactions [16], or reactions of aryllithium with oxygen or peroxides [17].

We report the synthesis by Kumada cross-coupling reactions and the structural characterization in solution and solid state of the novel substituted phenols with a m-terphenyl backbone 2,4,6-R₃C₆H₂OH [R=2,4,6-Me₃C₆H₂ (1), Me₅C₆ (2)].

2 Results and discussion

The compounds 1 and 2 were synthesized using as starting materials 2,4,6-I₃C₆H₂OH and five equivalents of the corresponding Grignard reagent (Scheme 1). The complexes [(IPr)PdCl₂(3-ClC₅H₄N)] (IPr=1,3-bis-(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene) and [(IPr)PdCl(μ-Cl)]₂, respectively, were used as catalysts. Compound 1 was also obtained using [(IPr)PdCl(μ-Cl)]₂ as catalyst, and 2,4,6-X₃C₆H₂OH as starting materials, in 28 % (X=Br) and 50 % (X=I) yields. Both compounds were characterized in solution by ¹H and ¹³C NMR spectroscopy and by high-resolution mass spectrometry.

Scheme 1

Synthesis of 1 and 2.

In the ¹H NMR spectra of 1 and 2, the singlet resonance signals corresponding to the OH group have a chemical shift of δ=4.57 and 4.58 ppm, respectively. These values are comparable to those reported for 2,6-(2′,4′,6′-Me₃C₆H₂)₂C₆H₃OH (δ=4.53 ppm) [12], 2,6-(2′,6′-iPr₂C₆H₃)₂C₆H₃OH (δ=4.46 ppm), or 2,6-(2′,4′,6′-iPr₃C₆H₂)₂C₆H₃OH (δ=4.57 ppm) [11]. In the aromatic region of the ¹H NMR spectrum of 1, there are three singlet resonance signals corresponding to the three nonequivalent aromatic hydrogen atoms, whereas in the spectrum of 2, as expected, only one singlet resonance signal was observed. In the aliphatic region of the spectrum of 1, the resonance signals corresponding to the methyl groups in ortho-positions of the two nonequivalent mesityl groups overlap. Also, in the spectrum of 2, the resonance signals corresponding to six types of methyl groups are overlapping. In the ¹³C NMR spectra of 1 and 2, there are 12 resonance signals in the aromatic region, and four and six resonances, respectively, in the aliphatic region.

In the HRMS (+)-APCI spectra of 1 and 2, the pseudo-molecular ions [M+H]⁺ were observed, and for both compounds, the mass measurement accuracy of the monoisotopic ions is within 5 ppm.

The molecular structures of compounds 1 and 2 were determined by single-crystal X-ray diffraction. The crystals of 1 contain two crystallographically independent molecules. Graphical representations of one of the independent molecules of 1 and of the molecule of 2 are depicted in Figs. 1 and 2, respectively.

Fig. 1

Displacement ellipsoid (25 %) representation of one of the crystallographically independent molecules of 1. The hydrogen atoms bonded to carbon atoms were omitted for clarity. The smaller components of the disordered hydroxyl groups (O1B and O1C and the corresponding hydrogen atoms) are drawn in gray.

Fig. 2

Displacement ellipsoid (50 %) representation of 2. The hydrogen atoms bonded to carbon atoms were omitted for clarity. The smaller components of the disordered hydroxyl groups (O1B and O1C and the corresponding hydrogen atoms) are drawn in gray.

The C–O bond lengths, including those of disordered hydroxyl groups, have values ranging from 1.27(5) to 1.377(12) Å in 1, and from 1.305(4) to 1.368(5) Å in 2. These values are similar to those determined for 2,6-Ph₂C₆H₃OH (1.381(4) Å) [18], 2,6-(2′,4′,6′-Me₃C₆H₂)₂C₆H₃OH (1.356(3), 1.375(3) Å) [12], 2,6-(2′,6′-iPr₂C₆H₃)₂C₆H₃OH (1.407(2) Å) [11], or 2,6-(2′,4′,6′-iPr₃C₆H₂)₂C₆H₃OH (1.381(2) Å) [11].

In compound 1, the angles between the planes containing the mesityl groups and the plane of the central aromatic ring range from 76.5(2) to 88.1(3)°, whereas in 2, the analogous angles between the pentamethylphenyl groups and the plane of the central ring are 70.5(1), 82.6(1), and 84.3(1)°. These values are similar to those reported for related substituted phenols with a m-terphenyl backbone [11, 12], but larger than those found for 2,6-Ph₂C₆H₃OH [18].

Only the disordered component of 1 containing O2A was observed to form dimers through hydrogen bonds (O2A–H2A 0.82 Å, H2A···O2Aⁱ 2.09 Å, O2A–H2A···O2Aⁱ 2.833(12) Å, O2A–H2A···O2Aⁱ 151°). The lack of dimer associations for the other molecules is consistent with the situation observed for 2,6-(2′,6′-iPr₂C₆H₃)₂C₆H₃OH and 2,6-(2′,4′,6′-iPr₃C₆H₂)₂C₆H₃OH [11], compounds in which the steric repulsions between the flanking groups hinder the association into dimers through hydrogen bonds.

In the crystals of 1, the molecules of the asymmetric unit containing O1A and O2A are involved in seven and three, respectively, intermolecular C–H···π interactions with other neighboring molecules. Additionally, there are two C–H···π interactions between one of the dichloromethane molecules and the molecules containing O1A. In 2, the molecule of the asymmetric unit is connected through C–H···π interactions to two neighboring molecules and to two dichloromethane molecules. In the crystals of 2, the dichloromethane molecules are also connected to the arene backbone through C–Cl···π interactions (Cl···Cg: 3.716(3), 3.852(4), 3.825(5) Å).

3 Experimental section

The Kumada cross-coupling reactions were performed in dry tetrahydrofuran (distilled under argon atmosphere from potassium prior to use), under argon atmosphere, and the work-up was carried out in air. 2,4,6-Triiodophenol [19], bromopentamethylbenzene [20], [(IPr)PdCl(μ-Cl)]₂ (IPr=1,3-bis-(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene) [21] and [(IPr)PdCl₂(3-ClC₅H₄N)] (PEPPSI-IPr) [22] were prepared according to methods reported in the literature. All other reagents were commercially available and used as received.

The NMR spectra were recorded on a Bruker Avance III 400 spectrometer. The chemical shifts are reported in δ units (ppm) relative to the residual peak of solvent (CHCl₃, 7.26 ppm) for the ¹H NMR spectra and to the peak of the deuterated solvent (CDCl₃, 77.16 ppm) for the ¹³C NMR spectra [23].

HRMS (+)-APCI spectra were recorded on a Thermo Scientific Orbitrap XL spectrometer. Data analysis and calculations of the theoretical isotopic patterns were carried out with the Xcalibur software package [24].