1. Chemical context

Complexes of early transition- and rare-earth metals featuring di­amine­bis­(phenols) have been employed as efficient catalysts for the polymerization of olefins and cyclic esters (Tshuva et al., 2000; Carpentier et al., 2015), while those of late transition metals have been shown to be effective at promoting cross-coupling (Hasan et al., 2011; Qian et al., 2011; Reckling et al., 2011). Several reports have noted that the coordination mode and donor-atom identity play an important role in the activity of the resulting complexes (Tshuva et al., 2001; Qian et al., 2011; Chard et al., 2014). We have previously observed both κ² and κ³ coordination modes for Pd^II complexes of related amine­bis­(phenols), in which steric parameters of the phenolate moiety played a significant role in the coordination behavior (Graziano, Collins et al., 2019; Graziano, Wile et al., 2019).

Di­amine­bis­(phonols) may be readily prepared via a Mannich reaction (Tshuva et al., 2000, 2001; Kasting et al., 2015), and the ligand framework may be modified by altering the steric or electronic parameters of the commercially available reaction components. Both bridging and pendant di­amine variants are known, depending on whether the ligand precursor is prepared using an N,N- or N,N′-disubstituted amine. Prior reports of Fe^II complexes supported by halogenated amine­bis­(phenols) bearing an alkyl ether donor group suggest poorer catalytic activity when compared with ligands bearing bulky alkyl-substituted phenols (Hasan et al., 2011; Reckling et al., 2011). However, it is speculated that the inferior catalytic activity is related to the air sensitivity of these Fe complexes, and potential catalyst decomposition pathways under the conditions employed for this Kumada coupling. Based on these reports and our inter­est in extending the range of amine­bis­(phenols) suitable for use as ligands, we prepared the title compound 1 and obtained single crystals suitable for X-ray diffraction studies. It was speculated that a direct comparison of the metrical parameters for 1 with those of related amine­bis­(phenols) with pendant ether groups would provide insight into the choice of halogenated phenols in the design of this ligand, for use in combination with late transition metals.

2. Structural commentary

Compound 1 exhibits bond lengths and angles consistent with the depiction as an aliphatic amine with ether and phenol moieties depicted in Fig. 1. C—N bond lengths [1.472 (2), 1.475 (2), and 1.476 (2) Å], C—O_phenol bond lengths [1.354 (1) and 1.346 (2) Å], and C—Cl bond lengths [1.734 (1), 1.732 (1), 1.728 (1), and 1.732 (9) Å] are not significantly different from one another, within ±3 esd. The sum of C—N—C angles about N1 is 337.7°, representing a deviation of 0.41093 (1) Å from the plane defined by C1/C8/C15. This extent of pyramidalization is consistent with an sp³-hybridized (tertiary) amine, and is influenced by the presence of an intra­molecular O2—H2⋯N1 hydrogen bond (Table 1). This hydrogen-bonding inter­action generates a six-membered ring with an S(6) graph-set descriptor, consistent with our prior observations for similar mol­ecules (Bowser et al., 2016). The ether fragment was modeled as a two-component disorder involving C16, O3, and C17, with a C16—O3—C17 bond angle of 112.0 (3)°. The methyl­ene [C16—O3, 1.405 (3) Å] and methyl [C17—O3, 1.413 (4) Å] C—O bond lengths are not significantly different from one another, within ±3 esd. Atom Cl2 was also modeled as having two-component disorder.

Table 1 Hydrogen-bond geometry (Å, °) D—H⋯A D—H H⋯A D⋯A D—H⋯A O1—H1⋯Cl1 0.82 (2) 2.58 (2) 3.0455 (12) 117.4 (17) O2—H2⋯N1 0.87 (2) 1.83 (2) 2.6365 (16) 153 (2) O1—H1⋯O2i 0.82 (2) 2.01 (2) 2.7709 (14) 152.5 (19) Symmetry code: (i) .

Figure 1 Labeled depiction of the title compound, with displacement ellipsoids drawn at the 50% probability level.

Compound 1 is chemically similar to the related ligands featuring alkyl substituents in place of the Cl substituents in 1. A comparison of bond lengths and angles for compound 1 and CAKDUP (Hasan et al., 2011), ZAVTEX (Dean et al., 2012), SOJBIE and SOJBUQ (Chapurina et al., 2014) is presented in Table 2. Despite the differences in space group, all compounds exhibit similar metrical parameters. The most notable differences between these structures are the shorter C—O_phenol bond lengths for compound 1 [1.354 (1) and 1.346 (2) Å], consistent with the electron-withdrawing effect of the Cl substituents on the phenol rings. In contrast, compounds containing electron-donating alkyl substituents exhibit slightly longer C—O_phenol bond lengths. Bond lengths for other moieties are more similar between 1 and these previously reported structures. The sum of C—N—C bond angles and the C—O—C bond angles indicate a similar electronic environment for the amine and ether donors of all compounds. This supports the hypothesis that compound 1 would have similar steric parameters to closely related ligands, but function as a more electrophilic donor.

3. Supra­molecular features

The hydrogen-bond geometry is noted in Table 1. A short contact was noted between O2 and N1 [2.6365 (14) Å], consistent with a hydrogen bond between the phenol and tertiary amine moieties, O2—H2⋯N1. By refining the position of H2, the H2⋯N1 distance was found to be 1.83 (2) Å, suggesting a strong hydrogen-bonding inter­action that supports the observed pyramidalization of the tertiary amine. Hydrogen bonding is also observed between O1—H1⋯O2′ (and conversely O1′—H1′⋯O2), resulting in the formation of a centrosymmetric dimer with an R₂²(20) graph-set descriptor, as shown in Fig. 2. The H1⋯O2′ distance [2.01 (2) Å] suggests a strong hydrogen-bonding inter­action.

Figure 2 Depiction of the centrosymmetric dimer formed as a result of hydrogen bonding. See Table 1 for symmetry codes.

An additional short contact was noted between O1 and Cl1 [3.0459 (12) Å] with a corresponding H1⋯Cl1 distance of 2.58 (2) Å, suggesting a weak inter­action. Close contacts between Cl1⋯Cl4′ [3.468 (3) Å] and Cl1⋯O2′ [3.266 (2) Å] centers are inconsistent with weak halogen bonding, and instead are attributed to packing effects. Further evidence is provided by the small observed angles around Cl1 (104.10° for C4—Cl1⋯O2′ and 72.24° for C4—Cl1⋯Cl4′) and Cl4 (147.46° for C13—Cl4⋯Cl1′) compared with 180° expected for a halogen bond.

4. Database survey

A search of the Cambridge Structural Database (CSD, update of November 2022; Groom et al., 2016) for related amine bis­(phenols) featuring a pendant ether moiety returned 19 results, all featuring alkyl or hydrogen substituents on the phenol. Of these, the most closely related were reported by Kozak and co-workers, and feature 2,4-dimethyl or 2-tert-butyl-4-methyl phenol substituents in place of the Cl substit­uents reported in this work. These include CSD refcodes CAKDUP (Hasan et al., 2011), HITHIC (Chowdhury et al., 2008), and ZAVTEX (Dean et al., 2012). Structures XAQWUL, XAQXAS, XARCOM, XARCUS, XARDAZ, and XARHOR (Fazekas et al., 2021) are derived from various amino-acid ethyl esters and feature 2,4-dimethyl or 2,4-di-tert-butyl substituents. TIDLIC (Safaei et al., 2007) features a similar 2,4-di-tert-butyl substitution pattern in combination with a pendant methyl-tetra­hydro­furanyl amine substituent. Structure UZOZOA (Kuźnik et al., 2019) contains a di­eth­oxy­ethyl amine moiety as well as otherwise unsubstituted 2-naphthol donors as a synthetic precursor to the target ligand. Structures SOJBIE and SOJBUQ (Chapurina et al., 2014) featuring bulky cumyl substituents were reported as synthetic precursors to the corresponding Sc and Y complexes.

A series of compounds featuring amino phenols as part of a larger structure or macrocycle have been reported. KEWFUP, KEWGAW, and KEWGEA (Riisiö et al., 2012) feature two amine-bis­(phenol) moieties connected by an ethyl-bis­(eth­oxy­eth­yl) linkage and exhibit significant hydrogen bonding in the solid state. Two related macrocycles featuring an ethyl-bis­(eth­oxy­eth­yl) PEXNOY (Takemura et al., 2018) or di­sulfide MEQFUJ (Ito et al., 2000) bridge have been reported. Entry TAXLIN (Hampton et al., 1996) is a tri-aza-calix[3]arene featuring a glycine-derived amino ester moiety.

5. Synthesis and crystallization

Compound 1 was prepared using a method analogous to that reported for related compounds (Graziano, Collins et al., 2019; Reckling et al., 2011). This reaction scheme is shown in Fig. 3. 2,4-Di­chloro­phenol (1.957 g, 12.0 mmol, 2 eq.) and a 37 wt.% aqueous solution of formaldehyde (0.974 g, 12.0 mmol, 2 eq.) were added to a 20 mL scintillation vial containing 5.0 mL of methanol and a PTFE-coated magnetic stir bar. 2-Meth­oxy­ethyl­amine (0.521 mL, 6.00 mmol, 1 eq.) was added, and the vial was immediately capped and placed in an aluminum heating block maintained at 343 K. The clear colorless solution turned bright yellow within 1 h of heating, and maintained this appearance for 18 h, at which time the vial was removed from the heating block. The reaction mixture was poured into cold water (20 mL), and extracted with ethyl acetate (3 × 20 mL). The organic layers were combined, dried over MgSO₄, and concentrated in vacuo to yield a yellow oil. The product was purified using an automated column chromatography system with an ethyl acetate/hexa­nes gradient (0% EtOAc hold 1 min → 20% EtOAc in 2 min, hold 4 min → 100% EtOAc in 4 min, hold 2 min). The desired product was isolated as a yellow oil (0.594 g, 1.40 mmol, 23%, R_f = 0.40 in 40% EtOAc) that generated single crystals suitable for X-ray diffraction studies upon standing.

Figure 3 Reaction scheme.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3. Atoms H1 and H2 were located in difference-Fourier maps and freely refined. All other hydrogen atoms were placed at calculated positions (aromatic: 0.93 Å, methyl­ene: 0.97 Å, meth­yl: 0.96 Å) using suitable HFIX commands and refined as riding with U_iso(H) = 1.2–1.5U_eq(C). The methyl group was refined as an idealized rotating group. Cl2 was modeled as a two-component disorder with partial occupancies of 0.49 (3) and 0.51 (3). The pendant ether group was modeled as a two-component disorder with partial occupancies of 0.867 (3) and 0.133 (3). Atomic displacement parameters were restrained using SIMU with a sigma of 0.01 for inter­nal and 0.02 for terminal atoms. The atoms within the disordered group were restrained to have similar bond distances. Cl2 was modeled as a two-component disorder with partial occupancies of 0.52 (4) and 0.48 (4).

Table 3 Experimental details Crystal data Chemical formula C17H17Cl4NO3 Mr 425.11 Crystal system, space group Triclinic, P Temperature (K) 293 a, b, c (Å) 9.4912 (2), 10.0464 (2), 11.1169 (3) α, β, γ (°) 103.930 (2), 113.048 (2), 90.543 (2) V (Å3) 940.32 (4) Z 2 Radiation type Mo Kα μ (mm−1) 0.65 Crystal size (mm) 0.56 × 0.36 × 0.31   Data collection Diffractometer XtaLAB Mini II Absorption correction Analytical (CrysAlis PRO; Rigaku OD, 2019) Tmin, Tmax 0.886, 0.940 No. of measured, independent and observed [I > 2σ(I)] reflections 56643, 5724, 4418 Rint 0.056 (sin θ/λ)max (Å−1) 0.722   Refinement R[F2 > 2σ(F2)], wR(F2), S 0.035, 0.100, 1.05 No. of reflections 5724 No. of parameters 274 No. of restraints 71 H-atom treatment H atoms treated by a mixture of independent and constrained refinement Δρmax, Δρmin (e Å−3) 0.34, −0.25 Computer programs: CrysAlis PRO 1.171.40.55a (Rigaku OD, 2019), SHELXT (Sheldrick, 2015a), SHELXL2016/6 (Sheldrick, 2015b), OLEX2 1.3-ac4 (Dolomanov et al., 2009), PLATON (Spek, 2020).