Low-Dimensional Architectures in Isomeric cis-PtCl2{Ph2PCH2N(Ar)CH2PPh2} Complexes Using Regioselective-N(Aryl)-Group Manipulation

The solid-state behaviour of two series of isomeric, phenol-substituted, aminomethylphosphines, as the free ligands and bound to PtII, have been extensively studied using single crystal X-ray crystallography. In the first library, isomeric diphosphines of the type Ph2PCH2N(Ar)CH2PPh2 [1a–e; Ar = C6H3(Me)(OH)] and, in the second library, amide-functionalised, isomeric ligands Ph2PCH2N{CH2C(O)NH(Ar)}CH2PPh2 [2a–e; Ar = C6H3(Me)(OH)], were synthesised by reaction of Ph2PCH2OH and the appropriate amine in CH3OH, and isolated as colourless solids or oils in good yield. The non-methyl, substituted diphosphines Ph2PCH2N{CH2C(O)NH(Ar)}CH2PPh2 [2f, Ar = 3-C6H4(OH); 2g, Ar = 4-C6H4(OH)] and Ph2PCH2N(Ar)CH2PPh2 [3, Ar = 3-C6H4(OH)] were also prepared for comparative purposes. Reactions of 1a–e, 2a–g, or 3 with PtCl2(η4-cod) afforded the corresponding square-planar complexes 4a–e, 5a–g, and 6 in good to high isolated yields. All new compounds were characterised using a range of spectroscopic (1H, 31P{1H}, FT–IR) and analytical techniques. Single crystal X-ray structures have been determined for 1a, 1b∙CH3OH, 2f∙CH3OH, 2g, 3, 4b∙(CH3)2SO, 4c∙CHCl3, 4d∙½Et2O, 4e∙½CHCl3∙½CH3OH, 5a∙½Et2O, 5b, 5c∙¼H2O, 5d∙Et2O, and 6∙(CH3)2SO. The free phenolic group in 1b∙CH3OH, 2f∙CH3OH, 2g, 4b∙(CH3)2SO, 5a∙½Et2O, 5c∙¼H2O, and 6∙(CH3)2SO exhibits various intra- or intermolecular O–H∙∙∙X (X = O, N, P, Cl) hydrogen contacts leading to different packing arrangements.


Introduction
Tertiary phosphines, and their phosphine oxides, have played an important role in the study of supramolecular and self-assembly processes [1][2][3]. Their synthetic versatility, coupled with ease of substituent modification, has no doubt played a significant contribution over the years. Hydrogen bonding interactions are routinely encountered in supramolecular ligand systems as illustrated by the elegant studies from Breit [4], Reek [5], and others [6,7]. More recently, amongst other common types of non-covalent interactions, those based on halogen bonding [8,9] and H δ+ ···H δ− have been reported [10].
For a number of years, we [11][12][13][14][15][16], and others [17][18][19][20][21][22], have been interested in aminomethylphosphines, readily amenable by Mannich condensation reactions. Such interest stems from the relative ease of accessing P-monodentate ligands based on a P-C-N linker [11,15,16,19,20,22] or P/P-bidentate derivatives bearing a P-C-N-C-P backbone [12][13][14][17][18][19]21]. Previously, we have shown that the N-arene group can be easily tuned with, for example, various H-bonding donor/acceptor sites based on -CO 2 H/OH groups [12][13][14][15][16]. In continuation of these studies, we report here our work on the regioselective positioning of amide/hydroxy and methyl groups within a series of aminomethylphosphines, both as the free ligands and when coordinated to a square-planar Pt(II) metal centre. Our rationale for introducing an -C(O)NH-group is based on the known use of 16]. In continuation of these studies, we report here our work on the regioselective positioning of amide/hydroxy and methyl groups within a series of aminomethylphosphines, both as the free ligands and when coordinated to a square-planar Pt(II) metal centre. Our rationale for introducing an -C(O)NH-group is based on the known use of this functionality in supramolecular chemistry [23] and, furthermore, the recent interest in amide-modified phosphines for their variable coordination chemistry [24][25][26], binding nitroaromatics [27], and relevance to catalysis based on Pd [28]. Our choice of metal fragment in this work, "cis-PtCl2", is based on its capability to support a relatively small bite angle diphosphine ligand in a cis, six-membered ring conformation, and to provide up to two "acceptor" sites for potential H-bonding [29]. For this purpose, we elected to pursue a double Mannich condensation reaction of Ph2PCH2OH with a series of isomeric primary amines bearing either OH/CH3 groups and/or an amide spacer between the arene and P-C-N-C-P backbone (Chart 1).

Linker can easily be modified
Highly tuneable arene (Ar) group N P P
For 1a-e, colourless solids were isolated in 38-97% yields and found to be air stable in the solid state, but oxidise rapidly in solution. Compounds 1a-e and 3 exhibit single resonances in their 31 P{ 1 H} NMR spectra (in d 6 -dmso) around δ(P) −26 ppm [12][13][14][15]29], indicating the presence of only one P III environment. The ligands were also characterised by 1 H NMR, FT-IR, and elemental analysis (Table 1). In particular, the absence of an NH resonance, in the 1 H NMR spectra, confirmed that double condensation had occurred. Chart 1. Potential modification sites of a Ph 2 P-C-N(Ar)-C-PPh 2 backbone.

Ligand Synthesis
We [11][12][13][14][15][16]29], and others [17,[19][20][21][22], have previously used Mannich condensations as a versatile method for the synthesis of aminomethylphosphines. Accordingly, two equivalents of Ph 2 PCH 2 OH were reacted with one equivalent of the amine, for 24 h at r.t. under N 2 , yielding the desired phenol-substituted ditertiary phosphines 1a-e and 3 (Scheme 1). For 1a-e, colourless solids were isolated in 38-97% yields and found to be air stable in the solid state, but oxidise rapidly in solution. Compounds 1a-e and 3 exhibit single resonances in their 31 P{ 1 H} NMR spectra (in d 6 -dmso) around δ(P) −26 ppm [12][13][14][15]29], indicating the presence of only one P III environment. The ligands were also characterised by 1 H NMR, FT-IR, and elemental analysis (Table 1). In particular, the absence of an NH resonance, in the 1 H NMR spectra, confirmed that double condensation had occurred. The synthesis of ditertiary phosphines, containing a flexible backbone presenting extra donor/acceptor sites with additional H-bonding capability, is described here with the opportunity to enhance solid-state packing behaviour. The precursors for the synthesis of the desired functionalised ditertiary phosphines 2a-g were prepared using, in step (i), 1 equiv. of primary amine, N-carbobenzyloxyglycine (1 equiv.) and dicyclohexylcarbodi-imide (DCC, 1 equiv.) in THF affording the corresponding carbamates followed by, in step (ii), treatment with Pd/C and cyclohexene in C 2 H 5 OH, to give the desired primary alkylamines in moderate to good yields [30,31]. Using a similar procedure to that described for 1a-e, the amide-functionalised diphosphines 2a-e were prepared in 65-89% yields by condensation using 1 equiv. of primary amine and two equiv. of Ph 2 PCH 2 OH at r.t. in CH 3 OH (Scheme 1). Furthermore, the phenol-substituted phosphines 2f and 2g were synthesised to investigate what effect, if any, an absent methyl group on the N-arene ring displays. In the case of 2d-g, the diphosphines were obtained as solids whereas 2a-c were obtained as yellow oils that were sufficiently pure to be used in complexation studies. All compounds displayed a single 31 P NMR resonance around δ(P) −26 ppm [12][13][14][15]29] indicating the inclusion of an amide spacer has negligible effect on the 31 P chemical shift. Other spectroscopic and analytical data are given in Table 1.

2.2.
Single Crystal X-ray Studies of 1a, 1b·CH 3 OH , 2f·CH 3 OH, 2g, and 3 X-ray quality crystals of 1a, 1b·CH 3 OH , 2f·CH 3 OH, 2g, and 3 were obtained by slow evaporation of a methanol solution, while for 2g diethyl ether was diffused into a deuterochloroform/methanol solution (Table 2). The geometry around each phosphorus atom is essentially pyramidal as would be anticipated (Figures 1-5). The P III atoms are in an anti conformation, presumably to minimise steric repulsions between the phenyl groups. The geometry about the N(1) centre is approx. pyramidal [Σ(C-N(1)-C) angles: 337.0(3) • for 1a; 335(2) • for 1b·CH 3 OH; 335.2(2)/336.6(2) • for 2f·CH 3 OH; 333.7(2) • for 2g] and approximately trigonal planar for 3 [Σ(C-N-C) = 359.05 (11) • ]. In 1a and 1b·CH 3 OH, the N-arene ring [C(3) > C(8)] is twisted by ca. 88 • (1a) and 86 • (1b·CH 3 OH) [12,32] such that it is almost perpendicular to the C(1)-N(1)-C(2) plane, whereas for 3, the twist of the C(1)-N(1)-C(2) fragment is around 9 • from co-planarity with the N-arene group, apparently as a result of the intermolecular H-bonding requirements (vide infra).      Table 3.        The synthons observed in the solid state for these highly modular ligands may be dictated by various factors including the nature of the ligand, the flexibility of the P-C-N-C-P backbone, the predisposition of the OH/CH 3 groups about the N-arene ring, and the solvent used in the crystallisation. In order to probe the OH/CH 3 interplay of groups, the crystal structure of 1a, with the -OH group in the ortho position with respect to the N(1) atom, is described first. Ligand 1a crystallises with an intramolecular S(5) [33][34][35] H-bonded ring with d = 2.26(5) Å [denoting the hydrogen (H) to acceptor (A) distance in an H-bond D-H···A] [36] for the O-H···N interaction ( Figure 1). The intramolecular Hbonding in 1a limits the dimensionality of the packing of the diphosphine ligand. Therefore, the structure of 1a is essentially zero-dimensional (Table 3). Compound 3, where the −OH functional group is in the meta position with respect to the tertiary N(1) atom, aggregates in the solid state in such a way that fairly weak hydrogen bonds, O−H···P [d = 2.60(2) Å], form between symmetry-related molecules, creating dimers in which two ligands are held in an R 2 2 (16) H-bonding motif ( Figure 2). The distance between symmetry-related nitrogen atoms is 8.257 Å. The structure of 3 shows a 0D arrangement.
Compound 1b·CH 3 OH, which contains the −OH group in a para position with respect to the N-arene, displays a similar structure to 3 with intramolecular O-H···P interactions at d = 2.60 Å. However, instead of forming dimers, there are 1D zig-zag chains in the c direction ( Figure 3). The para hydroxyl oxygen acts as an acceptor for an O-H···O intermolecular H-bond from approximately alternate CH 3 OH molecules of crystallisation with d = 2.05 Å. These CH 3 OH molecules are 50/50 disordered with the second component H-bonding to its neighbour with d = 1.95 Å. Selected hydrogen parameters for 1b·CH 3 OH are listed in Table 3.
Complex 5a· 1 2 Et 2 O was crystallised from a diethyl ether solution, including half a solvent molecule per complex molecule in the crystal lattice. There are two Pt complexes and two, half-occupied, Et 2 O solvent molecules of crystallisation in the asymmetric unit. The packing adopted by this second complex with an ortho hydroxyl group is very different to 5c (Figure 12). Here there is no intramolecular N-H···N H-bond, instead the ortho hydroxyl forms an intramolecular H-bond with the amide oxygen with d = 1.80 and 1.77(4) Å in the molecules containing Pt(1) and Pt(2), respectively. This does leave the two unique amide NH atoms free to form intermolecular interactions, which they do via highly asymmetric, bifurcated H-bonds with the coordinated chloride ligands on adjacent Pt complexes. From H(2) d = 2.60(11) and 2.95(13) Å to Cl (3) and Cl(4), respectively, while d = 2.52 (7)  Either, or both of these differences might account for the different intra-and intermolecular packing motifs observed. Selected hydrogen bonding parameters for 5a· 1 2 Et 2 O are shown in Table 9.  Molecules of 5d·Et 2 O lie on a mirror plane, passing through Pt(1), between pairs of P and Cl atoms, and including the atoms from N(1) to the terminal hydroxy-substituted ring. Again, here the amide NH is involved in the 1D chain propagation (Figure 13 ring. Again, here the amide NH is involved in the 1D chain propagation (Figure 13), forming a symmetrical bifurcated H-bond with the two coordinated chloride ligands on the adjacent molecule with d = 2.66(15) Å. Supporting this is an additional (Ar)C-H(5)•••Pt(1) interaction at 2.78 Å. The twist angle between the P(1)/P(1A)/C(1)/C(1A) plane and the ring C(4) > C(9) = 90° due to the imposed crystallographic symmetry. The hinge angle at P(1)-P(1A) = 29.5(5)°. Atoms N(1) and Pt(1) lie 0.79(2) and 0.782 (14) Å away from the P(1)/P(2)/C(1)/C(2) plane, respectively. So, this is the most chair shaped core Pt-P-C-N-C-P 6-membered ring. The meta hydroxyl group is not involved in the chain propagating intermolecular interactions and points into a cleft between a pair of Ph rings. It does not make an H-bond with the solvent of crystallisation.

Conclusions
In summary, we have shown that the position of the OH/CH3 groups with respect to the N-arene, the inclusion of an amide spacer, and the solvent used in the crystallisation can dictate the solid-state packing behaviour of both non coordinated and cis-PtCl2 bound diphosphine ligands. Unsurprisingly, the use of highly polar solvents (DMSO, CH3OH) in this study has been shown to play an important role in disrupting packing behaviour. Our work reinforces the importance of substituent effects, not only those commonly associated with −PR2 groups which may be alkyl or aryl based [37,38], but also those functional moieties positioned on the arene group of the central tertiary amine.

General Procedures
The synthesis of ligands 1a-e, 2a-g, and 3 were undertaken using standard Schlenkline techniques and an inert nitrogen atmosphere. Ph2PCH2OH was prepared according to a known procedure [39]. All coordination reactions were carried out in air, using reagent grade quality solvents. The compound PtCl2(η 4 -cod) (cod = cycloocta-1,5-diene) was prepared according to a known procedure [40]. All other chemicals were obtained from commercial sources and used directly without further purification

Conclusions
In summary, we have shown that the position of the OH/CH 3 groups with respect to the N-arene, the inclusion of an amide spacer, and the solvent used in the crystallisation can dictate the solid-state packing behaviour of both non coordinated and cis-PtCl 2 bound diphosphine ligands. Unsurprisingly, the use of highly polar solvents (DMSO, CH 3 OH) in this study has been shown to play an important role in disrupting packing behaviour. Our work reinforces the importance of substituent effects, not only those commonly associated with −PR 2 groups which may be alkyl or aryl based [37,38], but also those functional moieties positioned on the arene group of the central tertiary amine.

General Procedures
The synthesis of ligands 1a-e, 2a-g, and 3 were undertaken using standard Schlenkline techniques and an inert nitrogen atmosphere. Ph 2 PCH 2 OH was prepared according to a known procedure [39]. All coordination reactions were carried out in air, using reagent grade quality solvents. The compound PtCl 2 (η 4 -cod) (cod = cycloocta-1,5-diene) was prepared according to a known procedure [40]. All other chemicals were obtained from commercial sources and used directly without further purification

Instrumentation
Infrared spectra were recorded as KBr pellets on a Perkin-Elmer Spectrum 100S (4000-250 cm −1 range) Fourier-Transform spectrometer. 1 H NMR spectra (400 MHz) were recorded on a Bruker DPX-400 spectrometer with chemical shifts (δ) in ppm to high frequency of Si(CH 3 ) 4 and coupling constants (J) in Hz. 31 P{ 1 H} NMR (162 MHz) spectra were recorded on a Bruker DPX-400 spectrometer with chemical shifts (δ) in ppm to high frequency of 85% H 3 PO 4 . NMR spectra were measured in CDCl 3 or (CD 3 ) 2 SO at 298 K. Elemental analyses (Perkin-Elmer 2400 CHN Elemental Analyser) were performed by the Loughborough University Analytical Service within the Department of Chemistry. 1a-e, 2a-g, and 3 The following general procedure was used for the synthesis of 1a-e, 2a-g, and 3. A mixture of Ph 2 PCH 2 OH (2 equiv.) and the appropriate amine (1 equiv.) in CH 3 OH (20 mL) was stirred under N 2 for 24 h. The volume of the solution was evaporated to ca. 2-3 mL, under reduced pressure, to afford the desired ligands which were collected by suction filtration (except 2a-c) and dried in vacuo. Isolated yields in range 38-97%. Characterising details are given in Table 1. Complexes 4a-e, 5a-g, and 6 The following general procedure was used for the synthesis of 4a-e, 5a-g, and 6. To a solution of PtCl 2 (η 4 -cod) (1 equiv.) in CH 2 Cl 2 (5 mL) was added a solution of the appropriate ligand (1 equiv.) in CH 2 Cl 2 (5 mL). The colourless (or pale yellow) solution was stirred for 30 min at r.t., evaporated to ca. 2-3 mL under reduced pressure, and diethyl ether (10 mL) added. The solids were collected by suction filtration and dried in vacuo. Isolated yields in range 73-99%. Characterising details are given in Table 4.

Single Crystal X-ray Crystallography
Suitable crystals of 1a, 1b·CH 3 OH, 2f·CH 3 OH, and 3 were obtained by slow evaporation of a CH 3 OH solution whereas 2g was obtained by vapour diffusion of Et 2 O into a CDCl 3 /CH 3 OH solution. Crystals of 4b·(CH 3 ) 2 SO, 5a· 1 2 Et 2 O, 5b, and 5c· 1 4 H 2 O were obtained by slow diffusion of Et 2 O into a CDCl 3 /(CH 3 ) 2 SO/CH 3 OH solution. Slow diffusion of hexanes [for 6·(CH 3 ) 2 SO] into a CDCl 3 /(CH 3 ) 2 SO solution or vapour diffusion of Et 2 O into a CHCl 3 /(CH 3 ) 2 SO/CH 3 OH [for 4c·CHCl 3 , 4e· 1 2 CHCl 3 · 1 2 CH 3 OH) or CH 2 Cl 2 /CH 3 OH (for 5d·Et 2 O)]. Slow evaporation of a CH 2 Cl 2 /Et 2 O/hexanes solution gave suitable crystals of 4d· 1 2 Et 2 O. Tables 2, 5 and 6 summarise the key data collection and structure refinement parameters. Diffraction data for compounds 1a, 1b·CH 3 OH, 2f·CH 3 OH 3, 4b·(CH 3 ) 2 SO, 4c·CHCl 3 , 4d 4e· 1 2 CHCl 3 · 1 2 CH 3 OH, 5d·Et 2 O, and 6·(CH 3 ) 2 SO, were collected using a Bruker or Bruker-Nonius APEX 2 CCD diffractometer using graphitemonochromated Mo-K α radiation. Data for compounds 5b and 5c· 1 4 H 2 O, were collected using a Bruker APEX 2 CCD diffractometer using synchrotron radiation at Daresbury SRS Station 9.8 or 16.2 SMX for 5a· 1 2 Et 2 O. Data for compound 2g was collected using a Bruker SMART 1000 CCD diffractometer using graphite-monochromated Mo-K α radiation. All structures were solved by direct methods [except structures 4b·(CH 3 ) 2 SO, 5a· 1 2 Et 2 O, and 5b which were solved using Patterson synthesis] and refined by full-matrix least-squares methods on F 2 . All CH atoms were placed in geometrically calculated positions and were refined using a riding model (aryl C-H 0.95 Å, methyl C-H 0.98 Å, methylene C-H 0.99 Å. Where data quality allowed, OH and NH atom coordinates and U iso were freely refined, or refined with mild geometrical restraints; otherwise, they were placed geometrically with O/N-H = 0.84 Å. U iso (H) values were set to be 1.2 times U eq of the carrier atom for aryl CH and NH, and 1.5 times U eq of the carrier atom for OH and CH 3 . Throughout the text and tabulated data, where H atom geometry does not include a SU, the coordinates were constrained. Unless stated, all structural determinations proceeded without the need for restraints or disorder modelling. Where disorder was modelled it was supported with appropriate geometrical and U value restraints. In 1b·CH 3 OH, the methanol was modelled as disordered over two equally occupied sets of positions. In 2f·CH 3 OH the methanol was modelled using the Platon Squeeze procedure [41]. Compound 3 was found to contain a disordered methanol and was modelled over two sets of positions, each at half weight. In 4d· 1 2 Et 2 O, atoms C(1) > C (7) and N(1) were modelled with U value restraints. The Et 2 O was modelled using Platon Squeeze due to significant disorder. In 4e· 1 2 CHCl 3 · 1 2 CH 3 OH the chloroform molecule was modelled over two sets of positions with major occupancy 57.1(7)% Restraints were applied to that molecule and also ring C(55) > C(60). In 5a· 1 2 Et 2 O three Ph rings were modelled as disordered over two sets of positions with occupancies close to 50%. Restraints were applied to these rings and also the two half-occupancy Et 2 O solvent molecules of crystallisation. In 5c· 1 4 H 2 O, atoms Cl(1) and C(3) > C(11), O(1), O(2) and N(1) were modelled as split over two sets of positions with major occupancy 56(4) and 50.9(6)%, respectively and restraints were applied. In 5d·Et 2 O the Et 2 O was modelled as a diffuse area of electron density by the Platon Squeeze procedure and restraints were applied to atoms C(1) > C(10), C(11) > C (22) and N(2) O(2). In 6·(CH 3 ) 2 SO the DMSO was modelled with restraints as disordered over two sets of positions with major component 71.0(5)% and with C(33) coincident for both components Programs used during data collection, refinement and production of graphics were Bruker SMART, Bruker APEX 2, SAINT, SHELXTL, COLLECT, DENZO and local programs [41][42][43][44][45][46][47][48][49][50][51]. CCDC 2101643-2101656 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures (accessed on 3 November 2021).