Supramolecular Chemistry of BrettPhos and BrettPhos Oxide: Breakup

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Supramolecular Chemistry of BrettPhos and BrettPhos Oxide: Break-up of Isostructurality via Order-disorder Phase Transitions Amol G. Dikundwar, Pema Chodon, Sajesh P. Thomas, and Hemant Bhutani Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/acs.cgd.6b01905 • Publication Date (Web): 15 Feb 2017 Downloaded from http://pubs.acs.org on February 16, 2017

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Crystal Growth & Design

2. EXPERIMENTAL SECTION Materials. BrettPhos was procured commercially (Beijing Golden Fruit Technology Co., Ltd.) and used as such for crystallization. BrettPhos oxide was synthesized from BrettPhos using aqueous hydrogen peroxide as oxidizing agent (see Supporting Information (SI) for details). Crystallization. Single crystals of BP and BPO were obtained by slow evaporation from various solvents at room temperature (RT, 298 ± 2 K). Square plate shaped single crystals of BP were obtained from 2-propanol (isopropyl alcohol, IPA) solution. BPO was crystallized from ethyl acetate solution by solvent evaporation as block shaped crystals. Four solvatomorphs of BPO were obtained from methanol, acetonitrile: water mixture (1:1 v/v), IPA, and chloroform. Crystallography. Single crystal X-ray diffraction data were collected on a Bruker SMART APEX II diffractometer using Mo Kα radiation (λ = 0.71073 Å) at RT and at 100 K for BP and BPO (Table 1) and at RT for four solvatomorphs (BPOH1, BPO-H2, BPO-IPA and BPO-CH)11 of BPO. The intensity data were collected as phi and omega scans. Scaling and data reduction was carried out with SAINTPlus.12 The absorption correction of the collected intensities was done using the SADABS program.13 The structures were solved by direct methods using SHELX-97 and refined using full-matrix leastsquares methods in SHELXL.14,15 OLEX 2 was used for further refinements and data files preparation.16 Non-hydrogen

atoms in BP and BPO RT structures were refined isotropically or anisotropically depending on the occurrence of disorder in the structures. All non-hydrogen atoms in BP and BPO 100 K structures were refined anisotropically. All hydrogen atoms were placed geometrically and refined with a riding model for their isotropic temperature factors. Diagrams were generated using OLEX2 or Mercury.17 Simulated powder X-ray diffractograms overlay was made using MDI Jade 9. Differential scanning calorimetry (DSC). Measurements were done on Q2000 differential scanning calorimeter with RCS90 cooling unit attachment (by TA Instruments). The instrument was calibrated using Indium DSC calibration standard (NIST® SRM® 2232) for temperature and enthalpy of fusion. The sample (3-5 mg) was filled uniformly in Tzero Aluminum pan and sealed hermetically with a pin hole on the lid. The sample was first equilibrated at 40 °C, cooled to -70 °C with a ramp rate 10 °C/min, held isothermal for 1min and heated to 40°C with a ramp rate of 10 °C/min. Computational calculations. The calculations of electrostatic potentials on Hirshfeld surfaces and energy framework analyses of BP and BPO were carried out using Crystal Explorer.18 Single point geometries from the crystal structure analysis were used for these calculations. One of the half occupancy components was chosen for the coordinates of disordered groups in BP and BPO RT structures.

Table 1: Crystallographic details of BP and BPO structures at RT (~ 298 K) and at 100 K Structure

BP (RT)

BPO (RT)

BP (100K)

BPO (100K)

Mol. formula, Formula wt.

C35H53O2P, 536.77

C35H53O3P, 552.77

C35H53O2P, 536.77

C35H53O3P, 552.77

Crystal system, Space group

Monoclinic, P21/c

Monoclinic, P21/c

Monoclinic, P21/c

Triclinic, P-1

a (Å)

13.4307(5)

14.3226(13)

19.3597(7)

13.1867(11)

b (Å)

14.7976(4)

14.2342(12)

14.5046(5)

14.9190(14)

c (Å)

17.2953(5)

17.1169(16)

34.4255(11)

33.592(3)

α (°)

90

90

90

89.766(5)

β (°)

101.917(2)

101.054(3)

91.223(2)

79.699(4)

90

90

90

89.761(5)

3363.22(18)

3424.9(5)

9664.6(6)

6502.0(10)

1, 4

1, 4

3, 12

4, 8

1.060

1.072

1.107

1.129

Absorption coefficient (mm )

0.108

0.110

0.113

0.116

θ range

1.55-27.53

1.449-27.54

1.052-25.00

1.232-25.00

Reflections collected

29871

17077

75124

68575

No. data I > 2σ(I)

4065

2528

11803

16624

0.0748; 0.1351

0.0863; 0.2027

0.0468; 0.0784

0.1008; 0.1323

Goodness-of-fit on F

1.056

1.011

1.024

1.066

CCDC no.

1524496

1524497

1524498

1524499

γ (°) 3

V (Å ) Z’, Z −3

Dc, calc density (g cm ) −1

Final R [I > 2σ(I)]; R (all data) 2

ACS Paragon Plus Environment


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3. RESULTS AND DISCUSSION: 3.1 Crystal structures of BP, BPO and solvatomorphs of BPO 3.1.1 Crystal Structure of BP: Structure analysis at RT revealed that BP crystallized as monoclinic crystals belonging to the centrosymmetric P21/c space group containing one molecule in the asymmetric unit [Fig. 1(a)]. The crystallographic details are provided in Table 1. While most of the fragments of this bulky molecule appeared in order, one of the two cyclohexyl groups and one of the three iso-propyl groups in the molecule were found to exhibit positional disorder (encircled in Fig. 1(a)). Notably, the disorder in both the fragments could be resolved successfully into two major components each with 50% occupancies. The intermolecular packing is mainly supported by C-H…O and C-H…π hydrogen bonds and nondirectional dispersion forces in the structure as discussed in detail in section 3.2. Interestingly, the conformation of BP, where P is bound to three bulky groups, leaves an empty space near phosphorous atom (“phosphorus-headspace”). 3.1.2 Crystal Structure of BPO: Further, in order to examine the structural (conformational, electronic and supramolecular) changes that would be induced by the substitution of P with P=O, the crystal structure of BrettPhos oxide (BPO) was analyzed. The analysis revealed that BPO formed crystals that are isostructural to BP, with the monoclinic space group P21/c; Z=4 (Table 1). The molecular conformation remained very similar to BP, even after the substitution of P atom in BP with P=O in BPO as shown in Figure 1(b). While one of the two cyclohexyl groups is disordered in similar fashion as seen in BP, all the three iso-propyl groups are ordered in this structure. Similar to that in BP, C-H…O and C-H…π hydrogen bonds appears to be the main intermolecular packing factors in this structure. 3.1.3 Solvatomorphs of BPO: In order to explore potential polymorphs of both BP and BPO apart from their known isostructural crystalline forms, both these compounds were screened for polymorphism using different solvents. While BP consistently produced the same pristine form (discussed above), BPO generated a variety of hydrates and solvates depending on the solvent system used for crystallization. From the limited solvents tried for crystal growth, single crystals of two different hydrates (BPO-H1 and BPO-H2)11, an iso-propyl alcohol solvate (BPO-IPA)11 and a chloroform solvate (BPOCH)11 were obtained for BPO suggesting its exclusive propensity for the formation of solvatomorphs, utilizing the additional hydrogen bond acceptor site rendered by P=O group. Two different monohydrates (polymorphs) namely, BPOH1 and BPO-H2 were obtained by slow evaporation of methanol and acetonitrile:water (1:1), respectively. In both H-1 and H-2, the water molecules are linked to BPO molecules by OH…O=P hydrogen bonds and are further connected with surrounding BPO molecules by C-H…Owater hydrogen bonds.

(a) BP (b) BPO Figure 1. Crystal state molecular conformations of (a) BP and (b) BPO. Disordered fragments are encircled.

(a) BPO-H1

(b) BPO-H2

(c) BPO-IPA (d) BPO-CH Figure 2. Crystal state molecular conformations (asymmetric units) of (a) monohydrate, BPO-H-1; (b) monohydrate, BPOH-2; (c) iso-propyl alcohol solvate, BPO-IPA and (d) chloroform solvate, BPO-CH of BPO.

The modes and extent of hydrogen bonding of water to the P=O group of BPO are different in the two forms, as d(O···O) = 2.69 Å in BPO-H1 and d(O···O) = 2.63 Å in BPO-H2; Figure 2 (a) and (b)). Notably, the IPA and chloroform solvates also show similar solvent-phosphorous oxide interaction motifs (solventD…O=P) as shown in Figure 2(c) and (d), respectively. In BPO-IPA, the IPA molecules bind to the BPO ‘host’ molecules via P=O∙∙∙H-O hydrogen bonds (2.10 Å). In BPOCH, although the chloroform molecules lack typical strong hydrogen bond donor group such as O-H, they


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(a) BPO-H-1

(b) BPO-H-2

(c) BPO-IPA (d) BPO-CH Figure 3. Packing diagrams of (a) monohydrate, BPO-H-1; (b) monohydrate, BPO-H-2; (c) iso-propyl alcohol solvate, BPO-IPA and (d) chloroform solvate, BPO-CH of BPO viewed along appropriate axes (hydrogen atoms of BPO molecules are not shown for the purpose of clarity).

form notably short C-H∙∙∙O hydrogen bonds with O=P group of BPO (d(H∙∙∙O) = 1.97 Å; C-H bond in chloroform is quite polarized due to presence of three Cl atoms). The crystal packing in BPO-IPA is supported by multiple C-H…O(IPA) hydrogen bonds while in BPO-CH, it is accomplished with involvement of chlorines in C-H…Cl hydrogen bonds. It is evident that the P=O group that renders a strong H-bond acceptor site leads to the generation of these solvates/hydrates by BPO. It is important to note that, although all the above hydrates and solvates of BPO possess similar basic hydrogen bonded unit where the water/solvent resides in the concave cavity of BPO mimicking host-guest systems, their intermolecular packing patterns are strikingly different. The two hydrates BPO-H1 and BPO-H2 form a pair of packing polymorphs of a monohydrate due to their entirely different packing preferences (Figure 3(a) and (b)). Such phenomena of polymorphism in multicomponent systems (solvates/hydrates) has been of interest in the context of crystal engineering (a well-known case being Gallic acid monohydrate).19-21 Likewise, the intermolecular arrangements in IPA and chloroform solvates differ significantly from each other and also from that of the hydrates (Figure 3, a-d).

3.2 Isostructurality of BP and BPO at RT As discussed earlier, the overall molecular and supramolecular organization in BP and BPO structures is strikingly similar. Figure 4 shows molecular and crystal structure overlays of BP and BPO illustrating their isostructural relationship. Analysis of intermolecular packing features reveals that both BP and

(a) (b) Figure 4. (a) Molecular and (b) crystal structure overlay of BP and BPO illustrating their isostructural relationship (rootmean-square deviation, RMSD = 0.16). Only single component of the disordered parts were included in the overlays for the sake of clarity.

BPO crystal structures are mainly stabilized by antiparallel methoxy-methoxy dimers formed with weak C-H…O hydrogen bonds as shown in figure 5 (a) and (b). Occurrence of slightly uncommon interactions such as methoxyC-H...Ccyclohexyl and methoxyC-H…H-Ccyclohexyl were noted in both the structures [Figure 5 (a) and (b)] along with commonly seen C-H…π contacts. The Phosphorus atom (P) in BP, in spite of carrying a lone pair of electrons, does not seem to participate in any intra- or inter-molecular hydrogen bonds (at-least based on the distance-angle



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BP

BPO

dimer-I (-72 kJ/mol)

dimer-I (-73 kJ/mol)

dimer-II (-54 kJ/mol)

dimer-II (-69 kJ/mol)

dimer-III (-37 kJ/mol)

dimer-III (-44 kJ/mol)

dimer-IV (-35 kJ/mol)

dimer-IV (-38 kJ/mol)

(a)

(b)

(c)

(d)

Figure 5. Intermolecular interactions in (a) BP and (b) BPO highlighting the presence of C-H…O hydrogen bonds and CH…H/C contacts. Figures (c) and (d) shows the noninvolvement and involvement of P and P=O groups (shown in Space fill model) in BP and BPO, resp. [d(P=O…Cmethoxy)BPO = 3.05 Å].

criteria generally considered for the existence of hydrogen bonds)22-25 whereas, P=O acts as a H-bond acceptor in BPO [Figure 5 (c) and (d)]. 3.2.1 Quantitative analysis of intermolecular interactions by energy framework analysis: A computational tool recently introduced by Spackman et al provides a means to efficiently and accurately calculate the intermolecular interaction energies of each distinct pair of molecules in a crystal structure.26,27 When applied to the crystal structures of BP and BPO, it was found that four molecular dimers dominate the crystal packing in terms of interaction strengths (Figure 6). Remarkably, the intermolecular geometries and orientations observed for the corresponding dimers in BP and BPO are very similar, in agreement with the isostructurality observed. The dimers I characterized by C−H···O hydrogen bonds are the strongest binding ones with interaction energies -72 and -73 kJ/mol for BP and BPO, respectively. It has been shown that multiple C− H···O hydrogen bonds acting in co-operative fashion can render strong supramolecular motifs.28 However, in the present case of BP and BPO, it is found that the C−H···O hydrogen bonded dimers are predominantly stabilized by dispersion contribution originating from the complementary molecular surfaces of these relatively large molecules (Figure 7). In case of dimers II, the interaction energies are different for BP and BPO (-54 and -69 kJ/mol respectively). The extra stabilization of dimer II in BPO can be attributed to the additional C−H···O hydrogen bond formed with the help of P=O group in BPO.

Figure 6. Corresponding molecular dimers in BP and BPO, with their interaction energies.

Figure 7. Interaction energies (magnitudes) and their components for corresponding molecular dimers in BP and BPO.


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Crystal Growth & Design Electrostatic

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Dispersion

Net interaction energy

BP (viewed down c axis)

BPO (viewed down c axis) Figure 8. 3D-topologies of the intermolecular interactions represented as energy frameworks. Topology of electrostatic, dispersion and total energy terms have been shown as energy frameworks coloured as red, green, and blue respectively

Similarly, corresponding pairs of dimers III and IV in BPO exhibit higher values of interaction energies as compared to those in BP. The polar P=O group adds to dipolar nature of the molecule, and that explains the increased interaction energies of dimers III and IV in BPO which show centrosymmetric intermolecular orientations. Analysis of the interaction energy components reveals that dispersion contribution stabilizes all the dimers (Figure 7). The electrostatic contribution is significant only in dimers I and II. Notably, even the individual interaction energy components exhibit remarkable similarity for the corresponding molecular dimers of BP and BPO. On the other hand, analysis of the interactions of BPO with solvent molecules IPA and CHCl3, in BPO-IPA and BPO-CH structures respectively, shows that the electrostatic terms dominate over the dispersion contributions in these host-guest type H-bonded complexes (see Table S3 in SI). Further, in order to visualize the 3D topology of these interactions, energy frameworks were plotted for BP and BPO. In this method, the values of interaction energies are used to construct cylinders connecting molecules, and the thickness of

the cylinders are set proportional to the interaction energy values. The resulting 3D topologies of interactions are termed as energy frameworks. The usefulness of this technique has been demonstrated by its applications in various contexts such as, the analysis of supramolecular recognition units for crystal engineering,29,30 rationalizing unusual mechanical properties of crystals,26 and in understanding isostructurality and quasiisostructural polymorphism.31,32 Energy frameworks corresponding to the crystal structures of BP and BPO show the 3D-topologies of the intermolecular interactions (including those discussed above, see Figure 8). The fact that the dispersion forces dominate the crystal packing in these structures is also evident from their energy frameworks. The isostructurality of BP and BPO are obvious from the remarkable similarity in their interaction topologies or energy frameworks. Such a similarity is found for energycomponent frameworks corresponding to electrostatic and dispersion terms too. The thicker cylinders corresponding to the higher values of electrostatic components in BPO for dimers I and II as compared to BP (Figure 7) is also clear from the energy frameworks (Figure 8).



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(a) BP

(b) BPO

(c) BP

(d) BPO

Figure 9. (a) A comparison of Hirshfeld surfaces of BP and BPO, and (b) corresponding fingerprint plots.

3.2.2 Isostructurality manifested in Hirshfeld surface analysis: Further, in order to obtain a quantitative estimation of intermolecular interactions in terms of interaction surfaces/or intermolecular boundary surfaces, Hirshfeld surface analysis was performed on BP and BPO using CrystalExplorer.18 Thomas et al have shown that chemical analogues exhibit similar proportions of intermolecular interaction types in Hirshfeld fingerprint analysis.33 Based on fingerprint plots, H···H contact predominates the Hirshfeld surfaces of both BP (92%) and BPO (91%) molecules. Percentages of C···H contacts also turned out to be significantly similar (6.5% in BP and 5.5% in BPO). The H-bond acceptor role of P=O was clearly evident with the increased proportion of H···O contacts in BPO (3.4%) compared that in BP (1%). Interestingly, the isostructurality of BP and BPO manifests in their Hirshfeld surfaces and corresponding finger print plots too (Figure 9; see SI for details). 3.2.3 Spatial vs. electrostatic complementarity: The empty “headspace” on the top of P atom, which virtually remains unaccounted in the crystal structure of BP; when filled with oxygen in BPO, does not seem to affect the molecular conformation as well as overall crystal packing (Figure 4). In addition to the spatial similarity between BP and BPO molecules, the isostructurality in their crystal structures indicates similarities in their electrostatics. The electrostatic nature of these molecules was analyzed using Tonto interface in CrystalExplorer at B3LYP/6-31G(d,p) level. The electrostatic potential (ESP) plotted on the promolecule surface (isoelectron density surface of 0.02 au) and the Hirshfeld surface34-36

Figure 10. (a) and (b): The electrostatic potential (esp) plotted on the promolecule surfaces (iso electron density surface of 0.002 au) of BP and BPO highlighting the major electronegative and positive regions (ESP cut off +/-0.04). (c) and (d): ESP plotted on Hirshfeld surfaces of BP and BPO (ESP cut off +/-0.02). The nearest neighbors in the crystal packing are marked with characteristic intermolecular interaction.

generated using the crystal geometries are shown in Figure 10 (a), (c) and (b), (d), respectively for BP and BPO. ESP values plotted on the Hirshfeld surfaces can provide insights into the role of electrostatics in supramolecular assembly and crystal packing34-36 and the differences in the binding modes of the molecules.37 The esp surfaces for BP and BPO exhibit remarkable similarities, albeit with quantitative differences. In case of BP, the minimum of esp (electronegative region) is found around P atom and inside the cavity of the cup shaped BP molecule (-0.078 au). Notably, second most electronegative region was found outside the cup, near one of the methoxy O atoms, and the triisopropylphenyl ring (-0.064 au). The most electropositive regions are found on the opposite side of the cavity near the protons of the methoxy groups (0.036 au). In BPO, with the introduction of P=O functional group in place of P atom, esp values get tuned over the molecular surface. Nevertheless, the trends with respect to the most electronegative and electropositive regions remain the same. The electronegative maximum was found inside the cup, near O atom in P=O functional group (-0.11 au) and the electropositive maxima around the methoxy protons as in case of BP (0.043 au). It is found that both shape complementarity and electrostatic complementarity (ESC) play hand in hand in stabilizing the crystal packing of BP and BPO. The packing of molecules is strikingly similar in BP and BPO and the

7


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Figure 11. Low temperature DSC plots for BP (blue) and BPO (red). The expanded views of feeble transition peaks for BP are shown in insets.

(a) (b) Figure 12. Molecular overlays [2 of 3 symmetry independent molecules (Blue, Green and Red) at a time] of BP-100K structure with 1 (green) molecule common in both the overlays.

structural origin of the isostructurality can be attributed to the very similar electrostatic features on their molecular surfaces (Figure 10). ESP plotted on Hirshfeld surfaces further highlight these similarities. Figure 10 (c) and (d) shows ESP plots for BP and BPO with the nearest neighbours in the crystal packing (molecules having at least one atom within 2.5 Å from the central molecule). Three of these neighbouring molecules are bound to the central one with help of strong electrostatic complementarity. The remaining molecular dimers are characterized C−H···H−C interactions and mainly stabilized by dispersion contribution as discussed in the previous section (3.2.1).

3.3 Temperature dependent phase transformations in BP and BPO The single crystals of BP and BPO were cooled slowly (30 K/hour) to 100 K and the diffraction data were acquired with a main intend to resolve the cyclohexyl ring disorders. Interestingly, both BP and BPO were found to transform their structures at lower temperatures. DSC thermograms for both BP and BPO also substantiate the observed phase changes at lower temperatures (Figure 11). The different structural preferences of BP and BPO in low temperature structures are noteworthy in light of their isostructurality at room temperature discussed in detail in the previous sections. Salient features of low temperature structures of BP and BPO (BP-100K and BPO-100K, respectively) are discussed below. 3.3.1 BP-100K: Similar to its RT counterpart, the 100 K structure of BP belongs to a monoclinic space group P21/c but with a different (increased) set of cell parameters (see Table 1 for crystallographic details). The asymmetric unit contains 3 molecules of BP, with all their molecular fragments in perfect crystallographic order. Notably, the 3 symmetry independent molecules differ quite

Figure 13. Simulated PXRD comparison for BP (RT and 100 K) and BPO (RT and 100 K) structures showing the similarities and differences in the overall crystal structure before and after the phase transitions.

significantly in their conformations (Figure 12). Despite considerable changes at the molecular level, the packing features of BP-100K structure mostly remain similar to that of RT structure with a slight strengthening of C-H…O mediated methoxy-methoxy dimers and C-H…π interactions (see SI for details). Relatively broader transition peaks in the DSC thermogram (Figure 11) and minor differences in the simulated powder XRD patterns (Figure 13) are indicative of these minute yet appreciable differences in the overall crystal structures of BP at RT and at 100 K. 3.3.2 BPO-100K: The 100 K structure of BPO is remarkably different from its RT counterpart. It belongs to a triclinic space group P-1 with four molecules in the asymmetric unit (see Table 1 for crystallographic details). The 4 symmetry independent molecules of BPO differ in their molecular

8



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4. CONCLUSIONS

Figure 14. Asymmetric unit (4 symmetry independent molecules) of BPO-100K structure. Notice the molecular level differences among these molecules mainly in the conformation of cyclohexyl rings and in the orientation P=O groups (marked with arrows).

conformations, with all their molecular fragments in perfect crystallographic order. Apart from the changes in conformation of cyclohexyl rings, the orientation and associated Hbonding features of P=O appears to be a major distinguishing factor among these four BPO molecules. (Figure 14; see SI for details). P=O…Hmethoxy hydrogen bonds appear to be more competitive with the methoxy-methoxy dimers and C-H…π interactions as noticed by shortening of these contacts, as compared to the RT structure (see SI for details). Interestingly, there appears to be a phase transition associated partial rotation of the iso-propyl groups of BPO, as reported previously for a Carvacrol derivative.38 Occurrence of sharp transition peaks in the thermogram (Figure 11) and comparison of simulated powder X-ray diffractograms for the RT and 100 K structures (Figure 13) clearly brings out pronounced changes in the overall crystal structure of BPO before and after the transition. It is important to mention that, the low temperature transformed phase of BPO is found to possess a partial merohedral twinning. The twinned nature of crystals at 100K was confirmed by structure analysis at RT (not twinned) and at 100 K (twinned) on multiple crystals (and also for crystals obtained from different batches). The crystal structure was refined with appropriate twinning law using BASF command in SHELXL (details are provided in CIF under SI). Thus, both the molecules undergo an order-disorder phase transition wherein the disorder with respect to cyclohexyl (both in BP and BPO) and iso-propyl (in BP) groups in the RT structures gets eliminated in their respective low temperature (100 K) structures. These transitions were reversible with both BP and BPO resuming their isostructural relationship at RT. Similar phase transformations have been reported for a well known anti-HIV drug Efavirenz where the temperature dependant phases are related by order-disorder with respect to the cyclopropyl group.39 Though they look quite similar qualitatively, small differences in the RT structures of BP and BPO are indeed revealing (Energy Framework Analysis, Figure 8). Hypothetically, at room temperatures (~ 298 K), these differences might get averaged out and be overweighed by geometry based crystal packing factors (Kitaigorodskii’s ‘bumpsinto-hollows’ packing)40,41 for bulky molecules like BP and BPO. The order-disorder phase transitions in these molecules appear to act as a “contrast agent” magnifying these minute structural differences in their respective low temperature structures.

A pair of structurally related molecules ― BrettPhos (BP) and BrettPhos oxide (BPO) ― serves as an excellent example of a system, where the crystal structures at a first glance seem to be isostructural in all respects but possess critical elements of distinctness. The isostructurality of BP and BPO is illustrated with qualitative (molecular and structure overlay, hydrogen bonding patterns) and quantitative (Hirshfeld surface analysis and fingerprint plots, molecular electrostatic potential maps, energy framework analysis) tools for structure analysis. At the same time, their distinctness is revealed with molecular level differences, temperature dependant phase transformations, and preferences for the formation of solvatomorphs. Distinct preferences of BP and BPO for respective low temperature structures and the distinguishable molecular and supramolecular patterns therein bring out their unique identities which remain “hidden” in their isostructural crystalline forms at RT. The observed ‘isostructurality’ suggests a possibility of formation of solid solution phases of BP and BPO.31,32 This may be of concern with regard to the phase purity and separation of these compounds.31 Structures of a series of H…O=P hydrogen bond mediated BPO solvates wherein, solvent molecule fits the concave cavity of the parent molecule, indicates potential of BPO to be used as a versatile host in host-guest chemistry. Acknowledgements. The authors are thankful to BBRC and BMS management for their support and encouragement towards this research work. We are grateful to Qi Gao, Pankaj Shah and Rajappa Vaidyanathan for review of manuscript. Thanks are due to Sharmistha Pal and Hyunsoo Park for valuable discussions and inputs during the execution of the research work and to Balvinder Vig for his guidance. We thank S. Meenakshi Sundaram for his contribution on DSC experiments and Tamilarasan Subramani and Somanadham Mummadi for the synthesis of BrettPhos oxide. Special thanks are due to Prof. Mark Spackman for permitting use of the latest version of Crystal Explorer. SPT thanks ARC and The University of Western Australia for providing Post Doctoral fellowship.

Supporting Information. Synthesis and characterization of BPO, Crystallographic details of BP, BPO and BPO-H1, BPOH2, BPO-IPA and BPO-CH structures, Computational details.

5. REFERENCES 1. 2.

3. 4.

Lehn, J. M. Supramolecular Chemistry: Concepts and Perspectives; VCH: Weinheim, Germany 1995. Nunez, A. J.; Shear, L. N.; Dahal, N.; Ibarra, I. A.; Yoon, J.; Hwang, Y. K.; Chang, J.; Humphrey, S. M. Chem. Commun., 2011, 47, 11855-11857. Qiao, S.; Huang, W.; Du, Z.; Chen, X.; Shieh, F.; Yang, R. New J. Chem. 2015, 39, 136-141. Tan, X.; Li, L.; Zhang, J.; Han, X.; Jiang, L.; Li, F.; Su, C. Chem. Mater. 2012, 24, 480-485.

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Crystal Growth & Design 5.

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Falkowski, J. M.; Sawano, T.; Zhang, T.; Tsun, G.; Chen, Y.; Lockard, J. V.; Lin, W. J. Am. Chem. Soc. 2014, 136, 5213-5216. Surry, D. S.; Buchwald, S. L. Chem. Sci., 2011, 2, 27-50. Hartwig, J. F. Nature 2008, 455, 314–322. Surry, D. S.; Buchwald, S. L. Angew. Chem., Int. Ed. 2008, 47, 6338–6361. Fors, B. P.; Watson, D. A.; Biscoe, M. R.; Buchwald, S. L. J. Am. Chem. Soc. 2008, 130, 13552–13554. CCDC refcodes for complexes of BrettPhos reported in CCDC: PUSSAZ, PUSSED, ONOCEA, PUBYUH, WETFAE, WOJJIP, WUQREG, WUQRIK. Crystal data. (1) BPO-H1, CCDC no. 1524500, C35H53O4P (M =568.74 g/mol): triclinic, space group P-1, a = 9.043(3) Å, b = 9.652(4) Å, c = 20.119(7) Å, α = 89.35(2)°, β = 86.03(2)°, γ = 77.70(2)°, V = 1711.6(11) Å3, Z = 2, T = ~298 K, µ(MoKα) = 0.114 mm-1, Dcalc = 1.104 g/cm3, Final R1 = 0.0621 (I > 2σ(I)), wR2 = 0.1919 (all data). (2) BPO-H2, CCDC no. 1524501, C35H53O4P (M =568.74 g/mol): monoclinic, space group P21/c, a = 20.779(3) Å, b = 8.8375(10) Å, c = 19.194(3) Å, β = 102.614(7)°, V = 3439.7(8) Å3, Z = 4, T = ~298 K, µ(MoKα) = 0.113 mm-1, Dcalc = 1.098 g/cm3, Final R1 = 0.0790 (I > 2σ(I)), wR2 = 0.2307 (all data). (3) BPO-IPA, CCDC no. 1524502, C38H61O4P (M =612.83 g/mol): monoclinic, space group P21/c, a = 9.804(2) Å, b = 18.734(3) Å, c = 20.789(4) Å, β = 95.920(10)°, V = 3798.0(13) Å3, Z = 4, T = ~298 K, µ(MoKα) = 0.107 mm-1, Dcalc = 1.072 g/cm3, Final R1 = 0.1047 (I > 2σ(I)), wR2 = 0.3507 (all data). (4) BPO-CH, CCDC no. 1524503, C36H54O3PCl3 (M =672.11 g/mol): triclinic, space group P-1 (no. 2), a = 9.901(3) Å, b = 14.044(4) Å, c = 14.301(5) Å, α = 85.503(17)°, β = 76.751(16)°, γ = 87.352(14)°, V = 1928.8(9) Å3, Z = 2, T = ~298 K, µ(MoKα) = 0.310 mm-1, Dcalc = 1.157 g/cm3, Final R1 = 0.0888 (I > 2σ(I)), wR2 = 0.2988 (all data). Bruker (2012). SAINT-Plus, Version 7.12; Bruker AXS Inc.: Madison, Wisconsin, USA. Sheldrick, G. M. SADABS: Program for Area Detector Absorption Correction; University of Gottingen: Germany, 1996; pp 33−38. Sheldrick, G. M. Acta Cryst., 2008, A64, 112–122. Sheldrick, G. M. Acta Crystallogr C Struct Chem., 2015, 1, 3–8.

16. Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J; Howard, J. A. K.; Puschmann, H., J. Appl. Cryst. 2009, 42, 339-341. 17. Macrae, C. F.; Edgington, P. R.; McCabe, P.; Pidcock, E.; Shields, G. P.; Taylor, R.; Towler, M.; van de Streek, J. J. Appl. Cryst., 2006, 39, 453-457. 18. Turner, M. J.; McKinnon, J. J.; Wolff, S. K.; Grimwood, D. J.; Jayatilaka, D.; Spackman, M. A. CrystalExplorer, version 3.2; University of Western Australia: Crawley, Australia, 2014. 19. Clarke, H. D.; Arora, K. K.; Wojtas, L.; Zaworotko, M. J. Cryst. Growth Des., 2011, 11, 964−966.

20. Doris E. Braun, D. E.; Bhardwaj, R. M.; Florence, A. J.; Tocher, D. A.; Price, S. L. Cryst. Growth Des., 2013, 13, 19–23. 21. Thomas, S. P.; Kaur, R.; Kaur, J.; Sankolli, R.; Nayak, S. K.; Row, T. N. G. J. Mol. Struct., 2013, 1032, 88–92. 22. Scheiner, S. Hydrogen Bonding: A Theoretical Perspective, Oxford University Press, Oxford 1997. 23. Jeffrey, G. A. An Introduction to Hydrogen Bonding, Oxford University Press, Oxford 1997. 24. Desiraju, G. R.; Steiner, T. The Weak Hydrogen Bond, Oxford University Press, Oxford 1999. 25. Steiner, T. Angew. Chem. Int. Ed., 2002, 41, 48– 76. 26. Turner, M. J.; Thomas, S. P.; Shi, M. W.; Jayatilaka, D.; Spackman, M. A. Chem. Commun., 2015, 51, 3735-3738. 27. Turner, M. J.; Grabowsky, S.; Jayatilaka, D.; Spackman, M. A. J. Phys. Chem. Lett., 2014, 5, 4249-4255. 28. Thomas, S. P.; Pavan, M. S.; Row, T. N. G. Cryst. Growth Des. 2012, 12, 6083−6091. 29. Shi, M. W.; Thomas, S. P.; Koutsantonis, G. A.; Spackman, M. A. Cryst. Growth Des., 2015, 15, 5892-5900. 30. Thomas, S. P.; Jayatilaka D.; Row, T. N. G. Phys. Chem. Chem. Phys., 2015, 17, 25411-25420. 31. Thomas, S. P.; Sathishkumar, R.; Row, T. N. G. Chem. Commun., 2015, 51, 14255-14258. 32. Dey, D.; Thomas, S. P.; Spackman, M. A.; Chopra, D. Chem. Commun., 2016, 52, 2141-2144. 33. Thomas, S. P.; Shashiprabha, K.; Vinutha, K. R.; Nayak, S. P.; Nagarajan, K.; Row, T. N. G. Cryst. Growth Des. 2014 , 14, 3758−3766. 34. Spackman, M. A.; Jayatilaka, D. CrystEngComm, 2009, 11, 19-32. 35. Spackman, M. A.; Mckinnon, J. J. CrystEngComm, 2002, 4, 378-392. 36. Mckinnon, J. J.; Jayatilaka, D.; Spackman, M. A. Chem. Commun., 2007, 3814-3816. 37. Thomas, S. P.; Veccham, S. P. K. P.; Farrugia, L. J.; Row, T. N. G. Cryst. Growth Des. 2015, 15, 2110−2118. 38. Pete, U. D.; Dikundwar, A. G.; Sharma, V. M.; Gejji, S. P.; Bendre, R. S.; Guru Row, T. N. CrystEngComm 2015, 17, 7482-7485. 39. Mahapatra, S.; Thakur, T. S.; Joseph, S.; Varughese, S.; Desiraju, G. R. Cryst. Growth Des. 2010, 10, 3191-3202. 40. Kitaigorodskii, A. I. Organic chemical crystallography; Consultants Bureau, New York 1961. 41. Kitaigorodskii, A. I. Molecular Crystals and Molecules; Academic Press, New York 1973.

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For Table of Contents Use Only

Supramolecular chemistry of BrettPhos and BrettPhos oxide: Break-up of Isostructurality via Order-disorder Phase Transitions Amol G. Dikundwara*, Pema Chodona, Sajesh P. Thomasb, and Hemant Bhutanic* …………………………………………………………………………………………………………………………………………..

Temperature dependant solid state isostructurality between a metal binding ligand BrettPhos (BP) and its oxidized counterpart, BrettPhos oxide (BPO) is discussed along with four solvatomorphs of BPO indicating its potential to be used as a host in host-guest chemistry.

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Supramolecular Chemistry of BrettPhos and BrettPhos Oxide: Breakup

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