Crystal structure of 2,3-dimethoxy-meso-tetrakis(pentafluorophenyl)morpholinochlorin methylene chloride 0.44-solvate

The title morpholinochlorin adopts a ruffled conformation of its porphyrinic π-system chromophore inducing a red-shift of its optical spectrum compared to its chlorin analog.

The title morpholinochlorin, C 46 H 16 F 20 N 4 O 3 , was crystallized from hexane/ methylene chloride as its 0.44 methylene chloride solvate, C 46 H 16 F 20 N 4 O 3 Á0.44CH 2 Cl 2 . The morpholinochlorin was synthesized by stepwise oxygen insertion into a porphyrin using a 'breaking and mending strategy': NaIO 4 -induced diol cleavage of the corresponding 2,3-dihydroxychlorin with in situ methanol-induced, acid-catalyzed intramolecular ring closure of the intermediate secochlorins bisaldehyde. Formally, one of the pyrrolic building blocks was thus replaced by a 2,3-dimethoxymorpholine moiety. Like other morpholinochlorins, the macrocycle of the title compound adopts a ruffled conformation, and the modulation of the porphyrinic -system chromophore induces a red-shift of its optical spectrum compared to its corresponding chlorin analog. Packing in the crystal is governed by interactions involving the fluorine atoms of the pentafluorophenyl substituents, dominated by C-HÁ Á ÁF interactions, and augmented by short fluorineÁ Á Áfluorine contacts, C-FÁ Á Á interactions, and one severely slipped -stacking interaction between two pentafluorophenyl rings. The solvate methylene chloride molecule is disordered over two independent positions around an inversion center with occupancies of two Â 0.241 (5) and two Â 0.199 (4), for a total site occupancy of 88%.
One member of the family of porphyrinoids incorporating non-pyrrolic heterocycles are the morpholinochlorins (1) (Fig. 1) in which one pyrrolic building block is replaced by a morpholine (Brü ckner et al., 1998(Brü ckner et al., , 2011McCarthy et al., 2003). This formal replacement is achieved by a stepwise oxygen insertion into a porphyrin using a so-called 'breaking and mending' strategy (Brü ckner, 2016). As a consequence of the atom insertion, morpholinochlorins are non-planar (McCarthy et al., 2003;Brü ckner et al., 2011;Sharma et al., 2017). The twisted (ruffled) conformation of helimeric chirality of the morpholinochlorins was found to be affected by the size and number of alkoxy substituents, the presence of covalent links between the morpholine unit and the flanking aryl group, and the presence and type of central metal (Daniell & Brü ckner, 2004;Brü ckner et al., 2011;Sharma et al., 2017). Porphyrinoids containing two morpholine moieties are known (Daniell & Brü ckner, 2004;Guberman-Pfeffer et al., 2017), as well as other porphyrinoids containing morpholine building blocks (Lara et al., 2005;Samankumara et al., 2015;Akhigbe et al., 2016). The modulation of the conformation of the porphyrinic -system also affects their electronic properties; morpholinochlorins are more red-shifted than a corresponding chlorin (Brü ckner et al., 2011;Guberman-Pfeffer et al., 2017). The influence of the meso-substituents on the conformation and electronics of the morpholinochlorins has not been investigated.
For porphyrinoids at large, the introduction of mesopentafluorophenyl-groups (or fluorine atoms, in general) has long been known to alter their electronic properties (Spellane et al., 1980;Leroy & Bondon, 2008;Nardi et al., 2013); they often become slightly blue-shifted compared to their nonfluorinated analogues and are harder to oxidize. Also, the meso-pentafluorophenyl-groups are very convenient handles for the further synthetic manipulation of the porphyrinoids (Costa et al., 2011;Golf et al., 2015;Hewage et al., 2015;Bhupathiraju et al., 2016). Their effect on the conformation of the molecules, when compared to their hydrogen analogs, has been shown to be frequently minimal (Leroy & Bondon, 2008).

Structural commentary
The title compound 1d was obtained in crystalline form from hexane/methylene chloride as its 0.44 methylene chloride solvate (Fig. 2). 1d crystallizes as a racemic mixture of two helimers in the monoclinic space group C2/c, and its structure is generally in line with that of the other three free base morpholinochlorins that have been structurally described ( Fig. 1): the meso-tolyl derivative 1b with two ethoxy substituents in the 2,3 positions of the morpholine (McCarthy et al., 2003); the meso-phenyl derivative 1e with a single methoxy substituent (Brü ckner et al., 2011), and the mesophenyl derivative 1f lacking any morpholine substitution (Brü ckner et al., 2011). The macrocycle in all morpholinochlorins is non-planar. In the symmetrically substituted morpholinochlorins, 1b, 1d and 1f, individual molecules are ruffled (Shelnutt et al., 1998), feature a chiral axis and are helimeric. Derivative 1e with only a single methoxy substituent on the morpholine (Brü ckner et al., 2011) features a more The structure of 1d with the atom-labeling scheme. Probability ellipsoids are drawn at the 50% level. Symmetry-created atoms are shown in capped-stick mode and are unlabeled. Dashed bonds indicate minor moiety disordered and symmetry-related atoms. Some carbon atom labels are omitted for clarity.

Figure 1
Structures of select morpholinochlorins saddled conformation of its macrocycle (Brü ckner et al., 2011). The geometries of the morpholino rings also vary between the four structures. In the two 2,3-substituted derivatives, title compound 1d and meso-tolyl derivative 1b, the substituents are arranged anti to each other, and the morpholino rings adopt a conformation that is best described as half-twist. This stereoselective arrangement had been rationalized on steric and stereoelectronic grounds (Brü ckner et al., 2011). The morpholine moiety in the mono-alkoxy derivative 1e adopts a half-boat conformation (Brü ckner et al., 2011).
Out-of-plane plots of the macrocycle conformations of 1b and 1d directly compare their ruffled conformation that allows the central nitrogen atoms to remain idealized in the central plane (Fig. 3). The conformation of the C 20 N 4 O morpholinochlorin macrocycle in 1d is slightly more ruffled (r.m.s. = 0.323 Å ) (Shelnutt et al., 1998) than in 1b (r.m.s. = 0.276 Å ; Sharma et al., 2017). While the tripyrrolic portion of 1d is significantly more ruffled than the corresponding section of 1b, the morpholine moieties are, except for the position of the ring oxygen, rather similar.
Similar to other meso-aryl porphyrinoids, the torsion angles in the morpholinochlorins between the meso-aryl substituents and the mean plane of the macrocycle vary with the steric demand of the groups flanking the aryl substituents. The mesopentafluorophenyl groups neighboring the pyrrolic units (C 5 F 6 rings of C27 and C33) face little steric constraints and adopt dihedral angles of 71.92 (2) and 74.95 (3) , respectively. Those adjacent to the morpholine moiety (C 6 F 5 rings of C21 and C39) are more sterically encumbered and are about 10 closer to perpendicular to the macrocycle plane, with values of 82.70 (3) and 81.44 (2) . The corresponding values for compound 1b are very similar, with values of 71.89 and 73.73 , and 89.55 and 86.32 , respectively.
The close structural relationship between the 2,3-disubstituted derivatives 1b and 1d allows us to investigate how minor conformational changes might affect the optical properties of the morpholinochlorins. The torsion angles between the two C-C bonds in the morpholine units [C a -C b -(N)-C b -C a , C2-C1-(N1)-C4-C3 in 1d] in the two morpholinochlorins 1b and 1d vary slightly, with this angle being smaller in the title compound [35.2 in 1b and 25.5 (4) 1d]. This angle is important as it strongly affects the max of the morpholinochlorins (Guberman-Pfeffer et al., 2017), with a larger torsion angle being correlated to a longer max in their UV-vis absorption spectra. However, while the UV-vis spectra of the two species show distinct differences, their max values are essentially the same (680 nm in 1d vs 678 nm in 1b; Fig. 4), likely as the result of the combination of their differing conformation and electron-withdrawing natures of their mesosubstituents (phenyl in 1b and pentafluorophenyl in 1d).

Figure 3
Out-of-plane displacement plots of macrocycles of the title compound 1d (black trace) and morpholinochlorin 1b (gray trace).
FÁ Á Á interactions (towards the system of a the macrocycle), and one severely slipped -stacking interaction between two pentafluorophenyl rings.
The most prominent C-HÁ Á ÁF interactions (Levina et al., 2019) involve the two methyl groups of the 2,3-dimethoxymorpholino unit (Fig. 5a). Both methoxy substituents are engaged in several of these interactions: C45 exhibits interactions with fluorine atoms from three different pentafluorophenyl groups: with meta fluorine atoms F12 iii and F19 iv [symmetry codes: (iii) Àx + 1, y, Àz + 1 2 ; (iv) Àx + 1, Ày + 1, Àz + 1], and one intramolecular interaction with F20, an ortho-fluorine atom. Angular and HÁ Á ÁF distance values for this intramolecular interaction appear quite unfavorable: the C-HÁ Á ÁF angle is only 103 , and the HÁ Á ÁF distance is 2.82 Å . However, only a slight rotation of the methyl H atoms is required to create a much more favorable geometry, and the CÁ Á ÁF distance between C45 and F20 is at 3.184 (3) quite short (the shortest of all C-HÁ Á ÁF interactions observed in 1d).
Interactions involving the methoxy group of C46 involve F10 v and F1 vi , two ortho-fluorine atoms [symmetry codes: (v) x À 1 2 , y À 1 2 , z; (vi) Àx + 1 2 , Ày + 3 2 , Àz + 1]. Two C-HÁ Á ÁF interactions originate from pyrrole moieties, involving H atoms at the pyrrole moieties flanking the morpholine unit: H8 towards F18 i , and H18 towards F8 ii , with both F8 and F18 being parafluorine atoms [symmetry codes: (i) x, y + 1, z; (ii) x, y À 1, z]. These two interactions work in tandem with each other and with a severely slippedstacking interaction, between the rings of F6-F10 and F16 i -F20 i , connecting two opposite ends of the morpholinochlorin molecule with its neighbors to create infinite chains connected via C-HÁ Á ÁF and slippedstacking interactions (Fig. 5b). The centroid-to-centroid distance of the -stacking interaction is 4.3551 (15) Å , with a ring slippage of 2.795 Å and a centroid-to-mean-plane distance of 3.1661 (12) Å . The last C-HÁ Á ÁF interaction involves the methylene group of the minor moiety solvate methylene chloride molecule. Given the degree of disorder of the solvate molecules (see Refinement section), this interaction is probably vaguely defined at best and will not be discussed in detail.
Besides C-HÁ Á ÁF interactions, which are generally considered as directional interactions similar in strength to the better investigated C-HÁ Á ÁO interactions, 1d also features a number of short FÁ Á ÁF contacts. In contrast to halogen-Á Á Áhalogen bonds involving chlorine, and especially bromine and iodine (the classical halogen bonds), interactions between two fluorine atoms are different and much weaker in nature (Cavallo et al., 2016). C-FÁ Á ÁF-C interactions are generally not directional and do usually not play any structure-directing role. The energy of intermolecular C-FÁ Á ÁF-C interactions in molecular compounds is estimated at <4 kJ mol À1 , substantially lower that of C-HÁ Á ÁF interactions, which tend to range from 5 to 7 kJ mol À1 . They are, however, still (a) C-HÁ Á ÁF interactions involving the methoxy hydrogen atoms (turquoise dashed lines). Accepting moieties are truncated to their pentafluorophenyl groups, and symmetry-related atoms not directly involved in an interaction are shown in stick mode for clarity. (b) C-HÁ Á ÁF and slippedstacking interactions (turquoise dashed lines) connecting molecules into infinite chains. Red spheres indicate the centroids of the respective aromatic rings, green dashed lines the distance between centroids (in Å ). For symmetry codes, see Table 1. FÁ Á ÁF interactions (turquoise dashed lines) creating a triangular motif. Symmetry-related moieties are truncated to their pentafluorophenyl groups, and atoms not directly involved in an interaction are shown in stick mode for clarity. Symmetry codes: (vii) Àx + 1 2 , y À 1 2 , Àz + 1 2 ; (viii) Àx + 1 2 , Ày + 3 2 , Àz + 1.
regarded as weakly attractive and contributing to the overall stability of the packing arrangement (Levina et al., 2019). Three distinct interactions of this kind with FÁ Á ÁF distances under 3.0 Å are observed in 1d. Fluorine atom F5 forms close contacts with F7 and F8 located at the C 6 F 5 ring of a neighboring molecule. The FÁ Á ÁF distances are 2.797 (2) Å (F5Á Á ÁF7 vii ) and 2.828 (3) Å (F5Á Á ÁF8 vii ) [symmetry code: (vii) 1 2 À x, À 1 2 + y, 1 2 À z]. With the intramolecular distance between F7 and F8 being 2.726 (2) Å , this leads to the formation of a nearly equilateral triangle of F atoms (Fig. 6a). It should be noted that atom F8 of this F 3 -triangle also acts as the acceptor of the C18-H18Á Á ÁF8 ii contact and the backside of the aromatic ring of F8 is involved in the slippedstacking interaction (see discussion above). Fluorine atom F11 features a close contact with a symmetry-created copy of itself, created by a twofold axis. The FÁ Á ÁF iii distance here is 2.783 (3) Å , and the C-FÁ Á ÁF iii angle is 125.5 (2) [symmetry code: (iii) Àx + 1, y, Àz + 1 2 ]. F11 also interacts with the system of the macrocycle created by the same twofold axis, with FÁ Á ÁC distances towards C14 iii and C15 iii of 3.046 (3) and 3.035 (3) Å , and F12 acts as the acceptor of the C45-H45CÁ Á ÁF12 iii interaction, thus creating a larger multi-interaction contact between the two neighboring molecules with mutually stabilizing interactions (Fig. 7a). The last clearly recognizable interaction between fluorine atoms is an inversion-symmetric pair of two FÁ Á ÁF contacts, involving F14 and F15 of one C 6 F 5 ring and their symmetry-related counterparts across a crystallographic inversion center (Fig. 6b). The F14Á Á ÁF15 viii distance is 7.248 (2) Å . The C37-F14Á Á ÁF15 viii angle here is 168.6 (2) [symmetry code: (viii) 1 2 À x, 3 2 À y, Àz]. Besides F11, F2 and F3 are also involved in intermolecular C-FÁ Á Á interactions, pointing nearly perpendicularly towards C atoms (C41 vi and C42 vi ) of another pentafluorophenyl ring [symmetry code: (vi) Àx + 1 2 , Ày + 3 2 , Àz + 1]. The FÁ Á ÁC distances are 3.034 (3) and 2.978 (3) Å for F2 and F3, respectively. There are two interactions of this kind per molecule, one as the C-F donor and one as the -density moiety accepting the C-FÁ Á Á bond, connecting molecules into centrosymmetric dimers. One of the methyl C-HÁ Á ÁF contacts (towards F1) is also involved in the formation of these dimers (Fig. 7b).

Database survey
A CSD search (Version 5.41 with updates up to May 2020; Groom et al., 2016) for porphyrinic macrocyles of three pyrroles and a single six-membered ring while retaining the porphyrin-like architecture of four central nitrogen atoms reveals 24 structures: six pyriporphyrins (i.e., porphyrinoids containing a pyridine building block), fifteen morpholinochlorins, two thiomorpholines [UCIKOJ and UCILIE (Sharma et al., 2016)], and a single 1,3-oxazinochlorin (WUDMIT; Meehan et al., 2015). Among the 1,4morpholinochlorins, six are free base structures, the remainder are metal complexes [of Cu II , Ni II -most frequently, Zn II , Ag II and Pd II , see

Synthesis and crystallization
We prepared the title compound 1d according to an established strategy from the corresponding 2,3-dihydroxychlorin 2 ( Fig. 1) (Brü ckner et al., 2011): Oxidative diol cleavage is followed, in a one-pot approach, by a nucleophile-induced (methanol), acid-catalyzed intramolecular ring closure and subsequent double-acetalization. Specifically, meso-tetrakis(pentafluorophenyl)-2,3-dihydroxychlorin 2 (Hyland et al., 2012) (30 mg, 2.97 Â 10 À5 mol) was dissolved in a 50 mL twonecked round-bottom flask equipped with a stir bar and gas in/ outlets in CHCl 3 (7 mL, amylene stabilized). The vessel was put under a protective atmosphere of N 2 . Freshly prepared NaIO 4 heterogenized on silica (Zhong & Shing, 1997 Table 1. acidified with the vapors from a conc. aqueous HCl bottle (36%), delivered to the surface of the solution as puffs (3 Â $1 mL) from a Pasteur pipette topped by a small latex bulb. The reaction was shielded from light by aluminum foil, stirred at ambient temperature and monitored by TLC (silica gel/ CH 2 Cl 2 ). After 24 h reaction time, no further reaction was observed; the solution was filtered (glass frit M) and the filtrate reduced to dryness by rotary evaporation. The crude product was dissolved in CH 2 Cl 2 ($1 mL), loaded onto a preparative TLC plate (500 mm silica gel, 10 Â 20 cm) that was developed with a 1:1 CH 2 Cl 2 :hexane mixture as eluent. The main brown band was retrieved, ground into a fine powder, and extracted in a cotton-plugged small column with CH 2 Cl 2 . The addition of $20 vol% MeOH to the filtrate and slow removal of the CH 2 Cl 2 by rotary evaporation precipitated the product, which could be isolated by filtration (Kontes microfiltration setup). After vacuum-drying at ambient temperature, 1d was retrieved as a dark-purple powder in 66% yield (21 mg

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2.
Crystals for diffraction analysis were taken directly out of the mother liquor (methylene chloride/hexane), mounted immediately on a MiTeGen micromesh mount with the help of a trace of Fomblin oil (a perfluorinated ether), and flash cooled in the cold stream of the diffractometer. Over several hours, no desolvation was observed for crystals remaining immersed in Fomblin oil on the crystal mounting microscope slide.
The solvate methylene chloride molecule is disordered over four positions around an inversion center (each two being symmetry equivalent). The C-Cl and ClÁ Á ÁCl distances were restrained to target values and U ij components of ADPs for disordered atoms closer to each other than 2.0 Å were restrained to be similar. Occupancies of each of the two symmetry-equivalent sites were freely refined, resulting in a total occupancy slightly below unity [two Â 0.241 (5) and two Â 0.199 (4), for a total site occupancy of 88%]. Disorder with hexane, the other type of solvent used during crystallization, was excluded as a possibility due to the limited size of the solvate pocket, and it is thus assumed that 12% of void spaces in the crystal structure remained unoccupied during the crystallization process.
N-bound H atoms were located in a difference electrondensity map and were freely refined. H atoms attached to carbon atoms were positioned geometrically and constrained to ride on their parent atoms. C-H bond distances were constrained to 0.95 Å for pyrrole CH moieties, and to 1.00, 0.99 and 0.98 Å for aliphatic CH, CH 2 and CH 3 moieties, respectively. Methyl CH 3 groups were allowed to rotate but not to tip to best fit the experimental electron density. U iso (H) values were set to a multiple of U eq (C) with 1.5 for CH 3 , and 1.2 for CH and CH 2 units, respectively.  Data collection: APEX3 (Bruker, 2016); cell refinement: SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015) and shelXle (Hübschle et al., 2011); molecular graphics: Mercury (Macrae et al., 2020); software used to prepare material for publication: publCIF (Westrip, 2010) and PLATON (Spek, 2020).

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.