Structures of S-(pyridin-2-yl) 4-nitrobenzothioate, S-(pyridin-2-yl) 4-methylbenzothioate and S-(pyridin-2-yl) 4-methoxybenzothioate: building blocks for low-symmetry multifunctional tetrapyrroles

The structures of three S-(Pyridn-2-yl) benzothioesters are presented with varying para-phenyl motifs (NO2 in 1, CH3 in 2, and OCH3 in 3). These structures presented are the first in their class. Distinct changes are observed in the interaction types present in the crystal lattice as a direct result of the electronic influence of the para-phenyl motif.


Chemical context
In the continual search of evermore functional tetrapyrroles, the tedious separation of multiple regioisomeric porphyrins from mixed Adler-Longo (Adler et al., 1967) or Lindsey-style syntheses (Lindsey et al., 1986) no longer suits the desires of the few in this research field. Instead, multiple elegant yet simple routes have been developed for the functionalization of the porphyrin core (Hiroto et al., 2017;Sample et al., 2021), as well as from the modification of pyrrolic precursors (Lindsey, 2010). One route of note is via the monoacylation of mesosubstituted dipyrromethanes (I, Fig. 1). Initially reported with the use of acyl chlorides by Lindsey and coworkers (Lee et al., 1995), the procedure also yields the diacylated products in substantial yield. The same group reported the selective monoacylation of meso-aryl dipyrromethanes through the use of S-(pyridin-2-yl) benzothioesters (Rao et al., 2000).
S-(Pyridin-2-yl)benzothioesters were first synthesized for the determination of ionization constants for heterocyclic substances (Albert & Barlin, 1959). This methodology was later elaborated upon to generate a wide variety of alkyl, aryl and heteroaryl ketones (Araki et al., 1974). These compounds were also utilized to generate 2-ketopyrroles (Nicolau et al., 1981). Their versatility was recently highlighted (Lee, 2020). The developments that have led to this point now enable the generation of diverse substitution patterns for both porphyrins (Rao et al., 2000;Senge, 2011)

Structural commentary
The single-crystal XRD structures of title compounds 1, 2 and 3 (Figs. 2-4), all present asymmetric units consisting of one molecule of compound and no solvate. Compound 1 was found to crystallize in the orthorhombic system (Pna2 1 , Z = 4), compound 2 was found to crystallize in the triclinic system (P1, Z = 2) and compound 3 was found to crystallize in the monoclinic system (P2 1 /c, Z = 4). Each molecular structure shows an S-(pyridin-2-yl) benzothioate where the para-phenyl motif is modified, from NO 2 in 1, CH 3 in 2, and OCH 3 in 3. All of the groups utilized herein are found extensively in the field of tetrapyrroles.
In all structures 1-3, the substituted phenyl moieties are all essentially planar with the pyridine ring twisted relative to this plane. This is seen in the plane normal to plane normal angle Transformation of simple meso-substituted dipyrromethanes (I) to monoacyl-dipyrromethanes (II) through the use of S-(pyridin-2-yl) thioesters. A, B = aryl, R = Et, iPr, X = Br, Cl.

Figure 2
Molecular structure of 1. Anisotropic displacement ellipsoids are drawn at the 50% probability level. Generated using OLEX2.

Figure 3
Molecular structure of 2. Anisotropic displacement ellipsoids are drawn at the 50% probability level. Generated using OLEX2.

Figure 4
Molecular structure of 3. Anisotropic displacement ellipsoids are drawn at the 50% probability level. Generated using OLEX2. and the torsion angle described by C8-S1-C6-N1. The twist of the methanethioate moiety to the phenyl ring also describes the change in the angle of the rings to each other. These values are shown in Table 1.
In compound 1 (Fig. 2), the angle between the para-nitrobenzaldehyde moiety, C8-O18, and the pyridine ring is similar to the angle between the benzaldehyde moiety, C8-C16 and the pyridine ring in compound 2 (Fig. 3). The phenyl planepyridine plane angle and C8-S1-C6-N1 torsion angle in 3 ( Fig. 4) are very different to those of both 1 and 2.

Supramolecular features
Of the varying para-phenyl motifs presented across the series, the NO 2 group in 1 is the most electron withdrawing, according to its tabulated Hammett constant ( p = 0.78; McDaniel & Brown, 1958) but also observed by the differing shifts in the resonances presented for the para-substituted phenyl ring, with extensive deshielding of the respective protons (Figs. S1, S4 in the supporting information). Furthermore, considering the respective previously determined Hammett constants, it is observed that the most electron donating is the OCH 3 group in 3 ( p = À0.27), with 2 (CH 3 ) lying somewhere in between ( p = À0.17) (McDaniel & Brown, 1958); again, this is reflected in the 1 H NMR spectra.

Figure 5
Overlay of 1-3 and CEFMOR showing the orientation of the pyridine ring in 3 (red) relative to the other structures. Generated using OLEX2.

Figure 6
Excerpt of the packing structure of 1 viewed in the direction of thestack normal. Generated using OLEX2.
Compound 3 presents a multitude of non-classical hydrogen-bonding interactions, of the C-HÁ Á ÁO carbonyl and the C-HÁ Á ÁN pyridyl type ( stacking is evident in both 1 and 2. Weak dimeric offset stacking is observed in 1 with columns of anti-parallel non-interacting molecules when viewed normal to (001) (Fig. 6). The closest centroid-centroid distance in 1 (C10-C15 to C10 i -C15 i and N1-C6 to N1 i -C6 i [symmetry transformation: (i) x, y, À1 + z; x, y, 1 + z] is 3.850 (3) Å with a slippages of 1.823 and 1.856 Å , respectively, and angles between planes of 0.0 (2) . In 2, -stacking occurs only through phenyl ring pairs with the closest centroid-centroid distance being 3.8783 (11) Å , a slippage of 1.575 Å , and an angle between planes of 0.03 (9) , as seen normal to the (011) plane. In 3 there is no relevantstacking, with the closest centroidcentroid distance being 4.0847 (7) Å , with a slippage of 2.042 Å and an angle between the planes of 5.14 (6) .

Database survey
A search in the Cambridge Structural Database (CSD, Version 5.43, update November 2022; Groom et al., 2016) shows that no pyridine-substituted benzothioester structures are in the database. The unsubstituted S-phenyl benzothioate (CEFMOR; Belay et al., 2012) is similar structurally to 1 with only slight ring-twisting differences. However, the packing is quite different with only weak dimeric offsetstacking present in 1, with columns of anti-parallel non-interacting molecules when viewed normal to (001). The distinct C-HÁ Á ÁN interactions seen particularly in 3 do not exist in the phenyl homologue.

Synthesis and crystallization
Compounds 1, 2, and 3 were synthesized following the reported procedure (Rao et al., 2000). Briefly, the respective acyl chloride (1 eq., ca 0.2 M) in a solution of CH 2 Cl 2 was added dropwise over 0.5 h to a stirring solution of 2-mercaptopyridine (1 eq., ca 0.2 M) in CH 2 Cl 2 . The solution was left to stir for a further 2 h at room temperature.   Hydrogen-bonding networks represented by dotted lines shown in a excerpt of the packing structure of 3 viewed normal to the b axis. Generated using OLEX2.
Throughout the addition processes, minor exotherms were noted, particularly for 1. The solution was diluted with the same volume again of CH 2 Cl 2 , and the solution was washed with NaOH (2 M), water, brine, and the organic layer then dried (MgSO 4 ). Excess solvent was removed under reduced pressure and the title compounds were purified in the following ways: for 1, crystals were generated via hot recrystallization from ethyl acetate, and for 2 and 3, crystals were generated via precipitation from diethyl ether and hexanes. Compound 1 was yielded in 69%, with yields for 2 and 3 comparable to those previously reported (Rao et al., 2000). 1 H NMR spectroscopic data matched previously reported synthesized compounds 2 and 3. Whilst the synthesis of compound 1 has been reported previously, no characterization data has been reported for it (Perrin et al., 2011). Below we present analytical data for 1, and within the supporting information we have attached the appropriate spectra, Figs. S1-S3. We also present there the NMR spectra for 2 and 3, to exhibit the electronic differences between the three compounds studied herein (Fig. S4).
Analytical data for 1:

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 5. Hydrogen atoms were positioned geometrically and refined isotropically using a riding model with C-H = 0.93-0.98 Å and U iso (H) = 1.2-1.5U eq (C).

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.

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.