Crystal structures of 4-bromo-2-formyl-1-tosyl-1H-pyrrole, (E)-4-bromo-2-(2-nitrovinyl)-1-tosyl-1H-pyrrole and 6-(4-bromo-1-tosylpyrrol-2-yl)-4,4-dimethyl-5-nitrohexan-2-one

Crystal structures of three substituted N-tosylpyrrole compounds are reported; these compounds show a variety of ‘weak’ intermolecular interactions owing to different substitution patterns and supramolecular arrangements. The benefits of collecting crystal structure data to extreme resolution (0.5 Å) are discussed.


Chemical context
Dipyrrins -2,2 0 -dipyrromethenes -are molecular building blocks for multi-pyrrole fluorophores such as BODIPYs and porphyrins (e.g., Boyle et al., 1999) employed as ligands in medicinal and materials chemistry (e.g., Hohlfeld et al., 2021) made through facile condensation reactions, and widely exploited in chemistry. Partially reduced analogues of dipyrrins, containing one pyrrole and one pyrroline unit, are conceptually similar to chlorins -e.g. chlorophylls -where reduction of a macrocycle bond introduces electronic and photophysical changes (Senge et al., 2014). Synthetic chlorins are produced throught these intermediates by stepwise formation of a pyrroline ring (Taniguchi & Lindsey, 2017), pioneered by Battersby and coworkers (Dutton et al., 1983) and refined by Lindsey and coworkers (Laha et al., 2006). The compounds presented here are intermediates in the synthesis of derivatives of tetrahydrodipyrrin 4, a versatile precursor that can be formed in high yield from inexpensive reagents.
Compound 1 crystallizes in the chiral space group P2 1 2 1 2 1 ; although this compound exhibits no individual chiral atom centre, the pyrrole and toluenesulfonyl groups can have many possible orientations, with positive and negative rotation around the N-S bond breaking hypothetical reflection symmetry. The demands of the space-group symmetry of P2 1 2 1 2 1 with Z 0 = 1 are such that only one of these conformations is found in the unit cell. A Flack parameter of À0.016 (2), although anomalously low, strongly suggests that this individual crystal consists only of this pseudo-atropisomer. No evidence of any barrier to inversion is implied in solution, and enrichment of a preferred orientation in the solid state for this intermediate, without similar packing observed for other compounds here, underscores the difficulty in predicting solidstate conformations.
Compound 2 shows comparatively larger displacement ellipsoids than compounds 1 and 3, but excellent agreement between observations and model, simply without the excessive-resolution data. Compound 3 is the only compound in this series to exhibit a chiral centre -both enantiomers exist within the unit cell, as this is a conglomerate structure (Viedma et al., 2015). Both stereoisomers will form identical cyclized (oxidised) products upon conversion to compound 4 or similar species. ORTEP plots of the molecular units in the crystal structures of compounds 1, 2 and 3. Displacement ellipsoids (non-H) are presented at the 50% probability level, with H atoms presented as spheres of fixed radius (0.2 Å ). Table 1 Bond distances (Å ) in the shared pyrrole fragment of compounds 1, 2 and 3.

Supramolecular features
Each example reported here has a different mode of interactions with neighbouring molecules, with no consistent packing in the crystalline solid state. With a lack of heteroatom-bound protons, the solid-state architectures of each of these compounds lack traditional protic structuredirecting mortar. Common features are the traditionally overlooked intermolecular C-HÁ Á ÁO and C-HÁ Á ÁBr interactions, from the H atoms on the pyrrolyl, vinyl and aryl units to oxygen atoms in the sulfonyl, nitro or ketone moieties. This type of interaction is assisted by the partial charge separation in these components (Steiner, 2002). Individual molecules of compound 1 stack directly on top of one another down the crystallographic a-axis direction, and show a C-HÁ Á ÁO chelate to molecules in an adjacent stack (Table 2), related by the 2 1 screw coincident with the a axis. This interaction is shown in Fig. 2. Compound 2 shows coplanar intermolecular interactions of the nitrovinylpyrrole unit (Table 3), in which short contacts can be observed as a C-HÁ Á ÁO pseudo-chelate (3.36 and 3.30 Å , CÁ Á ÁO), as well as C-HÁ Á ÁBr (3.84 Å ) interactions at the limit of notability. These two interactions serve to form ribbon-like arrange-ments, which propagate coincident with the crystallographic axes [210] vector. Compound 3 demonstrates C-HÁ Á ÁO (3.28 and 3.29 Å , CÁ Á ÁO) and C-HÁ Á ÁBr (3.88 Å ) close-contact interactions; due to the length, these are likely superficial rather than structure directing.
In each of the compounds reported here, a multitude of unremarkable interactions around the van der Waals limit are observed to constrain individual molecules. The presence of C-HÁ Á ÁO interactions would likely be unremarkable if not for the chelate motif -these so-called weak interactions can be far stronger with partial charge separation, such as in a sulfonyl, and when occurring at multiple preorganized sites simultaneously (Kingsbury et al., 2019). Collection of multiple crystal structures along the synthetic pathway of organic compounds is, we believe, good practice to assist data science investigations, and offers potential insight into the electronic structure of intermediates (Senge & Smith, 2005).

Database survey
A search of the Cambridge Structural Database (CSD v 2020.3; Groom et al., 2016) revealed 37 closely related structures with the 2-carbo-4-halo-pyrrole substructure. These structures can be divided into BODIPYs and analogues (13/ 37), other isolated organic molecules (23/37), including intermediates in the total synthesis of (AE)-sceptrin, and a lone Cu coordination complex.
A data analysis of a further 851 structures with an Nbenzenesulfonyl-pyrrole substructure shows that the component torsional angles (in the range of 0-90 ), critcal in determining the solid-state conformation, each tend toward 90 . These values are consistent with our observations of an approximately adjacent-faces-of-a-cube arrangement of these two components. A Ramachandran-style plot illustrating the structural confluence of these two torsion angles is shown in  Table 2 Hydrogen-bond geometry (Å , ) for 1. Symmetry code: (i) x þ 1 2 ; Ày þ 3 2 ; Àz þ 1. Table 3 Hydrogen-bond geometry (Å , ) for 2. Symmetry code: (i) Àx; Ày þ 2; Àz þ 1.

Figure 2
Intermolecular C-HÁ Á ÁO interactions which control the intermolecular packing of compound 1. Displacement ellipsoids are shown at 50% for non-H atoms. Four equivalent molecules -in red, orange, green and blue -are related by a 2 1 screw coincident with the a axis.

Synthesis and crystallization
The synthesis of these compounds has been previously reported (Krayer et al., 2009). Crystals of the compounds 1, 2 and 3 were grown by hot recrystallization from ethyl acetate/ hexane mixture (1) or isopropanol (2) or slow evaporation of acetonitrile (3).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 4. The collection of high-resolution data (to 0.7 Å for 1 and 0.5 Å for 3, with Mo K) appears to have an effect on the quality of the structure solution and refinement. Residual electron density at the centre of each bond is apparent, as shown in Fig. 4; displacement ellipsoids are small. This additional data allows for bond distances to be determined at greater precision, as indicated in Table 1, and for the time involved in collection of this data to be extended artificially by 3-4 times. While unnecessary, this additional precision merits Ramachandran-style plot of torsion angles ( ) of central S-C and S-N bonds within N-benzenesulfonylpyrrole substructures of crystal structures in the CSD v2020.3 (n = 851). Compounds 1, 2 and 3 are highlighted in red within the main orientation cluster.  collection on crystals of sufficient quality when shorter collections are inconvenient. The suppression of presumably non-thermal character of displacement ellipsoids, such as that shown in compound 2, implies that the true thermal character at cryogenic temperatures is able to be better identified in high-resolution structures, though this could be the coincident effect of additional redundancy.

Funding information
This work has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 764837.

Figure 4
Residual electron density in the high-resolution data structure of 3; isosurface at 0.4 e À Å À3 (+ve in green, -ve in red). H atoms omitted from view. This plot shows residual positive electron density at the centre point of a significant fraction of the C-C bonds.

Computing details
For all structures, data collection: APEX3 (Bruker, 2015); cell refinement: SAINT (Bruker, 2015); data reduction: SAINT (Bruker, 2015); program(s) used to solve structure: SHELXT2018/2 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015b); molecular graphics: shelXle (Hübschle, 2011); software used to prepare material for publication: publCIF (Westrip, 2010).  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.

(E)-4-bromo-2-(2-nitrovinyl)-1-tosyl-1H-pyrrole (2)
Crystal data where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.80 e Å −3 Δρ min = −0.63 e Å −3 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.

6-(4-bromo-1-tosylpyrrol-2-yl)-4,4-dimethyl-5-nitrohexan-2-one (3)
Crystal data 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.