Hydrogen Bonding in Crystals of Pyrrol-2-yl Chloromethyl Ketone Derivatives and Methyl Pyrrole-2-Carboxylate

: The crystal and molecular structure of three derivatives of carbonyl 2-substituted pyrroles was determined by the single crystal X-ray diffraction. There are 2,2-dichloro-1-(1-methyl-1 H -pyrrol- 2-yl)ethan-1-one ( I ), 2-chloro-1-(1 H -pyrrol-2-yl)ethan-1-one ( II ) and methyl 1 H -pyrrole-2-carboxylate ( III ). All compounds crystallize with one molecule in the asymmetric unit in P 2 1 2 1 2 1 for I and II , and P 2 1 /c group for III . Despite the similar structures of the investigated compounds, the hydrogen bonds formed in their crystal structures adopt different H-bond motifs. In structure I , the dimers R 12 (5) and R 21 (7) form a chain along the b -axis, while in structures II and III , chain C(5) structural motifs are formed. The single point calculations at a ω B97XD/6-311++G(d,p) level of theory indicate that systems with N-H · · · O bonds have greater interaction energies (are more stable) compared with systems featuring C-H · · · O/Cl bonds. A descriptive Hirshfeld analysis showed that the greatest differences are visible for the H · · · H interactions. These H · · · H interactions predominate in structure III , accounting for 45% of the intermolecular interactions, while in structures I and II , they account for only 25%. Although compounds I - II contain Cl-atoms, the percentage of Cl · · · Cl interactions is rather low. In structure with two Cl-atoms ( I ), the contribution of the Cl · · · Cl contacts is 8.7% and for II , the contribution accounts for only 0.4% of the interactions.


Introduction
Five-membered heterocyclic compounds are among the most widespread and important building blocks of molecular structures.Among them, the pyrrole ring, which is a building element in many natural products, such as hem [1], chlorophylls [2], and bioactive alkaloids [3][4][5][6][7], is the most common.Although the parent pyrrole has been characterized experimentally [8] and analyzed [9][10][11][12] by theoretical methods, relatively little is known about its derivatives, particularly the noncovalent governing of the crystal structure of this class of compounds.
Halogen bonds also impart directionally in crystal structures, and may be considered as counterparts of hydrogen bonds [25][26][27][28][29][30][31].Halogen bonds involving C-Cl• • • O have been observed in the crystal structure of 1-methylpyrrol-2-yl trichloromethyl ketone [32].Analyses of other interactions of carbonyl 2-substituted pyrroles show mainly different kinds of hydrogen bonds [16][17][18][19]32].Density Functional Theory (DFT) calculations indicated that for the s-cis conformation of pyrrole-2-carboxylic acid, where the NH and COO bonds are located on the same side of the moiety, two centrosymmetric dimers are possible [33].For each dimer, there are two equivalent hydrogen bonds, two O-H• • • O bonds creating R 2 2 (8) motifs according to Etter's rules [34,35] or two N-H• • • O hydrogen bonds forming R 2 2 (10) motifs.H-bonded motifs in crystal structures are described by graph set assignments [34,35].R denotes the ring, and the number of atoms that make up the ring is given in parentheses.Therefore, for R 2 2 (8) there are eight ring atoms linked through covalent and hydrogen bonds, since two hydrogen bonds form between two carboxylic groups.The superscript and subscript denote the number of proton acceptors and proton donors, respectively.For R 2 2 (8) there are two equivalent proton acceptor O centers (since the dimer is linked through two equivalent molecules) and two equivalent proton-donating bonds (OH).Etter also described other motifs [34,35]: C denotes the chain of atoms containing hydrogen bonds which repeat in the crystal structure, S refers to intramolecular hydrogen bonds and D replays to a dimer where a single hydrogen bond exists.
In the case of the s-trans conformer of pyrrole-2-carboxylic acid, there is only the possibility that the dimer contains two equivalent O-H• • • O bonds within the R 2 2 (8) motif.An X-ray structure analysis confirmed that pyrrole-2-carboxylic acid forms crystals with s-cis conformers that form the motifs R 2 2 (8) and R 2 2 (10) mentioned above [19].Recently, 2-pyrrolecarboxylic acid and 1-methyl-2-pyrrolecarboxylic acid have been studied by thermochemical measurements and computational analyses [36], and pyrrole-2-carboxamide has been analyzed by spectroscopic and X-ray methods, and DFT calculations [19].For the latter compound, the s-cis conformer was revealed and the presence of centrosymmetric dimers in crystals connected through N-H• • • O bonds.
Due to the importance and prevalence of pyrrole compounds in organic chemistry, we have conducted research aimed at extending knowledge of the structural properties in some pyrrol-2-yl carbonyl compounds, particularly focusing on the role of the intermolecular interactions in their crystal structures.When searching the Cambridge Structural Database [37], we found more than 26,500 compounds containing pyrrole rings.Among them, there are almost 930 structures with a 2-substituted pyrrole core and only 153 with a 2-pyrrol-2-yl core, and 14 of the 27 pyrrol-2-yl halogenated ketone contain a chlorine atom.

Synthesis of Pyrrol-2-yl Chloromethyl Ketones
The conventional Friedel-Crafts acylation method was applied for the preparation of aromatic ketones I and II (Scheme 1) [38].The title pyrroloketones were generally obtained using acid chlorides as acylating agents and stoichiometric amounts of AlCl 3 as a reaction promoter.Dichloroacetyl chloride or chloroacetyl chloride (0.02 mol) was dissolved in 10 mL of anhydrous ethyl ether and 0.02 mol of AlCl 3 was added.Then, the 0.02 mol of freshly distilled pyrrole was added dropwise and the reaction mixture was stirred for one hour at room temperature.After that time, an aqueous solution of potassium carbonate (0.02 mol) was added.The resulting mixtures were extracted twice with ether and the crude products were purified by crystallization from hexane.Spectroscopic data are available in [39].

Synthesis of Methyl Pyrrole-2-Carboxylate
Methyl pyrrole-2-carboxylate (III) was synthesized (Scheme 2) according to the method of Bailey et al. [40].Sodium (0.08 g) was dissolved in 50 mL of anhydrous methanol, and 5.3 g (0.025 mol) of pyrrol-2-yl trichloromethyl ketone was added portion by portion over a 10-minute period.The solution was stirred for 30 min and then concentrated to dryness using a rotary evaporator.The oil residue was partitioned between ethyl ether and 3M HCl (1:1, V:V).The ether layer was separated, and the aqueous layer was washed once with ether.The combined ether solutions were washed once with an aqueous sodium hydrogen carbonate solution (10%), dried with magnesium sulfate, and concentrated by distillation.The crude products were purified by crystallization from a mixture of hexane and ethyl acetate (1:1; V:V), giving 2.5 g of ester.Spectroscopic data are available in [16,17].Scheme 2. Reaction scheme of III.

X-ray Diffraction Analysis
Measurements of structure I was performed on a Stoe IPDS diffractometer with graphite monochromated MoKα radiation (λ = 0.71073 Å ).For the compound, data reductions were performed with Stoe IPDS [41].The intensities were corrected for Lorentz and polarization effects.An empirical absorption correction was applied for compound I [42].The structures of II and III were measured on Rigaku SuperNova Dual Source diffractometer, also with MoKα radiation (λ = 0.71073 Å ).For both compounds, analytical absorption corrections were applied [43].The data collection and refinement parameters are given in Table 1, and the structures of the molecules are shown in Figure 1.The structure was solved by direct methods with SIR-97 [44] for structures I and by SHELXS [45] for structures II and III, which revealed the positions of all non-H-atoms.Non-H-atoms were refined anisotropically.For structure I, all of the H-atoms were located in a difference electron density map, whereas for structures II and III, they were placed in geometrically calculated positions.Then, for all structures, positions of H-atoms were allowed to refine together with individual isotropic temperature factors.The refinement of each structure

Synthesis of Methyl Pyrrole-2-Carboxylate
Methyl pyrrole-2-carboxylate (III) was synthesized (Scheme 2) according to the method of Bailey et al. [40].Sodium (0.08 g) was dissolved in 50 ml of anhydrous methanol, and 5.3 g (0.025 mol) of pyrrol-2-yl trichloromethyl ketone was added portion by portion over a 10-minute period.The solution was stirred for 30 min and then concentrated to dryness using a rotary evaporator.The oil residue was partitioned between ethyl ether and 3M HCl (1:1, V:V).The ether layer was separated, and the aqueous layer was washed once with ether.The combined ether solutions were washed once with an aqueous sodium hydrogen carbonate solution (10%), dried with magnesium sulfate, and concentrated by distillation.The crude products were purified by crystallization from a mixture of hexane and ethyl acetate (1:1; V:V), giving 2.5 g of ester.Spectroscopic data are available in [16,17].Scheme 2. Reaction scheme of III.

X-ray Diffraction Analysis
Measurements of structure I was performed on a Stoe IPDS diffractometer with graphite monochromated MoKα radiation (λ = 0.71073 Å ).For the compound, data reductions were performed with Stoe IPDS [41].The intensities were corrected for Lorentz and polarization effects.An empirical absorption correction was applied for compound I [42].The structures of II and III were measured on Rigaku SuperNova Dual Source diffractometer, also with MoKα radiation (λ = 0.71073 Å ).For both compounds, analytical absorption corrections were applied [43].The data collection and refinement parameters are given in Table 1, and the structures of the molecules are shown in Figure 1.The structure was solved by direct methods with SIR-97 [44] for structures I and by SHELXS [45] for structures II and III, which revealed the positions of all non-H-atoms.Non-H-atoms were refined anisotropically.For structure I, all of the H-atoms were located in a difference electron density map, whereas for structures II and III, they were placed in geometrically calculated positions.Then, for all structures, positions of H-atoms were allowed to refine together with individual isotropic temperature factors.The refinement of each structure Scheme 2. Reaction scheme of III.

X-ray Diffraction Analysis
Measurements of structure I was performed on a Stoe IPDS diffractometer with graphite monochromated MoKα radiation (λ = 0.71073 Å).For the compound, data reductions were performed with Stoe IPDS [41].The intensities were corrected for Lorentz and polarization effects.An empirical absorption correction was applied for compound I [42].The structures of II and III were measured on Rigaku SuperNova Dual Source diffractometer, also with MoKα radiation (λ = 0.71073 Å).For both compounds, analytical absorption corrections were applied [43].The data collection and refinement parameters are given in Table 1, and the structures of the molecules are shown in Figure 1.The structure was solved by direct methods with SIR-97 [44] for structures I and by SHELXS [45] for structures II and III, which revealed the positions of all non-H-atoms.Non-H-atoms were refined anisotropically.For structure I, all of the H-atoms were located in a difference electron density map, whereas for structures II and III, they were placed in geometrically calculated positions.Then, for all structures, positions of H-atoms were allowed to refine together with individual isotropic temperature factors.The refinement of each structure was carried out on F 2 using full-matrix least-square procedures, which minimized the function ∑w(F 2 o -F 2 c ) 2 with SHELXL-2014/7 [46].Geometry analysis and molecular plots were obtained using the PLATON program [47] and Mercury [48].

Hirshfeld Surface Analysis
Hirshfeld analysis was performed using Crystal Explorer [49,50].The Hirshfeld surface maps intermolecular contacts, and it is computed at the sum of de and di, the distances from the external atoms to the surface and the internal atoms to the surface, respectively [49].Sums of distances shorter than the sum of the van der Waals radii of two neighboring atoms are marked with red spots, distances close to the van der Waals radii are marked in white, and distances larger than the sum of van der Waals radii are marked in blue.A qualitative description of all relevant contacts in the crystal structure is shown in fingerprint graphs [50] by plotting the distances from contact atoms to the Hirshfeld surface, di and de, in a 2D graph, creating a 'heatmap' of noncovalent interactions.

Full Interaction Maps Analysis
The Full Interaction Maps feature is included with mercury [48].This tool generates

Hirshfeld Surface Analysis
Hirshfeld analysis was performed using Crystal Explorer [49,50].The Hirshfeld surface maps intermolecular contacts, and it is computed at the sum of d e and d i , the distances from the external atoms to the surface and the internal atoms to the surface, respectively [49].Sums of distances shorter than the sum of the van der Waals radii of two neighboring atoms are marked with red spots, distances close to the van der Waals radii are marked in white, and distances larger than the sum of van der Waals radii are marked in blue.A qualitative description of all relevant contacts in the crystal structure is shown in fingerprint graphs [50] by plotting the distances from contact atoms to the Hirshfeld surface, d i and d e , in a 2D graph, creating a 'heatmap' of noncovalent interactions.

Full Interaction Maps Analysis
The Full Interaction Maps feature is included with mercury [48].This tool generates a picture of the interaction landscape of a molecule from its 3D coordinates.Using statistical distributions from structures included in the CSD, it predicts the most likely locations for a variety of functional groups.By comparing this distribution with a 3D packing diagram, it can determine whether a crystal structure fulfils the desired interactions of a particular conformation of a particular molecule.

Theoretical Calculations
All molecular systems were examined using the ωB97XD [51] variant of DFT with the 6-311++G(d,p) base set [52][53][54][55].This level of theory gives good results in the case of hydrogen bonds or other weak interactions with the contribution of dispersion effects, and is appropriate for the calculation of relatively large systems [56,57].All three systems (I-III) were calculated with use of single point calculations in geometries taken from the crystal state.Only the positions of H-atoms were normalized according to neutron diffraction data [58], which is a standard procedure for model system in geometries extracted from Xray experiments.All calculations were carried out using the Gaussian09 package (revision D.01) [59].Interaction energies for the analyzed systems have been computed as the difference between the total energy of the complex and the energies of monomers, and were corrected for the basis set superposition error (BSSE) using the counterpoise procedure [60].The monomers were in the same geometries as those in a dimer complex or chain system; thus, we exclude the deformation energy from our consideration.

Results and Discussion
In a recent study, we investigated centrosymmetric dimers formed by pyrrol-2-yl chloromethyl ketones in their s-cis conformers [39].According to current knowledge [20,61], the s-cis conformer, in which the NH and COO groups are located on the same side of the moiety, is more stable than the s-trans conformer.Theoretical calculations and crystal structure data show that, in general, the carbonyl group lies in the same plane as the pyrrole ring [17,19].It is worth noting that the flat arrangement of the carbonyl group with respect to the pyrrole ring favors the formation of centrosymmetric dimers with two equivalent N-H• • • O hydrogen bonds.
Spectroscopic and theoretical research on the conformations and intermolecular interactions of pyrrol-2-yl chloromethyl ketones and their N-methyl derivatives [39] show that the weakest hydrogen bond exists in the dimer of the pyrrol-2-yl trichloromethyl ketone, while the dimers of chloromethyl and dichloromethyl ketones have stronger hydrogen bonds, all of which are comparable in strength.All investigated pyrrol-2-yl chloromethyl ketones created the R 2 2 (10) motif [34,35] containing two equivalent hydrogen bonds N-H• • • O.It is interesting that such motifs were barely sensitive to the number of Cl-atoms.It seems that the rigid skeletons of the pyrrole rings hamper the π-electron delocalization within the above-mentioned motif, and thus, the influence of the strength of the Cl substituents on the N-H• • • O hydrogen bond strength was restricted for the pyrrol-2-yl chloromethyl ketones.On the other hand, X-ray investigations on 1-methylpyrrol-2-yl trichloromethyl ketone [32] show that in this structure, there is no centrosymmetric dimer motif, but two kinds of interactions are responsible for the arrangement of molecules in a crystal structure, C-H• • • O and C-Cl• • • O.The O-atom of the carbonyl group acts as an acceptor in both the hydrogen and halogen bond.
To extend this study, we investigated two pyrrol-2-yl chloroketones and one methyl pyrrole-2 carboxylate structures by single-crystal XRD analysis.According to this study, all the compounds crystallize with one molecule in the asymmetric unit and all show s-cis conformations, as depicted in Figure 1.Compound III crystallizes in the P2 1 /c centrosymmetric groups, while the other two compounds (I and II) crystallize in the P2 1 2 1 2 1 space group.This is reflected in the hydrogen bond motifs that are formed in the structures of these compounds.A ring motif of H-bonds [34,35] is present in the structures of I, and forms between the chain motifs in III.

XRD Analysis
The molecular crystal structures of compounds I, II and III were examined in terms of the geometric relationship between the pyrrole ring and carbonyl group.The structural variation of the three pyrrolylketones was ensured by the different numbers of halogen atoms or the methyl group substituted to the N atom from the pyrrole ring.Their structural overlay is shown in Figure 2.
All of the investigated compounds I-III have a flat pyrrole ring in their structure.The C6 carbonyl carbon atom deviates from the best plane calculated for the rings atoms N1-C2-C3-C4-C5 (Cg1) of −0.079(2)Å, 0.054(2)Å and 0.002(2)Å and oxygen atom O6 of −0.035(2)Å, 0.10(2)Å and −0.56(2)Å for structures I, II and III, respectively.Comparing the values of selected geometric parameters listed in Table S1, it can be seen that both the bond lengths and the valence angles show no significant differences between the compounds.To verify the geometric parameters, a Cambridge Structural Database search [37] was performed, from which 15 structures most resembling the investigated ketones and 11 structures corresponding to carboxylic acid were found.One of the esters found (Refcode DUCYOQ, [62]) is identical to the structure of III examined here.Although the geometry of both structures is essentially identical, we decided to include structure III in this study since its structure was measured at a lower temperature, giving a better figure of merit for structure refinement.We also found structure I (Refcode UHIQEJ, [63]), but there is no structure description included in the cited work, so we decided to use our own data.The search schemes for fragments of molecules and the geometry parameters are given in Schemes S1 and S2 and Tables S3-S6.Figures S2 and S3 present a graphical representation [64] of the structures found in CSD.The values of all the geometrical parameters of the investigated compounds are comparable with those found in the CSD.

XRD Analysis
The molecular crystal structures of compounds I, II and III were examined in terms of the geometric relationship between the pyrrole ring and carbonyl group.The structural variation of the three pyrrolylketones was ensured by the different numbers of halogen atoms or the methyl group substituted to the N atom from the pyrrole ring.Their structural overlay is shown in Figure 2.  S1, it can be seen that both the bond lengths and the valence angles show no significant differences between the compounds.To verify the geometric parameters, a Cambridge Structural Database search [37] was performed, from which 15 structures most resembling the investigated ketones and 11 structures corresponding to carboxylic acid were found.One of the esters found (Refcode DUCYOQ, [62]) is identical to the structure of III examined here.Although the geometry of both structures is essentially identical, we decided to include structure III in this study since its structure was measured at a lower temperature, giving a better figure of merit for structure refinement.We also found structure I (Refcode UHIQEJ, [63]), but there is no structure description included in the cited work, so we decided to use our own data.The search schemes for fragments of molecules and the geometry parameters are given in Schemes S1 and S2 and Tables S3-S6.Figures S2 and S3 present a graphical representation [64] of the structures found in CSD.The values of all the geometrical parameters of the investigated compounds are comparable with those found in the CSD.
The crystal packing analysis for the compounds investigated has revealed a variety of supramolecular architectures.The structure of the intermolecular interaction nets are guided by the presence of different types of H-bonds and stacking interactions.Despite the presence of the chlorine atoms in the structures, the classical halogen bond is not formed.The Cl atom either participates in hydrogen bonds as a proton acceptor for weak C-H donors, or in a C-Cl⋯π interaction.
The predictions of the most likely locations for a variety of functional groups (acceptors and donors) for the investigated compounds are presented on the full interaction maps (FIMs) [48] in Figure 3.The red regions of the maps denote areas that are identified as similar to a H-bond acceptor.The blue regions denote H-bond donors and the brown regions indicate hydrophobic groups.The FIMs of studied structures I-III show the The crystal packing analysis for the compounds investigated has revealed a variety of supramolecular architectures.The structure of the intermolecular interaction nets are guided by the presence of different types of H-bonds and stacking interactions.Despite the presence of the chlorine atoms in the structures, the classical halogen bond is not formed.The Cl atom either participates in hydrogen bonds as a proton acceptor for weak C-H donors, or in a C-Cl• • • π interaction.
The predictions of the most likely locations for a variety of functional groups (acceptors and donors) for the investigated compounds are presented on the full interaction maps (FIMs) [48] in Figure 3.The red regions of the maps denote areas that are identified as similar to a H-bond acceptor.The blue regions denote H-bond donors and the brown regions indicate hydrophobic groups.The FIMs of studied structures I-III show the expected directions for the formation of hydrogen bonds or others noncovalent interactions.The FIMs of studied structures I-III are shown in Figure 3 and Figure S1.In compound I, the carbonyl oxygen atom serves as a bifurcated acceptor in two C-H⋯O interactions, giving an R2 1 (7) motif.Additionally, the C-H as a bifurcated-donating group participates in a C-H⋯Cl bond, forming the R1 2 (5) motif.Both motifs create chains along b-axis.The chains form the C-H⋯π interaction, and create a zigzag 3D pattern, as shown in Figure 4.This structural motif is also stabilized by C-Cl⋯π interactions.In compound I, the carbonyl oxygen atom serves as a bifurcated acceptor in two C-H⋯O interactions, giving an R2 1 (7) motif.Additionally, the C-H as a bifurcated-donating group participates in a C-H⋯Cl bond, forming the R1 2 (5) motif.Both motifs create chains along b-axis.The chains form the C-H⋯π interaction, and create a zigzag 3D pattern, as shown in Figure 4.This structural motif is also stabilized by C-Cl⋯π interactions.In structure II, the infinite chain along the a-axis is created by N-H⋯O hydrogen bonds, forming a C(5) chain motif (Figure 5).The molecule contains only one chlorine atom, which participates in H-bonding.The chain is stabilized by N-H⋯Cl and C-H⋯O interactions.Additionally, the 3D network is stabilized by C-H⋯π interactions.

Theoretical Calculations
Energy parameters from single point calculations were determined for the investigated H-bonded motifs found in the crystals of I-III using the ωB97XD/G-311++G(d,p) level of theory, and are given in Table 1.The positions of H-atoms were normalized according to neutron diffraction data [58].Since the geometries of the studied molecules were taken from the crystal structures, the energy values apply to all possible interactions between the given molecules in each crystal.The energy of a single interaction N-H• • • O in structure III is about 8.36 kcal/mol and is higher than the energy for centrosymmetric dimer motif optimized on the level of the B3LYP/6-311++G(d,p) theory investigated earlier in [39] by more than 2 kcal/mol (dealing with a centrosymmetric dimer, we can divide the interaction energies in half for each of the two N-H• • • O bonds, and the energy of a single N-H• • • O bond was −6.63 kcal/mol).Such a difference may result both from the fact that for the interactions studied here, we chose single point calculations using the geometry from the crystal state, while previously, the optimization of the geometry was carried out and the B3LYP functional was used.Here, we used the ωB97XD functional because we noticed in our earlier research [56,57] that it gives results similar to those of the MP2 method.It should be noted that this functional contains Grimme's D2 numerical correction for dispersion effects [65].Thus, additional effects included in the theory approximation may give a relatively larger interaction energy.
In structure I, the interaction energy is the lowest at 7.62 kcal/mol.This is expected since, in general, C-H is a relatively weaker donating group compared with O-H [66].In the case of I, the nitrogen atom in the pyrrole ring is substituted with a methyl group, meaning that only weak H-bonds involving the C-H donor group may form, as opposed to the relatively stronger interactions with a N-H donor group.
In structure II, in addition to the N-H• • • O interactions, there is also the N-H• • • Cl interaction, a total interaction energy (for both mentioned interactions) is close to 11.02 kcal/mol.The calculations for the optimized dimer of this derivative showed that the energy of a single interaction was 6.34 kcal/mol [39].However, the geometry of the system studied here, taken from experimental conditions, differs from the optimized dimer as it features a H-bond to Cl atom.Stronger H-bonding in the compound investigated here may therefore be associated with the additional interaction to the Cl atom.
It is worth mentioning that theoretically estimated interaction energies are in a straight relation with the physical macroscopic properties of the crystals.As it can be seen in Table 1, the melting points of studied crystals of pyrrolylketone derivatives are related to the estimated energies of interactions.The more negative value of E int CP , the higher the melting point.

Hirshfeld Surface Analysis
Figure 7 shows the Hirshfeld surfaces of the investigated compounds, showing red spots corresponding to contacts with a length shorter than the sum of van der Waals radii and white spots corresponding to contacts with a length equal to the sum of van der Waals radii.In the examined compounds II and III, the N1-H1• • • O6 interaction is the shortest distance in the hydrogen bridge, and thus, the strongest.For compound I, in which no H-bond involving an N atom is formed, there are three such short interactions.These

Hirshfeld Surface Analysis
Figure 7 shows the Hirshfeld surfaces of the investigated compounds, showing red spots corresponding to contacts with a length shorter than the sum of van der Waals radii and white spots corresponding to contacts with a length equal to the sum of van der Waals radii.In the examined compounds II and III, the N1-H1⋯O6 interaction is the shortest distance in the hydrogen bridge, and thus, the strongest.For compound I, in which no Hbond involving an N atom is formed, there are three such short interactions.These are C3-H3⋯O6, C7-H7⋯O6 and C5-H5⋯π.Red spots on the Hirshfeld surface of II correspond to the N1-H1⋯O6 and C4-H4⋯O6 interactions.In the structure of III, there is also a short interaction, C5-H5⋯π.The fingerprint plots [49,50] presented in Figure 8 show all the molecular interactions, and the most occurring interactions that have been extracted from the Hirshfeld surface.The fingerprint plots [49,50] presented in Figure 8 show all the molecular interactions, and the most occurring interactions that have been extracted from the Hirshfeld surface.

I II III
. Hirshfeld surfaces of compound I-III mapped over dnorm.
The fingerprint plots [49,50] presented in Figure 8 show all the molecular interactions, and the most occurring interactions that have been extracted from the Hirshfeld surface.The most different types of contacts can be observed for II, while III has the fewest.The most frequent contacts are H⋯H, H⋯C/C⋯H and H⋯Cl/Cl⋯H.The H⋯H contacts account for 25% to 45% of the total interactions, H⋯Cl/Cl⋯H interactions account for 26% to 29%, and H⋯C/C⋯H interactions account for 14% to 21% of all interactions.In structure I, which features an N-methyl group instead of an H-atom, the share of H⋯H contacts is about 25% at the expense of H⋯Cl/Cl⋯H (29%).For structure II, which features one Clatom, the shares of H⋯H, H⋯Cl/Cl⋯H interactions are equal at 25% and H⋯C/C⋯H interactions account for 20%.In III, in which there are no Cl-atoms and a methyl group instead  S2. of N-H, H⋯H contacts account for 45% of the interactions and the share of H⋯O/O⋯H interactions is the highest one, at 25%.It is worth noting that for the H⋯C/C⋯H, H⋯O/O⋯H contacts, their percentage share does not change drastically between the compounds.It is interesting that compounds I-II contain Cl-atoms, and yet the percentage of Cl⋯Cl interactions is rather low; in the structure with two Cl-atoms, they account for only 8.7% (I) and the lowest contribution of the Cl⋯Cl contacts is in the structure with one Cl-atom, (II), which accounts for only 0.4% of the interactions.These interactions are longer than sum of the van der Waals radii, and cannot be recognized as typical halogen bonds (e.g., for I the distance is 3.581Å).The graphical representations of the composition of different types of interactions in compound I-III are shown in Figure 9, and the fingerprint plots for the most frequently occurring interactions are shown in Table S2.

Conclusions
The crystal and molecular structure of three derivatives of carbonyl 2-substituted pyrroles was determined by the single crystal X-ray diffraction combined with the single

Figure 2 .
Figure 2. Structural overlay of molecular structures for all compounds in stick style (lavender color denotes I, green-II, blue-III).All of the investigated compounds I-III have a flat pyrrole ring in their structure.The C6 carbonyl carbon atom deviates from the best plane calculated for the rings atoms N1-C2-C3-C4-C5 (Cg1) of −0.079(2)Å, 0.054(2)Å and 0.002(2)Å and oxygen atom O6 of −0.035(2)Å, 0.10(2)Å and −0.56(2)Å for structures I, II and III, respectively.Comparing the values of selected geometric parameters listed in TableS1, it can be seen that both the bond lengths and the valence angles show no significant differences between the compounds.To verify the geometric parameters, a Cambridge Structural Database search[37] was performed, from which 15 structures most resembling the investigated ketones and 11 structures corresponding to carboxylic acid were found.One of the esters found (Refcode DUCYOQ,[62]) is identical to the structure of III examined here.Although the geometry of both structures is essentially identical, we decided to include structure III in this study since its structure was measured at a lower temperature, giving a better figure of merit for structure refinement.We also found structure I (Refcode UHIQEJ,[63]), but there is no structure description included in the cited work, so we decided to use our own data.The search schemes for fragments of molecules and the geometry parameters are given in Schemes S1 and S2 and TablesS3-S6.FiguresS2 and S3present a graphical representation[64] of the structures found in CSD.The values of all the geometrical parameters of the investigated compounds are comparable with those found in the CSD.The crystal packing analysis for the compounds investigated has revealed a variety of supramolecular architectures.The structure of the intermolecular interaction nets are guided by the presence of different types of H-bonds and stacking interactions.Despite the presence of the chlorine atoms in the structures, the classical halogen bond is not formed.The Cl atom either participates in hydrogen bonds as a proton acceptor for weak C-H donors, or in a C-Cl⋯π interaction.The predictions of the most likely locations for a variety of functional groups (acceptors and donors) for the investigated compounds are presented on the full interaction maps (FIMs)[48] in Figure3.The red regions of the maps denote areas that are identified as similar to a H-bond acceptor.The blue regions denote H-bond donors and the brown regions indicate hydrophobic groups.The FIMs of studied structures I-III show the

Figure 2 .
Figure 2. Structural overlay of molecular structures for all compounds in stick style (lavender color denotes I, green-II, blue-III).

Figure 3 .
Figure 3. Full interactions maps for investigated compounds I-III.In compound I, the carbonyl oxygen atom serves as a bifurcated acceptor in two C-H• • • O interactions, giving an R 2 1 (7) motif.Additionally, the C-H as a bifurcated-donating group participates in a C-H• • • Cl bond, forming the R 1 2 (5) motif.Both motifs create chains along b-axis.The chains form the C-H• • • π interaction, and create a zigzag 3D pattern, as shown in Figure 4.This structural motif is also stabilized by C-Cl• • • π interactions.
Figure7shows the Hirshfeld surfaces of the investigated compounds, showing red spots corresponding to contacts with a length shorter than the sum of van der Waals radii and white spots corresponding to contacts with a length equal to the sum of van der Waals radii.In the examined compounds II and III, the N1-H1• • • O6 interaction is the shortest distance in the hydrogen bridge, and thus, the strongest.For compound I, in which no H-bond involving an N atom is formed, there are three such short interactions.These are C3-H3• • • O6, C7-H7• • • O6 and C5-H5• • • π.Red spots on the Hirshfeld surface of II correspond to the N1-H1• • • O6 and C4-H4• • • O6 interactions.In the structure of III, there is also a short interaction, C5-H5• • • π.

Figure 7 .
Figure 7. Hirshfeld surfaces of compound I-III mapped over d norm .

Figure 8 .
Figure 8. Fingerprint plots of compound I-III showing all the interactions taken from the Hirshfeld surface.

Figure 8 .
Figure 8. Fingerprint plots of compound I-III showing all the interactions taken from the Hirshfeld surface.The most different types of contacts can be observed for II, while III has the fewest.The most frequent contacts are H• • • H, H• • • C/C• • • H and H• • • Cl/Cl• • • H.The H• • • H contacts account for 25% to 45% of the total interactions, H• • • Cl/Cl• • •H interactions account for 26% to 29%, and H• • • C/C• • • H interactions account for 14% to 21% of all interactions.In structure I, which features an N-methyl group instead of an H-atom, the share of H• • • H contacts is about 25% at the expense of H• • • Cl/Cl• • • H (29%).For structure II, which features one Cl-atom, the shares of H• • • H, H• • • Cl/Cl• • • H interactions are equal at 25% and H• • • C/C• • • H interactions account for 20%.In III, in which there are no Cl-atoms and a methyl group instead of N-H, H• • • H contacts account for 45% of the interactions and the share of H• • • O/O• • • H interactions is the highest one, at 25%.It is worth noting that for the H• • • C/C• • • H, H• • • O/O• • • H contacts, their percentage share does not change drastically between the compounds.It is interesting that compounds I-II contain Cl-atoms, and yet the percentage of Cl• • • Cl interactions is rather low; in the structure with two Cl-atoms, they account for only 8.7% (I) and the lowest contribution of the Cl• • • Cl contacts is in the structure with one Cl-atom, (II), which accounts for only 0.4% of the interactions.These interactions are longer than sum of the van der Waals radii, and cannot be recognized as typical halogen bonds (e.g., for I the distance is 3.581Å).The graphical representations of the composition of different types of interactions in compound I-III are shown in Figure 9, and the fingerprint plots for the most frequently occurring interactions are shown in TableS2.

Figure 9 .
Figure 9. Fingerprint plots of compound I-III showing all the interactions taken from the Hirshfeld surface.

Figure 9 .
Figure 9. Fingerprint plots of compound I-III showing all the interactions taken from the Hirshfeld surface.

Table 1 .
Selected geometric parameters and energy of interactions for two interacting molecules in crystal obtained at the ωB97XD/G-311++G(d,p) level of theory.Looking at the obtained results, it can be seen that systems with the N-H• • • O bonds have greater interaction energies compared to those with C-H• • • O/Cl interactions.