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Article

Impressive 1D (Ferrocenyl⋯C6F5R⋯)n Stacking Due to Cooperative Interactions in N-(Ferrocenylmethyl)Pentafluorobenzenecarboxamide: Four Crystal Structures and Contacts Analyses in N-(Ferrocenylalkyl)Benzenecarboxamides

by
John F. Gallagher
1,*,
Christian Jelsch
2,
Peter T. M. Kenny
1,3,† and
Alan J. Lough
4
1
School of Chemical Sciences, Dublin City University, D09 V209 Dublin, Ireland
2
CRM2, CNRS UMR 7036, Faculté des Sciences et Technologies, Université de Lorraine, 54000 Nancy, France
3
National Institute for Cellular Biotechnology, Dublin City University, D09 V209 Dublin, Ireland
4
Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada
*
Author to whom correspondence should be addressed.
†
This research paper is dedicated to our great friend and colleague, Professor Peter T. M. Kenny (1958–2022); a passionate and lifelong Glasgow Celtic and Chelsea football supporter.
Crystals 2025, 15(4), 299; https://doi.org/10.3390/cryst15040299
Submission received: 20 February 2025 / Revised: 14 March 2025 / Accepted: 18 March 2025 / Published: 25 March 2025
(This article belongs to the Section Crystal Engineering)
Browse Figures
Versions Notes

Abstract

:
The crystal structures, interactions, and contacts analyses of four N-(ferrocenylalkyl)benzene-carboxamide derivatives are described as the N-(ferrocenylmethyl)benzenecarboxamide 4a, N-(ferrocenylmethyl)-2,6-difluorobenzenecarboxamide 4e, N-(ferrocenylmethyl)pentafluorobenzenecarboxamide 4f and N-(ferrocenylethyl)-4-fluorobenzenecarboxamide 5. Intermolecular amide⋯amide hydrogen-bonding interactions as 1D intermolecular chains are present in all four crystal structures, with N⋯O distances ranging from 2.819 (2) to 2.924 (3) Å. Three of the crystal structures have one molecule per asymmetric unit, except the phenyl 4a, which has Z’=2. In the structure of 4a, Fc(C-H)⋯(phenyl) and phenylC-H⋯π(C5H4) ring interactions dominate the interaction landscape, together with (1:1) face-to-face (phenyl)⋯(phenyl) and (C5H5)⋯(C5H5) ring stacked pairs (Fc = ferrocenyl moiety). In 4e, interlocking ferrocenyls, short C-H⋯(C-F) and C-H⋯O hydrogen bonds are the only additional notable intermolecular interactions. In the pentafluorophenyl derivative 4f, a remarkable selection of interactions is present with interwoven 1D ferrocenyl⋯(C6F5) stacking and C-H⋯F interactions; molecules aggregate forming impressive 1D columns comprising intertwined (Fc⋯C6F5⋯)n ring stacking. In the ethyl bridged system 5, C-H⋯F and C-H⋯π (arene) contacts with (4-fluorobenzene) ring⋯ring pairs combine and stack about inversion centres. The reported para-F substituted structure REYWOU (4d) is used for comparisons with the 4a, 4e, 4f, and 5 crystal structures. In view of the rich interaction chemistry, contacts enrichment analyses of the Hirshfeld surface highlights several interesting features in all five ferrocenylalkylcarboxamide structures.

Graphical Abstract

1. Introduction

After 70+ years of enormous developments, ferrocene chemistry continues to progress and grow unabated in a multitude of areas in chemistry and science [1,2,3,4,5,6,7,8,9]. There are many research fields that have overlapped with ferrocenes and aided in its development. Significant branching into expanding multidisciplinary studies has arisen, and, overall, the growth and study of ferrocene crystal structures diversifies and shows no sign of abating [10]. This is noted by the number of structures incorporating ferrocene or as a derivative which is currently ~19,000 (18,797 structures without restrictions and including repeat structures 01/02), as listed in the Cambridge Structural Database (CSD) in January 2025 [10]. Of on-going interest in structural science, the ferrocene molecule [as Fe(cp)2] and its derivatives are notable on account of their rich, robust chemistry and remarkable stability [1,2,3]. It is widely used due to the physicochemical changes and improvements imparted on the molecular systems under study. For example, areas such as bioorganometallic and related chemistry (incorporating the ferrocenyl moiety—Fc) have seen spectacular growth over the past few decades with applications in medicinal and anti-cancer studies [10,11,12,13,14,15,16,17,18].
Our research interests in ferrocene derivatives have focused on two specific areas as (i) hydrogen bonding and crystal engineering studies [9,19] and (ii) bioorganometallic ferrocene chemistry [13,14,20,21]. In the latter studies, ferrocenyl and ferrocenoyl groups were incorporated with conjugated linker groups such as benzene and naphthalene bonded specifically to amino acids and dipeptides [20,21]. An impetus for this research is their utilisation as new biomaterials and in medicinal chemistry/anti-cancer studies [20,21].
Of note and particular interest to the present manuscript is the recent publication by Cockcroft and co-workers, where they reported the structure and properties of (C6F6)∙ferrocene [or (C6F6)∙FeCp2] in a temperature range from 100 K up to ~309 K [5]. In this C6F6∙FeCp2 solvate adduct (from 100→290 K), the crystal structure comprises closely packed columns of alternating hexafluorobenzene C6F6 and FeCp2 molecules arranged so that the hexafluorobenzene is sandwiched between the ferrocenes. It is stated that intermolecular quadrupolar forces between the C6F6 and FeCp2 components are the main driving forces in the observed columnar and structural aggregation [5].
In the present manuscript, four new ferrocenecarboxamide crystal structures are reported [13,14] and analysed for comparisons using contacts enrichment analyses (Scheme 1). The structural changes that arise on changing the substitution pattern from phenyl to pentafluorobenzene derivatives are analysed. Comparisons are made with the published 4-fluorobenzene structure 4d (REYWOU) [14] and the related literature [5,10]. Additionally, the ethylene-bridged group (-CH2CH2-) in 5 provides an extra degree of flexibility in molecular structure. Previously, we have published research on conjugated ferrocene derivatives in structural systematic studies and biomaterials [9,19] and have noted that the number of compounds incorporating the ‘FcCH2NHC=O (arene)’ moiety is still relatively low, with only eight structures available in the CSD, ([Fc = (η5-C5H5)Fe(η5-C5H4)]) [10]. These structures include UYENUJ [15] and MIRYIZ [18]. A total of thirty ‘FcCH2NHCO-C structures are noted in a more general study [10]. In order to further develop and expand this area of ferrocene structural research, four new ferrocene derivatives are presented with their crystal structures. It is noted in particular the diversity of packing modes and the importance of thorough analysis of the 3D structures for comparisons with related molecules [5,10].

2. Experimental

2.1. Materials and Characterisation

The chemicals, materials, spectroscopic, X-ray diffraction methods, and analytical equipment are as reported previously [9,13,14]. All chemicals used in the synthetic reactions were used as purchased from Sigma-Aldrich, Dublin, Ireland and the synthetic reactions utilised standard organic synthetic procedures, as described in earlier work [14] (ESI). The original numbering system for the compounds and structures presented herein is retained. Compounds 4b and 4c are the related ortho-F and meta-F isomers of the para-F substituted structure REYWOU (4d) [14]. Single crystals of 4a, 4e, 4f, 5 were grown from dichloromethane solutions [14]. Single crystal X-ray diffraction methods and data collection strategies were routine [22] and structure solution and refinement for 4a, 4e, 4f, 5 undertaken using the SHELXS and SHELXL14 programs [23]. Molecular graphics using the Mercury program provided ORTEP diagrams (with displacement ellipsoids drawn at the 30% probability level) and the hydrogen-bonding diagrams [24]. Analyses of the geometric data for comparison purposes were performed using SHELXL14 output together with the ‘CALC ALL’ routine in PLATON [25]. Salient features of the four structures are provided in Table 1 and Table 2. Comparisons and analyses of the CSD [10] were undertaken using the latest version available in 2024 [Conquest version 24.2.0 (5.45 + update 3); build 415171].

2.2. Methods: Hirshfeld Surface Analysis Details

Analyses of the Hirshfeld surface (ESI; Figure S10 and Table S3) [26] and contacts enrichment ratio were performed to analyse different types of intermolecular interactions using procedures and programs previously reported [26,27].
The fingerprint plots of contacts around the molecules in the four crystal packings of 4a, 4e, 4f, 5 were computed with the CrystalExplorer17 program [26]. The contact statistics and enrichment ratios were obtained using the MoProViewer program (2024 version) [27]. In the case of compound 4a (with Z’ = 2), the Hirshfeld surface was computed around two independent molecules not in contact with each other in the crystal packing. In the contacts analysis, the charged HN hydrogen atoms bound to nitrogen were differentiated from the hydrophobic hydrogen HC atoms linked to a carbon.
In the asymmetric unit of the phenyl derivative 4a, molecules A and B have similar conformations, and although PLATON [25] suggests space group C2/c, the results do not support this space group assignment (as noted in the following section and ESI). Geometric differences between molecules A and B can be demonstrated by the Fe1A-C11A-C2A-N1A dihedral angle = −179.48 (18)° and for Fe1B-C11B-C2B-N1B = 175.51 (19)°. This demonstrates a significant 4° angle difference (with a detailed explanation provided in the ESI). Additional differences can be noted between molecules A and B (e.g., amide⋯amide distances) in the following section on the crystal and molecular structure discussion of 4a. The root mean square deviation of molecule A with the inverted B molecule is 0.10 Å and maximum atomic deviation is 0.16 Å.

2.3. Four Crystal and Molecular Structures

N-(Ferrocenylmethyl)benzenecarboxamide structure (4a) with Z’ = 2
The phenyl derivative 4a crystallises with two molecules A and B (Z’ = 2) in the asymmetric unit of space group P21/n (No. 14) (Scheme 1; Figure 1). Molecules A and B adopt similar conformations, and molecular similarities are demonstrated by their root mean square (rms) bond and angle deviations of 0.007 Å and 0.47° (Mercury = 0.10 Å) [25]. In the ferrocenyl moiety, the C5 rings are almost eclipsed, as noted by the five HC⋯CH torsion angles. Pairs of molecules aggregate in a hydrogen bonded cyclic arrangement by face-to-face C6⋯C6 stacked rings and C-H⋯π(C5H4) interactions. The amide conformation is shown by cpC-C-N-C=O torsion angles of −80.9 (3)° in (A) and 79.0 (3)° in (B), as influenced by the C2A/B hinge, whereas the C5H4/C6 interplanar angles are 73.16 (11)° and 79.12 (11)° (Table 2). Molecular differences are exemplified by the cross-molecule Fe1A/B⋯C34A/B distances of 9.207 (3) Å and 9.147 (3) Å for A and B, respectively, differing by 0.06 Å. The packing index (KPI) = 71.3 [25].
The asymmetric unit in 4a comprises A and B molecules in a cyclic arrangement, linked by two phenylC-H⋯π(C5H4) interactions and oriented with their NHCOC6H5 groups parallel as a face-to-face C6⋯C6 pair (Figure 1b). Geometric data reveal the C-H⋯C5 (centroid) as C34A-H34A⋯Cg4i [2.78 Å, 156°, 3.663 (3) Å] and C34B-H34B⋯Cg1i [2.84 Å, 158°, 3.744 (4) Å]; the C6⋯C5H4 interplanar angles are 78.19 (11)° and 74.12 (11)°. For the NHCOC6H5⋯C6H5CONH stacked pair, the shortest contacts are C31A⋯C33B = 3.401 (4) Å and C31B⋯C33A = 3.411 (4) Å, with an interplanar angle of 2.93 (17)°; the C6⋯C6 centroid distance = 3.8141 (18) Å [25]. The A/B molecular C5H5 interplanar angle within the asymmetric unit is 5.60 (10)°.
4a exhibits a wide range of intermolecular interactions comprising 1D intermolecular amide⋯amide chains, Fc(C-H)⋯C6 ring, C-H⋯π(C5H4) interactions, (1:1) face-to-face (phenyl) ring⋯ring and (C5H5) ring⋯ring pairs, where [Fc = (η5-C5H5)Fe(η5-C5H4)]). These interactions are noted including those in the A, B intricate molecular pair. The 1D amide⋯amide interactions form (A⋯A⋯)n and (B⋯B⋯)n chains along the b-axis direction with hydrogen-bonding distances N1A⋯O1Ai = 2.924 (3) Å and N1B⋯O1Bii = 2.869 (3) Å (symmetry operations i, ii; ESI, Table S2). The amide⋯amide interaction between molecules of A is augmented by a C5H4 ring oriented side on and interacting with a symmetry related (C31A, …, C36A)i phenyl ring as C12A-H12A⋯π(Cg3)i; [2.73 Å, 163°, 3.652 (3) Å]. The asymmetric Fc-H⋯C6 interaction in molecule A differs from that in B, where two FcC-H⋯C6 manifest in side-on 2 × (C5-H)⋯C6 contacts rather than as a single C-H⋯Cg (in A). The associated data are C15B-H15B⋯C31Bii [2.83 Å; 159°; 3.730 (4) Å] and C25B-H25B⋯C34Bii [2.84 Å; 156°; 3.730 (5) Å].
Both 1D undulating molecular chains (and interlinked by phenylC-H⋯π(C5H4) interactions and (1:1) C6⋯C6 stacked pairs) generate a 1D column aligned along the b-axis and ½ × c cell length wide. Columns, comprising the (A⋯)n and (B⋯)n chains, are linked by face-to-face C5H5⋯C5H5 ring overlaps and paired into slightly ruffled sheets parallel to (2 0–5). The cpC⋯Ccp contact separations are rather short, i.e., C23A⋯C24Bxv = 3.303 (5) Å. The C5H5⋯C5H5 interplanar angle is 8.15 (19)°, and rings are moderately offset with a C5H5 ring centroid with Cg⋯Cg distance = 3.857 (2) Å. This is depicted by face-to-face C5H5⋯C5H5 and C-H⋯π weak H-bonds (Figure 1c). Sheets are linked by the remaining face-to-face C5H4⋯C5H4 contacts. In addition, ferrocene moieties interlock (using their C-Hs), and this is particularly notable for molecule A where the cp rings and Fc(C-H) form a dual ‘cog-like’ intermolecular aggregation.
The rmsd of molecular overlap between 4a (molecule B or inverted A) and the REYWOU (4d) structure (N-(ferrocenylmethyl)-para-fluorobenzene carboxamide) is 0.3 Å [14]. Differences are primarily due to the orientation of the unsubstituted η5-C5H5 cyclopentadienyl ring. As such, REYWOU will therefore be discussed primarily in terms of molecular interactions [14].
N-(Ferrocenylmethyl)-4-fluorobenzenecarboxamide [REYWOU; 10], 4d [14]
The molecular structure of 4d has been described [14] (Figure 2) and salient features of the crystal structure are only provided herein for comparisons with 4a, 4e, 4f, and 5. It is noted that 4d has a similar conformation to 4a with cpC-C-N-C=O torsion angle of 89.6 (3)° as influenced by the C2A/B hinge; the C5H4/C6 interplanar angle = 77.80 (8)°. Amide⋯amide interactions dominate with molecules aligning in the a-axis direction (N1⋯O1xvi = 2.972 (2) Å). This H-bond is bifurcated, being augmented by ortho-C32-H32⋯O1xvi contacts (dC⋯O = 3.485 (3) Å), generating 1D chains incorporating R12 (7) hydrogen bonded rings (symmetry operations as noted in Table S2, ESI). This type of H-bond aggregation is frequently observed in benzamide structures and 1D chains aggregate through a combination of intermolecular contacts [9].
Molecules pack along the b-axis direction via an extensive combination of face-to-face C5H5⋯C6 stacked pairs [interplanar angle = 8.45 (13)°], relays of C5-H⋯π(C5H4) interactions [C21-H21⋯Cg1xvii; 2.75 Å, 176°, 3.680 (3) Å] and HC-H⋯C5H4 contacts [H2B⋯C13xvii = 2.79 Å] (Figure 2). Weak intermolecular contacts as F34⋯C1-N1xviii = 3.185 (2) Å, with an angle for C34-F34⋯C1xviii = 134.46 (15)° augment the interactions. In summary, key interactions involve amide⋯amide/C32-H32…O1xvi pairing along the a-axis direction and the interaction rich combination of (1:1) stacking and contacts along [010]. The zig-zag relay of [Fc(C5-H)⋯π(C5H4)Fe(C5-H)⋯]n contacts, with the C5H5 capped by a (1:1) stack with the C6 ring, is notable and can also be denoted simply by (Fc-H⋯Fc-H⋯)n (Figure 2).
N-(Ferrocenylmethyl)-2,6-difluorobenzenecarboxamide or 4e
In the structure of 4e (Figure 3), intermolecular amide⋯amide hydrogen bonding generates 1D chains along the a-axis direction with N1-H1⋯O1iii data as 2.00 (3) Å, 156 (2)°, 2.819 (2) Å (iii = ½ + x,½-y,z; ESI, Table S2). The interactions arise in tandem with alkylC2-H2A⋯(C36-F36)iii interactions [for C36; data are 2.72 Å, 164°, 3.679 (2) Å; ESI, Figure S4]. The 1D chains are linked by intermolecular C35-H35⋯O1iv interactions [2.44 Å, 150°, 3.295 (3) Å] (iv = ½ − x, −½ + y, 1 − z), with the formation of the (C31, …, C36) sandwich about inversion centres, with Cg3⋯Cg3xix = 3.5765 (12) Å; Cg3⋯C6xix = 3.3773 (9) Å, (xix = 1 − x, −y, 1 − z; ESI, Table S2).
The ortho-fluorine F32 and F36 atoms do not partake directly in significant intermolecular interactions. However, F36 is positioned at 2.81 Å from H2A (0.15 Å longer than the sum of the van der Waals radii 1.20 + 1.47 Å) [25]. The C2-H2A⋯F36iii angle = 139° and assisting the C2-H2A⋯C36iii contact. Of interest is that the unsubstituted C5H5 ring does not form any face-to-face stacks with either of the C5 or C6 rings. On the other hand, there are two phenyl C-H⋯π interactions on one side of the C5H5. It can be stated that heterocycles are more likely to be involved in parallel stacking than carbocyclic rings [27,28]. Not surprisingly, the C6H3F2 rings form face-to-face pairs about inversion centres and the closest C⋯C contact is C34⋯C36xix = 3.410 (3) Å and the centroid Cg3⋯Cg3xix distance is 3.5765 (12) Å.
Impressive, intricate stacking in N-(Ferrocenylmethyl)pentafluorobenzenecarboxamide
The pentafluorobenzene derivative (4f) (Figure 4) exhibits an array of intermolecular interactions that incorporate N-H⋯O=C hydrogen bonding as 1D chains in the c-axis direction in tandem with local (1:1) C5H4⋯C6F5 ring overlay between the substituted C5H4 and C6F5 rings. Chains crosslink, forming sheets via C-H⋯O/F contacts and tight C5H5⋯C6F5 ring stacking on the opposite side of the C6F5 ring. Sheets aggregate by C-H⋯F contacts and sheet formation involves all three carbocyclic rings (as 2 × C5; C6). The ferrocenyl (Fc) moiety is effectively sandwiched by C6F5 rings forming a 1D stack. Four C-H⋯F interactions per 4f molecule involve three of the C6F5 fluorine atoms as F32, F35, and F36, (symmetry codes vi to ix) with shortest C-H⋯F-C contact being C13-H13⋯F35vi = 2.55 Å for H⋯F (angle = 133°).
Overall, the impressive feature of the 4f crystal packing is the intricate (ferrocene⋯C6F5⋯)n alternating (Fc group)⋯ring overlap, where the Fc group and C6F5 ring alternate as (1:1)n pairing in 1D columns that lie parallel to the (−1 0 1) plane (ESI, Figures S5–S8). Each 4f molecule contributes the ferrocenyl and C6F5 to two distinct 1D columns that are reinforced by crosslinking amide⋯amide interactions (alternate explanation as above), (ESI, Figure S6). At a local level the C6F5CONH- moiety can be analysed further. Each amide⋯amide interaction facilitates formation of a compact, localised (1:1) face-to-face C5H4⋯C6F5 ring stacking (per amide⋯amide link). Therefore, the C5H4⋯C6F5 ring overlap as a (1:1) stacked pair arises in tandem with each amide⋯amide interaction as it propagates in the c-axis direction. The crystal structure aggregation is enhanced as the remaining C5H5 ring (in each 4f molecule) is critical in the formation of sheets with 1D columns of (Fc⋯C6F5⋯)n ring stacking. Overall the (Fc⋯C6F5⋯)n ring stacking is both elegant and efficient, where the Fc group is sandwiched between two C6F5 rings of 4f molecules from different 1D chains. Diagrams are used to highlight and show how it manifests in the 4f crystal structure (ESI, Figures S4–S7).
Table 3 highlights the geometric details of 4f and stacking distances Cg1⋯Cg3v = 3.5720 (12) Å between the C5H4 (Cg1 centroid) and C6F5 rings (Cg3 centroid). The tighter Cg2⋯Cg3xx is 3.5399 (13) Å (Cg2 = C5H5), where Cg represents the ring centroids. The perpendicular centroid⋯ring distances are 3.2530 (10) Å and 3.3133 (8) Å, with three C⋯C distances < 3.40 Å [and the shortest is C25⋯C32xx = 3.319 (3) Å]. The C5 and C6 ring interplanar angle is 10.05 (12)°. For comparison with 4f and of particular note is the SUFLIR crystal structure of a (1:1) co-crystal of ferrocene∙C6F6 [5,10] and with thirteen datasets collected over a temperature range (from 100 K to 304 K). In Table 3, comparisons are made between SUFLIR at 100 K (KPI = 72.4 [25]) and the present study of 4f (at 150 K).
Structural differences between SUFLIR and 4f (as noted in Table 3) are relatively small [25]. Distances between stacked rings (from the centroid⋯centroid for C5, C6F6) are 0.03–0.04 Å shorter in 4f, while the interplanar (dihedral) angles are closer to co-planarity and differing by 5–6° from SUFLIR [5]. The reason for the differences may be more steric than electronic and influenced by the carboxamide⋯carboxamide hydrogen bonding in 4f and short contacts involving the methylene CH2 group H2B hydrogen atom. The C-F⋯C5 geometric data are more symmetrical in SUFLIR [5], but with shorter contact distances in 4f. However, the cpC-H⋯F-C distances are shorter in SUFLIR (by 0.05–0.10 Å) for their three shortest H⋯F contacts and this may be influenced to an extent by differences in data collection temperatures (100 vs. 150 K).
In the stacking behaviour of SUFLIR [5] and 4f, it is important to consider factors that influence their packing. Benzene (−33.3 ± 2.1) [29] and Ferrocene (−30 ± 7) [30] have large negative molecular quadrupole moments (QM), expressed in 10−40 C m2. This contrasts with hexafluorobenzene (C6F6) which has a moment of similar magnitude but with a positive value as determined experimentally as +31.7 (±1.7) × 10−40 C m2 [29]. Therefore, it can be evaluated that the quadrupole moments for the Fc-C and C-C6F5 moieties are relatively similar in magnitude but opposite in sign. A guideline estimate of quadrupole moments are ca. −20 and +20 × 10−40 C m−2 for the Fc-C and C-C6F5 moieties, respectively [29,30,31]. Hence, the observation for 4f that favourable ring stacking occurs with conformational change and in tandem with amide⋯amide directed hydrogen bonding in the crystal state. In 4f, the methylene -CH2- spacer group facilitates conformational change and the ability to form interweaved 1D stacked columns using the ferrocenyl moiety (Fc) and the pentafluorobenzene C6F5 rings.
N-(Ferrocenylethyl)-4-fluorobenzene-carboxamide or 5.
The molecular conformation of 5 (Figure 5) (with an ethylene -CH2CH2- bridge as compared to the methylene -CH2- bridge for the 4x series) is broadly similar to the pentafluorobenzene derivative 4f. Having the additional -CH2- spacer group provides extra molecular flexibility. In terms of molecular conformation, the C11-C3-C2-N1 torsion angle is 176.19 (19)° and C3-C2-N1-C1 is 81.0 (3)°. The ferrocenyl C5 rings are effectively eclipsed and with all five H-C⋯(C)H < 0.3°, whereas in 4f the C5 rings deviate from being fully eclipsed by ~18°.
Amide⋯amide interactions dominate as N1-H1⋯O1x forming 1D chains along the b-axis direction. These chains are linked about inversion centres by C21-H21⋯F34xii contacts (ESI; Table S2). The F34 atom also engages in a weak contact as C25-H25⋯F34xi = 3.554 (3) Å (Table S2); with two C-H⋯F34 forming a bifurcated hydrogen-bonding system. In addition, compact ring⋯ring pairing about inversion centres involves the aromatic C6 groups and with shortest C31⋯C32xii contact distance of 3.451 (3) Å. In addition, weak C-H⋯π(arene) contacts form as C36-H36⋯C32x (H36⋯C32x = 2.82 Å; C36-H36⋯C32x = 173°) with C33-H33⋯O1xiii interactions. Of further structural interest is that ferrocene carboxamide structures containing an ethylene (-CH2-CH2-) group or even just a two-carbon atom chain as a linker group are relatively rare in the CSD [10].

2.4. Hirshfeld Surface Analysis: Contacts Enrichment Analyses of Five Structures (4a, 4d–f, and 5)

MoProViewer software (version 2024) [27] was used to investigate the intermolecular interactions and the contacts enrichment on the Hirshfeld surfaces of the five molecules (4a, 4d–f, and 5) in their crystal packings [26]. The enrichment values (EXY) were obtained as the ratio between the proportions of actual contacts (CXY) and equiprobable (random) contacts (RXY), the latter being obtained via probability products (RXY = SX × SY), where SX is the surface content in chemical species X. Contacts X⋯Y, which are over-represented with respect to the share of X and Y chemical species on the Hirshfeld surface, have enrichments larger than unity. The chemical nature of the contacts and their enrichment data values in the crystal structures are listed in the ESI (Table S3).
In all five crystal packings, the strong N-H⋯O=C hydrogen bond between amide groups has extremely high enrichment ratios EO,Hn greater than 14.8, as it constitutes by far the most attractive electrostatic interaction (ESI, Table S3). The fingerprint plots (ESI, Figure S10) display all two spikes at short distance corresponding to this N-H⋯O=C hydrogen bond. The hydrophilic content (O and HN) on the surface is always below 7%. As a consequence of the high hydrophobic content in HC and C atoms, the most abundant contacts in all cases (except in the fluorine rich 4f) are C⋯HC followed by HC⋯HC hydrophobic contacts. All of the fingerprint plots show abundant C⋯H and H⋯H contacts (ESI, Figure S10). The next most abundant contacts in the crystal structures of 4a, 4d, 4e, and 5 are the C⋯C and the F⋯HC weak hydrogen bonds in 4d, 4e, and 5. The H⋯F contacts show spikes within the fingerprint clouds at the shortest distances of di = 1.2/de = 1.4 Å. In all structures, with the exception of the penta-fluorobenzene derivative 4f, the enrichments of the hydrophobic contacts C⋯C, HC⋯HC, and C⋯HC do not deviate much from the unitary ratios (in the range 0.83 < E < 1.23).
The penta-fluorinated compound 4f is peculiar in that the C⋯C contacts are significantly enriched (with ECC = 2.2) due to the (Fc⋯C6F5⋯)n 1D ring⋯ring stacking. The Cδ−Hδ+ and Cδ+Fδ- groups in the two carbocyclic rings form attractive electrostatic interactions. The fluorine content on the surface is 23.9% and with an enrichment value of 1.54. Therefore, the F⋯HC weak hydrogen bonds turn out to be the most abundant contact type in the penta-fluorinated 4f crystal structure. The F⋯F contact is 3.9% in 4f, whereas the other four structures 4a, 4d, 4e, and 5 (which contain less fluorine atoms) have this value at 0. On the other hand, the C⋯HC weak hydrogen bonds are quite under-represented in 4f (with E = 0.49), presumably due to competition of the slightly stronger F⋯HC interactions. The fingerprint plots for 4f are depicted in Figure 6 and can be compared with the other four crystal structures of 4a, 4d, 4e, and 5 (ESI; Figure S10).

2.5. Comparisons with Ferrocene Derivatives That Exhibit Distinct Aggregation and Packing

Analysis of the Cambridge Structural Database was performed (with ca. 400 structures retrieved in a search as Fc_C6F1) for structures similar to 4f and C6F6∙FcCp2 (SUFLIR) [5]. The search demonstrates that the vast majority of ferrocene derivatives incorporating at least one aromatic fluorine (as C6F) do not stack in extended columns but rather are ‘capped’ in a variety of ways by either C-H⋯π(arene), C-F⋯(cp) contacts or (1:1) face to face pairing of aromatic rings [10]. There are several notable examples of a diverse range of packing types involving ferrocene groups either on their own or in combination with other rings. These structures include GEHNAJ (ferrocene∙decafluorobiphenyl) [6], LUZJIB (ferrocene∙decafluorophenanthrene) [32], SUFLIR01-09 (ferrocene∙hexafluorobenzene) [5,10].
The crystal structure of UNEWES reveals slight undulating 1D chains incorporating alternating ferrocenyl Fc⋯C6FH4 pairs sandwiched and linked between C-H⋯π(cp) interactions (ESI, Figure S9) [33]. At the other extreme, in the crystal structure of UYIHER or 3-ferrocenyl-1-(4-fluorophenyl)-5-methyl-1H-pyrazole, zigzag chains of ferrocenyl moieties are linked solely by C-H⋯π(cp) interactions [34]. In ADIQAF or rac-1,1′-bis(pentafluorophenyl)-3,3′-di-t-butylferrocene the pentafluorobenzene ring forms a 1D column [35], whereas in LUZJIB, the decafluorophenanthrene (X) forms stacks as (Fc⋯X⋯X⋯)n [32]. Another structural example is that of FANNUE (01) (ESI, Figure S9) where the ferrocene stacks and interacts with a hexakis(μ2-3,4,5,6-tetrafluorobenzene-1,2-diyl)Hg6 (L) complex such that the structure consists of (L⋯ferrocene⋯L⋯)n stacking [36]. In QAPYAI [37] the Fc moiety and a pyrrotriazole ring form a stack along the b-axis direction and this aggregation arrangement is reminiscent of the 4f crystal structure.
A related search of the CSD [10] was undertaken specifically for ferrocene centroid…C6 ring centroid distances that are <3.60 Å, with C5/C6 interplanar angles < 15° (arbitrary values) and with optional fluorine atoms. This CSD search reveals several structures including MANRIC, SAMTEH, APUJIH, QIGRUW, and VIBSEF [10,38]. The vast majority of these structures exhibit a short range stack (depending on the structures and symmetry) and are usually capped at either end by C-H⋯π(arene) contacts, thereby preventing 1D stack formation. In the 1D stack of MANRIC, the unsubstituted C5 and C6 ring [C14, …, C19] centroids are separated by 3.457 (2) Å with an interplanar angle of 4.22 (18)°, arising in a centrosymmetric stacked dimer that stacks with symmetry related dimers [38]. Dimers link into 1D chains by overlapping rings with interplanar distances of 3.4154 (8) Å. Much research is on-going and as this is not a review, a more extensive analysis will be published at a future date. Of additional note is that Horie and co-workers have studied ferrocene ring rotation in interlocked molecules in single crystals [39].
Competition between hydrogen and halogen bonding in intermolecular interactions continues to attract much attention, aiding in our understanding of intermolecular interactions and aggregation in molecular crystals [40,41,42,43,44,45]. In this present structural study, we show the roles that ferrocenyl moieties and fluorinated benzene rings play in aggregation and stacking [5,10]. Several recent publications have compared series of related structures in terms of the effects of the different types of interactions that can arise with substitution pattern [41,42,43,44,45]. Understanding the competition between intermolecular processes in structures and the profound effects that they can have in aggregation and packing where compounds differ as isomers, or by one atom substitution has been explored in halogenated benzamides [42], carboxamides [43], isophthalamides [44], and Schiff bases [45]. The future of this structural research will expand with even more expansive studies (and resulting structural data) on how substitution patterns influence structure together with the range and types of competition between intermolecular interactions [10].

3. Conclusions and Future Work

In the five ferrocenyl carboxamide crystal structures (including REYWOU 4d [14]), the structural effects on molecular geometry and conformations are assessed in structural packing for the phenyl 4a, para-fluorobenzene 4d, 2,6-difluorobenzene 4e, and the penta-fluorobenzene derivatives 4f. Competition between amide⋯amide hydrogen bonding and various types of ring⋯ring stacking, as well as weaker interactions such as C-H⋯O and C-H⋯π(arene), is analysed and comparisons are made [46,47,48,49,50].
Stacking of C6 rings of the mono- and di-fluorinated rings with ferrocenyl groups does not dominate in the crystal packing due to competition with stronger hydrogen-bonding interactions. However, additional fluorine atoms on the aromatic ring promote 1D ring stacking. The additional F atoms on a benzene ring system push the molecular quadrupole from benzene as negative (−) towards that of the positive (+) hexafluorobenzene molecule [30,31]. This can induce a favourable stacking arrangement with ferrocenes or ferrocenyl moieties (having a negative molecular quadrupole). With the possibility of ferrocenes stacking relatively easily with penta-fluorobenzene-based systems and with a favourable stacking conformation, it may be that there is a strong possibility that trifluoro- or tetra-fluorobenzenes (of whichever F atom substitution pattern) may be enough to influence and participate in stacking patterns such as the tight 1D stacking observed in 4f.
We recognise that a rich, diverse range of fluoro-derived ferrocenes is available and are examining incorporation of fluoroaromatics into various ferrocenyl moieties or through the formation of co-crystals with ferrocene [5,10,51]. The ability of trifluoro- and tetrafluorinated aromatic rings is under examination to study the structural diversity types and tipping points towards capped or 1D stacked structures. This requires a large number of closely related crystal structures so that in-depth comparisons can be made [10]. The present series represents a basis for the development of a general class of fluorinated ferrocenyl carboxamides [14]. There is a vast research space for exploring combinations with halogenated aromatics with chlorine, bromine, and iodine [10,52,53,54,55,56]. Recent structures with interesting interactions and packing include ZOHFIP [52], IDUGAT [53], WUMWEJ [54], APUJON [55], and UYUPEM [56].

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/cryst15040299/s1, Scheme S1: The four ferrocene crystal structures 4a, 4e, 4f, and 5, together with the previously reported 4d structure [REYWOU] [10,14]; Table S1: Crystallographic Experimental details; Table S2: Selected hydrogen-bond parameters in 4a, 4e, 4f and 5; Figure S1: A view of the asymmetric unit (Z’ = 2) highlighting differences between the A and B molecules in the crystal structure of 4a. These applies to distances, torsion angles and amide⋯amide hydrogen bonding where differences of ca. 0.05−0.06 Å and 4−5° are noted between A and B; Figure S2: A view of the interactions in 4a. The central cyclic hydrogen bonded A and B molecules with key H atoms in black with the (1:1) (C5H5) ring⋯ring* overlap depicted by the CPK atoms as noted in the diagram (left) and with all atoms as a CPK model (right); Figure S3: A cross-section of the multitude of interactions that are present in 4d or REYWOU [14]. The ferrocenyl moieties are depicted in dark green to highlight the relay of interactions; Figure S4: A view of the amide⋯amide interaction in 4e together with the H2A⋯(C36-F36)iii contact (ball and stick model: left) and with atoms as their van der Waals spheres (right); Figure S5: Views of the molecular chain generated by the 4f molecules. 1D molecular zigzag chains as generated by the [C5H5⋯C6F5] ring pairs are shown and parallel to (-101) (in tandem with the amide⋯amide interaction); Figure S6: Three 4f molecules in green have a C6F5 group from symmetry related molecules inserted between their ferrocenyl groups and the three 4f have their C6F5 groups effectively forming a ‘sandwich’ with the ferrocenyl moieties of the molecules in red. This stacking propagates through the 4f structure; Figure S7: Four views of a 1D chain involving seven molecules of 4f. The fluorine atoms are depicted in light green colour on the C6F5 ring with a ferrocenyl moiety sandwiched between two C6F5 rings; Figure S8: A view of the stacking with two 1D stacks indicated by arrows in 4f. One stack is effectively contained within the (-101) and (-202) planes. A similar CPK view (atoms as their van der Waals spheres) with molecules involved in one column highlighted in red and blue and how they contribute to the other neighbouring columns and molecules in grey; Figure S9: Notable structures as SUFLIR [5], FANNUE, LOTCUS and UNEWES [10]; Figure S10: Fingerprint plots of the main contacts on the Hirshfeld surface of the five compounds (CrystalExplorer21 program); Table S3: Contacts Enrichments Data.

Author Contributions

Conceptualization, J.F.G.; Methodology, C.J. and P.T.M.K.; Software, J.F.G., C.J. and A.J.L.; Validation, J.F.G., C.J. and A.J.L.; Formal analysis, P.T.M.K. and A.J.L.; Investigation, C.J. and P.T.M.K.; Data curation, J.F.G. and A.J.L.; Writing—review & editing, J.F.G.; funding acquisition, J.F.G. All authors have read and agreed to the published version of the manuscript.

Funding

The research was funded by PRTLI-III programme (Ireland). John F. Gallagher thanks the Faculty of Science and Health in Dublin City University for research funding.

Informed Consent Statement

All ethical guidelines in the experiments have been adhered to.

Data Availability Statement

CCDC (Deposition Number 2409147−2409150) contains the Supplementary Crystallographic Data for this paper. The CIF data can be obtained free of charge via https://www.ccdc.cam.ac.uk/ (or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44 1223 336033; E-mail: deposit@ccdc.cam.ac.uk). The data are available as CIF files from the corresponding author Professor John F. Gallagher (Dublin City University).

Acknowledgments

We thank Paula Kelly for initial technical support. We especially pay tribute to Peter Kenny, a colleague with whom we shared many hours of witty conversation and laughter in The ‘Slipper’, Mulligans of Poolbeg street, discussing a variety of topics such as the Borg collective, the Baby’s arm, Glasgow Celtic, Chelsea, Guinness, Pipes, Tobacco flavours, sign removal, and the infamous Cork ‘2000′ incident, to name but a few….

Conflicts of Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the research work as reported in this scientific paper.

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Crystals 15 00299 sch001
Scheme 1. Schematic diagram of the ferrocene derivatives 4a, 4d [14], 4e, 4f, and 5.
Scheme 1. Schematic diagram of the ferrocene derivatives 4a, 4d [14], 4e, 4f, and 5.
Crystals 15 00299 sch001
Crystals 15 00299 g001aCrystals 15 00299 g001b
Figure 1. a–c ORTEP diagrams of molecules A and B (top), together with the asymmetric unit (centre) in 4a. A view of the areneC-H⋯π(cp) and cpC-H⋯(arene) interactions with the principal interacting H atoms coloured in green (bottom). The arrow highlights both the Fc⋯Fc stacking and Fc(C-H)⋯C6 ring interactions.
Figure 1. a–c ORTEP diagrams of molecules A and B (top), together with the asymmetric unit (centre) in 4a. A view of the areneC-H⋯π(cp) and cpC-H⋯(arene) interactions with the principal interacting H atoms coloured in green (bottom). The arrow highlights both the Fc⋯Fc stacking and Fc(C-H)⋯C6 ring interactions.
Crystals 15 00299 g001aCrystals 15 00299 g001b
Crystals 15 00299 g002
Figure 2. Crystallographic autostereogram of an array of interactions in the (100) plane in 4d [REYWOU] [14] showing a relay of [Fe(C5-H)⋯π(C5H4)Fe(C5-H)⋯π(C5H4)…]n contacts and including the unit cell. The C5, as indicated, highlights the capped (stacked) nature of the (1:1) C5:C6 (face-to-face) ring overlap.
Figure 2. Crystallographic autostereogram of an array of interactions in the (100) plane in 4d [REYWOU] [14] showing a relay of [Fe(C5-H)⋯π(C5H4)Fe(C5-H)⋯π(C5H4)…]n contacts and including the unit cell. The C5, as indicated, highlights the capped (stacked) nature of the (1:1) C5:C6 (face-to-face) ring overlap.
Crystals 15 00299 g002
Crystals 15 00299 g003
Figure 3. ORTEP diagrams of 4e with displacement ellipsoids at the 30% probability level. A view of the face-to-face ring⋯ring stacked pair with tandem amide⋯amide and C-H⋯C interactions (interacting H atoms coloured in dark green). A general CPK view of the amide⋯amide (N1⋯O1) chain and crystal packing and showing the unit cell.
Figure 3. ORTEP diagrams of 4e with displacement ellipsoids at the 30% probability level. A view of the face-to-face ring⋯ring stacked pair with tandem amide⋯amide and C-H⋯C interactions (interacting H atoms coloured in dark green). A general CPK view of the amide⋯amide (N1⋯O1) chain and crystal packing and showing the unit cell.
Crystals 15 00299 g003
Crystals 15 00299 g004
Figure 4. (a) ORTEP diagram of 4f with displacement ellipsoids at the 30% probability level. Three CPK packing diagrams of the (Fc⋯C6F5⋯)n 1D stacking along the a + c direction, (b) as a chain with amides (ball and stick), and the space where Fc moieties occupy, (c) an autostereogram of the stacking and including the unit cell, and (d) a view of the C6F5 groups in green and five C6F5 groups depicted as ball and stick.
Figure 4. (a) ORTEP diagram of 4f with displacement ellipsoids at the 30% probability level. Three CPK packing diagrams of the (Fc⋯C6F5⋯)n 1D stacking along the a + c direction, (b) as a chain with amides (ball and stick), and the space where Fc moieties occupy, (c) an autostereogram of the stacking and including the unit cell, and (d) a view of the C6F5 groups in green and five C6F5 groups depicted as ball and stick.
Crystals 15 00299 g004
Crystals 15 00299 g005aCrystals 15 00299 g005b
Figure 5. (a) ORTEP diagram of the molecular structure of 5 with displacement ellipsoids at the 30% probability level. Structure 5 differs from 4d [REYWOU] by an extra -CH2- group. (b) An ORTEP diagram of 5 showing the amide⋯amide 1D chains along the b-axis direction. (c) Two identical views (ORTEP, CPK) of a molecular pair of 5 highlighting the arene ring⋯ring stacking and C-H⋯F hydrogen-bonding interactions.
Figure 5. (a) ORTEP diagram of the molecular structure of 5 with displacement ellipsoids at the 30% probability level. Structure 5 differs from 4d [REYWOU] by an extra -CH2- group. (b) An ORTEP diagram of 5 showing the amide⋯amide 1D chains along the b-axis direction. (c) Two identical views (ORTEP, CPK) of a molecular pair of 5 highlighting the arene ring⋯ring stacking and C-H⋯F hydrogen-bonding interactions.
Crystals 15 00299 g005aCrystals 15 00299 g005b
Crystals 15 00299 g006
Figure 6. Fingerprint plots of the main contacts on the Hirshfeld surface of 4f [26].
Figure 6. Fingerprint plots of the main contacts on the Hirshfeld surface of 4f [26].
Crystals 15 00299 g006
Table 1. Selected crystallographic data (full details are available; ESI, Table S1).
Table 1. Selected crystallographic data (full details are available; ESI, Table S1).
StructuresCrystal System;
Space Group		Z’Volume (Å3); KPIR, wR2R-Factors, GoF
4aMonoclinic; P21/n22851.36 (18); 71.30.044, 0.126, 0.98
4d [14] Orthorhombic; P21212111435.97 (4); 71.80.031, 0.065, 1.05
4eMonoclinic; P21/a11524.92 (8); 69.30.034, 0.085, 1.05
4fMonoclinic; P21/c11577.44 (10); 71.20.034, 0.086, 1.06
5Orthorhombic; Pbca13145.27 (16); 69.80.037, 0.092, 1.03
R-factor definitions as R [F2 > 2σ(F2)], wR (F2).
Table 2. Selected interplanar angles and intermolecular distances (°, Å).
Table 2. Selected interplanar angles and intermolecular distances (°, Å).
StructuresC5H4/C6 (°)C5H4/Amide (°)Amide…Amide Interaction (Å)O=C-N-Ctorsion
4a73.16 (11)/79.12 (11)64.77 (12)/68.16 (12)2.924 (3)/2.869 (3)−1.6 (4)/4.1 (4)
4d [14] 77.80 (8)69.80 (10)2.972 (3)2.1 (3)
4e81.24 (7)68.55 (10)2.819 (2)−7.6 (3)
4f11.34 (11)57.31 (9)2.892 (2)3.0 (3)
561.66 (7)34.08 (12)2.853 (2)−3.8 (3)
Table 3. Comparative analysis of the Fc⋯C6 stacking in SUFLIR [5] and 4f (present work) [25].
Table 3. Comparative analysis of the Fc⋯C6 stacking in SUFLIR [5] and 4f (present work) [25].
Geometric DataSUFLIR (100 K) [5] (Å,°)4f (Å,°)
Fe⋯C5 (centroid); (Å,°) a1.6467 (8), 1.6479 (8); 179.53 (4)1.6482 (9), 1.6530 (10); 178.75 (6)
C5⋯C6F6 [5] or C5⋯C6F5 b3.5825 (10); 3.6052 (11)3.5399 (13); 3.5720 (12)
Dihedral angle (planes)° c7.67( 9); 8.86 (9) d2.76 (12); 2.88 (10)
C-F⋯C5 ring centroid (Å)3.5949 (13); 3.6210 (14)3.5179 (16); 3.6620 (15)
C-F⋯C5 ring centroid (Å)3.3342 (18); 3.3370 (18)3.257 (2); 3.377 (2)
C-F⋯C5 (°)68.05 (8); 67.13 (8)67.79 (10); 67.22 (9)
Shortest stack cpC⋯Carene3.310 (2), 3.337 (2), 3.340 (2)3.319 (3), 3.327 (3), 3.387 (3)
Shortest stack cpH⋯F-C3.089, 3.167, 3.176, 3.2263.21, 3.29, 3.29, 3.35
a Ferrocene C5 ring geometric data (distances in Å; angle °). b Defined as centroid⋯centroid (Cg) distances (Å) for the C5 or C6 rings. c Dihedral angle between the Fc C5 ring and C5⋯C6F6 [5] or C5⋯C6F5 present work ring planes [25]. d As 7.8° and 9.1° using Mercury [5,24].
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Gallagher, J.F.; Jelsch, C.; Kenny, P.T.M.; Lough, A.J. Impressive 1D (Ferrocenyl⋯C6F5R⋯)n Stacking Due to Cooperative Interactions in N-(Ferrocenylmethyl)Pentafluorobenzenecarboxamide: Four Crystal Structures and Contacts Analyses in N-(Ferrocenylalkyl)Benzenecarboxamides. Crystals 2025, 15, 299. https://doi.org/10.3390/cryst15040299

AMA Style

Gallagher JF, Jelsch C, Kenny PTM, Lough AJ. Impressive 1D (Ferrocenyl⋯C6F5R⋯)n Stacking Due to Cooperative Interactions in N-(Ferrocenylmethyl)Pentafluorobenzenecarboxamide: Four Crystal Structures and Contacts Analyses in N-(Ferrocenylalkyl)Benzenecarboxamides. Crystals. 2025; 15(4):299. https://doi.org/10.3390/cryst15040299

Chicago/Turabian Style

Gallagher, John F., Christian Jelsch, Peter T. M. Kenny, and Alan J. Lough. 2025. "Impressive 1D (Ferrocenyl⋯C6F5R⋯)n Stacking Due to Cooperative Interactions in N-(Ferrocenylmethyl)Pentafluorobenzenecarboxamide: Four Crystal Structures and Contacts Analyses in N-(Ferrocenylalkyl)Benzenecarboxamides" Crystals 15, no. 4: 299. https://doi.org/10.3390/cryst15040299

APA Style

Gallagher, J. F., Jelsch, C., Kenny, P. T. M., & Lough, A. J. (2025). Impressive 1D (Ferrocenyl⋯C6F5R⋯)n Stacking Due to Cooperative Interactions in N-(Ferrocenylmethyl)Pentafluorobenzenecarboxamide: Four Crystal Structures and Contacts Analyses in N-(Ferrocenylalkyl)Benzenecarboxamides. Crystals, 15(4), 299. https://doi.org/10.3390/cryst15040299

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