2-Amino-4-ferrocenyl-5-oxo-5,6,7,8-tetra­hydro-4H-chromene-3-carbo­nitrile monohydrate

Carren Nyapola; David O Juma; Sizwe J Zamisa; Eric M Njogu; Bernard Omondi

doi:10.1107/S2414314625004687

. 2025 May 30;10(Pt 5):x250468. doi: 10.1107/S2414314625004687

2-Amino-4-ferrocenyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile monohydrate

Carren Nyapola ^a,^*, David O Juma ^a, Sizwe J Zamisa ^a, Eric M Njogu ^b, Bernard Omondi ^a

Editor: M Zeller^c

PMCID: PMC12142392 PMID: 40487508

The crystal packing is consolidated by O—H⋯N, O—H⋯O, N—H⋯O, and N—H⋯π hydrogen bonds, with the solvent water molecule acting as both donor and acceptor. This results in a two-dimensional hydrogen-bonded network extending parallel to the bc plane.

Keywords: crystal structure, ferrocenyl, chromene

Abstract

In the title hydrate, [Fe(C₅H₅)(C₁₅H₁₃N₂O₂)]·H₂O, the pendent ferrocenyl substituent is significantly rotated against the chromene backbone, with a torsion angle of 56.8 (2)°. Rotational disorder is observed in one of the Cp rings of the ferrocenyl substituents. The crystal packing is consolidated by a network of O—H⋯N, O—H⋯O, N—H⋯O and N—H⋯π hydrogen bonds, prominently involving a solvent water molecule. The water molecule functions as both a hydrogen-bond donor and acceptor, bridging adjacent molecules, leading to the formation of a layer with a distinctive hydrogen-bonded motif propagating parallel to the bc plane

Structure description

Recent pharmacological investigations have highlighted 2-amino-4H-pyran carbonitrile derivatives as promising anticancer agents, driven by their unique molecular architecture and versatility (Mansouri et al., 2011 ▸; Wang et al., 2014 ▸, 2025 ▸). These compounds belong to the heterocyclic pyran family, renowned for diverse pharmacological applications ranging from antimicrobial to antitumor activities (Fouda, 2016 ▸; Kathrotiya & Patel, 2012 ▸; Veena et al., 2022 ▸). Aryl-substituted 4H-chromene-3-carbonitriles exhibit strong DNA-binding affinities via hydrogen-bonding interactions at their amino groups, suggesting a mechanistic link to their biological activity (Zamisa et al., 2022 ▸). Building upon the above findings, our recent work (Nyapola et al., 2025 ▸) continues to expand the exploration of 4H-pyran derivatives for enhanced pharmacokinetic properties.

The molecule of the title compound consists of a tetrahydrochromene moiety with ferrocenyl, cyano, amino, and oxo substituents, as shown in Fig. 1 ▸. The compound crystallizes in a centrosymmetric space group with one molecule in the asymmetric unit. The pendent ferrocenyl substituent is significantly rotated against the chromene backbone, with a C1—C9—C11—C12 torsion angle of 56.8 (2)°. This is notably larger compared to the torsion angle of the pendant p-tolyl substituent in the closely related compound 2-amino-7,7-dimethyl-5-oxo-4-(p-tolyl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (CSD ref code BOZMAI; Veeranagaiah et al., 2025 ▸), where the torsion angle is 39.42 (14)°. The crystal structure of the title compound is consolidated by O—H⋯N, O—H⋯O, N—H⋯O and N—H⋯π hydrogen bonds (Table 1 ▸). The solvent water molecule serves as a trifunctional hydrogen-bonding group, donating both of its hydrogen atoms to form O3—H3C⋯O1 and O3—H3D⋯N2 hydrogen bonds, thereby bridging two adjacent molecules. Simultaneously, the oxygen atom of the water molecule acts as a hydrogen-bond acceptor, participating in an N1—H1A⋯O3 interaction, where the amine group donates one of its H atoms. The second amine H atom does not form a classical hydrogen bond but appears to form an N1—H1B⋯π interaction towards the Cp ring C16–C20 at symmetry position x, 1 + y, z. Together, these interactions generate a supramolecular layer structure featuring a characteristic hydrogen-bonded ring described by an Inline graphic (16) graph-set motif, which extends parallel to the crystallographic bc plane (Fig. 2 ▸).

Molecular structure of the title compound showing the atom-numbering scheme and displacement ellipsoids drawn at the 50% probability level. The minor disordered part of the Cp ring is given in a faint color.

Table 1. Hydrogen-bond geometry (Å, °).

Cg1 and Cg2 are the centroids of the Cp rings C16–C20 and C16A–C20A, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3C⋯O1	0.84 (1)	2.01 (1)	2.842 (2)	175 (3)
O3—H3D⋯N2ⁱ	0.83 (1)	2.28 (2)	3.011 (3)	147 (3)
N1—H1A⋯O3ⁱⁱ	0.86 (1)	2.01 (1)	2.859 (3)	168 (3)
N1—H1B⋯Cg1ⁱⁱⁱ	0.86 (2)	2.86 (2)	3.696 (7)	164 (3)
N1—H1B⋯Cg2ⁱⁱⁱ	0.84 (2)	2.86 (2)	3.677 (7)	165 (3)

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Hydrogen bonds in the crystal structure of the title compound. Symmetry codes: (i) −x + 2, −y + 1, −z + 1; (ii) x, y, z + 1; (iii) 2 − x, 1 − y, -z.

Synthesis and crystallization

The title compound was synthesized via a one-pot reaction involving 1,3-cyclohexanedione (0.015 mmol), malononitrile (0.015 mmol), and ferrocene carboxaldehyde (0.015 mmol). Two drops of triethylamine catalysed the reaction. Following the established synthetic procedure (Nyapola et al., 2025 ▸), the reaction mixture was placed in a 35 ml snap-on microwave vessel and subjected to microwave irradiation at 100°C for 10 min. The reaction mixture was filtered off under vacuum and recrystallized from ethanol, yielding a light-green-coloured solid. Slow evaporation from acetone solution yielded single crystals.

Refinement

Crystallographic data and structure refinement details are summarized in Table 2 ▸. The unsubstituted cyclopentadienyl ring of the ferrocenyl substituent was refined as disordered over two positions. PART 1 and 2 instructions were used to model the disorder, and the major component site occupancy refined to a value of 0.515 (18). All disordered C—C bond lengths and C—C—C bond angles were restrained to be similar to each other (SADI restraints, e.s.d. 0.02 Å) and U^ij components of ADPs for disordered atoms closer to each other than 2.0 Å were restrained to be similar (SIMU restraint, e.s.d. 0.01 Å²). Amine and water H-atom positions were refined and restrained to target values of 0.84 (1) and 0.86 (1) Å, respectively. U_iso(H) values were set to a multiple of U_eq(C/N/O) with 1.5 for water, and 1.2 for C—H, CH₂, and NH₂ units, respectively.

Table 2. Experimental details.

Crystal data
Chemical formula	[Fe(C₅H₅)(C₁₅H₁₃N₂O₂)]·H₂O
M _r	392.23
Crystal system, space group	Triclinic, P
Temperature (K)	296
a, b, c (Å)	9.2440 (4), 10.3415 (4), 11.0093 (5)
α, β, γ (°)	65.358 (3), 66.714 (2), 81.236 (2)
V (Å³)	878.59 (7)
Z	2
Radiation type	Mo Kα
μ (mm⁻¹)	0.88
Crystal size (mm)	0.22 × 0.14 × 0.11

Data collection
Diffractometer	Bruker APEXII CCD
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 ▸)
T_min, T_max	0.456, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections	11443, 3810, 3248
R _int	0.047
(sin θ/λ)_max (Å⁻¹)	0.641

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.039, 0.105, 1.06
No. of reflections	3810
No. of parameters	293
No. of restraints	244
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.61, −0.21

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Computer programs: APEX2 and SAINT (Bruker, 2009 ▸), SHELXT2018/2 (Sheldrick, 2015a ▸), SHELXL2019/3 (Sheldrick, 2015b ▸) and OLEX2 (Dolomanov et al., 2009 ▸).

Supplementary Material

Crystal structure: contains datablock(s) I. DOI: 10.1107/S2414314625004687/zl4082sup1.cif

x-10-x250468-sup1.cif^{(358.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2414314625004687/zl4082Isup2.hkl

x-10-x250468-Isup2.hkl^{(303.7KB, hkl)}

CCDC reference: 2453792

Additional supporting information: crystallographic information; 3D view; checkCIF report

Acknowledgments

The authors would like to thank the University of KwaZulu Natal for the research facilities.

full crystallographic data