Crystal structure of a hydrogen-bonded 2:1 co-crystal of 4-nitro­phenol and 4,4′-bi­pyridine

Gotingco, A.; Villanueva Contreras, M.; Wolfarth, J.A.; Stieber, S.C.E.; Marr, Z.Y.

doi:10.1107/S205698902400971X

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Volume 80| Part 11| November 2024| Pages 1135-1137

https://doi.org/10.1107/S205698902400971X

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Crystal structure of a hydrogen-bonded 2:1 co-crystal of 4-nitrophenol and 4,4′-bipyridine

Angela Gotingco,^a Merary Villanueva Contreras,^a Jeanette A. Wolfarth,^a S. Chantal E. Stieber ^a and Zoe Y. Marr ^a ^*

^aDepartment of Chemistry & Biochemistry, California State Polytechnic University, Pomona, 3801 W. Temple Ave., Pomona, CA 91768, USA
^*Correspondence e-mail: zymarr@cpp.edu

Edited by J. Reibenspies, Texas A & M University, USA (Received 28 August 2024; accepted 2 October 2024; online 8 October 2024)

In the title compound, C₁₀H₈N₂·2C₆H₅NO₃, 4-nitrophenol and 4,4′-bipyridine crystallized together in a 2:1 ratio in the space group P2₁/n. There is a hydrogen-bonding interaction between the nitrogen atoms on the 4,4′-bipyridine molecule and the hydrogen atom on the hydroxyl group on the 4-nitrophenol, resulting in trimolecular units. This structure is a polymorph of a previously reported structure [Nayak & Pedireddi (2016 ). Cryst. Growth Des. 16, 5966–5975], which differs mainly due to a twist in the 4,4′-bipyridine molecule.

Keywords: crystal structure; co-crystal; hydrogen bonding.

CCDC reference: 2388458

1. Chemical context

Co-crystals are a growing field of science as crystalline solids can be engineered to have improved physical-chemical properties such as better solubility, stability, and bioavailability (Karimi-Jafari et al., 2018 ). Co-crystals are defined as crystalline solids composed of two or more different molecular and/or ionic compounds in a specific stoichiometric ratio and are neither solvates nor simple salts (Aitipamula et al., 2012 ). They are held together by intermolecular interactions such as hydrogen bonding, halogen bonding, and π–π stacking (Wang et al., 2022 ). Generally, co-crystals are high yielding, making them an appealing candidate for crystal engineering in the realm of pharmaceutical purposes (Chettri et al., 2024 ).

The chemicals used in this co-crystal consist of 4,4′-bipyridine and 4-nitrophenol. 4,4′-Bipyridine can be found in a multitude of crystal structures due the pyridyl groups being suitable for both coordination polymers and co-crystals (Richard et al., 2021 ). 4-Nitrophenol is commonly found as a drug manufacturing and synthesis intermediate in the pharmaceutical industry. Specifically, this compound has been used in the production of compounds such as acetaminophen, a drug used for pain relief, where it is nitrated and converted to 4-aminophenol, an intermediate for acetaminophenol (Abdollahi et al., 2014 ). This is a highly appealing synthesis process for its greener approach to science in comparison to other intermediates used. Additionally, since 4-nitrophenol takes on the color of a yellow crystalline solid, it is also a suitable candidate that is used to produce pigments/dyes such as leather darkener (National Center for Biotechnology Information, 2024 ).

2. Structural commentary

4,4′-Bipyridine and 4-nitrophenol co-crystallized in a 1:2 ratio with the asymmetric unit containing one molecule of 4-nitrophenol and half of a 4,4′-bipyridine molecule in the P2₁/n space group. Half of the atoms from the 4,4′-bipyridine molecule sit on Wyckoff position 4e, and the other half is generated by the center of inversion (0, 1/2, 0) (Fig. 1). The nitro groups exhibit a trigonal–planar geometry with bond angles of 122.44 (16)° for O1—N2—O2, 118.51 (14)° for O1—N2—C6, and 119.06 (15) for O2—N2—C6. The N—O/N=O bonds have lengths of 1.232 (2) and 1.2346 (19) Å, which are in between the average values for N—O and N=O bonds, as expected due to resonance. The molecular geometry of the hydroxyl group is bent with with an angle of 110.4 (19)° for H3—O3—C9. The aromatic benzene ring has bond angles ranging between 119.32 (15) and 121.33 (15)°, as expected for sp²-hybridized carbons.

Figure 1
A view of the structure containing 4,4′-bipyridine and 4-nitrophenol showing the atom-labeling scheme. Atoms that contain _a in the label are symmetry generated (−x + 2, − y + 1, −z). The displacement ellipsoids are drawn at 50% probability.

3. Supramolecular features

In the structure, each nitrogen on the 4,4′-bipyridine is hydrogen bonded to the hydroxyl group from the 4-nitrophenol, which results in the formation of trimolecular units that propagate along [001] (Fig. 2). There is a hydrogen-bonding interaction (Table 1) between the two molecules with a D⋯A distance between H3 and N1 of 1.84 (3) Å. In addition to hydrogen bonding, there are also π–π interactions between the ring systems of the adjacent 4,4′-bipyridine molecules having a plane centroid to plane centroid distance of 3.8255 (11) Å.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3⋯N1ⁱ	0.86 (3)	1.84 (3)	2.6921 (19)	174 (3)
Symmetry code: (i) $[-x+{\script{3\over 2}}, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

Figure 2
Diagram of the packed unit cell highlighting the hydrogen-bonding interaction between the hydrogen on the 4-nitrophenol and the nitrogen atom on the 4,4′-bipyridine. View down [010].

4. Database survey

The crystal structure that is reported herein is a polymorph of a co-crystal (refcode AWEVUV) published by Nayak & Pedireddi (2016). Similar synthesis and crystallization conditions were used but there are slight differences in the structure. The asymmetric unit of the previous structure contains three molecules, two 4-nitrophenol and one 4,4′-bipyridine, and the 4,4′-bipyridine does not lie on a symmetry operation. In the previously published structure, the pyridyl groups are rotated about the C13—C22 bond with a plane twist angle of 24.60 (8)° whereas the pyridyl rings sit in plane with one another in the structure reported above. The unit-cell parameters and space group for the two structures also differ (Table 2).

Table 2
Comparison of unit-cell parameters (Å, °)

Parameter	Nayak & Pedireddi (2016)	Title compound
Crystal system	Monoclinic	Monoclinic
Space group	P2₁/c	P2₁/n
a	19.090 (4)	12.3711 (7)
b	3.8080 (10)	3.8255 (2)
c	27.3470 (10)	21.4175 (12)
β	98.38 (3)	104.195 (2)

5. Synthesis and crystallization

The synthesis for the newly reported co-crystal is modified from the procedure published by Nayak & Pedireddi (2016) with a 2:1 rather than a 1:1 ratio of 4,4′-bipyridine and 4-nitrophenol used. In addition, the method of heating was changed from a warm water bath to gentle heating directly on a hot plate. These differences in the synthesis could contribute to the deviation of the packing of the molecules from the original structure.

A 2:1 molar ratio of 4,4′-bipyridine and 4-nitrophenol was used to synthesize the new co-crystal. 20.0 mg (0.128 mmol, 2 eq) of 4,4′-bipyridine and 8.9 mg (0.0640 mmol, 1 eq) of 4-nitrophenol were added to a 20 mL scintillation vial. 4.4 mL of methanol was added to the vial and then the solution was warmed up on a hot plate to dissolve the solids. Once fully dissolved, the solution was cooled to room temperature. The sample underwent slow evaporation and to control evaporation rate, small holes were punctured on the parafilm covering as the solution was left to evaporate for 2 weeks. The resulting crystals were clear, colorless prisms. These crystals were grown as part of class CHM 5720 ‘Current advances in Inorganic Chemistry – Introduction to Crystallography’ at Cal Poly Pomona.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3. All hydrogens except H3 were placed at calculated positions using AFIX commands and refined using a riding model. The position of H3 was determined using the Fourier difference map and refined freely.

Table 3
Experimental details

Crystal data
Chemical formula	C₁₀H₈N₂·2C₆H₅NO₃
M_r	434.40
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	123
a, b, c (Å)	12.3711 (7), 3.8255 (2), 21.4175 (12)
β (°)	104.195 (2)
V (Å³)	982.65 (9)
Z	2
Radiation type	Mo Kα
μ (mm⁻¹)	0.11
Crystal size (mm)	0.47 × 0.07 × 0.03

Data collection
Diffractometer	Bruker D8 Venture
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 )
T_min, T_max	0.501, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections	24119, 2957, 2302
R_int	0.076
(sin θ/λ)_max (Å⁻¹)	0.711

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.057, 0.161, 1.10
No. of reflections	2957
No. of parameters	149
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.47, −0.37
Computer programs: APEX4 and SAINT V8.40B (Bruker, 2018 ), SHELXT2018/2 (Sheldrick, 2015a ), SHELXL (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

Supporting information

CCDC reference: 2388458

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S205698902400971X/jy2052sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S205698902400971X/jy2052Isup3.hkl

Supporting information file. DOI: https://doi.org/10.1107/S205698902400971X/jy2052Isup3.cml

checkCIF report

Computing details top

4,4'-Bipyridine–4-nitrophenol (1/2) top

Crystal data top

C₁₀H₈N₂·2C₆H₅NO₃	F(000) = 452
M_r = 434.40	D_x = 1.468 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
a = 12.3711 (7) Å	Cell parameters from 5585 reflections
b = 3.8255 (2) Å	θ = 2.2–30.3°
c = 21.4175 (12) Å	µ = 0.11 mm⁻¹
β = 104.195 (2)°	T = 123 K
V = 982.65 (9) Å³	Prism, clear colourless
Z = 2	0.47 × 0.07 × 0.03 mm

Data collection top

Bruker D8 Venture diffractometer	2302 reflections with I > 2σ(I)
φ and ω scans	R_int = 0.076
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	θ_max = 30.4°, θ_min = 2.0°
T_min = 0.501, T_max = 0.746	h = −17→17
24119 measured reflections	k = −5→5
2957 independent reflections	l = −30→30

Refinement top

Refinement on F²	Primary atom site location: dual
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.057	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.161	w = 1/[σ²(F_o²) + (0.0648P)² + 0.7817P] where P = (F_o² + 2F_c²)/3
S = 1.10	(Δ/σ)_max < 0.001
2957 reflections	Δρ_max = 0.47 e Å⁻³
149 parameters	Δρ_min = −0.37 e Å⁻³
0 restraints

Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O3	0.36469 (10)	0.2681 (4)	0.20323 (6)	0.0241 (3)
O1	0.76718 (11)	1.0265 (4)	0.13543 (7)	0.0315 (3)
O2	0.66554 (13)	0.9310 (5)	0.03941 (6)	0.0372 (4)
N1	1.07530 (12)	0.6778 (4)	0.16823 (7)	0.0224 (3)
N2	0.68271 (12)	0.9075 (4)	0.09853 (7)	0.0243 (3)
C3	1.01552 (13)	0.5393 (4)	0.03500 (7)	0.0184 (3)
C6	0.60089 (14)	0.7357 (4)	0.12575 (8)	0.0196 (3)
C11	0.49848 (14)	0.6398 (5)	0.08606 (8)	0.0220 (3)
H11	0.482527	0.682639	0.041035	0.026*
C7	0.62601 (14)	0.6748 (4)	0.19178 (8)	0.0209 (3)
H7	0.696365	0.741876	0.218231	0.025*
C1	0.97805 (15)	0.5281 (5)	0.13953 (8)	0.0227 (4)
H1	0.928687	0.468694	0.165566	0.027*
C9	0.44362 (14)	0.4190 (4)	0.17947 (8)	0.0202 (3)
C8	0.54795 (14)	0.5162 (4)	0.21849 (8)	0.0211 (3)
H8	0.564758	0.472398	0.263503	0.025*
C2	0.94480 (14)	0.4545 (5)	0.07449 (8)	0.0223 (3)
H2	0.874671	0.347421	0.056842	0.027*
C10	0.42023 (14)	0.4814 (5)	0.11295 (8)	0.0228 (4)
H10	0.350120	0.414291	0.086214	0.027*
C5	1.14324 (14)	0.7645 (5)	0.13058 (8)	0.0238 (4)
H5	1.212254	0.874593	0.149718	0.029*
C4	1.11678 (14)	0.6999 (5)	0.06463 (8)	0.0230 (4)
H4	1.167421	0.764784	0.039720	0.028*
H3	0.386 (2)	0.254 (8)	0.2445 (15)	0.053 (8)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O3	0.0195 (6)	0.0320 (7)	0.0194 (6)	−0.0049 (5)	0.0022 (5)	0.0017 (5)
O1	0.0236 (6)	0.0378 (8)	0.0325 (7)	−0.0049 (6)	0.0056 (5)	0.0044 (6)
O2	0.0364 (8)	0.0536 (10)	0.0226 (7)	−0.0013 (7)	0.0094 (6)	0.0087 (6)
N1	0.0234 (7)	0.0230 (7)	0.0203 (7)	0.0029 (6)	0.0044 (5)	−0.0015 (5)
N2	0.0222 (7)	0.0275 (8)	0.0238 (7)	0.0040 (6)	0.0066 (5)	0.0048 (6)
C3	0.0183 (7)	0.0169 (7)	0.0198 (7)	0.0014 (6)	0.0044 (6)	−0.0002 (6)
C6	0.0201 (7)	0.0202 (7)	0.0187 (7)	0.0029 (6)	0.0052 (6)	0.0017 (6)
C11	0.0240 (8)	0.0252 (8)	0.0153 (7)	0.0043 (7)	0.0018 (6)	0.0005 (6)
C7	0.0195 (7)	0.0220 (8)	0.0185 (7)	−0.0005 (6)	−0.0004 (6)	0.0004 (6)
C1	0.0234 (8)	0.0245 (8)	0.0213 (8)	0.0000 (6)	0.0077 (6)	−0.0009 (6)
C9	0.0196 (7)	0.0202 (8)	0.0196 (7)	0.0015 (6)	0.0028 (6)	−0.0009 (6)
C8	0.0232 (8)	0.0223 (8)	0.0159 (7)	−0.0005 (6)	0.0009 (6)	0.0003 (6)
C2	0.0200 (8)	0.0254 (8)	0.0212 (8)	−0.0030 (6)	0.0044 (6)	−0.0024 (6)
C10	0.0200 (8)	0.0279 (9)	0.0175 (7)	0.0010 (6)	−0.0010 (6)	−0.0015 (6)
C5	0.0190 (8)	0.0283 (9)	0.0227 (8)	0.0002 (6)	0.0023 (6)	−0.0025 (7)
C4	0.0182 (7)	0.0283 (9)	0.0224 (8)	−0.0015 (6)	0.0048 (6)	−0.0011 (7)

Geometric parameters (Å, º) top

O3—C9	1.338 (2)	C11—C10	1.382 (2)
O3—H3	0.86 (3)	C7—H7	0.9500
O1—N2	1.232 (2)	C7—C8	1.378 (2)
O2—N2	1.2346 (19)	C1—H1	0.9500
N1—C1	1.338 (2)	C1—C2	1.381 (2)
N1—C5	1.341 (2)	C9—C8	1.405 (2)
N2—C6	1.444 (2)	C9—C10	1.403 (2)
C3—C3ⁱ	1.484 (3)	C8—H8	0.9500
C3—C2	1.396 (2)	C2—H2	0.9500
C3—C4	1.400 (2)	C10—H10	0.9500
C6—C11	1.391 (2)	C5—H5	0.9500
C6—C7	1.391 (2)	C5—C4	1.392 (2)
C11—H11	0.9500	C4—H4	0.9500

C9—O3—H3	110.4 (19)	C2—C1—H1	117.9
C1—N1—C5	117.07 (15)	O3—C9—C8	122.52 (15)
O1—N2—O2	122.44 (16)	O3—C9—C10	118.15 (15)
O1—N2—C6	118.51 (14)	C10—C9—C8	119.32 (15)
O2—N2—C6	119.06 (15)	C7—C8—C9	120.32 (15)
C2—C3—C3ⁱ	121.30 (18)	C7—C8—H8	119.8
C2—C3—C4	116.84 (15)	C9—C8—H8	119.8
C4—C3—C3ⁱ	121.86 (18)	C3—C2—H2	120.4
C11—C6—N2	119.80 (15)	C1—C2—C3	119.19 (16)
C11—C6—C7	121.33 (15)	C1—C2—H2	120.4
C7—C6—N2	118.86 (15)	C11—C10—C9	120.44 (15)
C6—C11—H11	120.4	C11—C10—H10	119.8
C10—C11—C6	119.16 (15)	C9—C10—H10	119.8
C10—C11—H11	120.4	N1—C5—H5	118.7
C6—C7—H7	120.3	N1—C5—C4	122.70 (16)
C8—C7—C6	119.41 (15)	C4—C5—H5	118.7
C8—C7—H7	120.3	C3—C4—H4	120.0
N1—C1—H1	117.9	C5—C4—C3	119.98 (16)
N1—C1—C2	124.22 (16)	C5—C4—H4	120.0

O3—C9—C8—C7	−179.23 (16)	C3ⁱ—C3—C4—C5	−179.13 (19)
O3—C9—C10—C11	179.35 (16)	C6—C11—C10—C9	0.2 (3)
O1—N2—C6—C11	171.57 (16)	C6—C7—C8—C9	−0.4 (3)
O1—N2—C6—C7	−7.4 (2)	C11—C6—C7—C8	0.0 (3)
O2—N2—C6—C11	−8.2 (2)	C7—C6—C11—C10	0.1 (3)
O2—N2—C6—C7	172.86 (16)	C1—N1—C5—C4	−1.0 (3)
N1—C1—C2—C3	−0.1 (3)	C8—C9—C10—C11	−0.6 (3)
N1—C5—C4—C3	0.2 (3)	C2—C3—C4—C5	0.6 (3)
N2—C6—C11—C10	−178.82 (16)	C10—C9—C8—C7	0.7 (3)
N2—C6—C7—C8	178.95 (15)	C5—N1—C1—C2	0.9 (3)
C3ⁱ—C3—C2—C1	179.06 (19)	C4—C3—C2—C1	−0.7 (2)

Symmetry code: (i) −x+2, −y+1, −z.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···N1ⁱⁱ	0.86 (3)	1.84 (3)	2.6921 (19)	174 (3)

Symmetry code: (ii) −x+3/2, y−1/2, −z+1/2.

Comparison of unit-cell parameters (Å, °) top

Parameter	Nayak & Pedireddi (2016)	Title compound
Crystal system	Monoclinic	Monoclinic
Space group	P2₁/c	P2₁/n
a	19.090 (4)	12.3711 (7)
b	3.8080 (10)	3.8255 (2)
c	27.3470 (10)	21.4175 (12)
β	98.38 (3)	104.195 (2)

Funding information

Funding for this research was provided by: Camille and Henry Dreyfus Foundation (award to S. Chantal E. Stieber); Office of Postsecondary Education (grant No. P031C210068 to Zoe Y. Marr, S. Chantal E. Stieber); National Science Foundation, Directorate for Mathematical and Physical Sciences (grant No. 1847926 to S. Chantal E. Stieber); U.S. Department of Defense, U.S. Army (award No. W911NF-17-1-0537 to S. Chantal E. Stieber).

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