Synthesis, characterization and supra­molecular analysis for (E)-3-(pyridin-4-yl)acrylic acid

In the title compound, the pyridine ring is fused to acrylic acid, forming an almost planar structure with an E-configuration about the double bond. In the crystal, O—H⋯N and C—H⋯O inter­actions together with π–π stacking inter­actions lead to the formation of the three-dimensional structure.

Abstract

The title compound, C₈H₇NO₂, crystallizes as prismatic colourless crystals in space group P , with one mol­ecule in the asymmetric unit. The pyridine ring is fused to acrylic acid, forming an almost planar structure with an E-configuration about the double bond with a torsion angle of −6.1 (2)°. In the crystal, strong O—H⋯N inter­actions link the mol­ecules, forming chains along the [101] direction. Weak C—H⋯O inter­actions link adjacent chains along the [100] direction, generating an R ² ₂(14) homosynthon. Finally, π–π stacking inter­actions lead to the formation of the three-dimensional structure. The supra­molecular analysis was supported by Hirshfeld surface and two-dimensional fingerprint plot analysis, indicating that the most abundant contacts are associated with H⋯H, O⋯H/H⋯O, N⋯H/H⋯N and C⋯H/H⋯C inter­actions.

1. Chemical context

Cinnamic acid and its derivatives have been used in several applications related to medicinal chemistry (Deng et al., 2023 ▸), organic synthesis (Chen et al., 2020 ▸), and coordination chemistry (Zhou et al., 2016 ▸). Cinnamic acids are reactive mol­ecules due to possessing an unsaturated carbonyl moiety, which can be considered a Michael acceptor and benzene ring. Both make it possible to modify them, resulting in synthetic cinnamic acid derivatives with a broad range of biological properties, including anti­bacterial (Ruwizhi & Aderibigbe, 2020 ▸) anti­tuberculosis (Teixeira et al., 2020 ▸), anti­malarial (Fonte et al., 2023 ▸), anti­diabetic (Adisakwattana, 2017 ▸; Feng et al., 2022 ▸), anti­cancer (Feng et al., 2022 ▸), anti­fungal (Liu et al., 2024 ▸), Alzheimer’s treatment (Drakontaeidi & Pontiki, 2024 ▸), anti­oxidant (Nouni et al., 2023 ▸), and cosmetic (Gunia-Krzyżak et al., 2018 ▸). Among the various types of cinnamic acids documented, 4-pyridyl­acrylic acid (4-Hpya) is considered a highly valuable ligand because of several structural characteristics that make it suitable for the construction of coord­ination compounds. These characteristics include multiple coordination sites, which enable the formation of higher-dimensional structures, and versatile coordination modes to form different structures (Khalfaoui et al., 2021 ▸). On the other hand, its capacity to function as both a hydrogen-bond donor and acceptor facilitates the creation of intricate hydrogen-bonded networks (Jiao et al., 2007 ▸; Zhu et al., 2005 ▸).

2. Structural commentary

The title compound crystallizes in space group P with one mol­ecule per asymmetric unit (Fig. 1 ▸). The pyridinic ring is fused to acrylic acid, forming an almost planar structure with an E-configuration about the double bond, with a C8—C4—C3—C2 torsion angle of −6.1 (2)°.

Figure 1.

The mol­ecule of (E)-3-(pyridin-4-yl)acrylic acid compound with displacement ellipsoids drawn at the 50% probability level.

3. Supra­molecular features

In the crystal, strong O1—H1⋯N1 inter­actions link the mol­ecules, forming chains along the [101] direction (Fig. 2 ▸ a, Table 1 ▸). Adjacent chains are linked along the [100] direction through weak C—H⋯O inter­actions, generating an (14) homosynthon (Fig. 2 ▸ b). Finally, the three-dimensional supra­molecular structure is finally formed by slipped π–π stacking inter­actions (Hunter & Sanders, 1990 ▸) between the pyridinic rings (N1/C4–C8) with distances of 3.8246 (10) Å, and π–π stacking inter­actions of the acrylic double bond (C2=C3) of 3.4322 (10)Å (Fig. 2 ▸ c). An inter­action between the nitro­gen atom of the pyridinic ring, N1, and the double bond of the acrylic group with a distance of 3.4044 (13) Å is also observed.

Figure 2.

Supra­molecular inter­actions in the title compound. (a) O—H⋯N inter­actions forming chains, (b) two chains joined by C—H⋯O inter­actions and (c) π–π stacking inter­actions between the pyridine rings and the acrylic group.

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯N1i	0.99 (3)	1.63 (3)	2.6147 (18)	177 (3)
C5—H5⋯O2ii	0.93	2.57	3.336 (2)	140

Symmetry codes: (i) ; (ii) .

A Hirshfeld surface analysis was performed to confirm, visualise and qu­antify the supra­molecular inter­actions present in title compound. The Hirshfeld surface mapped over d _norm and 2D fingerprint plots (Spackman & Jayatilaka, 2009 ▸) were generated using Crystal Explorer 17 (Spackman, et al., 2021 ▸). Fig. 3 ▸ shows the strongest inter­actions as red spots. These are associated with the donor and acceptor atoms, in this case for the O—H⋯N inter­action. The weakest inter­actions, associated with the C—H⋯O contacts, are shown as white areas. These inter­actions were qu­anti­fied through the fingerprint plots, indicating that the most abundant contacts are associated with H⋯H inter­actions (36.2%) while O⋯H/H⋯O, N⋯H/H⋯N and C⋯H/H⋯C inter­actions represent 27.8%, 8.7% and 10.7%, respectively. These results show that crystal packing is governed mainly by dispersion and electrostatic inter­actions.

Figure 3.

Hirshfeld surface and fingerprint plot analysis for the title compound.

4. Database survey

A search of the Cambridge Structural Database (Version 2023.3.0; Groom et al., 2016 ▸) using Conquest (Bruno et al., 2002 ▸) found seven entries for (E)-3-(pyridin-4-yl)acrylic acid derivative mol­ecules. In all cases, the protonation of the nitro­gen atom in the pyridine ring leads to the formation of pyridinium salts. These include halides (Hu, 2010 ▸; Kole et al., 2010 ▸), tri­fluoro­acetate (Kole et al., 2010 ▸), hydrogen sulfate (Kole et al., 2010 ▸), perchlorate and hexa­fluoro­phosphate (Kole et al., 2011 ▸).

5. Synthesis and crystallization

The synthesis of (E)-3-(pyridin-4-yl)acrylic acid compound was performed following the procedure reported by Kudelko et al. (2015 ▸) for the synthesis of 3-(pyrid­yl)acrylic acids (Fig. 4 ▸). In a 25 mL flat-bottomed flask, 728 mg of malonic acid (0.335 mmol) and 300 mg of 4-pyridincarb­oxy­aldehyde (0.33 5 mmol) were mixed with 2 ml of pyridine. The reaction mixture was refluxed under constant stirring for 3 h. The reaction synthesis was ice-cooled, and then drops of 37% HCl were added until precipitate formation was observed. The obtained solid was separated by filtration and washed with acetone. The solid product was recrystallized by slow water evaporation, giving a colourless crystalline powder and small prismatic crystals in 97.9% yield.

Figure 4.

Reaction scheme for obtaining (E)-3-(pyridin-4-yl)acrylic acid.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. The O-bound hydrogen atom (H1) was found in electron density maps and freely refined. C-bound hydrogen atoms were positioned geometrically and refined using a riding model [C—H = 0.93 Å, U _iso(H) = 1.2U _eq(C)].

Table 2. Experimental details.

Crystal data
Chemical formula	C8H7NO2
M r	149.15
Crystal system, space group	Triclinic, P
Temperature (K)	291
a, b, c (Å)	6.6279 (15), 7.3272 (12), 8.2308 (15)
α, β, γ (°)	67.271 (17), 83.403 (17), 73.006 (17)
V (Å3)	352.57 (13)
Z	2
Radiation type	Cu Kα
μ (mm−1)	0.85
Crystal size (mm)	0.09 × 0.06 × 0.05
Data collection
Diffractometer	SuperNova, Dual, Cu at home/near, Atlas
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2021 ▸)
T min, T max	0.831, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	3635, 1461, 1243
R int	0.035
(sin θ/λ)max (Å−1)	0.631
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.049, 0.153, 1.04
No. of reflections	1461
No. of parameters	104
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	0.14, −0.27

Computer programs: CrysAlis PRO (Rigaku OD, 2021 ▸), SHELXT (Sheldrick, 2015a ▸), SHELXL2016/6 (Sheldrick, 2015b ▸) and OLEX2 (Dolomanov et al., 2009 ▸).

Supplementary Material

CCDC reference: 2341592

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

supplementary crystallographic information

Crystal data

C8H7NO2	F(000) = 156
Mr = 149.15	Dx = 1.405 Mg m−3
Triclinic, P1	Melting point: 553 K
a = 6.6279 (15) Å	Cu Kα radiation, λ = 1.54184 Å
b = 7.3272 (12) Å	Cell parameters from 1657 reflections
c = 8.2308 (15) Å	θ = 6.8–74.9°
α = 67.271 (17)°	µ = 0.85 mm−1
β = 83.403 (17)°	T = 291 K
γ = 73.006 (17)°	Prismatic, colourless
V = 352.57 (13) Å3	0.09 × 0.06 × 0.05 mm
Z = 2

Data collection

SuperNova, Dual, Cu at home/near, Atlas diffractometer	1461 independent reflections
Radiation source: micro-focus sealed X-ray tube, SuperNova (Cu) X-ray Source	1243 reflections with I > 2σ(I)
Mirror monochromator	Rint = 0.035
Detector resolution: 10.6144 pixels mm-1	θmax = 76.6°, θmin = 5.8°
ω scans	h = −8→7
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2021)	k = −8→9
Tmin = 0.831, Tmax = 1.000	l = −10→10
3635 measured reflections

Refinement

Refinement on F2	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.049	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.153	w = 1/[σ2(Fo2) + (0.0977P)2 + 0.0215P] where P = (Fo2 + 2Fc2)/3
S = 1.04	(Δ/σ)max < 0.001
1461 reflections	Δρmax = 0.14 e Å−3
104 parameters	Δρmin = −0.27 e Å−3

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.48195 (18)	0.6974 (2)	0.64537 (15)	0.0609 (4)
O2	0.63738 (19)	0.8136 (2)	0.79722 (16)	0.0669 (4)
C2	0.3116 (2)	0.7317 (2)	0.89960 (18)	0.0484 (4)
H2	0.211812	0.676180	0.879516	0.058*
N1	−0.20475 (19)	0.72846 (17)	1.42131 (15)	0.0504 (4)
C5	0.1186 (2)	0.8159 (2)	1.31387 (18)	0.0490 (4)
H5	0.228403	0.862808	1.329376	0.059*
C4	0.1149 (2)	0.76641 (18)	1.16689 (16)	0.0426 (3)
C7	−0.2089 (2)	0.6805 (2)	1.28079 (19)	0.0507 (4)
H7	−0.320055	0.632669	1.269716	0.061*
C1	0.4937 (2)	0.75386 (19)	0.77647 (17)	0.0477 (4)
C3	0.2868 (2)	0.7884 (2)	1.03649 (18)	0.0456 (3)
H3	0.386535	0.847081	1.051782	0.055*
C8	−0.0552 (2)	0.6991 (2)	1.15114 (18)	0.0483 (4)
H8	−0.065343	0.666782	1.054192	0.058*
C6	−0.0433 (3)	0.7943 (2)	1.43650 (18)	0.0524 (4)
H6	−0.038863	0.827444	1.534078	0.063*
H1	0.600 (4)	0.713 (4)	0.561 (3)	0.099 (8)*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
O1	0.0601 (7)	0.0851 (8)	0.0546 (6)	−0.0366 (6)	0.0209 (5)	−0.0374 (5)
O2	0.0631 (7)	0.0930 (9)	0.0644 (7)	−0.0440 (6)	0.0193 (5)	−0.0389 (6)
C2	0.0493 (8)	0.0521 (7)	0.0490 (8)	−0.0225 (6)	0.0125 (6)	−0.0213 (6)
N1	0.0545 (7)	0.0513 (6)	0.0463 (6)	−0.0184 (5)	0.0129 (5)	−0.0197 (5)
C5	0.0523 (8)	0.0528 (7)	0.0489 (7)	−0.0218 (6)	0.0056 (6)	−0.0225 (6)
C4	0.0457 (7)	0.0396 (6)	0.0405 (7)	−0.0122 (5)	0.0055 (5)	−0.0139 (5)
C7	0.0482 (7)	0.0572 (7)	0.0524 (7)	−0.0224 (6)	0.0101 (6)	−0.0233 (6)
C1	0.0508 (7)	0.0488 (7)	0.0451 (7)	−0.0201 (5)	0.0097 (5)	−0.0167 (5)
C3	0.0455 (7)	0.0468 (6)	0.0450 (7)	−0.0168 (5)	0.0058 (5)	−0.0161 (5)
C8	0.0513 (7)	0.0552 (7)	0.0453 (7)	−0.0202 (6)	0.0075 (5)	−0.0240 (5)
C6	0.0621 (9)	0.0553 (7)	0.0458 (7)	−0.0199 (6)	0.0091 (6)	−0.0249 (6)

Geometric parameters (Å, º)

O1—C1	1.3135 (17)	C5—C4	1.3954 (18)
O1—H1	0.98 (3)	C5—C6	1.386 (2)
O2—C1	1.2110 (19)	C4—C3	1.4729 (19)
C2—H2	0.9300	C4—C8	1.392 (2)
C2—C1	1.4887 (18)	C7—H7	0.9300
C2—C3	1.322 (2)	C7—C8	1.384 (2)
N1—C7	1.3374 (18)	C3—H3	0.9300
N1—C6	1.332 (2)	C8—H8	0.9300
C5—H5	0.9300	C6—H6	0.9300
C1—O1—H1	113.5 (14)	C8—C7—H7	118.6
C1—C2—H2	118.9	O1—C1—C2	112.14 (13)
C3—C2—H2	118.9	O2—C1—O1	124.20 (13)
C3—C2—C1	122.27 (14)	O2—C1—C2	123.65 (13)
C6—N1—C7	117.87 (12)	C2—C3—C4	125.60 (14)
C4—C5—H5	120.4	C2—C3—H3	117.2
C6—C5—H5	120.4	C4—C3—H3	117.2
C6—C5—C4	119.18 (13)	C4—C8—H8	120.2
C5—C4—C3	119.41 (13)	C7—C8—C4	119.52 (12)
C8—C4—C5	117.36 (12)	C7—C8—H8	120.2
C8—C4—C3	123.22 (12)	N1—C6—C5	123.17 (12)
N1—C7—H7	118.6	N1—C6—H6	118.4
N1—C7—C8	122.88 (14)	C5—C6—H6	118.4
N1—C7—C8—C4	1.3 (2)	C3—C2—C1—O2	4.3 (2)
C5—C4—C3—C2	174.27 (12)	C3—C4—C8—C7	179.26 (12)
C5—C4—C8—C7	−1.2 (2)	C8—C4—C3—C2	−6.1 (2)
C4—C5—C6—N1	−0.2 (2)	C6—N1—C7—C8	−0.8 (2)
C7—N1—C6—C5	0.3 (2)	C6—C5—C4—C3	−179.79 (12)
C1—C2—C3—C4	−178.21 (11)	C6—C5—C4—C8	0.6 (2)
C3—C2—C1—O1	−176.96 (13)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···N1i	0.99 (3)	1.63 (3)	2.6147 (18)	177 (3)
C5—H5···O2ii	0.93	2.57	3.336 (2)	140

Symmetry codes: (i) x+1, y, z−1; (ii) −x+1, −y+2, −z+2.

Hydrogen bonds and interactions geometry, (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···N1i	0.990 (3)	1.630 (3)	2.61470 (18)	177.0 (3)
C5—H5···O2ii	0.9300	2.5700	3.3360 (2)	140.00
Cp1···Cp1			3.82460 (10)
Cp2···Cp2			3.43220 (10)
N1···Cp1			3.40440 (13)

Funding Statement

The authors all acknowledge the Universidad Santi­ago de Cali and Dirección General de Investigaciones for funding this research under call No. 01–2024 and projects 939–621121-3307 and 934–621122-3427. RD acknowledges the Vicerectoria de Investigaciones of Universidad del Cauca for 2024 inter­nal call, project No. ID-6161. MM is grateful for support from the Facultad de Ciencias and Departamento de Química at Universidad de los Andes, Bogotá, Colombia.