Startseite The crystal structure of 3-nitrobenzene-1,2-dicarboxylic acid—pyrazine-2-carboxamide(1/1), C13H10N4O7
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The crystal structure of 3-nitrobenzene-1,2-dicarboxylic acid—pyrazine-2-carboxamide(1/1), C13H10N4O7

  • Cheng-Jun Jiang ORCID logo EMAIL logo , Die Cheng , Ying-Fan Xia ORCID logo , Jia-rong Zhang und Shu-ting Lin
Veröffentlicht/Copyright: 1. November 2022

Abstract

C13H10N4O7, monoclinic, P21/n (no. 14), a = 10.7017(7) Å, b = 7.1240(5) Å, c = 19.0878(13) Å, β = 99.280(3)°, V = 1436.19(17) Å3, Z = 4, Rgt (F) = 0.0586, wRref (F 2) = 0.1746, T = 296.15 K.

CCDC no.: 2206393

The molecular structure is shown in the figure. Table 1 contains crystallographic data and Table 2 contains the list of the atoms including atomic coordinates and displacement parameters.

Table 1:

Data collection and handling.

Crystal: Colourless block
Size: 0.48 × 0.35 × 0.29 mm
Wavelength: Mo Kα radiation (0.71073 Å)
μ: 0.13 mm−1
Diffractometer, scan mode: Bruker D8 Venture, φ and ω
θ max, completeness: 27.2°, >99 %
N(hkl)measured, N(hkl)unique, R int: 20,755, 3189, 0.034
Criterion for I obs, N(hkl) gt: I obs > 2σ(I obs), 2684
N(param)refined: 219
Programs: Bruker [1], Olex2 [2], SHELX [3, 4]
Table 2:

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

Atom x y z U iso*/U eq
O1 0.56030 (14) 0.6521 (2) 0.80568 (8) 0.0554 (4)
N1 0.39272 (16) 1.0651 (2) 0.83422 (10) 0.0491 (4)
N2 0.60064 (18) 1.1038 (3) 0.94184 (10) 0.0539 (5)
N3 0.36314 (15) 0.7425 (2) 0.75681 (9) 0.0475 (4)
H3A 0.352312 0.647621 0.728643 0.057*
H3B 0.303967 0.824517 0.756137 0.057*
C1 0.4089 (2) 1.2159 (3) 0.87595 (14) 0.0618 (6)
H1 0.349051 1.311502 0.868907 0.074*
C2 0.5118 (2) 1.2347 (3) 0.92937 (13) 0.0597 (6)
H2 0.518990 1.342165 0.957370 0.072*
C3 0.58626 (19) 0.9533 (3) 0.89993 (10) 0.0463 (5)
H3C 0.647217 0.859162 0.906400 0.056*
C4 0.48247 (16) 0.9344 (2) 0.84700 (9) 0.0371 (4)
C5 0.47010 (17) 0.7623 (3) 0.80088 (10) 0.0382 (4)
O2 0.38517 (13) 0.3770 (2) 0.68504 (8) 0.0546 (4)
O3 0.58489 (14) 0.3501 (3) 0.73787 (10) 0.0666 (5)
H3 0.570195 0.452311 0.754514 0.100*
O4 0.19355 (13) 0.1258 (2) 0.59364 (8) 0.0515 (4)
O5 0.31431 (14) 0.2893 (2) 0.53055 (8) 0.0550 (4)
H5 0.246717 0.335789 0.512353 0.083*
O6 0.2637 (2) −0.0980 (3) 0.48266 (13) 0.1094 (10)
O7 0.3765 (2) −0.3365 (3) 0.48143 (12) 0.0877 (7)
N4 0.35091 (17) −0.1942 (2) 0.50934 (9) 0.0474 (4)
C6 0.50408 (16) 0.1122 (3) 0.65828 (9) 0.0374 (4)
C7 0.41254 (16) 0.0484 (2) 0.60224 (9) 0.0350 (4)
C8 0.43686 (17) −0.1239 (3) 0.57199 (9) 0.0383 (4)
C9 0.54172 (19) −0.2334 (3) 0.59650 (11) 0.0460 (5)
H9 0.552355 −0.349845 0.576264 0.055*
C10 0.6298 (2) −0.1668 (3) 0.65125 (11) 0.0507 (5)
H10 0.701304 −0.237663 0.668069 0.061*
C11 0.61190 (18) 0.0054 (3) 0.68128 (10) 0.0463 (5)
H11 0.672964 0.050936 0.717525 0.056*
C12 0.48513 (17) 0.2934 (3) 0.69422 (10) 0.0396 (4)
C13 0.29354 (16) 0.1587 (2) 0.57572 (9) 0.0364 (4)

Source of materials

The mixture of pyrazinamide and 3-nitrophthalic acid with a molar ratio of 1:1 was dissolved in deionized water, and the resulting mixed solution was stirred and dissolved in a constant temperature water bath at 30 °C to obtain a clear solution. The solution was filtered and placed in a sample vial, covered with membrane and punctured. The filtrate was slowly evaporated at room temperature to obtain crystals of the title compound.

Experimental details

Absorption corrections were applied by using multi-scan program [1]. Using Olex2 [2], the structure was solved with the ShelXT [3] structure solution program and refined with the ShelXL [4] refinement package. The H atoms were fixed, fixed U iso were set to 1.2 times of all C(H) groups and N(H, H) groups; 1.5 times of O(H) groups.

Comment

Pyrazinamide (PZA), a white crystalline powder, is the first-line drug for the treatment of pulmonary tuberculosis and the most effective antibacterial drug in short-course chemotherapy. Due to the low water solubility (15 μg/mL) and low bioavailability, its oral absorption effect is severely inhibited [5]. In recent years, drug co-crystal technology, as an emerging technology, enhances the efficacy of drugs by improving the solubility and permeability of drugs [6]. Therefore, PZA can be co-crystallized to improve its solubility and bioavailability. Cocrystals of pyrazinamide were obtained with 3-(4-hydroxyphenyl)prop-2-enoic acid (CCDC: 2026373, JAJYUS), thiophene-2,5-dicarboxylic acid (CCDC: 2026372, JAJZON), 2,6-dichlorobenzoic acid (CCDC: 2026371, JAJZED), 5-hydroxybenzene-1,3-dicarboxylic acid (CCDC: 2069727, JAJZIH) [7], hydrochlorothiazide (CCDC: 1510703, EGENIP01) [8], 4-nitrobenzoic acid (CCDC: 963629, MUDVUE) [9] and so on.

In the title crystal, the main intermolecular force is the formation of hydrogen bonds. The O2 atom on the carboxyl groups of 3-nitrophthalic acid is a hydrogen bond acceptor. The H3A and H3B atoms on the amide group (N3–H3) of the pyrazinamide molecule are hydrogen bond donors, forming the intermolecular hydrogen bond N3–H3A⋯O2 [length 2.969(2) Å, angle 138.0°]. The O1 atom on the amide group of the pyrazinamide molecule is a hydrogen bond acceptor, and the H2 atom on the carboxyl group (O3–H3) of the 3-nitrophthalic acid molecule is a hydrogen bond donor, forming the intermolecular hydrogen bond O3–H3⋯O1 [length 2.546(2) Å, angle 167.8°]. The N1 atom on the pyrazine ring of the pyrazinamide molecule is a hydrogen bond acceptor, the H5 atom on the carboxyl group (O5–H5) of the 3-nitrophthalic acid molecule is a hydrogen bond donor, forming an intermolecular hydrogen bond O3–H3⋯O1 (symmetry code: −1/2 + x, 3/2 − y, −1/2 + z) [length 2.725(2) Å, angle 160.2°].


Corresponding author: Cheng-Jun Jiang, School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Liuhe Road 318#, Hangzhou, China, E-mail:

Funding source: Zhejiang Provincial Natural Science Foundation of China http://dx.doi.org/10.13039/501100010248

Award Identifier / Grant number: LGJ20B060001

Acknowledgements

We gratefully acknowledge support by the Zhejiang Province Basic Public Welfare Research Project (LGJ20B060001).

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was financially supported by Zhejiang Provincial Natural Science Foundation of China (grant number: LGJ20B060001).

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

References

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Received: 2022-09-21
Accepted: 2022-10-11
Published Online: 2022-11-01
Published in Print: 2023-01-27

© 2022 the author(s), published by De Gruyter, Berlin/Boston

This work is licensed under the Creative Commons Attribution 4.0 International License.

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