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ISSN: 2056-9890

Crystal structure of a 1:1 salt of 4-amino­benzoic acid (vitamin B10) with pyrazinoic acid

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aG. A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, 1, Academicheskaya, Ivanovo 153045, Russian Federation, bNovosibirsk State University, Pirogova str. 2, Novosibirsk, 630090, Russian Federation, cInstitute of Solid State Chemistry and Mechanochemistry SB RAS, Kutateladze str. 18, Novosibirsk 630128, Russian Federation, and dG. K. Boreskov Institute of Catalysis SB RAS, Laverentiev Ave. 5, Novosibirsk 630090, Russian Federation
*Correspondence e-mail: ksdrozd@yandex.ru

Edited by C. Rizzoli, Universita degli Studi di Parma, Italy (Received 24 October 2018; accepted 23 November 2018; online 30 November 2018)

The title 1:1 salt, C7H8NO2+·C5H3N2O2 (systematic name: 4-carb­oxy­anilinium pyrazine-2-carboxyl­ate), was synthesized successfully by slow evaporation of a saturated solution from water–ethanol (1:1 v/v) mixture and characterized by X-ray diffraction (SCXRD, PXRD) and calorimetry (DSC). The crystal structure of the salt was solved and refined at 150 and 293 K. The salt crystallizes with one mol­ecule of 4-amino­benzoic acid (PABA) and one mol­ecule of pyrazinoic acid (POA) in the asymmetric unit. In the crystal, the PABA and POA mol­ecules are associated via COOH⋯Narom heterosynthons, which are connected by N—H⋯O hydrogen bonds, creating zigzag chains. The chains are further linked by N—H⋯O hydrogen bonds and ππ stacking inter­actions along the b axis [centroid-to-centroid distances = 3.7377 (13) and 3.8034 (13) Å at 150 and 293 K, respectively] to form a layered three-dimensional structure.

1. Chemical context

4-Amino­benzoic acid (PABA) is known as vitamin B10 and is involved in the production of folic acid in bacteria (Chang & Hu, 1996[Chang, T.-Y. & Hu, M.-L. (1996). J. Nutr. Biochem. 7, 408-413.]; Akberova, 2002[Akberova, S. I. (2002). Biol. Bull. Russ. Acad. Sci. 29, 390-393.]). It is used as an anti­bacterial (Richards et al., 1995[Richards, R. M. E., Xing, D. K. L. & King, T. P. (1995). J. Appl. Bacteriol. 78, 209-215.]), anti-inflammatory (Flindt-Hansen & Ebbesen, 1991[Flindt-Hansen, H. & Ebbesen, P. (1991). Br. J. Dermatol. 125, 222-226.]), anti­oxidant (Sirota et al., 2017[Sirota, T. V., Lyamina, N. E. & Weisfeld, L. I. (2017). Biophysics 62, 691-695.]; Galbinur et al., 2009[Galbinur, T., Obolensky, A., Berenshtein, E., Vinokur, V., Chowers, I., Chevion, M. & Banin, E. (2009). J. Ocul. Pharmacol. Ther. 25, 475-482.]), anti­coagulant (Stroeva et al., 1999[Stroeva, O. G., Akberova, S. I., Drozd, N. N., Makarov, V. A., Miftakhova, N. T. & Kalugin, S. S. (1999). Izv. Akad. Nauk Ser. Biol. 26, 329-336.]; Drozd et al., 2000[Drozd, N. A., Makarov, V. T., Miftakhova, N. A., Kalugin, S. G., Stroeva, O. & Akberova, S. I. (2000). Eksp. Klin. Farmakol. 63, 40-44.]), or dermatologic agent (Rothman & Henningsen, 1947[Rothman, S. & Henningsen, A. B. (1947). J. Invest. Dermatol. 9, 307-313.]; Xavier et al., 2006[Xavier, S., Macdonald, S., Roth, J., Caunt, M., Akalu, A., Morais, D., Buckley, M. T., Liebes, L., Formenti, S. C. & Brooks, P. C. (2006). Int. J. Radiat. Oncol. Biol. Phys. 65, 517-527.]; Hanson et al., 2006[Hanson, K. M., Gratton, E. & Bardeen, C. J. (2006). Free Radic. Biol. Med. 41, 1205-1212.]). Moreover, it is a building block used in the design of drug candidates and is frequently found as a structural moiety in drugs (Kluczyk et al., 2002[Kluczyk, A., Popek, T., Kiyota, T., de Macedo, P., Stefanowicz, P., Lazar, C. & Konishi, Y. (2002). Curr. Med. Chem. 9, 1871-1892.]). PABA has been the subject of many scientific investigations, due not only to its pharmaceutical and biological properties, but also its ability to form various multi-component solid forms. PABA is a simple organic mol­ecule with two functional groups: amine and carboxyl. This makes it unique in its ability to form various hydrogen-bonded network structures (Athimoolam & Natarajan, 2007[Athimoolam, S. & Natarajan, S. (2007). Acta Cryst. C63, o283-o286.]). Among all the multi-component crystals of PABA known to date, co-crystals and salts of PABA are especially numerous.

[Scheme 1]

Today, the formation of either salts or co-crystals of APIs is one of the promising strategies to modify the solid-state properties of pharmaceutical compounds, such as solubility, bioavailability, stability, etc. (Shevchenko et al., 2012[Shevchenko, A., Bimbo, L. M., Miroshnyk, I., Haarala, J., Jelínková, K., Syrjänen, K., van Veen, B., Kiesvaara, J., Santos, H. A. & Yliruusi, J. (2012). Int. J. Pharm. 436, 403-409.]; Perumalla & Sun, 2013[Perumalla, S. R. & Sun, C. C. (2013). CrystEngComm, 15, 5756-5759.]; Manin et al., 2018[Manin, A. N., Voronin, A. P., Drozd, K. V., Churakov, A. V. & Perlovich, G. L. (2018). Acta Cryst. C74, 797-806.]). The main difference between a salt and a co-crystal is in the position of a proton. A salt is formed if a proton is transferred from an acid to a base (Aakeröy et al., 2007[Aakeröy, C. B., Fasulo, M. E. & Desper, J. (2007). Mol. Pharm. 4, 317-322.]). Childs et al. (2007[Childs, S. L., Stahly, G. P. & Park, A. (2007). Mol. Pharm. 4, 323-338.]) and Cruz-Cabeza (2012[Cruz-Cabeza, A. J. (2012). CrystEngComm, 14, 6362-6365.]) have noticed a linear correlation between ΔpKa [pKa(base) – pKa(acid)] of the starting compounds and the probability of the formation of either a salt or a co-crystal. It is assumed that a salt is expected to be formed if ΔpKa > 3 (Childs et al., 2007[Childs, S. L., Stahly, G. P. & Park, A. (2007). Mol. Pharm. 4, 323-338.]) or ΔpKa > 4 (Cruz-Cabeza, 2012[Cruz-Cabeza, A. J. (2012). CrystEngComm, 14, 6362-6365.]), whereas a co-crystal forms when ΔpKa < 0 (Childs et al., 2007[Childs, S. L., Stahly, G. P. & Park, A. (2007). Mol. Pharm. 4, 323-338.]) or ΔpKa < −1 (Cruz-Cabeza, 2012[Cruz-Cabeza, A. J. (2012). CrystEngComm, 14, 6362-6365.]). In the inter­mediate ΔpKa range, the nature of multi-component crystal is difficult to predict – a so called `salt–co-crystal continuum' (Childs et al., 2007[Childs, S. L., Stahly, G. P. & Park, A. (2007). Mol. Pharm. 4, 323-338.]; Hathwar et al., 2010[Hathwar, V. R., Pal, R. & Guru Row, T. N. (2010). Cryst. Growth Des. 10, 3306-3310.]). Several examples have been documented where both a salt and a co-crystal could be formed by the same components from the same solutions under different crystallization conditions (Fu et al., 2016[Fu, X., Li, J., Wang, L., Wu, B., Xu, X., Deng, Z. & Zhang, H. (2016). RSC Adv. 6, 26474-26478.]; Losev & Boldyreva, 2018a[Losev, E. & Boldyreva, E. (2018a). CrystEngComm, 20, 2299-2305.],b[Losev, E. & Boldyreva, E. (2018b). Acta Cryst. C74, 177-185.]). A co-crystal can also be converted into a salt in the solid state upon temperature variations (Grobelny et al., 2011[Grobelny, P., Mukherjee, A. & Desiraju, G. R. (2011). CrystEngComm, 13, 4358-4364.]).

The present study reports the synthesis and crystallization of a novel salt of 4-amino­benzoic acid with pyrazinoic acid (pyrazine-2-carb­oxy­lic acid, POA), [PABA-POA], which was characterized using single crystal and powder X-ray diffraction (SCXRD, PXRD) and different scanning calorimetry (DSC).

2. Elucidation of the multi-component crystal nature

4-Amino­benzoic acid is an ampholyte mol­ecule with basic (–NH2) and acidic (–COOH) functional groups, and its pKa values are 2.46 and 4.62 (Avdeef, 2017[Avdeef, A. (2017). Eur. J. Pharm. Sci. 110, 2-18.]) respectively. Pyrazinoic acid is a weak acid with a pKa of 2.9 (Zhang et al., 1999[Zhang, Y., Scorpio, A., Nikaido, H. & Sun, Z. (1999). J. Bacteriol. 181, 2044-2049.]). According to the ΔpKa of PABA and POA, the two-component crystal is within the range of the `salt–co-crystal continuum'. Both a salt and a co-crystal can be expected to crystallize.

The crystal structure of the title compound was solved and refined at 150 K (Ia) and 293 K (Ib). The nature of the crystal form (salt/co-crystal) was identified from the structural characteristics, namely the C—N bond length of PABA and the C—O bond lengths of the carb­oxy­lic/carboxyl­ate groups of PABA and POA at both temperatures to eliminate the possibility of salt–co-crystal transition. In a neutral pure PABA mol­ecule, the length of the C—N bond between the N atom of the amine group and the C atom of the benzene ring is ca 1.37–1.4 Å. In the title compound, the protonation of the PABA amine group results in a significantly longer C—N bond [1.455 (5) Å at 150 K and 1.467 (3) Å at 293 K]. To define the deprotonation site, the C—O bond lengths of both PABA and POA were compared. In a neutral carb­oxy­lic group, C—O is longer than C=O by 0.08 Å, or more. Deprotonation of a –COOH group leads to a decrease in this difference to 0.03 Å or less (Childs et al., 2007[Childs, S. L., Stahly, G. P. & Park, A. (2007). Mol. Pharm. 4, 323-338.]; Chen et al., 2012[Chen, J.-M., Wang, Z.-Z., Wu, C.-B., Li, S. & Lu, T.-B. (2012). CrystEngComm, 14, 6221-6229.]). In the title compound, the difference d(C—O) is 0.104 (6) or 0.102 (8) Å for PABA and 0.007 (6) or 0.012 (6) Å for POA at 150 K and 293 K, respectively, indicating deprotonation of the POA –COOH group and the formation of a salt.

3. Structural commentary

The title compound crystallizes in the monoclinic non-centrosymmetric space group Pc with one mol­ecule of each component per asymmetric unit (Fig. 1[link]). The carboxyl planes of PABA and POA are slightly twisted from the aromatic ring planes [2.76 (16) and 8.4 (2)° for Ia; 2.89 (19) and 9.2 (3)° for Ib], which is a characteristic feature found in almost all known multi-component complexes of both compounds. No phase transitions occur in the temperature range between 293 and 150 K.

[Figure 1]
Figure 1
The asymmetric unit of the title compound at 150 K, with displacement ellipsoids drawn at the 50% probability level for non-H atoms. H atoms are shown as spheres of arbitrary radii.

4. Supra­molecular features

In the crystal, the O1—H1⋯N3 hydrogen bond involving the carboxyl group of PABA and the pyridine one of POA forms an acid⋯pyridine heterosynthon (COOH⋯Narom, Tables 1[link] and 2[link]). The neighboring two-component units are linked by N1—H1B⋯N2ii hydrogen bonds, forming a zigzag C22(13) chain motif. Adjacent chains are linked to each other via N1—H1C⋯O4iii hydrogen bonds [C22(7)' chain motif] to form a 2D structure [Fig. 2[link](a)]. The crystal packing is stabilized by stacking of the parallel 2D structures along the b-axis direction through ππ inter­actions between neighboring benzene and pyrazine rings [Cg1⋯Cg2 = Cg3⋯Cg4 = 3.7377 (13) and 3.8034 (13) for Ia and Ib, respectively; Cg1 and Cg2 are centroids of the POA N2–C9 pyrazine ring, Cg3 and Cg4 are centroids of the PABA C2–C7 benzene ring], forming a 3D structure supported via N1—H1A⋯O3i hydrogen bonds [C22(7)'' chain motif] [Fig. 2[link](b)].

Table 1
Hydrogen-bond geometry (Å, °) for Ia[link]

D—H⋯A D—H H⋯A DA D—H⋯A
N1—H1A⋯O3i 0.89 (4) 1.83 (4) 2.707 (3) 167 (3)
N1—H1B⋯N2ii 0.79 (4) 2.21 (4) 2.907 (3) 148 (4)
N1—H1C⋯O4iii 0.87 (4) 1.88 (4) 2.732 (3) 167 (4)
O1—H1⋯N3 0.80 (5) 1.87 (6) 2.670 (3) 175 (5)
Symmetry codes: (i) [x+1, -y+2, z+{\script{1\over 2}}]; (ii) [x+1, -y+1, z+{\script{1\over 2}}]; (iii) [x, -y+2, z+{\script{1\over 2}}].

Table 2
Hydrogen-bond geometry (Å, °) for Ib[link]

D—H⋯A D—H H⋯A DA D—H⋯A
O1—H1⋯N3 0.82 1.87 2.677 (3) 167
N1—H1A⋯O3i 0.89 1.85 2.716 (3) 164
N1—H1B⋯N2ii 0.89 2.13 2.920 (3) 148
N1—H1C⋯O4iii 0.89 1.87 2.732 (3) 163
Symmetry codes: (i) [x+1, -y+2, z+{\script{1\over 2}}]; (ii) [x+1, -y+1, z+{\script{1\over 2}}]; (iii) [x, -y+2, z+{\script{1\over 2}}].
[Figure 2]
Figure 2
(a) The formation of zigzag C22(13) chains through O1—H1⋯N3 and N1—H1B⋯N2ii inter­actions joined by an N1—H1C⋯O4iii hydrogen bond [C22(7)' chain motif] to generate the two-dimensional structure. (b) Layered arrangements of the salt via N1—H1A⋯O3i inter­actions [C22(7)'' chain motif] and aromatic ππ stacking inter­actions (dotted black lines) to generate the three-dimensional structure. Symmetry codes are in Table 1[link].

5. Thermal analysis

The thermal behavior of the title compound was investigated by DSC techniques. The DSC curve [PABA+POA] is shown in Fig. 3[link]. For a comparison, the DSC curves of the starting compounds are also plotted. PABA and POA show single endothermic peaks at 188.5 and 224.8°C, respectively. [PABA+POA] exhibits a sharp endothermic peak at 166.1°C. The melting temperature of the salt is ca 20 and 60°C lower than that of the starting compounds, suggesting the formation of a new crystalline phase. A single endothermic peak for the salt indicates that the solid state is homogeneous, and also suggests that there is no solvent in the crystal.

[Figure 3]
Figure 3
DSC curves of PABA (black), POA (red) and [PABA+POA] (blue).

6. Database survey

A search of the Cambridge Structural Database (CSD version 5.39, May 2018 update; Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) for organic multi-component crystals (salts/co-crystals, their polymorphs and solvates) gave 88 structures for PABA and only five structures for POA. Analysis of the PABA crystal structures showed that the two most typical hydrogen-bonded motifs for them are: the acid⋯pyridine (COOH⋯Narom) heterosynthon as in the title compound and the acid⋯acid (COOH⋯COOH) homosynthon between PABA mol­ecules or PABA and conformer mol­ecules with carb­oxy­lic functional group.

7. Synthesis and crystallization

A commercial sample of PABA (Merck, 99%) was co-crystallized with POA (Acros organics, 99%) by either liquid-assisted grinding, or by slow evaporation from solution under ambient conditions. Single crystals of [PABA+POA] were grown at room temperature by slow evaporation of a water–ethanol (1:1 v/v) solution in a 1:1 stoichiometric ratio. The powder sample of the title compound for DSC analysis was obtained by liquid-assisted grinding of the physical mixture in the presence of ethanol using a planetary micro mill. The ground material was characterized using PXRD to verify the formation of a new phase by comparing the diffraction pattern with the powder pattern calculated based on the single crystal X-ray diffraction data obtained in this work (Fig. 4[link]).

[Figure 4]
Figure 4
Comparison of the experimental PXRD patterns of [PABA+POA] prepared by liquid-assisted grinding (blue) of PABA (black) and POA (red) and calculated (green) using single-crystal X-ray diffraction data.

8. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3[link]. The positions of all H atoms at 293 K were optimized geometrically and refined using a riding model, with the following assumptions and restraints: N—H = 0.89 Å, C—H = 0.93 Å and O—H = 0.82 Å with Uiso(H) = 1.5Ueq(O) for the hydroxyl groups, and 1.2Ueq(C, N) otherwise. The positions of the H atoms at 150 K were refined freely in an isotropic approximation.

Table 3
Experimental details

  150 K 293 K
Crystal data
Chemical formula C7H8NO2+·C5H3N2O2 C7H8NO2+·C5H3N2O2
Mr 261.24 261.24
Crystal system, space group Monoclinic, Pc Monoclinic, Pc
a, b, c (Å) 5.95842 (16), 3.73769 (10), 25.5943 (6) 5.95233 (16), 3.80345 (11), 25.6879 (7)
β (°) 95.362 (2) 95.037 (2)
V3) 567.51 (3) 579.31 (3)
Z 2 2
Radiation type Mo Kα Mo Kα
μ (mm−1) 0.12 0.12
Crystal size (mm) 0.24 × 0.19 × 0.18 0.24 × 0.19 × 0.18
 
Data collection
Diffractometer Rigaku Oxford Diffraxction Xcalibur Ruby Gemini ultra Rigaku Oxford Diffraction Xcalibur Ruby Gemini ultra
Absorption correction Multi-scan (CrysAlis PRO; Rigaku OD, 2018[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]) Multi-scan (CrysAlis PRO; Rigaku OD, 2018[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.])
Tmin, Tmax 0.933, 1.000 0.822, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections 9340, 3426, 3244 8036, 2981, 2746
Rint 0.024 0.033
(sin θ/λ)max−1) 0.727 0.694
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.044, 0.131, 1.13 0.049, 0.145, 1.11
No. of reflections 3426 2981
No. of parameters 216 174
No. of restraints 2 2
H-atom treatment All H-atom parameters refined H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.39, −0.28 0.29, −0.28
Computer programs: CrysAlis PRO (Rigaku OD, 2018[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]), SHELXT2014 (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2017 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]) and OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]).

Supporting information


Computing details top

For both structures, data collection: CrysAlis PRO (Rigaku OD, 2018); cell refinement: CrysAlis PRO (Rigaku OD, 2018); data reduction: CrysAlis PRO (Rigaku OD, 2018); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2017 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

4-Carboxyanilinium pyrazine-2-carboxylate (Ia) top
Crystal data top
C7H8NO2+·C5H3N2O2F(000) = 272
Mr = 261.24Dx = 1.529 Mg m3
Monoclinic, PcMo Kα radiation, λ = 0.71073 Å
a = 5.95842 (16) ÅCell parameters from 5674 reflections
b = 3.73769 (10) Åθ = 3.2–30.9°
c = 25.5943 (6) ŵ = 0.12 mm1
β = 95.362 (2)°T = 150 K
V = 567.51 (3) Å3Block, light colourless
Z = 20.24 × 0.19 × 0.18 mm
Data collection top
Rigaku Oxford Diffraction Xcalibur Ruby Gemini ultra
diffractometer
3426 independent reflections
Radiation source: fine-focus sealed X-ray tube, Enhance (Mo) X-ray Source3244 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.024
Detector resolution: 10.3457 pixels mm-1θmax = 31.1°, θmin = 3.2°
ω scansh = 88
Absorption correction: multi-scan
(CrysAlis PRO; Rigaku OD, 2018)
k = 55
Tmin = 0.933, Tmax = 1.000l = 3636
9340 measured reflections
Refinement top
Refinement on F22 restraints
Least-squares matrix: fullHydrogen site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.044All H-atom parameters refined
wR(F2) = 0.131 w = 1/[σ2(Fo2) + (0.0925P)2]
where P = (Fo2 + 2Fc2)/3
S = 1.13(Δ/σ)max = 0.001
3426 reflectionsΔρmax = 0.39 e Å3
216 parametersΔρmin = 0.28 e Å3
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
xyzUiso*/Ueq
O30.3138 (3)0.3939 (5)0.25476 (7)0.0243 (4)
O40.6224 (3)0.5432 (6)0.30735 (7)0.0277 (4)
O10.4407 (3)0.5831 (6)0.53444 (8)0.0294 (4)
O20.7570 (4)0.7455 (6)0.50022 (7)0.0315 (5)
N20.1012 (3)0.1876 (5)0.33842 (7)0.0188 (4)
N10.9340 (3)1.2049 (5)0.74469 (7)0.0168 (3)
N30.2855 (3)0.3515 (6)0.43916 (8)0.0216 (4)
C80.4243 (4)0.4341 (6)0.29860 (8)0.0182 (4)
C50.8626 (3)1.0835 (6)0.69173 (8)0.0158 (4)
C90.3040 (4)0.3411 (6)0.34657 (8)0.0166 (4)
C60.6482 (4)0.9450 (6)0.68152 (8)0.0183 (4)
C10.6445 (4)0.7247 (6)0.53737 (9)0.0215 (4)
C70.5784 (3)0.8259 (6)0.63124 (8)0.0186 (4)
C20.7220 (4)0.8505 (6)0.59139 (8)0.0176 (4)
C30.9376 (4)0.9931 (7)0.60225 (9)0.0200 (4)
C120.3970 (4)0.4200 (6)0.39723 (8)0.0188 (4)
C41.0095 (4)1.1100 (6)0.65252 (9)0.0187 (4)
C100.0077 (4)0.1148 (6)0.38037 (9)0.0208 (4)
C110.0822 (4)0.1982 (6)0.43081 (9)0.0210 (4)
H70.437 (6)0.717 (10)0.6221 (13)0.021 (8)*
H100.150 (8)0.003 (11)0.3727 (18)0.037 (10)*
H41.156 (6)1.214 (9)0.6619 (14)0.020 (8)*
H31.033 (6)1.003 (9)0.5770 (15)0.021 (8)*
H120.550 (6)0.517 (9)0.4054 (14)0.020 (8)*
H1A1.046 (7)1.362 (10)0.7450 (15)0.028 (9)*
H110.005 (6)0.147 (10)0.4628 (15)0.027 (9)*
H1B0.978 (7)1.037 (11)0.7611 (17)0.034 (10)*
H60.553 (6)0.919 (9)0.7079 (14)0.020 (7)*
H1C0.823 (7)1.291 (9)0.7600 (15)0.026 (8)*
H10.399 (8)0.505 (14)0.506 (2)0.046 (12)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O30.0226 (8)0.0359 (9)0.0146 (7)0.0076 (7)0.0026 (6)0.0009 (7)
O40.0201 (8)0.0422 (10)0.0210 (8)0.0057 (7)0.0034 (6)0.0067 (7)
O10.0264 (9)0.0470 (11)0.0151 (8)0.0116 (8)0.0028 (6)0.0063 (8)
O20.0337 (10)0.0464 (11)0.0157 (8)0.0122 (9)0.0085 (7)0.0059 (7)
N20.0165 (8)0.0229 (9)0.0171 (8)0.0001 (7)0.0014 (6)0.0016 (7)
N10.0163 (8)0.0204 (8)0.0138 (8)0.0004 (7)0.0013 (6)0.0006 (6)
N30.0238 (10)0.0272 (9)0.0138 (8)0.0024 (7)0.0021 (7)0.0009 (7)
C80.0174 (9)0.0237 (10)0.0140 (9)0.0042 (8)0.0042 (7)0.0021 (7)
C50.0174 (9)0.0183 (9)0.0118 (8)0.0014 (7)0.0017 (7)0.0003 (7)
C90.0166 (9)0.0196 (9)0.0138 (9)0.0021 (7)0.0018 (7)0.0008 (7)
C60.0166 (9)0.0243 (10)0.0144 (9)0.0017 (7)0.0036 (7)0.0005 (7)
C10.0253 (11)0.0242 (10)0.0147 (9)0.0018 (8)0.0005 (8)0.0011 (8)
C70.0172 (9)0.0243 (10)0.0142 (8)0.0033 (8)0.0017 (7)0.0005 (7)
C20.0191 (9)0.0216 (10)0.0122 (8)0.0001 (7)0.0018 (7)0.0002 (7)
C30.0208 (10)0.0271 (10)0.0128 (9)0.0017 (8)0.0057 (7)0.0019 (8)
C120.0161 (9)0.0242 (10)0.0161 (9)0.0029 (8)0.0015 (7)0.0004 (8)
C40.0160 (9)0.0243 (10)0.0161 (9)0.0033 (7)0.0034 (7)0.0015 (7)
C100.0183 (9)0.0248 (10)0.0193 (10)0.0035 (8)0.0027 (7)0.0017 (8)
C110.0214 (10)0.0255 (10)0.0168 (10)0.0019 (8)0.0050 (8)0.0015 (8)
Geometric parameters (Å, º) top
O3—C81.256 (3)C5—C41.395 (3)
O4—C81.249 (3)C9—C121.393 (3)
O1—C11.320 (3)C6—C71.388 (3)
O1—H10.80 (5)C6—H60.93 (4)
O2—C11.216 (3)C1—C21.492 (3)
N2—C91.336 (3)C7—C21.394 (3)
N2—C101.334 (3)C7—H70.95 (4)
N1—C51.455 (3)C2—C31.394 (3)
N1—H1A0.89 (4)C3—C41.388 (3)
N1—H1B0.79 (4)C3—H30.90 (4)
N1—H1C0.87 (4)C12—H120.99 (4)
N3—C121.338 (3)C4—H40.97 (4)
N3—C111.340 (3)C10—C111.386 (3)
C8—C91.519 (3)C10—H100.96 (5)
C5—C61.380 (3)C11—H110.99 (4)
C1—O1—H1114 (4)O2—C1—C2124.0 (2)
C10—N2—C9117.57 (18)C6—C7—C2120.38 (19)
C5—N1—H1A112 (2)C6—C7—H7123 (2)
C5—N1—H1B108 (3)C2—C7—H7116 (2)
C5—N1—H1C112 (2)C7—C2—C1119.9 (2)
H1A—N1—H1B108 (4)C7—C2—C3119.75 (19)
H1A—N1—H1C111 (3)C3—C2—C1120.30 (19)
H1B—N1—H1C107 (4)C2—C3—H3120 (2)
C12—N3—C11117.6 (2)C4—C3—C2120.2 (2)
O3—C8—C9116.57 (19)C4—C3—H3120 (2)
O4—C8—O3127.4 (2)N3—C12—C9121.5 (2)
O4—C8—C9116.05 (19)N3—C12—H12115 (2)
C6—C5—N1118.57 (18)C9—C12—H12124 (2)
C6—C5—C4121.47 (19)C5—C4—H4118 (2)
C4—C5—N1119.95 (19)C3—C4—C5119.0 (2)
N2—C9—C8117.39 (18)C3—C4—H4123 (2)
N2—C9—C12120.8 (2)N2—C10—C11122.0 (2)
C12—C9—C8121.83 (19)N2—C10—H10115 (3)
C5—C6—C7119.17 (19)C11—C10—H10123 (3)
C5—C6—H6121 (2)N3—C11—C10120.7 (2)
C7—C6—H6119 (2)N3—C11—H11116 (2)
O1—C1—C2112.5 (2)C10—C11—H11124 (2)
O2—C1—O1123.6 (2)
O3—C8—C9—N27.2 (3)C5—C6—C7—C20.9 (3)
O3—C8—C9—C12171.1 (2)C9—N2—C10—C110.9 (3)
O4—C8—C9—N2172.9 (2)C6—C5—C4—C30.2 (3)
O4—C8—C9—C128.7 (3)C6—C7—C2—C1179.4 (2)
O1—C1—C2—C72.9 (3)C6—C7—C2—C30.5 (4)
O1—C1—C2—C3177.2 (2)C1—C2—C3—C4180.0 (2)
O2—C1—C2—C7178.0 (2)C7—C2—C3—C40.1 (3)
O2—C1—C2—C31.9 (4)C2—C3—C4—C50.2 (3)
N2—C9—C12—N31.3 (3)C12—N3—C11—C100.0 (3)
N2—C10—C11—N31.1 (4)C4—C5—C6—C70.7 (3)
N1—C5—C6—C7179.6 (2)C10—N2—C9—C8178.14 (19)
N1—C5—C4—C3179.9 (2)C10—N2—C9—C120.2 (3)
C8—C9—C12—N3177.0 (2)C11—N3—C12—C91.1 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1A···O3i0.89 (4)1.83 (4)2.707 (3)167 (3)
N1—H1B···N2ii0.79 (4)2.21 (4)2.907 (3)148 (4)
N1—H1C···O4iii0.87 (4)1.88 (4)2.732 (3)167 (4)
O1—H1···N30.80 (5)1.87 (6)2.670 (3)175 (5)
Symmetry codes: (i) x+1, y+2, z+1/2; (ii) x+1, y+1, z+1/2; (iii) x, y+2, z+1/2.
4-Carboxyanilinium pyrazine-2-carboxylate (Ib) top
Crystal data top
C7H8NO2+·C5H3N2O2F(000) = 272
Mr = 261.24Dx = 1.498 Mg m3
Monoclinic, PcMo Kα radiation, λ = 0.71073 Å
a = 5.95233 (16) ÅCell parameters from 4235 reflections
b = 3.80345 (11) Åθ = 3.2–29.2°
c = 25.6879 (7) ŵ = 0.12 mm1
β = 95.037 (2)°T = 293 K
V = 579.31 (3) Å3Block, light colourless
Z = 20.24 × 0.19 × 0.18 mm
Data collection top
Rigaku Oxford Diffraction Xcalibur Ruby Gemini ultra
diffractometer
2981 independent reflections
Radiation source: fine-focus sealed X-ray tube, Enhance (Mo) X-ray Source2746 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.033
Detector resolution: 10.3457 pixels mm-1θmax = 29.6°, θmin = 1.6°
ω scansh = 78
Absorption correction: multi-scan
(CrysAlis PRO; Rigaku OD, 2018)
k = 55
Tmin = 0.822, Tmax = 1.000l = 3533
8036 measured reflections
Refinement top
Refinement on F22 restraints
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.049H-atom parameters constrained
wR(F2) = 0.145 w = 1/[σ2(Fo2) + (0.0973P)2]
where P = (Fo2 + 2Fc2)/3
S = 1.11(Δ/σ)max = 0.001
2981 reflectionsΔρmax = 0.29 e Å3
174 parametersΔρmin = 0.28 e Å3
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
xyzUiso*/Ueq
O30.3114 (4)0.4159 (6)0.25493 (8)0.0428 (6)
O40.6195 (4)0.5580 (8)0.30677 (9)0.0505 (6)
O10.4431 (4)0.5870 (8)0.53404 (9)0.0547 (7)
H10.4150030.5019470.5048590.082*
O20.7585 (5)0.7517 (8)0.50073 (10)0.0588 (7)
N20.1020 (4)0.2017 (6)0.33869 (9)0.0328 (5)
N10.9323 (4)1.1834 (6)0.74503 (8)0.0282 (5)
H1A1.0421851.3414700.7442450.034*
H1B0.9821360.9993370.7640650.034*
H1C0.8156161.2795540.7591800.034*
N30.2877 (4)0.3635 (7)0.43878 (10)0.0383 (6)
C80.4229 (4)0.4514 (8)0.29826 (10)0.0314 (6)
C50.8611 (4)1.0681 (7)0.69163 (9)0.0262 (5)
C90.3039 (4)0.3555 (7)0.34649 (10)0.0273 (5)
C60.6491 (4)0.9282 (8)0.68141 (10)0.0312 (6)
H60.5529720.9093270.7079320.037*
C10.6453 (5)0.7272 (9)0.53745 (10)0.0365 (6)
C70.5796 (4)0.8159 (8)0.63147 (11)0.0319 (6)
H70.4368120.7188440.6244230.038*
C20.7226 (4)0.8473 (8)0.59157 (10)0.0301 (5)
C30.9362 (5)0.9920 (8)0.60255 (11)0.0356 (6)
H31.0320691.0144080.5760300.043*
C120.3970 (5)0.4333 (8)0.39670 (11)0.0335 (6)
H120.5389870.5365430.4011200.040*
C41.0070 (4)1.1027 (8)0.65257 (11)0.0330 (6)
H41.1499481.1987950.6599630.040*
C100.0051 (5)0.1270 (8)0.38076 (13)0.0376 (6)
H100.1447610.0160450.3764520.045*
C110.0861 (5)0.2102 (9)0.43080 (12)0.0390 (7)
H110.0053530.1583450.4592370.047*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O30.0390 (12)0.0655 (15)0.0241 (10)0.0140 (10)0.0039 (8)0.0003 (9)
O40.0356 (12)0.0830 (18)0.0336 (12)0.0103 (11)0.0068 (9)0.0122 (11)
O10.0491 (13)0.0908 (18)0.0241 (10)0.0236 (13)0.0034 (9)0.0131 (11)
O20.0618 (16)0.0920 (19)0.0244 (10)0.0238 (15)0.0149 (10)0.0122 (12)
N20.0273 (10)0.0424 (12)0.0285 (11)0.0009 (9)0.0011 (8)0.0052 (9)
N10.0288 (10)0.0343 (11)0.0211 (10)0.0011 (8)0.0007 (7)0.0007 (8)
N30.0429 (14)0.0498 (14)0.0221 (11)0.0049 (10)0.0027 (9)0.0028 (10)
C80.0295 (12)0.0427 (14)0.0226 (12)0.0078 (10)0.0059 (9)0.0036 (10)
C50.0292 (12)0.0305 (13)0.0190 (11)0.0026 (9)0.0022 (9)0.0009 (9)
C90.0269 (12)0.0331 (12)0.0218 (11)0.0028 (9)0.0022 (9)0.0011 (9)
C60.0288 (12)0.0441 (15)0.0215 (12)0.0042 (10)0.0067 (9)0.0011 (10)
C10.0420 (15)0.0458 (15)0.0217 (12)0.0049 (12)0.0033 (11)0.0035 (11)
C70.0278 (12)0.0429 (14)0.0253 (12)0.0056 (11)0.0045 (10)0.0015 (10)
C20.0339 (13)0.0363 (14)0.0202 (11)0.0010 (10)0.0028 (9)0.0004 (9)
C30.0349 (14)0.0514 (16)0.0218 (12)0.0053 (11)0.0092 (10)0.0024 (11)
C120.0287 (12)0.0443 (16)0.0274 (13)0.0059 (11)0.0017 (10)0.0027 (11)
C40.0265 (12)0.0441 (15)0.0286 (13)0.0065 (10)0.0042 (9)0.0035 (11)
C100.0303 (13)0.0466 (16)0.0364 (15)0.0082 (12)0.0061 (10)0.0033 (12)
C110.0413 (16)0.0484 (16)0.0285 (14)0.0042 (12)0.0109 (11)0.0001 (11)
Geometric parameters (Å, º) top
O3—C81.252 (3)C5—C41.390 (4)
O4—C81.240 (4)C9—C121.390 (4)
O1—H10.8200C6—H60.9300
O1—C11.313 (4)C6—C71.380 (4)
O2—C11.210 (4)C1—C21.497 (4)
N2—C91.336 (4)C7—H70.9300
N2—C101.332 (4)C7—C21.394 (4)
N1—H1A0.8900C2—C31.391 (4)
N1—H1B0.8900C3—H30.9300
N1—H1C0.8900C3—C41.382 (4)
N1—C51.467 (3)C12—H120.9300
N3—C121.336 (4)C4—H40.9300
N3—C111.334 (4)C10—H100.9300
C8—C91.524 (4)C10—C111.388 (4)
C5—C61.374 (3)C11—H110.9300
C1—O1—H1109.5O2—C1—C2123.6 (3)
C10—N2—C9117.4 (2)C6—C7—H7119.8
H1A—N1—H1B109.5C6—C7—C2120.3 (2)
H1A—N1—H1C109.5C2—C7—H7119.8
H1B—N1—H1C109.5C7—C2—C1119.9 (2)
C5—N1—H1A109.5C3—C2—C1120.6 (2)
C5—N1—H1B109.5C3—C2—C7119.4 (2)
C5—N1—H1C109.5C2—C3—H3119.8
C11—N3—C12117.3 (3)C4—C3—C2120.5 (2)
O3—C8—C9116.7 (2)C4—C3—H3119.8
O4—C8—O3127.6 (3)N3—C12—C9121.7 (3)
O4—C8—C9115.7 (2)N3—C12—H12119.1
C6—C5—N1118.7 (2)C9—C12—H12119.1
C6—C5—C4121.4 (2)C5—C4—H4120.5
C4—C5—N1120.0 (2)C3—C4—C5118.9 (2)
N2—C9—C8117.3 (2)C3—C4—H4120.5
N2—C9—C12120.8 (2)N2—C10—H10119.1
C12—C9—C8121.8 (2)N2—C10—C11121.8 (3)
C5—C6—H6120.2C11—C10—H10119.1
C5—C6—C7119.5 (2)N3—C11—C10121.0 (3)
C7—C6—H6120.2N3—C11—H11119.5
O1—C1—C2113.0 (2)C10—C11—H11119.5
O2—C1—O1123.3 (3)
O3—C8—C9—N28.0 (4)C5—C6—C7—C20.7 (4)
O3—C8—C9—C12170.1 (3)C9—N2—C10—C111.1 (5)
O4—C8—C9—N2172.4 (3)C6—C5—C4—C30.3 (4)
O4—C8—C9—C129.5 (4)C6—C7—C2—C1179.6 (3)
O1—C1—C2—C72.3 (4)C6—C7—C2—C30.2 (4)
O1—C1—C2—C3177.9 (3)C1—C2—C3—C4180.0 (3)
O2—C1—C2—C7178.7 (3)C7—C2—C3—C40.2 (4)
O2—C1—C2—C31.0 (5)C2—C3—C4—C50.2 (4)
N2—C9—C12—N31.1 (5)C12—N3—C11—C100.1 (5)
N2—C10—C11—N31.2 (5)C4—C5—C6—C70.7 (4)
N1—C5—C6—C7179.6 (3)C10—N2—C9—C8178.1 (2)
N1—C5—C4—C3180.0 (3)C10—N2—C9—C120.0 (4)
C8—C9—C12—N3176.9 (3)C11—N3—C12—C91.1 (5)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1···N30.821.872.677 (3)167
N1—H1A···O3i0.891.852.716 (3)164
N1—H1B···N2ii0.892.132.920 (3)148
N1—H1C···O4iii0.891.872.732 (3)163
Symmetry codes: (i) x+1, y+2, z+1/2; (ii) x+1, y+1, z+1/2; (iii) x, y+2, z+1/2.
 

Acknowledgements

KD thanks Dr Alex Manin and Dr Denis Rychkov for their inter­est in this work and helpful discussions.

Funding information

Funding for this research was provided by: RFBR (grant No. 17-33-50073 mol_nr).

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