4-Amino-3,5-di­chloro­pyridinium 3-hy­droxy­pico­linate monohydrate

The title hydrated salt features a dense array of hydrogen bonds, forming a three-dimensional network.

Abstract

In the title hydrated salt, C₅H₅Cl₂N₂ ⁺·C₆H₄NO₃ ⁻·H₂O, the pyridine N atom of the cation is protonated and an intra­molecular O—H⋯O hydrogen bond is observed in the anion, which generates an S(6) ring. The crystal packing features N—H⋯N, O—H⋯O, N—H⋯O, C—H⋯Cl and C—H⋯O hydrogen bonds, which generate a three-dimensional network.

Structure description

4-Amino­pyridine and its derivatives are used clinically to treat Lambert–Eaton myasthenic syndrome and multiple sclerosis because they block potassium channels, which prolongs action potentials and increases transmitter release at the neuromuscular junction (Judge & Bever, 2006 ▸). Picolinic acid, which contains N and O donors, has attracted much attention for the design and synthesis of self-assembling systems (e.g., Steiner, 2002 ▸). In this regard, 3-hy­droxy­picolinic acid is of inter­est because it can be used as a neutral ligand or, depending on the pH value, as an anionic or cationic ligand. In addition, due to the arrangement of its functional groups, it can act as a monodentate or bidentate ligand, which allows it to form five- or six-membered chelate rings. As part of our work in this area, we now report the synthesis and structure of the title hydrated mol­ecular salt.

The asymmetric unit (Fig. 1 ▸) of the title salt contains a 4-amino-3,5-di­chloro­pyridinium cation, a 3-hy­droxy picolinate anion and a water mol­ecule. The pyridinium cation is essentially planar, with a maximum deviation of 0.010 (2) Å for atom C2. A wider than normal angle [C5—N1—C1 = 120.41 (12)°] is subtended at the protonated N1 atom. In the anion, a typical intra­molecular O—H⋯O hydrogen bond, which generates an S(6) ring, is seen. In the extended structure, the cations, anions and water mol­ecules are connected by N—H⋯N, O—H⋯O, C—H⋯Cl, N—H⋯O and C—H⋯O hydrogen bonds (Table 1 ▸), forming a three-dimensional network (Figs. 2 ▸ and 3 ▸).

Figure 1.

The mol­ecular structure of the title compound showing 50% displacement ellipsoids. The intra­molecular hydrogen bond is shown with dashed lines.

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3⋯O2	0.82	1.79	2.5155 (17)	147
N1—H1⋯N3i	0.86	1.90	2.7546 (17)	171
N2—H2A⋯O1W ii	0.86	2.13	2.9414 (17)	157
N2—H2B⋯O1W iii	0.86	2.05	2.8269 (17)	149
O1W—H1W⋯O2	0.85	1.90	2.7442 (17)	170
O1W—H2W⋯O1iv	0.85	1.98	2.8181 (18)	170
C5—H5⋯O1i	0.93	2.31	2.9864 (18)	129
C5—H5⋯Cl2v	0.93	2.97	3.7363 (16)	141
C7—H7⋯O3vi	0.93	2.52	3.399 (2)	157

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) ; (vi) .

Figure 2.

One-dimensional supra­molecular hydrogen-bonded chain mediated by water mol­ecules in the title compound.

Figure 3.

Crystal packing viewed down [100] in the title compound.

A search of the Cambridge Structural Database (Version 5.43, update November 2022; Groom et al., 2016 ▸) for the 3,5-di­chloro-4-amino pyridine fragment with additional substit­uents yielded hexa­aqua­magnesium(II) bis­(4-amino-3,5,6-tri­chloro-picolinate) tetra­hydrate (CSD refcode BAWGOV; Smith et al., 1981 ▸), [(4-amino-3,5-di­chloro-6-fluoro­pyridin-2-yl)­oxy]acetic acid (EZONOY; Park et al., 2016 ▸), sodium picloramate hexa­hydrate (CURLIM; Smith et al., 2015 ▸), guanidinium 4-amino-3,5,6-tri­chloro­picolinate (GUPICL10; Parthasarathi et al., 1982 ▸), and 6-chloro-3-(tri­fluoro­meth­oxy)pyridine-2-carb­oxy­lic acid (MAFTEU; Manteau et al., 2010 ▸).

Synthesis and crystallization

A hot methanol solution of 3-hy­droxy picolinic acid (40 mg) was mixed with a hot aqueous solution of 4-amino 3,5-di­chloro pyridine (34 mg). The mixture was cooled slowly and kept at room temperature. After a few days, colourless block shaped crystals were obtained.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸.

Table 2. Experimental details.

Crystal data
Chemical formula	C5H5Cl2N2 +·C6H4NO3 −·H2O
M r	320.13
Crystal system, space group	Monoclinic, P21/c
Temperature (K)	296
a, b, c (Å)	8.4267 (19), 14.084 (3), 10.900 (2)
β (°)	91.953 (8)
V (Å3)	1292.9 (5)
Z	4
Radiation type	Mo Kα
μ (mm−1)	0.52
Crystal size (mm)	0.46 × 0.32 × 0.13
Data collection
Diffractometer	Agilent Xcalibur, Atlas, Gemini
Absorption correction	Multi-scan
T min, T max	0.819, 0.937
No. of measured, independent and observed [I > 2σ(I)] reflections	45801, 3296, 2853
R int	0.038
(sin θ/λ)max (Å−1)	0.675
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.033, 0.091, 1.03
No. of reflections	3296
No. of parameters	185
H-atom treatment	H-atom parameters constrained
Δρmax, Δρmin (e Å−3)	0.24, −0.35

Computer programs: CrysAlis PRO (Agilent, 2012 ▸), SHELXT2018/2 (Sheldrick, 2015a ▸), SHELXL2018/3 (Sheldrick, 2015b ▸) and PLATON (Spek, 2020 ▸).

Supplementary Material

CCDC reference: 2294939

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

full crystallographic data

Crystal data

C5H5Cl2N2+·C6H4NO3−·H2O	F(000) = 656
Mr = 320.13	Dx = 1.645 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 8.4267 (19) Å	Cell parameters from 3676 reflections
b = 14.084 (3) Å	θ = 2.5–28.8°
c = 10.900 (2) Å	µ = 0.52 mm−1
β = 91.953 (8)°	T = 296 K
V = 1292.9 (5) Å3	Plate, colourless
Z = 4	0.46 × 0.32 × 0.13 mm

Data collection

Agilent Xcalibur, Atlas, Gemini diffractometer	2853 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.038
ω scans	θmax = 28.7°, θmin = 2.4°
Absorption correction: multi-scan	h = −11→11
Tmin = 0.819, Tmax = 0.937	k = −18→18
45801 measured reflections	l = −14→14
3296 independent reflections

Refinement

Refinement on F2	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.033	H-atom parameters constrained
wR(F2) = 0.091	w = 1/[σ2(Fo2) + (0.0465P)2 + 0.3959P] where P = (Fo2 + 2Fc2)/3
S = 1.03	(Δ/σ)max < 0.001
3296 reflections	Δρmax = 0.24 e Å−3
185 parameters	Δρmin = −0.35 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.

Refinement. The water H atoms were located in a difference Fourier map and allowed to refine freely. The remaining H atoms were positioned geometrically (C—H = 0.93 and N—H = 0.86 Å) and were refined using a riding model, with Uiso(H) = 1.2 Ueq(C).

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

	x	y	z	Uiso*/Ueq
Cl1	0.85851 (4)	0.68420 (3)	0.15096 (4)	0.04683 (12)
Cl2	0.89478 (5)	0.30311 (2)	0.10521 (4)	0.04737 (12)
O1	0.42463 (12)	0.67099 (7)	0.27823 (11)	0.0439 (3)
O2	0.61861 (13)	0.71788 (7)	0.40818 (11)	0.0459 (3)
O3	0.82471 (14)	0.60173 (8)	0.48694 (13)	0.0535 (3)
H3	0.780642	0.653220	0.477230	0.080*
N3	0.50360 (13)	0.48436 (8)	0.31752 (10)	0.0321 (2)
N1	1.19792 (14)	0.49866 (8)	0.22147 (11)	0.0371 (3)
H1	1.294531	0.500301	0.249479	0.045*
N2	0.73770 (13)	0.49223 (8)	0.08094 (11)	0.0355 (3)
H2A	0.685153	0.544264	0.072057	0.043*
H2B	0.694906	0.439155	0.059109	0.043*
C10	0.59379 (14)	0.55395 (9)	0.36845 (11)	0.0288 (3)
C11	0.53872 (15)	0.65512 (9)	0.34965 (13)	0.0326 (3)
C3	0.88438 (14)	0.49383 (9)	0.12820 (11)	0.0291 (3)
C4	0.96128 (15)	0.57881 (9)	0.16585 (12)	0.0321 (3)
C6	0.73510 (16)	0.53325 (10)	0.43364 (13)	0.0353 (3)
C2	0.97853 (16)	0.41096 (9)	0.14404 (12)	0.0325 (3)
C5	1.11412 (16)	0.57934 (10)	0.21103 (13)	0.0362 (3)
H5	1.160941	0.636508	0.234961	0.043*
C1	1.13192 (17)	0.41529 (10)	0.18845 (13)	0.0373 (3)
H1A	1.191375	0.359836	0.195919	0.045*
C9	0.55198 (17)	0.39478 (10)	0.32671 (14)	0.0388 (3)
H9	0.488901	0.347163	0.291583	0.047*
C8	0.69351 (18)	0.37002 (10)	0.38699 (15)	0.0428 (3)
H8	0.725723	0.306886	0.390273	0.051*
C7	0.78549 (17)	0.43927 (11)	0.44166 (15)	0.0431 (3)
H7	0.880028	0.423758	0.483433	0.052*
O1W	0.48614 (13)	0.86692 (8)	0.53048 (11)	0.0441 (3)
H1W	0.518086	0.816660	0.495934	0.066*
H2W	0.462944	0.849278	0.602250	0.066*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
Cl1	0.0388 (2)	0.03527 (19)	0.0658 (3)	0.00513 (13)	−0.00686 (17)	−0.01076 (16)
Cl2	0.0497 (2)	0.03070 (18)	0.0608 (3)	−0.00776 (14)	−0.01108 (18)	0.00405 (15)
O1	0.0385 (5)	0.0339 (5)	0.0585 (7)	0.0032 (4)	−0.0120 (5)	0.0042 (5)
O2	0.0429 (6)	0.0320 (5)	0.0621 (7)	−0.0008 (4)	−0.0073 (5)	−0.0116 (5)
O3	0.0416 (6)	0.0449 (6)	0.0723 (8)	−0.0023 (5)	−0.0249 (6)	−0.0072 (6)
N3	0.0294 (5)	0.0297 (5)	0.0371 (6)	0.0000 (4)	−0.0023 (4)	−0.0008 (4)
N1	0.0295 (5)	0.0419 (6)	0.0393 (6)	−0.0021 (5)	−0.0075 (5)	0.0026 (5)
N2	0.0278 (5)	0.0345 (6)	0.0438 (6)	−0.0027 (4)	−0.0051 (5)	−0.0019 (5)
C10	0.0268 (6)	0.0282 (6)	0.0313 (6)	−0.0006 (5)	0.0004 (5)	−0.0009 (5)
C11	0.0294 (6)	0.0290 (6)	0.0397 (7)	0.0010 (5)	0.0023 (5)	−0.0010 (5)
C3	0.0273 (6)	0.0342 (6)	0.0258 (6)	−0.0031 (5)	0.0007 (5)	0.0009 (5)
C4	0.0299 (6)	0.0327 (6)	0.0335 (6)	−0.0009 (5)	−0.0010 (5)	−0.0027 (5)
C6	0.0290 (6)	0.0371 (7)	0.0396 (7)	−0.0004 (5)	−0.0039 (5)	0.0003 (6)
C2	0.0340 (6)	0.0304 (6)	0.0329 (6)	−0.0047 (5)	−0.0028 (5)	0.0039 (5)
C5	0.0323 (6)	0.0387 (7)	0.0374 (7)	−0.0054 (5)	−0.0035 (5)	−0.0036 (6)
C1	0.0357 (7)	0.0363 (7)	0.0396 (7)	0.0008 (5)	−0.0048 (6)	0.0065 (6)
C9	0.0387 (7)	0.0292 (6)	0.0483 (8)	−0.0009 (5)	−0.0021 (6)	−0.0018 (6)
C8	0.0413 (8)	0.0320 (7)	0.0549 (9)	0.0084 (6)	0.0016 (7)	0.0068 (6)
C7	0.0327 (7)	0.0436 (8)	0.0526 (9)	0.0074 (6)	−0.0066 (6)	0.0075 (7)
O1W	0.0418 (6)	0.0358 (5)	0.0542 (7)	0.0069 (4)	−0.0077 (5)	−0.0016 (5)

Geometric parameters (Å, º)

Cl1—C4	1.7233 (14)	C10—C11	1.5103 (18)
Cl2—C2	1.7217 (14)	C3—C4	1.4151 (17)
O1—C11	1.2366 (17)	C3—C2	1.4184 (18)
O2—C11	1.2697 (17)	C4—C5	1.3631 (18)
O3—C6	1.3446 (17)	C6—C7	1.392 (2)
O3—H3	0.8200	C2—C1	1.3661 (19)
N3—C9	1.3287 (18)	C5—H5	0.9300
N3—C10	1.3481 (16)	C1—H1A	0.9300
N1—C5	1.3406 (18)	C9—C8	1.386 (2)
N1—C1	1.3430 (18)	C9—H9	0.9300
N1—H1	0.8600	C8—C7	1.370 (2)
N2—C3	1.3229 (16)	C8—H8	0.9300
N2—H2A	0.8600	C7—H7	0.9300
N2—H2B	0.8600	O1W—H1W	0.8499
C10—C6	1.3965 (18)	O1W—H2W	0.8500
C6—O3—H3	109.5	O3—C6—C10	121.79 (13)
C9—N3—C10	119.47 (12)	C7—C6—C10	118.91 (13)
C5—N1—C1	120.41 (12)	C1—C2—C3	121.66 (12)
C5—N1—H1	119.8	C1—C2—Cl2	120.10 (11)
C1—N1—H1	119.8	C3—C2—Cl2	118.24 (10)
C3—N2—H2A	120.0	N1—C5—C4	120.96 (13)
C3—N2—H2B	120.0	N1—C5—H5	119.5
H2A—N2—H2B	120.0	C4—C5—H5	119.5
N3—C10—C6	121.12 (12)	N1—C1—C2	120.81 (13)
N3—C10—C11	117.62 (11)	N1—C1—H1A	119.6
C6—C10—C11	121.24 (11)	C2—C1—H1A	119.6
O1—C11—O2	125.31 (13)	N3—C9—C8	122.09 (13)
O1—C11—C10	118.99 (12)	N3—C9—H9	119.0
O2—C11—C10	115.68 (12)	C8—C9—H9	119.0
N2—C3—C4	122.67 (12)	C7—C8—C9	119.48 (13)
N2—C3—C2	123.00 (12)	C7—C8—H8	120.3
C4—C3—C2	114.33 (11)	C9—C8—H8	120.3
C5—C4—C3	121.81 (12)	C8—C7—C6	118.88 (13)
C5—C4—Cl1	119.66 (11)	C8—C7—H7	120.6
C3—C4—Cl1	118.52 (10)	C6—C7—H7	120.6
O3—C6—C7	119.29 (12)	H1W—O1W—H2W	104.5
C9—N3—C10—C6	−1.8 (2)	C4—C3—C2—C1	−1.97 (19)
C9—N3—C10—C11	176.65 (12)	N2—C3—C2—Cl2	−2.54 (18)
N3—C10—C11—O1	−7.84 (19)	C4—C3—C2—Cl2	178.22 (10)
C6—C10—C11—O1	170.60 (13)	C1—N1—C5—C4	−0.6 (2)
N3—C10—C11—O2	173.80 (12)	C3—C4—C5—N1	0.0 (2)
C6—C10—C11—O2	−7.76 (19)	Cl1—C4—C5—N1	−178.74 (11)
N2—C3—C4—C5	−178.05 (13)	C5—N1—C1—C2	−0.2 (2)
C2—C3—C4—C5	1.20 (19)	C3—C2—C1—N1	1.5 (2)
N2—C3—C4—Cl1	0.74 (18)	Cl2—C2—C1—N1	−178.65 (11)
C2—C3—C4—Cl1	179.99 (10)	C10—N3—C9—C8	−0.2 (2)
N3—C10—C6—O3	−178.70 (13)	N3—C9—C8—C7	1.6 (2)
C11—C10—C6—O3	2.9 (2)	C9—C8—C7—C6	−0.9 (2)
N3—C10—C6—C7	2.4 (2)	O3—C6—C7—C8	−179.94 (15)
C11—C10—C6—C7	−175.97 (13)	C10—C6—C7—C8	−1.0 (2)
N2—C3—C2—C1	177.27 (13)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···O2	0.82	1.79	2.5155 (17)	147
N1—H1···N3i	0.86	1.90	2.7546 (17)	171
N2—H2A···O1Wii	0.86	2.13	2.9414 (17)	157
N2—H2B···O1Wiii	0.86	2.05	2.8269 (17)	149
O1W—H1W···O2	0.85	1.90	2.7442 (17)	170
O1W—H2W···O1iv	0.85	1.98	2.8181 (18)	170
C5—H5···O1i	0.93	2.31	2.9864 (18)	129
C5—H5···Cl2v	0.93	2.97	3.7363 (16)	141
C7—H7···O3vi	0.93	2.52	3.399 (2)	157

Symmetry codes: (i) x+1, y, z; (ii) x, −y+3/2, z−1/2; (iii) −x+1, y−1/2, −z+1/2; (iv) x, −y+3/2, z+1/2; (v) −x+2, y+1/2, −z+1/2; (vi) −x+2, −y+1, −z+1.

Funding Statement

MH thanks SERB-IRE for financial support (Ref. No. SIR/2022/000011). SJK thanks TANSCHE for financial support (File No. RGP/2019–20/MTWU/HECP-0080).