Crystallographic and spectroscopic characterization of 5-chloro-pyridine-2,3-di-amine.

The two ortho-amino groups of the title compound, C5H6ClN3, twist out of the plane of the mol-ecule to minimize intra-molecular inter-action between the amino hydrogen atoms. In the crystal, the amino groups and the pyridine N atom engage in inter-molecular hydrogen bonding. The mol-ecules pack into spiral hydrogen-bonded columns with offset face-to-face π-stacking.

Chemical context

The title compound, 5-chloro­pyridine-2,3-di­amine, is a tri­sub­stituted pyridine featuring ortho-amino groups and a chlorine atom. While all of the sixteen isomers of 5-chloro­pyridine-2,3-di­amine are commercially available, none of their crystal structures have been reported in the literature. 5-Chloro­pyridine-2,3-di­amine may be produced by nitrating 2-amino-5-chloro­pyridine with nitric acid to give 2-amino-3-nitro-5-chloro­pyridine, which is then reduced with sodium di­thio­nite (Israel & Day, 1959 ▸). The reduction may also be accomplished with hydrogen gas and Pd/C (Xie et al., 2016 ▸). 5-Chloro­pyridine-2,3-di­amine has proven useful as a reagent in complex syntheses, such as in the synthesis of aldose reductase inhibitors with anti­oxidant activity (Han et al., 2016 ▸), the regioselective functionalization of imidazo­pyridines via alkenylation catalyzed by a Pd/Cu catalyst (Baladi et al., 2016 ▸), the preparation of amino acid oxidase inhibitors (Xie et al., 2016 ▸), the preparation of β-glucuronidase inhibitors (Taha et al., 2016 ▸), the preparation of imidazo­pyridine derivatives with activity against MCF-7 breast adenocarcinoma (Püsküllü et al., 2015 ▸) and the preparation of di­hydroxy­arene-substituted benzimidazoles, quinazolines and larger rings via cyclo­condensation of di­amines (Los et al., 2012 ▸).

Structural commentary

The mol­ecular structure of the title compound 5-chloro­pyridine-2,3-di­amine (Fig. 1 ▸) shows that the mol­ecule is nearly planar with r.m.s deviation from the mean plane of all non-hydrogen atoms of 0.013 (3) Å. The amino groups ortho and meta to the pyridine nitro­gen atom twist out of the plane of the mol­ecule in such a way as to minimize contact with one another, with NH2 plane to mol­ecular plane angles of 45 (3) and 34 (3)° for N2 and N3, respectively. It is notable that the achiral title compound crystallizes in a non-enanti­ogenic (Söhncke) space group, although not a polar space group.

Figure 1

A view of 5-chloro­pyridine-2,3-di­amine (I) with the atom-numbering scheme. Displacement ellipsoids are shown at the 50% probability level.

Supra­molecular features

Notable inter­molecular inter­actions observed in the structure of 5-chloro­pyridine-2,3-di­amine (I) include Namine—H⋯Npyr and Namine—H⋯Namine hydrogen bonding inter­actions and offset face-to-face π-stacking. The mol­ecules connect into a one-dimensional strip running parallel to the crystallographic b axis (Fig. 2 ▸) with long N3amine—H21⋯N2ii amine [symmetry code (ii) −x + 2, y − , −z + ] and N3amine—H22⋯N1iii pyr [symmetry code (iii) −x + 2, y + , −z + ] hydrogen bonding inter­actions with donor–acceptor distances of 3.250 (4) and 3.075 (4) Å, respectively (Table 1 ▸). A third Namine—H⋯Npyr hydrogen-bonding contact and offset face-to-face π-stacking can be seen to extend along the crystallographic a axis (Fig. 3 ▸), acting to link the one-dimensional strips into two-dimensional sheets. The N2amine—H12⋯N1pyr i [symmetry code (i) −x + 1, y + , −z + ] contact exhibits a donor–acceptor distance 3.264 (3) Å. The π-stacking is characterized by a centroid-to-centroid distance of 3.756 (1) Å, plane-to-plane distances of 3.414 (2) Å and a ring offset of 1.568 (3) Å (Hunter & Saunders, 1990 ▸; Lueckheide et al., 2013 ▸). Alternatively, the three hydrogen-bonding contacts and the π-stacking taken together can be seen to form a spiral of 5-chloro­pyridine-2,3-di­amine (I) mol­ecules extending along the a-axis direction (Fig. 4 ▸).

Figure 2

A view of the inter­molecular N3amine—H21⋯N2ii amine and N3amine—H22⋯N1iii pyr one-dimensional hydrogen bonding in 5-chloro­pyridine-2,3-di­amine (I). [Symmetry codes: (ii) −x + 2, y − , −z + ; (iii) −x + 2, y + , −z + .]

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H12⋯N1i	0.86 (2)	2.48 (3)	3.264 (3)	151 (3)
N3—H21⋯N2ii	0.89 (2)	2.38 (2)	3.250 (4)	166 (3)
N3—H22⋯N1iii	0.90 (2)	2.19 (2)	3.075 (4)	167 (3)

Symmetry codes: (i) ; (ii) ; (iii) .

Figure 3

A view of the packing in 5-chloro­pyridine-2,3-di­amine (I) indicating hydrogen bonding connecting the one-dimensional strips into two-dimensional sheets along with offset face-to-face π-stacking.

Figure 4

A view of the spiral hydrogen-bonded chain in 5-chloro­pyridine-2,3-di­amine (I) highlighting the N2amine—H12⋯N1i pyr contact. [Symmetry code: (i) −x + 1, y + , −z + .]

Database survey

The Cambridge Structural Database (Groom et al., 2016 ▸) contains about fifty structurally similar compounds to 5-chloro­pyridine-2,3-di­n class="Chemical">amine (I), with 2-amino-5-chloro­pyridine (AMCLPY12) (Pourayoubi et al., 2007 ▸) and 2-amino-3-chloro­pyridine (URAXER) (Hu et al., 2011 ▸) being the most chemically and structurally similar. The C—Cl bond length in the title compound, with distance 1.748 (3) Å, is comparable to those in 2-amino-5-chloro­pyridine (AMCLPY12) and 2-amino-3-chloro­pyridine (URAXER), with distances 1.7404 (14) and 1.735 (3) Å, respectively. The C—Namine distances in the title compound, 1.406 (4) and 1.385 (4) Å, however, are somewhat longer than in 2-amino-5-chloro­pyridine (AMCLPY12) [1.3602 (19) Å] and 2-amino-3-chloro­pyridine (URAXER) [1.351 (4) Å]. 2-amino-5-chloro­pyridine (AMCLPY12), which does not have the meta-NH2 substitution of the title compound, packs in a herringbone formation featuring centrosymmetric head-to-tail Namine—H⋯Npyr hydrogen bonding dimers with donor–acceptor distance 3.031 (2) Å. 2-Amino-3-chloro­pyridine (URAXER), has a meta-Cl substitution in place of the meta-NH2 in the title compound. Like 2-amino-5-chloro­pyridine (AMCLPY12), 2-amino-3-chloro­pyridine (URAXER) features a herringbone packing with centrosymmetric head-to-tail Namine—H⋯Npyr hydrogen-bonded dimer with a similar donor–acceptor distance of 3.051 (5) Å. The similar hydrogen-bonding motif in these two related compounds differs from the title compound, which does not exhibit centrosymmetric hydrogen-bonding dimerization. 2-Amino-3-chloro­pyridine (URAXER) also has short inter­molecular Cl⋯Cl inter­actions of 3.278 (3) Å, where no such short halogen–halogen contact was observed in 2-amino-5-chloro­pyridine (AMCLPY12) or the title compound.

Synthesis and crystallization

5-Chloro­pyridine-2,3-di­amine (97%) was purchased from Aldrich Chemical Company, USA. A single crystal suitable for analysis was selected from the purchased sample and used as received.

Analytical data

1H NMR (Bruker Avance 400 MHz, DMSO d 6): δ 4.99 (br s, 2 H, NH 2), 5.55 (br s, 2 H, NH 2), 6.69 (d, 1 H, J = 2.3 Hz, Car­yl H), 7.21 (d, 1 H, J = 2.3 Hz, Car­yl H). 13C NMR (13C{1H}, 100.6 MHz, DMSO d 6): δ 116.58 (C ar­ylH), 118.38 (C ar­yl), 131.32 (C ar­yl), 131.66 (C ar­ylH), 147.10 (C ar­yl). IR (Thermo Nicolet iS50, ATR, cm−1): 3392 (m, N—H str), 3309 (m, N—H str), 3172 (m, aryl C—H str), 1637 (s, aryl C=C str), 1572 (m), 1472 (s), 1421 (m), 1347 (w), 1307 (w), 1280 (w), 1240 (m), 1068 (m), 939 (w), 887 (w), 861 (m), 792 (m), 770 (m), 680 (s), 630 (s), 568 (s), 490 (s), 449 (s). GC/MS (Hewlett-Packard MS 5975/GC 7890): M + = 143 (calc. exact mass = 143.03).

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. All non-hydrogen atoms were refined anisotropically. n class="Chemical">Hydrogen atoms on carbon were included in calculated positions and refined using a riding model with C—H = 0.95 Å and U iso(H) = 1.2U eq(C) of the aryl C-atoms. The positions of the four amino hydrogen atoms were found in the difference map and they were refined semi-freely using a distance restraint d(N—H) = 0.91 Å, and U iso(H) = 1.2U eq(N).

Table 2

Experimental details

Crystal data
Chemical formula	C5H6ClN3
M r	143.58
Crystal system, space group	Orthorhombic, P212121
Temperature (K)	125
a, b, c (Å)	3.7565 (8), 8.7002 (17), 18.350 (4)
V (Å3)	599.7 (2)
Z	4
Radiation type	Mo Kα
μ (mm−1)	0.53
Crystal size (mm)	0.10 × 0.05 × 0.04
Data collection
Diffractometer	Bruker APEXII CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2013 ▸)
T min, T max	0.75, 0.98
No. of measured, independent and observed [I > 2σ(I)] reflections	14989, 1845, 1477
R int	0.087
(sin θ/λ)max (Å−1)	0.714
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.041, 0.084, 1.07
No. of reflections	1845
No. of parameters	94
No. of restraints	4
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	0.37, −0.38
Absolute structure	Flack x determined using 511 quotients [(I +)−(I −)]/[(I +)+(I −)] (Parsons et al., 2013 ▸)
Absolute structure parameter	0.01 (6)

Computer programs: APEX2 and SAINT (Bruker, 2013 ▸), SHELXT2014 (Sheldrick, 2015a ▸), SHELXL2014 (Sheldrick, 2015b ▸), SHELXTL2014 (Sheldrick, 2008 ▸), OLEX2 (Dolomanov et al., 2009 ▸) and Mercury (Macrae et al., 2008 ▸).

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2056989017010489/fy2122sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989017010489/fy2122Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989017010489/fy2122Isup3.cml

CCDC reference: 1562267

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

C5H6ClN3	Dx = 1.590 Mg m−3
Mr = 143.58	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121	Cell parameters from 4306 reflections
a = 3.7565 (8) Å	θ = 2.6–29.7°
b = 8.7002 (17) Å	µ = 0.53 mm−1
c = 18.350 (4) Å	T = 125 K
V = 599.7 (2) Å3	Plate, colourless
Z = 4	0.10 × 0.05 × 0.04 mm
F(000) = 296

Bruker APEXII CCD diffractometer	1845 independent reflections
Radiation source: fine-focus sealed tube	1477 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.087
Detector resolution: 8.3333 pixels mm-1	θmax = 30.5°, θmin = 2.2°
φ and ω scans	h = −5→5
Absorption correction: multi-scan (SADABS; Bruker, 2013)	k = −12→12
Tmin = 0.75, Tmax = 0.98	l = −26→26
14989 measured reflections

Refinement on F2	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.041	w = 1/[σ2(Fo2) + (0.0308P)2 + 0.2158P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.084	(Δ/σ)max < 0.001
S = 1.07	Δρmax = 0.37 e Å−3
1845 reflections	Δρmin = −0.38 e Å−3
94 parameters	Absolute structure: Flack x determined using 511 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
4 restraints	Absolute structure parameter: 0.01 (6)

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.

	x	y	z	Uiso*/Ueq
Cl1	0.5035 (2)	0.46707 (8)	0.47194 (3)	0.01872 (16)
N1	0.8538 (6)	0.4647 (3)	0.67658 (12)	0.0148 (5)
N2	0.5894 (7)	0.8717 (3)	0.67694 (14)	0.0153 (5)
H11	0.464 (9)	0.928 (3)	0.6466 (14)	0.018*
H12	0.530 (10)	0.872 (3)	0.7224 (12)	0.018*
N3	0.8976 (7)	0.6490 (3)	0.76777 (13)	0.0154 (5)
H21	1.032 (9)	0.580 (3)	0.7905 (15)	0.018*
H22	0.955 (10)	0.748 (3)	0.7772 (16)	0.018*
C1	0.7608 (8)	0.4231 (3)	0.60820 (16)	0.0157 (6)
H1	0.7977	0.3199	0.5931	0.019*
C2	0.6148 (7)	0.5258 (4)	0.56011 (14)	0.0138 (5)
C3	0.5497 (7)	0.6759 (3)	0.58152 (14)	0.0121 (6)
H3	0.445	0.747	0.5486	0.015*
C4	0.6388 (7)	0.7209 (3)	0.65122 (15)	0.0122 (6)
C5	0.8035 (7)	0.6100 (3)	0.69716 (15)	0.0125 (6)

	U11	U22	U33	U12	U13	U23
Cl1	0.0204 (3)	0.0220 (3)	0.0138 (3)	−0.0021 (4)	−0.0034 (3)	−0.0035 (3)
N1	0.0154 (11)	0.0144 (11)	0.0145 (11)	0.0014 (11)	−0.0007 (9)	−0.0001 (11)
N2	0.0182 (14)	0.0137 (12)	0.0140 (11)	0.0036 (9)	−0.0003 (9)	0.0000 (9)
N3	0.0162 (14)	0.0152 (12)	0.0148 (11)	−0.0009 (10)	−0.0036 (9)	0.0004 (10)
C1	0.0176 (15)	0.0126 (14)	0.0171 (14)	0.0008 (11)	0.0014 (12)	−0.0019 (11)
C2	0.0101 (12)	0.0202 (13)	0.0112 (11)	−0.0036 (12)	0.0002 (9)	−0.0016 (12)
C3	0.0061 (14)	0.0157 (12)	0.0146 (12)	−0.0022 (10)	0.0009 (10)	0.0040 (10)
C4	0.0064 (12)	0.0142 (14)	0.0160 (14)	−0.0003 (10)	0.0026 (11)	0.0004 (11)
C5	0.0066 (13)	0.0184 (15)	0.0125 (13)	−0.0017 (11)	0.0021 (10)	0.0011 (11)

Cl1—C2	1.748 (3)	N3—H22	0.90 (2)
N1—C5	1.333 (4)	C1—C2	1.371 (4)
N1—C1	1.352 (4)	C1—H1	0.95
N2—C4	1.406 (4)	C2—C3	1.385 (4)
N2—H11	0.88 (2)	C3—C4	1.379 (4)
N2—H12	0.86 (2)	C3—H3	0.95
N3—C5	1.385 (4)	C4—C5	1.423 (4)
N3—H21	0.89 (2)
C5—N1—C1	118.7 (3)	C1—C2—Cl1	120.1 (2)
C4—N2—H11	112 (2)	C3—C2—Cl1	119.7 (2)
C4—N2—H12	111 (2)	C4—C3—C2	119.2 (3)
H11—N2—H12	118 (3)	C4—C3—H3	120.4
C5—N3—H21	115 (2)	C2—C3—H3	120.4
C5—N3—H22	118 (2)	C3—C4—N2	123.0 (3)
H21—N3—H22	114 (3)	C3—C4—C5	117.5 (3)
N1—C1—C2	121.8 (3)	N2—C4—C5	119.4 (3)
N1—C1—H1	119.1	N1—C5—N3	117.5 (3)
C2—C1—H1	119.1	N1—C5—C4	122.5 (2)
C1—C2—C3	120.2 (3)	N3—C5—C4	119.9 (3)
C5—N1—C1—C2	−0.5 (4)	C1—N1—C5—N3	179.3 (2)
N1—C1—C2—C3	−1.7 (4)	C1—N1—C5—C4	3.3 (4)
N1—C1—C2—Cl1	179.3 (2)	C3—C4—C5—N1	−4.0 (4)
C1—C2—C3—C4	1.0 (4)	N2—C4—C5—N1	179.0 (3)
Cl1—C2—C3—C4	−180.0 (2)	C3—C4—C5—N3	−179.8 (3)
C2—C3—C4—N2	178.5 (3)	N2—C4—C5—N3	3.2 (4)
C2—C3—C4—C5	1.7 (4)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H12···N1i	0.86 (2)	2.48 (3)	3.264 (3)	151 (3)
N3—H21···N2ii	0.89 (2)	2.38 (2)	3.250 (4)	166 (3)
N3—H22···N1iii	0.90 (2)	2.19 (2)	3.075 (4)	167 (3)