Low-temperature crystal structure of 4-chloro-1H-pyrazole

The crystal structure of 4-chloro-1H-pyrazole has been determined at 170 K, showing a hydrogen-bonded trimeric mol­ecular assembly that is isostructural to its bromo analogue, 4-bromo-1H-pyrazole.

Abstract

The structure of 4-chloro-1H-pyrazole, C₃H₃ClN₂, at 170 K has ortho­rhom­bic (Pnma) symmetry and is isostructural to its bromo analogue. Data were collected at low temperature since 4-chloro-1H-pyrazole sublimes when subjected to the localized heat produced by X-rays. The structure displays inter­molecular N—H⋯N hydrogen bonding and the packing features a trimeric mol­ecular assembly bis­ected by a mirror plane (m normal to b) running through one chlorine atom, one carbon atom and one N—N bond. The asymmetric unit therefore consists of one and one-half 4-chloro-1H-pyrazole mol­ecules. Thus, the N—H proton is crystallographically disordered over two positions of 50% occupancy each.

Chemical context  

Pyrazoles are a family of five-membered, π-excess aromatic heterocycles with adjacent nitro­gen atoms (Krishnakumar et al., 2011 ▸; Karrouchi et al., 2018 ▸). They serve as scaffolds for numerous pharmaceutically active compounds and agrochemicals as they are stable and amenable to substitution (Naim et al., 2016 ▸). They readily coordinate to metals, forming a large group of complexes where typically pyrazoles are monodentate or bridging bidentate pyrazolido ligands (Pettinari et al., 2010 ▸; Viciano-Chumillas et al., 2010 ▸). In the solid state, pyrazoles form hydrogen-bonded aggregates whose topology depends on the steric bulk of peripheral substituents and the acidity of the N1—H proton and basicity of the N2 atom. For example, 4-bromo-pyrazole and 3-methyl-pyrazole form approximately planar triangular assemblies (Foces-Foces et al., 1999 ▸; Goddard et al., 1999 ▸), 3,5-diphenyl-pyrazole and 3,5-bis­(tri­fluoro­meth­yl)pyrazole form tetra­nuclear assemblies (Raptis et al., 1993 ▸; Alkorta et al., 1999 ▸), while pyrazole forms a one-dimensional polymeric chain (Krebs Larsen et al., 1970 ▸).

Structural commentary  

4-Chloro-1H-pyrazole crystallizes with one and one-half mol­ecules in the asymmetric unit (Z′ = 1.5) as shown in Fig. 1 ▸. The second mol­ecule is bis­ected by a mirror plane normal to b (x, 3/4, z), which runs through C5, Cl2, and the N3—N3ⁱ bond [symmetry code: (i) x,  − y, z]. As a result of this mirror plane, the NH protons are crystallographically disordered over two positions. As with the bromo analogue (Foces-Foces et al., 1999 ▸), 4-chloro-1H-pyrazole crystallizes in the Pnma space group and forms trimeric units (Fig. 2 ▸).

Figure 1.

Perspective view of the asymmetric unit of 4-chloro-1H-pyrazole. Displacement ellipsoids are shown at 50% probability and half the disordered protons are removed for clarity.

Figure 2.

Packing of 4-chloro-1H-pyrazole, viewed parallel to the c axis, showing the formation of trimeric units. Half the disordered protons have been removed for clarity.

Also disordered in this structure are the C and N atoms. Without disorder, pyrazoles have one ‘pyrrole-like’ side and one ‘pyridine-like’ side, as was discussed in the neutron diffraction study of 1H-pyrazole (Krebs Larsen et al., 1970 ▸). The C—N, C—C, and C—H bonds on either side of the mol­ecule are crystallographically distinct and resemble either pyrrole or pyridine. However, due to the disorder of the N—H protons in the current structure, only average positions of the C and N atoms have been obtained. Therefore, the C—N, C—C, and C—H bonds on either side of the mol­ecule are indistinguishable. This is most apparent in the C—N bonds. In the current structure, the C—N bonds are 1.335 (2), 1.334 (2), and 1.334 (2) Å for C1—N1, C3—N2, and C4 —N3, respectively. In the 1H-pyrazole structure, the C—N bond lengths are 1.356 and 1.350 Å for the ‘pyrrole-like’ side and the ‘pyridine-like’ side, respectively. The C—N bond lengths of the current structure are in agreement with those previously reported in the 4-bromo analogue with C—N bond lengths of 1.343 (10), 1.331 (10), and 1.327 (10) Å (Foces-Foces et al., 1999 ▸). Furthermore, these bond lengths are also in agreement with the 4-chloro-1H-pyrazol-2-ium chloride salt, which exhibits C—N bond lengths of 1.334 (2) and 1.331 (2) Å (Farmiloe et al., 2019 ▸). The N—N bonds of the present mol­ecule are 1.346 (2) and 1.345 (3) Å, for N1—N2 and N3—N3ⁱ, respectively, and are similar to those of 4-methyl-1H-pyrazole (which is refined without proton disorder in Pca2₁) with N—N bond lengths of 1.343 (2), 1.344 (2), and 1.349 (2) Å (Goddard et al., 1999 ▸). However, the N—N bonds of the 4-bromo analogue are slightly shorter at 1.335 (9) Å each (Foces-Foces et al., 1999 ▸).

Supra­molecular features  

Pyrazoles are known to crystallize in a variety of hydrogen-bonded motifs – dimers, trimers, tetra­mers, and catemers (Infantes & Motherwell, 2004 ▸; Pérez & Riera, 2009 ▸). The current structure of 4-chloro-1H-pyrazole crystallizes in trimeric units, as do the 4-bromo and 4-methyl analogues. The inter­molecular N1⋯N1ⁱ, N2⋯N3ⁱⁱ, and N3⋯N2ⁱⁱ [symmetry codes: (i) x, −y + , z; (ii) −x + 1, −y + 1, −z] are 2.885 (3), 2.858 (2), and 2.858 (2), respectively, as shown in Table 1 ▸. These values are in agreement with other inter­molecular hydrogen-bond inter­actions of pyrazoles. Just as with the 4-bromo derivative, 4-chloro-1H-pyrazole packs in a herringbone arrangement when viewed down the b axis (Fig. 3 ▸). The current structure exhibits no π-stacking inter­actions.

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯N1i	0.88	2.03	2.885 (3)	165
N2—H2⋯N3ii	0.88	1.99	2.8582 (19)	169
N3—H3A⋯N2ii	0.88	1.99	2.8582 (19)	169

Symmetry codes: (i) x, -y+{\script{3\over 2}}, z; (ii) -x+1, -y+1, -z.

Figure 3.

Packing of 4-chloro-1H-pyrazole, viewed parallel to the b axis, showing the formation of a herringbone motif.

Synthesis and crystallization  

4-Chloro-1H-pyrazole was purchased commercially and crystals were grown from the slow evaporation of a methyl­ene chloride solution.

Refinement  

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. The data were collected at 170 K on a Bruker D8 CMOS diffractometer equipped with a Photon II detector. CrysAlis PRO was used for scaling and absorption correction. All C—H protons were refined freely while the N—H protons were fixed using an AFIX command and constrained to half occupancy due to the proton disorder.

Table 2. Experimental details.

Crystal data
Chemical formula	C3H3ClN2
M r	102.52
Crystal system, space group	Orthorhombic, P n m a
Temperature (K)	170
a, b, c (Å)	14.9122 (10), 17.6410 (9), 4.9878 (3)
V (Å3)	1312.13 (14)
Z	12
Radiation type	Mo Kα
μ (mm−1)	0.69
Crystal size (mm)	0.29 × 0.14 × 0.08
Data collection
Diffractometer	Bruker D8 CMOS
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2019 ▸)
Tmin, Tmax	0.760, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	25891, 1798, 1481
R int	0.043
(sin θ/λ)max (Å−1)	0.682
Refinement
R[F2 > 2σ(F 2)], wR(F 2), S	0.033, 0.092, 1.06
No. of reflections	1798
No. of parameters	97
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	0.27, −0.26

Computer programs: APEX3 (Brker, 2020 ▸), CrysAlis PRO (Rigaku OD, 2019 ▸), SHELXS (Sheldrick, 2008 ▸), SHELXL2018/3 (Sheldrick, 2015 ▸), and OLEX2 (Dolomanov et al., 2009 ▸).

To remove the proton disorder, an attempt was made to refine the mol­ecule in the non-centrosymmetric Pn2₁ a space group, which is also consistent with the systematic absences. In Pn2₁ a, hydrogen atoms were refined in both possible positions – on the odd-labeled N atoms or on the even-labeled N atoms. However, as Foces-Foces et al. (1999 ▸) found with the 4-bromo-analogue, refinement in the lower symmetry space group did not improve the refinement. For the trial Pn2₁ a structure with protons on the even-labeled N atoms, the R ₁ and wR ₂ values slightly increased to 3.67% and 9.67%, respectively, and the shifting of the carbon atoms could not be consolidated. For the trial Pn2₁ a structure with protons on the odd-labeled N atoms, the R ₁ and wR ₂ values increased even more to 3.71% and 9.69%, respectively, and the coordinates of the non-proton­ated N atoms could not converge. Therefore, the best refined model was chosen to be in the centrosymmetric Pnma space group with NH protons disordered over two positions.

Supplementary Material

CCDC reference: 2103822

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

supplementary crystallographic information

Crystal data

C3H3ClN2	Dx = 1.557 Mg m−3
Mr = 102.52	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pnma	Cell parameters from 6701 reflections
a = 14.9122 (10) Å	θ = 2.3–30.2°
b = 17.6410 (9) Å	µ = 0.69 mm−1
c = 4.9878 (3) Å	T = 170 K
V = 1312.13 (14) Å3	Rect. Prism, clear colourless
Z = 12	0.28 × 0.14 × 0.08 mm
F(000) = 624

Data collection

Bruker D8 CMOS diffractometer	1481 reflections with I > 2σ(I)
ω scans	Rint = 0.043
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2019)	θmax = 29.0°, θmin = 2.3°
Tmin = 0.760, Tmax = 1.000	h = −20→20
25891 measured reflections	k = −23→23
1798 independent reflections	l = −6→6

Refinement

Refinement on F2	Primary atom site location: dual
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.033	Hydrogen site location: mixed
wR(F2) = 0.092	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	w = 1/[σ2(Fo2) + (0.0418P)2 + 0.5547P] where P = (Fo2 + 2Fc2)/3
1798 reflections	(Δ/σ)max = 0.001
97 parameters	Δρmax = 0.27 e Å−3
0 restraints	Δρmin = −0.26 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	Occ. (<1)
Cl1	0.65912 (3)	0.45830 (2)	0.73672 (9)	0.04510 (15)
C1	0.66638 (11)	0.61504 (9)	0.6893 (4)	0.0375 (3)
C2	0.63595 (10)	0.54554 (8)	0.6008 (3)	0.0330 (3)
N1	0.63427 (9)	0.66822 (7)	0.5248 (3)	0.0390 (3)
H1A	0.644141	0.717242	0.538844	0.047*	0.5
C3	0.58468 (11)	0.56001 (10)	0.3776 (3)	0.0389 (4)
N2	0.58435 (9)	0.63462 (8)	0.3340 (3)	0.0405 (3)
H2	0.556236	0.657939	0.202649	0.049*	0.5
Cl2	0.70256 (4)	0.250000	0.59928 (11)	0.03892 (16)
C5	0.62343 (15)	0.250000	0.3495 (4)	0.0326 (4)
N3	0.52730 (9)	0.28813 (7)	0.0432 (3)	0.0395 (3)
H3A	0.494432	0.317237	−0.061095	0.047*	0.5
C4	0.58543 (12)	0.31226 (10)	0.2276 (3)	0.0396 (4)
H3	0.5571 (14)	0.5266 (11)	0.253 (4)	0.043 (5)*
H1	0.7031 (12)	0.6279 (11)	0.839 (4)	0.040 (5)*
H4	0.5962 (12)	0.3661 (12)	0.261 (4)	0.051 (6)*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
Cl1	0.0525 (3)	0.0303 (2)	0.0525 (3)	0.00392 (16)	−0.00952 (19)	0.00342 (16)
C1	0.0379 (8)	0.0335 (8)	0.0412 (8)	−0.0017 (6)	−0.0027 (7)	−0.0020 (7)
C2	0.0340 (7)	0.0281 (7)	0.0371 (8)	0.0020 (6)	0.0008 (6)	−0.0006 (6)
N1	0.0408 (7)	0.0330 (6)	0.0431 (7)	−0.0007 (6)	0.0017 (6)	−0.0012 (6)
C3	0.0429 (9)	0.0345 (8)	0.0391 (8)	0.0028 (6)	−0.0053 (7)	−0.0032 (7)
N2	0.0450 (8)	0.0383 (7)	0.0384 (7)	0.0053 (6)	−0.0022 (6)	0.0028 (6)
Cl2	0.0416 (3)	0.0395 (3)	0.0356 (3)	0.000	−0.0053 (2)	0.000
C5	0.0359 (11)	0.0311 (10)	0.0309 (10)	0.000	−0.0011 (9)	0.000
N3	0.0432 (7)	0.0370 (7)	0.0384 (7)	0.0068 (6)	−0.0036 (6)	−0.0001 (6)
C4	0.0483 (10)	0.0306 (8)	0.0401 (8)	0.0052 (7)	−0.0035 (7)	−0.0040 (7)

Geometric parameters (Å, º)

Cl1—C2	1.7169 (15)	N2—H2	0.8800
C1—C2	1.380 (2)	Cl2—C5	1.716 (2)
C1—N1	1.335 (2)	C5—C4	1.377 (2)
C1—H1	0.952 (19)	C5—C4i	1.377 (2)
C2—C3	1.374 (2)	N3—N3i	1.345 (3)
N1—H1A	0.8800	N3—H3A	0.8800
N1—N2	1.3457 (19)	N3—C4	1.334 (2)
C3—N2	1.334 (2)	C4—H4	0.98 (2)
C3—H3	0.951 (19)
C2—C1—H1	130.6 (11)	N1—N2—H2	125.7
N1—C1—C2	108.04 (14)	C3—N2—N1	108.50 (14)
N1—C1—H1	121.4 (11)	C3—N2—H2	125.7
C1—C2—Cl1	127.15 (13)	C4i—C5—Cl2	127.11 (10)
C3—C2—Cl1	126.74 (12)	C4—C5—Cl2	127.11 (10)
C3—C2—C1	106.09 (14)	C4—C5—C4i	105.8 (2)
C1—N1—H1A	125.6	N3i—N3—H3A	125.7
C1—N1—N2	108.87 (13)	C4—N3—N3i	108.61 (9)
N2—N1—H1A	125.6	C4—N3—H3A	125.7
C2—C3—H3	131.0 (12)	C5—C4—H4	129.2 (11)
N2—C3—C2	108.49 (15)	N3—C4—C5	108.50 (15)
N2—C3—H3	120.2 (12)	N3—C4—H4	122.3 (11)
Cl1—C2—C3—N2	−178.73 (13)	N1—C1—C2—Cl1	178.76 (12)
C1—C2—C3—N2	0.03 (19)	N1—C1—C2—C3	0.01 (18)
C1—N1—N2—C3	0.07 (18)	Cl2—C5—C4—N3	179.74 (15)
C2—C1—N1—N2	−0.05 (18)	N3i—N3—C4—C5	−0.20 (16)
C2—C3—N2—N1	−0.06 (19)	C4i—C5—C4—N3	0.3 (3)

Symmetry code: (i) x, −y+1/2, z.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···N1ii	0.88	2.03	2.885 (3)	165
N2—H2···N3iii	0.88	1.99	2.8582 (19)	169
N3—H3A···N2iii	0.88	1.99	2.8582 (19)	169

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

Funding Statement

This work was funded by U.S. Nuclear Regulatory Commission grant NRC-HQ-84-14-G-0040 to Kelly Rue.