Pyrazine-2(1H)-thione

Olszewski, A.; Wzgarda-Raj, K.

doi:10.1107/S2414314621011020

organic compounds

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ISSN: 2414-3146

Volume 6| Part 10| October 2021| x211102

https://doi.org/10.1107/S2414314621011020

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Pyrazine-2(1H)-thione

Adrian Olszewski ^a and Kinga Wzgarda-Raj ^a ^*

^aDepartment of Physical Chemistry, Faculty of Chemistry, University of Lodz, Pomorska 163/165, 90-236 Lodz, Poland
^*Correspondence e-mail: kinga.raj@chemia.uni.lodz.pl

Edited by G. Diaz de Delgado, Universidad de Los Andes, Venezuela (Received 22 September 2021; accepted 21 October 2021; online 29 October 2021)

The title compound, C₄H₄N₂S, was obtained by the reduction of 2-mercaptopyrazine (during its crystallization with 2-mercaptopyrazine and isonicotinic acid N-oxide in ethanol solution. It crystallizes in the monoclinic space group P2₁/m. In the crystal, the molecules are linked by N—H⋯N and C—H⋯S hydrogen bonds.

Keywords: crystal structure; 2-mercaptopyrazine; hydrogen bonds; Hirshfeld surface analysis.

CCDC reference: 2117037

Structure description

Pyrazine is an aromatic six-membered hetrocyclic that contains two nitrogen atoms in positions 1 and 4. As a result, pyrazine has weaker basic properties than pyridine, pyridazine and pyrimidine. Pyrazine derivatives play an important role in chemotherapy (Wu et al., 2012 ; Polshettiwar & Varma 2008 ; Goya et al., 1997 ). Its derivatives possess diverse biological activities such as antidiabetic, diuretic (Pranab et al., 2011 ), anti-inflammatory (Chandrakant & Naresh, 2004 ), antimicrobial (Mallesha & Mohana 2011 ), analgesic (Doležal et al., 2007 ) and anticancer (Kayagil & Demirayak, 2011 ). In addition, 2-mercaptopyrinosine derivatives are known to be cancer inhibitors (Mallesha & Mohana, 2011; Bonde & Gaikwad, 2004).

The title compound pyrazine-2(1H)-thione (I) was obtained as a yellow solid by reduction of 2-mercaptopyrazine (II) during its crystallization with 2-mercaptopyrazine (II) and isonicotinic acid N-oxide (III) in ethanol solution (Fig. 1). Pyrazine-2(1H)-thione crystallizes in the monoclinic space group P2₁/m. The atomic labelling scheme is shown in Fig. 2. In pyrazine-2(1H)-thione, being a reduced form of (II), there is one hydrogen atom at atom N1.

Figure 1
. Molecular formulae of pyrazine-2(1H)-thione (I), 2-mercaptopyrazine (II) and isonicotinic acid N-oxide (III).

Figure 2
The molecular structure of pyrazine-2(1H)-thione, showing the atom-labelling scheme and displacement ellipsoids at the 50% probability level.

The C—C bond lengths are within the expected values known for aromatic systems. The N1—C2 and N1—C6 bond lengths [1.354 (3) and 1.355 (3) Å, respectively] are longer than those for N4—C3 and N4—C5 [1.299 (3) Å and 1.366 (3) Å)], respectively. This is the result of the protonation of the N1 atom. The C2—S2 bond length [1.671 (2) Å] is comparable within the 3σ criterion. All of the angles have usual values.

The crystal packing of pyrazine-2(1H)-thione is determined by hydrogen bonds of the N—H⋯N and C—H⋯S type (Table 1). Firstly, N1—H1⋯N4 hydrogen bonds [C⋯S = 2.893 (2) Å] between neighbouring molecules form a chain. As a result, the molecules are ordered along the [100] direction. This parallel arrangement is additionally stabilized by further interactions between adjacent molecules [C3—H3⋯S2 = 3.716 (2) Å, C5—H5⋯S2 = 3.797 (3) Å and C6—H6⋯S2 = 3.775 (3) Å], as shown in Fig. 3.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C5—H5⋯S2ⁱ	0.86 (3)	2.94 (3)	3.797 (3)	171 (3)
C6—H6⋯S2ⁱⁱ	0.90 (3)	2.88 (3)	3.775 (2)	173 (2)
C3—H3⋯S2ⁱⁱⁱ	0.99 (3)	2.98 (3)	3.716 (2)	132 (2)
N1—H1⋯N4^iv	0.85 (4)	2.04 (4)	2.893 (3)	178 (3)
C5—H5⋯S2ⁱ	0.86 (3)	2.94 (3)	3.797 (3)	171 (3)
C6—H6⋯S2ⁱⁱ	0.90 (3)	2.88 (3)	3.775 (2)	173 (2)
C3—H3⋯S2ⁱⁱⁱ	0.99 (3)	2.98 (3)	3.716 (2)	132 (2)
N1—H1⋯N4^iv	0.85 (4)	2.04 (4)	2.893 (3)	178 (3)
Symmetry codes: (i) ; (ii) ; (iii) ; (iv) x+1, y, z.

Figure 3
N–H⋯N and C—H⋯S hydrogen bonds between adjacent pyrazine-2(1H)-thione molecules.

Molecular Hirshfeld surface (Spackman & Jayatilaka, 2009 ) and fingerprint plots (Spackman & McKinnon, 2002 ), were generated with Crystal Explorer 3.1 (Wolff et al., 2012 ) using the automatic procedures implemented in the program. The surfaces are mapped with a normalized contact distance (d_norm), with values ranging from −0.58 to 1.05 a.u. Graphical representations of the Hirshfeld fingerprint plots for selected types of intermolecular interactions are presented in Fig. 4. The C—H⋯S and N—H⋯N hydrogen bonds make major contribution to the overall Hirshfeld surface with 36.8% and 13.8% contributions, respectively. In addition, H⋯H (24.8%) and H⋯C (11.7%) contacts make a significant contribution to the crystal packing.

Figure 4
The molecular Hirshfeld surfaces of pyrazine-2(1H)-thione mapped with d_norm. Red areas represent intermolecular contacts of distances shorter than the van der Waals separation.

A search of the Cambridge Structural Database (CSD version 5.41, November 2019; Groom et al., 2016) for 2-mercaptopyrazine with no disorder, no other errors and only organic compounds yielded 79 structures. However, the structure of this compound and its oxidised form were not found.

Synthesis and crystallization

Crystals suitable for X-ray measurements were obtained from commercially available reagents (Aldrich Chemical Co.) which were used without further purification. 0.5 mmol of 2-mercaptopyrazine (II) was mixed with 0.5 mmol of isonicotinic acid N-oxide (III) and dissolved in ethanol (4 ml). The obtained solution was kept at room temperature. Crystals (yellow plates) for X-ray diffraction were obtained after slow evaporation of the solvent within 2 weeks.

Refinement

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

Table 2
Experimental details

Crystal data
Chemical formula	C₄H₄N₂S
M_r	112.15
Crystal system, space group	Monoclinic, P2₁/m
Temperature (K)	150
a, b, c (Å)	5.6113 (3), 6.4370 (6), 7.0923 (4)
β (°)	100.325 (6)
V (Å³)	252.03 (3)
Z	2
Radiation type	Mo Kα
μ (mm⁻¹)	0.49
Crystal size (mm)	0.18 × 0.06 × 0.04

Data collection
Diffractometer	XtaLAB Synergy, Dualflex, HyPix
Absorption correction	Analytical (CrysAlis PRO; Rigaku OD, 2015 $[Rigaku OD (2015). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ )
T_min, T_max	0.991, 0.997
No. of measured, independent and observed [I > 2σ(I)] reflections	2812, 562, 496
R_int	0.035
(sin θ/λ)_max (Å⁻¹)	0.627

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.031, 0.088, 1.13
No. of reflections	562
No. of parameters	55
H-atom treatment	All H-atom parameters refined
Δρ_max, Δρ_min (e Å⁻³)	0.24, −0.19
Computer programs: CrysAlis PRO (Rigaku OD, 2015 $[Rigaku OD (2015). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ ), SHELXT2018/2 (Sheldrick, 2015a ), SHELXL2018/3 (Sheldrick, 2015b ) and SHELXTL (Sheldrick, 2008 ).

Structural data

CCDC reference: 2117037

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314621011020/dj4001sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314621011020/dj4001Isup2.hkl

checkCIF report

Computing details top

Data collection: CrysAlis PRO (Rigaku OD, 2015); cell refinement: CrysAlis PRO (Rigaku OD, 2015); data reduction: CrysAlis PRO (Rigaku OD, 2015); program(s) used to solve structure: SHELXT2018/2 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015b); molecular graphics: SHELXTL (Sheldrick, 2008).

Pyrazine-2(1H)-thione top

Crystal data top

C₄H₄N₂S	F(000) = 116
M_r = 112.15	D_x = 1.478 Mg m⁻³
Monoclinic, P2₁/m	Mo Kα radiation, λ = 0.71073 Å
a = 5.6113 (3) Å	Cell parameters from 1374 reflections
b = 6.4370 (6) Å	θ = 3.2–29.1°
c = 7.0923 (4) Å	µ = 0.49 mm⁻¹
β = 100.325 (6)°	T = 150 K
V = 252.03 (3) Å³	Plate, yellow
Z = 2	0.18 × 0.06 × 0.04 mm

Data collection top

XtaLAB Synergy, Dualflex, HyPix diffractometer	496 reflections with I > 2σ(I)
Detector resolution: 10.4052 pixels mm^-1	R_int = 0.035
ω scans	θ_max = 26.5°, θ_min = 2.9°
Absorption correction: analytical (CrysAlisPro; Rigaku OD, 2015)	h = −7→6
T_min = 0.991, T_max = 0.997	k = −7→8
2812 measured reflections	l = −8→8
562 independent reflections

Refinement top

Refinement on F²	Primary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F² > 2σ(F²)] = 0.031	All H-atom parameters refined
wR(F²) = 0.088	w = 1/[σ²(F_o²) + (0.0411P)² + 0.0767P] where P = (F_o² + 2F_c²)/3
S = 1.13	(Δ/σ)_max < 0.001
562 reflections	Δρ_max = 0.24 e Å⁻³
55 parameters	Δρ_min = −0.19 e Å⁻³
0 restraints

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.

Refinement. Hydrogen atoms of aromatic rings were introduced in calculated positions with idealized geometry and constrained using a rigid body model with isotropic displacement parameters equal to 1.2 the equivalent displacement parameters of the parent atoms. The H atom of the NH group was located in a difference Fourier map and freely refined.

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

	x	y	z	U_iso*/U_eq
S2	0.96392 (11)	0.750000	0.80505 (9)	0.0517 (3)
N1	0.8466 (3)	0.750000	0.4242 (3)	0.0354 (5)
N4	0.3609 (3)	0.750000	0.4191 (3)	0.0371 (5)
C3	0.5132 (4)	0.750000	0.5802 (3)	0.0335 (5)
C2	0.7722 (4)	0.750000	0.5956 (3)	0.0321 (5)
C6	0.6909 (4)	0.750000	0.2544 (4)	0.0418 (6)
C5	0.4506 (4)	0.750000	0.2523 (4)	0.0436 (6)
H5	0.355 (5)	0.750000	0.143 (5)	0.051 (8)*
H6	0.743 (5)	0.750000	0.142 (4)	0.047 (8)*
H3	0.458 (5)	0.750000	0.704 (4)	0.037 (7)*
H1	0.999 (7)	0.750000	0.426 (5)	0.069 (10)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S2	0.0290 (4)	0.0950 (6)	0.0300 (4)	0.000	0.0026 (2)	0.000
N1	0.0185 (9)	0.0561 (13)	0.0327 (10)	0.000	0.0074 (8)	0.000
N4	0.0215 (9)	0.0495 (12)	0.0409 (11)	0.000	0.0069 (8)	0.000
C3	0.0217 (10)	0.0436 (13)	0.0371 (12)	0.000	0.0108 (9)	0.000
C2	0.0231 (10)	0.0414 (13)	0.0326 (11)	0.000	0.0076 (9)	0.000
C6	0.0301 (12)	0.0672 (18)	0.0292 (12)	0.000	0.0085 (10)	0.000
C5	0.0270 (12)	0.0693 (18)	0.0323 (13)	0.000	−0.0008 (10)	0.000

Geometric parameters (Å, º) top

S2—C2	1.671 (2)	C3—C2	1.437 (3)
N1—C2	1.354 (3)	C3—H3	0.99 (3)
N1—C6	1.355 (3)	C6—C5	1.346 (3)
N1—H1	0.85 (4)	C6—H6	0.90 (3)
N4—C3	1.299 (3)	C5—H5	0.86 (3)
N4—C5	1.366 (3)

C2—N1—C6	123.0 (2)	N1—C2—S2	123.03 (17)
C2—N1—H1	117 (2)	C3—C2—S2	123.25 (18)
C6—N1—H1	120 (2)	C5—C6—N1	119.6 (2)
C3—N4—C5	118.37 (19)	C5—C6—H6	118.2 (19)
N4—C3—C2	124.3 (2)	N1—C6—H6	122.2 (19)
N4—C3—H3	121.6 (15)	C6—C5—N4	121.0 (2)
C2—C3—H3	114.1 (15)	C6—C5—H5	118 (2)
N1—C2—C3	113.7 (2)	N4—C5—H5	121 (2)

C5—N4—C3—C2	0.000 (1)	N4—C3—C2—S2	180.000 (1)
C6—N1—C2—C3	0.000 (1)	C2—N1—C6—C5	0.000 (1)
C6—N1—C2—S2	180.000 (1)	N1—C6—C5—N4	0.000 (1)
N4—C3—C2—N1	0.000 (1)	C3—N4—C5—C6	0.000 (1)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C5—H5···S2ⁱ	0.86 (3)	2.94 (3)	3.797 (3)	171 (3)
C6—H6···S2ⁱⁱ	0.90 (3)	2.88 (3)	3.775 (2)	173 (2)
C3—H3···S2ⁱⁱⁱ	0.99 (3)	2.98 (3)	3.716 (2)	132 (2)
N1—H1···N4^iv	0.85 (4)	2.04 (4)	2.893 (3)	178 (3)
C5—H5···S2ⁱ	0.86 (3)	2.94 (3)	3.797 (3)	171 (3)
C6—H6···S2ⁱⁱ	0.90 (3)	2.88 (3)	3.775 (2)	173 (2)
C3—H3···S2ⁱⁱⁱ	0.99 (3)	2.98 (3)	3.716 (2)	132 (2)
N1—H1···N4^iv	0.85 (4)	2.04 (4)	2.893 (3)	178 (3)

Symmetry codes: (i) x−1, y, z−1; (ii) x, y, z−1; (iii) x−1, y, z; (iv) x+1, y, z.

References

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IUCrDATA

ISSN: 2414-3146

Volume 6| Part 10| October 2021| x211102

https://doi.org/10.1107/S2414314621011020

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Pyrazine-2(1H)-thione

Structure description

Synthesis and crystallization

Refinement

Structural data

References

organic compounds