Crystal structure of 4-methyl­sulfanyl-2-(2H-tetra­zol-2-yl)pyrimidine

Andreas Thomann; Volker Huch; Rolf W Hartmann

doi:10.1107/S2056989015023634

. 2015 Dec 16;71(Pt 12):o1051–o1052. doi: 10.1107/S2056989015023634

Crystal structure of 4-methylsulfanyl-2-(2H-tetrazol-2-yl)pyrimidine

Andreas Thomann ^a, Volker Huch ^b, Rolf W Hartmann ^a,^c,^*

PMCID: PMC4719974 PMID: 26870493

Abstract

The title compound, C₆H₆N₆S, crystallized with two independent molecules (A and B) in the asymmetric unit. The conformation of the two molecules differs slightly. While the tetrazole ring is inclined to the pyrimidene ring by 5.48 (7) and 4.24 (7)° in molecules A and B, respectively, the N—C—S—C torsion angles of the thiomethyl groups differ by ca 180°. In the crystal, the A and B molecules are linked via a C—H⋯N hydrogen bond. They stack along the b-axis direction forming columns within which there are weak π–π interactions present [shortest inter-centroid distance = 3.6933 (13) Å].

Keywords: crystal structure, tetrazole, pyrimidine, thio, heterocyles, S_NAr reactions, π–π interactions

Related literature

For applications of tetrazolyl-substituted aromatic systems in metal–ligand research, see: Kim et al. (2008 ▸); Stoessel et al. (2010 ▸); in drug development, see: Pasternak et al. (2012 ▸); Biswas et al. (2015 ▸); in polymer synthesis, see: Yu et al. (2008 ▸); Sengupta et al. (2010 ▸). For the synthesis of 4-methylsulfanyl-2-(1H-tetrazol-1-yl)pyrimidine and the title compound, see: Thomann et al. (2014 ▸). graphic file with name e-71-o1051-scheme1.jpg

Experimental

Crystal data

C₆H₆N₆S
M _r = 194.23
Triclinic,
a = 6.3001 (17) Å
b = 7.393 (2) Å
c = 18.159 (5) Å
α = 91.407 (7)°
β = 95.864 (7)°
γ = 102.695 (8)°
V = 819.9 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.35 mm⁻¹
T = 143 K
0.22 × 0.22 × 0.01 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2010 ▸) T _min = 0.716, T _max = 0.746
15501 measured reflections
4581 independent reflections
3596 reflections with I > 2σ(I)
R _int = 0.028

Refinement

R[F ² > 2σ(F ²)] = 0.034
wR(F ²) = 0.086
S = 1.01
4581 reflections
283 parameters
All H-atom parameters refined
Δρ_max = 0.35 e Å⁻³
Δρ_min = −0.30 e Å⁻³

Data collection: APEX2 (Bruker, 2010 ▸); cell refinement: SAINT (Bruker, 2010 ▸); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick 2008 ▸); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015 ▸); molecular graphics: PLATON (Spek, 2009 ▸); software used to prepare material for publication: SHELXL2014 and PLATON.

Supplementary Material

Crystal structure: contains datablock(s) I. DOI: 10.1107/S2056989015023634/su5253sup1.cif

e-71-o1051-sup1.cif^{(521.2KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015023634/su5253Isup2.hkl

e-71-o1051-Isup2.hkl^{(364.7KB, hkl)}

Click here for additional data file.^{(3.7KB, cml)}

Supporting information file. DOI: 10.1107/S2056989015023634/su5253Isup3.cml

Click here for additional data file.^{(1.3MB, tif)}

A B . DOI: 10.1107/S2056989015023634/su5253fig1.tif

The molecular structure of the two independent molecules (A and B) of the title compound (2), with atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

Click here for additional data file.^{(1.4MB, tif)}

A B a . DOI: 10.1107/S2056989015023634/su5253fig2.tif

The crystal packing of the two independent molecules (A black; B red) of the title compound (2), viewed along the a axis. Hydrogen bonds are shown as dashed lines (see Table 1).

Click here for additional data file.^{(66.3KB, tif)}

. DOI: 10.1107/S2056989015023634/su5253fig3.tif

Compounds (1) and (2).

CCDC reference: 1441424

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

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C2—H1⋯N9ⁱ	0.89 (2)	2.58 (2)	3.203 (2)	129 (2)

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Symmetry code: (i) Inline graphic .

Acknowledgments

We thank Nadja Klippel for the synthesis of the title compound.

supplementary crystallographic information

S1. Comment

4-tetrazolylpyrimidines are well reported scaffolds in many bioactive entities. Besides synthetic chemistry, tetrazolyl substituted aromatic systems are also of high interest for example, in metal-ligand research (Kim et al., 2008; Stoessel et al., 2010), drug development (Pasternak et al., 2012; Biswas et al., 2015) and polymer discovery (Yu et al., 2008; Sengupta et al., 2010). Thus, the knowledge of the three dimensional structure of these moieties is of crucial importance for the rational design in these fields of research. Recently, we have reported a novel method to synthesize such compounds (Thomann et al., 2014). We have reported the synthesis of 4-(methylthio)-2-(1H-tetrazol-1-yl)pyrimidine (1). Interestingly, when scaling up the reaction, another product was found in small amounts. NMR analytical characterization revealed the compound to be the 2-tetrazolyl regioisomer (2). To determine unequivocally proof of the structure of this compound, we determined its crystal structure.

The title compound (2), crystallized with two independent molecules (A and B) in the asymmetric unit (Fig. 1). Interestingly, the two molecules differ in their conformation. While the tetrazole moieties are arranged similarly, with the tetrazole ring is inclined to the pyrimidene ring by 5.48 (7) and 4.24 (7) ° in molecules A and B, respectively, the thiomethyl groups have a difference of the torsion angle about the C_ar···S bond of ca 180° [for example, torsion angle N5—C4—S1—C6 = 0.89 (12) °, compared to torsion angle N11—C10—S2—C12 = −176.78 (10) °] indicating higher rotational freedom than the tetrazoles (Fig. 1). The latter finding is of importance for computational chemists in medicinal chemistry, as the polarized hydrogen at atom C5 of the tetrazole ring is able to form non-classical hydrogen bonds. Therefore, the results from the crystal structure may favour this conformational isomer for in silico predictions.

In the crystal, the A and B molecules are linked via a C—H···N hydrogen bond (Table 1 and Fig. 2). They stack along the b axis direction forming columns within which there are weak π-π interactions present [shortest inter-centroid distance is Cg2···Cg4ⁱ = 3.6918 (5) Å; Cg2 and Cg4 are the centroids of rings N5/N6/C1—C4 and N11/N12/C7—C10, respectively; symmetry code: (i) x, y + 1, z].

S2. Synthesis and crystallization

The title compound (2), was synthesized following a previously reported procedure (Thomann et al., 2014). A mixture of 4-chloro-2-(methylthio)pyrimidine, 1H-tetrazole and triethylamine, in the ratio 1:1:1, was stirred under microwave irradiation at 50 W, 353 K for 1 h. The crude product was purified by flash chromatography (hexane:ethyl acetate, 8:2, R_f = 1/4) to yield a white solid (9%). Crystals formed at 294 K after 16 h from a saturated solution of 2 in ethyl acetate.¹H NMR (CDCl₃, 300 MHz) 8.80 (dd, J = 5.3, 0.6 Hz, 1 H), 8.77 (s, 1 H), 7.77 (dd, J = 5.3, 0.7 Hz, 1 H), 2.69 p.p.m. (d, J = 0.7 Hz, 3 H).

S3. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. H atoms were located in a difference Fourier map and freely refined.