5-(Thio­phen-2-ylmeth­yl)-1,3,4-thia­diazol-2-amine

In the title mol­ecule, C₇H₇N₃S₂, the dihedral angle between the thio­phene and thia­diazole rings is 72.99 (5)°; the two rings are oriented so that the S atoms in each ring are on the same side. In the crystal, the three-dimensional network involves strong N—H⋯O hydrogen bonds, as well as C—H⋯π and π–π stacking inter­actions [centroid–centroid distances = 3.654 (1) and 3.495 (1) Å].

Related literature

For the anti­tumor activity of 2-amino-1,3,4-thia­diazole, 2-ethyl­amino-1,3,4-thia­diazole and 2,2′-(methyl­enediamino)­bis-1,3,4-thia­diazole, see: Olesan et al. (1955); Mishra et al. (1995). For their anti-HIV, anti­proliferative, germicidal and D2 dopamine­rgic activity, see: Mohareb et al. (2004). For the synthesis of the title compound, see: Sancak et al., (2007). For standard bond lengths, see: Allen et al. (1987).

Experimental

Crystal data

• C₇H₇N₃S₂

• M_r = 197.28

• Monoclinic, P 2₁ /c

• a = 11.2970 (6) Å

• b = 6.6094 (3) Å

• c = 11.2480 (6) Å

• β = 97.243 (5)°

• V = 833.15 (7) ų

• Z = 4

• Cu Kα radiation

• μ = 5.33 mm⁻¹

• T = 173 K

• 0.46 × 0.28 × 0.15 mm

Data collection

• Agilent Xcalibur Eos Gemini diffractometer

• Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010) T_min = 0.209, T_max = 0.450

• 4375 measured reflections

• 1539 independent reflections

• 1497 reflections with I > 2σ(I)

• R_int = 0.036

Refinement

• R[F² > 2σ(F²)] = 0.045

• wR(F²) = 0.120

• S = 1.09

• 1539 reflections

• 110 parameters

• H-atom parameters constrained

• Δρ_max = 0.64 e Å⁻³

• Δρ_min = −0.38 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

Cg is the centroid of the S1/C1–C4 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3B⋯N1^i	0.86	2.13	2.991 (2)	175
N3—H3A⋯N2^ii	0.86	2.17	3.013 (2)	167
C1—H1⋯Cg^iii	0.93	2.83	3.549 (2)	135
Symmetry codes: (i) ; (ii) -x+2, -y+3, -z+1; (iii) .

Data collection: CrysAlis PRO (Agilent, 2010); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.

Supporting information

S1. Comment

The antitumor activites of 2-amino-1,3,4-thiadiazole (ATDA, NSC-4728) and the related compounds: 2-ethylamino-1,3,4-thiadiazole (EATDA), 2,2'-(methylene-diamino) bis-1,3,4-thiadiazole (NSC-143019) were found in several experimental tumor systems about 50 years ago (Olesan et al., 1955). 2-Amino-1,3,4-thiadiazole (ATDA), as the most promising compound, was used in phase II clinical trials in patients with different tumors: renal, colon, ovarian, and others. Recently new derivatives with the 1,3,4-thiadiazole nucleus as well as Fe(II) / Fe (III) complexes of 2-amino-1,3,4-thiadiazoles have been synthesized and evaluated for their antiproliferative activity against a panel of human cancer cell lines (Mishra et al., 1995). Over recent years, there has been an increasing interest in the chemistry of thiophenes because of their biological significance. Many of them have been widely investigated for therapeutic uses, especially as antifungal, antibacterial, anti-inflammatory, anticonvulsant, antiasthmatic, and analgesic agents. They also were known to show anti-HIV, antiproliferative, germicidal, and D2 dopaminergic activities (Mohareb et al., 2004). In view of these facts, the aim of this present study is to obtain a structure of 1,3,4-oxadiazole incorporating the thiophene ring.

In the molecule of the title compound (Fig 1), the bond lengths are within normal ranges (Allen et al., 1987). In the molecule of (I) atom S1 is oriented towards the thiadiazol ring, Fig. 1. The dihedral angle between the planar thiophene (r.m.s. deviation = 0.007 Å) and planar thiadiazol (r.m.s. deviation = 0.004 Å) rings of 72.99 (5)° indicates a twist between planes as seen in the S1–C4–C5–C6 torsion angle of 94.86 (17) °. The amine group is effectively co-planar with the thiadiazol ring to which it is attached as seen in the N3–C7–S2–C6 torsion angle of 178.53 (16) °.

In the crystal structure, there are strong intermolecular N–H···N hydrogen bonds which lead to the formation of centrosymmetric dimers in the crystal. In addition there are C—H···π and π-π stacking interactions [Cg1···Cg1(1 - x, -y, -z) = 3.654 (1) Å and Cg2···Cg2(-x, 1 - y, -z) = 3.495 (1) Å, Cg1(S1/C1—C4) and Cg2(S2/N1/N2/C6/C7) are the centroids of the thiophene and thiadiazol rings]. This pattern is the primary supramolecular structure for this compound (Fig. 2).

Related literature

For the antitumor activity of 2-amino-1,3,4-thiadiazole, 2-ethylamino-1,3,4-thiadiazole and 2,2'-(methylenediamino)bis-1,3,4-thiadiazole, see: Olesan et al. (1955); Mishra et al. (1995). For their anti-HIV, antiproliferative, germicidal and D2 dopaminergic activity, see: Mohareb et al. (2004). For the synthesis of the title compound, see: Sancak et al., (2007). For standard bond lengths, see: Allen et al. (1987).

S2. Experimental

The title compound was synthesized using the published method (Sancak et al., 2007).

S3. Refinement

The amine H atoms were seen in a difference Fourier map and then idealized with U_iso(H) = 1.2U_eq(N) with N–H bond length of 0.86 Å. The C-bound H-atoms were positioned geometrically with C—H = 0.93 and 0.97 Å, for aromatic and CH₂ H-atoms, respectively, and constrained to ride on their parent atoms, with U_iso(H) = 1.2U_eq(C). During the refinement it was noticed that for the strongest reflections (F_c/F_c(max) close to 1.00) the observed value (F_o) was much smaller than the calculated value (F_c) indicating detector saturation problems. These reflections were omitted from the refinement.

Computing details

Data collection: CrysAlis PRO (Agilent, 2010); cell refinement: CrysAlis PRO (Agilent, 2010); data reduction: CrysAlis PRO (Agilent, 2010); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures

	Fig. 1. View of the molecular structure of the title compound with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level for non-hydrogen atoms.
	Fig. 2. The packing view showing the hydrogen bonds network. Dashed lines indicate intermolecular N—H···N hydrogen bonds (see Table 1 for details).

5-(Thiophen-2-ylmethyl)-1,3,4-thiadiazol-2-amine

Crystal data

C7H7N3S2	F(000) = 408
Mr = 197.28	Dx = 1.573 Mg m^−3
Monoclinic, P21/c	Cu Kα radiation, λ = 1.54184 Å
Hall symbol: -P 2ybc	Cell parameters from 2744 reflections
a = 11.2970 (6) Å	θ = 3.9–70.0°
b = 6.6094 (3) Å	µ = 5.33 mm^−1
c = 11.2480 (6) Å	T = 173 K
β = 97.243 (5)°	Chunk, colorless
V = 833.15 (7) Å^3	0.46 × 0.28 × 0.15 mm
Z = 4

Data collection

Agilent Xcalibur Eos Gemini diffractometer	1539 independent reflections
Radiation source: Enhance (Cu) X-ray Source	1497 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.036
Detector resolution: 16.1500 pixels mm^-1	θmax = 70.1°, θmin = 3.9°
ω scans	h = −13→13
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010)	k = −5→8
Tmin = 0.209, Tmax = 0.450	l = −12→13
4375 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.045	H-atom parameters constrained
wR(F^2) = 0.120	w = 1/[σ^2(Fo^2) + (0.0928P)^2 + 0.0849P] where P = (Fo^2 + 2Fc^2)/3
S = 1.09	(Δ/σ)max = 0.001
1539 reflections	Δρmax = 0.64 e Å^−3
110 parameters	Δρmin = −0.38 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.035 (3)

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq
S1	0.64166 (4)	0.57641 (7)	0.32224 (4)	0.0210 (2)
S2	0.82410 (4)	1.05521 (6)	0.34150 (3)	0.0182 (2)
N1	0.87197 (12)	1.0981 (2)	0.56747 (13)	0.0175 (4)
N2	0.91662 (12)	1.2714 (2)	0.51908 (13)	0.0179 (4)
N3	0.93579 (14)	1.4168 (2)	0.33358 (14)	0.0251 (4)
H3A	0.9732	1.5198	0.3665	0.030*
H3B	0.9220	1.4085	0.2568	0.030*
C1	0.48911 (16)	0.5889 (3)	0.30609 (17)	0.0216 (4)
H1	0.4395	0.5306	0.2430	0.026*
C2	0.44958 (15)	0.6943 (3)	0.39653 (16)	0.0226 (4)
H2	0.3693	0.7160	0.4030	0.027*
C3	0.54422 (16)	0.7680 (3)	0.48045 (16)	0.0206 (4)
H3	0.5323	0.8420	0.5483	0.025*
C4	0.65455 (15)	0.7192 (2)	0.45147 (15)	0.0171 (4)
C5	0.77380 (16)	0.7709 (3)	0.51957 (16)	0.0212 (4)
H5A	0.8306	0.6668	0.5044	0.025*
H5B	0.7667	0.7689	0.6046	0.025*
C6	0.82264 (14)	0.9732 (3)	0.48849 (14)	0.0159 (4)
C7	0.89906 (14)	1.2698 (3)	0.40174 (15)	0.0165 (4)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0161 (3)	0.0215 (4)	0.0250 (4)	−0.00005 (14)	0.0010 (2)	−0.00692 (15)
S2	0.0184 (3)	0.0192 (3)	0.0158 (3)	−0.00404 (13)	−0.0027 (2)	−0.00264 (13)
N1	0.0172 (7)	0.0156 (7)	0.0191 (7)	−0.0010 (5)	0.0000 (6)	0.0004 (5)
N2	0.0170 (7)	0.0175 (8)	0.0184 (7)	−0.0032 (5)	−0.0012 (5)	−0.0010 (5)
N3	0.0272 (9)	0.0290 (9)	0.0172 (8)	−0.0138 (6)	−0.0039 (6)	0.0017 (6)
C1	0.0172 (8)	0.0152 (8)	0.0311 (9)	−0.0020 (6)	−0.0017 (7)	0.0002 (7)
C2	0.0176 (8)	0.0169 (9)	0.0337 (10)	0.0024 (6)	0.0052 (7)	0.0078 (7)
C3	0.0248 (9)	0.0135 (9)	0.0239 (9)	0.0041 (6)	0.0054 (7)	0.0012 (6)
C4	0.0211 (8)	0.0084 (8)	0.0213 (9)	−0.0011 (6)	0.0007 (7)	0.0000 (6)
C5	0.0236 (9)	0.0130 (9)	0.0251 (9)	−0.0007 (6)	−0.0039 (7)	0.0016 (7)
C6	0.0139 (7)	0.0152 (8)	0.0179 (8)	0.0022 (6)	−0.0004 (6)	−0.0003 (6)
C7	0.0100 (7)	0.0184 (9)	0.0199 (8)	−0.0002 (6)	−0.0025 (6)	−0.0031 (6)

Geometric parameters (Å, º)

S1—C1	1.7119 (18)	C1—C2	1.354 (3)
S1—C4	1.7237 (17)	C1—H1	0.9300
S2—C6	1.7419 (17)	C2—C3	1.420 (3)
S2—C7	1.7445 (17)	C2—H2	0.9300
N1—C6	1.287 (2)	C3—C4	1.366 (2)
N1—N2	1.390 (2)	C3—H3	0.9300
N2—C7	1.310 (2)	C4—C5	1.503 (2)
N3—C7	1.336 (2)	C5—C6	1.505 (2)
N3—H3A	0.8600	C5—H5A	0.9700
N3—H3B	0.8600	C5—H5B	0.9700
C1—S1—C4	92.29 (9)	C3—C4—C5	127.66 (16)
C6—S2—C7	86.93 (8)	C3—C4—S1	110.36 (13)
C6—N1—N2	113.90 (14)	C5—C4—S1	121.96 (13)
C7—N2—N1	111.83 (14)	C4—C5—C6	114.53 (14)
C7—N3—H3A	120.0	C4—C5—H5A	108.6
C7—N3—H3B	120.0	C6—C5—H5A	108.6
H3A—N3—H3B	120.0	C4—C5—H5B	108.6
C2—C1—S1	111.59 (14)	C6—C5—H5B	108.6
C2—C1—H1	124.2	H5A—C5—H5B	107.6
S1—C1—H1	124.2	N1—C6—C5	123.32 (15)
C1—C2—C3	112.57 (16)	N1—C6—S2	113.61 (13)
C1—C2—H2	123.7	C5—C6—S2	123.00 (12)
C3—C2—H2	123.7	N2—C7—N3	123.65 (16)
C4—C3—C2	113.16 (16)	N2—C7—S2	113.71 (13)
C4—C3—H3	123.4	N3—C7—S2	122.63 (13)
C2—C3—H3	123.4
C6—N1—N2—C7	−0.27 (19)	N2—N1—C6—C5	176.73 (15)
C4—S1—C1—C2	−1.08 (14)	N2—N1—C6—S2	−0.36 (18)
S1—C1—C2—C3	0.4 (2)	C4—C5—C6—N1	136.56 (17)
C1—C2—C3—C4	0.7 (2)	C4—C5—C6—S2	−46.6 (2)
C2—C3—C4—C5	−179.68 (15)	C7—S2—C6—N1	0.64 (13)
C2—C3—C4—S1	−1.50 (19)	C7—S2—C6—C5	−176.45 (15)
C1—S1—C4—C3	1.47 (14)	N1—N2—C7—N3	−178.55 (16)
C1—S1—C4—C5	179.78 (14)	N1—N2—C7—S2	0.78 (18)
C3—C4—C5—C6	−87.1 (2)	C6—S2—C7—N2	−0.80 (13)
S1—C4—C5—C6	94.86 (17)	C6—S2—C7—N3	178.53 (16)

Hydrogen-bond geometry (Å, º)

Cg is the centroid of the S1/C1–C4 ring.

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3B···N1^i	0.86	2.13	2.991 (2)	175
N3—H3A···N2^ii	0.86	2.17	3.013 (2)	167
C1—H1···Cg^iii	0.93	2.83	3.549 (2)	135

Symmetry codes: (i) x, −y+5/2, z−1/2; (ii) −x+2, −y+3, −z+1; (iii) −x+1, y−1/2, −z+1/2.