1H-Pyrazolo[4,3-g]benzothia­zol-7-amine

The mol­ecule of the title compound, C₈H₆N₄S, is almost planar [maximum deviation from the mean plane = 0.020 (1) Å for the S atom]. In the crystal, a supra­molecular three-dimensional arrangement arises from N—H...N hydrogen bonds and weak aromatic stacking interactions along the a axis [centroid–centroid separation = 3.582 (2) Å].

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.043
• wR factor = 0.117
• Data-to-parameter ratio = 13.3

checkCIF/PLATON results

No syntax errors found



Alert level C
            Value of measurement temperature given =   293.000
            Value of melting point given =     0.000
PLAT029_ALERT_3_C _diffrn_measured_fraction_theta_full Low .......       0.96
PLAT951_ALERT_1_C Reported and Calculated Kmax Values Differ by ..          2
PLAT952_ALERT_1_C Reported and Calculated Lmax Values Differ by ..          2

Alert level G
REFLT03_ALERT_1_G ALERT: Expected hkl max differ from CIF values
           From the CIF: _diffrn_reflns_theta_max           27.80
           From the CIF: _reflns_number_total               1564
           From the CIF: _diffrn_reflns_limit_ max hkl    5.   17.   13.
           From the CIF: _diffrn_reflns_limit_ min hkl   -5.  -17.  -10.
           TEST1: Expected hkl limits for theta max
           Calculated maximum hkl    5.   19.   15.
           Calculated minimum hkl   -5.  -19.  -15.
PLAT199_ALERT_1_G Check the Reported _cell_measurement_temperature        293 K
PLAT200_ALERT_1_G Check the Reported _diffrn_ambient_temperature .        293 K

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   3 ALERT level C = Check and explain
   3 ALERT level G = General alerts; check

   5 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   1 ALERT type 3 Indicator that the structure quality may be low
   0 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

Most of the significant advances against diseases have been made by designing and testing new structures, which are often heteroaromatic derivatives. Actually, the discovery of new compounds with antitumoral activity has become one of the most important goals in medicinal chemistry. One interesting group of potential chemotherapeutic agents includes molecules which interact with DNA like intercalator agents (Martínez & Chacón-García, 2005). Intercalation occurs when ligands of an appropriate size and chemical nature, fit themselves in between base pairs of DNA. Such ligands are mostly polycyclic, aromatic and planar. These kinds of agents are used in chemotherapeutic treatment to inhibit DNA replication in rapidly growing cancer cells. The title compound (I) is a polycyclic, aromatic and heterocyclic molecule and could be used to develop a new type of DNA intercalators agents (Chakrabarty et al. 2008).

The molecular structure is shown in figure 1, with its respective labels. The molecule adopts a conformation essenciality planar, with maximum deviation of the mean plane of 0.020 (1)Å for atom S1. The crystal structure of (I), consists of the self-assembly of the molecules through hydrogen bonding interactions of the kind N—H···N. The crystal packing (Fig. 2), consists of infinite chains in zigzag along the b axis generated by intermolecular interactions of hydrogen bond between the amino group and N atom of the imidazole ring [N1···N4 = 3.019 (3)Å]. These chains are connected through the interaction between the atoms N2 and N3 forming a two-dimensional wavy-like arrangement in the bc plane These layers are stacking through weak π–π interactions along the a axis (Cg3···Cg1, where Cg3 = C2/C3/C4/C5/C7/C8 and Cg1 = S1/C6/N3/C5/C7) together with an additional hydrogen bond lead to the formation of a three-dimensional hydrogen bonded network.

Related literature

For background on DNA intercalation agents, see: Cagnoli et al. (1968); Martínez & Chacón-García (2005); Chakrabarty et al. (2008). For further synthetic details, see: Salazar & Dorta (2004).

S2. Experimental

To a solution of 6-aminoindazole (2.00 g, 15 mmol) and NH₄SCN (2.29 g, 30 mmol) in acetic acid (25 ml) was added dropwise pentylpyridinium tribromide (5.86 g, 15 mmol) (Salazar & Dorta, 2004). The resulting solution was stirred for 3 h at room temperature and then, 3 h at 80°C. The reaction mixture was then poured into ice (50 g), the precipitate was filtered and discarded. The resulting solution was neutralized with K₂CO₃, and the formed precipitate was filtered, washed with AcOEt and dried; to give a yellow powder corresponding to the title compound. Yield: 1.80 g (63%). The melting point (uncorrected) was measured with a Fischer-Johns micro hot-stage apparatus: d 563 K.

The yellow powder was dissolved in a minimum amount of 1,4-dioxane and the solution was left for several days at room temperature, during which the solution gradually reduced its volume to give light brown blocks of (I).

IR data [KBr pellets, (cm^-1)]: 3367, 3314, 3181, 1629. ¹H NMR [500 MHz, DMSO-d₆, d (p.p.m.)]: 13.04 (brs, 1H, NH), 8.05 (s, 1H,), 7.57 (d, 1H, J = 6.84 Hz), 7.45 (brs, 2H, NH₂), 7.21 (d, 1H, J = 6.88 Hz).13 C NMR [126 MHz, DMSO-d₆, d (p.p.m.)]: 166.97 (C6), 152.21 (C5), 135.41 (C1), 134.99 (C2), 119.13 (C8), 118.01 (C3), 113.95 (C4), 109.39 (C7).

S3. Refinement

The N-bound H atoms were located in difference maps and refined as riding in their as found relative positions with U_iso(H) = 1.2U_eq(N). The C-bound H atoms were placed in idealized positions (C—H = 0.93–0.98 Å) and refined as riding with U_iso(H) = 1.2U_eq(C).

Computing details

Data collection: CrystalClear (Rigaku, 2002); cell refinement: CrystalClear (Rigaku, 2002); data reduction: CrystalStructure (Rigaku/MSC, 2004); program(s) used to solve structure: SHELXTL-NT (Sheldrick, 2008); program(s) used to refine structure: SHELXTL-NT (Sheldrick, 2008); molecular graphics: SHELXTL-NT (Sheldrick, 2008) and DIAMOND (Brandenburg, 1999); software used to prepare material for publication: SHELXTL-NT (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures

	Fig. 1. The molecular structure of (I), showing displacement elipsoids drawn at the 35% probability level and H atoms shown as spheres of arbitrary radius.
	Fig. 2. View of the hydrogen bonded layer in the bc plane in (I). The H atoms have been omitted for clarity and dashed lines indicate the donor···acceptor interactions for hydrogen bonds.

(I)

Crystal data

C8H6N4S	F(000) = 392
Mr = 190.23	Dx = 1.549 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71070 Å
Hall symbol: -P 2ybc	Cell parameters from 5546 reflections
a = 4.499 (2) Å	θ = 1.4–27.8°
b = 14.979 (8) Å	µ = 0.35 mm^−1
c = 12.112 (7) Å	T = 293 K
β = 92.442 (19)°	Block, light brown
V = 815.6 (7) Å^3	0.50 × 0.48 × 0.28 mm
Z = 4

Data collection

Rigaku AFC7S Mercury diffractometer	1564 independent reflections
Radiation source: Normal-focus sealed tube	1356 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.027
ω scans	θmax = 27.8°, θmin = 2.2°
Absorption correction: multi-scan (Jacobson, 1998)	h = −5→5
Tmin = 0.837, Tmax = 0.904	k = −17→17
8415 measured reflections	l = −10→13

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.043	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.117	H-atom parameters constrained
S = 1.12	w = 1/[σ^2(Fo^2) + (0.0537P)^2 + 0.4259P] where P = (Fo^2 + 2Fc^2)/3
1564 reflections	(Δ/σ)max = 0.001
118 parameters	Δρmax = 0.21 e Å^−3
0 restraints	Δρmin = −0.39 e Å^−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	1.01959 (12)	0.29819 (4)	0.80928 (4)	0.0375 (2)
N1	0.4558 (5)	0.03847 (13)	0.69844 (15)	0.0469 (5)
N2	0.6362 (4)	0.11194 (12)	0.70868 (14)	0.0399 (5)
H2	0.7275	0.1305	0.6432	0.048*
N3	0.8801 (4)	0.31237 (12)	1.01512 (15)	0.0374 (4)
N4	1.2153 (5)	0.42105 (13)	0.95801 (16)	0.0467 (5)
H6	1.3202	0.4479	0.8999	0.056*
H5	1.2408	0.4424	1.0345	0.056*
C1	0.3414 (6)	0.02732 (16)	0.79596 (19)	0.0447 (6)
H1	0.2103	−0.0183	0.8125	0.054*
C2	0.4424 (5)	0.09335 (14)	0.87253 (17)	0.0364 (5)
C3	0.3893 (5)	0.11384 (15)	0.98363 (18)	0.0425 (5)
H3	0.2600	0.0790	1.0233	0.051*
C4	0.5305 (5)	0.18567 (15)	1.03243 (18)	0.0408 (5)
H4	0.4976	0.1996	1.1057	0.049*
C5	0.7267 (5)	0.23892 (14)	0.97160 (16)	0.0352 (5)
C6	1.0420 (5)	0.34903 (14)	0.94037 (17)	0.0354 (5)
C7	0.7767 (5)	0.22046 (13)	0.86132 (16)	0.0319 (5)
C8	0.6336 (5)	0.14676 (14)	0.81177 (16)	0.0333 (5)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0429 (4)	0.0374 (4)	0.0325 (4)	−0.0007 (2)	0.0051 (2)	0.00195 (19)
N1	0.0621 (14)	0.0372 (11)	0.0414 (11)	−0.0055 (9)	0.0022 (9)	−0.0022 (8)
N2	0.0526 (12)	0.0365 (10)	0.0308 (10)	−0.0003 (9)	0.0058 (8)	−0.0021 (7)
N3	0.0424 (11)	0.0372 (10)	0.0326 (10)	0.0027 (8)	0.0028 (8)	−0.0032 (7)
N4	0.0574 (13)	0.0421 (11)	0.0405 (11)	−0.0088 (9)	0.0014 (9)	0.0000 (8)
C1	0.0550 (15)	0.0365 (12)	0.0426 (13)	−0.0047 (10)	0.0028 (10)	0.0023 (9)
C2	0.0414 (13)	0.0312 (11)	0.0367 (11)	0.0028 (9)	0.0031 (9)	0.0043 (8)
C3	0.0489 (14)	0.0417 (13)	0.0375 (12)	−0.0020 (10)	0.0084 (10)	0.0051 (9)
C4	0.0503 (14)	0.0439 (13)	0.0290 (11)	0.0011 (10)	0.0091 (10)	0.0018 (8)
C5	0.0385 (12)	0.0340 (11)	0.0331 (11)	0.0060 (9)	0.0029 (8)	0.0005 (8)
C6	0.0363 (12)	0.0334 (11)	0.0364 (11)	0.0055 (9)	−0.0002 (8)	0.0019 (8)
C7	0.0346 (12)	0.0323 (11)	0.0289 (10)	0.0054 (9)	0.0038 (8)	0.0016 (8)
C8	0.0384 (12)	0.0312 (11)	0.0303 (10)	0.0083 (9)	0.0011 (8)	0.0007 (8)

Geometric parameters (Å, º)

S1—C7	1.734 (2)	C1—C2	1.418 (3)
S1—C6	1.760 (2)	C1—H1	0.9300
N1—C1	1.319 (3)	C2—C8	1.405 (3)
N1—N2	1.370 (3)	C2—C3	1.411 (3)
N2—C8	1.354 (3)	C3—C4	1.371 (3)
N2—H2	0.9500	C3—H3	0.9300
N3—C6	1.307 (3)	C4—C5	1.419 (3)
N3—C5	1.391 (3)	C4—H4	0.9300
N4—C6	1.343 (3)	C5—C7	1.392 (3)
N4—H6	0.9529	C7—C8	1.400 (3)
N4—H5	0.9822
C7—S1—C6	88.59 (10)	C2—C3—H3	120.4
C1—N1—N2	105.85 (18)	C3—C4—C5	120.3 (2)
C8—N2—N1	111.39 (18)	C3—C4—H4	119.9
C8—N2—H2	132.7	C5—C4—H4	119.9
N1—N2—H2	115.8	N3—C5—C7	115.03 (19)
C6—N3—C5	110.62 (18)	N3—C5—C4	123.89 (19)
C6—N4—H6	121.6	C7—C5—C4	121.1 (2)
C6—N4—H5	117.1	N3—C6—N4	124.3 (2)
H6—N4—H5	121.2	N3—C6—S1	115.53 (17)
N1—C1—C2	111.8 (2)	N4—C6—S1	120.12 (16)
N1—C1—H1	124.1	C5—C7—C8	118.54 (19)
C2—C1—H1	124.1	C5—C7—S1	110.22 (16)
C8—C2—C3	120.5 (2)	C8—C7—S1	131.23 (16)
C8—C2—C1	103.94 (19)	N2—C8—C7	132.6 (2)
C3—C2—C1	135.5 (2)	N2—C8—C2	107.05 (19)
C4—C3—C2	119.2 (2)	C7—C8—C2	120.32 (19)
C4—C3—H3	120.4

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···N3^i	0.95	1.92	2.864 (3)	170
N4—H5···N1^ii	0.98	2.19	3.123 (3)	158
N4—H6···N1^iii	0.95	2.09	3.019 (3)	164

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