4-Amino-3-{5-[(3,5-dimethyl-1H-pyra­zol-1-yl)carbon­yl]-2,6-dimethyl-3-pyri­dyl}-1H-1,2,4-triazole-5(4H)-thione

The title compound, C₁₅H₁₇N₇OS, is a new heterocyclic compound and this is the first time its synthesis has been reported. The compound, which contains a 1,2,4-triazole ring, a pyridine ring and a pyrazole ring, has potential biological activity and pharmacological properties. Mol­ecules are linked by inter­molecular N—H...N hydrogen bonds.

Key indicators

• Single-crystal X-ray study
• T = 273 K
• Mean [sigma](C-C) = 0.004 Å
• R factor = 0.051
• wR factor = 0.136
• Data-to-parameter ratio = 12.9

checkCIF/PLATON results

No syntax errors found



Alert level B
PLAT031_ALERT_4_B Refined Extinction Parameter within Range ......       1.33 Sigma
PLAT414_ALERT_2_B Short Intra D-H..H-X       H4B    ..  H7      ..       1.81 Ang.

Alert level C
PLAT066_ALERT_1_C Predicted and Reported Transmissions Identical .          ?
PLAT125_ALERT_4_C No _symmetry_space_group_name_Hall Given .......          ?
PLAT420_ALERT_2_C D-H Without Acceptor       N4     -   H4A    ...          ?
PLAT420_ALERT_2_C D-H Without Acceptor       N4     -   H4B    ...          ?

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

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

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S1. Comment

Nitrogen-containing heterocycles compounds are well known natural products moieties which represent interesting biological activities and pharmacological properties (Pandeya et al., 2000; Soudi et al., 2005). For example, the 1,2,4-triazole nucleus with the nitrogen-bridged heterocycles always show antibacterial (Holla & Kalluraya, 1988) and antifungal (Prasad et al., 1989) properties. In addition, the substituted 1,2,4-triazol is a well established N-donor heterocyclic ligand (Elwahy & Abbas, 2000). More recently, it was reported that 1,2,4-triazole derivatives complexed with metal have higher biological activity (Tardito et al., 2007). Further more, the substituted 3,5-Dimethylpyrazoles contribute significant activities to diabetes (Soliman & Darwish,1983). These useful applications for the important class of nitrogen-containing heterocycles attracted our attention. Here, we report the synthesis and structure of a new multi-heterocyclic compound.

In the molecule of the title compound, (I), (Fig. 1), the C1—N2, C2—N3 bond distances [average =1.317 (3) Å] and N2—N3 bond distance [1.369 (3) Å] are in good agreement with those found for structures containing the 1,2,4-trizole ring Özbey et al., 2000; Bruno et al., 2003). The C=S double bond [1.663 (3) Å] is equal to the corresponding double bond (Xue et al., 2004). In the pyrazole ring, the bond distances between atoms are similar with those in the literature (Yang & Liu, 2005).

It is interesting to find that the three rings are not coplanar, due to steric hinderance. The angle between triazole plane and pyridine plane is 28.90 (3)°, whereas the angle between pyrazole plane and pyridine plane is 53.26 (9)°. Furthermore, the planes of triazole and pyrazole form a dihedral angle 55.55 (2)°. As a result of the torsional angle of the title compound, the steric hinderance has been reduced that make the compound more stable.

Related literature

For general backgroud, see: Soliman & Darwish (1983); Holla & Kalluraya (1988); Prasad et al. (1989); Elwahy & Abbas (2000); Pandeya et al. (2000); Soudi et al. (2005); Tardito et al. (2007). For related literature, see: Özbey et al. (2000); Bruno et al. (2003); Xue et al. (2004); Yang & Liu (2005).

S2. Experimental

The synthetic route is depicted in Scheme 1. For the synthesis of I, 5-carbethoxy-2,6-dimethylpyridine-3-carboxhydrazide (0.47 g, 2 mmol) was dissolved in anhydrous ethanol(5 ml) in the presence of carbon bisulfide (0.23 g, 3 mmol) and potassium hydroxide (0.17 g, 3 mmol). The mixture was stirred at room temperature for 4 h. After removal of the solvent, hydrazine hydrate was added as solvent, heated and stirred under reflux for 3 h. After cooling to room temperature, the mixture was neutralized with dilute hydrochloric acid. The precipitate formed was filtered and washed with water. A colorless solid was obtained and directly used for next step without further purification. The obtained product (0.28 g, 1 mmol) and acetylacetone (0.1 g, 1 mmol) were put together in chloroform (5 ml) with hydrochloric acid as catalyst. The mixture was heated to reflux for 3 h, cooled to room temperature and then solvent removed. The crude product was filtered, washed with water and dried. It was recrystallized from ethanol to give a colorless compound in a yield of 76% (m. p. 414 K– 415 K). IR(ν, cm^-1): 3302 (NH), 3097 (pyridine CH), 2925 (CH), 1699 (C=O), 1603–1481 (C=C, C=N), 1338 (C=S); ¹H-NMR (500 MHz, DMSO-d₆): δ 14.03 (s, 1H, triazole NH), 8.06 (s, 1H, pyridine CH), 6.32 (s, 1H, pyrazole CH), 5.60 (s, 1H, triazole NH), 2.60 (s, 3H, pyridine CH), 2.53 (s, 3H, pyridine CH), 2.39 (s, 3H, pyrazole CH), 2.11(s, 3H, pyrazole CH); Elemental analysis, required for C₁₅H₁₇N₇OS: C 52.46, H 4.99, N 28.55%; Found: C 52.33, H 4.87, N 28.65%. Single crystals suitable for X-ray analysis were obtained from ethanol by slow evaporation at room temperature.

S3. Refinement

All H atoms were placed in calculated positions, with C—H=0.93–0.96 Å; N—H=0.86 Å, and included in the final cycles of refinement using a riding model,U_iso(H) = 1.2U_eq(C).

Computing details

Data collection: SMART (Bruker, 2000); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 2000); software used to prepare material for publication: SHELXTL.

Figures

	Fig. 1. The molecular structure of the title molecule, with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. Diagram showing hydrogen bonding for (I). Hydrogen bonds are shown as dashed lines.
	Fig. 3. The formation of the title compound.

4-Amino-3-{5-[(3,5-dimethyl-1H-pyrazol-1-yl)carbonyl]-2,6-dimethyl-3-pyridyl}- 1H-1,2,4-triazole-5(4H)-thione

Crystal data

C15H17N7OS	Z = 2
Mr = 343.42	F(000) = 360
Triclinic, P1	Dx = 1.390 Mg m^−3
a = 8.039 (5) Å	Mo Kα radiation, λ = 0.71073 Å
b = 8.428 (5) Å	Cell parameters from 1268 reflections
c = 12.391 (8) Å	θ = 2.7–23.5°
α = 102.186 (7)°	µ = 0.22 mm^−1
β = 90.633 (8)°	T = 273 K
γ = 90.074 (8)°	Block, colorless
V = 820.5 (9) Å^3	0.20 × 0.20 × 0.15 mm

Data collection

Bruker APEX II CCD area-detector diffractometer	2861 independent reflections
Radiation source: fine-focus sealed tube	2142 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.018
φ and ω scans	θmax = 25.1°, θmin = 2.5°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −6→9
Tmin = 0.958, Tmax = 0.968	k = −10→9
4304 measured reflections	l = −14→14

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)] = 0.051	H-atom parameters constrained
wR(F^2) = 0.136	w = 1/[σ^2(Fo^2) + (0.0567P)^2 + 0.5239P] where P = (Fo^2 + 2Fc^2)/3
S = 1.03	(Δ/σ)max < 0.001
2861 reflections	Δρmax = 0.38 e Å^−3
222 parameters	Δρmin = −0.45 e Å^−3
0 restraints	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.004 (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 basedon 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	0.43077 (10)	0.93706 (11)	−0.18895 (7)	0.0538 (3)
C1	0.2477 (4)	0.8830 (3)	−0.1465 (2)	0.0384 (6)
C2	0.0464 (3)	0.7909 (3)	−0.0528 (2)	0.0351 (6)
C3	−0.0417 (3)	0.7246 (3)	0.0307 (2)	0.0348 (6)
C4	−0.1962 (3)	0.6475 (3)	0.0077 (2)	0.0369 (6)
C5	−0.2259 (4)	0.6266 (3)	0.1905 (2)	0.0424 (7)
C6	−0.0675 (3)	0.6903 (3)	0.2172 (2)	0.0369 (6)
C7	0.0229 (3)	0.7418 (3)	0.1367 (2)	0.0364 (6)
H7	0.1275	0.7882	0.1537	0.044*
C8	0.0107 (3)	0.6855 (4)	0.3260 (2)	0.0410 (7)
C9	0.1963 (3)	1.0647 (4)	0.4101 (2)	0.0427 (7)
C10	0.2723 (4)	0.9843 (4)	0.4868 (2)	0.0470 (7)
H10	0.3484	1.0294	0.5418	0.056*
C11	0.2150 (4)	0.8312 (4)	0.4659 (2)	0.0444 (7)
C12	0.2215 (4)	1.2347 (4)	0.3972 (3)	0.0566 (9)
H12A	0.1676	1.2492	0.3305	0.085*
H12B	0.3384	1.2562	0.3935	0.085*
H12C	0.1749	1.3083	0.4592	0.085*
C13	0.2588 (5)	0.6943 (4)	0.5193 (3)	0.0661 (10)
H13A	0.3405	0.7300	0.5764	0.099*
H13B	0.3031	0.6065	0.4651	0.099*
H13C	0.1609	0.6581	0.5509	0.099*
C14	−0.3432 (4)	0.5825 (5)	0.2724 (3)	0.0671 (10)
H14A	−0.4510	0.6267	0.2629	0.101*
H14B	−0.3025	0.6259	0.3459	0.101*
H14C	−0.3513	0.4664	0.2611	0.101*
C15	−0.2747 (4)	0.6067 (4)	−0.1048 (2)	0.0465 (7)
H15A	−0.3550	0.5214	−0.1076	0.070*
H15B	−0.1906	0.5714	−0.1588	0.070*
H15C	−0.3291	0.7010	−0.1201	0.070*
N1	0.2156 (3)	0.8125 (3)	−0.05885 (17)	0.0360 (5)
N2	0.0964 (3)	0.8979 (3)	−0.18831 (19)	0.0436 (6)
H2	0.0793	0.9383	−0.2456	0.052*
N3	−0.0292 (3)	0.8433 (3)	−0.13175 (19)	0.0433 (6)
N4	0.3343 (3)	0.7712 (3)	0.01276 (19)	0.0471 (7)
H4A	0.4379	0.7897	0.0038	0.057*
H4B	0.3041	0.7271	0.0661	0.057*
N5	−0.2849 (3)	0.6039 (3)	0.08698 (19)	0.0425 (6)
N6	0.1045 (3)	0.8203 (3)	0.37803 (17)	0.0382 (6)
N7	0.0934 (3)	0.9668 (3)	0.34468 (18)	0.0394 (6)
O1	−0.0008 (3)	0.5692 (3)	0.36724 (18)	0.0606 (6)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0503 (5)	0.0658 (6)	0.0487 (5)	−0.0140 (4)	0.0003 (4)	0.0197 (4)
C1	0.0490 (17)	0.0332 (15)	0.0329 (14)	−0.0039 (12)	−0.0013 (12)	0.0069 (11)
C2	0.0382 (15)	0.0368 (15)	0.0301 (13)	0.0014 (12)	−0.0031 (11)	0.0064 (11)
C3	0.0357 (14)	0.0340 (15)	0.0346 (14)	0.0017 (11)	−0.0029 (11)	0.0071 (11)
C4	0.0384 (15)	0.0350 (15)	0.0367 (14)	0.0014 (12)	−0.0046 (12)	0.0063 (12)
C5	0.0469 (17)	0.0422 (17)	0.0374 (15)	−0.0078 (13)	−0.0011 (13)	0.0066 (12)
C6	0.0413 (15)	0.0354 (15)	0.0337 (14)	−0.0041 (12)	−0.0037 (12)	0.0067 (12)
C7	0.0350 (15)	0.0350 (15)	0.0382 (15)	−0.0017 (11)	−0.0029 (12)	0.0056 (12)
C8	0.0424 (16)	0.0458 (17)	0.0355 (15)	−0.0056 (13)	−0.0022 (12)	0.0102 (13)
C9	0.0418 (16)	0.0470 (17)	0.0372 (15)	−0.0033 (13)	0.0004 (13)	0.0045 (13)
C10	0.0452 (17)	0.0539 (19)	0.0400 (16)	−0.0069 (14)	−0.0110 (13)	0.0062 (14)
C11	0.0431 (17)	0.0540 (19)	0.0372 (15)	−0.0027 (14)	−0.0064 (13)	0.0121 (14)
C12	0.070 (2)	0.0453 (19)	0.0527 (19)	−0.0090 (16)	−0.0065 (16)	0.0070 (15)
C13	0.073 (2)	0.070 (2)	0.062 (2)	−0.0075 (19)	−0.0284 (18)	0.0305 (18)
C14	0.059 (2)	0.094 (3)	0.0483 (19)	−0.032 (2)	−0.0001 (16)	0.0162 (19)
C15	0.0461 (17)	0.0526 (19)	0.0397 (16)	−0.0055 (14)	−0.0110 (13)	0.0077 (14)
N1	0.0368 (13)	0.0366 (13)	0.0350 (12)	−0.0020 (10)	−0.0022 (10)	0.0082 (10)
N2	0.0469 (14)	0.0512 (15)	0.0368 (13)	−0.0003 (11)	−0.0021 (11)	0.0186 (11)
N3	0.0403 (13)	0.0511 (15)	0.0415 (13)	0.0020 (11)	−0.0001 (11)	0.0167 (11)
N4	0.0328 (13)	0.0736 (18)	0.0436 (14)	−0.0076 (12)	−0.0081 (10)	0.0323 (13)
N5	0.0396 (13)	0.0462 (15)	0.0405 (13)	−0.0066 (11)	−0.0042 (10)	0.0068 (11)
N6	0.0417 (13)	0.0418 (14)	0.0324 (12)	−0.0034 (10)	−0.0047 (10)	0.0106 (10)
N7	0.0439 (14)	0.0383 (13)	0.0370 (12)	−0.0008 (10)	−0.0027 (10)	0.0106 (10)
O1	0.0802 (17)	0.0545 (14)	0.0542 (13)	−0.0188 (12)	−0.0156 (12)	0.0284 (11)

Geometric parameters (Å, º)

S1—C1	1.663 (3)	C10—H10	0.9300
C1—N2	1.333 (4)	C11—N6	1.385 (3)
C1—N1	1.370 (3)	C11—C13	1.487 (4)
C2—N3	1.301 (3)	C12—H12A	0.9600
C2—N1	1.377 (3)	C12—H12B	0.9600
C2—C3	1.463 (4)	C12—H12C	0.9600
C3—C7	1.386 (4)	C13—H13A	0.9600
C3—C4	1.400 (4)	C13—H13B	0.9600
C4—N5	1.333 (4)	C13—H13C	0.9600
C4—C15	1.495 (4)	C14—H14A	0.9600
C5—N5	1.338 (4)	C14—H14B	0.9600
C5—C6	1.390 (4)	C14—H14C	0.9600
C5—C14	1.496 (4)	C15—H15A	0.9600
C6—C7	1.382 (4)	C15—H15B	0.9600
C6—C8	1.490 (4)	C15—H15C	0.9600
C7—H7	0.9300	N1—N4	1.390 (3)
C8—O1	1.201 (3)	N2—N3	1.369 (3)
C8—N6	1.398 (4)	N2—H2	0.8600
C9—N7	1.313 (3)	N4—H4A	0.8600
C9—C10	1.412 (4)	N4—H4B	0.8600
C9—C12	1.489 (4)	N6—N7	1.385 (3)
C10—C11	1.341 (4)
N2—C1—N1	102.8 (2)	C9—C12—H12C	109.5
N2—C1—S1	129.0 (2)	H12A—C12—H12C	109.5
N1—C1—S1	128.2 (2)	H12B—C12—H12C	109.5
N3—C2—N1	110.1 (2)	C11—C13—H13A	109.5
N3—C2—C3	123.1 (2)	C11—C13—H13B	109.5
N1—C2—C3	126.8 (2)	H13A—C13—H13B	109.5
C7—C3—C4	117.8 (2)	C11—C13—H13C	109.5
C7—C3—C2	120.8 (2)	H13A—C13—H13C	109.5
C4—C3—C2	121.4 (2)	H13B—C13—H13C	109.5
N5—C4—C3	121.3 (2)	C5—C14—H14A	109.5
N5—C4—C15	114.7 (2)	C5—C14—H14B	109.5
C3—C4—C15	124.0 (2)	H14A—C14—H14B	109.5
N5—C5—C6	120.8 (3)	C5—C14—H14C	109.5
N5—C5—C14	115.2 (3)	H14A—C14—H14C	109.5
C6—C5—C14	124.0 (3)	H14B—C14—H14C	109.5
C7—C6—C5	118.7 (2)	C4—C15—H15A	109.5
C7—C6—C8	120.4 (2)	C4—C15—H15B	109.5
C5—C6—C8	120.6 (2)	H15A—C15—H15B	109.5
C6—C7—C3	120.2 (3)	C4—C15—H15C	109.5
C6—C7—H7	119.9	H15A—C15—H15C	109.5
C3—C7—H7	119.9	H15B—C15—H15C	109.5
O1—C8—N6	120.2 (3)	C1—N1—C2	108.8 (2)
O1—C8—C6	122.2 (3)	C1—N1—N4	125.6 (2)
N6—C8—C6	117.5 (2)	C2—N1—N4	125.7 (2)
N7—C9—C10	110.6 (3)	C1—N2—N3	114.0 (2)
N7—C9—C12	120.8 (3)	C1—N2—H2	123.0
C10—C9—C12	128.6 (3)	N3—N2—H2	123.0
C11—C10—C9	107.7 (3)	C2—N3—N2	104.4 (2)
C11—C10—H10	126.1	N1—N4—H4A	120.0
C9—C10—H10	126.1	N1—N4—H4B	120.0
C10—C11—N6	105.6 (3)	H4A—N4—H4B	120.0
C10—C11—C13	129.8 (3)	C4—N5—C5	120.9 (2)
N6—C11—C13	124.6 (3)	C11—N6—N7	111.0 (2)
C9—C12—H12A	109.5	C11—N6—C8	127.8 (2)
C9—C12—H12B	109.5	N7—N6—C8	121.2 (2)
H12A—C12—H12B	109.5	C9—N7—N6	105.1 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···N7^i	0.86	2.11	2.873 (3)	148

Symmetry code: (i) −x, −y+2, −z.