Crystal structure of 3-(thio­phen-2-yl)-5-p-tolyl-4,5-di­hydro-1H-pyrazole-1-carbo­thio­amide

In the title compound, the central pyrazole ring adopts a twisted conformation on the –CH—CH₂– bond and its mean plane makes dihedral angles of 7.19 (12) and 71.13 (11)° with the attached thio­phene and toluene rings, respectively. In the crystal, mol­ecules are linked by N—H...S hydrogen bonds, forming chains propagating along [010].

Key indicators

• Single-crystal X-ray study
• T = 296 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.046
• wR factor = 0.127
• Data-to-parameter ratio = 13.1

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Alert level C
THETM01_ALERT_3_C  The value of sine(theta_max)/wavelength is less than 0.590
            Calculated sin(theta_max)/wavelength =    0.5834
PLAT023_ALERT_3_C Resolution (too) Low [sin(theta)/Lambda < 0.6]..      64.09 Degree
PLAT420_ALERT_2_C D-H Without Acceptor        N12    -   H12B   ..     Please Check
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.583         48 Report
PLAT913_ALERT_3_C Missing # of Very Strong Reflections in FCF ....          1 Note

Alert level G
PLAT007_ALERT_5_G Number of Unrefined Donor-H Atoms ..............          2 Report
PLAT793_ALERT_4_G The Model has Chirality at C9      (Centro SPGR)          R Verify
PLAT909_ALERT_3_G Percentage of Observed Data at Theta(Max) still          85 %
PLAT910_ALERT_3_G Missing # of FCF Reflection(s) Below Th(Min) ...          1 Report

   0 ALERT level A = Most likely a serious problem - resolve or explain
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   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
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PUBL024_ALERT_1_A The number of authors is greater than 5.
              Please specify the role of each of the co-authors
              for your paper.

Author Response: ... All the authors have equal contributions to this work.

 NS    -- Data collection and processing
 PG    -- Synthesis
 MM    -- Crystallization and Corresponding Author
 AKK   -- Designed the synthesis and Spectoscopic studies
 IW    -- Solved and analyzed the structure
 NKL   -- Final analysis, write up.


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S1. Chemical context

Five-membered heterocyclic pyrazole analogues have been used extensively as building blocks in organic synthesis. They have been transformed efficiently into molecules of potential medicinal and pharmaceutical important. Pyrazole derivatives have known to exhibit diverse biological applications such as anti­diabetic,anaesthetic, anti­microbial and anti­oxidant. In addition, they have also shown potential anti­cancer and anti­amoebic activity and to be potent and selective inhibitors of tissue-nonspecific alkaline phosphatase (Sidique et al. 2009). Earlier we synthesized α and β-unsaturated compounds which served as useful inter­mediates for the synthesis of pyrazolines (Manjula et al., 2013) and thia­zepines (Manjunath et al., 2014). As part of our ongoing research on pyrazole analogues, the title compound was synthesized and we report herein on its crystal structure. Studies of the biological activity of the title compound are underway and will be reported elsewhere.

S2. Structural commentary

The molecular structure of the title compound is illustrated in Fig. 1. The central pyrazole ring (N7/N8/C8–C10) adopts a twisted conformation with respect to the C9—C10 bond and its mean plane makes dihedral angles of 7.19 (12) and 71.13 (11)° with the thio­phene (S1/C2–C5) and toluene (C14–C19) rings, respectively. The carbothi­amide group [C11(═S13)N12] lies in the plane of the pyrazole ring, as indicated by the torsion angles N12—C11—N8—N7 = 0.6 (3) and S13—C11—N8—N7 = 179.96 (16)°, and adopts +synperiplanar and +anti­periplanar conformations, respectively. The title compound possess a chiral center at atom C9 but crystallized as a racemate.

S3. Supra­molecular features

In the crystal, molecules are linked by N—H···S hydrogen bonds, forming chains propagating along [010]. Within the chains there are N—H···π inter­actions involving the toluene ring (Fig. 2 and Table 1). Between the chains there are weak parallel slipped π–π inter­actions involving inversion-related thio­phene and pyrazole rings [Cg1···Cg2ⁱ = 3.7516 (14) Å; inter-planar distance = 3.5987 (10) Å; slippage = 1.06 Å; Cg1 and Cg2 are the centroids of rings S1/C2–C5 and N7/N8/C8–C10, respectively; symmetry code: (i) -x + 2, -y + 1, -z + 1].

S4. Database survey

A search of the Cambridge Structural Database (Version 5.36, May 2015; Groom & Allen, 2014) revealed seven structures containing the 3-(thio­phen-2-yl)-pyrazole unit. Amongst these are two thio­amides; the phenyl derivative of the title compound, 5-phenyl-3-(2-thienyl)-2-pyrazoline-1-thio­amide (HEFXEW; Işık et al., 2006), and 1-(N-ethyl­thio­carbamoyl)-3,5-bis­(2-thienyl)-2-pyrazoline (YINFUX; Köysal et al., 2007). In these two compounds, the pyrazole rings have envelope conformations with the methine C atom as the flap, and the mean planes of the two rings are inclined to one another by 11.98 and 10.13°, respectively. This is in contrast to the situation in the title compound where the pyrazole ring has a twisted conformation on the –CH–CH₂– bond and its mean plane is inclined to the thio­phene ring by 7.19 (12)°. In the crystal of the phenyl derivative (HEFXEW), molecules are also linked by N—H···S hydrogen bonds, forming chains.

S5. Synthesis and crystallization

A mixture of 3-(4-methyl­phenyl)-1-(thio­phen-2-yl)prop-2-en-1-one (0.001 mol) and thio­semicarbazine hydro­chloride (0.01 mol) and potassium hydroxide (0.02 mol) in ethyl alcohol (20 ml) was refluxed on a water bath for 6–8 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was poured into ice-cold water and stirred. The solid that separated was filtered, and washed with ice-cold water. The product was recrystallized from ethyl alcohol to give the title compound as re­cta­ngular yellow crystals. Analysis calculated for C₁₅H₁₅N₃S₂: C, 59.77; H, 5.02; N, 13.94 %; found: C, 59.74; H, 5.06; N, 13.88 %. ¹H NMR (CDCl₃): δ 2.297 (s, 3H, CH3), (dd, 1H, C4—Hb: J = 18.0, 8.5 Hz), (dd, 1H, C4—Hb: J 18.0, 8.5 Hz), 5.976–6.013 (dd, 1H, C—Ha: J = 18.0, 12.0 Hz), 6.163–7.169 (m, 7H, Ar—H and thio­phene ring-H), 7.330 (s, 2H, –NH₂). ¹³C NMR (CDCl₃): δ 43.77, 1 C, C-4), 63.34 (1 C, C-5), 125.35 (2C, Ar—C), 127.88 (1C, 5 m ring-C), 129.57 (1C, Ar—C), 129.67 (1C, Ar—C), 129.72 (1C, 5 m ring-C), 130.01 (1C, 5 m ring-C), 134.12, (1C, 5 m ring-C), 137.31 (1C, Ar—C), 138.67 (1C, Ar—C), 151.38 (1C, C-3), 176.36 (1C, C═S). MS (m/z): 303 (M+2, 10) 302 (M+1, 18), 301 (M+, 100), 284 (40), 161 (15).

S6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. H atoms were fixed geometrically and allowed to ride on their parent atoms: C—H = 0.93 – 0.98 Å with U_iso(H) = 1.5U_eq(C) for methyl H atoms and 1.2U_eq(C) for other H atoms.

Related literature

For related literature, see: Groom & Allen (2014); Işık, Köysal, Özdemir & Bilgin (2006); Köysal et al. (2007); Manjula et al. (2013); Manjunath et al. (2014); Sidique et al. (2009).

Computing details

Data collection: APEX2 (Bruker, 2013); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures

	Fig. 1. View of the molecular structure of the title compound, showing the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. A view along the a axis of the crystal packing of the title compound. The hydrogen bonds and C—H···π interactions are shown as dashed lines (see Table 1 for details). C-bound H atoms have been omitted for clarity.

5-(4-Methylphenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-carbothioamide

Crystal data

C15H15N3S2	F(000) = 632
Mr = 301.44	Dx = 1.362 Mg m^−3
Monoclinic, P21/c	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ybc	Cell parameters from 2262 reflections
a = 8.1035 (4) Å	θ = 5.5–64.1°
b = 12.0193 (5) Å	µ = 3.22 mm^−1
c = 15.1312 (7) Å	T = 296 K
β = 94.347 (2)°	Rectangle, yellow
V = 1469.52 (12) Å^3	0.27 × 0.25 × 0.24 mm
Z = 4

Data collection

Bruker X8 Proteum diffractometer	2397 independent reflections
Radiation source: Bruker MicroStar microfocus rotating anode	2262 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.044
Detector resolution: 18.4 pixels mm^-1	θmax = 64.1°, θmin = 5.5°
ϕ and ω scans	h = −9→9
Absorption correction: multi-scan (SADABS; Bruker, 2013)	k = −13→13
Tmin = 0.477, Tmax = 0.512	l = −16→17
11926 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)] = 0.046	H-atom parameters constrained
wR(F^2) = 0.127	w = 1/[σ^2(Fo^2) + (0.074P)^2 + 0.626P] where P = (Fo^2 + 2Fc^2)/3
S = 1.07	(Δ/σ)max < 0.001
2397 reflections	Δρmax = 0.37 e Å^−3
183 parameters	Δρmin = −0.44 e Å^−3
0 restraints	Extinction correction: SHELXL, FC^*=KFC[1+0.001XFC^2Λ^3/SIN(2Θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0160 (12)

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F² for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > σ(F²) is used only for calculating -R-factor-obs 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	0.83886 (8)	0.35843 (5)	0.55113 (4)	0.0527 (2)
S13	0.41488 (9)	0.76951 (5)	0.77019 (4)	0.0611 (3)
N7	0.6560 (2)	0.55350 (14)	0.63166 (11)	0.0396 (5)
N8	0.5837 (2)	0.65224 (14)	0.65865 (11)	0.0418 (6)
N12	0.5024 (3)	0.55813 (17)	0.77851 (13)	0.0572 (7)
C2	0.9012 (3)	0.3098 (2)	0.45389 (18)	0.0561 (8)
C3	0.8661 (3)	0.3801 (2)	0.38623 (17)	0.0613 (9)
C4	0.7858 (3)	0.4794 (2)	0.41081 (15)	0.0494 (8)
C5	0.7627 (3)	0.47817 (18)	0.50124 (13)	0.0400 (6)
C6	0.6841 (2)	0.56438 (17)	0.54966 (13)	0.0368 (6)
C9	0.5786 (3)	0.73914 (17)	0.58990 (13)	0.0381 (6)
C10	0.6257 (3)	0.67214 (18)	0.50885 (13)	0.0417 (6)
C11	0.5039 (3)	0.65429 (18)	0.73411 (14)	0.0438 (7)
C14	0.6974 (2)	0.83434 (15)	0.61077 (13)	0.0326 (5)
C15	0.8130 (3)	0.83437 (18)	0.68204 (14)	0.0421 (7)
C16	0.9258 (3)	0.92083 (19)	0.69439 (15)	0.0469 (7)
C17	0.9243 (3)	1.00979 (18)	0.63663 (14)	0.0437 (7)
C18	0.8065 (3)	1.00989 (18)	0.56564 (15)	0.0470 (7)
C19	0.6951 (3)	0.92360 (18)	0.55243 (14)	0.0419 (6)
C20	1.0453 (4)	1.1050 (2)	0.65103 (19)	0.0688 (10)
H2	0.95400	0.24170	0.44810	0.0670*
H3	0.89180	0.36530	0.32850	0.0740*
H4	0.75340	0.53690	0.37220	0.0590*
H9	0.46560	0.76780	0.57940	0.0460*
H10A	0.53080	0.66110	0.46670	0.0500*
H10B	0.71300	0.70870	0.47930	0.0500*
H12A	0.55020	0.50040	0.75860	0.0690*
H12B	0.45370	0.55400	0.82700	0.0690*
H15	0.81560	0.77590	0.72240	0.0500*
H16	1.00410	0.91880	0.74260	0.0560*
H18	0.80230	1.06920	0.52610	0.0560*
H19	0.61750	0.92520	0.50390	0.0500*
H20A	0.98990	1.16790	0.67420	0.1030*
H20B	1.08790	1.12470	0.59560	0.1030*
H20C	1.13490	1.08270	0.69240	0.1030*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0578 (4)	0.0494 (4)	0.0530 (4)	−0.0001 (3)	0.0172 (3)	−0.0061 (2)
S13	0.0750 (5)	0.0495 (4)	0.0628 (4)	−0.0051 (3)	0.0306 (3)	−0.0180 (3)
N7	0.0483 (10)	0.0317 (9)	0.0408 (9)	−0.0044 (7)	0.0164 (7)	−0.0045 (7)
N8	0.0561 (11)	0.0321 (9)	0.0395 (9)	−0.0044 (8)	0.0188 (8)	−0.0026 (7)
N12	0.0786 (14)	0.0492 (12)	0.0478 (11)	−0.0064 (10)	0.0304 (10)	0.0030 (9)
C2	0.0557 (14)	0.0474 (14)	0.0681 (16)	−0.0092 (11)	0.0240 (12)	−0.0190 (12)
C3	0.0728 (17)	0.0637 (16)	0.0506 (14)	−0.0182 (13)	0.0258 (12)	−0.0257 (13)
C4	0.0583 (14)	0.0489 (13)	0.0429 (12)	−0.0148 (11)	0.0156 (10)	−0.0163 (10)
C5	0.0403 (11)	0.0424 (12)	0.0386 (10)	−0.0145 (9)	0.0112 (8)	−0.0087 (9)
C6	0.0377 (10)	0.0362 (11)	0.0372 (10)	−0.0118 (8)	0.0084 (8)	−0.0055 (8)
C9	0.0409 (11)	0.0348 (11)	0.0391 (11)	−0.0036 (8)	0.0070 (8)	−0.0004 (8)
C10	0.0509 (12)	0.0387 (11)	0.0357 (10)	−0.0121 (9)	0.0050 (9)	−0.0036 (9)
C11	0.0491 (12)	0.0444 (12)	0.0398 (11)	−0.0122 (10)	0.0157 (9)	−0.0080 (9)
C14	0.0362 (10)	0.0275 (9)	0.0349 (9)	0.0015 (8)	0.0087 (8)	−0.0029 (7)
C15	0.0504 (12)	0.0342 (11)	0.0410 (11)	0.0016 (9)	−0.0004 (9)	0.0053 (8)
C16	0.0491 (12)	0.0474 (13)	0.0430 (11)	−0.0019 (10)	−0.0040 (9)	−0.0065 (10)
C17	0.0495 (12)	0.0371 (12)	0.0459 (11)	−0.0077 (9)	0.0137 (9)	−0.0128 (9)
C18	0.0642 (14)	0.0324 (11)	0.0451 (11)	−0.0070 (10)	0.0090 (10)	0.0057 (9)
C19	0.0508 (12)	0.0375 (11)	0.0366 (10)	−0.0002 (9)	−0.0010 (9)	0.0022 (8)
C20	0.0790 (19)	0.0592 (17)	0.0697 (17)	−0.0309 (15)	0.0151 (14)	−0.0182 (14)

Geometric parameters (Å, º)

S1—C2	1.695 (3)	C15—C16	1.387 (3)
S1—C5	1.718 (2)	C16—C17	1.381 (3)
S13—C11	1.672 (2)	C17—C18	1.382 (3)
N7—N8	1.398 (2)	C17—C20	1.512 (4)
N7—C6	1.285 (3)	C18—C19	1.380 (3)
N8—C9	1.473 (3)	C2—H2	0.9300
N8—C11	1.354 (3)	C3—H3	0.9300
N12—C11	1.337 (3)	C4—H4	0.9300
N12—H12B	0.8600	C9—H9	0.9800
N12—H12A	0.8600	C10—H10A	0.9700
C2—C3	1.341 (4)	C10—H10B	0.9700
C3—C4	1.422 (3)	C15—H15	0.9300
C4—C5	1.395 (3)	C16—H16	0.9300
C5—C6	1.445 (3)	C18—H18	0.9300
C6—C10	1.496 (3)	C19—H19	0.9300
C9—C14	1.513 (3)	C20—H20A	0.9600
C9—C10	1.539 (3)	C20—H20B	0.9600
C14—C19	1.389 (3)	C20—H20C	0.9600
C14—C15	1.374 (3)
C2—S1—C5	91.62 (11)	C18—C17—C20	120.9 (2)
N8—N7—C6	107.73 (16)	C17—C18—C19	121.2 (2)
N7—N8—C9	112.69 (15)	C14—C19—C18	120.8 (2)
N7—N8—C11	119.94 (17)	S1—C2—H2	124.00
C9—N8—C11	126.37 (17)	C3—C2—H2	124.00
H12A—N12—H12B	120.00	C2—C3—H3	123.00
C11—N12—H12A	120.00	C4—C3—H3	123.00
C11—N12—H12B	120.00	C3—C4—H4	125.00
S1—C2—C3	112.67 (19)	C5—C4—H4	125.00
C2—C3—C4	113.8 (2)	N8—C9—H9	110.00
C3—C4—C5	110.2 (2)	C10—C9—H9	110.00
S1—C5—C4	111.68 (17)	C14—C9—H9	110.00
S1—C5—C6	122.38 (15)	C6—C10—H10A	111.00
C4—C5—C6	125.9 (2)	C6—C10—H10B	111.00
N7—C6—C10	114.39 (17)	C9—C10—H10A	111.00
N7—C6—C5	122.27 (18)	C9—C10—H10B	111.00
C5—C6—C10	123.33 (17)	H10A—C10—H10B	109.00
N8—C9—C10	101.33 (16)	C14—C15—H15	120.00
N8—C9—C14	113.93 (17)	C16—C15—H15	120.00
C10—C9—C14	111.69 (18)	C15—C16—H16	119.00
C6—C10—C9	102.35 (16)	C17—C16—H16	119.00
N8—C11—N12	115.5 (2)	C17—C18—H18	119.00
S13—C11—N12	122.08 (18)	C19—C18—H18	119.00
S13—C11—N8	122.39 (16)	C14—C19—H19	120.00
C9—C14—C15	123.31 (18)	C18—C19—H19	120.00
C9—C14—C19	118.29 (18)	C17—C20—H20A	109.00
C15—C14—C19	118.32 (18)	C17—C20—H20B	109.00
C14—C15—C16	120.6 (2)	C17—C20—H20C	109.00
C15—C16—C17	121.4 (2)	H20A—C20—H20B	110.00
C16—C17—C20	121.4 (2)	H20A—C20—H20C	109.00
C16—C17—C18	117.7 (2)	H20B—C20—H20C	110.00
C5—S1—C2—C3	−0.2 (2)	C4—C5—C6—N7	174.6 (2)
C2—S1—C5—C4	0.1 (2)	C4—C5—C6—C10	−4.2 (3)
C2—S1—C5—C6	179.6 (2)	C5—C6—C10—C9	−171.56 (19)
C6—N7—N8—C9	−5.9 (2)	N7—C6—C10—C9	9.6 (2)
C6—N7—N8—C11	163.41 (18)	C10—C9—C14—C15	−107.0 (2)
N8—N7—C6—C5	178.34 (17)	C10—C9—C14—C19	69.6 (2)
N8—N7—C6—C10	−2.8 (2)	N8—C9—C14—C19	−176.34 (18)
C11—N8—C9—C14	82.7 (3)	N8—C9—C10—C6	−11.5 (2)
C9—N8—C11—N12	168.3 (2)	C14—C9—C10—C6	110.18 (18)
N7—N8—C11—S13	179.96 (16)	N8—C9—C14—C15	7.1 (3)
N7—N8—C9—C10	11.3 (2)	C9—C14—C15—C16	175.7 (2)
C11—N8—C9—C10	−157.2 (2)	C19—C14—C15—C16	−0.9 (3)
N7—N8—C11—N12	0.6 (3)	C9—C14—C19—C18	−176.6 (2)
N7—N8—C9—C14	−108.84 (18)	C15—C14—C19—C18	0.2 (3)
C9—N8—C11—S13	−12.4 (3)	C14—C15—C16—C17	0.9 (4)
S1—C2—C3—C4	0.3 (3)	C15—C16—C17—C18	−0.1 (4)
C2—C3—C4—C5	−0.3 (3)	C15—C16—C17—C20	178.9 (2)
C3—C4—C5—S1	0.1 (3)	C16—C17—C18—C19	−0.6 (3)
C3—C4—C5—C6	−179.4 (2)	C20—C17—C18—C19	−179.6 (2)
S1—C5—C6—N7	−4.9 (3)	C17—C18—C19—C14	0.6 (3)
S1—C5—C6—C10	176.33 (17)

Hydrogen-bond geometry (Å, º)

Cg3 is the centroid of the benzene ring C14–C19.

D—H···A	D—H	H···A	D···A	D—H···A
N12—H12A···S13^i	0.86	2.83	3.620 (2)	154
N12—H12B···Cg3^i	0.86	2.81	3.443 (2)	132

Symmetry code: (i) −x+1, y−1/2, −z+3/2.