Crystal structure of (E)-2-[(2S,5R)-2-isopropyl-5-methyl­cyclo­hexyl­idene]hydrazine-1-carbo­thio­amide

The title compound, C₁₁H₂₁N₃S, consists of a menthone moiety attached to an extended thio­semicarbazone group with the N—N—C—N torsion angle being 11.92 (16)°. The cyclo­hexane ring has a chair conformation and the conformation about the C=N bond is E. In the crystal, mol­ecules are linked via pairs of N—H...S hydrogen bonds, forming chains along the a axis. The absolute structure could be assigned with reference to the starting material, i.e. enanti­opure (−)-menthone [Flack parameter = 0.05 (5)].

Key indicators

• Single-crystal X-ray study
• T = 123 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.025
• wR factor = 0.060
• Data-to-parameter ratio = 13.8

checkCIF/PLATON results

No syntax errors found



Alert level B
PLAT230_ALERT_2_B Hirshfeld Test Diff for    S1     --  C11     ..        7.4 su

Alert level G
PLAT005_ALERT_5_G No _iucr_refine_instructions_details  in the CIF     Please Do !
PLAT066_ALERT_1_G Predicted and Reported Tmin&Tmax Range Identical          ? Check
PLAT720_ALERT_4_G Number of Unusual/Non-Standard Labels ..........          3 Note
PLAT791_ALERT_4_G The Model has Chirality at C2      .............          S Verify
PLAT791_ALERT_4_G The Model has Chirality at C5      .............          R Verify
PLAT910_ALERT_3_G Missing # of FCF Reflections Below Th(Min) .....          2 Why ?

   0 ALERT level A = Most likely a serious problem - resolve or explain
   1 ALERT level B = A potentially serious problem, consider carefully
   0 ALERT level C = Check. Ensure it is not caused by an omission or oversight
   6 ALERT level G = General information/check it is not something unexpected

   1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 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
   3 ALERT type 4 Improvement, methodology, query or suggestion
   1 ALERT type 5 Informative message, check

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S1. Structural commentary

Several thio­semicarbazone derivatives have a wide range of pharmacological properties. For example, some thio­semicarbazone derivatives of the peppermint essential oil show anti-HIV activity (Mishra et al., 2012). As part of our studies on synthesis and structural chemistry of thio­semicarbazone derivatives of natural products, we report herein the crystal structure of (-)-3-menthone thio­semicarbazone.

In the molecular structure of the title compound, Fig, 1, the thio­semicarbazone unit is not completely planar, but shows a torsion angle N1–N2–C11–N3 of 11.92 (16)°. The cyclo­hexane ring of the menthone unit is in the chair conformation. The molecule, shows also a trans conformation about the N1—N2 bond.

For the synthesis, enanti­opure (-)-menthone was used. No change in chirality occurred in the course of the reaction with thio­semicarbazide and the obtained product emerged as chiral crystals in the non-centrosymmetric space group P2₁2₁2₁.

In the crystal, molecules are connected by a pair of N—H···S hydrogen bonds, with bridging sulfur atoms, into a one-dimensional chain along the a-axis (Fig. 2 and Table 1).

S2. Synthesis and crystallization

The synthesis of the title compound was adapted from a previously reported procedure (Freund & Schander, 1902). In a hydro­chloric acid catalyzed reaction, a mixture of (-)-menthone (10 mmol) and thio­semicarbazide (10 mmol) in ethanol (80 ml) was refluxed for 5 h. After cooling and filtering, the title compound was obtained. Colourless needles were obtained by slow evaporation of a solution in the solvent DMSO.

S3. Refinement

All the H atoms were located in a difference Fourier map and freely refined. The assignment of the correct absolute configuration was assured by the Flack parameter of 0.05 (5).

Related literature

For one of the first reports of the synthesis of thiosemicarbazone derivatives, see: Freund & Schander (1902). For a report of the anti-HIV activity of thiosemicarbazone derivatives of menthone, see: Mishra et al. (2012).

Computing details

Data collection: COLLECT (Nonius, 1998); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO and SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg, 2006); software used to prepare material for publication: publCIF (Westrip, 2010).

Figures

	Fig. 1. The molecular structure of the title molecule, with atom labelling. Displacement ellipsoids are drawn at the 40% probability level.
	Fig. 2. A partial view along the c-axis of the crystal structure of the title compound, showing the hydrogen bonded chains (hydrogen bonds are shown as dashed lines; see Table 1 for details).

(E)-2-[(2S,5R)-2-Isopropyl-5-methylcyclohexylidene]hydrazine-1-carbothioamide

Crystal data

C11H21N3S	F(000) = 496
Mr = 227.37	Dx = 1.141 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 37558 reflections
a = 8.2139 (1) Å	θ = 2.9–27.5°
b = 11.6117 (2) Å	µ = 0.22 mm^−1
c = 13.8820 (2) Å	T = 123 K
V = 1324.03 (3) Å^3	Needle, colourless
Z = 4	0.54 × 0.10 × 0.06 mm

Data collection

Nonius KappaCCD diffractometer	3033 independent reflections
Radiation source: fine-focus sealed tube, Nonius KappaCCD	2848 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.046
Detector resolution: 9 pixels mm^-1	θmax = 27.5°, θmin = 2.9°
CCD rotation images, thick slices scans	h = −10→10
Absorption correction: analytical (Alcock, 1970)	k = −15→15
Tmin = 0.890, Tmax = 0.988	l = −17→18
22998 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)] = 0.025	All H-atom parameters refined
wR(F^2) = 0.060	w = 1/[σ^2(Fo^2) + (0.0305P)^2 + 0.1951P] where P = (Fo^2 + 2Fc^2)/3
S = 1.05	(Δ/σ)max = 0.001
3033 reflections	Δρmax = 0.15 e Å^−3
220 parameters	Δρmin = −0.19 e Å^−3
0 restraints	Absolute structure: Flack (1983), ???? Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.05 (5)

Special details

Experimental. Alcock, N. W., 1970

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	−0.08952 (3)	−0.30315 (2)	0.48771 (2)	0.02034 (8)
N1	0.04374 (12)	0.00856 (9)	0.41416 (7)	0.0177 (2)
N2	0.04891 (13)	−0.11130 (9)	0.42555 (8)	0.0186 (2)
N3	−0.22424 (13)	−0.09979 (10)	0.45259 (9)	0.0231 (2)
C1	0.16488 (14)	0.05821 (10)	0.37313 (8)	0.0168 (2)
C2	0.16273 (15)	0.18913 (11)	0.36955 (8)	0.0192 (2)
C3	0.20800 (17)	0.23095 (11)	0.26796 (10)	0.0238 (3)
C4	0.36682 (16)	0.17718 (11)	0.23241 (11)	0.0263 (3)
C5	0.35351 (16)	0.04665 (11)	0.22932 (9)	0.0217 (3)
C6	0.31196 (15)	−0.00025 (11)	0.32996 (9)	0.0193 (2)
C7	0.00597 (17)	0.24498 (11)	0.40902 (10)	0.0244 (3)
C8	−0.14038 (18)	0.23265 (14)	0.34230 (13)	0.0337 (3)
C9	0.0343 (3)	0.37222 (13)	0.43286 (15)	0.0406 (4)
C10	0.50872 (19)	−0.00988 (14)	0.19164 (12)	0.0320 (3)
C11	−0.09004 (15)	−0.16286 (9)	0.45455 (8)	0.0166 (2)
HN2	0.139 (2)	−0.1453 (14)	0.4388 (12)	0.030 (4)*
HN3A	−0.308 (2)	−0.1263 (15)	0.4708 (13)	0.038 (5)*
HN3B	−0.214 (2)	−0.0304 (16)	0.4401 (12)	0.032 (4)*
H2	0.2510 (19)	0.2111 (14)	0.4104 (11)	0.025 (4)*
H3A	0.1221 (19)	0.2081 (13)	0.2244 (11)	0.026 (4)*
H3B	0.2167 (19)	0.3172 (14)	0.2688 (11)	0.026 (4)*
H4A	0.395 (2)	0.2061 (14)	0.1673 (12)	0.038 (4)*
H4B	0.4556 (19)	0.1942 (14)	0.2754 (11)	0.027 (4)*
H5	0.2651 (19)	0.0275 (13)	0.1881 (11)	0.022 (4)*
H6A	0.2988 (18)	−0.0818 (14)	0.3277 (11)	0.024 (4)*
H6B	0.4050 (19)	0.0163 (12)	0.3714 (10)	0.021 (3)*
H7	−0.0193 (19)	0.2058 (13)	0.4704 (11)	0.032 (4)*
H8A	−0.124 (2)	0.2778 (16)	0.2830 (13)	0.046 (5)*
H8B	−0.237 (2)	0.2586 (16)	0.3744 (12)	0.040 (5)*
H8C	−0.160 (2)	0.1543 (16)	0.3249 (12)	0.033 (4)*
H9A	−0.058 (2)	0.4100 (15)	0.4585 (12)	0.037 (5)*
H9B	0.123 (3)	0.3810 (18)	0.4819 (17)	0.067 (6)*
H9C	0.063 (2)	0.4138 (15)	0.3757 (14)	0.045 (5)*
H10A	0.606 (2)	0.0073 (14)	0.2334 (12)	0.039 (4)*
H10B	0.494 (2)	−0.0917 (18)	0.1884 (13)	0.041 (5)*
H10C	0.533 (2)	0.0126 (17)	0.1271 (15)	0.053 (6)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.01461 (12)	0.01597 (13)	0.03044 (16)	−0.00151 (11)	−0.00087 (12)	0.00710 (12)
N1	0.0187 (5)	0.0138 (5)	0.0206 (5)	−0.0008 (4)	−0.0011 (4)	0.0037 (4)
N2	0.0155 (5)	0.0140 (5)	0.0264 (6)	−0.0001 (4)	0.0001 (4)	0.0059 (4)
N3	0.0150 (5)	0.0163 (5)	0.0380 (7)	−0.0007 (4)	0.0031 (5)	0.0053 (5)
C1	0.0183 (5)	0.0171 (6)	0.0151 (5)	−0.0002 (5)	−0.0028 (5)	0.0026 (4)
C2	0.0201 (5)	0.0157 (5)	0.0217 (6)	−0.0026 (5)	−0.0036 (5)	0.0016 (5)
C3	0.0251 (6)	0.0191 (6)	0.0272 (6)	0.0005 (5)	0.0023 (6)	0.0079 (5)
C4	0.0263 (7)	0.0213 (7)	0.0314 (7)	−0.0008 (5)	0.0073 (6)	0.0095 (5)
C5	0.0219 (6)	0.0219 (6)	0.0213 (6)	−0.0003 (5)	0.0018 (5)	0.0048 (5)
C6	0.0183 (5)	0.0174 (6)	0.0223 (6)	−0.0014 (5)	0.0000 (5)	0.0053 (5)
C7	0.0301 (7)	0.0171 (6)	0.0259 (7)	0.0015 (5)	0.0053 (6)	0.0013 (5)
C8	0.0249 (7)	0.0326 (8)	0.0435 (9)	0.0071 (6)	0.0017 (6)	0.0066 (7)
C9	0.0557 (11)	0.0205 (7)	0.0455 (10)	0.0015 (7)	0.0114 (8)	−0.0055 (7)
C10	0.0324 (7)	0.0295 (8)	0.0342 (8)	0.0045 (6)	0.0108 (7)	0.0073 (6)
C11	0.0159 (5)	0.0174 (5)	0.0165 (5)	−0.0012 (5)	−0.0010 (5)	0.0007 (4)

Geometric parameters (Å, º)

S1—C11	1.6928 (11)	C4—H4B	0.963 (16)
N1—C1	1.2833 (15)	C5—C10	1.5264 (19)
N1—N2	1.4015 (14)	C5—C6	1.5377 (17)
N2—C11	1.3502 (15)	C5—H5	0.951 (15)
N2—HN2	0.858 (17)	C6—H6A	0.954 (16)
N3—C11	1.3237 (16)	C6—H6B	0.976 (15)
N3—HN3A	0.794 (19)	C7—C8	1.524 (2)
N3—HN3B	0.829 (18)	C7—C9	1.5318 (19)
C1—C6	1.5098 (17)	C7—H7	0.988 (16)
C1—C2	1.5211 (16)	C8—H8A	0.984 (19)
C2—C3	1.5372 (17)	C8—H8B	0.961 (19)
C2—C7	1.5423 (18)	C8—H8C	0.955 (18)
C2—H2	0.955 (15)	C9—H9A	0.947 (18)
C3—C4	1.5282 (18)	C9—H9B	1.00 (2)
C3—H3A	0.966 (16)	C9—H9C	0.96 (2)
C3—H3B	1.004 (16)	C10—H10A	1.008 (19)
C4—C5	1.5202 (17)	C10—H10B	0.96 (2)
C4—H4A	0.991 (16)	C10—H10C	0.95 (2)
C1—N1—N2	118.21 (10)	C1—C6—C5	112.27 (10)
C11—N2—N1	116.64 (10)	C1—C6—H6A	111.6 (9)
C11—N2—HN2	117.4 (11)	C5—C6—H6A	110.3 (9)
N1—N2—HN2	120.5 (11)	C1—C6—H6B	107.7 (8)
C11—N3—HN3A	120.0 (13)	C5—C6—H6B	107.0 (8)
C11—N3—HN3B	117.0 (12)	H6A—C6—H6B	107.6 (12)
HN3A—N3—HN3B	122.3 (17)	C8—C7—C9	109.98 (13)
N1—C1—C6	126.49 (10)	C8—C7—C2	113.76 (11)
N1—C1—C2	117.03 (11)	C9—C7—C2	110.83 (12)
C6—C1—C2	116.47 (10)	C8—C7—H7	108.4 (9)
C1—C2—C3	110.06 (10)	C9—C7—H7	106.8 (9)
C1—C2—C7	114.73 (10)	C2—C7—H7	106.7 (9)
C3—C2—C7	113.27 (10)	C7—C8—H8A	110.6 (11)
C1—C2—H2	103.8 (10)	C7—C8—H8B	110.0 (10)
C3—C2—H2	106.1 (9)	H8A—C8—H8B	109.4 (16)
C7—C2—H2	108.1 (9)	C7—C8—H8C	112.0 (10)
C4—C3—C2	111.94 (11)	H8A—C8—H8C	108.5 (15)
C4—C3—H3A	108.0 (9)	H8B—C8—H8C	106.2 (15)
C2—C3—H3A	108.1 (9)	C7—C9—H9A	113.9 (10)
C4—C3—H3B	110.5 (9)	C7—C9—H9B	110.8 (12)
C2—C3—H3B	108.8 (9)	H9A—C9—H9B	106.3 (15)
H3A—C3—H3B	109.4 (12)	C7—C9—H9C	110.1 (10)
C5—C4—C3	110.80 (10)	H9A—C9—H9C	106.0 (15)
C5—C4—H4A	109.2 (9)	H9B—C9—H9C	109.5 (16)
C3—C4—H4A	110.8 (10)	C5—C10—H10A	112.4 (10)
C5—C4—H4B	106.1 (10)	C5—C10—H10B	109.9 (11)
C3—C4—H4B	111.2 (9)	H10A—C10—H10B	108.7 (15)
H4A—C4—H4B	108.6 (13)	C5—C10—H10C	112.4 (12)
C4—C5—C10	112.23 (11)	H10A—C10—H10C	108.5 (15)
C4—C5—C6	110.09 (10)	H10B—C10—H10C	104.6 (16)
C10—C5—C6	110.15 (11)	N3—C11—N2	116.90 (10)
C4—C5—H5	107.7 (9)	N3—C11—S1	122.69 (9)
C10—C5—H5	109.3 (9)	N2—C11—S1	120.37 (9)
C6—C5—H5	107.2 (9)
C1—N1—N2—C11	−169.70 (11)	C3—C4—C5—C6	−58.39 (15)
N2—N1—C1—C6	3.59 (18)	N1—C1—C6—C5	133.17 (12)
N2—N1—C1—C2	−174.83 (9)	C2—C1—C6—C5	−48.41 (14)
N1—C1—C2—C3	−133.96 (11)	C4—C5—C6—C1	52.25 (14)
C6—C1—C2—C3	47.46 (14)	C10—C5—C6—C1	176.53 (11)
N1—C1—C2—C7	−4.82 (15)	C1—C2—C7—C8	−73.69 (14)
C6—C1—C2—C7	176.60 (11)	C3—C2—C7—C8	53.83 (15)
C1—C2—C3—C4	−52.04 (14)	C1—C2—C7—C9	161.77 (12)
C7—C2—C3—C4	178.03 (11)	C3—C2—C7—C9	−70.71 (15)
C2—C3—C4—C5	59.56 (15)	N1—N2—C11—N3	11.92 (16)
C3—C4—C5—C10	178.54 (12)	N1—N2—C11—S1	−170.14 (8)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—HN2···S1^i	0.858 (17)	2.525 (18)	3.3551 (11)	163.1 (15)
N3—HN3A···S1^ii	0.794 (19)	2.52 (2)	3.3104 (12)	173.0 (17)

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