(2E)-2-(5-Bromo-2-hy­droxy-3-meth­oxy­benzyl­idene)-N-cyclo­hexyl­hydrazine­carbothio­amide

The title compound, C₁₅H₂₀BrN₃O₂S, crystallizes in the thio­amide form and adopts an E,E conformation with respect to the azomethine and hydrazinic bonds, respectively. The mol­ecules are paired through N—H...O and O—H...S hydrogen bonds, leading to the formation of centrosymmetric dimers in the crystal. These dimers are stacked along the a axis and are inter­connected through N—H...S hydrogen bonds to generate polymeric chains. The structure also features C—H...π interactions. An intra­molecular O—H...O bond is also present.

Key indicators

• Single-crystal X-ray study
• T = 296 K
• Mean [sigma](C-C) = 0.005 Å
• R factor = 0.035
• wR factor = 0.098
• Data-to-parameter ratio = 13.7

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT717_ALERT_1_C D...A   Unknown or Inconsistent Label ..........    <I>CG</
PLAT910_ALERT_3_C Missing # of FCF Reflections Below Th(Min) .....          3
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.595         11

Alert level G
PLAT002_ALERT_2_G Number of Distance or Angle Restraints on AtSite          6
PLAT005_ALERT_5_G No _iucr_refine_instructions_details in CIF ....          ?
PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints .......          3
PLAT909_ALERT_3_G Percentage of Observed Data at Theta(Max) still          71 Perc.

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
   3 ALERT level C = Check. Ensure it is not caused by an omission or oversight
   4 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
   4 ALERT type 3 Indicator that the structure quality may be low
   0 ALERT type 4 Improvement, methodology, query or suggestion
   1 ALERT type 5 Informative message, check

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S1. Comment

The hydrazinecarbothioamides of aromatic aldehydes and ketones have been shown to possess a diverse range of biological activities (Parrilha et al., 2011) and catalytic activity (Barber et al., 1992). The pharmacological activity of hydrazinecarbothioamides of o-hydroxyaromatic aldehydes is correlated to their ability to form chelates with biologically important metal ions by bonding through O, N and S atoms (Dutta et al., 1997) and reductive capacity.

The title compound adopts an E configuration with respect to the C8—N2 bond (Fig. 1) similar to salicylaldehyde-N(4)-phenylthiosemicarbazone (Seena et al., 2008) but in contrast to 2-hydroxyacetophenone-N(4)-phenylthiosemicarbazone (Seena et al., 2006), where a Z configuration exists. This is confirmed by the N1—N2—C8—S1 torsion angle of -175.9 (2)°. Also E configuration is perceived about the azomethine bond [N2—N1—C7—C6 = -175.5 (3)°] (Nisha et al., 2011). Atom O1 lies cis to O2, with an O1—C4—C5—O2 torsion angle of 0.7 (4)°. This favours the intramolecular hydrogen bonding interaction between O1 and H attached to O2 atom.

The C8—S1 bond distance [1.685 (3) Å] is closer to C═S bond length [1.60 Å] than to C—S bond length [1.81 Å] (Huheey et al., 1993) which confirms the existence of the compound in the thioamido form in solid state. Also the C7—N1 bond distance [1.267 (4) Å] is appreciably close to that of a C═N double bond [1.28 Å] (March, 1992), confirming the azomethine bond formation.

The mean plane deviation calculations show that the molecule as a whole is non-planar. But the central hydrazinecarbothioamide group (C7/N1/N2/C8/S1/N3/C9) is almost planar with a maximum deviation from the mean plane of -0.054 (2) Å for atom N1. This is similar to that observed in salicylaldehyde-N(4)-phenyl thiosemicarbazone (Seena et al., 2008). The ring Cg1ⁱⁱⁱ (comprising atoms C1—C6, with a maximum deviation of 0.005 (3) Å for C3) makes a dihedral angle of 18.90 (12)° with the hydrazinecarbothioamide moiety. Ring puckering analysis (Cremer & Pople, 1975) and least square plane calculations show that the cyclohexyl ring adopts a chair conformation (Q_T = 0.568 (4) Å) with the equatorial substitution at C9 for N3.

Fig. 2 shows the packing diagram of the title compound. The crystal packing involves one intramolecular and three intermolecular hydrogen bonds (Table 1). The intramolecular hydrogen bonding interaction, O2—H2'···O1 leads to the formation of a five membered ring comprising of atoms C4, C5, O2, H2' and O1 and facilitates almost planar geometry in part of the molecule. The intermolecular hydrogen bonds N2—H2···O2ⁱ and O2—H2'···S1ⁱ cause the pairing of molecules leading to the formation of centrosymmetric dimers in the crystal lattice. These dimers are stacked along the a axis and are interconnected through a third intermolecular hydrogen bond N3—H3'···S1ⁱⁱ to produce independent polymeric chains in the packing. Further stabilization is provided by C13—H13A···Cg1ⁱⁱⁱ interaction.

Related literature

For applications of hydrazinecarbothioamide and its derivatives, see: Barber et al. (1992); Parrilha et al. (2011). For the synthesis, see: Klayman et al. (1979). For related structures, see: Dutta et al. (1997); Seena et al. (2006, 2008); Nisha et al. (2011). For standard bond-length data, see: Huheey et al. (1993); March (1992). For ring puckering analysis, see: Cremer & Pople (1975).

S2. Experimental

The preparation of this compound involves a two step process (Klayman et al., 1979). In the first step, cyclohexyl isothiocyanate (15 mmol, 2 ml) in 15 ml methanol and hydrazine hydrate (90 mmol, 4.3 ml) in 15 ml methanol were mixed and the resulting solution was stirred for an hour. The white product, N(4)-cyclohexylthiosemicarbazide formed was filtered, washed with methanol and dried in vacuo. In the second step, a methanolic (20 ml) solution of 4-cyclohexylthiosemicarbazide (1 mmol, 0.1732 g) was added to a solution of 5-bromo-3-methoxysalicylaldehyde (1 mmol, 0.2310 g) in 15 ml methanol and the reaction mixture was refluxed for 2 h in acid medium. The product formed was filtered, washed with methanol and dried in vacuo. Suitable crystals were grown by slow evaporation of its solution in 1:1 mixture of DMF and methanol over 2 days.

S3. Refinement

All H atoms on C were placed in calculated positions, guided by difference maps, with C—H bond distances 0.93–0.97 Å. H atoms were assigned as U_iso=1.2Ueq (1.5 for Me). N2—H2, N3—H3' and O2—H2' H atoms were located from difference maps and restrained using DFIX instructions.

Computing details

Data collection: APEX2 (Bruker, 2004); cell refinement: APEX2 and SAINT (Bruker, 2004); data reduction: SAINT and XPREP (Bruker, 2004); program(s) used to solve structure: SIR92 (Altomare et al., 1993); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008) and ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and publCIF (Westrip, 2010).

Figures

	Fig. 1. The title compound, showing 50% probability displacement ellipsoids and the atom-numbering scheme.
	Fig. 2. A view of the unit cell along a axis.

(2E)-2-(5-Bromo-2-hydroxy-3-methoxybenzylidene)-N- cyclohexylhydrazinecarbothioamide

Crystal data

C15H20BrN3O2S	Z = 2
Mr = 386.31	F(000) = 396
Triclinic, P1	Dx = 1.541 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 5.7883 (4) Å	Cell parameters from 6391 reflections
b = 11.412 (1) Å	θ = 2.7–27.9°
c = 13.1312 (12) Å	µ = 2.60 mm^−1
α = 75.194 (4)°	T = 296 K
β = 86.493 (3)°	Block, colourless
γ = 83.489 (3)°	0.30 × 0.25 × 0.25 mm
V = 832.72 (12) Å^3

Data collection

Bruker APEXII CCD diffractometer	2923 independent reflections
Radiation source: fine-focus sealed tube	2521 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.070
Detector resolution: 8.33 pixels mm^-1	θmax = 25.0°, θmin = 2.7°
ω and ϕ scan	h = −6→6
Absorption correction: multi-scan (SADABS; Bruker, 2004)	k = −13→13
Tmin = 0.509, Tmax = 0.562	l = −15→15
12149 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)] = 0.035	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.098	w = 1/[σ^2(Fo^2) + (0.0194P)^2 + 0.6265P] where P = (Fo^2 + 2Fc^2)/3
S = 1.12	(Δ/σ)max = 0.001
2923 reflections	Δρmax = 0.27 e Å^−3
213 parameters	Δρmin = −0.41 e Å^−3
3 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: 0.0142 (18)

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
Br1	−0.42662 (6)	0.51878 (3)	0.63154 (3)	0.05382 (17)
S1	0.75115 (13)	0.88705 (7)	0.80347 (7)	0.0448 (2)
O1	−0.1322 (4)	0.2029 (2)	0.97526 (18)	0.0520 (6)
O2	0.1901 (4)	0.3362 (2)	0.99890 (19)	0.0471 (6)
N1	0.2789 (4)	0.6672 (2)	0.8130 (2)	0.0377 (6)
N2	0.4703 (4)	0.7170 (2)	0.8316 (2)	0.0398 (6)
N3	0.3358 (5)	0.8967 (2)	0.7247 (2)	0.0407 (6)
C1	−0.0696 (5)	0.5340 (3)	0.7638 (2)	0.0384 (7)
H1	−0.0523	0.6089	0.7167	0.046*
C2	−0.2371 (5)	0.4647 (3)	0.7502 (2)	0.0391 (7)
C3	−0.2709 (5)	0.3530 (3)	0.8186 (2)	0.0405 (7)
H3	−0.3877	0.3081	0.8082	0.049*
C4	−0.1268 (5)	0.3105 (3)	0.9024 (2)	0.0379 (7)
C5	0.0459 (5)	0.3795 (3)	0.9177 (2)	0.0358 (7)
C6	0.0749 (5)	0.4910 (3)	0.8492 (2)	0.0360 (7)
C7	0.2600 (5)	0.5588 (3)	0.8659 (2)	0.0370 (7)
H7	0.3681	0.5218	0.9169	0.044*
C8	0.5028 (5)	0.8331 (3)	0.7839 (2)	0.0350 (7)
C9	0.3347 (5)	1.0238 (3)	0.6669 (2)	0.0387 (7)
H9	0.4949	1.0399	0.6439	0.046*
C10	0.1921 (7)	1.0438 (3)	0.5704 (3)	0.0517 (9)
H10A	0.0369	1.0206	0.5918	0.062*
H10B	0.2626	0.9922	0.5262	0.062*
C11	0.1758 (8)	1.1755 (4)	0.5079 (3)	0.0687 (11)
H11A	0.3286	1.1957	0.4788	0.082*
H11B	0.0734	1.1866	0.4496	0.082*
C12	0.0842 (8)	1.2596 (4)	0.5760 (4)	0.0710 (12)
H12A	−0.0747	1.2451	0.5992	0.085*
H12B	0.0838	1.3435	0.5351	0.085*
C13	0.2320 (7)	1.2397 (3)	0.6707 (3)	0.0602 (10)
H13A	0.1675	1.2930	0.7145	0.072*
H13B	0.3882	1.2601	0.6476	0.072*
C14	0.2423 (6)	1.1085 (3)	0.7344 (3)	0.0481 (8)
H14A	0.3423	1.0969	0.7936	0.058*
H14B	0.0878	1.0898	0.7620	0.058*
C15	−0.2900 (7)	0.1217 (3)	0.9629 (3)	0.0551 (9)
H15A	−0.4466	0.1577	0.9693	0.083*
H15B	−0.2659	0.0468	1.0165	0.083*
H15C	−0.2643	0.1055	0.8947	0.083*
H3'	0.211 (4)	0.866 (3)	0.723 (3)	0.041 (9)*
H2	0.576 (5)	0.672 (3)	0.868 (2)	0.040 (9)*
H2'	0.144 (6)	0.277 (2)	1.042 (2)	0.055 (11)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Br1	0.0582 (3)	0.0553 (3)	0.0480 (2)	−0.01859 (17)	−0.01714 (16)	−0.00386 (17)
S1	0.0339 (4)	0.0390 (5)	0.0610 (5)	−0.0161 (3)	−0.0082 (4)	−0.0048 (4)
O1	0.0655 (15)	0.0405 (13)	0.0502 (14)	−0.0291 (11)	−0.0122 (11)	0.0010 (11)
O2	0.0522 (14)	0.0394 (13)	0.0484 (14)	−0.0181 (11)	−0.0168 (11)	0.0008 (11)
N1	0.0335 (13)	0.0323 (14)	0.0491 (15)	−0.0107 (10)	−0.0055 (11)	−0.0096 (12)
N2	0.0335 (14)	0.0287 (14)	0.0568 (17)	−0.0083 (11)	−0.0134 (12)	−0.0050 (12)
N3	0.0372 (15)	0.0336 (14)	0.0506 (16)	−0.0158 (11)	−0.0100 (12)	−0.0019 (12)
C1	0.0387 (16)	0.0334 (16)	0.0433 (17)	−0.0078 (13)	−0.0013 (13)	−0.0081 (14)
C2	0.0411 (17)	0.0388 (17)	0.0390 (17)	−0.0107 (13)	−0.0054 (13)	−0.0088 (14)
C3	0.0400 (17)	0.0419 (18)	0.0435 (18)	−0.0168 (13)	−0.0023 (13)	−0.0123 (14)
C4	0.0413 (17)	0.0338 (16)	0.0396 (17)	−0.0147 (13)	0.0013 (13)	−0.0068 (13)
C5	0.0368 (16)	0.0323 (16)	0.0402 (17)	−0.0090 (12)	−0.0027 (13)	−0.0097 (13)
C6	0.0351 (16)	0.0311 (16)	0.0443 (17)	−0.0081 (12)	−0.0020 (13)	−0.0117 (13)
C7	0.0358 (16)	0.0312 (16)	0.0451 (18)	−0.0089 (12)	−0.0047 (13)	−0.0083 (14)
C8	0.0333 (15)	0.0342 (16)	0.0393 (17)	−0.0099 (12)	0.0014 (12)	−0.0103 (13)
C9	0.0399 (16)	0.0325 (16)	0.0429 (17)	−0.0129 (12)	−0.0049 (13)	−0.0030 (13)
C10	0.066 (2)	0.044 (2)	0.0432 (19)	−0.0136 (16)	−0.0122 (16)	−0.0028 (15)
C11	0.094 (3)	0.050 (2)	0.054 (2)	−0.014 (2)	−0.016 (2)	0.0069 (19)
C12	0.067 (3)	0.044 (2)	0.086 (3)	−0.0003 (18)	0.001 (2)	0.010 (2)
C13	0.071 (3)	0.0349 (19)	0.075 (3)	−0.0115 (17)	0.014 (2)	−0.0166 (18)
C14	0.057 (2)	0.0419 (19)	0.048 (2)	−0.0148 (15)	0.0006 (16)	−0.0106 (15)
C15	0.064 (2)	0.044 (2)	0.060 (2)	−0.0312 (17)	−0.0025 (18)	−0.0071 (17)

Geometric parameters (Å, º)

Br1—C2	1.891 (3)	C7—H7	0.9300
S1—C8	1.685 (3)	C9—C14	1.506 (4)
O1—C4	1.352 (4)	C9—C10	1.508 (4)
O1—C15	1.417 (4)	C9—H9	0.9800
O2—C5	1.351 (4)	C10—C11	1.513 (5)
O2—H2'	0.826 (19)	C10—H10A	0.9700
N1—C7	1.267 (4)	C10—H10B	0.9700
N1—N2	1.363 (3)	C11—C12	1.507 (6)
N2—C8	1.342 (4)	C11—H11A	0.9700
N2—H2	0.840 (18)	C11—H11B	0.9700
N3—C8	1.308 (4)	C12—C13	1.507 (6)
N3—C9	1.454 (4)	C12—H12A	0.9700
N3—H3'	0.842 (18)	C12—H12B	0.9700
C1—C2	1.366 (4)	C13—C14	1.513 (5)
C1—C6	1.392 (4)	C13—H13A	0.9700
C1—H1	0.9300	C13—H13B	0.9700
C2—C3	1.385 (4)	C14—H14A	0.9700
C3—C4	1.374 (4)	C14—H14B	0.9700
C3—H3	0.9300	C15—H15A	0.9600
C4—C5	1.394 (4)	C15—H15B	0.9600
C5—C6	1.379 (4)	C15—H15C	0.9600
C6—C7	1.449 (4)
C4—O1—C15	118.5 (3)	C10—C9—H9	108.5
C5—O2—H2'	113 (3)	C9—C10—C11	111.4 (3)
C7—N1—N2	115.6 (3)	C9—C10—H10A	109.3
C8—N2—N1	120.9 (2)	C11—C10—H10A	109.3
C8—N2—H2	120 (2)	C9—C10—H10B	109.3
N1—N2—H2	119 (2)	C11—C10—H10B	109.3
C8—N3—C9	125.6 (2)	H10A—C10—H10B	108.0
C8—N3—H3'	119 (2)	C12—C11—C10	111.1 (3)
C9—N3—H3'	115 (2)	C12—C11—H11A	109.4
C2—C1—C6	119.1 (3)	C10—C11—H11A	109.4
C2—C1—H1	120.4	C12—C11—H11B	109.4
C6—C1—H1	120.4	C10—C11—H11B	109.4
C1—C2—C3	122.6 (3)	H11A—C11—H11B	108.0
C1—C2—Br1	119.6 (2)	C11—C12—C13	110.8 (3)
C3—C2—Br1	117.8 (2)	C11—C12—H12A	109.5
C4—C3—C2	118.1 (3)	C13—C12—H12A	109.5
C4—C3—H3	120.9	C11—C12—H12B	109.5
C2—C3—H3	120.9	C13—C12—H12B	109.5
O1—C4—C3	126.0 (3)	H12A—C12—H12B	108.1
O1—C4—C5	113.8 (3)	C12—C13—C14	110.8 (3)
C3—C4—C5	120.2 (3)	C12—C13—H13A	109.5
O2—C5—C6	119.3 (3)	C14—C13—H13A	109.5
O2—C5—C4	120.0 (3)	C12—C13—H13B	109.5
C6—C5—C4	120.7 (3)	C14—C13—H13B	109.5
C5—C6—C1	119.2 (3)	H13A—C13—H13B	108.1
C5—C6—C7	119.2 (3)	C9—C14—C13	110.4 (3)
C1—C6—C7	121.5 (3)	C9—C14—H14A	109.6
N1—C7—C6	121.9 (3)	C13—C14—H14A	109.6
N1—C7—H7	119.1	C9—C14—H14B	109.6
C6—C7—H7	119.1	C13—C14—H14B	109.6
N3—C8—N2	116.6 (3)	H14A—C14—H14B	108.1
N3—C8—S1	124.5 (2)	O1—C15—H15A	109.5
N2—C8—S1	118.8 (2)	O1—C15—H15B	109.5
N3—C9—C14	111.7 (3)	H15A—C15—H15B	109.5
N3—C9—C10	108.2 (2)	O1—C15—H15C	109.5
C14—C9—C10	111.4 (3)	H15A—C15—H15C	109.5
N3—C9—H9	108.5	H15B—C15—H15C	109.5
C14—C9—H9	108.5
C7—N1—N2—C8	−176.8 (3)	C2—C1—C6—C7	178.1 (3)
C6—C1—C2—C3	0.5 (5)	N2—N1—C7—C6	−175.5 (3)
C6—C1—C2—Br1	−177.5 (2)	C5—C6—C7—N1	−172.0 (3)
C1—C2—C3—C4	−1.0 (5)	C1—C6—C7—N1	10.1 (5)
Br1—C2—C3—C4	177.1 (2)	C9—N3—C8—N2	179.5 (3)
C15—O1—C4—C3	3.8 (5)	C9—N3—C8—S1	−0.6 (5)
C15—O1—C4—C5	−175.5 (3)	N1—N2—C8—N3	4.1 (4)
C2—C3—C4—O1	−178.6 (3)	N1—N2—C8—S1	−175.9 (2)
C2—C3—C4—C5	0.7 (5)	C8—N3—C9—C14	−86.2 (4)
O1—C4—C5—O2	0.7 (4)	C8—N3—C9—C10	150.8 (3)
C3—C4—C5—O2	−178.7 (3)	N3—C9—C10—C11	178.1 (3)
O1—C4—C5—C6	179.4 (3)	C14—C9—C10—C11	54.9 (4)
C3—C4—C5—C6	0.0 (5)	C9—C10—C11—C12	−54.6 (5)
O2—C5—C6—C1	178.2 (3)	C10—C11—C12—C13	55.9 (5)
C4—C5—C6—C1	−0.4 (5)	C11—C12—C13—C14	−57.4 (4)
O2—C5—C6—C7	0.2 (4)	N3—C9—C14—C13	−177.2 (3)
C4—C5—C6—C7	−178.4 (3)	C10—C9—C14—C13	−56.0 (4)
C2—C1—C6—C5	0.2 (5)	C12—C13—C14—C9	57.3 (4)

Hydrogen-bond geometry (Å, º)

Cg1 is the centroid of the C1-C6 ring.

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2′···O1	0.83 (2)	2.21 (4)	2.616 (3)	110 (3)
O2—H2′···S1^i	0.83 (2)	2.43 (3)	3.142 (2)	145 (3)
N2—H2···O2^i	0.84 (2)	2.25 (2)	2.959 (3)	142 (3)
N3—H3′···S1^ii	0.84 (2)	2.81 (3)	3.483 (3)	138 (3)
C13—H13A···Cg1^iii	0.97	2.71	3.664 (4)	168

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