1-(2-Chloro-5-nitro­phen­yl)-3-(2,2-di­methyl­propion­yl)thio­urea

With the exception of the C atoms of two of the methyl groups of the tert-butyl substituent, all of the non-H atoms of the title compound, C₁₂H₁₄ClN₃O₃S, lie on a mirror plane. The 2-chloro-5-nitro­phenyl and 2,2-dimethyl­propionyl substituents are, respectively, cis and trans relative to the thio­carbonyl S atom across the two C—N bonds. Intra­molecular N—H...O and C—H...S hydrogen bonds form S(6) ring motifs, also in the mirror plane. Despite the presence of two N—H subsituents, no inter­molecular hydrogen bonds are observed in the crystal structure. Weak π–π contacts [centroid–centroid distances of 4.2903 (17) Å] involving adjacent aromatic rings link the mol­ecules in a head-to-tail fashion above and below the mol­ecular plane.

Key indicators

• Single-crystal X-ray study
• T = 89 K
• Mean [sigma](C-C) = 0.004 Å
• R factor = 0.033
• wR factor = 0.092
• Data-to-parameter ratio = 11.0

checkCIF/PLATON results

No syntax errors found





Alert level C
SHFSU01_ALERT_2_C  Test not performed. _refine_ls_shift/su_max and
            _refine_ls_shift/esd_max not present.
            Absolute value of the parameter shift to su ratio given   0.001
PLAT420_ALERT_2_C D-H Without Acceptor       N1     -   H1N    ...          ?
PLAT152_ALERT_1_C Supplied and Calc Volume s.u. Inconsistent .....          ?

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   3 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
   2 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
   0 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

---

S1. Comment

Substituted thioureas are versatile building blocks for the synthesis of a variety of heterocyclic compounds with a broad range of useful applications and exhibiting a wide range of bioactivity. Solid-phase Biginelli pyrimidine synthesis (Eynde & Watte, 2003) and synthesis of imidazoline derivatives (Fu et al., 1999) have been carried out using resin-bound thioureas. Pyridyl thioureas are switchable anion receptors (Rashdan et al., 2006); thioureas are also efficient guanylating agents (Maryanoff et al., 1986) while N,N-dialkyl-N-aroyl thioureas are efficient ligands for the separation of platinum group metals (Koch, 2001). Acyl thioureas are well known for their superior pesticidal, fungicidal, antiviral and plant-growth regulatory activities (Upadhyaya & Srivastava, 1982). 1,3-Dialkyl or diaryl thioureas show powerful antifungal activity against plant pathogens Pyricularia oryzae and Drechslera oryzae (Krishnamurthy et al., 1999). Substituted thioureas are potent enhancers of 30S dynein ATPase activity and inhibitors of 14S dynein ATPase activity (Blum & Hayes, 1979). Aryl and alkyl-aryl thioureas display strong hypnotic potency in mice (DeBeer et al., 1936). 1-Aroyl-3-arylthioureas are an exceptionally important group of thioureas which have attracted recent interest. They have been used in the synthesis of imidazole-2-thiones (Wang et al., 2005) and 2-(aroylimino)-3-aryl-4-phenyl-1,3-thiazolines (Saeed et al., 2008). We report here the structure of the title thiourea derivative (I), Fig. 1.

With the exception of the C12 atoms of two methyl groups of the t-butyl substituent all of the non-hydrogen atoms of the title compound, C₁₃H₁₅N₂O₃SCl lie on a mirror plane. Intramolecular N2—H2N···O1 and C9—H9···S1 hydrogen bonds each form a 6-membered ring, also in the mirror plane. Bond distances within the molecule are normal (Allen et al. 1987) and similar to those observed in comparable structures (Saeed & Flörke 2007a,b; Yusof et al. 2006, 2008). Despite the presence of both amide and thioamide groups in the molecule, no intermolecular hydrogen bonds are observed in the crystal structure. Weak π–π contacts between neighbouring C4···C9 rings, Fig 2, with centroid···centroid distances 4.2903 (17)Å and perpendicular distances between the molecular planes of 3.273Å link adjacent molecules above and below the molecular plane along b. These stacks of molecules form sheets parallel to the c axis, Fig. 3.

Related literature

For the use of thiourea derivatives in organic synthesis, see: Eynde & Watte (2003); Fu et al. (1999); Rashdan et al. (2006); Maryanoff et al. (1986); Wang et al. (2005); Saeed et al. (2008); and in analysis, see: Koch (2001). For their bioactivity and pharmaceutical applications, see: Upadhyaya & Srivastava (1982); Krishnamurthy et al. (1999); Blum & Hayes (1979); DeBeer et al. (1936). For related structures, see: Saeed & Flörke (2007a,b); Yusof et al. (2006, 2008). For reference structural data, see: Allen et al. (1987).

S2. Experimental

A solution of pivaloyl chloride (10 mmol) in anhydrous acetone (50 ml) was added dropwise to a suspension of potassium thiocyanate (10 mmol) in acetone (30 ml) and the reaction mixture was refluxed for 30 min. After cooling to room temperature, a solution of 2-chloro-5-nitroaniline (1.28 g, 10 mmol) in acetone (10 ml) was added and the resulting mixture refluxed for 2 h. The reaction mixture was poured into cold water and the thiourea was precipitated as a white solid. Recrystallization from ethanol gave colorless crystals of (I) (8.6 mmol, 86%). IR (KBr) cm^-1: 3351 (free NH), 3200 (assoc. NH), 1667 (CO), 1610 (arom.), 1529 (thioureido I) 1325 II, 1160 III, 744, 762.

S3. Refinement

The H atoms bound to N1 and N2 and C11 were located in a difference Fourier map and their coordinates refined with U_iso= 1.2U_eq (N/C). All other H atoms were refined using a riding model with d(C—H) = 0.95 Å, for aromatic H atoms with U_iso= 1.2U_eq (C). For the remaining methyl groups d(C—H) = 0.98 Å, U_iso = 1.5U_eq (C).

Computing details

Data collection: APEX2 (Bruker, 2006); cell refinement: APEX2 and SAINT (Bruker, 2006); data reduction: SAINT (Bruker, 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008) and TITAN2000 (Hunter & Simpson, 1999); molecular graphics: SHELXTL (Sheldrick, 2008) and Mercury (Macrae et al., 2006); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008), enCIFer (Allen et al., 2004), PLATON (Spek, 2009) and publCIF (Westrip, 2009).

Figures

	Fig. 1. The structure of (I) with displacement ellipsoids for the non-hydrogen atoms drawn at the 50% probability level. Intramolecular hydrogen bonds are drawn as dashed lines. The atom labeled C12A is related to the C12 atom by the symmetry operation x, -y + 1/2, z.
	Fig. 2. π–π interactions for (1).
	Fig. 3. Crystal packing for (I) viewed down the a axis.

1-(2-Chloro-5-nitrophenyl)-3-(2,2-dimethylpropanoyl)thiourea

Crystal data

C12H14ClN3O3S	F(000) = 656
Mr = 315.77	Dx = 1.517 Mg m^−3
Orthorhombic, Pnma	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2n	Cell parameters from 2410 reflections
a = 9.529 (2) Å	θ = 2.3–24.6°
b = 6.546 (2) Å	µ = 0.44 mm^−1
c = 22.166 (6) Å	T = 89 K
V = 1382.7 (7) Å^3	Needle, colourless
Z = 4	0.36 × 0.09 × 0.06 mm

Data collection

Bruker APEXII CCD area-detector diffractometer	1434 independent reflections
Radiation source: fine-focus sealed tube	1166 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.069
ω scans	θmax = 25.7°, θmin = 1.8°
Absorption correction: multi-scan (SADABS; Bruker, 2006)	h = −11→11
Tmin = 0.833, Tmax = 0.974	k = −6→8
12525 measured reflections	l = −26→26

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)] = 0.033	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.092	H atoms treated by a mixture of independent and constrained refinement
S = 1.09	w = 1/[σ^2(Fo^2) + (0.0461P)^2 + 0.3426P] where P = (Fo^2 + 2Fc^2)/3
1434 reflections	(Δ/σ)max < 0.001
130 parameters	Δρmax = 0.27 e Å^−3
0 restraints	Δρmin = −0.43 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
C1	0.1946 (3)	0.2500	0.36075 (12)	0.0163 (6)
O1	0.3187 (2)	0.2500	0.34713 (8)	0.0217 (5)
N1	0.1523 (3)	0.2500	0.42088 (10)	0.0184 (5)
H1N	0.070 (4)	0.2500	0.4268 (16)	0.037 (11)*
C2	0.2314 (3)	0.2500	0.47417 (11)	0.0143 (6)
S1	0.14289 (7)	0.2500	0.53901 (3)	0.0192 (2)
N2	0.3713 (2)	0.2500	0.46466 (10)	0.0143 (5)
H2N	0.397 (3)	0.2500	0.4222 (15)	0.030 (9)*
C4	0.4846 (3)	0.2500	0.50580 (12)	0.0130 (6)
C5	0.6210 (3)	0.2500	0.48174 (11)	0.0147 (6)
Cl1	0.64439 (7)	0.2500	0.40389 (3)	0.0181 (2)
C6	0.7399 (3)	0.2500	0.51801 (12)	0.0168 (6)
H6	0.8305	0.2500	0.5002	0.020*
C7	0.7261 (3)	0.2500	0.58025 (12)	0.0183 (6)
H7	0.8060	0.2500	0.6059	0.022*
C8	0.5911 (3)	0.2500	0.60368 (11)	0.0167 (6)
N3	0.5743 (3)	0.2500	0.67027 (10)	0.0204 (5)
O2	0.6808 (2)	0.2500	0.70124 (9)	0.0286 (5)
O3	0.4544 (2)	0.2500	0.69074 (9)	0.0317 (6)
C9	0.4711 (3)	0.2500	0.56877 (11)	0.0147 (6)
H9	0.3810	0.2500	0.5871	0.018*
C10	0.0727 (3)	0.2500	0.31561 (11)	0.0170 (6)
C11	0.1330 (3)	0.2500	0.25185 (13)	0.0308 (8)
H11A	0.059 (4)	0.2500	0.2261 (16)	0.037*
H11B	0.188 (2)	0.132 (3)	0.2442 (10)	0.037*
C12	−0.0158 (2)	0.0571 (3)	0.32488 (9)	0.0229 (5)
H12A	−0.0897	0.0515	0.2942	0.034*
H12B	−0.0585	0.0602	0.3651	0.034*
H12C	0.0442	−0.0638	0.3213	0.034*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0149 (14)	0.0200 (15)	0.0142 (14)	0.000	−0.0001 (11)	0.000
O1	0.0135 (10)	0.0360 (12)	0.0155 (9)	0.000	0.0018 (8)	0.000
N1	0.0109 (13)	0.0317 (14)	0.0125 (11)	0.000	0.0003 (10)	0.000
C2	0.0129 (13)	0.0185 (14)	0.0113 (13)	0.000	−0.0021 (10)	0.000
S1	0.0149 (4)	0.0307 (4)	0.0121 (3)	0.000	0.0020 (3)	0.000
N2	0.0124 (12)	0.0196 (12)	0.0110 (11)	0.000	−0.0008 (9)	0.000
C4	0.0134 (13)	0.0108 (13)	0.0146 (13)	0.000	−0.0025 (10)	0.000
C5	0.0183 (14)	0.0129 (13)	0.0128 (13)	0.000	−0.0007 (11)	0.000
Cl1	0.0149 (4)	0.0262 (4)	0.0132 (3)	0.000	0.0020 (2)	0.000
C6	0.0128 (14)	0.0169 (14)	0.0209 (14)	0.000	0.0010 (11)	0.000
C7	0.0190 (15)	0.0148 (14)	0.0210 (14)	0.000	−0.0057 (12)	0.000
C8	0.0213 (15)	0.0150 (14)	0.0139 (13)	0.000	−0.0018 (11)	0.000
N3	0.0258 (14)	0.0213 (13)	0.0142 (12)	0.000	−0.0011 (10)	0.000
O2	0.0284 (12)	0.0391 (13)	0.0182 (10)	0.000	−0.0114 (9)	0.000
O3	0.0266 (12)	0.0527 (15)	0.0157 (10)	0.000	0.0031 (9)	0.000
C9	0.0165 (14)	0.0122 (13)	0.0154 (13)	0.000	−0.0002 (11)	0.000
C10	0.0147 (14)	0.0258 (15)	0.0104 (13)	0.000	−0.0018 (11)	0.000
C11	0.0193 (17)	0.062 (2)	0.0115 (14)	0.000	−0.0013 (13)	0.000
C12	0.0222 (11)	0.0220 (11)	0.0245 (10)	0.0000 (9)	−0.0078 (8)	−0.0021 (9)

Geometric parameters (Å, º)

C1—O1	1.221 (3)	C7—C8	1.387 (4)
C1—N1	1.392 (3)	C7—H7	0.9500
C1—C10	1.533 (4)	C8—C9	1.380 (4)
N1—C2	1.401 (3)	C8—N3	1.485 (3)
N1—H1N	0.80 (4)	N3—O2	1.226 (3)
C2—N2	1.349 (3)	N3—O3	1.229 (3)
C2—S1	1.667 (3)	C9—H9	0.9500
N2—C4	1.414 (3)	C10—C11	1.526 (4)
N2—H2N	0.97 (3)	C10—C12	1.533 (3)
C4—C9	1.402 (3)	C10—C12^i	1.533 (3)
C4—C5	1.405 (4)	C11—H11A	0.91 (4)
C5—C6	1.389 (4)	C11—H11B	0.95 (2)
C5—Cl1	1.740 (3)	C12—H12A	0.9800
C6—C7	1.386 (4)	C12—H12B	0.9800
C6—H6	0.9500	C12—H12C	0.9800
O1—C1—N1	121.1 (2)	C9—C8—C7	123.9 (2)
O1—C1—C10	124.9 (2)	C9—C8—N3	117.9 (2)
N1—C1—C10	113.9 (2)	C7—C8—N3	118.2 (2)
C1—N1—C2	130.6 (2)	O2—N3—O3	124.3 (2)
C1—N1—H1N	116 (3)	O2—N3—C8	117.9 (2)
C2—N1—H1N	113 (3)	O3—N3—C8	117.8 (2)
N2—C2—N1	113.6 (2)	C8—C9—C4	118.8 (2)
N2—C2—S1	129.4 (2)	C8—C9—H9	120.6
N1—C2—S1	117.0 (2)	C4—C9—H9	120.6
C2—N2—C4	130.8 (2)	C11—C10—C12	109.35 (14)
C2—N2—H2N	113.7 (19)	C11—C10—C12^i	109.35 (14)
C4—N2—H2N	115.5 (19)	C12—C10—C12^i	111.0 (2)
C9—C4—C5	117.6 (2)	C11—C10—C1	108.6 (2)
C9—C4—N2	124.9 (2)	C12—C10—C1	109.25 (14)
C5—C4—N2	117.5 (2)	C12^i—C10—C1	109.25 (14)
C6—C5—C4	122.3 (2)	C10—C11—H11A	107 (2)
C6—C5—Cl1	118.0 (2)	C10—C11—H11B	111.9 (14)
C4—C5—Cl1	119.7 (2)	H11A—C11—H11B	108.5 (18)
C7—C6—C5	119.9 (2)	C10—C12—H12A	109.5
C7—C6—H6	120.0	C10—C12—H12B	109.5
C5—C6—H6	120.0	H12A—C12—H12B	109.5
C6—C7—C8	117.4 (2)	C10—C12—H12C	109.5
C6—C7—H7	121.3	H12A—C12—H12C	109.5
C8—C7—H7	121.3	H12B—C12—H12C	109.5
O1—C1—N1—C2	0.0	C6—C7—C8—N3	180.0
C10—C1—N1—C2	180.0	C9—C8—N3—O2	180.0
C1—N1—C2—N2	0.0	C7—C8—N3—O2	0.000 (1)
C1—N1—C2—S1	180.0	C9—C8—N3—O3	0.000 (1)
N1—C2—N2—C4	180.0	C7—C8—N3—O3	180.0
S1—C2—N2—C4	0.000 (1)	C7—C8—C9—C4	0.000 (1)
C2—N2—C4—C9	0.000 (1)	N3—C8—C9—C4	180.0
C2—N2—C4—C5	180.0	C5—C4—C9—C8	0.000 (1)
C9—C4—C5—C6	0.0	N2—C4—C9—C8	180.0
N2—C4—C5—C6	180.0	O1—C1—C10—C11	0.0
C9—C4—C5—Cl1	180.0	N1—C1—C10—C11	180.0
N2—C4—C5—Cl1	0.0	O1—C1—C10—C12	119.21 (15)
C4—C5—C6—C7	0.000 (1)	N1—C1—C10—C12	−60.79 (15)
Cl1—C5—C6—C7	180.0	O1—C1—C10—C12^i	−119.21 (15)
C5—C6—C7—C8	0.000 (1)	N1—C1—C10—C12^i	60.79 (15)
C6—C7—C8—C9	0.000 (1)

Symmetry code: (i) x, −y+1/2, z.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C9—H9···S1	0.95	2.51	3.197 (3)	130
N2—H2N···O1	0.97 (3)	1.82 (3)	2.653 (3)	141 (3)