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Acta Crystallogr Sect E Struct Rep Online. 2008 January 1; 64(Pt 1): o288–o289.
Published online 2007 December 18. doi:  10.1107/S1600536807066524
PMCID: PMC2915340

Benzyl N-[2-(1H-indol-3-yl)eth­yl]dithio­carbamate

Abstract

The indole and phenyl ring systems in the title compound, C18H18N2S2, are nearly coplanar, the indole and phenyl planes forming a dihedral angle of 6.5 (1)°. Supra­molecular aggregation is effected by N—H(...)S, C—H(...)S, N—H(...)π and C—H(...)π inter­actions. The crystal studied exhibited inversion twinning.

Related literature

For a detailed account of the indole­amine 2,3-dioxy­genase (IDO) inhibitory properties of the title compound and other brassinin derivatives, see: Gaspari et al. (2006 [triangle]) and references cited therein. For hydrogen-bond criteria, see: Desiraju & Steiner (1999 [triangle]); Desiraju (1989 [triangle]). For graph-set notations, see: Bernstein et al. (1995 [triangle]); Etter (1990 [triangle]).

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Object name is e-64-0o288-scheme1.jpg

Experimental

Crystal data

  • C18H18N2S2
  • M r = 326.46
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-0o288-efi1.jpg
  • a = 34.554 (10) Å
  • b = 5.459 (2) Å
  • c = 8.875 (3) Å
  • β = 102.522 (18)°
  • V = 1634.3 (9) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.32 mm−1
  • T = 90 K
  • 0.30 × 0.27 × 0.05 mm

Data collection

  • Nonius KappaCCD diffractometer with an Oxford Cryosystems Cryostream cooler
  • Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997 [triangle]) T min = 0.909, T max = 0.984
  • 14452 measured reflections
  • 3638 independent reflections
  • 2846 reflections with I > 2σ(I)
  • R int = 0.013

Refinement

  • R[F 2 > 2σ(F 2)] = 0.038
  • wR(F 2) = 0.083
  • S = 1.06
  • 3638 reflections
  • 271 parameters
  • 2 restraints
  • All H-atom parameters refined
  • Δρmax = 0.28 e Å−3
  • Δρmin = −0.36 e Å−3
  • Absolute structure: Flack (1983 [triangle]), 1615 Friedel pairs
  • Flack parameter: 0.44 (6)

Data collection: COLLECT (Nonius, 2000 [triangle]); cell refinement: DENZO and SCALEPACK (Otwinowski & Minor, 1997 [triangle]); data reduction: DENZO and SCALEPACK; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997 [triangle]); molecular graphics: PLATON (Spek, 2003 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536807066524/sj2455sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536807066524/sj2455Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

CP and MD thank the Irish Government under its ‘Programme for Research in Third Level Institutions’ and the Research committee of the Royal College of Surgeons in Ireland for financial support. The purchase of the diffractometer was made possible by grant No. LEQSF(1999–2000)-ENH-TR-13, administered by the Louisiana Board of Regents.

supplementary crystallographic information

Comment

The enzyme indoleamine 2,3-dioxygenase (IDO) has been reported to play a role in tumour immunosuppression. IDO inhibitors have been reported to be novel therapeutics for cancer treatment. The natural product brassinin has been shown to be a moderately active competitive IDO inhibitor. The title compound, (I), Fig. 1, is a brassinin derivative and its IDO inhibitory properties have been reported (Gaspari et al., 2006). The present investigation is aimed at the study of the molecular and supramolecular architecture of the title compound. This study may serve as a forerunner to an investigation of the correlation between the molecular and supramolecular features of this compound with its biological activity.

In (I), the dithiocarbamate moiety is essentially planar, as shown by the small deviation of N12 [0.0036 (6) Å], C13 [-0.009 (2) Å], S14 [0.0032 (5) Å] & S15 [0.0027 (5) Å] atoms from their mean plane. The interplanar angle between the indole and the phenyl ring is 6.5 (1)° thereby confirming their near coplanarity.

The crystal structure of (I) is stabilized by the interplay of N—H···S, C—H···S, N—H···π and C—H···π interactions, Fig. 2, Table 1. The H-bond distances found in (I) agree with those reported in literature (Desiraju & Steiner, 1999; Desiraju, 1989). The C11—H11B···S14 interaction generates a motif of graph set (Bernstein et al., 1995; Etter, 1990) S(5). Another S(5) motif is formed by the C16—H16···S14 interaction. The N12—H12···S14i interaction generates an infinite one-dimensional chain along [001]. The N12—H12···S14i and C16—H16A···S15ii interactions generate a binary motif of graph set R22(9). The C8—H8···Cg2ii and C9—H9···Cg1ii interactions generate an R22(6) motif in which each of the aromatic rings are considered as single acceptor atoms. Cg1 is the centroid of the N1, C2, C3, C4 & C5 ring, Cg2 that of the C4, C5, C6, C7, C8 & C9 ring and Cg3 that of the C17, C18, C19, C20, C21 & C22 ring, Table 1.

Experimental

The title compound was prepared by the reported procedure (Gaspari et al., 2006). Diffraction quality crystals were obtained by recrystallizing the crude product from a 1:1 mixture of dichloromethane and petroleum ether.

Refinement

All H-atoms were located in difference maps and their positions and isotropic displacement parameters freely refined. Refinement of the Flack (1983) parameter indicated an inversion twin with components of slightly different size.

Figures

Fig. 1.
The asymmetric unit of (I) with the atoms labelled and displacement ellipsoids depicted at the 50% probability level for all non-H atoms. H-atoms are drawn as spheres of arbitrary radius.
Fig. 2.
The molecular packing viewed down the b-axis. Dashed lines represent the weak N—H···S and C—H···S interactions within the lattice.

Crystal data

C18H18N2S2F000 = 688
Mr = 326.46Dx = 1.327 Mg m3
Monoclinic, CcMo Kα radiation λ = 0.71073 Å
Hall symbol: C -2ycCell parameters from 1986 reflections
a = 34.554 (10) Åθ = 2.5–28.3º
b = 5.459 (2) ŵ = 0.32 mm1
c = 8.875 (3) ÅT = 90 K
β = 102.522 (18)ºPlate, colorless
V = 1634.3 (9) Å30.30 × 0.27 × 0.05 mm
Z = 4

Data collection

Nonius KappaCCD diffractometer with an Oxford Cryosystems Cryostream cooler3638 independent reflections
Radiation source: fine-focus sealed tube2846 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.013
T = 90 Kθmax = 28.3º
ω scans with κ offsetsθmin = 3.6º
Absorption correction: multi-scan(SCALEPACK; Otwinowski & Minor, 1997)h = −45→45
Tmin = 0.909, Tmax = 0.984k = −7→7
14452 measured reflectionsl = −11→11

Refinement

Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullAll H-atom parameters refined
R[F2 > 2σ(F2)] = 0.038  w = 1/[σ2(Fo2) + (0.0459P)2 + 0.298P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.083(Δ/σ)max < 0.001
S = 1.06Δρmax = 0.28 e Å3
3638 reflectionsΔρmin = −0.36 e Å3
271 parametersExtinction correction: none
2 restraintsAbsolute structure: Flack (1983), 1615 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: 0.44 (6)
Secondary atom site location: difference Fourier map

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 (Å2)

xyzUiso*/Ueq
N10.46964 (6)−0.5161 (4)1.1785 (2)0.0254 (4)
C20.43138 (7)−0.4259 (4)1.1409 (3)0.0226 (5)
C30.42960 (6)−0.2308 (4)1.0432 (2)0.0213 (4)
C40.46901 (6)−0.1951 (4)1.0199 (2)0.0193 (4)
C50.49326 (6)−0.3788 (4)1.1043 (2)0.0212 (5)
C60.53368 (7)−0.4004 (4)1.1042 (3)0.0255 (5)
C70.54953 (7)−0.2338 (4)1.0168 (2)0.0267 (5)
C80.52616 (7)−0.0488 (4)0.9323 (3)0.0251 (5)
C90.48610 (6)−0.0264 (4)0.9334 (3)0.0221 (5)
C100.39402 (6)−0.0822 (4)0.9696 (3)0.0220 (5)
C110.35556 (7)−0.1763 (4)1.0067 (3)0.0223 (5)
N120.32086 (5)−0.0433 (4)0.9222 (2)0.0220 (4)
C130.29978 (6)−0.1080 (4)0.7835 (2)0.0197 (4)
S140.309251 (17)−0.35477 (9)0.68619 (5)0.02339 (14)
S150.261499 (15)0.10448 (9)0.71423 (4)0.02185 (14)
C160.22633 (7)−0.0708 (4)0.5720 (3)0.0213 (5)
C170.19391 (6)0.1051 (4)0.4973 (2)0.0201 (5)
C180.15460 (7)0.0621 (5)0.5069 (3)0.0264 (5)
C190.12465 (7)0.2181 (5)0.4336 (3)0.0307 (5)
C200.13319 (8)0.4170 (4)0.3499 (3)0.0288 (5)
C210.17215 (7)0.4632 (4)0.3412 (3)0.0264 (5)
C220.20258 (7)0.3073 (4)0.4145 (2)0.0232 (5)
H10.4773 (8)−0.640 (5)1.233 (3)0.027 (7)*
H20.4095 (7)−0.498 (4)1.181 (3)0.018 (5)*
H60.5501 (7)−0.527 (5)1.159 (3)0.024 (6)*
H70.5796 (8)−0.242 (5)1.017 (3)0.024 (6)*
H80.5382 (8)0.073 (5)0.881 (3)0.040 (8)*
H90.4699 (8)0.095 (5)0.878 (3)0.033 (7)*
H10A0.3964 (7)0.086 (5)0.999 (3)0.032 (7)*
H10B0.3906 (7)−0.083 (4)0.866 (3)0.024 (6)*
H11A0.3577 (7)−0.155 (4)1.127 (3)0.016 (6)*
H11B0.3517 (7)−0.341 (5)0.973 (3)0.015 (5)*
H120.3127 (7)0.076 (5)0.967 (3)0.024 (6)*
H16A0.2415 (7)−0.147 (4)0.500 (3)0.016 (6)*
H16B0.2166 (7)−0.205 (5)0.624 (3)0.026 (6)*
H180.1495 (8)−0.084 (5)0.576 (3)0.033 (7)*
H190.0993 (10)0.188 (5)0.433 (3)0.037 (7)*
H200.1109 (10)0.512 (6)0.297 (4)0.047 (8)*
H210.1775 (7)0.597 (5)0.283 (3)0.028 (7)*
H220.2336 (8)0.353 (4)0.412 (3)0.026 (6)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
N10.0281 (10)0.0213 (10)0.0267 (10)0.0045 (8)0.0061 (8)0.0075 (9)
C20.0258 (12)0.0206 (11)0.0221 (11)−0.0015 (9)0.0067 (9)−0.0007 (9)
C30.0239 (11)0.0188 (11)0.0201 (10)−0.0019 (8)0.0023 (8)−0.0004 (9)
C40.0230 (11)0.0166 (10)0.0181 (11)−0.0013 (8)0.0039 (8)−0.0030 (9)
C50.0230 (12)0.0199 (11)0.0194 (11)0.0015 (8)0.0015 (9)0.0000 (8)
C60.0271 (12)0.0231 (12)0.0238 (12)0.0058 (9)−0.0001 (10)−0.0001 (10)
C70.0230 (13)0.0260 (13)0.0308 (13)0.0004 (9)0.0051 (9)−0.0044 (10)
C80.0247 (12)0.0238 (12)0.0267 (12)−0.0035 (9)0.0052 (9)−0.0014 (10)
C90.0217 (12)0.0209 (11)0.0219 (11)−0.0005 (9)0.0009 (9)−0.0005 (9)
C100.0221 (12)0.0214 (12)0.0216 (13)−0.0001 (8)0.0027 (9)−0.0003 (10)
C110.0234 (12)0.0223 (12)0.0204 (12)−0.0001 (9)0.0031 (9)−0.0006 (9)
N120.0216 (10)0.0238 (10)0.0215 (10)−0.0003 (8)0.0069 (8)−0.0037 (8)
C130.0199 (11)0.0208 (11)0.0194 (11)−0.0050 (8)0.0069 (8)0.0015 (9)
S140.0290 (3)0.0189 (3)0.0217 (3)0.0002 (2)0.0043 (2)−0.0010 (2)
S150.0224 (3)0.0210 (3)0.0213 (3)−0.0007 (2)0.0029 (2)−0.0029 (2)
C160.0220 (12)0.0203 (10)0.0216 (11)−0.0019 (9)0.0046 (9)−0.0006 (10)
C170.0227 (11)0.0197 (11)0.0174 (10)−0.0015 (8)0.0031 (8)−0.0042 (9)
C180.0244 (12)0.0252 (12)0.0305 (12)−0.0041 (9)0.0081 (9)−0.0020 (10)
C190.0183 (12)0.0314 (13)0.0422 (14)−0.0011 (10)0.0058 (10)−0.0043 (11)
C200.0291 (13)0.0241 (12)0.0304 (13)0.0045 (10)0.0008 (10)−0.0028 (11)
C210.0345 (14)0.0211 (11)0.0229 (12)0.0015 (10)0.0046 (9)−0.0015 (10)
C220.0276 (12)0.0220 (11)0.0202 (10)−0.0018 (9)0.0057 (9)−0.0020 (9)

Geometric parameters (Å, °)

N1—C51.377 (3)C11—H11A1.06 (2)
N1—C21.382 (3)C11—H11B0.95 (3)
N1—H10.84 (3)N12—C131.335 (3)
C2—C31.366 (3)N12—H120.84 (3)
C2—H20.99 (3)C13—S141.670 (2)
C3—C41.434 (3)C13—S151.767 (2)
C3—C101.499 (3)S15—C161.822 (2)
C4—C91.408 (3)C16—C171.515 (3)
C4—C51.413 (3)C16—H16A1.00 (2)
C5—C61.402 (3)C16—H16B0.97 (3)
C6—C71.383 (3)C17—C221.394 (3)
C6—H60.96 (3)C17—C181.399 (3)
C7—C81.405 (3)C18—C191.388 (4)
C7—H71.04 (3)C18—H181.04 (3)
C8—C91.391 (3)C19—C201.383 (4)
C8—H80.95 (3)C19—H190.89 (3)
C9—H90.94 (3)C20—C211.388 (4)
C10—C111.526 (3)C20—H200.96 (3)
C10—H10A0.95 (3)C21—C221.399 (3)
C10—H10B0.90 (3)C21—H210.93 (3)
C11—N121.462 (3)C22—H221.10 (3)
C5—N1—C2109.01 (19)C10—C11—H11A107.8 (12)
C5—N1—H1124.7 (18)N12—C11—H11B105.6 (14)
C2—N1—H1126.2 (18)C10—C11—H11B108.8 (14)
C3—C2—N1109.9 (2)H11A—C11—H11B113.1 (19)
C3—C2—H2127.5 (13)C13—N12—C11124.4 (2)
N1—C2—H2122.6 (13)C13—N12—H12117.8 (17)
C2—C3—C4106.49 (19)C11—N12—H12117.6 (17)
C2—C3—C10128.1 (2)N12—C13—S14124.15 (17)
C4—C3—C10125.35 (19)N12—C13—S15111.41 (16)
C9—C4—C5118.86 (19)S14—C13—S15124.42 (13)
C9—C4—C3133.7 (2)C13—S15—C16103.47 (10)
C5—C4—C3107.44 (18)C17—C16—S15106.81 (15)
N1—C5—C6130.44 (19)C17—C16—H16A115.0 (13)
N1—C5—C4107.16 (18)S15—C16—H16A107.4 (13)
C6—C5—C4122.40 (19)C17—C16—H16B112.9 (14)
C7—C6—C5117.4 (2)S15—C16—H16B108.4 (14)
C7—C6—H6119.8 (14)H16A—C16—H16B106.1 (19)
C5—C6—H6122.7 (14)C22—C17—C18119.2 (2)
C6—C7—C8121.4 (2)C22—C17—C16120.64 (18)
C6—C7—H7119.0 (14)C18—C17—C16120.16 (19)
C8—C7—H7119.5 (14)C19—C18—C17120.2 (2)
C9—C8—C7121.1 (2)C19—C18—H18122.7 (15)
C9—C8—H8118.6 (17)C17—C18—H18117.0 (15)
C7—C8—H8120.0 (17)C20—C19—C18120.6 (2)
C8—C9—C4118.8 (2)C20—C19—H19117.8 (17)
C8—C9—H9122.9 (17)C18—C19—H19121.5 (17)
C4—C9—H9118.3 (17)C19—C20—C21119.7 (2)
C3—C10—C11113.23 (19)C19—C20—H20116.5 (19)
C3—C10—H10A112.7 (16)C21—C20—H20123.8 (19)
C11—C10—H10A107.0 (16)C20—C21—C22120.3 (2)
C3—C10—H10B110.8 (16)C20—C21—H21118.9 (16)
C11—C10—H10B107.0 (16)C22—C21—H21120.8 (16)
H10A—C10—H10B106 (2)C17—C22—C21120.1 (2)
N12—C11—C10112.22 (19)C17—C22—H22120.5 (13)
N12—C11—H11A109.5 (13)C21—C22—H22119.3 (13)
C5—N1—C2—C3−0.1 (2)C2—C3—C10—C11−3.0 (3)
N1—C2—C3—C4−0.7 (2)C4—C3—C10—C11175.5 (2)
N1—C2—C3—C10178.0 (2)C3—C10—C11—N12−174.57 (19)
C2—C3—C4—C9−179.8 (2)C10—C11—N12—C1390.3 (2)
C10—C3—C4—C91.4 (4)C11—N12—C13—S141.2 (3)
C2—C3—C4—C51.3 (2)C11—N12—C13—S15−177.21 (16)
C10—C3—C4—C5−177.5 (2)N12—C13—S15—C16−158.35 (15)
C2—N1—C5—C6−179.1 (2)S14—C13—S15—C1623.20 (17)
C2—N1—C5—C40.9 (2)C13—S15—C16—C17−175.57 (14)
C9—C4—C5—N1179.51 (19)S15—C16—C17—C2262.1 (2)
C3—C4—C5—N1−1.4 (2)S15—C16—C17—C18−119.77 (19)
C9—C4—C5—C6−0.5 (3)C22—C17—C18—C190.6 (3)
C3—C4—C5—C6178.6 (2)C16—C17—C18—C19−177.6 (2)
N1—C5—C6—C7179.8 (2)C17—C18—C19—C200.2 (3)
C4—C5—C6—C7−0.2 (3)C18—C19—C20—C21−1.0 (4)
C5—C6—C7—C80.5 (3)C19—C20—C21—C221.0 (3)
C6—C7—C8—C90.0 (3)C18—C17—C22—C21−0.5 (3)
C7—C8—C9—C4−0.7 (3)C16—C17—C22—C21177.59 (19)
C5—C4—C9—C80.9 (3)C20—C21—C22—C17−0.2 (3)
C3—C4—C9—C8−177.9 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C11—H11B···S140.95 (3)2.65 (2)3.103 (2)109.6 (17)
C16—H16A···S141.00 (2)2.80 (2)3.222 (2)106.1 (15)
N12—H12···S14i0.84 (3)2.50 (3)3.283 (2)156 (2)
C16—H16A···S15ii1.00 (2)2.78 (2)3.642 (3)144.8 (17)
N1—H1···Cg2iii0.84 (3)2.6583.373143.65
C8—H8···Cg2ii0.95 (3)3.2443.868124.79
C9—H9···Cg1ii0.94 (3)2.8073.574140.03
C18—H18···Cg3iv1.04 (3)3.1744.053142.60
C21—H21···Cg3v0.93 (3)3.2123.946136.93

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: SJ2455).

References

  • Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N. (1995). Angew. Chem. Int. Ed. Engl.34, 1555–1573.
  • Desiraju, G. R. (1989). Crystal Engineering: The Design of Organic Solids Amsterdam: Elsevier.
  • Desiraju, G. R. & Steiner, T. (1999). The Weak Hydrogen Bond in Structural Chemistry and Biology. New York: Oxford University Press.
  • Etter, M. C. (1990). Acc. Chem. Res.23, 120–126.
  • Flack, H. D. (1983). Acta Cryst. A39, 876–881.
  • Gaspari, P., Banerjee, T., Malachowski, W. P., Muller, A. J., Prendergast, G. C., DuHadaway, J., Bennett, S. & Donovan, A. M. (2006). J. Med. Chem.49, 684–692. [PMC free article] [PubMed]
  • Nonius (2000). COLLECT Nonius BV, Delft, The Netherlands.
  • Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307–326. New York: Academic Press.
  • Sheldrick, G. M. (1997). SHELXS97 and SHELXL97 University of Göttingen, Germany.
  • Spek, A. L. (2003). J. Appl. Cryst.36, 7–13.

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