supplementary materials


kj2226 scheme

Acta Cryst. (2013). E69, o979    [ doi:10.1107/S1600536813014001 ]

5-Benzyloxy-3-methyl-1-tosyl-1H-indole

G. Pozza Silveira, A. G. Oliver and B. C. Noll

Abstract top

The title compound, C23H21NO3S, represents one of the few examples of a 5-substituted indole with a toluenesulfonyl group bonded to the N atom. The benzyl group adopts a synclinal geometry with respect to the indole ring [dihedral angle = 59.95 (4)°], while the tolyl ring is oriented close to perpendicular to the indole ring, making a dihedral angle of 81.85 (3)°. The indole N atom exhibits a slight pyramidalization.

Comment top

Substituted indoles serve as unique precursors for medicinally important physostigmine alkaloids, which are anticholinesterases and miotics. This alkaloid skeleton has been found in marine alkaloids from Broyoza Flustra foliacea in the flustramines (Marino et al., 1989) The literature presents a great number of enantiocontrolled syntheses for the natural and unnatural physostigmine (Marino et al., 1992) Our interest in physostigmine emanated from our recent asymmetric synthesis of naphthyl lactams (Silveira & Marino, 2013) using chiral vinyl sulfilimines (Pozza Silveira et al., 2012). Herein we report 5-(benzyloxy)-3-methyl-1-tosyl-1H-indole as a potential physostigmine precursor.

The title compound, C23H21NO3S, exhibits no unusual structural features and represents one of the few examples of an indole with a toluenesulfonyl bonded to the nitrogen and an oxygen bridging moiety bonded in the 5-position on the indole ring. The two other examples are 5-cyano-2-methoxy-4-trifluoromethyl-6-[3'-(N-toluenesulfonyl-5'-µethoxyindolyl)]pyridine (Xiong et al., 2001) and 1-(4-methylphenyl)sulfonyl-3-((E)-2-(benzyl((4-methylphenyl)sulfonyl)αmino)ethenyl)-5-methoxy-1H-indole (Witulski et al., 2000). In both of these examples the 5-position is occupied by a methoxy group.

Bond distances and angles are within normal, acceptable ranges (Allen et al. 1995). The benzyl moiety adopts a syn-clinal geometry with respect to the indole ring (interplanar angle = 59.95 (4)°), while the tolyl ring is oriented close to perpendicular to the indole ring (interplanar angle = 81.85 (3)°). The complement of this angle, 108.15°, is close to the N1—S1—C16 angle (104.19 (5)°). The difference is a consequence of a slight pyramidalization of the indolic nitrogen.

Related literature top

For background to physostigmine and related marine natural products, see: Marino et al. (1989, 1992). For recent, related structural and synthetic studies, see: Pozza Silveira et al. (2012); Silveira & Marino (2013). For related compounds, see: Xiong et al. (2001); Witulski et al. (2000). For reference structural data see: Allen et al. (1995).

Experimental top

To a stirred solution of dimsylsodium [prepared from 110 mg (2.75 mmol) of NaH 60% dispersion in mineral oil and dimethylsulfoxide dry (0.58 ml) at 338 to 343 K until H2 is no longer evolved] was added a solution of 5-benzyloxy-3-methylindole (325 mg, 1.37 mmol) in dry THF (0.9 ml) under ice cooling. After stirring at room temperature for 1 h a solution of 4-methylbenzenesulfonyl chloride (225 mg, 1.18 mmol) in THF (0.9 ml) was added to this mixture at 273 K. After being stirred at room temperature for 16 h, the reaction product was poured into water and extracted with ethyl acetate. The extract was washed with water, dried over Na2SO4, and evaporated. The remaining residue was recrystallized from ethyl acetate/hexanes to give 482 mg of the desired product as white needle crystals (90%): mp 402 to 403 K. A suitably sized, block-like crystal was cut from a larger, columnar crystal for the diffraction study.

Refinement top

Hydrogen atoms were included in geometrically calculated positions. C—H distances were constrained to 0.95 Å for aromatic and 0.98 - 0.99 Å for aliphatic hydrogen atoms. Methyl hydrogen atoms were refined with thermal parameters restrained to UisoH = 1.5 × UeqC and all other hydrogen atoms = 1.2 × UeqC of the carbon to which they are bonded.

Computing details top

Data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2012 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: publCIF (Westrip, 2010).

Figures top
[Figure 1] Fig. 1. Labelling scheme for the title compound. Displacement ellipsoids depicted at 50% probability level. The labeling scheme follows the convention for indoles.
5-Benzyloxy-3-methyl-1-tosyl-1H-indole top
Crystal data top
C23H21NO3SDx = 1.358 Mg m3
Mr = 391.47Melting point: 402 K
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
a = 8.317 (3) ÅCell parameters from 9980 reflections
b = 15.601 (6) Åθ = 2.6–31.6°
c = 14.752 (5) ŵ = 0.19 mm1
β = 90.884 (11)°T = 100 K
V = 1914.1 (12) Å3Block, colourless
Z = 40.39 × 0.33 × 0.15 mm
F(000) = 824
Data collection top
Bruker APEXII
diffractometer
6415 independent reflections
Radiation source: fine-focus sealed tube5550 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.026
Detector resolution: 8.33 pixels mm-1θmax = 31.6°, θmin = 1.9°
combination of ω and φ–scansh = 1012
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
k = 2222
Tmin = 0.636, Tmax = 0.746l = 2121
30660 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.037Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.102H-atom parameters constrained
S = 1.04 w = 1/[σ2(Fo2) + (0.0536P)2 + 0.775P]
where P = (Fo2 + 2Fc2)/3
6415 reflections(Δ/σ)max = 0.001
255 parametersΔρmax = 0.59 e Å3
0 restraintsΔρmin = 0.42 e Å3
Crystal data top
C23H21NO3SV = 1914.1 (12) Å3
Mr = 391.47Z = 4
Monoclinic, P21/nMo Kα radiation
a = 8.317 (3) ŵ = 0.19 mm1
b = 15.601 (6) ÅT = 100 K
c = 14.752 (5) Å0.39 × 0.33 × 0.15 mm
β = 90.884 (11)°
Data collection top
Bruker APEXII
diffractometer
6415 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
5550 reflections with I > 2σ(I)
Tmin = 0.636, Tmax = 0.746Rint = 0.026
30660 measured reflectionsθmax = 31.6°
Refinement top
R[F2 > 2σ(F2)] = 0.037H-atom parameters constrained
wR(F2) = 0.102Δρmax = 0.59 e Å3
S = 1.04Δρmin = 0.42 e Å3
6415 reflectionsAbsolute structure: ?
255 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
N10.84082 (10)0.26302 (5)0.60391 (6)0.01478 (15)
O10.35145 (9)0.40007 (6)0.39442 (5)0.02043 (16)
S10.98068 (3)0.19050 (2)0.58368 (2)0.01438 (6)
O21.08199 (9)0.19022 (5)0.66274 (5)0.01998 (15)
C20.77142 (12)0.27143 (6)0.69017 (6)0.01592 (17)
H20.82030.25340.74560.019*
O31.04493 (9)0.21088 (5)0.49733 (5)0.01909 (15)
C30.62522 (12)0.30883 (6)0.68241 (6)0.01519 (17)
C3'0.59545 (12)0.32359 (6)0.58690 (6)0.01410 (17)
C40.46627 (12)0.36208 (7)0.54150 (6)0.01652 (18)
H40.37770.38460.57370.020*
C50.47154 (12)0.36630 (7)0.44789 (6)0.01665 (18)
C60.60430 (13)0.33495 (7)0.40057 (7)0.01818 (19)
H60.60500.33900.33630.022*
C70.73415 (12)0.29828 (7)0.44561 (7)0.01689 (18)
H70.82460.27770.41360.020*
C7'0.72720 (12)0.29276 (6)0.53938 (6)0.01406 (16)
C80.51260 (13)0.33196 (7)0.75577 (7)0.0202 (2)
H8A0.56230.31870.81480.030*
H8B0.41290.29910.74840.030*
H8C0.48840.39340.75250.030*
C90.21302 (12)0.42980 (7)0.44164 (7)0.01792 (18)
H9A0.24260.47920.48060.022*
H9B0.17130.38360.48080.022*
C100.08711 (11)0.45595 (6)0.37411 (6)0.01452 (17)
C110.02533 (13)0.53835 (7)0.37424 (7)0.01724 (18)
H110.06740.57950.41570.021*
C120.09749 (14)0.56142 (7)0.31438 (7)0.0217 (2)
H120.13900.61810.31480.026*
C130.15915 (13)0.50175 (8)0.25425 (7)0.0240 (2)
H130.24470.51710.21400.029*
C140.09673 (13)0.41950 (8)0.25233 (7)0.0222 (2)
H140.13800.37880.21010.027*
C150.02576 (13)0.39676 (7)0.31194 (7)0.01826 (18)
H150.06850.34030.31050.022*
C160.87513 (12)0.09408 (6)0.57724 (6)0.01472 (17)
C170.82732 (14)0.06170 (7)0.49366 (7)0.0208 (2)
H170.85710.08970.43920.025*
C180.73530 (15)0.01231 (7)0.49093 (7)0.0232 (2)
H180.70260.03520.43390.028*
C190.68993 (13)0.05376 (7)0.56976 (7)0.01902 (19)
C200.73877 (14)0.01942 (7)0.65257 (7)0.0206 (2)
H200.70760.04690.70700.025*
C210.83179 (13)0.05392 (7)0.65732 (7)0.01885 (19)
H210.86550.07650.71430.023*
C220.59305 (15)0.13461 (8)0.56597 (9)0.0263 (2)
H22A0.52940.13600.50950.040*
H22B0.52090.13660.61780.040*
H22C0.66540.18420.56810.040*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0144 (4)0.0164 (4)0.0135 (3)0.0039 (3)0.0007 (3)0.0004 (3)
O10.0149 (3)0.0329 (4)0.0135 (3)0.0072 (3)0.0001 (3)0.0038 (3)
S10.01210 (11)0.01661 (11)0.01444 (11)0.00244 (8)0.00002 (8)0.00062 (7)
O20.0160 (3)0.0249 (4)0.0189 (3)0.0024 (3)0.0046 (3)0.0003 (3)
C20.0187 (4)0.0165 (4)0.0125 (4)0.0018 (3)0.0011 (3)0.0009 (3)
O30.0167 (3)0.0226 (3)0.0180 (3)0.0019 (3)0.0042 (3)0.0027 (3)
C30.0174 (4)0.0165 (4)0.0116 (4)0.0017 (3)0.0001 (3)0.0003 (3)
C3'0.0146 (4)0.0158 (4)0.0119 (4)0.0009 (3)0.0003 (3)0.0002 (3)
C40.0149 (4)0.0211 (4)0.0135 (4)0.0037 (3)0.0005 (3)0.0011 (3)
C50.0148 (4)0.0214 (4)0.0137 (4)0.0021 (3)0.0011 (3)0.0027 (3)
C60.0172 (4)0.0249 (5)0.0124 (4)0.0024 (4)0.0010 (3)0.0021 (3)
C70.0154 (4)0.0219 (4)0.0135 (4)0.0027 (3)0.0021 (3)0.0011 (3)
C7'0.0139 (4)0.0152 (4)0.0130 (4)0.0011 (3)0.0007 (3)0.0010 (3)
C80.0221 (5)0.0251 (5)0.0136 (4)0.0054 (4)0.0027 (3)0.0001 (3)
C90.0151 (4)0.0245 (5)0.0142 (4)0.0038 (4)0.0000 (3)0.0008 (3)
C100.0123 (4)0.0173 (4)0.0140 (4)0.0002 (3)0.0002 (3)0.0024 (3)
C110.0183 (5)0.0173 (4)0.0161 (4)0.0017 (3)0.0008 (3)0.0004 (3)
C120.0221 (5)0.0246 (5)0.0186 (4)0.0094 (4)0.0021 (4)0.0036 (4)
C130.0169 (5)0.0378 (6)0.0171 (4)0.0061 (4)0.0024 (4)0.0019 (4)
C140.0182 (5)0.0293 (5)0.0191 (4)0.0035 (4)0.0025 (4)0.0031 (4)
C150.0181 (5)0.0166 (4)0.0201 (4)0.0013 (3)0.0003 (3)0.0003 (3)
C160.0146 (4)0.0155 (4)0.0140 (4)0.0031 (3)0.0007 (3)0.0000 (3)
C170.0269 (5)0.0216 (5)0.0140 (4)0.0009 (4)0.0005 (4)0.0006 (3)
C180.0292 (6)0.0226 (5)0.0178 (4)0.0022 (4)0.0025 (4)0.0025 (4)
C190.0169 (4)0.0171 (4)0.0231 (5)0.0021 (3)0.0019 (4)0.0016 (3)
C200.0231 (5)0.0202 (4)0.0187 (4)0.0007 (4)0.0054 (4)0.0007 (4)
C210.0228 (5)0.0196 (4)0.0142 (4)0.0009 (4)0.0023 (3)0.0007 (3)
C220.0227 (5)0.0219 (5)0.0344 (6)0.0032 (4)0.0025 (4)0.0030 (4)
Geometric parameters (Å, º) top
N1—C7'1.4096 (13)C17—C181.3855 (16)
N1—C21.4116 (13)C18—C191.3881 (16)
N1—S11.6531 (9)C19—C201.3889 (16)
O1—C51.3687 (12)C19—C221.4973 (16)
O1—C91.4320 (13)C20—C211.3824 (16)
S1—O31.4249 (9)C2—H20.9500
S1—O21.4284 (9)C4—H40.9500
S1—C161.7436 (11)C6—H60.9500
C2—C31.3521 (14)C7—H70.9500
C3—C3'1.4454 (14)C8—H8A0.9800
C3—C81.4866 (14)C8—H8B0.9800
C3'—C41.3933 (14)C8—H8C0.9800
C3'—C7'1.3955 (13)C9—H9A0.9900
C4—C51.3839 (14)C9—H9B0.9900
C5—C61.4035 (14)C11—H110.9500
C6—C71.3831 (14)C12—H120.9500
C7—C7'1.3880 (14)C13—H130.9500
C9—C101.4912 (14)C14—H140.9500
C10—C111.3844 (14)C15—H150.9500
C10—C151.3928 (14)C17—H170.9500
C11—C121.3874 (15)C18—H180.9500
C12—C131.3793 (17)C20—H200.9500
C13—C141.3847 (18)C21—H210.9500
C14—C151.3818 (15)C22—H22A0.9800
C16—C171.3852 (14)C22—H22B0.9800
C16—C211.3897 (14)C22—H22C0.9800
C7'—N1—C2107.40 (8)C20—C21—C16118.84 (10)
C7'—N1—S1124.73 (7)C3—C2—H2125.0
C2—N1—S1121.67 (7)N1—C2—H2125.0
C5—O1—C9115.43 (8)C5—C4—H4121.2
O3—S1—O2120.40 (5)C3'—C4—H4121.2
O3—S1—N1106.46 (5)C7—C6—H6119.3
O2—S1—N1105.22 (5)C5—C6—H6119.3
O3—S1—C16109.83 (5)C6—C7—H7121.3
O2—S1—C16109.39 (5)C7'—C7—H7121.3
N1—S1—C16104.19 (5)C3—C8—H8A109.5
C3—C2—N1110.09 (8)C3—C8—H8B109.5
C2—C3—C3'106.96 (9)H8A—C8—H8B109.5
C2—C3—C8128.25 (9)C3—C8—H8C109.5
C3'—C3—C8124.79 (9)H8A—C8—H8C109.5
C4—C3'—C7'120.85 (9)H8B—C8—H8C109.5
C4—C3'—C3131.03 (9)O1—C9—H9A109.9
C7'—C3'—C3108.11 (9)C10—C9—H9A109.9
C5—C4—C3'117.65 (9)O1—C9—H9B109.9
O1—C5—C4124.01 (9)C10—C9—H9B109.9
O1—C5—C6114.85 (9)H9A—C9—H9B108.3
C4—C5—C6121.14 (9)C10—C11—H11119.7
C7—C6—C5121.30 (9)C12—C11—H11119.7
C6—C7—C7'117.41 (9)C13—C12—H12120.1
C7—C7'—C3'121.62 (9)C11—C12—H12120.1
C7—C7'—N1130.97 (9)C12—C13—H13119.9
C3'—C7'—N1107.32 (8)C14—C13—H13119.9
O1—C9—C10108.98 (8)C15—C14—H14120.1
C11—C10—C15118.98 (9)C13—C14—H14120.1
C11—C10—C9120.67 (9)C14—C15—H15119.7
C15—C10—C9120.32 (9)C10—C15—H15119.7
C10—C11—C12120.64 (10)C16—C17—H17120.6
C13—C12—C11119.80 (10)C18—C17—H17120.6
C12—C13—C14120.18 (10)C17—C18—H18119.3
C15—C14—C13119.86 (10)C19—C18—H18119.3
C14—C15—C10120.52 (10)C21—C20—H20119.3
C17—C16—C21121.18 (10)C19—C20—H20119.3
C17—C16—S1120.03 (8)C20—C21—H21120.6
C21—C16—S1118.66 (8)C16—C21—H21120.6
C16—C17—C18118.73 (10)C19—C22—H22A109.5
C17—C18—C19121.41 (10)C19—C22—H22B109.5
C18—C19—C20118.53 (10)H22A—C22—H22B109.5
C18—C19—C22120.95 (10)C19—C22—H22C109.5
C20—C19—C22120.52 (10)H22A—C22—H22C109.5
C21—C20—C19121.32 (10)H22B—C22—H22C109.5
C7'—N1—S1—O342.42 (9)S1—N1—C7'—C727.34 (16)
C2—N1—S1—O3168.81 (8)C2—N1—C7'—C3'3.62 (11)
C7'—N1—S1—O2171.26 (8)S1—N1—C7'—C3'156.08 (7)
C2—N1—S1—O239.96 (9)C5—O1—C9—C10174.12 (9)
C7'—N1—S1—C1673.66 (9)O1—C9—C10—C11122.47 (10)
C2—N1—S1—C1675.11 (9)O1—C9—C10—C1559.84 (12)
C7'—N1—C2—C33.23 (11)C15—C10—C11—C120.98 (15)
S1—N1—C2—C3156.71 (8)C9—C10—C11—C12176.74 (10)
N1—C2—C3—C3'1.52 (11)C10—C11—C12—C130.17 (16)
N1—C2—C3—C8178.24 (10)C11—C12—C13—C141.24 (17)
C2—C3—C3'—C4178.08 (11)C12—C13—C14—C151.14 (17)
C8—C3—C3'—C41.69 (18)C13—C14—C15—C100.02 (16)
C2—C3—C3'—C7'0.77 (11)C11—C10—C15—C141.07 (15)
C8—C3—C3'—C7'179.46 (10)C9—C10—C15—C14176.66 (10)
C7'—C3'—C4—C51.80 (15)O3—S1—C16—C1717.23 (10)
C3—C3'—C4—C5179.47 (10)O2—S1—C16—C17151.44 (9)
C9—O1—C5—C41.70 (15)N1—S1—C16—C1796.46 (9)
C9—O1—C5—C6178.08 (9)O3—S1—C16—C21166.80 (8)
C3'—C4—C5—O1178.12 (10)O2—S1—C16—C2132.59 (10)
C3'—C4—C5—C61.65 (16)N1—S1—C16—C2179.50 (9)
O1—C5—C6—C7179.40 (10)C21—C16—C17—C180.29 (16)
C4—C5—C6—C70.38 (17)S1—C16—C17—C18176.15 (9)
C5—C6—C7—C7'0.75 (16)C16—C17—C18—C190.40 (17)
C6—C7—C7'—C3'0.59 (15)C17—C18—C19—C200.04 (17)
C6—C7—C7'—N1176.76 (10)C17—C18—C19—C22178.85 (11)
C4—C3'—C7'—C70.71 (15)C18—C19—C20—C210.61 (17)
C3—C3'—C7'—C7179.70 (9)C22—C19—C20—C21178.29 (10)
C4—C3'—C7'—N1176.26 (9)C19—C20—C21—C160.71 (16)
C3—C3'—C7'—N12.73 (11)C17—C16—C21—C200.25 (16)
C2—N1—C7'—C7179.80 (11)S1—C16—C21—C20175.66 (8)
Acknowledgements top

We thank the University of Notre Dame for its generous support of this program.

references
References top

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