5 Meth­oxy 2,3 di­methyl­indole

organic papers

o642

Structure Reports Online

ISSN 1600-5368

5-Methoxy-2,3-dimethylindole

Alan R. Kennedy,* John N. Sherwood and Paul A. Slavin

Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, Scotland

Correspondence e-mail: [email protected]

Key indicators

Single-crystal X-ray study T= 123 K

Mean(C±C) = 0.004 AÊ Rfactor = 0.044 wRfactor = 0.095 Data-to-parameter ratio = 9.3

For details of how these key indicators were automatically derived from the article, see http://journals.iucr.org/e.

#2002 International Union of Crystallography Printed in Great Britain ± all rights reserved

The attempted sublimation of the anti-in¯ammatory drug indomethacin gave a decomposition reaction from which crystals of 5-methoxy-2,3-dimethylindole, C11H13NO, were

isolated. The crystal structure includes a close intermolecular approach of the amine H atom to the face of an indole ring.

Comment

During the course of studies on the polymorphic nature of the anti-in¯ammatory and antipyretic drug indomethacin [1-(p -chlorobenzoyl)-5-methoxy-2-methlindolylacetic acid; Shen et al., 1963; Winter et al., 1963], we attempted to grow single crystals by sublimation. Unexpectedly, the compound decomposed and only colourless, acicular crystals of 5-methoxy-2,3-dimethylindole, (I), andpara-chlorobenzoic acid could be isolated.

As expected, the molecular structure of (I) is ¯at with no non-H atom lying more than 0.035 AÊ from the molecular plane (Fig. 1). The bond lengths and angles are also unexceptional, although the C2ÐC3 distance of 1.441 (4) AÊ does indicate a

Received 1 May 2002 Accepted 8 May 2002 Online 17 May 2002

Figure 1

lesser degree of conjugation than is general. The most inter-esting feature is the intermolecular contacts of the amine H1 atom. It approaches the face of a neighbouring ®ve-membered ring [the angle between molecular planes is 73.33 (5)_{] in an}

offset manner, such that the shortest contacts are not with nitrogen but with the C1 and C2 atoms. [Distances from H1 to N1i_{, C1}i_{, C2}i_{, C3}i _{and C4}i _{are 2.68 (4), 2.51 (3), 2.50 (3),}

2.66 (3) and 2.77 (4) AÊ, respectively; symmetry code: (i) 1ÿx,

1

2+y, 2ÿz]. This is reminiscent of the preference of cations to

interact with the heteroaromatic ring of indoles, discussed by Gokelet al.(2000) with respect to biological systems.

Experimental

Indomethacin (-polymorph) was placed at the bottom of an evac-uated sublimation tube and heated to 425 K. Crystals of (I) grew at the furthest end of the tube, where the temperature was approxi-mately 295 K.

Crystal data

C11H13NO Mr= 175.22

Monoclinic,P21 a= 7.7769 (4) AÊ b= 6.2492 (3) AÊ c= 9.6263 (5) AÊ

= 92.749 (2)

V= 467.29 (4) AÊ3 Z= 2

Dx= 1.245 Mg mÿ3

MoKradiation Cell parameters from 1140

re¯ections

= 1.0±27.5

= 0.08 mmÿ1 T= 123 (2) K Needle, colourless 0.600.100.04 mm

Data collection

Nonius KappaCCD diffractometer

!and'scans

6426 measured re¯ections 1163 independent re¯ections 810 re¯ections withI> 2(I)

Rint= 0.051

max= 27.5 h=ÿ9!10 k=ÿ8!8 l=ÿ12!12

Re®nement

Re®nement onF2 R[F2_{> 2(F}2_{)] = 0.044} wR(F2_{) = 0.095} S= 1.03 1163 re¯ections 125 parameters

H atoms treated by a mixture of independent and constrained re®nement

w= 1/[2_(F

o2) + (0.0488P)2]

whereP= (Fo2+ 2Fc2)/3

(/)max< 0.001

max= 0.18 e AÊÿ3

min=ÿ0.23 e AÊÿ3

H1, the atom bonded to N1, was re®ned isotropically, but all other H atoms were placed in calculated positions with riding modes. The methyl groups were allowed to rotate but not to tip.

Data collection: DENZO (Otwinowski & Minor, 1997) and COLLECT (Nonius, 1998); cell re®nement: DENZO and COLLECT; data reduction:DENZO and COLLECT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to re®ne structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication:SHELXL97.

References

Gokel, G. W., De Wall, S. L. & Meadows, E. S. (2000).Eur. J. Org. Chem.pp. 2967±2978.

Johnson, C. K. (1976).ORTEPII. Report ORNL-5138. Oak Ridge National Laboratory, Tennessee, USA.

Nonius (1998).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). SHELXL97 and SHELXS97. University of GoÈttingen, Germany.

Shen, T. Y., Ellis, R. L., Windholz, T. B., Matzuk, A. R., Rosegay, A., Lucas, S., Witzel, B. E., Stammer, C. H., Wilson, A. N., Holly, F. W., Willett, J. B., Sarett, L. H., Holtz, W. J., Winter, C. A., Risley, E. A. & Nuss, G. W. (1963). J. Am. Chem. Soc.85, 488±489.

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Acta Cryst. (2002). E58, o642–o643

supporting information

Acta Cryst. (2002). E58, o642–o643 [https://doi.org/10.1107/S1600536802008383]

5-Methoxy-2,3-dimethylindole

Alan R. Kennedy, John N. Sherwood and Paul A. Slavin

(I)

Crystal data

C11H13NO

Mr = 175.22

Monoclinic, P21

a = 7.7769 (4) Å

b = 6.2492 (3) Å

c = 9.6263 (5) Å

β = 92.749 (2)°

V = 467.29 (4) Å3

Z = 2

F(000) = 188

Dx = 1.245 Mg m−3

Mo Kα radiation, λ = 0.71073 Å Cell parameters from 1140 reflections

θ = 1.0–27.5°

µ = 0.08 mm−1

T = 123 K Needle, colourless 0.60 × 0.10 × 0.04 mm

Data collection

Nonius KappaCCD diffractometer

Radiation source: fine-focus sealed tube Graphite monochromator

ω and φ scans

6426 measured reflections 1163 independent reflections

810 reflections with I > 2σ(I)

Rint = 0.051

θmax = 27.5°, θmin = 2.1°

h = −9→10

k = −8→8

l = −12→12

Refinement

Refinement on F2

Least-squares matrix: full

R[F2 _{> 2σ(F}2_{)] = 0.044}

wR(F2_{) = 0.095}

S = 1.03 1163 reflections 125 parameters 1 restraint

Primary atom site location: structure-invariant direct methods

Secondary atom site location: difference Fourier map

Hydrogen site location: inferred from neighbouring sites

H atoms treated by a mixture of independent and constrained refinement

w = 1/[σ2_(F

o2) + (0.0488P)2]

where P = (Fo2 + 2Fc2)/3

(Δ/σ)max < 0.001

Δρmax = 0.18 e Å−3

Δρmin = −0.23 e Å−3

Special details

Refinement. H on N refined isotropically. All others in calc positions and riding modes. The methyl groups were allowed to rotate but not to tip.

Friedel pairs were merged for the final refinement. This made no significant change to the geometric parameters.

Refinement of F2 _{against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F}2_{, conventional}

R-factors R are based on F, with F set to zero for negative F2_{. The threshold expression of F}2 _{> σ(F}2_{) 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₎

x y z Uiso*/Ueq

O1 0.7746 (2) 0.3981 (3) 0.50995 (17) 0.0264 (5) N1 0.6070 (3) 0.8496 (4) 0.9741 (2) 0.0247 (6) C1 0.6962 (3) 0.7380 (5) 1.0786 (2) 0.0220 (6) C2 0.7812 (3) 0.5693 (4) 1.0220 (3) 0.0205 (6) C3 0.7435 (3) 0.5769 (5) 0.8740 (2) 0.0190 (6) C4 0.6330 (3) 0.7516 (4) 0.8479 (2) 0.0210 (6) C5 0.5682 (3) 0.8008 (5) 0.7145 (3) 0.0245 (7)

H5 0.4910 0.9170 0.6985 0.029*

C6 0.6196 (3) 0.6756 (5) 0.6066 (3) 0.0267 (7)

H6 0.5774 0.7061 0.5145 0.032*

C7 0.7330 (3) 0.5042 (4) 0.6299 (3) 0.0210 (7) C8 0.7953 (3) 0.4500 (4) 0.7620 (2) 0.0207 (7)

H8 0.8705 0.3315 0.7771 0.025*

C9 0.6912 (3) 0.8130 (5) 1.2249 (2) 0.0272 (7)

H9A 0.5716 0.8407 1.2474 0.041*

H9B 0.7584 0.9449 1.2364 0.041*

H9C 0.7401 0.7027 1.2875 0.041*

C10 0.8945 (3) 0.4101 (5) 1.0966 (3) 0.0287 (7)

H10A 0.8855 0.4275 1.1971 0.043*

H10B 1.0140 0.4329 1.0723 0.043*

H10C 0.8584 0.2652 1.0694 0.043*

C11 0.8822 (4) 0.2142 (5) 0.5252 (3) 0.0333 (8)

H11A 0.8252 0.1060 0.5806 0.050*

H11B 0.9919 0.2547 0.5723 0.050*

H11C 0.9035 0.1553 0.4332 0.050*

H1 0.528 (4) 0.961 (6) 0.985 (4) 0.051 (11)*

Atomic displacement parameters (Å2₎

U11 _U22 _U33 _U12 _U13 _U23

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Acta Cryst. (2002). E58, o642–o643

C7 0.0201 (13) 0.0244 (16) 0.0188 (15) −0.0039 (14) 0.0040 (11) −0.0021 (13) C8 0.0173 (13) 0.0254 (17) 0.0195 (15) −0.0003 (12) 0.0008 (11) 0.0000 (13) C9 0.0318 (15) 0.0285 (16) 0.0216 (14) 0.0017 (14) 0.0023 (12) −0.0024 (13) C10 0.0311 (15) 0.0300 (18) 0.0247 (15) 0.0063 (14) −0.0014 (12) −0.0011 (14) C11 0.0401 (17) 0.0319 (19) 0.0277 (16) 0.0004 (16) 0.0002 (13) −0.0094 (15)

Geometric parameters (Å, º)

O1—C7 1.383 (3) C6—C7 1.399 (4)

O1—C11 1.425 (3) C6—H6 0.9500

N1—C1 1.383 (3) C7—C8 1.381 (3)

N1—C4 1.384 (3) C8—H8 0.9500

N1—H1 0.94 (4) C9—H9A 0.9800

C1—C2 1.371 (4) C9—H9B 0.9800

C1—C9 1.487 (3) C9—H9C 0.9800

C2—C3 1.441 (4) C10—H10A 0.9800

C2—C10 1.490 (4) C10—H10B 0.9800

C3—C4 1.405 (3) C10—H10C 0.9800

C3—C8 1.412 (4) C11—H11A 0.9800

C4—C5 1.391 (3) C11—H11B 0.9800

C5—C6 1.375 (4) C11—H11C 0.9800

C5—H5 0.9500

C7—O1—C11 117.4 (2) C8—C7—C6 121.8 (2)

C1—N1—C4 109.0 (2) O1—C7—C6 113.8 (2)

C1—N1—H1 127 (2) C7—C8—C3 117.7 (2)

C4—N1—H1 123 (2) C7—C8—H8 121.2

C2—C1—N1 109.5 (2) C3—C8—H8 121.2

C2—C1—C9 130.8 (2) C1—C9—H9A 109.5

N1—C1—C9 119.7 (2) C1—C9—H9B 109.5

C1—C2—C3 106.8 (2) H9A—C9—H9B 109.5

C1—C2—C10 127.4 (2) C1—C9—H9C 109.5

C3—C2—C10 125.9 (2) H9A—C9—H9C 109.5

C4—C3—C8 119.6 (2) H9B—C9—H9C 109.5

C4—C3—C2 107.2 (2) C2—C10—H10A 109.5

C8—C3—C2 133.2 (2) C2—C10—H10B 109.5

N1—C4—C5 130.6 (2) H10A—C10—H10B 109.5

N1—C4—C3 107.5 (2) C2—C10—H10C 109.5

C5—C4—C3 121.9 (2) H10A—C10—H10C 109.5

C6—C5—C4 117.8 (3) H10B—C10—H10C 109.5

C6—C5—H5 121.1 O1—C11—H11A 109.5

C4—C5—H5 121.1 O1—C11—H11B 109.5

C5—C6—C7 121.2 (2) H11A—C11—H11B 109.5

C5—C6—H6 119.4 O1—C11—H11C 109.5

C7—C6—H6 119.4 H11A—C11—H11C 109.5

C8—C7—O1 124.5 (2) H11B—C11—H11C 109.5

C4—N1—C1—C9 179.2 (2) C2—C3—C4—C5 −178.4 (2)

N1—C1—C2—C3 0.2 (3) N1—C4—C5—C6 178.8 (3)