organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2056-9890
Volume 68| Part 5| May 2012| Page o1372

1-(3,5-Dimeth­­oxy­benz­yl)-1H-pyrrole

aSchool of Pharmaceutical Science and Technology, Dalian Unversity of Technology, PO Box G303, Linggong Road 2, Dalian 116024, People's Republic of China
*Correspondence e-mail: zyzhao@dlut.edu.cn

(Received 13 March 2012; accepted 5 April 2012; online 13 April 2012)

The title compound, C13H15NO2, was synthesized from 3,5-dimeth­oxy­benzaldehyde. The dihedral angle between the pyrrole and benzene rings is 89.91 (5)°. In the crystal, weak C—H⋯O and C—H⋯π interactions link the mol­ecules into a three-dimensional network.

Related literature

For the anti-HIV-1 activity of N-(aryl­meth­yl)-pyrrole, see: Liu et al. (2008[Liu, K., Lu, H., Hou, L., Qi, Z., Teixeira, C., Barbault, F., Fan, B. T., Liu, S., Jiang, S. & Xie, L. (2008). J. Med. Chem. 51, 7843-7854.]); Teixeira et al. (2008[Teixeira, C., Barbault, F., Rebehmed, J., Liu, K., Xie, L., Lu, H., Jiang, S., Fan, B. T. & Maurel, F. (2008). Bioorg. Med. Chem. 16, 3039-3048.]). For a related structure, see: Wang et al. (2011[Wang, C. J., Zeng, X. C. & Xu, S. H. (2011). Acta Cryst. E67, o2235.]). For the synthesis of 3,5-dimeth­oxy-benzyl­amine, see: Yraola et al. (2006[Yraola, F., Garcia-Vicente, S., Fernandez-Recio, J., Albericio, F., Zorzano, A., Marti, L. & Royo, M. (2006). J. Med. Chem. 49, 6197-6208.]).

[Scheme 1]

Experimental

Crystal data
  • C13H15NO2

  • Mr = 217.26

  • Monoclinic, P 21 /n

  • a = 9.7569 (11) Å

  • b = 12.2303 (10) Å

  • c = 10.4181 (10) Å

  • β = 113.720 (7)°

  • V = 1138.2 (2) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.09 mm−1

  • T = 153 K

  • 0.21 × 0.21 × 0.16 mm

Data collection
  • Bruker APEXII CCD diffractometer

  • 7643 measured reflections

  • 2230 independent reflections

  • 1717 reflections with I > 2σ(I)

  • Rint = 0.027

Refinement
  • R[F2 > 2σ(F2)] = 0.041

  • wR(F2) = 0.140

  • S = 0.99

  • 2230 reflections

  • 145 parameters

  • H-atom parameters constrained

  • Δρmax = 0.15 e Å−3

  • Δρmin = −0.18 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

Cg is the centroid of the C6–C11 ring.

D—H⋯A D—H H⋯A DA D—H⋯A
C1—H1ACgi 0.93 2.79 3.694 (2) 165
C2—H2A⋯O2ii 0.93 2.72 3.527 (2) 146
C5—H5A⋯O2iii 0.97 2.68 3.609 (2) 161
Symmetry codes: (i) [x+{\script{1\over 2}}, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]; (ii) [-x+{\script{1\over 2}}, y+{\script{1\over 2}}, -z+{\script{3\over 2}}]; (iii) -x, -y, -z+1.

Data collection: APEX2 (Bruker, 2005[Bruker (2005). APEX2. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT-Plus (Bruker, 2001[Bruker (2001). SAINT-Plus. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXTL.

Supporting information


Comment top

A lot of N-(arylmethyl)-pyrrole derivatives show anti-HIV-1 activities, such as inhibitory activity on gp41 six-helix bundle formation in both molecule modeling study (Teixeira et al., 2008) and activity assay (Liu et al., 2008). The title compound may possess the same qualities. The title compound is prepared via two steps and the product of the first step can be added to the solution of the second step without purification.

In the title compound, as shown in Fig. 1, the pyrrole and benzene rings are on the different plane. The dihedral angle between the two plane is 89.91 (5)° and close to the dihedral angle in 1-benzyl-N-methyl-1H-pyrrole-2-carboxamide (Wang et al., 2011). The N-C5-C6-C7 torsion angle is 26.37 (20)°. The structure is stabilized by the non-classical hydogen bonds (Table 1). The packing diagram is presented in Fig. 2.

Related literature top

For the anti-HIV-1 activity of N-(arylmethyl)-pyrrole, see: Liu et al. (2008); Teixeira et al. (2008). For a related structure, see: Wang et al. (2011). For the synthesis of 3,5-dimethoxy-benzylamine, see: Yraola et al. (2006).

Experimental top

Starting material is 3,5-dimethoxy-benzaldehyde (20.9 g, 126 mmol) (Fig. 3). For the first step, 3,5-dimethoxy-benzylamine is prepared according to (Yraola et al., 2006). 2,5-Dimethoxytetrahydrofuran (14.2 g, 108 mmol) and glacial acetic acid (150 ml) were added to the first step product. After stirring at 333 K for 6 h, solvent was removed under reduced pressure. The crude product was purified by flash column chromatography (petrol ether / EtOAc (10 / 1), yielding the title compound (0.98 g, 52%) as a white solid. The product (16 mg) was dissolved in ethyl ether (1 ml) and methanol (0.05 ml). Single crystals suitable for X-ray diffraction experiment was obtained from the solution by cooling at 273 K for seven days. The molecule was characterized by NMR (Fig. 4).

1H NMR (400 MHz, CDCl3): δ 6.68(t, J = 2.1 Hz, 2H, H-2, H-5), 6.36(t, J = 2.2 Hz, 1H, H-4'), 6.25(d, J = 2.2 Hz, 2H, H-2', H-6'), 6.18(t, J = 2.1 Hz, 2H, H-3, H-4), 4.99(s, 2H, CH2), 3.73(s, 6H, OCH3). 13C NMR (100 MHz, CDCl3): δ 161.2, 140.7, 121.3, 108.6, 105.07, 99.4, 55.3, 53.4. HRMS (ES+): M/z [M+Na]+ calcd. for C13H15NO2Na: 240.1001; found: 240.1006.

Refinement top

All H atoms attached to C atoms were treated as riding, withC–H = 0.96Å for methyl group, C–H = 0.97Å for methylene group, and C–H = 0.93Å for aromatic ring, with Uiso(H) = 1.2Ueq(C) of the carrier atoms to which they are attached and Uiso(H) = 1.5Ueq(C) for the methyl groups.

Computing details top

Data collection: APEX2 (Bruker, 2005); cell refinement: SAINT-Plus (Bruker, 2001); data reduction: SAINT-Plus (Bruker, 2001); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure of title compound, showing the atom numbering scheme. Displacement ellipsoids are drawn at 30% probability level. H atoms are presented as a small spheres of arbitrary radius.
[Figure 2] Fig. 2. A view of the packing of the title compound along b axis.
[Figure 3] Fig. 3. The synthetic route of the title compound.
[Figure 4] Fig. 4. The structure of title compound, with atoms labeling corresponding to the characterization by NMR.
1-(3,5-Dimethoxybenzyl)-1H-pyrrole top
Crystal data top
C13H15NO2F(000) = 464
Mr = 217.26Dx = 1.268 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 2351 reflections
a = 9.7569 (11) Åθ = 2.8–26.0°
b = 12.2303 (10) ŵ = 0.09 mm1
c = 10.4181 (10) ÅT = 153 K
β = 113.720 (7)°Needle, colorless
V = 1138.2 (2) Å30.21 × 0.21 × 0.16 mm
Z = 4
Data collection top
Bruker APEXII CCD
diffractometer
1717 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.027
Graphite monochromatorθmax = 26.0°, θmin = 2.7°
ϕ and ω scansh = 128
7643 measured reflectionsk = 1515
2230 independent reflectionsl = 1112
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)] = 0.041Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.140H-atom parameters constrained
S = 0.99 w = 1/[σ2(Fo2) + (0.1P)2]
where P = (Fo2 + 2Fc2)/3
2230 reflections(Δ/σ)max = 0.014
145 parametersΔρmax = 0.15 e Å3
0 restraintsΔρmin = 0.18 e Å3
Crystal data top
C13H15NO2V = 1138.2 (2) Å3
Mr = 217.26Z = 4
Monoclinic, P21/nMo Kα radiation
a = 9.7569 (11) ŵ = 0.09 mm1
b = 12.2303 (10) ÅT = 153 K
c = 10.4181 (10) Å0.21 × 0.21 × 0.16 mm
β = 113.720 (7)°
Data collection top
Bruker APEXII CCD
diffractometer
1717 reflections with I > 2σ(I)
7643 measured reflectionsRint = 0.027
2230 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0410 restraints
wR(F2) = 0.140H-atom parameters constrained
S = 0.99Δρmax = 0.15 e Å3
2230 reflectionsΔρmin = 0.18 e Å3
145 parameters
Special details top

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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) top
xyzUiso*/Ueq
N0.14877 (13)0.21993 (9)0.87889 (11)0.0396 (3)
O10.13871 (14)0.44438 (8)0.47582 (11)0.0572 (4)
O20.08702 (13)0.07035 (8)0.30839 (10)0.0536 (3)
C110.13905 (15)0.11206 (11)0.54195 (14)0.0397 (4)
H11A0.14070.03730.55910.048*
C70.16360 (16)0.29689 (11)0.62375 (14)0.0407 (4)
H7A0.18140.34690.69590.049*
C90.10819 (16)0.26083 (11)0.37960 (14)0.0384 (4)
H9A0.08840.28580.28950.046*
C50.19169 (18)0.14323 (12)0.79460 (15)0.0478 (4)
H5A0.13580.07590.78500.057*
H5B0.29710.12610.84370.057*
C80.13589 (16)0.33349 (11)0.48959 (14)0.0394 (4)
C100.11093 (15)0.14936 (10)0.40823 (14)0.0381 (4)
C10.24214 (17)0.29419 (12)0.96984 (15)0.0455 (4)
H1A0.34530.29800.99770.055*
C60.16472 (15)0.18558 (11)0.65030 (14)0.0380 (4)
C120.0972 (2)0.48874 (13)0.33928 (16)0.0573 (5)
H12A0.10150.56710.34480.086*
H12B0.00280.46620.28080.086*
H12C0.16500.46290.30000.086*
C40.00631 (16)0.24161 (13)0.86324 (15)0.0475 (4)
H4A0.07880.20350.80590.057*
C20.15797 (19)0.36182 (13)1.01276 (16)0.0514 (4)
H2A0.19320.41971.07540.062*
C30.00937 (18)0.32851 (14)0.94572 (16)0.0528 (4)
H3A0.07260.35990.95560.063*
C130.0520 (2)0.10539 (13)0.16790 (15)0.0537 (4)
H13A0.03600.04270.10820.081*
H13B0.13360.14780.16510.081*
H13C0.03700.14930.13590.081*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N0.0424 (7)0.0461 (7)0.0284 (6)0.0016 (5)0.0122 (5)0.0034 (5)
O10.0951 (9)0.0343 (6)0.0415 (6)0.0005 (5)0.0266 (6)0.0034 (4)
O20.0836 (8)0.0395 (6)0.0364 (6)0.0022 (5)0.0230 (6)0.0046 (4)
C110.0453 (8)0.0327 (7)0.0388 (8)0.0017 (6)0.0146 (7)0.0029 (6)
C70.0502 (9)0.0380 (8)0.0321 (8)0.0007 (6)0.0146 (6)0.0032 (6)
C90.0433 (8)0.0409 (8)0.0304 (7)0.0010 (6)0.0142 (6)0.0035 (6)
C50.0616 (10)0.0434 (8)0.0366 (8)0.0042 (7)0.0180 (7)0.0038 (6)
C80.0473 (8)0.0329 (7)0.0387 (8)0.0005 (6)0.0180 (6)0.0012 (6)
C100.0433 (8)0.0362 (7)0.0343 (7)0.0005 (6)0.0150 (6)0.0028 (6)
C10.0442 (8)0.0564 (9)0.0331 (8)0.0090 (7)0.0126 (6)0.0010 (7)
C60.0401 (8)0.0393 (8)0.0326 (7)0.0021 (6)0.0126 (6)0.0025 (6)
C120.0857 (12)0.0398 (8)0.0516 (10)0.0030 (8)0.0332 (9)0.0121 (7)
C40.0390 (8)0.0630 (10)0.0367 (8)0.0048 (7)0.0114 (7)0.0107 (7)
C20.0703 (11)0.0494 (9)0.0366 (8)0.0056 (8)0.0237 (8)0.0016 (7)
C30.0556 (10)0.0625 (10)0.0472 (9)0.0140 (8)0.0278 (8)0.0130 (8)
C130.0745 (11)0.0525 (9)0.0329 (8)0.0035 (8)0.0203 (8)0.0068 (7)
Geometric parameters (Å, º) top
N—C41.3589 (19)C5—C61.5097 (19)
N—C11.3631 (18)C5—H5A0.9700
N—C51.4568 (18)C5—H5B0.9700
O1—C81.3652 (16)C1—C21.362 (2)
O1—C121.4207 (17)C1—H1A0.9300
O2—C101.3693 (16)C12—H12A0.9600
O2—C131.4284 (17)C12—H12B0.9600
C11—C61.3849 (19)C12—H12C0.9600
C11—C101.3845 (19)C4—C31.359 (2)
C11—H11A0.9300C4—H4A0.9300
C7—C61.3883 (19)C2—C31.393 (2)
C7—C81.3868 (19)C2—H2A0.9300
C7—H7A0.9300C3—H3A0.9300
C9—C81.3880 (19)C13—H13A0.9600
C9—C101.3934 (19)C13—H13B0.9600
C9—H9A0.9300C13—H13C0.9600
C4—N—C1108.58 (13)C2—C1—H1A126.0
C4—N—C5125.56 (13)N—C1—H1A126.0
C1—N—C5125.05 (13)C11—C6—C7119.33 (13)
C8—O1—C12118.35 (12)C11—C6—C5119.39 (12)
C10—O2—C13117.65 (11)C7—C6—C5121.27 (13)
C6—C11—C10120.26 (12)O1—C12—H12A109.5
C6—C11—H11A119.9O1—C12—H12B109.5
C10—C11—H11A119.9H12A—C12—H12B109.5
C6—C7—C8120.00 (13)O1—C12—H12C109.5
C6—C7—H7A120.0H12A—C12—H12C109.5
C8—C7—H7A120.0H12B—C12—H12C109.5
C8—C9—C10117.98 (12)N—C4—C3108.38 (13)
C8—C9—H9A121.0N—C4—H4A125.8
C10—C9—H9A121.0C3—C4—H4A125.8
N—C5—C6113.71 (12)C1—C2—C3107.53 (15)
N—C5—H5A108.8C1—C2—H2A126.2
C6—C5—H5A108.8C3—C2—H2A126.2
N—C5—H5B108.8C4—C3—C2107.42 (14)
C6—C5—H5B108.8C4—C3—H3A126.3
H5A—C5—H5B107.7C2—C3—H3A126.3
O1—C8—C7115.00 (13)O2—C13—H13A109.5
O1—C8—C9123.69 (13)O2—C13—H13B109.5
C7—C8—C9121.31 (13)H13A—C13—H13B109.5
O2—C10—C11115.85 (12)O2—C13—H13C109.5
O2—C10—C9123.04 (12)H13A—C13—H13C109.5
C11—C10—C9121.11 (13)H13B—C13—H13C109.5
C2—C1—N108.07 (14)
Hydrogen-bond geometry (Å, º) top
Cg is the centroid of the C6–C11 ring.
D—H···AD—HH···AD···AD—H···A
C1—H1A···Cgi0.932.793.6935 (19)165
C2—H2A···O2ii0.932.723.527 (2)146
C5—H5A···O2iii0.972.683.609 (2)161
Symmetry codes: (i) x+1/2, y+1/2, z+1/2; (ii) x+1/2, y+1/2, z+3/2; (iii) x, y, z+1.

Experimental details

Crystal data
Chemical formulaC13H15NO2
Mr217.26
Crystal system, space groupMonoclinic, P21/n
Temperature (K)153
a, b, c (Å)9.7569 (11), 12.2303 (10), 10.4181 (10)
β (°) 113.720 (7)
V3)1138.2 (2)
Z4
Radiation typeMo Kα
µ (mm1)0.09
Crystal size (mm)0.21 × 0.21 × 0.16
Data collection
DiffractometerBruker APEXII CCD
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
7643, 2230, 1717
Rint0.027
(sin θ/λ)max1)0.617
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.041, 0.140, 0.99
No. of reflections2230
No. of parameters145
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.15, 0.18

Computer programs: APEX2 (Bruker, 2005), SAINT-Plus (Bruker, 2001), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top
Cg is the centroid of the C6–C11 ring.
D—H···AD—HH···AD···AD—H···A
C1—H1A···Cgi0.93002.793.6935 (19)165
C2—H2A···O2ii0.93002.7153.527 (2)146.3
C5—H5A···O2iii0.97002.6783.609 (2)160.9
Symmetry codes: (i) x+1/2, y+1/2, z+1/2; (ii) x+1/2, y+1/2, z+3/2; (iii) x, y, z+1.
 

Acknowledgements

The financial support of this work by the Fundamental Research Funds for the Central Universities (No. DUT11LK26) is gratefully acknowledged.

References

First citationBruker (2001). SAINT-Plus. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationBruker (2005). APEX2. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationLiu, K., Lu, H., Hou, L., Qi, Z., Teixeira, C., Barbault, F., Fan, B. T., Liu, S., Jiang, S. & Xie, L. (2008). J. Med. Chem. 51, 7843–7854.  Web of Science CrossRef PubMed CAS Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationTeixeira, C., Barbault, F., Rebehmed, J., Liu, K., Xie, L., Lu, H., Jiang, S., Fan, B. T. & Maurel, F. (2008). Bioorg. Med. Chem. 16, 3039–3048.  Web of Science CrossRef PubMed CAS Google Scholar
First citationWang, C. J., Zeng, X. C. & Xu, S. H. (2011). Acta Cryst. E67, o2235.  Web of Science CSD CrossRef IUCr Journals Google Scholar
First citationYraola, F., Garcia-Vicente, S., Fernandez-Recio, J., Albericio, F., Zorzano, A., Marti, L. & Royo, M. (2006). J. Med. Chem. 49, 6197–6208.  Web of Science CrossRef PubMed CAS Google Scholar

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Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 68| Part 5| May 2012| Page o1372
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