1-(3,5-Dimeth­oxy­benz­yl)-1H-pyrrole

Li, Y.; Zhang, X.; Huo, S.; Huang, W.; Zhao, W.

doi:10.1107/S1600536812015024

organic compounds

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Volume 68| Part 5| May 2012| Page o1372

doi:10.1107/S1600536812015024

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

Yueqing Li,^a Xu Zhang,^a Shiyong Huo,^a Wei Huang ^a and Weijie Zhao ^a ^*

^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 ); 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

Crystal data

C₁₃H₁₅NO₂
M_r = 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)
R_int = 0.027

Refinement

R[F² > 2σ(F²)] = 0.041
wR(F²) = 0.140
S = 0.99
2230 reflections
145 parameters
H-atom parameters constrained
Δρ_max = 0.15 e Å⁻³
Δρ_min = −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	D⋯A	D—H⋯A
C1—H1A⋯Cgⁱ	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 ); cell refinement: SAINT-Plus (Bruker, 2001 ); data reduction: SAINT-Plus; 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.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536812015024/rk2345sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812015024/rk2345Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536812015024/rk2345Isup3.cml

checkCIF report

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.

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

	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.
	Fig. 2. A view of the packing of the title compound along b axis.
	Fig. 3. The synthetic route of the title compound.
	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

C₁₃H₁₅NO₂	F(000) = 464
M_r = 217.26	D_x = 1.268 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 2351 reflections
a = 9.7569 (11) Å	θ = 2.8–26.0°
b = 12.2303 (10) Å	µ = 0.09 mm⁻¹
c = 10.4181 (10) Å	T = 153 K
β = 113.720 (7)°	Needle, colorless
V = 1138.2 (2) Å³	0.21 × 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 tube	R_int = 0.027
Graphite monochromator	θ_max = 26.0°, θ_min = 2.7°
ϕ and ω scans	h = −12→8
7643 measured reflections	k = −15→15
2230 independent reflections	l = −11→12

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.041	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.140	H-atom parameters constrained
S = 0.99	w = 1/[σ²(F_o²) + (0.1P)²] where P = (F_o² + 2F_c²)/3
2230 reflections	(Δ/σ)_max = 0.014
145 parameters	Δρ_max = 0.15 e Å⁻³
0 restraints	Δρ_min = −0.18 e Å⁻³

Crystal data top

C₁₃H₁₅NO₂	V = 1138.2 (2) Å³
M_r = 217.26	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 9.7569 (11) Å	µ = 0.09 mm⁻¹
b = 12.2303 (10) Å	T = 153 K
c = 10.4181 (10) Å	0.21 × 0.21 × 0.16 mm
β = 113.720 (7)°

Data collection top

Bruker APEXII CCD diffractometer	1717 reflections with I > 2σ(I)
7643 measured reflections	R_int = 0.027
2230 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.041	0 restraints
wR(F²) = 0.140	H-atom parameters constrained
S = 0.99	Δρ_max = 0.15 e Å⁻³
2230 reflections	Δρ_min = −0.18 e Å⁻³
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

	x	y	z	U_iso*/U_eq
N	0.14877 (13)	0.21993 (9)	0.87889 (11)	0.0396 (3)
O1	0.13871 (14)	0.44438 (8)	0.47582 (11)	0.0572 (4)
O2	0.08702 (13)	0.07035 (8)	0.30839 (10)	0.0536 (3)
C11	0.13905 (15)	0.11206 (11)	0.54195 (14)	0.0397 (4)
H11A	0.1407	0.0373	0.5591	0.048*
C7	0.16360 (16)	0.29689 (11)	0.62375 (14)	0.0407 (4)
H7A	0.1814	0.3469	0.6959	0.049*
C9	0.10819 (16)	0.26083 (11)	0.37960 (14)	0.0384 (4)
H9A	0.0884	0.2858	0.2895	0.046*
C5	0.19169 (18)	0.14323 (12)	0.79460 (15)	0.0478 (4)
H5A	0.1358	0.0759	0.7850	0.057*
H5B	0.2971	0.1261	0.8437	0.057*
C8	0.13589 (16)	0.33349 (11)	0.48959 (14)	0.0394 (4)
C10	0.11093 (15)	0.14936 (10)	0.40823 (14)	0.0381 (4)
C1	0.24214 (17)	0.29419 (12)	0.96984 (15)	0.0455 (4)
H1A	0.3453	0.2980	0.9977	0.055*
C6	0.16472 (15)	0.18558 (11)	0.65030 (14)	0.0380 (4)
C12	0.0972 (2)	0.48874 (13)	0.33928 (16)	0.0573 (5)
H12A	0.1015	0.5671	0.3448	0.086*
H12B	−0.0028	0.4662	0.2808	0.086*
H12C	0.1650	0.4629	0.3000	0.086*
C4	0.00631 (16)	0.24161 (13)	0.86324 (15)	0.0475 (4)
H4A	−0.0788	0.2035	0.8059	0.057*
C2	0.15797 (19)	0.36182 (13)	1.01276 (16)	0.0514 (4)
H2A	0.1932	0.4197	1.0754	0.062*
C3	0.00937 (18)	0.32851 (14)	0.94572 (16)	0.0528 (4)
H3A	−0.0726	0.3599	0.9556	0.063*
C13	0.0520 (2)	0.10539 (13)	0.16790 (15)	0.0537 (4)
H13A	0.0360	0.0427	0.1082	0.081*
H13B	0.1336	0.1478	0.1651	0.081*
H13C	−0.0370	0.1493	0.1359	0.081*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N	0.0424 (7)	0.0461 (7)	0.0284 (6)	−0.0016 (5)	0.0122 (5)	0.0034 (5)
O1	0.0951 (9)	0.0343 (6)	0.0415 (6)	−0.0005 (5)	0.0266 (6)	0.0034 (4)
O2	0.0836 (8)	0.0395 (6)	0.0364 (6)	−0.0022 (5)	0.0230 (6)	−0.0046 (4)
C11	0.0453 (8)	0.0327 (7)	0.0388 (8)	0.0017 (6)	0.0146 (7)	0.0029 (6)
C7	0.0502 (9)	0.0380 (8)	0.0321 (8)	−0.0007 (6)	0.0146 (6)	−0.0032 (6)
C9	0.0433 (8)	0.0409 (8)	0.0304 (7)	0.0010 (6)	0.0142 (6)	0.0035 (6)
C5	0.0616 (10)	0.0434 (8)	0.0366 (8)	0.0042 (7)	0.0180 (7)	0.0038 (6)
C8	0.0473 (8)	0.0329 (7)	0.0387 (8)	0.0005 (6)	0.0180 (6)	0.0012 (6)
C10	0.0433 (8)	0.0362 (7)	0.0343 (7)	0.0005 (6)	0.0150 (6)	−0.0028 (6)
C1	0.0442 (8)	0.0564 (9)	0.0331 (8)	−0.0090 (7)	0.0126 (6)	0.0010 (7)
C6	0.0401 (8)	0.0393 (8)	0.0326 (7)	0.0021 (6)	0.0126 (6)	0.0025 (6)
C12	0.0857 (12)	0.0398 (8)	0.0516 (10)	0.0030 (8)	0.0332 (9)	0.0121 (7)
C4	0.0390 (8)	0.0630 (10)	0.0367 (8)	−0.0048 (7)	0.0114 (7)	0.0107 (7)
C2	0.0703 (11)	0.0494 (9)	0.0366 (8)	−0.0056 (8)	0.0237 (8)	−0.0016 (7)
C3	0.0556 (10)	0.0625 (10)	0.0472 (9)	0.0140 (8)	0.0278 (8)	0.0130 (8)
C13	0.0745 (11)	0.0525 (9)	0.0329 (8)	−0.0035 (8)	0.0203 (8)	−0.0068 (7)

Geometric parameters (Å, º) top

N—C4	1.3589 (19)	C5—C6	1.5097 (19)
N—C1	1.3631 (18)	C5—H5A	0.9700
N—C5	1.4568 (18)	C5—H5B	0.9700
O1—C8	1.3652 (16)	C1—C2	1.362 (2)
O1—C12	1.4207 (17)	C1—H1A	0.9300
O2—C10	1.3693 (16)	C12—H12A	0.9600
O2—C13	1.4284 (17)	C12—H12B	0.9600
C11—C6	1.3849 (19)	C12—H12C	0.9600
C11—C10	1.3845 (19)	C4—C3	1.359 (2)
C11—H11A	0.9300	C4—H4A	0.9300
C7—C6	1.3883 (19)	C2—C3	1.393 (2)
C7—C8	1.3868 (19)	C2—H2A	0.9300
C7—H7A	0.9300	C3—H3A	0.9300
C9—C8	1.3880 (19)	C13—H13A	0.9600
C9—C10	1.3934 (19)	C13—H13B	0.9600
C9—H9A	0.9300	C13—H13C	0.9600

C4—N—C1	108.58 (13)	C2—C1—H1A	126.0
C4—N—C5	125.56 (13)	N—C1—H1A	126.0
C1—N—C5	125.05 (13)	C11—C6—C7	119.33 (13)
C8—O1—C12	118.35 (12)	C11—C6—C5	119.39 (12)
C10—O2—C13	117.65 (11)	C7—C6—C5	121.27 (13)
C6—C11—C10	120.26 (12)	O1—C12—H12A	109.5
C6—C11—H11A	119.9	O1—C12—H12B	109.5
C10—C11—H11A	119.9	H12A—C12—H12B	109.5
C6—C7—C8	120.00 (13)	O1—C12—H12C	109.5
C6—C7—H7A	120.0	H12A—C12—H12C	109.5
C8—C7—H7A	120.0	H12B—C12—H12C	109.5
C8—C9—C10	117.98 (12)	N—C4—C3	108.38 (13)
C8—C9—H9A	121.0	N—C4—H4A	125.8
C10—C9—H9A	121.0	C3—C4—H4A	125.8
N—C5—C6	113.71 (12)	C1—C2—C3	107.53 (15)
N—C5—H5A	108.8	C1—C2—H2A	126.2
C6—C5—H5A	108.8	C3—C2—H2A	126.2
N—C5—H5B	108.8	C4—C3—C2	107.42 (14)
C6—C5—H5B	108.8	C4—C3—H3A	126.3
H5A—C5—H5B	107.7	C2—C3—H3A	126.3
O1—C8—C7	115.00 (13)	O2—C13—H13A	109.5
O1—C8—C9	123.69 (13)	O2—C13—H13B	109.5
C7—C8—C9	121.31 (13)	H13A—C13—H13B	109.5
O2—C10—C11	115.85 (12)	O2—C13—H13C	109.5
O2—C10—C9	123.04 (12)	H13A—C13—H13C	109.5
C11—C10—C9	121.11 (13)	H13B—C13—H13C	109.5
C2—C1—N	108.07 (14)

Hydrogen-bond geometry (Å, º) top

Cg is the centroid of the C6–C11 ring.

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1A···Cgⁱ	0.93	2.79	3.6935 (19)	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+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 formula	C₁₃H₁₅NO₂
M_r	217.26
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	153
a, b, c (Å)	9.7569 (11), 12.2303 (10), 10.4181 (10)
β (°)	113.720 (7)
V (Å³)	1138.2 (2)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.21 × 0.21 × 0.16

Data collection
Diffractometer	Bruker APEXII CCD diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	7643, 2230, 1717
R_int	0.027
(sin θ/λ)_max (Å⁻¹)	0.617

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.041, 0.140, 0.99
No. of reflections	2230
No. of parameters	145
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	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···A	D—H	H···A	D···A	D—H···A
C1—H1A···Cgⁱ	0.9300	2.79	3.6935 (19)	165
C2—H2A···O2ⁱⁱ	0.9300	2.715	3.527 (2)	146.3
C5—H5A···O2ⁱⁱⁱ	0.9700	2.678	3.609 (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

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