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Acta Cryst. (2007). E63, o2782    [ doi:10.1107/S1600536807020600 ]

3,5-Dimethoxyacetanilide

Q.-L. Lai, Q.-J. Zhao, Z. Liu and J.-S. Shen

Abstract top

The title compound, C10H13NO3, crystallizes with two molecules in the asymmetric unit. Molecules related by an a-axis translation are stacked over each other, bound by [pi]-[pi] interactions with a perpendicular distance of 3.455 Å. Molecules in adjacent stacks are linked to each other through N-H...O hydrogen bonds.

Comment top

The title compound, (I), is an important intermediate used to synthesize a variety of pharmaceuticals, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (Traxler et al., 1999). In our recent research for the synthesis of potential PDE5 inhitiors, 3,5-dimethoxyanilide (I) was synthesized as one of the structural units. We report here the crystal structure of the title compound, which crystallizes with two molecules in the asymmetric unit.

A view of the molecular structure of (I) is depicted in Fig. 1. In the two distinct molecules, the N-acetyl group is oriented at angles of 3.10 (2)° and 20.00 (3)° to the aromatic plane. All bond lengths and angles are normal (Allen et al., 1987). Molecules related by an a-axis translation are stacked over each other and the perpendicular distance between the stacking planes is 3.455Å (Fig. 2). It is, therefore, inferred that the stacked molecules are bound to each other by π-π interactions (Hunter & Sanders, 1990). The stacked columns are linked together via an intermolecular hydrogen bond in which the amide H act as a donor to O atom (Fig. 2 and Table 1).

Related literature top

For related literature, see: Allen et al. (1987); Hall et al. (1992); Hunter & Sanders (1990); Traxler et al. (1999).

Experimental top

The title compound was prepared by acetylation of 3,5-dimethoxyaniline according to the method described by Hall et al., (1992). Single crystals suitable for X-ray analysis (m.p. 426 K) were obtained by slow evaporation of a dichloromethane solution at 298 K.

Refinement top

All H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms, with C—H = 0.93 - 0.96 Å, N—H = 0.86 Å, and Uiso = 1.2Ueq(C) or (N).

Computing details top

Data collection: APEX2 (Bruker, 2000); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Sheldrick, 2000); software used to prepare material for publication: SHELXTL.

Figures top
[Figure 1] Fig. 1. View of the molecule of (I) showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
[Figure 2] Fig. 2. The crystal packing of (I), viewed along the 〈i〉a〈/i〉 axis. Hydrogen bonds are shown as dashed lines.
3,5-Dimethoxyacetanilide top
Crystal data top
C10H13NO3Dx = 1.296 Mg m−3
Mr = 195.21Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, PbcaCell parameters from 4958 reflections
a = 7.1956 (6) Åθ = 2.5–24.7°
b = 16.8320 (14) ŵ = 0.10 mm−1
c = 33.054 (3) ÅT = 293 K
V = 4003.4 (6) Å3Block, colourless
Z = 160.30 × 0.20 × 0.20 mm
F(000) = 1664
Data collection top
Bruker SMART APEXII
diffractometer		3548 independent reflections
Radiation source: fine-focus sealed tube2808 reflections with I > 2σ(I)
graphiteRint = 0.033
φ and ω scansθmax = 25.1°, θmin = 2.5°
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)		h = −8→8
Tmin = 0.972, Tmax = 0.981k = −19→20
19389 measured reflectionsl = −30→39
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.042H-atom parameters constrained
wR(F2) = 0.108 w = 1/[σ2(Fo2) + (0.047P)2 + 1.2714P]
where P = (Fo2 + 2Fc2)/3
S = 1.03(Δ/σ)max = 0.001
3548 reflectionsΔρmax = 0.25 e Å−3
260 parametersΔρmin = −0.14 e Å−3
0 restraintsExtinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0015 (4)
Crystal data top
C10H13NO3V = 4003.4 (6) Å3
Mr = 195.21Z = 16
Orthorhombic, PbcaMo Kα radiation
a = 7.1956 (6) ŵ = 0.10 mm−1
b = 16.8320 (14) ÅT = 293 K
c = 33.054 (3) Å0.30 × 0.20 × 0.20 mm
Data collection top
Bruker SMART APEXII
diffractometer		3548 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)		2808 reflections with I > 2σ(I)
Tmin = 0.972, Tmax = 0.981Rint = 0.033
19389 measured reflectionsθmax = 25.1°
Refinement top
R[F2 > 2σ(F2)] = 0.042H-atom parameters constrained
wR(F2) = 0.108Δρmax = 0.25 e Å−3
S = 1.03Δρmin = −0.14 e Å−3
3548 reflectionsAbsolute structure: ?
260 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.

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
C10.9040 (2)0.66216 (10)0.91166 (5)0.0360 (4)
C20.7495 (2)0.70799 (10)0.92004 (5)0.0416 (4)
H20.73990.75900.90950.050*
C30.6087 (2)0.67783 (11)0.94428 (5)0.0430 (4)
C40.6212 (3)0.60184 (11)0.96012 (5)0.0464 (5)
H40.52770.58170.97660.056*
C50.7761 (3)0.55664 (10)0.95083 (5)0.0428 (4)
C60.9191 (2)0.58522 (10)0.92700 (5)0.0404 (4)
H61.02260.55400.92140.048*
C71.2042 (2)0.66862 (10)0.87336 (5)0.0410 (4)
C81.3073 (3)0.72307 (12)0.84542 (7)0.0596 (6)
H8A1.42910.73310.85610.089*
H8B1.24090.77230.84300.089*
H8C1.31810.69870.81930.089*
C90.3195 (3)0.70352 (14)0.97704 (7)0.0659 (6)
H9A0.26300.65620.96650.099*
H9B0.22750.74460.97920.099*
H9C0.37050.69261.00330.099*
C100.9237 (3)0.42958 (11)0.95603 (7)0.0647 (6)
H10A0.92810.42400.92710.097*
H10B0.90470.37840.96820.097*
H10C1.03880.45160.96550.097*
C110.7292 (2)0.50583 (10)0.83936 (5)0.0371 (4)
C120.8709 (2)0.45172 (10)0.83355 (5)0.0412 (4)
H120.86500.40160.84540.049*
C131.0227 (2)0.47288 (10)0.80982 (5)0.0420 (4)
C141.0337 (3)0.54668 (11)0.79191 (5)0.0460 (4)
H141.13590.56040.77610.055*
C150.8897 (3)0.60002 (10)0.79786 (5)0.0454 (5)
C160.7373 (3)0.58076 (10)0.82121 (5)0.0426 (4)
H160.64140.61710.82480.051*
C170.5121 (2)0.41904 (10)0.87722 (5)0.0424 (4)
C180.3505 (3)0.42184 (12)0.90562 (7)0.0607 (6)
H18A0.29660.36980.90780.091*
H18B0.25910.45830.89550.091*
H18C0.39190.43920.93180.091*
C191.3080 (3)0.43027 (14)0.78001 (6)0.0651 (6)
H19A1.26300.43930.75300.098*
H19B1.39030.38540.78000.098*
H19C1.37360.47650.78930.098*
C200.7776 (3)0.73162 (12)0.78511 (7)0.0663 (6)
H20A0.65890.71350.77560.099*
H20B0.81270.77870.77060.099*
H20C0.76970.74340.81350.099*
N11.03993 (19)0.69747 (8)0.88680 (4)0.0405 (4)
H11.01440.74490.87890.049*
N20.5737 (2)0.49023 (8)0.86409 (4)0.0418 (4)
H2A0.51050.53100.87170.050*
O10.46382 (18)0.72883 (8)0.95061 (4)0.0596 (4)
O20.77427 (19)0.48116 (8)0.96687 (4)0.0603 (4)
O31.26690 (17)0.60353 (7)0.88250 (4)0.0516 (4)
O41.15542 (19)0.41493 (8)0.80618 (4)0.0606 (4)
O50.9123 (2)0.67166 (8)0.77872 (5)0.0684 (4)
O60.58211 (19)0.35588 (7)0.86658 (4)0.0593 (4)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0339 (9)0.0350 (9)0.0390 (9)−0.0056 (7)−0.0013 (7)0.0005 (7)
C20.0427 (10)0.0338 (9)0.0483 (10)−0.0018 (8)0.0016 (8)0.0004 (8)
C30.0389 (10)0.0420 (10)0.0481 (10)−0.0026 (8)0.0049 (8)−0.0096 (8)
C40.0449 (11)0.0473 (11)0.0472 (11)−0.0106 (9)0.0100 (9)−0.0012 (9)
C50.0464 (10)0.0379 (10)0.0442 (10)−0.0077 (8)0.0019 (9)0.0046 (8)
C60.0393 (9)0.0346 (9)0.0472 (10)−0.0029 (8)0.0015 (8)0.0032 (8)
C70.0388 (9)0.0355 (10)0.0488 (10)−0.0020 (8)0.0023 (8)0.0045 (8)
C80.0496 (12)0.0519 (12)0.0772 (14)0.0034 (10)0.0167 (11)0.0182 (10)
C90.0507 (12)0.0783 (16)0.0687 (14)−0.0001 (11)0.0212 (11)−0.0086 (12)
C100.0717 (14)0.0412 (11)0.0811 (15)0.0054 (10)0.0221 (12)0.0182 (10)
C110.0434 (10)0.0345 (9)0.0334 (9)−0.0049 (8)0.0004 (8)−0.0004 (7)
C120.0476 (10)0.0356 (9)0.0402 (10)−0.0011 (8)0.0036 (8)0.0060 (8)
C130.0433 (10)0.0430 (10)0.0395 (10)0.0013 (8)0.0008 (8)0.0013 (8)
C140.0432 (10)0.0491 (11)0.0458 (10)−0.0093 (9)0.0047 (8)0.0052 (9)
C150.0540 (11)0.0349 (10)0.0473 (10)−0.0089 (9)−0.0012 (9)0.0072 (8)
C160.0475 (10)0.0328 (9)0.0474 (10)−0.0007 (8)0.0019 (9)0.0020 (8)
C170.0418 (10)0.0371 (10)0.0484 (11)−0.0006 (8)0.0018 (9)0.0091 (8)
C180.0609 (13)0.0515 (12)0.0698 (14)0.0009 (10)0.0218 (11)0.0146 (10)
C190.0476 (12)0.0824 (16)0.0652 (14)0.0079 (11)0.0153 (11)0.0046 (12)
C200.0742 (15)0.0407 (11)0.0838 (16)−0.0050 (11)−0.0032 (13)0.0169 (11)
N10.0377 (8)0.0306 (7)0.0533 (9)0.0007 (6)0.0051 (7)0.0097 (6)
N20.0471 (9)0.0312 (8)0.0473 (9)0.0012 (7)0.0114 (7)0.0023 (6)
O10.0494 (8)0.0505 (8)0.0788 (10)0.0038 (6)0.0238 (7)−0.0031 (7)
O20.0619 (9)0.0446 (8)0.0742 (9)−0.0014 (7)0.0207 (8)0.0197 (7)
O30.0492 (8)0.0363 (7)0.0694 (9)0.0076 (6)0.0107 (7)0.0104 (6)
O40.0530 (8)0.0597 (9)0.0691 (9)0.0127 (7)0.0207 (7)0.0153 (7)
O50.0704 (10)0.0442 (8)0.0907 (11)−0.0032 (7)0.0199 (8)0.0249 (7)
O60.0538 (8)0.0321 (7)0.0920 (11)0.0036 (6)0.0194 (8)0.0095 (7)
Geometric parameters (Å, °) top
C1—C21.381 (2)C11—C161.398 (2)
C1—C61.395 (2)C11—N21.410 (2)
C1—N11.409 (2)C12—C131.391 (2)
C2—C31.388 (2)C12—H120.9300
C2—H20.9300C13—O41.371 (2)
C3—O11.366 (2)C13—C141.378 (2)
C3—C41.385 (3)C14—C151.385 (3)
C4—C51.384 (3)C14—H140.9300
C4—H40.9300C15—O51.371 (2)
C5—O21.377 (2)C15—C161.379 (2)
C5—C61.382 (2)C16—H160.9300
C6—H60.9300C17—O61.228 (2)
C7—O31.223 (2)C17—N21.349 (2)
C7—N11.353 (2)C17—C181.495 (3)
C7—C81.498 (2)C18—H18A0.9600
C8—H8A0.9600C18—H18B0.9600
C8—H8B0.9600C18—H18C0.9600
C8—H8C0.9600C19—O41.421 (2)
C9—O11.423 (2)C19—H19A0.9600
C9—H9A0.9600C19—H19B0.9600
C9—H9B0.9600C19—H19C0.9600
C9—H9C0.9600C20—O51.415 (3)
C10—O21.428 (2)C20—H20A0.9600
C10—H10A0.9600C20—H20B0.9600
C10—H10B0.9600C20—H20C0.9600
C10—H10C0.9600N1—H10.8600
C11—C121.381 (2)N2—H2A0.8600
C2—C1—C6120.54 (16)C13—C12—H12120.3
C2—C1—N1116.11 (14)O4—C13—C14124.29 (16)
C6—C1—N1123.34 (15)O4—C13—C12114.49 (15)
C1—C2—C3119.96 (16)C14—C13—C12121.23 (17)
C1—C2—H2120.0C13—C14—C15118.67 (17)
C3—C2—H2120.0C13—C14—H14120.7
O1—C3—C4124.89 (16)C15—C14—H14120.7
O1—C3—C2114.56 (16)O5—C15—C16124.01 (17)
C4—C3—C2120.56 (17)O5—C15—C14114.53 (16)
C5—C4—C3118.43 (16)C16—C15—C14121.46 (16)
C5—C4—H4120.8C15—C16—C11119.05 (17)
C3—C4—H4120.8C15—C16—H16120.5
O2—C5—C6123.21 (16)C11—C16—H16120.5
O2—C5—C4114.46 (16)O6—C17—N2122.81 (16)
C6—C5—C4122.32 (16)O6—C17—C18121.76 (16)
C5—C6—C1118.18 (16)N2—C17—C18115.43 (16)
C5—C6—H6120.9C17—C18—H18A109.5
C1—C6—H6120.9C17—C18—H18B109.5
O3—C7—N1124.26 (16)H18A—C18—H18B109.5
O3—C7—C8121.16 (16)C17—C18—H18C109.5
N1—C7—C8114.57 (15)H18A—C18—H18C109.5
C7—C8—H8A109.5H18B—C18—H18C109.5
C7—C8—H8B109.5O4—C19—H19A109.5
H8A—C8—H8B109.5O4—C19—H19B109.5
C7—C8—H8C109.5H19A—C19—H19B109.5
H8A—C8—H8C109.5O4—C19—H19C109.5
H8B—C8—H8C109.5H19A—C19—H19C109.5
O1—C9—H9A109.5H19B—C19—H19C109.5
O1—C9—H9B109.5O5—C20—H20A109.5
H9A—C9—H9B109.5O5—C20—H20B109.5
O1—C9—H9C109.5H20A—C20—H20B109.5
H9A—C9—H9C109.5O5—C20—H20C109.5
H9B—C9—H9C109.5H20A—C20—H20C109.5
O2—C10—H10A109.5H20B—C20—H20C109.5
O2—C10—H10B109.5C7—N1—C1130.28 (14)
H10A—C10—H10B109.5C7—N1—H1114.9
O2—C10—H10C109.5C1—N1—H1114.9
H10A—C10—H10C109.5C17—N2—C11127.76 (15)
H10B—C10—H10C109.5C17—N2—H2A116.1
C12—C11—C16120.29 (16)C11—N2—H2A116.1
C12—C11—N2122.95 (15)C3—O1—C9117.57 (16)
C16—C11—N2116.74 (15)C5—O2—C10117.22 (14)
C11—C12—C13119.30 (16)C13—O4—C19117.55 (15)
C11—C12—H12120.3C15—O5—C20118.46 (16)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O6i0.862.032.8857 (18)171
N2—H2A···O3ii0.862.172.9799 (19)158
Symmetry codes: (i) −x+3/2, y+1/2, z; (ii) x−1, y, z.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O6i0.862.032.8857 (18)171
N2—H2A···O3ii0.862.172.9799 (19)158
Symmetry codes: (i) −x+3/2, y+1/2, z; (ii) x−1, y, z.
Acknowledgements top

Acknowledgement is made to the crew of Topharman Shanghai Co., Ltd for their active cooperation in this work. We also thank the Instrument Analysis and Research Center of Shanghai University for structural confirmation.

references
References top

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