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Acta Crystallogr Sect E Struct Rep Online. 2008 June 1; 64(Pt 6): o1155.
Published online 2008 May 24. doi:  10.1107/S1600536808015134
PMCID: PMC2961427

4-[2-(3,4-Dimethoxy­phenethyl­amino)prop­oxy]-2-methoxy­benzamide

Abstract

The title compound, C21H28N2O5, has two intra­molecular N—H(...)O hydrogen bonds. Inter­molecular N—H(...)O hydrogen bonds [graph-set motif R 2 2(8)] give rise to a dimer. Weak N—H(...)N hydrogen bonds between neighboring dimers further extend the crystal structure, which exhibits an infinite chain motif.

Related literature

For related literature, see: Allen et al. (1987 [triangle]); Beduschi & Beduachi (1998 [triangle]); Bernstein et al.(1995 [triangle]); Boonnak et al. (2005 [triangle]); Gunderman et al. (1995 [triangle]); Hieble et al. (1995 [triangle]); Kasztreiner et al. (1989 [triangle]); Ng et al. (2005 [triangle]); Xi et al. (2005 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-64-o1155-scheme1.jpg

Experimental

Crystal data

  • C21H28N2O5
  • M r = 388.45
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-o1155-efi1.jpg
  • a = 7.7564 (3) Å
  • b = 9.3509 (4) Å
  • c = 29.9987 (12) Å
  • β = 95.370 (3)°
  • V = 2166.24 (15) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 296 (2) K
  • 0.21 × 0.18 × 0.17 mm

Data collection

  • Bruker APEXII area-detector diffractometer
  • Absorption correction: none
  • 26019 measured reflections
  • 3909 independent reflections
  • 1966 reflections with I > 2σ(I)
  • R int = 0.069

Refinement

  • R[F 2 > 2σ(F 2)] = 0.062
  • wR(F 2) = 0.183
  • S = 1.03
  • 3909 reflections
  • 260 parameters
  • 1 restraint
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.24 e Å−3
  • Δρmin = −0.22 e Å−3

Data collection: APEX2 (Bruker, 2004 [triangle]); cell refinement: APEX2; data reduction: APEX2; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: XP in SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808015134/zl2117sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808015134/zl2117Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

The authors acknowledge the National Natural Science Foundation of China for funding (grant No. 30600776).

supplementary crystallographic information

Comment

α1-Adrenoreceptors (α1-AR) are members of the super family of seven transmembrane G protein coupled receptors (GPCR) (Gunderman et al., 1995) and regulate several important physiological processes (Hieble et al., 1995). In recent years, the search for new α1-adrenoreceptor antagonists has increased in parallel with the development of postsynaptically selective α-adrenoreceptor antagonists due to their importance in the treatment of hypertension (Kasztreiner et al., 1989) and for prostatic hypertrophy (Beduschi & Beduachi, 1998). In the course of our studies on phenoxylalkylamine-phenylethanamine derivatives as potential antagonists of α1-adrenoreceptors, we have synthesized a library of compounds (Xi et al. , 2005) that show good activity. The title compound is one such phenoxylalkylamine-phenylethanamine derivative with α1-adrenoreceptor antagonist properties.

In the title compound (Fig. 1), the C—C bond lengths show normal values (Allen et al., 1987), and the C—O and C=O bond lengths are comparable to those observed in simliar structures (Ng et al., 2005; Boonnak et al., 2005), while the C—N distances in the structure fall in the range of 1.308 (3)–1.469 (4) Å. The title molecular structure acts as hydrogen bonding donor and acceptor with two intramolecular N—H···O hydrogen bonds. The compound forms dimers with neighboring molecules through N—H···O hydrogen bonding with a R22(8) graph set motif (Bernstein et al., 1995), which are further self-assembled by N—H···N hydrogen bonds (table 1) to form an infinite chain (Fig. 2).

Experimental

A mixture of 2-methoxy-4-(2-oxopropoxy)benzamide (0.4 g), 2-(3,4-dimethoxy- phenyl)ethanamine (0.4 ml), TsOH (3 drops), and methanol (20 ml) were heated to reflux of the solvent for 3 h. After cooling KBH4 (0.2 g) was added to the mixture portion wise over a period of 1 h and the mixture was stirred at room temperature for another 2 h. The methanol was evaporated, and water (15 ml) was added to the residue. The aqueous solution was extracted with ethyl acetate and the extract was dried over MgSO4, and evaporated. The residue was chromatographed on silica gel with petroleum ether and ethyl acetate (1:2 with triethylamine) as the eluent to obtain the colorless block crystals (0.3 g, 69.6%).

Refinement

H atoms on carbon atoms and N2 were placed in calculated positions and were treated as riding on the parent C or N atoms with C—H = 0.92–0.97 Å and N—H = 0.86 Å. The H atom on N1 atom was tentatively located in a difference electron density Fourier map and was refined with distance restraint of N–H = 0.90 (2) Å. Uiso(H) were set to 1.2 or 1.5 Ueq(C) and 1.2 Ueq(N).

Figures

Fig. 1.
The molecular structure showing the atomic-numbering scheme. Displacement ellipsoids drawn at the 30% probability level. Intramolecular hydrogen bonds are shown as dashed lines.
Fig. 2.
The molecular packing showing the intermolecular hydrogen bonding interactions as broken lines.

Crystal data

C21H28N2O5F000 = 832
Mr = 388.45Dx = 1.191 Mg m3
Monoclinic, P21/cMo Kα radiation λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 2279 reflections
a = 7.7564 (3) Åθ = 2.3–28.0º
b = 9.3509 (4) ŵ = 0.09 mm1
c = 29.9987 (12) ÅT = 296 (2) K
β = 95.370 (3)ºBlock, colorless
V = 2166.24 (15) Å30.21 × 0.18 × 0.17 mm
Z = 4

Data collection

Bruker APEXII area-detector diffractometer1966 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.069
Monochromator: graphiteθmax = 25.2º
T = 296(2) Kθmin = 2.3º
[var phi] and ω scansh = −8→9
Absorption correction: nonek = −11→11
26019 measured reflectionsl = −35→35
3909 independent reflections

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.062H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.183  w = 1/[σ2(Fo2) + (0.0802P)2 + 0.288P] where P = (Fo2 + 2Fc2)/3
S = 1.03(Δ/σ)max < 0.001
3909 reflectionsΔρmax = 0.24 e Å3
260 parametersΔρmin = −0.22 e Å3
1 restraintExtinction correction: none
Primary atom site location: structure-invariant direct methods

Special details

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)

xyzUiso*/Ueq
C11.0849 (4)0.9275 (3)0.68939 (10)0.0707 (8)
C21.0775 (4)0.8967 (3)0.73403 (10)0.0730 (9)
H21.00120.82640.74190.088*
C31.1788 (4)0.9662 (3)0.76742 (11)0.0768 (9)
C41.2923 (4)1.0728 (3)0.75616 (13)0.0802 (9)
C51.3002 (4)1.1052 (4)0.71190 (14)0.0894 (10)
H51.37521.17620.70380.107*
C61.1968 (5)1.0324 (4)0.67897 (12)0.0854 (10)
H61.20401.05580.64910.102*
C70.2048 (4)0.3654 (3)0.58051 (10)0.0731 (9)
H70.17680.29410.60020.088*
C80.2697 (4)0.4909 (4)0.59783 (10)0.0786 (9)
H80.28760.50340.62870.094*
C90.3086 (4)0.5986 (3)0.56951 (10)0.0652 (8)
C100.2844 (3)0.5786 (3)0.52359 (9)0.0637 (8)
H100.30930.65210.50430.076*
C110.2230 (3)0.4489 (3)0.50650 (9)0.0571 (7)
C120.1785 (3)0.3388 (3)0.53488 (9)0.0604 (7)
C131.0809 (9)0.8210 (6)0.82400 (14)0.194 (3)
H13A0.96000.84420.81910.292*
H13B1.10950.79840.85500.292*
H13C1.10540.74000.80590.292*
C140.4230 (4)0.8365 (3)0.56233 (10)0.0785 (9)
H14A0.32070.88590.54910.094*
H14B0.48740.80140.53840.094*
C150.5335 (4)0.9363 (3)0.59209 (10)0.0752 (9)
H150.47260.96160.61820.090*
C160.8086 (4)0.9358 (3)0.63960 (10)0.0766 (9)
H16A0.74750.95780.66550.092*
H16B0.84221.02540.62660.092*
C170.9687 (4)0.8500 (4)0.65416 (10)0.0833 (10)
H17A1.03210.83130.62840.100*
H17B0.93480.75880.66600.100*
C181.5228 (7)1.2293 (6)0.78212 (16)0.171 (2)
H18A1.59991.18120.76380.257*
H18B1.58581.25940.80960.257*
H18C1.47381.31130.76640.257*
C190.5701 (5)1.0702 (3)0.56651 (13)0.1053 (12)
H19A0.63201.13710.58630.158*
H19B0.46281.11210.55440.158*
H19C0.63881.04650.54250.158*
C200.2483 (4)0.5301 (3)0.43139 (9)0.0771 (9)
H20A0.17760.61330.43430.116*
H20B0.23030.49450.40130.116*
H20C0.36790.55510.43810.116*
C210.1018 (4)0.1977 (3)0.52065 (11)0.0676 (8)
N10.6938 (3)0.8582 (2)0.60697 (8)0.0666 (7)
H10.662 (4)0.780 (2)0.6217 (8)0.080*
N20.0991 (3)0.1560 (3)0.47879 (8)0.0817 (8)
H2A0.05480.07470.47080.098*
H2B0.14170.21020.45940.098*
O10.3744 (3)0.7205 (2)0.58938 (6)0.0838 (7)
O21.1798 (4)0.9383 (3)0.81226 (8)0.1191 (10)
O31.3892 (3)1.1353 (3)0.79165 (9)0.1160 (9)
O40.2023 (3)0.4228 (2)0.46171 (6)0.0753 (6)
O50.0413 (4)0.1217 (2)0.54918 (8)0.1049 (9)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.063 (2)0.075 (2)0.073 (2)0.0073 (17)0.0014 (16)0.0039 (17)
C20.065 (2)0.071 (2)0.082 (2)−0.0139 (16)0.0032 (16)−0.0044 (17)
C30.079 (2)0.076 (2)0.076 (2)−0.0129 (19)0.0067 (18)−0.0039 (17)
C40.072 (2)0.070 (2)0.099 (3)−0.0126 (18)0.0079 (19)−0.011 (2)
C50.073 (2)0.077 (2)0.120 (3)−0.0097 (19)0.019 (2)0.015 (2)
C60.081 (2)0.090 (3)0.086 (2)0.011 (2)0.012 (2)0.018 (2)
C70.082 (2)0.070 (2)0.069 (2)−0.0096 (18)0.0146 (16)0.0086 (16)
C80.091 (2)0.083 (2)0.0625 (18)−0.0174 (19)0.0095 (17)0.0007 (18)
C90.0610 (19)0.0651 (19)0.069 (2)−0.0088 (15)0.0022 (15)−0.0018 (16)
C100.0598 (19)0.0609 (18)0.069 (2)−0.0022 (15)−0.0005 (14)0.0091 (15)
C110.0533 (17)0.0567 (17)0.0608 (18)0.0012 (14)0.0018 (13)0.0001 (14)
C120.0518 (17)0.0616 (18)0.0688 (19)−0.0031 (14)0.0103 (14)0.0015 (15)
C130.327 (8)0.172 (5)0.088 (3)−0.131 (6)0.039 (4)−0.003 (3)
C140.081 (2)0.066 (2)0.085 (2)−0.0101 (17)−0.0076 (17)0.0068 (17)
C150.069 (2)0.0654 (19)0.088 (2)−0.0055 (17)−0.0093 (17)0.0026 (17)
C160.074 (2)0.075 (2)0.079 (2)−0.0001 (17)−0.0057 (17)−0.0088 (16)
C170.083 (2)0.087 (2)0.077 (2)0.0133 (19)−0.0053 (18)−0.0072 (17)
C180.145 (4)0.178 (5)0.192 (5)−0.105 (4)0.023 (4)−0.035 (4)
C190.101 (3)0.071 (2)0.137 (3)−0.008 (2)−0.022 (2)0.009 (2)
C200.089 (2)0.073 (2)0.0697 (19)0.0018 (18)0.0097 (17)0.0126 (16)
C210.067 (2)0.0626 (19)0.074 (2)−0.0052 (16)0.0160 (16)0.0004 (17)
N10.0687 (17)0.0610 (15)0.0689 (15)−0.0033 (13)0.0005 (13)−0.0027 (12)
N20.101 (2)0.0681 (16)0.0786 (18)−0.0248 (15)0.0219 (15)−0.0060 (14)
O10.0948 (17)0.0803 (15)0.0759 (14)−0.0244 (13)0.0059 (12)−0.0059 (12)
O20.157 (2)0.126 (2)0.0737 (16)−0.0677 (19)0.0075 (15)−0.0092 (14)
O30.1067 (19)0.113 (2)0.128 (2)−0.0478 (17)0.0056 (16)−0.0250 (16)
O40.0972 (16)0.0654 (13)0.0627 (13)−0.0120 (11)0.0038 (11)0.0065 (10)
O50.147 (2)0.0836 (16)0.0905 (16)−0.0453 (16)0.0465 (15)−0.0088 (13)

Geometric parameters (Å, °)

C1—C61.365 (4)C14—C151.503 (4)
C1—C21.376 (4)C14—H14A0.9700
C1—C171.509 (4)C14—H14B0.9700
C2—C31.377 (4)C15—N11.475 (4)
C2—H20.9300C15—C191.509 (4)
C3—O21.369 (4)C15—H150.9800
C3—C41.393 (4)C16—N11.454 (3)
C4—C51.369 (4)C16—C171.508 (4)
C4—O31.375 (4)C16—H16A0.9700
C5—C61.391 (5)C16—H16B0.9700
C5—H50.9300C17—H17A0.9700
C6—H60.9300C17—H17B0.9700
C7—C81.361 (4)C18—O31.408 (4)
C7—C121.387 (4)C18—H18A0.9600
C7—H70.9300C18—H18B0.9600
C8—C91.369 (4)C18—H18C0.9600
C8—H80.9300C19—H19A0.9600
C9—O11.363 (3)C19—H19B0.9600
C9—C101.385 (4)C19—H19C0.9600
C10—C111.383 (4)C20—O41.422 (3)
C10—H100.9300C20—H20A0.9600
C11—O41.360 (3)C20—H20B0.9600
C11—C121.400 (4)C20—H20C0.9600
C12—C211.493 (4)C21—O51.238 (3)
C13—O21.403 (5)C21—N21.313 (3)
C13—H13A0.9600N1—H10.903 (17)
C13—H13B0.9600N2—H2A0.8600
C13—H13C0.9600N2—H2B0.8600
C14—O11.426 (3)
C6—C1—C2117.3 (3)N1—C15—C19111.8 (3)
C6—C1—C17122.4 (3)C14—C15—C19109.7 (3)
C2—C1—C17120.3 (3)N1—C15—H15109.5
C1—C2—C3122.4 (3)C14—C15—H15109.5
C1—C2—H2118.8C19—C15—H15109.5
C3—C2—H2118.8N1—C16—C17111.4 (2)
O2—C3—C2125.1 (3)N1—C16—H16A109.3
O2—C3—C4115.4 (3)C17—C16—H16A109.3
C2—C3—C4119.5 (3)N1—C16—H16B109.3
C5—C4—O3125.9 (3)C17—C16—H16B109.3
C5—C4—C3118.7 (3)H16A—C16—H16B108.0
O3—C4—C3115.4 (3)C16—C17—C1111.6 (3)
C4—C5—C6120.4 (3)C16—C17—H17A109.3
C4—C5—H5119.8C1—C17—H17A109.3
C6—C5—H5119.8C16—C17—H17B109.3
C1—C6—C5121.7 (3)C1—C17—H17B109.3
C1—C6—H6119.1H17A—C17—H17B108.0
C5—C6—H6119.1O3—C18—H18A109.5
C8—C7—C12123.2 (3)O3—C18—H18B109.5
C8—C7—H7118.4H18A—C18—H18B109.5
C12—C7—H7118.4O3—C18—H18C109.5
C7—C8—C9119.5 (3)H18A—C18—H18C109.5
C7—C8—H8120.3H18B—C18—H18C109.5
C9—C8—H8120.3C15—C19—H19A109.5
O1—C9—C8116.0 (3)C15—C19—H19B109.5
O1—C9—C10123.9 (3)H19A—C19—H19B109.5
C8—C9—C10120.0 (3)C15—C19—H19C109.5
C11—C10—C9119.8 (3)H19A—C19—H19C109.5
C11—C10—H10120.1H19B—C19—H19C109.5
C9—C10—H10120.1O4—C20—H20A109.5
O4—C11—C10121.9 (2)O4—C20—H20B109.5
O4—C11—C12117.1 (2)H20A—C20—H20B109.5
C10—C11—C12121.0 (3)O4—C20—H20C109.5
C7—C12—C11116.5 (3)H20A—C20—H20C109.5
C7—C12—C21117.3 (3)H20B—C20—H20C109.5
C11—C12—C21126.2 (3)O5—C21—N2121.2 (3)
O2—C13—H13A109.5O5—C21—C12118.4 (3)
O2—C13—H13B109.5N2—C21—C12120.4 (3)
H13A—C13—H13B109.5C16—N1—C15113.7 (2)
O2—C13—H13C109.5C16—N1—H1104.8 (18)
H13A—C13—H13C109.5C15—N1—H1106.9 (19)
H13B—C13—H13C109.5C21—N2—H2A120.0
O1—C14—C15107.5 (2)C21—N2—H2B120.0
O1—C14—H14A110.2H2A—N2—H2B120.0
C15—C14—H14A110.2C9—O1—C14119.7 (2)
O1—C14—H14B110.2C3—O2—C13116.3 (3)
C15—C14—H14B110.2C4—O3—C18117.9 (3)
H14A—C14—H14B108.5C11—O4—C20119.4 (2)
N1—C15—C14106.8 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N2—H2A···O5i0.862.052.909 (3)178
N2—H2B···O40.862.042.684 (3)131
N2—H2B···N1ii0.862.543.161 (3)129
N1—H1···O10.903 (17)2.41 (3)2.798 (3)106 (2)

Symmetry codes: (i) −x, −y, −z+1; (ii) −x+1, −y+1, −z+1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: ZL2117).

References

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