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Acta Cryst. (2008). E64, o1005    [ doi:10.1107/S1600536808012804 ]

N-Isopropylbenzamide

E. M. van Oosten, A. J. Lough and N. Vasdev

Abstract top

In the title compound, C10H13NO, the dihedral angle between the amide group and the phenyl ring is 30.0 (3)°. In the crystal structure, intermolecular N-H...O hydrogen bonds link molecules into one-dimensional chains along the a axis.

Comment top

The isopropylamine moiety is a common structural feature in many pharmaceutical compounds, in particular among β-adrenergic receptor antagonists (β-blockers) (Van Waarde et al., 2004; Kopka et al., 2005). Recent work in our laboratory (Stephenson, Wilson et al., 2008; Stephenson, van Oosten et al., 2008) and others (Van Waarde et al., 2004; Kopka et al., 2005) has focused on developing β-blockers labeled with the positron emitting isotope fluorine-18 (t1/2 = 109.7 min) at the isopropyl moiety for medical imaging with positron emission tomography. It is established that substitution of fluorine into a drug often enhances its biological properties (Smart, 2001). Our goal is to structurally characterize the isopropylamine group for comparison with fluorinated analogs developed in our laboratory. Herein we report the single-crystal X-ray structure of the title compound, (I), (Fig. 1).

The dihedral angle between the essentially planar set of atoms C7/O1/N1/C8 [r.m.s. deviation 0.006 Å] and the benzene ring (C1–C6) in (I) is 30.0 (3)°. In the crystal structure, intermolecular N—H···O hydrogen bonds link molecules into one-dimensional chains along the a axis (Table 1, Fig. 2).

Related literature top

For related literature, see: Clayden et al. (2006); Kopka et al. (2005); Smart (2001); Van Waarde et al. (2004); Stephenson, Wilson et al. (2008); Stephenson, van Oosten et al. (2008).

Experimental top

N-Isopropylbenzamide was made according to a literature procedure (Clayden et al., 2006), with minor modifications. Benzoyl chloride (0.825 ml, 7.11 mmol) was added to CH2Cl2 (17 ml, 0.4 M) under nitrogen. The mixture was cooled in an ice bath to 273 K and stirred for 10 min. Isopropylamine (1.8 ml, 21.33 mmol) was added dropwise. Upon completion of this addition the ice bath was removed and the reaction mixture was stirred at room temperature for 1.5 h. When the starting material was consumed (monitored by TLC) the reaction mixture was diluted with H2O (150 ml), extracted with CH2Cl2 (3 × 50 ml), washed with H2O (2 × 100 ml) followed by brine (2 × 100 ml), dried over Na2SO4, and concentrated. No further purification was necessary. Colourless blocks of (I) were obtained by slow evaporation of a solution of the title compound in CDCl3. 1H NMR (CDCl3, 300 MHz) d = 7.78–7.67 (m, 2H), 7.51–7.36 (m, 3H), 5.99 (br, 1H), 4.37–4.18 (m, 1H), 1.25 (d, J = 6.5 Hz, 6H) 13C NMR (CDCl3, 75 MHz) d = 166.9, 135.2, 131.5, 128.7, 127.0, 42.1, 23.1.

Refinement top

In the absence of significant anamlous dispersion effects, Friedel pairs were merged before refinement. The H atoms bonded to C atoms were placed in calculated positions with C—H = 0.95 Å and 0.98 Å (methyl). They were included in the refinement in the riding-model approximation with Uiso(H) = 1.2Ueq(C) or Uiso(H) = 1.5Ueq(C) for methyl H atoms. The position of the H atom bonded to the N atom was refined independently with Uiso(H) = 1.2Ueq(N).

Computing details top

Data collection: COLLECT (Nonius, 2002); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997); data reduction: DENZO-SMN (Otwinowski & Minor, 1997); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I) showing 30% probability displacement ellipsoids (arbitrary spheres for H atoms).
[Figure 2] Fig. 2. Part of the crystal structure of (I) showing hydrogen bonds as dashed lines.
N-Isopropylbenzamide top
Crystal data top
C10H13NOF000 = 176
Mr = 163.21Dx = 1.140 Mg m−3
Monoclinic, P21Mo Kα radiation
λ = 0.71073 Å
Hall symbol: P 2ybCell parameters from 2462 reflections
a = 5.0093 (7) Åθ = 3.0–25.0º
b = 10.1250 (13) ŵ = 0.07 mm−1
c = 9.6714 (14) ÅT = 150 (1) K
β = 104.133 (7)ºBlock, colourless
V = 475.68 (11) Å30.14 × 0.13 × 0.08 mm
Z = 2
Data collection top
Bruker Nonius KappaCCD
diffractometer		887 independent reflections
Radiation source: fine-focus sealed tube621 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.061
Detector resolution: 9 pixels mm-1θmax = 25.0º
T = 150(1) Kθmin = 3.0º
φ scans and ω scans with κ offsetsh = −5→5
Absorption correction: multi-scan
(SORTAV; Blessing 1995)		k = −12→10
Tmin = 0.954, Tmax = 0.996l = −11→11
2462 measured reflections
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)] = 0.057H atoms treated by a mixture of
independent and constrained refinement
wR(F2) = 0.148  w = 1/[σ2(Fo2) + (0.0784P)2]
where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max < 0.001
887 reflectionsΔρmax = 0.18 e Å−3
114 parametersΔρmin = −0.21 e Å−3
1 restraintExtinction correction: none
Primary atom site location: structure-invariant direct methods
Crystal data top
C10H13NOV = 475.68 (11) Å3
Mr = 163.21Z = 2
Monoclinic, P21Mo Kα
a = 5.0093 (7) ŵ = 0.07 mm−1
b = 10.1250 (13) ÅT = 150 (1) K
c = 9.6714 (14) Å0.14 × 0.13 × 0.08 mm
β = 104.133 (7)º
Data collection top
Bruker Nonius KappaCCD
diffractometer		887 independent reflections
Absorption correction: multi-scan
(SORTAV; Blessing 1995)		621 reflections with I > 2σ(I)
Tmin = 0.954, Tmax = 0.996Rint = 0.061
2462 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.057H atoms treated by a mixture of
independent and constrained refinement
wR(F2) = 0.148Δρmax = 0.18 e Å−3
S = 1.06Δρmin = −0.21 e Å−3
887 reflectionsAbsolute structure: ?
114 parametersFlack parameter: ?
1 restraintRogers 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
O10.6751 (6)0.1703 (3)0.8045 (3)0.0424 (8)
N10.2696 (8)0.1717 (4)0.8673 (4)0.0411 (10)
H1N0.103 (11)0.188 (5)0.839 (5)0.049*
C10.3226 (9)0.3127 (4)0.6749 (5)0.0350 (11)
C20.4247 (10)0.3165 (5)0.5544 (5)0.0452 (13)
H2A0.56010.25450.54320.054*
C30.3286 (11)0.4116 (6)0.4493 (5)0.0535 (14)
H3A0.39570.41260.36550.064*
C40.1377 (10)0.5034 (5)0.4666 (6)0.0516 (14)
H4A0.07340.56820.39510.062*
C50.0391 (11)0.5014 (5)0.5883 (6)0.0523 (14)
H5A−0.09120.56560.60100.063*
C60.1296 (9)0.4064 (5)0.6915 (5)0.0451 (13)
H6A0.05970.40510.77440.054*
C70.4356 (8)0.2117 (4)0.7864 (4)0.0362 (12)
C80.3461 (10)0.0743 (5)0.9808 (5)0.0474 (13)
H8A0.54890.05860.99960.057*
C90.1984 (13)−0.0561 (5)0.9351 (6)0.0648 (16)
H9A0.2525−0.09030.85120.097*
H9B−0.0011−0.04170.91160.097*
H9C0.2488−0.12001.01320.097*
C100.2833 (11)0.1271 (6)1.1160 (5)0.0556 (15)
H10A0.37430.21261.14000.083*
H10B0.35100.06471.19420.083*
H10C0.08390.13801.10130.083*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0319 (17)0.0442 (18)0.0515 (17)0.0024 (15)0.0112 (13)0.0032 (16)
N10.0326 (19)0.046 (2)0.047 (2)0.003 (2)0.0149 (18)0.012 (2)
C10.033 (2)0.035 (2)0.039 (3)−0.006 (2)0.012 (2)0.000 (2)
C20.049 (3)0.044 (3)0.046 (3)0.001 (2)0.019 (2)0.003 (2)
C30.057 (3)0.061 (3)0.046 (3)−0.003 (3)0.019 (3)0.012 (3)
C40.049 (3)0.051 (3)0.050 (3)−0.002 (3)0.004 (3)0.020 (3)
C50.053 (3)0.040 (3)0.066 (3)0.007 (3)0.017 (3)0.013 (3)
C60.046 (3)0.042 (3)0.051 (3)0.003 (2)0.017 (2)0.005 (3)
C70.035 (3)0.034 (3)0.037 (2)−0.004 (2)0.005 (2)−0.008 (2)
C80.041 (3)0.054 (3)0.048 (3)0.012 (3)0.012 (2)0.017 (3)
C90.085 (4)0.043 (3)0.064 (3)0.010 (3)0.014 (3)0.012 (3)
C100.062 (3)0.062 (4)0.044 (3)−0.001 (3)0.015 (2)0.012 (3)
Geometric parameters (Å, °) top
O1—C71.242 (5)C5—C61.380 (7)
N1—C71.337 (6)C5—H5A0.9500
N1—C81.455 (6)C6—H6A0.9500
N1—H1N0.83 (5)C8—C101.516 (7)
C1—C21.383 (6)C8—C91.525 (8)
C1—C61.392 (6)C8—H8A1.0000
C1—C71.493 (6)C9—H9A0.9800
C2—C31.398 (8)C9—H9B0.9800
C2—H2A0.9500C9—H9C0.9800
C3—C41.373 (7)C10—H10A0.9800
C3—H3A0.9500C10—H10B0.9800
C4—C51.384 (7)C10—H10C0.9800
C4—H4A0.9500
C7—N1—C8124.0 (4)O1—C7—N1122.2 (4)
C7—N1—H1N118 (4)O1—C7—C1121.0 (4)
C8—N1—H1N117 (4)N1—C7—C1116.7 (4)
C2—C1—C6119.2 (4)N1—C8—C10109.9 (4)
C2—C1—C7118.3 (4)N1—C8—C9110.4 (4)
C6—C1—C7122.4 (4)C10—C8—C9111.5 (4)
C1—C2—C3120.0 (5)N1—C8—H8A108.3
C1—C2—H2A120.0C10—C8—H8A108.3
C3—C2—H2A120.0C9—C8—H8A108.3
C4—C3—C2120.3 (5)C8—C9—H9A109.5
C4—C3—H3A119.9C8—C9—H9B109.5
C2—C3—H3A119.9H9A—C9—H9B109.5
C3—C4—C5119.8 (5)C8—C9—H9C109.5
C3—C4—H4A120.1H9A—C9—H9C109.5
C5—C4—H4A120.1H9B—C9—H9C109.5
C6—C5—C4120.2 (5)C8—C10—H10A109.5
C6—C5—H5A119.9C8—C10—H10B109.5
C4—C5—H5A119.9H10A—C10—H10B109.5
C5—C6—C1120.5 (4)C8—C10—H10C109.5
C5—C6—H6A119.8H10A—C10—H10C109.5
C1—C6—H6A119.8H10B—C10—H10C109.5
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···O1i0.83 (5)2.10 (5)2.890 (5)160 (5)
Symmetry codes: (i) x−1, y, z.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···O1i0.83 (5)2.10 (5)2.890 (5)160 (5)
Symmetry codes: (i) x−1, y, z.
Acknowledgements top

The authors thank Dr Karin A. Stephenson, Dr Andrei K. Yudin and Dr Alan A. Wilson for helpful discussions. We thank Dr Sylvain Houle for allowing the CAMH PET Centre facilities to be used for this research. Financial support for this work was provided by the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Canadian Institutes for Health Research in the form of a Collaborative Health Research Projects Grant (CHRPJ 322787-06).

references
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