N-Isopropyl­benzamide

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

doi:10.1107/S1600536808012804

organic compounds

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ISSN: 2056-9890

Volume 64| Part 6| June 2008| Page o1005

doi:10.1107/S1600536808012804

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N-Isopropylbenzamide

Erik M. van Oosten,^a Alan J. Lough ^a ^* and Neil Vasdev ^b

^aDepartment of Chemistry, University of Toronto, 80 St George Street, Toronto, Ontario, Canada M5S 3H6, and ^bPET Centre, Centre for Addiction and Mental Health, and Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, Canada M5T 1R8
^*Correspondence e-mail: alough@chem.utoronto.ca

(Received 29 April 2008; accepted 30 April 2008; online 7 May 2008)

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.

Related literature

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

Crystal data

C₁₀H₁₃NO
M_r = 163.21
Monoclinic, P 2₁
a = 5.0093 (7) Å
b = 10.1250 (13) Å
c = 9.6714 (14) Å
β = 104.133 (7)°
V = 475.68 (11) Å³
Z = 2
Mo Kα radiation
μ = 0.07 mm⁻¹
T = 150 (1) K
0.14 × 0.13 × 0.08 mm

Data collection

Bruker Nonius KappaCCD diffractometer
Absorption correction: multi-scan (SORTAV; Blessing 1995 ) T_min = 0.954, T_max = 0.996
2462 measured reflections
887 independent reflections
621 reflections with I > 2σ(I)
R_int = 0.061

Refinement

R[F² > 2σ(F²)] = 0.057
wR(F²) = 0.148
S = 1.06
887 reflections
114 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N⋯O1ⁱ	0.83 (5)	2.10 (5)	2.890 (5)	160 (5)
Symmetry code: (i) x-1, y, z.

Data collection: COLLECT (Nonius, 2002 ); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997 ); data reduction: DENZO-SMN; 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.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808012804/hb2729sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808012804/hb2729Isup2.hkl

checkCIF report

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 (t_1/2 = 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.

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

	Fig. 1. The molecular structure of (I) showing 30% probability displacement ellipsoids (arbitrary spheres for H atoms).
	Fig. 2. Part of the crystal structure of (I) showing hydrogen bonds as dashed lines.

N-Isopropylbenzamide top

Crystal data top

C₁₀H₁₃NO	F(000) = 176
M_r = 163.21	D_x = 1.140 Mg m⁻³
Monoclinic, P2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 2462 reflections
a = 5.0093 (7) Å	θ = 3.0–25.0°
b = 10.1250 (13) Å	µ = 0.07 mm⁻¹
c = 9.6714 (14) Å	T = 150 K
β = 104.133 (7)°	Block, colourless
V = 475.68 (11) Å³	0.14 × 0.13 × 0.08 mm
Z = 2

Data collection top

Bruker Nonius KappaCCD diffractometer	887 independent reflections
Radiation source: fine-focus sealed tube	621 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.061
Detector resolution: 9 pixels mm^-1	θ_max = 25.0°, θ_min = 3.0°
ϕ scans and ω scans with κ offsets	h = −5→5
Absorption correction: multi-scan (SORTAV; Blessing 1995)	k = −12→10
T_min = 0.954, T_max = 0.996	l = −11→11
2462 measured reflections

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)] = 0.057	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.148	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	w = 1/[σ²(F_o²) + (0.0784P)²] where P = (F_o² + 2F_c²)/3
887 reflections	(Δ/σ)_max < 0.001
114 parameters	Δρ_max = 0.18 e Å⁻³
1 restraint	Δρ_min = −0.21 e Å⁻³

Crystal data top

C₁₀H₁₃NO	V = 475.68 (11) Å³
M_r = 163.21	Z = 2
Monoclinic, P2₁	Mo Kα radiation
a = 5.0093 (7) Å	µ = 0.07 mm⁻¹
b = 10.1250 (13) Å	T = 150 K
c = 9.6714 (14) Å	0.14 × 0.13 × 0.08 mm
β = 104.133 (7)°

Data collection top

Bruker Nonius KappaCCD diffractometer	887 independent reflections
Absorption correction: multi-scan (SORTAV; Blessing 1995)	621 reflections with I > 2σ(I)
T_min = 0.954, T_max = 0.996	R_int = 0.061
2462 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.057	1 restraint
wR(F²) = 0.148	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	Δρ_max = 0.18 e Å⁻³
887 reflections	Δρ_min = −0.21 e Å⁻³
114 parameters

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

	x	y	z	U_iso*/U_eq
O1	0.6751 (6)	0.1703 (3)	0.8045 (3)	0.0424 (8)
N1	0.2696 (8)	0.1717 (4)	0.8673 (4)	0.0411 (10)
H1N	0.103 (11)	0.188 (5)	0.839 (5)	0.049*
C1	0.3226 (9)	0.3127 (4)	0.6749 (5)	0.0350 (11)
C2	0.4247 (10)	0.3165 (5)	0.5544 (5)	0.0452 (13)
H2A	0.5601	0.2545	0.5432	0.054*
C3	0.3286 (11)	0.4116 (6)	0.4493 (5)	0.0535 (14)
H3A	0.3957	0.4126	0.3655	0.064*
C4	0.1377 (10)	0.5034 (5)	0.4666 (6)	0.0516 (14)
H4A	0.0734	0.5682	0.3951	0.062*
C5	0.0391 (11)	0.5014 (5)	0.5883 (6)	0.0523 (14)
H5A	−0.0912	0.5656	0.6010	0.063*
C6	0.1296 (9)	0.4064 (5)	0.6915 (5)	0.0451 (13)
H6A	0.0597	0.4051	0.7744	0.054*
C7	0.4356 (8)	0.2117 (4)	0.7864 (4)	0.0362 (12)
C8	0.3461 (10)	0.0743 (5)	0.9808 (5)	0.0474 (13)
H8A	0.5489	0.0586	0.9996	0.057*
C9	0.1984 (13)	−0.0561 (5)	0.9351 (6)	0.0648 (16)
H9A	0.2525	−0.0903	0.8512	0.097*
H9B	−0.0011	−0.0417	0.9116	0.097*
H9C	0.2488	−0.1200	1.0132	0.097*
C10	0.2833 (11)	0.1271 (6)	1.1160 (5)	0.0556 (15)
H10A	0.3743	0.2126	1.1400	0.083*
H10B	0.3510	0.0647	1.1942	0.083*
H10C	0.0839	0.1380	1.1013	0.083*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0319 (17)	0.0442 (18)	0.0515 (17)	0.0024 (15)	0.0112 (13)	0.0032 (16)
N1	0.0326 (19)	0.046 (2)	0.047 (2)	0.003 (2)	0.0149 (18)	0.012 (2)
C1	0.033 (2)	0.035 (2)	0.039 (3)	−0.006 (2)	0.012 (2)	0.000 (2)
C2	0.049 (3)	0.044 (3)	0.046 (3)	0.001 (2)	0.019 (2)	0.003 (2)
C3	0.057 (3)	0.061 (3)	0.046 (3)	−0.003 (3)	0.019 (3)	0.012 (3)
C4	0.049 (3)	0.051 (3)	0.050 (3)	−0.002 (3)	0.004 (3)	0.020 (3)
C5	0.053 (3)	0.040 (3)	0.066 (3)	0.007 (3)	0.017 (3)	0.013 (3)
C6	0.046 (3)	0.042 (3)	0.051 (3)	0.003 (2)	0.017 (2)	0.005 (3)
C7	0.035 (3)	0.034 (3)	0.037 (2)	−0.004 (2)	0.005 (2)	−0.008 (2)
C8	0.041 (3)	0.054 (3)	0.048 (3)	0.012 (3)	0.012 (2)	0.017 (3)
C9	0.085 (4)	0.043 (3)	0.064 (3)	0.010 (3)	0.014 (3)	0.012 (3)
C10	0.062 (3)	0.062 (4)	0.044 (3)	−0.001 (3)	0.015 (2)	0.012 (3)

Geometric parameters (Å, º) top

O1—C7	1.242 (5)	C5—C6	1.380 (7)
N1—C7	1.337 (6)	C5—H5A	0.9500
N1—C8	1.455 (6)	C6—H6A	0.9500
N1—H1N	0.83 (5)	C8—C10	1.516 (7)
C1—C2	1.383 (6)	C8—C9	1.525 (8)
C1—C6	1.392 (6)	C8—H8A	1.0000
C1—C7	1.493 (6)	C9—H9A	0.9800
C2—C3	1.398 (8)	C9—H9B	0.9800
C2—H2A	0.9500	C9—H9C	0.9800
C3—C4	1.373 (7)	C10—H10A	0.9800
C3—H3A	0.9500	C10—H10B	0.9800
C4—C5	1.384 (7)	C10—H10C	0.9800
C4—H4A	0.9500

C7—N1—C8	124.0 (4)	O1—C7—N1	122.2 (4)
C7—N1—H1N	118 (4)	O1—C7—C1	121.0 (4)
C8—N1—H1N	117 (4)	N1—C7—C1	116.7 (4)
C2—C1—C6	119.2 (4)	N1—C8—C10	109.9 (4)
C2—C1—C7	118.3 (4)	N1—C8—C9	110.4 (4)
C6—C1—C7	122.4 (4)	C10—C8—C9	111.5 (4)
C1—C2—C3	120.0 (5)	N1—C8—H8A	108.3
C1—C2—H2A	120.0	C10—C8—H8A	108.3
C3—C2—H2A	120.0	C9—C8—H8A	108.3
C4—C3—C2	120.3 (5)	C8—C9—H9A	109.5
C4—C3—H3A	119.9	C8—C9—H9B	109.5
C2—C3—H3A	119.9	H9A—C9—H9B	109.5
C3—C4—C5	119.8 (5)	C8—C9—H9C	109.5
C3—C4—H4A	120.1	H9A—C9—H9C	109.5
C5—C4—H4A	120.1	H9B—C9—H9C	109.5
C6—C5—C4	120.2 (5)	C8—C10—H10A	109.5
C6—C5—H5A	119.9	C8—C10—H10B	109.5
C4—C5—H5A	119.9	H10A—C10—H10B	109.5
C5—C6—C1	120.5 (4)	C8—C10—H10C	109.5
C5—C6—H6A	119.8	H10A—C10—H10C	109.5
C1—C6—H6A	119.8	H10B—C10—H10C	109.5

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O1ⁱ	0.83 (5)	2.10 (5)	2.890 (5)	160 (5)

Symmetry code: (i) x−1, y, z.

Experimental details

Crystal data
Chemical formula	C₁₀H₁₃NO
M_r	163.21
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	150
a, b, c (Å)	5.0093 (7), 10.1250 (13), 9.6714 (14)
β (°)	104.133 (7)
V (Å³)	475.68 (11)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.07
Crystal size (mm)	0.14 × 0.13 × 0.08

Data collection
Diffractometer	Bruker Nonius KappaCCD diffractometer
Absorption correction	Multi-scan (SORTAV; Blessing 1995)
T_min, T_max	0.954, 0.996
No. of measured, independent and observed [I > 2σ(I)] reflections	2462, 887, 621
R_int	0.061
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.057, 0.148, 1.06
No. of reflections	887
No. of parameters	114
No. of restraints	1
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.18, −0.21

Computer programs: COLLECT (Nonius, 2002), DENZO-SMN (Otwinowski & Minor, 1997), SIR92 (Altomare et al., 1994), SHELXTL (Sheldrick, 2008), PLATON (Spek, 2003).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O1ⁱ	0.83 (5)	2.10 (5)	2.890 (5)	160 (5)

Symmetry code: (i) x−1, y, z.

Acknowledgements

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).

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