Crystal structure of 2-pentyl­oxybenzamide

Bugenhagen, B.; Al Jasem, Y.; Thiemann, T.

doi:10.1107/S1600536814020571

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Volume 70| Part 10| October 2014| Pages 231-234

doi:10.1107/S1600536814020571

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Crystal structure of 2-pentyloxybenzamide

Bernhard Bugenhagen,^a Yosef Al Jasem ^b and Thies Thiemann ^c ^*

^aInstitute of Inorganic Chemistry, University of Hamburg, Hamburg, Germany, ^bDepartment of Chemical Engineering, United Arab Emirates University, AL Ain, Abu Dhabi, United Arab Emirates, and ^cDepartment of Chemistry, United Arab Emirates University, AL Ain, Abu Dhabi, United Arab Emirates
^*Correspondence e-mail: thies@uaeu.ac.ae

Edited by H. Stoeckli-Evans, University of Neuchâtel, Switzerland (Received 31 August 2014; accepted 14 September 2014; online 20 September 2014)

In the title molecule, C₁₂H₁₇NO₂, the amide NH₂ group is oriented toward the pentyloxy substituent and an intramolecular N—H⋯O hydrogen bond is formed with the pentyloxy O atom. The benzene ring forms dihedral angles of 2.93 (2) and 5.60 (2)° with the amide group and the pentyloxy group mean planes, respectively. In the crystal, molecules are linked by pairs of N—H⋯O hydrogen bonds, forming inversion dimers with their molecular planes parallel, but at an offset of 0.45 (1) Å to each other. These dimers are ordered into two types of symmetry-related columns extended along the a axis, with the mean plane of one set of dimers in a column approximately parallel to (121) and the other in a column approximately parallel to (1-21). The two planes form a dihedral angle of 85.31 (2)°, and are linked via C—H⋯O hydrogen bonds and C—H⋯π interactions, forming a three-dimensional framework structure.

Keywords: crystal structure; 2-alkoxybenzamide; hydrogen bonding..

CCDC reference: 1024316

1. Chemical context

In our efforts to use 2-alkoxybenzamides as components in co-crystal formation (Aitipamula et al., 2012 ), we prepared the title compound, 2-pentyloxybenzamide, and report herein on its crystal structure. 2-Pentyloxybenzamide was first studied for its antipyretic and analgesic properties (Bavin et al., 1952 ; Macrae & Seymour, 1956 ). Afterwards, it was found to have antifungal activity and to be useful in the treatment of dermatomycosis (Simmonite & Tattersall, 1962 ; Coates et al., 1957 ). Under the name pentalamide, it is still used as an ingredient in antifungal agents for topical use.

2. Structural commentary

In the title molecule, Fig. 1, the benzene ring is nearly coplanar with the amide group [C6—C1—C7—O1 = −2.48 (18)°] and the pentyloxy group [C3—C2—O2—C8 = 0.37 (18)°]. The amide NH₂ group is oriented towards the ether group allowing for an intramolecular hydrogen bond (N1—H1B⋯O2; Fig. 1 and Table 1). The latter is also present in analogous compounds, such as 3-hydroxy-2-methoxybenzamide (Wilbrand et al., 2012 ), 2-propoxybenzamide (Al Jasem et al., 2012 ) and 2-(prop-2-enyloxy)benzamide (Bugenhagen et al., 2012 ). 2-Ethoxybenzamide is the only studied 2-alkoxybenzamide that does not exhibit an intramolecular hydrogen bond in the single component crystal (Pagola & Stephens, 2009 ). However, it shows a similar conformation to the other 2-alkoxybenzamides in the co-crystal form with thiourea (Moribe et al., 2004 ), and with salicylic acid (Back et al., 2012 ).

Table 1
Hydrogen-bond geometry (Å, °)

Cg1 is the centroid of the C1–C6 benzene ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1B⋯O2	0.915 (17)	1.921 (18)	2.6510 (15)	135.4 (15)
N1—H1A⋯O1ⁱ	0.919 (19)	1.964 (19)	2.8824 (15)	177.8 (17)
C3—H3⋯O1ⁱⁱ	0.93	2.62	3.546 (2)	178
C4—H4⋯O1ⁱⁱⁱ	0.93	2.53	3.306 (2)	141
C11—H11A⋯Cg1^iv	0.97	2.90	3.7283 (16)	141
Symmetry codes: (i) -x, -y+1, -z; (ii) $[x, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]$ ; (iii) $[-x+1, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (iv) x-1, y, z.

Figure 1
A view of the molecular structure of the title molecule, with atom labelling. Displacement ellipsoids are shown at the 50% probability level. The intramolecular N—H⋯O hydrogen bond is shown as a green dashed line (see Table 1

for details).

3. Supramolecular features

In the crystal, molecules are linked by pairs of N-H⋯O (N1—H1A⋯O1) hydrogen bonds forming inversion dimers (Fig. 2 and Table 1). These dimers form a nested network of molecules, made of two layers, (121) and (1 $[\overline{2}]$ 1), which form an angle of 85.31 (2)° between their planes (Fig. 3). The dimers in the layers are linked by C—H⋯O (C4—H4⋯O1) hydrogen bonds and C—H⋯π interactions, forming a three-dimensional framework (Fig. 3 and Table 1). Within two parallel layers, pairs of molecules lie with an offset to each other without any noticeable, direct interaction between them; the parallel layers are at a distance of 3.81 (3) Å from each other. Along the a axis the pairs are ordered in two symmetry-related columns. The plane of the benzene ring (C1–C6) of the 2-pentyloxybenzamide forms an angle of 25.29 (2)° with the column axis.

Figure 2
A partial view of the crystal packing of the title compound. The hydrogen bonds are shown as green dashed lines [see Table 1

for details; symmetry codes: (i) −x + 1, y + $[{1\over 2}]$ , −z + $[{1\over 2}]$ ; (ii) x, y, z; (iii) x, −y + $[{1\over 2}]$ , z + $[{1\over 2}]$ ; (iv) −x, y − $[{1\over 2}]$ , −z + $[{1\over 2}]$ ]

Figure 3
A view of the crystal network formed by the layers of inversion dimers in the planes (121) in red, and (1 $[\overline{2}]$ 1) in blue. The hydrogen bonds are shown as green dashed lines (see Table 1

for details; H atoms have been omitted for clarity).

4. Database survey

From a database survey (Cambridge Structural Database, Version 5.35, last update May 2014; Allen, 2002 ), the following were picked as relevant comparable structures: 3-hydroxy-2-methoxybenzamide (Wilbrand et al., 2012), 2-methoxybenzamide (Moribe et al., 2006 ), 2-ethoxybenzamide (Pagola & Stephens, 2009; Back et al., 2012), 2-propoxybenzamide (Al Jasem et al., 2012) and 2-(prop-2-enyloxy)benzamide (Bugenhagen et al., 2012). For 2-propoxybenzamide, a homologue of the title compound, a similar formation of inversion-related molecular pairs in the crystal was reported, hence the two compounds exhibit a similar packing. The noticeable difference between the two compounds is the larger dihedral angle between the carboxamide group and the benzene ring in 2-propoxybenzamide, 12.41 (2)° compared to 3.30 (15)° in the title compound, 2-pentyloxybenzamide. Also, the parallel layers of molecules in the title compound are further apart [separated by 3.81 (3) Å] than is found for a similar packing of 2-propoxybenzamide [3.69 (2) Å]. Similarly, inversion-related pairs of molecules are formed by intermolecular (amide–amide) hydrogen bonding in 2-ethoxybenzamide and 3-hydroxy-2-methoxybenzamide. As 2-ethoxybenzamide exhibits no intramolecular hydrogen bonding, the freed acceptor–donor sites are used for additional intermolecular hydrogen bonding with the adjacent molecule.

In contrast, in 2-methoxybenzamide and in 2-(prop-2-enyloxy)benzamide the intermolecular N—H⋯O hydrogen bonds involving the amide groups do not lead to pair formation but generate C(4) and R₃²(7) motifs.

5. Synthesis and crystallization

The preparation of the title compound follows a Williamson ether synthesis using DMSO as solvent, analogous to a general procedure (Johnstone & Rose, 1979 ): To powdered KOH (1.12 g, 20.0 mmol) in DMSO (18 ml) was added salicylamide (1.37 g, 10.0 mmol), and the resulting mixture was stirred for 10 min. at rt. Then, n-amyl iodide (4.2 g, mmol, 21.2 mmol) was added dropwise. The solution was stirred for 12 h at rt. It was then poured into water (200 ml) and extracted with chloroform (3 × 75 ml). The organic phase was dried over anhydrous MgSO₄, concentrated in vacuo, and the residue was subjected to column chromatography on silica gel (CHCl₃/M^tBE/hexane v/v/v 1:1:1) to give the title compound (1.55 g, 75%) as colourless crystals (m.p. 362 K). IR (KBr, cm⁻¹) νmax 3434, 3168, 2948, 2868, 1664, 1593, 1387, 1232, 1164, 1018, 832, 788, 765, 575; ¹H NMR (400 MHz, CDCl₃, δ_H) 0.93 (3H, t, ³J = 7.2 Hz, CH₃), 1.38–1.48 (4H, m), 1.84–1.89 (2H, m), 4.11 (2H, d, ³J = 6.4 Hz); 6.03 (1H, bs, NH), 6.96 (1H, d, ³J = 8.4 Hz), 7.03–7.07 (1H, m), 7.42–7.46 (1H, m), 7.85 (1H, bs, NH), 8.20 (1H, dd, ³J = 7.6 Hz, ⁴J = 2.0 Hz), ¹³C NMR (100.5 MHz, CDCl₃, δ_C) 14.0 (CH₃), 22.4 (CH₂), 28.2 (CH₂), 28.9 (CH₂), 69.1 (OCH₂), 112.2 (CH), 120.7 (C_quat), 121.0 (CH), 132.5 (CH), 133.3 (C_quat), 157.4 (C_quat), 167.2 (C_quat, CO).

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. All C-bound H atoms were placed in calculated positions and refined as riding atoms: C—H distances of 0.95 − 1.00 Å with U_iso(H) = xU_eq(C), where x = 1.5 for methyl and = 1.2 for other H-atoms. The N-bound H atoms were located in a difference electron-density map and freely refined.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₂H₁₇NO₂
M_r	207.27
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	100
a, b, c (Å)	8.1830 (2), 11.2706 (2), 14.5386 (4)
β (°)	119.696 (2)
V (Å³)	1164.76 (5)
Z	4
Radiation type	Cu Kα
μ (mm⁻¹)	0.64
Crystal size (mm)	0.25 × 0.19 × 0.10

Data collection
Diffractometer	SuperNova, Dual, Cu at zero, Atlas
Absorption correction	Multi-scan (CrysAlis PRO; Agilent, 2012 )
T_min, T_max	0.854, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	6112, 2268, 1900
R_int	0.022
(sin θ/λ)_max (Å⁻¹)	0.621

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.041, 0.115, 1.03
No. of reflections	2268
No. of parameters	145
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.19, −0.22
Computer programs: CrysAlis PRO (Agilent, 2012), SHELXS97 and SHELXL97 (Sheldrick, 2008 ) within OLEX2 (Dolomanov et al., 2009 ), PLATON (Spek, 2009 ) and Mercury (Macrae et al., 2008 ).

Supporting information

CCDC reference: 1024316

Crystal structure: contains datablock I. DOI: 10.1107/S1600536814020571/su2779sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536814020571/su2779Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536814020571/su2779Isup3.cml

checkCIF report

Chemical context top

2-Alkoxybenzamide moieties can be found as structural units in medicinally active compounds, such in dopamine (DA) receptor antagonists (van de Waterbeemd & Testa, 1983). Typical such components are Sulpiride®, Metoclopramide® and Tiapride®. Other substituted 2-alkoxybenzamides have been found to be antagonists of chemotherapy-induced nausea (Monkovic et al., 1988). Also, 2-alkoxybenzamides have been proposed as agonists of the α7 nicotinic receptor (Bodnar et al., 2005) and as neuroleptic compounds (Florvall & Oegren, 1982). 2-Ethoxybenzamide, under the name ethenzamide, is a commonly used analgesicum (Darias et al., 1992). In our efforts to use 2-alkoxybenzamides as components in co-crystal formation (Aitipamula et al., 2012), we prepared the title compound, 2-pentyloxybenzamide, and report herein on its crystal structure. 2-Pentyloxybenzamide was first studied for its antipyretic and analgesic properties (Bavin et al., 1952; Macrae & Seymour, 1956). Afterwards, it was found to have antifungal activity and to be useful in the treatment of dermatomycosis (Simmonite & Tattersall, 1962; Coates et al., 1957). Under the name pentalamide, it is still used as an ingredient in antifungal agents for topical use.

Structural commentary top

In the title molecule, Fig. 1, the benzene ring is nearly coplanar with the amide group [C6—C1—C7—O1 = -2.48 (18)°] and the pentyloxy group [C3—C2—O2—C8 = 0.37 (18)°]. The amide NH₂ group is oriented towards the ether group allowing for an intramolecular hydrogen bond (N1—H1B···O2; Fig. 1 and Table 1). The latter is also present in analogous compounds, such as 3-hydroxy-2-methoxybenzamide (Wilbrand et al., 2012), 2-propoxybenzamide (Al Jasem et al., 2012) and 2-(prop-2-enyloxy)benzamide (Bugenhagen et al., 2012). 2-Ethoxybenzamide is the only studied 2-alkoxybenzamide that does not exhibit an intramolecular hydrogen bond in the single component crystal (Pagola & Stephens, 2009). However, it shows a similar conformation to the other 2-alkoxybenzamides in the co-crystal form with thiourea (Moribe et al., 2004), and with salicylic acid (Back et al., 2012).

Supramolecular features top

In the crystal, molecules are linked by pairs of N—H···O (N1—H1A···O1) hydrogen bonds forming inversion dimers (Fig. 2 and Table 1). These dimers form a nested network of molecules, made of two layers, (121) and (121), which form an angle of 85.31 (2)° between their planes (Fig. 3). The dimers in the layers are linked by C—H···O (C4—H4···O1) hydrogen bonds and C—H···π interactions, forming a three-dimensional framework (Fig. 3 and Table 1). Within two parallel layers, pairs of molecules lie with an offset to each other without any noticeable, direct interaction between them; the parallel layers are at a distance of 3.81 (3) Å from each other. Along the a axis the pairs are ordered in two symmetry-related columns. The plane of the benzene ring (C1–C6) of the 2-pentyloxybenzamide forms an angle of 25.29 (2)° with the column axis.

Database survey top

From a database survey (Cambridge Structural Database, Version 5.35, last update May 2014; Allen, 2002), the following were picked as relevant comparable structures: 3-hydroxy-2-methoxybenzamide (Wilbrand et al., 2012), 2-methoxybenzamide (Moribe et al., 2006), 2-ethoxybenzamide (Pagola & Stephens, 2009; Back et al., 2012), 2-propoxybenzamide (Al Jasem et al., 2012) and 2-(prop-2-enyloxy)benzamide (Bugenhagen et al., 2012). For 2-propoxybenzamide, a homologue of the title compound, a similar formation of inversion-related molecular pairs in the crystal was reported, hence the two compounds exhibit a similar packing. The noticeable difference between the two compounds is the larger dihedral angle between the carboxamide group and the benzene ring in 2-propoxybenzamide, 12.41 (2)° compared to 3.30 (15)° in the title compound, 2-pentyloxybenzamide. Also, the parallel layers of molecules in the title compound are further apart [separated by 3.81 (3) Å] than is found for a similar packing of 2-propoxybenzamide [3.69 (2) Å]. Similarly, inversion-related pairs of molecules are formed by intermolecular (amide–amide) hydrogen bonding in 2-ethoxybenzamide and 3-hydroxy-2-methoxybenzamide. As 2-ethoxybenzamide exhibits no intramolecular hydrogen bonding, the freed acceptor–donor sites are used for additional intermolecular hydrogen bonding with the adjacent molecule.

In contrast, in 2-methoxybenzamide and in 2-(prop-2-enyloxy)benzamide the intermolecular N—H···O hydrogen bonds involving the amide groups do not lead to pair formation but generate C(4) and R²₃(7) motifs.

Synthesis and crystallization top

The preparation of the title compound follows a Williamson ether synthesis using DMSO as solvent, analogous to a general procedure (Johnstone & Rose, 1979): To powdered KOH (1.12 g, 20.0 mmol) in DMSO (18 ml) was added salicylamide (1.37 g, 10.0 mmol), and the resulting mixture was stirred for 10 min. at rt. Then, n-amyl iodide (4.2 g, mmol, 21.2 mmol) was added dropwise. The solution was stirred for 12 h at rt. It was then poured into water (200 ml) and extracted with chloroform (3 × 75 ml). The organic phase was dried over anhydrous MgSO₄, concentrated in vacuo, and the residue was subjected to column chromatography on silica gel (CHCl₃/M^tBE/hexane v/v/v 1:1:1) to give the title compound (1.55 g, 75%) as colourless crystals (m.p. 362 K). IR (KBr, cm^-1) νmax 3434, 3168, 2948, 2868, 1664, 1593, 1387, 1232, 1164, 1018, 832, 788, 765, 575; ¹H NMR (400 MHz, CDCl_3, δ_H ) 0.93 (3H, t, ³J = 7.2 Hz, CH₃), 1.38–1.48 (4H, m), 1.84–1.89 (2H, m), 4.11 (2H, d, ³J = 6.4 Hz); 6.03 (1H, bs, NH), 6.96 (1H, d, ³J = 8.4 Hz), 7.03–7.07 (1H, m), 7.42–7.46 (1H, m), 7.85 (1H, bs, NH), 8.20 (1H, dd, ³J = 7.6 Hz, ⁴J = 2.0 Hz), ¹³C NMR (100.5 MHz, CDCl_3, δ_C) 14.0 (CH₃), 22.4 (CH₂), 28.2 (CH₂), 28.9 (CH₂), 69.1 (OCH₂), 112.2 (CH), 120.7 (C_quat), 121.0 (CH), 132.5 (CH), 133.3 (C_quat), 157.4 (C_quat), 167.2 (C_quat, CO).

Refinement top

Crystal data, data collection and structure refinement details are summarized in Table 2. All C-bound H atoms were placed in calculated positions and refined as riding atoms: C—H distances of 0.95 - 1.00 Å with U_iso(H) = xU_eq(C), where x = 1.5 for methyl and = 1.2 for other H-atoms. The N-bound H atoms were located in a difference electron-density map and freely refined.

Related literature top

For related literature, see: Aitipamula et al. (2012); Al Jasem, al Hindawi, Thiemann & White (2012); Back et al. (2012); Bavin et al. (1952); Bodnar et al. (2005); Bugenhagen et al. (2012); Coates et al. (1957); Darias et al. (1992); Florvall & Oegren (1982); Johnstone & Rose (1979); Monkovic et al. (1988); Moribe et al. (2004, 2006); Pagola & Stephens (2009); Waterbeemd & Testa (1983); Wilbrand et al. (2012).

Computing details top

Data collection: CrysAlis PRO (Agilent, 2012); cell refinement: CrysAlis PRO (Agilent, 2012); data reduction: CrysAlis PRO (Agilent, 2012); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008) within OLEX2 (Dolomanov et al., 2009); molecular graphics: PLATON (Spek, 2009) and Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top

	Fig. 1. A view of the molecular structure of the title molecule, with atom labelling. Displacement ellipsoids are shown at the 50% probability level. The intramolecular N—H···O hydrogen bond is shown as a green dashed line (see Table 1 for details).
	Fig. 2. A partial view of the crystal packing of the title compound. The hydrogen bonds are shown as green dashed lines [see Table 1 for details; symmetry codes: (i) -x+1, y+1/2, -z+1/2; (ii) x, y, z; (iii) x, -y+1/2, z+1/2; (iv) -x, y-1/2, -z+1/2]
	Fig. 3. A view of the crystal network formed by the layers of inversion dimers in the planes (121) in red, and (121) in blue. The hydrogen bonds are shown as green dashed lines (see Table 1 for details; H atoms not involved in hydrogen bonding have been omitted for clarity).

2-pentyloxybenzamide top

Crystal data top

C₁₂H₁₇NO₂	F(000) = 448
M_r = 207.27	D_x = 1.182 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.5418 Å
a = 8.1830 (2) Å	Cell parameters from 2743 reflections
b = 11.2706 (2) Å	θ = 3.9–73.1°
c = 14.5386 (4) Å	µ = 0.64 mm⁻¹
β = 119.696 (2)°	T = 100 K
V = 1164.76 (5) Å³	Block, colourless
Z = 4	0.25 × 0.19 × 0.10 mm

Data collection top

SuperNova, Dual, Cu at zero, Atlas diffractometer	2268 independent reflections
Radiation source: SuperNova (Cu) X-ray Source	1900 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.022
Detector resolution: 10.4127 pixels mm^-1	θ_max = 73.3°, θ_min = 5.3°
ω scans	h = −10→5
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2012)	k = −13→14
T_min = 0.854, T_max = 1.000	l = −16→18
6112 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)] = 0.041	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.115	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	w = 1/[σ²(F_o²) + (0.0645P)² + 0.2593P] where P = (F_o² + 2F_c²)/3
2268 reflections	(Δ/σ)_max < 0.001
145 parameters	Δρ_max = 0.19 e Å⁻³
0 restraints	Δρ_min = −0.22 e Å⁻³

Crystal data top

C₁₂H₁₇NO₂	V = 1164.76 (5) Å³
M_r = 207.27	Z = 4
Monoclinic, P2₁/c	Cu Kα radiation
a = 8.1830 (2) Å	µ = 0.64 mm⁻¹
b = 11.2706 (2) Å	T = 100 K
c = 14.5386 (4) Å	0.25 × 0.19 × 0.10 mm
β = 119.696 (2)°

Data collection top

SuperNova, Dual, Cu at zero, Atlas diffractometer	2268 independent reflections
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2012)	1900 reflections with I > 2σ(I)
T_min = 0.854, T_max = 1.000	R_int = 0.022
6112 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.041	0 restraints
wR(F²) = 0.115	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	Δρ_max = 0.19 e Å⁻³
2268 reflections	Δρ_min = −0.22 e Å⁻³
145 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
C1	0.25614 (18)	0.29076 (11)	0.20599 (10)	0.0233 (3)
C10	−0.14119 (19)	0.33945 (13)	0.46481 (11)	0.0269 (3)
C11	−0.29380 (19)	0.41079 (13)	0.47067 (11)	0.0294 (3)
C12	−0.3051 (2)	0.37915 (16)	0.56955 (12)	0.0389 (4)
C2	0.21475 (18)	0.25854 (12)	0.28594 (10)	0.0240 (3)
C3	0.31443 (19)	0.16670 (12)	0.35597 (11)	0.0279 (3)
C4	0.45350 (19)	0.10654 (13)	0.34698 (11)	0.0303 (3)
C5	0.49609 (19)	0.13709 (13)	0.26885 (11)	0.0301 (3)
C6	0.39777 (18)	0.22849 (12)	0.19968 (10)	0.0266 (3)
C7	0.15680 (18)	0.38484 (11)	0.12366 (10)	0.0232 (3)
C8	0.03619 (19)	0.28821 (12)	0.37434 (10)	0.0263 (3)
C9	−0.11424 (18)	0.36885 (12)	0.37063 (10)	0.0256 (3)
H10A	−0.1714	0.2558	0.4618	0.032*
H10B	−0.0229	0.3526	0.5295	0.032*
H11A	−0.4142	0.3950	0.4082	0.035*
H11B	−0.2672	0.4948	0.4717	0.035*
H12A	−0.3329	0.2962	0.5683	0.058*
H12B	−0.4027	0.4250	0.5710	0.058*
H12C	−0.1869	0.3963	0.6315	0.058*
H1A	−0.056 (2)	0.4934 (17)	0.0658 (14)	0.042 (5)*
H1B	−0.021 (2)	0.4242 (16)	0.1713 (14)	0.041 (5)*
H3	0.2873	0.1458	0.4089	0.033*
H4	0.5188	0.0452	0.3937	0.036*
H5	0.5896	0.0967	0.2630	0.036*
H6	0.4270	0.2490	0.1475	0.032*
H8A	0.1495	0.2950	0.4427	0.032*
H8B	−0.0062	0.2065	0.3650	0.032*
H9A	−0.2313	0.3570	0.3049	0.031*
H9B	−0.0767	0.4511	0.3742	0.031*
N1	0.01348 (16)	0.44361 (11)	0.12198 (9)	0.0282 (3)
O1	0.20767 (12)	0.40558 (9)	0.05777 (7)	0.0264 (2)
O2	0.07616 (13)	0.32058 (8)	0.29182 (7)	0.0271 (2)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0293 (5)	0.0312 (5)	0.0239 (5)	−0.0023 (4)	0.0171 (4)	0.0000 (4)
O2	0.0312 (5)	0.0313 (5)	0.0271 (5)	0.0063 (4)	0.0207 (4)	0.0059 (4)
N1	0.0343 (6)	0.0299 (6)	0.0271 (6)	0.0063 (5)	0.0204 (5)	0.0060 (5)
C1	0.0233 (6)	0.0263 (6)	0.0213 (6)	−0.0034 (5)	0.0116 (5)	−0.0028 (5)
C2	0.0227 (6)	0.0269 (7)	0.0250 (6)	−0.0002 (5)	0.0139 (5)	−0.0021 (5)
C3	0.0293 (7)	0.0316 (7)	0.0266 (7)	0.0015 (5)	0.0168 (6)	0.0028 (5)
C4	0.0302 (7)	0.0313 (7)	0.0300 (7)	0.0060 (6)	0.0153 (6)	0.0045 (6)
C5	0.0279 (7)	0.0347 (8)	0.0309 (7)	0.0044 (6)	0.0169 (6)	−0.0018 (6)
C6	0.0259 (7)	0.0331 (7)	0.0244 (6)	−0.0013 (5)	0.0153 (6)	−0.0028 (5)
C7	0.0252 (7)	0.0244 (6)	0.0224 (6)	−0.0053 (5)	0.0135 (5)	−0.0046 (5)
C8	0.0303 (7)	0.0300 (7)	0.0250 (6)	0.0035 (5)	0.0186 (6)	0.0055 (5)
C9	0.0260 (7)	0.0296 (7)	0.0247 (6)	0.0022 (5)	0.0152 (5)	0.0034 (5)
C10	0.0281 (7)	0.0318 (7)	0.0259 (7)	0.0031 (6)	0.0173 (6)	0.0039 (5)
C11	0.0290 (7)	0.0357 (7)	0.0284 (7)	0.0037 (6)	0.0180 (6)	0.0032 (6)
C12	0.0405 (9)	0.0513 (10)	0.0375 (8)	0.0100 (7)	0.0288 (7)	0.0064 (7)

Geometric parameters (Å, º) top

O1—C7	1.2412 (15)	C6—H6	0.9300
O2—C2	1.3706 (15)	C8—H8A	0.9700
O2—C8	1.4381 (14)	C8—H8B	0.9700
N1—C7	1.3366 (17)	C8—C9	1.5095 (18)
N1—H1A	0.919 (19)	C9—H9A	0.9700
N1—H1B	0.915 (17)	C9—H9B	0.9700
C1—C2	1.4099 (17)	C9—C10	1.5272 (17)
C1—C6	1.3962 (18)	C10—H10A	0.9700
C1—C7	1.5013 (18)	C10—H10B	0.9700
C2—C3	1.3966 (19)	C10—C11	1.5227 (18)
C3—H3	0.9300	C11—H11A	0.9700
C3—C4	1.3853 (19)	C11—H11B	0.9700
C4—H4	0.9300	C11—C12	1.5278 (18)
C4—C5	1.3866 (19)	C12—H12A	0.9600
C5—H5	0.9300	C12—H12B	0.9600
C5—C6	1.385 (2)	C12—H12C	0.9600

C1—C6—H6	119.0	C6—C1—C7	116.23 (11)
C10—C11—C12	111.28 (12)	C6—C1—C2	118.09 (12)
C10—C11—H11B	109.4	C7—N1—H1B	118.2 (11)
C10—C11—H11A	109.4	C7—N1—H1A	118.0 (10)
C10—C9—H9B	110.0	C8—C9—C10	108.35 (11)
C10—C9—H9A	110.0	C8—C9—H9B	110.0
C11—C12—H12C	109.5	C8—C9—H9A	110.0
C11—C12—H12B	109.5	C9—C10—H10B	108.5
C11—C12—H12A	109.5	C9—C10—H10A	108.5
C11—C10—H10B	108.5	C9—C8—H8B	109.7
C11—C10—H10A	108.5	C9—C8—H8A	109.7
C11—C10—C9	114.98 (11)	H10A—C10—H10B	107.5
C12—C11—H11B	109.4	H11A—C11—H11B	108.0
C12—C11—H11A	109.4	H12A—C12—H12C	109.5
C2—C3—H3	119.9	H12A—C12—H12B	109.5
C2—C1—C7	125.65 (12)	H12B—C12—H12C	109.5
C2—O2—C8	117.38 (10)	H1A—N1—H1B	123.2 (14)
C3—C4—C5	120.48 (13)	H8A—C8—H8B	108.2
C3—C4—H4	119.8	H9A—C9—H9B	108.4
C3—C2—C1	119.99 (12)	N1—C7—C1	119.22 (11)
C4—C5—H5	120.4	O1—C7—C1	119.48 (11)
C4—C3—H3	119.9	O1—C7—N1	121.29 (12)
C4—C3—C2	120.29 (12)	O2—C8—C9	109.63 (10)
C5—C6—H6	119.0	O2—C8—H8B	109.7
C5—C6—C1	121.92 (12)	O2—C8—H8A	109.7
C5—C4—H4	119.8	O2—C2—C3	122.35 (11)
C6—C5—H5	120.4	O2—C2—C1	117.66 (11)
C6—C5—C4	119.22 (12)

C1—C2—C3—C4	−0.3 (2)	C6—C1—C2—O2	179.67 (11)
C2—C3—C4—C5	0.3 (2)	C7—C1—C6—C5	−177.98 (12)
C2—C1—C7—N1	−1.4 (2)	C7—C1—C2—C3	178.07 (12)
C2—C1—C7—O1	179.44 (12)	C7—C1—C2—O2	−2.27 (19)
C2—C1—C6—C5	0.3 (2)	C8—C9—C10—C11	−178.10 (12)
C2—O2—C8—C9	177.89 (11)	C8—O2—C2—C3	0.37 (18)
C3—C4—C5—C6	−0.1 (2)	C8—O2—C2—C1	−179.28 (11)
C4—C5—C6—C1	−0.2 (2)	C9—C10—C11—C12	−177.64 (12)
C6—C1—C7—N1	176.66 (12)	O2—C8—C9—C10	−175.11 (10)
C6—C1—C7—O1	−2.48 (18)	O2—C2—C3—C4	−179.95 (12)
C6—C1—C2—C3	0.02 (19)

Hydrogen-bond geometry (Å, º) top

Cg1 is the centroid of the C1–C6 benzene ring.

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1B···O2	0.915 (17)	1.921 (18)	2.6510 (15)	135.4 (15)
N1—H1A···O1ⁱ	0.919 (19)	1.964 (19)	2.8824 (15)	177.8 (17)
C3—H3···O1ⁱⁱ	0.93	2.62	3.546 (2)	178
C4—H4···O1ⁱⁱⁱ	0.93	2.53	3.306 (2)	141
C11—H11A···Cg1^iv	0.97	2.90	3.7283 (16)	141

Symmetry codes: (i) −x, −y+1, −z; (ii) x, −y+1/2, z+1/2; (iii) −x+1, y−1/2, −z+1/2; (iv) x−1, y, z.

Hydrogen-bond geometry (Å, º) top

Cg1 is the centroid of the C1–C6 benzene ring.

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1B···O2	0.915 (17)	1.921 (18)	2.6510 (15)	135.4 (15)
N1—H1A···O1ⁱ	0.919 (19)	1.964 (19)	2.8824 (15)	177.8 (17)
C3—H3···O1ⁱⁱ	0.93	2.616	3.546 (2)	178
C4—H4···O1ⁱⁱⁱ	0.93	2.534	3.306 (2)	141
C11—H11A···Cg1^iv	0.97	2.90	3.7283 (16)	141

Symmetry codes: (i) −x, −y+1, −z; (ii) x, −y+1/2, z+1/2; (iii) −x+1, y−1/2, −z+1/2; (iv) x−1, y, z.

Experimental details

Crystal data
Chemical formula	C₁₂H₁₇NO₂
M_r	207.27
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	100
a, b, c (Å)	8.1830 (2), 11.2706 (2), 14.5386 (4)
β (°)	119.696 (2)
V (Å³)	1164.76 (5)
Z	4
Radiation type	Cu Kα
µ (mm⁻¹)	0.64
Crystal size (mm)	0.25 × 0.19 × 0.10

Data collection
Diffractometer	SuperNova, Dual, Cu at zero, Atlas diffractometer
Absorption correction	Multi-scan (CrysAlis PRO; Agilent, 2012)
T_min, T_max	0.854, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	6112, 2268, 1900
R_int	0.022
(sin θ/λ)_max (Å⁻¹)	0.621

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.041, 0.115, 1.03
No. of reflections	2268
No. of parameters	145
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.19, −0.22

Computer programs: CrysAlis PRO (Agilent, 2012), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008) within OLEX2 (Dolomanov et al., 2009), PLATON (Spek, 2009) and Mercury (Macrae et al., 2008), SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

References

Agilent (2012). CrysAlis PRO. Agilent Technologies, Yarnton, England. Google Scholar
Aitipamula, S., Wong, A. B. H., Chow, P. S. & &Tan, R. B. H. (2012). CrystEngComm, 14, 8515–8524. Web of Science CSD CrossRef CAS Google Scholar
Al Jasem, Y., Hindawi, B. al, Thiemann, T. & White, F. (2012). Acta Cryst. E68, o2639–o2640. CSD CrossRef CAS IUCr Journals Google Scholar
Allen, F. H. (2002). Acta Cryst. B58, 380–388. Web of Science CrossRef CAS IUCr Journals Google Scholar
Back, K. R., Davey, R. J., Grecu, T., Hunter, C. A. & Taylor, L. S. (2012). Cryst. Growth Des. 12, 6110–6117. Web of Science CSD CrossRef CAS Google Scholar
Bavin, E. M., Macrae, F. J., Seymour, D. E. & Waterhouse, P. D. (1952). J. Pharm. Pharmacol. 4, 872–878. CrossRef PubMed CAS Google Scholar
Bodnar, A. L., Cortes-Burgos, L. A., Cook, K. K., Dinh, D. M., Groppi, V. E., Hajos, M., Higdon, N. R., Hoffmann, W. E., Hurst, R. S., Myers, J. K., Rogers, N. B., Wall, T. M., Wolfe, M. L. & Wong, E. (2005). J. Med. Chem. 48, 905–908. Web of Science CrossRef PubMed CAS Google Scholar
Bugenhagen, B., Al Jasem, Y., Barkhad, F., Hindawi, B. al & Thiemann, T. (2012). Acta Cryst. E68, o3169–o3170. Google Scholar
Coates, L. V., Drain, D. J., Kerridge, K. A., Macrae, F. J. & Tattersall, K. (1957). J. Pharm. Pharmacol. 9, 855–862. CrossRef PubMed CAS Google Scholar
Darias, V., Bravo, L., Abdallah, S. S., Sánchez Mateo, C. C., Expósito-Orta, M. A., Lissavetsky, J. & Manzanares, J. (1992). Arch. Pharm. 325, 83–87. CrossRef CAS Web of Science Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Florvall, L. & Oegren, S.-O. (1982). J. Med. Chem. 1982, 25, 1280–1286. Google Scholar
Johnstone, R. A. W. & Rose, M. E. (1979). Tetrahedron, 35, 2169–2173. CrossRef CAS Web of Science Google Scholar
Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466–470. Web of Science CrossRef CAS IUCr Journals Google Scholar
Macrae, F. J. & Seymour, D. E. (1956). GB 726786 (May 1955) [Herts Pharmaceuticals Ltd.], Chem. Abstr. 50, 28262. Google Scholar
Monkovic, I., Willner, D., Adam, M. A., Brown, M., Crenshaw, R. R., Fuller, C. E., Juby, P. F., Luke, G. M., Matiskella, J. A. & Montzka, T. A. (1988). J. Med. Chem. 31, 1548–1566. CrossRef CAS PubMed Web of Science Google Scholar
Moribe, K., Tsuchiya, M., Tosuka, Y., Yamaguchi, K., Oguchi, T. & Yamamoto, K. (2004). Chem. Pharm. Bull. 52, 524—529. CrossRef Google Scholar
Moribe, K., Tsuchiya, M., Tozuka, Y., Yamaguchi, K., Oguchi, T. & Yamamoto, K. (2006). J. Inclusion Phenom. Macrocycl. Chem. 54, 9–16. Web of Science CSD CrossRef CAS Google Scholar
Pagola, S. & Stephens, P. W. (2009). Acta Cryst. C65, o583–o586. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Simmonite, D. & Tattersall, K. (1962). GB 872891 (July 1961) [Smith, T. J. & Nephew Ltd.], Chem. Abstr. 56, 18626. Google Scholar
Spek, A. L. (2009). Acta Cryst. D65, 148–155. Web of Science CrossRef CAS IUCr Journals Google Scholar
Waterbeemd, H. van de & Testa, B. (1983). J. Med. Chem. 26, 203–207. PubMed Web of Science Google Scholar
Wilbrand, S., Neis, C. & Hegetschweiler, K. (2012). Acta Cryst. E68, o3494. CSD CrossRef IUCr Journals Google Scholar

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Volume 70| Part 10| October 2014| Pages 231-234

doi:10.1107/S1600536814020571

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