Crystal structure of 2-pentyl­oxybenzamide

In the nearly planar 2-pentyl­oxybenzamide mol­ecule, there is an intra­molecular N—H...O hydrogen bond involving one amide proton and the ether oxygen. In the crystal, pairs of N—H...O hydrogen bonds organize mol­ecules into inversion dimers lying in two planes, (121) and (11).

Key indicators

• Single-crystal X-ray study
• T = 100 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.041
• wR factor = 0.115
• Data-to-parameter ratio = 15.6

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT480_ALERT_4_C Long H...A H-Bond Reported H3     ..  O1      ..       2.62 Ang.
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.600          4 Report
PLAT913_ALERT_3_C Missing # of Very Strong Reflections in FCF ....          1 Note

Alert level G
PLAT005_ALERT_5_G No _iucr_refine_instructions_details  in the CIF     Please Do !
PLAT128_ALERT_4_G Alternate Setting for Input Space Group  P21/c        P21/n Note
PLAT912_ALERT_4_G Missing # of FCF Reflections Above STh/L=  0.600         59 Note

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
   3 ALERT level C = Check. Ensure it is not caused by an omission or oversight
   3 ALERT level G = General information/check it is not something unexpected

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   3 ALERT type 4 Improvement, methodology, query or suggestion
   1 ALERT type 5 Informative message, check

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S1. Chemical context

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.

S2. 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).

S3. 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 (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.

S4. 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 R²₃(7) motifs.

S5. 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, 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).

S6. 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.

Related literature

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

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

	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

Crystal data

C12H17NO2	F(000) = 448
Mr = 207.27	Dx = 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) Å^3	Block, colourless
Z = 4	0.25 × 0.19 × 0.10 mm

Data collection

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	Rint = 0.022
Detector resolution: 10.4127 pixels mm^-1	θmax = 73.3°, θmin = 5.3°
ω scans	h = −10→5
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2012)	k = −13→14
Tmin = 0.854, Tmax = 1.000	l = −16→18
6112 measured reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.041	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.115	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	w = 1/[σ^2(Fo^2) + (0.0645P)^2 + 0.2593P] where P = (Fo^2 + 2Fc^2)/3
2268 reflections	(Δ/σ)max < 0.001
145 parameters	Δρmax = 0.19 e Å^−3
0 restraints	Δρmin = −0.22 e Å^−3

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 (Ų)

	x	y	z	Uiso*/Ueq
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 (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
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)

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)

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···O1^i	0.919 (19)	1.964 (19)	2.8824 (15)	177.8 (17)
C3—H3···O1^ii	0.93	2.62	3.546 (2)	178
C4—H4···O1^iii	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.