Low-temperature study of 3-acetyl­indole at 110 K

The title compound, C₁₀H₉NO, contains an acetyl group that is nearly coplanar with the indole ring system, with an angle between the planes of the heterocyclic ring and the acetyl group of 1.75 (17)°. The planes of the benzene and pyrrole rings in the indole system make a dihedral angle of 2.05 (11)°. Each mol­ecule in the unit cell is linked through N-H...O hydrogen bonds to two other mol­ecules, forming hydrogen-bonded chains in the [101] direction with graph set C(6). The significance of this study lies in the analysis of the inter­actions occurring via hydrogen bonds in this structure, as well as in the comparison drawn between the mol­ecular structure of the title compound and those of several other indole derivatives possessing a 3-carbonyl group. The correlation between the IR spectrum of this compound and the structural data is also discussed.

S1. Comment

The indole ring system is the structural element of many natural and/or synthetic organic compounds exhibiting biological and pharmacological activities, such as anti-allergic (Shigenaga et al., 1993), antimicrobial (Oh et al., 2006), antifungal and antibacterial properties (Quetin-Leclercq et al., 1995; Singh et al.., 2000; Ablordeppey et al., 2002), as well as anti-cancer properties (Dashwood et al., 1994; Andreani et al., 2001; Gul & Hamann, 2005; Gupta et al., 2007). The most well known indole compounds are the tryptophan-derived tryptamine alkaloids, i.e. the neurotransmitter serotonin (Simonenkov & Fedorov, 2002; Nichols & Nichols, 2008), the hormone melatonin (Cardinali et al., 2004; Karasek, 2004), the hallucinogens psilocybin (Passie et al., 2002) and N,N-dimethyltryptamine (DMT) (Strassman, 1996), 2-(5-methoxy-1H-indol-3-yl)-N,N-dimethylethanamine (5-MeO-DMT) (Gouzoulis-Mayfrank et al., 2005) or the ergolines such as lysergic acid diethylamide (LSD) (Appel et al., 2004). The indolic derivatives, including the plant hormone auxin (indolyl-3-acetic acid, IAA) (Chandrasekhar & Raghunathan, 1982; Nigović et al., 2000), the anti-inflammatory drug indomethacin (Chen et al., 2002; Cox & Manson, 2003) and the betablocker pindolol (Nair et al., 2004), should also be mentioned. Over the last few years, the synthesis of indole derivatives, especially the triptans, has been a subject of fundamental interest to organic and medicinal chemists. Triptans are selective serotonin (5-HT_1B/D) agonists developed for the relief of migraine symptoms by targeting the disease pathology (Perry & Markham, 1998; de Vries et al., 1999; Ferrari et al., 2002; Pascual et al., 2007). So far, seven triptans have become available in the USA, viz. sumatriptan (Ravikumar et al., 2006), zolmitriptan (Ravikumar et al., 2007a), naratriptan (Massiou, 2001), rizatriptan (Ravikumar et al., 2007b), frovatriptan (Balbisi, 2006), eletriptan (Goadsby et al., 2000) and almotriptan (Ravikumar et al., 2008). Indole derivatives are also of great importance for the synthesis of pyrroloindoles and carbazoles via Diels–Adler cycloaddition or Suzuki–Miyaura reactions (Wenkert et al., 1988; Gribble, 2003; Pathak et al., 2006) or for nucleophilic addition reactions (Agbalyan et al., 1974; Ottoni et al., 1998; Pelkey et al., 1999).

3-Acetylindole, (I), and indole-3-carboxaldehyde have been the subject of a study by us of the generation mechanism of the IR spectra of hydrogen-bonded molecular crystals (Flakus & Hachuła, 2008; Hachuła et al., 2008). Measurement of the IR spectra of polycrystalline and monocrystalline samples of the indole derivatives and theoretical analysis of the results was mainly focused on spectroscopic effects corresponding to the intensity distribution, the influence of temperature, linear dichroism, and the isotopic substitution of deuterium in the above-mentioned molecules measured in the frequency range of the proton and the deuterium stretching vibration bands, ν_N–H and ν_N–D, respectively. These spectroscopic studies were preceded by an analysis of the X-ray crystal structures of the compounds. The crystal structure of indole-3-carboxaldehyde has been described previously (Ng, 2007). The molecules of this compound are linked into linear [helical in orginal article?] chains along the crystallographic c axis by intermolecular N—H···O hydrogen bonds. The structure of (I) has not yet been reported.

Compound (I) crystallizes with one molecule in the asymmetric unit (Fig. 1). The five- and six-membered rings are essentially planar, with r.m.s. deviations from the mean plane of 0.0178 Å. The largest deviations from the least-squares indole plane are observed for atoms C4 [-0.0304 (15) Å] and C6 [0.0225 (16) Å]. Atom N1 is out of the indole plane by -0.0185 (13) Å. The dihedral angle between the planes of the pyrrole and benzene rings is 2.05 (11)°. By comparison, this angle is 4.22° in indole-3-carboxaldehyde (Ng, 2007) and 0.29° in indole-3-carboxylic acid (Smith et al., 2003). The N1—C1 and N1—C8 bond lengths [1.392 (3) and 1.342 (3) Å] differ from the corresponding mean values of 1.372 (7) and 1.370 (12) Å, respectively, reported for the indole ring system by Allen et al. (1987). This significant asymmetry of the two endocyclic N—C bonds of the heterocyclic ring of (I) may be a result of the electron-withdrawing character of the acetyl group and the preferential conjugation of the C9═O1 bond with C7═C8. Moreover, the N1—C8 bond in (I) is shortened, whereas C7═C8 is elongated (Table 1). The C—C bond opposite to the heteroatom is considerably longer than the others. An almost identical shortening of N1—C8 and lengthening of the C7═C8 double bond are found in similar structures, e.g. indole-3-carboxaldehyde (Ng, 2007), 3-acetyl-1-methoxyindole (Acheson et al., 1980), indole-3-carboxylic acid (Smith et al., 2003) and indole-3-acetic acid (Karle et al., 1964), or in other indole derivatives possessing a 3-carbonyl group but which are unsubstituted at the ring N atom (Damak & Riche, 1977; Hu et al., 2005). This fact is consistent with electron delocalization from the N atom into the acetyl group. Thus, the substitution of an electronegative O atom on the pyrrole ring makes little difference to the π-donor ability of N (Morrin Acheson et al., 1980). The sum of the angles around the indole N atom is 359.88°, which indicates that the geometry around N is normal sp² coordination, as expected for π-conjugation of the indole ring (Huang et al., 2004). The endocyclic C—C bond distances and the bond angles in (I) are in the normal ranges and are comparable with those of other indole derivatives (Allen et al., 1987).

The acetyl group is almost coplanar with the heterocyclic ring [torsion angles C8—C7—C9—O1 = -176.80 (18)° and C6—C7—C9—C10 = -177.63 (17)°]. The dihedral angle between the plane of the indole ring system and the plane of the acetyl group, O1—C9—C10, is 1.75 (17)°. The C═O bond distance and O—C—C bond angle are similar to those in indole-3-carboxaldehyde and 3-acetyl-1-methoxyindole [C9—O1 = 1.228 (2) Å and O1—C9—C7 = 124.71 (18)°, and C9—O1 = 1.224 (2) Å and O1—C9—C7 = 120.9°, respectively]. The geometry of the acetyl group is governed by the repulsive interaction between the O1 carbonyl group and the heterocyclic ring, leading to an enlargement of the O1—C9—C7 and C9—C7—C6 angles and a diminution of O1—C9—C10 and C7—C9—C10 (Table 1). A similar repulsive interaction between the lone pairs on atom O1 and the neighbouring atoms of the indole ring system is observed in indole-3-carboxaldehyde (Ng, 2007). The crystal structure similarity between indole-3-carboxaldehyde and (I) leads to the conclusion that the replacement of the H atom in the aldehyde group of indole-3-carboxaldehyde by a methyl group does not significantly influence the crystal lattice parametrs.

There are four molecules in the unit cell at the symmetry positions (x, y, z), (3/2 - x, 1/2 + y, 1/2 - z), (1 - x, 1 - y, 1 - z) and (x - 1/2, 1/2 - y, 1/2 + z). Each of these molecules is linked by a single N—H···O hydrogen bond to the other two, forming zigzag chains. Atom N1 of the pyrrole N—H group in the molecule at (x, y, z) acts as a hydrogen-bond donor via atom H1 to carbonyl atom O1 belonging to the molecule at (1/2 + x, 1/2 - y, 1/2 + z) (Fig. 2). The result of this interaction is the formation of hydrogen-bonded chain with a graph-set motif of C(6) (Etter et al., 1990; Bernstein et al., 1995) running along the [101] direction. In the crystal structure of (I), two such chains, related to one another by an inversion centre symmetry operation, pass through each unit cell (Fig. 3). The same graph-set motif of C(6) is observed in indole-3-carboxaldehyde (Ng, 2007) and methyl indole-3-carboxylate (Hu et al., 2005). Similar molecular packing can also be found in 3-acetoxyindole (Chakraborty et al., 1991), in which the molecules are connected through N—H···O hydrogen bonds to form C(7) chains. Judging from the bond distances, the N—H···O hydrogen bond between two 3-acetylindole molecules appears to be slightly stronger [N1—H1···O1 = 2.788 (2) Å] than that involving two indole-3-carboxaldehyde molecules [N1—H1···O1 = 2.826 (2) Å]. The details of the hydrogen-bonding interactions are shown in Figs. 2 and 3 and given in Table 2.

The polycrystalline spectrum of (I) is shown in Fig. 4. The values of the H—N and N···O distances, as well as the N—H···O angle (Table 2), characterize this bond as a medium-strength hydrogen bond (Desiraju & Steiner, 1999; Steiner, 2002). The strength of the hydrogen bond in (I) is supported by spectroscopic measurements. The ν_N—H proton stretching vibration band of (I) extends over a frequency range of 3300–2400 cm^-1. The polycrystalline N—H band is shifted towards the lower frequencies by ca 280 cm^-1 compared with the unperturbed value of 3400 cm^-1. This shift in the N—H stretching frequency proves that this N—H··· O hydrogen bond is of medium strength. A familiar correlation between the hydrogen-bond energy and the frequency shift of the proton (or deuteron) stretching vibration band is used to justify this statement (Schuster et al., 1976; Schuster & Mikenda, 1999). The N—H···O bond length [N1···O1 = 2.788 (2) Å] in (I) appears to be slightly shorter than the those in other compounds, e.g. the N-methylamide derivatives [mean N···O distance 2.85 Å; Leiserowitz & Tuval, 1978]. Consequently, the stronger N—H···O hydrogen bonds correspond to a larger frequency shift.

S2. Experimental

3-Acetylindole (98% pure), purchased from Sigma–Aldrich, was dissolved in a mixture of acetone and water (1:1 v/v). After a few weeks, small single crystals of (I), suitable for X-ray diffraction, were grown from the solution by slow evaporation at 293 K. The IR spectrum of a polycrystalline sample of (I) dispersed in KBr was measured at the temperature of liquid nitrogen using an FT–IR Nicolet Magna 560 spectrometer operating at a resolution of 2 cm^-1. The IR spectrum was recorded in the range 1000–4000 cm^-1 using an Ever-Glo source, a KBr beamsplitter and a DTGS detector.

S3. Refinement

Aromatic H atoms were treated as riding on their parent C atoms, with C—H = 0.96 Å, and with U_iso(H) = 1.2U_eq(C). Methyl H atoms were also treated as riding on their parent C atoms, with C—H = 0.93 Å, and U_iso(H) = 1.5U_eq(C). Atom H1, which takes part in hydrogen bonding, was located in a difference Fourier map (ΔF) and refined freely with isotropic displacement parameters. [Please check rephrasing to reflect that only one atom was treated in this way]

Computing details

Data collection: CrysAlis CCD (Oxford Diffraction, 2006); cell refinement: CrysAlis RED (Oxford Diffraction, 2006); data reduction: CrysAlis RED (Oxford Diffraction, 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997) and Mercury (Macrae et al., 2006); software used to prepare material for publication: publCIF (Westrip, 2008).

Figures

	Fig. 1. The asymmetric unit of (I), with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. Part of the molecular framework of (I), viewed along the a axis, showing the C(6) chains. Atoms marked with an asterisk (*) or an ampersand (&) are at the symmetry positions (1/2 + x, 1/2 - y, 1/2 + z) or (x - 1/2, 1/2 - y, z - 1/2), respectively. Dashed lines indicate hydrogen-bonding interactions. For the sake of clarity, all H atoms bonded to C atoms have been omitted.
	Fig. 3. Part of the crystal structure of (I), showing the formation of the sheets via C(6) chains. The C atoms of the methyl groups and all H atoms not involved in hydrogen bonding have been omitted for clarity.
	Fig. 4. IR spectrum of a sample of 3-acetylindole dispersed in a KBr pellet.

3-acetylindole

Crystal data

C10H9NO	F(000) = 336
Mr = 159.18	Dx = 1.309 Mg m^−3
Monoclinic, P21/n	Melting point = 461–465 K
Hall symbol: -P 2yn	Mo Kα radiation, λ = 0.71073 Å
a = 9.5665 (19) Å	Cell parameters from 1709 reflections
b = 7.6553 (15) Å	θ = 2.8–32.8°
c = 11.031 (2) Å	µ = 0.09 mm^−1
β = 90.77 (3)°	T = 110 K
V = 807.8 (3) Å^3	Plate, colourless
Z = 4	0.54 × 0.32 × 0.03 mm

Data collection

Oxford Diffraction KM-4-CCD Sapphire3 diffractometer	974 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.069
Graphite monochromator	θmax = 25.0°, θmin = 2.8°
ω scans	h = −11→11
4759 measured reflections	k = −4→9
1405 independent reflections	l = −13→13

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)] = 0.048	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.117	H atoms treated by a mixture of independent and constrained refinement
S = 1.00	w = 1/[σ^2(Fo^2) + (0.0626P)^2] where P = (Fo^2 + 2Fc^2)/3
1405 reflections	(Δ/σ)max < 0.001
114 parameters	Δρmax = 0.23 e Å^−3
0 restraints	Δρmin = −0.32 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
O1	0.27957 (16)	0.17171 (18)	0.27207 (13)	0.0328 (4)
C1	0.6625 (2)	0.1790 (2)	0.47915 (17)	0.0212 (5)
C2	0.7988 (2)	0.1203 (2)	0.46763 (19)	0.0284 (5)
H2	0.8672	0.1404	0.5293	0.034*
C3	0.8308 (2)	0.0312 (2)	0.3624 (2)	0.0309 (5)
H3	0.9232	−0.0110	0.3516	0.037*
C4	0.7306 (2)	0.0020 (2)	0.27215 (19)	0.0288 (5)
H4	0.7553	−0.0628	0.2022	0.035*
C5	0.5958 (2)	0.0653 (2)	0.28195 (18)	0.0255 (5)
H5	0.5290	0.0481	0.2185	0.031*
C6	0.5597 (2)	0.1557 (2)	0.38817 (17)	0.0201 (5)
C7	0.4321 (2)	0.2334 (2)	0.43329 (16)	0.0215 (5)
C8	0.4657 (2)	0.2961 (2)	0.54712 (18)	0.0228 (5)
H8	0.4018	0.3538	0.5988	0.027*
C9	0.2987 (2)	0.2394 (2)	0.37279 (17)	0.0233 (5)
C10	0.1788 (2)	0.3329 (3)	0.43273 (19)	0.0288 (5)
H10A	0.1839	0.4580	0.4145	0.043*
H10B	0.1850	0.3156	0.5207	0.043*
H10C	0.0900	0.2858	0.4019	0.043*
N1	0.60021 (19)	0.2651 (2)	0.57561 (15)	0.0244 (4)
H1	0.654 (2)	0.288 (3)	0.649 (2)	0.036 (6)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0364 (10)	0.0411 (8)	0.0206 (9)	0.0021 (7)	−0.0071 (7)	−0.0027 (6)
C1	0.0244 (12)	0.0209 (9)	0.0183 (11)	−0.0026 (8)	0.0035 (8)	0.0045 (7)
C2	0.0273 (14)	0.0311 (11)	0.0266 (13)	−0.0050 (9)	−0.0024 (10)	0.0076 (9)
C3	0.0275 (13)	0.0323 (11)	0.0329 (13)	0.0027 (9)	0.0078 (10)	0.0078 (9)
C4	0.0347 (14)	0.0271 (10)	0.0249 (13)	0.0016 (10)	0.0115 (10)	0.0020 (9)
C5	0.0308 (14)	0.0256 (10)	0.0202 (11)	−0.0032 (9)	0.0023 (9)	0.0027 (8)
C6	0.0239 (12)	0.0198 (9)	0.0167 (11)	−0.0027 (8)	0.0026 (9)	0.0036 (7)
C7	0.0288 (13)	0.0201 (9)	0.0155 (10)	−0.0025 (8)	−0.0005 (8)	0.0033 (8)
C8	0.0256 (13)	0.0227 (10)	0.0200 (11)	−0.0004 (8)	0.0002 (9)	0.0029 (8)
C9	0.0299 (14)	0.0235 (10)	0.0164 (11)	−0.0034 (9)	−0.0022 (9)	0.0053 (8)
C10	0.0280 (13)	0.0314 (11)	0.0271 (13)	0.0007 (9)	−0.0004 (9)	0.0041 (9)
N1	0.0278 (12)	0.0287 (9)	0.0165 (9)	−0.0034 (8)	−0.0025 (8)	0.0020 (7)

Geometric parameters (Å, º)

O1—C9	1.238 (2)	C5—H5	0.9500
C1—C2	1.387 (3)	C6—C7	1.453 (3)
C1—N1	1.392 (3)	C7—C8	1.378 (3)
C1—C6	1.407 (3)	C7—C9	1.433 (3)
C2—C3	1.384 (3)	C8—N1	1.342 (3)
C2—H2	0.9500	C8—H8	0.9500
C3—C4	1.391 (3)	C9—C10	1.512 (3)
C3—H3	0.9500	C10—H10A	0.9800
C4—C5	1.383 (3)	C10—H10B	0.9800
C4—H4	0.9500	C10—H10C	0.9800
C5—C6	1.408 (3)	N1—H1	0.97 (2)
C2—C1—N1	129.50 (19)	C8—C7—C9	127.51 (19)
C2—C1—C6	122.84 (19)	C8—C7—C6	105.53 (18)
N1—C1—C6	107.66 (18)	C9—C7—C6	126.95 (17)
C3—C2—C1	117.11 (19)	N1—C8—C7	111.31 (19)
C3—C2—H2	121.4	N1—C8—H8	124.3
C1—C2—H2	121.4	C7—C8—H8	124.3
C2—C3—C4	121.4 (2)	O1—C9—C7	121.66 (19)
C2—C3—H3	119.3	O1—C9—C10	119.16 (18)
C4—C3—H3	119.3	C7—C9—C10	119.17 (17)
C5—C4—C3	121.5 (2)	C9—C10—H10A	109.5
C5—C4—H4	119.2	C9—C10—H10B	109.5
C3—C4—H4	119.2	H10A—C10—H10B	109.5
C4—C5—C6	118.43 (19)	C9—C10—H10C	109.5
C4—C5—H5	120.8	H10A—C10—H10C	109.5
C6—C5—H5	120.8	H10B—C10—H10C	109.5
C5—C6—C1	118.68 (19)	C8—N1—C1	108.88 (17)
C5—C6—C7	134.68 (19)	C8—N1—H1	131.1 (14)
C1—C6—C7	106.62 (17)	C1—N1—H1	119.9 (14)
N1—C1—C2—C3	177.25 (18)	C1—C6—C7—C8	−0.5 (2)
C6—C1—C2—C3	−1.8 (3)	C5—C6—C7—C9	−1.2 (3)
C1—C2—C3—C4	0.1 (3)	C1—C6—C7—C9	−179.14 (17)
C2—C3—C4—C5	1.9 (3)	C9—C7—C8—N1	178.82 (17)
C3—C4—C5—C6	−2.2 (3)	C6—C7—C8—N1	0.2 (2)
C4—C5—C6—C1	0.5 (3)	C8—C7—C9—O1	−176.80 (18)
C4—C5—C6—C7	−177.26 (18)	C6—C7—C9—O1	1.5 (3)
C2—C1—C6—C5	1.5 (3)	C8—C7—C9—C10	4.1 (3)
N1—C1—C6—C5	−177.72 (16)	C6—C7—C9—C10	−177.63 (17)
C2—C1—C6—C7	179.86 (16)	C7—C8—N1—C1	0.2 (2)
N1—C1—C6—C7	0.63 (19)	C2—C1—N1—C8	−179.68 (19)
C5—C6—C7—C8	177.5 (2)	C6—C1—N1—C8	−0.5 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1^i	0.97 (2)	1.83 (2)	2.788 (2)	171 (2)

Symmetry code: (i) x+1/2, −y+1/2, z+1/2.