1-(1H-Indol-3-ylcarbonyl)-N-(4-methoxy­benzyl)formamide

In the title compound, C₁₈H₁₆N₂O₃, the indole ring is planar and the two adjacent carbonyl groups are mutually trans oriented with a torsion angle of 144.8 (3)°. The single C—C bond linking the two carbonyl functionalities is 1.539 (4) Å. Mol­ecules are linked into a two-dimensional network by inter­molecular N—H...O hydrogen bonds.

S1. Comment

N-(Indol-3-ylglyoxylyl)benzylamine derivatives exhibit high affinity for the benzodiazepine receptor (BzR), with K_i values ranging from 67 to 11 nM (Da Settimo et al., 1996). In addition to their biological activities, these N-(indol-3-ylglyoxylyl)benzylamines are very good synthons for the preparation of N-benzyl-substituted tryptamines (Da Settimo et al., 1996). The title compound, (I), is a synthetic intermediate in the preparation of N-(4-methoxybenzyl)tryptamine and is prepared by treating indole with oxalyl chloride followed by quenching with 4-methoxybenzylamine. The product was characterized by spectroscopic analysis and its X-ray structure determination was carried out to study the conformation of the molecule.

X-ray crystallography confirmed the molecular structure and atom connectivity for (I), and selected geometric parameters are listed in Table 1. The indole ring is planar [From the Section Editor: Please see Abstract], with bond distances and angles comparable with those previously reported for indole derivatives (Mason et al., 2003). The two carbonyl groups are in a trans orientation, with an O1—C9—C10—O2 torsion angle of 144.8 (3)°. Since the C9═O1 group is coplanar with the indole nucleus, extended conjugation is present, from the O1 atom through to the indole ring. This is also evident from the C2—C9 bond length [1.437 (4) Å], which is shortened in comparison with the standard value for a single bond connecting a C_ar atom to a Csp² atom [1.470 (15) Å; Wilson, 1992]. Because of the above, the C9—C10 bond length of 1.539 (4) Å is longer than expected, the characteristic value for a Csp²—Csp² bond being 1.50 Å (Zukerman-Schpector et al., 1994).

The C10—N11 bond length [1.337 (4) Å] and the bond angles around atom N11 suggest that the lone pair of electrons on N11 undergoes delocalization, affording double-bond character to the C10—N11 bond and forcing the O2/C10/N11/C12 atoms into an almost planar conformation. [From the Section Editor: Please clarify the next sentence: `amide group' intended?] The 4-methoxyphenyl ring makes a dihedral angle of 74.55 (12)° with the amide bond. The observed O3—C16 [1.376 (3) Å] and O3—C19 [1.428 (3) Å] bond lengths are comparable with values found for aromatic methoxy O—CH₃ bonds. There is an asymmetry of the exocyclic angles at C16 for (I) [O3—C16—C15 115.1 (3)° and O3—C16—C17 124.8 (3)°], as is typical of anisoles. This is caused by the tendency of the methoxy group to be coplanar with the phenyl ring, due to conjugation of the O3 lone pair with the phenyl ring (Domiano et al., 1979).

The packing of compound (I), as viewed down the c axis, is illustrated in Fig. 2. Amides participate in extensive hydrogen bonding, but here, in addition to secondary amide functionality, a carbonyl group acts as a hydrogen-bond acceptor and the glyoxylamide torsion angle is variable. The molecules are linked by intermolecular hydrogen bonds [N1···O1ⁱ 2.944 (3) Å, H1N···O1ⁱ 2.08 (3) Å and N1—H1N···O1ⁱ 165 °, and N11···O2ⁱⁱ 2.881 (3) Å, H11···O2ⁱⁱ 2.04 (3) Å and N11—H11···O2ⁱⁱ 159°; symmetry codes: (i) 1 + x, y − 1, z; (ii) x − 1, y, z], resulting in a two-dimensional network, details of which are given in Table 2. In addition, two weak intramolecular hydrogen bonds, N11—H11···O1 and C1—H1···O2 (Table 2), form five- and six-membered rings, respectively. These weak hydrogen bonds introduce rigidity into the system (Black et al., 1996).

S2. Experimental

The title compound was prepared using the previously reported procedure of Da Settimo et al. (1996). The compound was obtained as pale-yellow crystals. Spectroscopic analysis: ¹H NMR (DMSO, δ, p.p.m.): 3.73 (s, 3H), 4.35 (d, 2H), 6.90 (d, 2H), 7.20–7.30 (m, 4H), 7.6 (m, 1H), 8.3 (m, 1H), 8.76 (d, 1H), 9.23 (t, 1H), 12.22 (s, 1H); ¹³C NMR (DMSO, δ, p.p.m.): 41.5, 55.0, 112.1, 112.4, 113.6, 121.1, 122.4, 123.3, 126.0, 128.6, 130.8, 136.1, 138.3, 158.1, 163.3, 181.9.

S3. Refinement

All H atoms were located in difference Fourier syntheses, and were subsequently positioned geometrically and refined with a riding model. Bond distances to parent atoms were set to 0.95 (C_ar—H), 0.98 (C_Me—H), 0.99 (C_sec—H) or 0.88 (N—H) Å, and U_iso(H) = 1.2U_eq(C_ar—H, C_sec—H or N—H) or 1.5U_eq(C_Me—H). Friedel opposites were merged before the final cycles of least-squares refinement.

Computing details

Data collection: COLLECT (Nonius, 1999); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO-SMN (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP in SHELXTL/PC (Siemens, 1995); software used to prepare material for publication: SHELXL97 and local procedures.

Figures

	Fig. 1. A view of the asymmetric unit of (I), showing 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. A packing diagram for (I), viewed approximately down the c axis, showing the hydrogen-bonding interactions (dashed lines). For clarity, only those H atoms involved in hydrogen bonding are shown. [From the Section Editor: Include different shading and definitions thereof for C, N and O atoms?]

1-(1H-Indol-3-ylcarbonyl)-N-(4-methoxybenzyl)formamide

Crystal data

C18H16N2O3	F(000) = 324
Mr = 308.33	Dx = 1.407 Mg m^−3
Monoclinic, Pn	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P -2yac	Cell parameters from 1741 reflections
a = 4.9402 (2) Å	θ = 1.0–27.5°
b = 5.6847 (3) Å	µ = 0.10 mm^−1
c = 25.9862 (13) Å	T = 90 K
β = 94.495 (2)°	Slab, colourless
V = 727.54 (6) Å^3	0.25 × 0.22 × 0.08 mm
Z = 2

Data collection

Nonius KappaCCD area-detector diffractometer	1663 independent reflections
Radiation source: fine-focus sealed tube	1336 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.037
Detector resolution: 18 pixels mm^-1	θmax = 27.5°, θmin = 1.6°
ω scans at fixed χ = 55°	h = −6→6
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997)	k = −7→7
Tmin = 0.976, Tmax = 0.992	l = −33→33
3052 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.039	H-atom parameters constrained
wR(F^2) = 0.091	w = 1/[σ^2(Fo^2) + (0.0385P)^2 + 0.1457P] where P = (Fo^2 + 2Fc^2)/3
S = 1.07	(Δ/σ)max < 0.001
1663 reflections	Δρmax = 0.21 e Å^−3
210 parameters	Δρmin = −0.21 e Å^−3
2 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.019 (5)

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. The quoted Flack x(u) parameter is from the penultimate round of refinement, and although such a value has no physical interpretation, this does not mean that it conveys no information; it serves to show that the data and refinement behave in the expected manner.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
N1	0.8284 (4)	0.1538 (5)	0.49905 (9)	0.0230 (6)
H1N	0.9528	0.0506	0.4919	0.028*
O1	0.2239 (4)	0.7693 (4)	0.49321 (8)	0.0239 (5)
O2	0.7317 (4)	0.7678 (4)	0.40948 (8)	0.0241 (5)
O3	−0.4712 (4)	1.5324 (4)	0.24371 (8)	0.0254 (5)
C1	0.7525 (6)	0.3408 (6)	0.46990 (12)	0.0228 (7)
H1	0.8243	0.3806	0.4382	0.027*
C2	0.5532 (5)	0.4682 (5)	0.49286 (11)	0.0203 (6)
C3	0.5056 (5)	0.3455 (5)	0.54002 (11)	0.0206 (6)
C4	0.3310 (6)	0.3769 (6)	0.57925 (11)	0.0230 (7)
H4	0.2121	0.5083	0.5790	0.028*
C5	0.3353 (6)	0.2126 (6)	0.61845 (12)	0.0245 (7)
H5	0.2170	0.2324	0.6453	0.029*
C6	0.5090 (6)	0.0174 (6)	0.61981 (12)	0.0266 (7)
H6	0.5049	−0.0929	0.6472	0.032*
C7	0.6859 (6)	−0.0169 (6)	0.58199 (11)	0.0242 (7)
H7	0.8064	−0.1473	0.5829	0.029*
C8	0.6798 (6)	0.1486 (5)	0.54225 (11)	0.0212 (6)
C9	0.4103 (5)	0.6720 (5)	0.47244 (11)	0.0197 (6)
C10	0.4931 (5)	0.7685 (5)	0.42063 (11)	0.0188 (6)
N11	0.2883 (5)	0.8522 (5)	0.38916 (10)	0.0210 (6)
H11	0.1238	0.8608	0.3998	0.025*
C12	0.3381 (6)	0.9294 (6)	0.33691 (11)	0.0230 (7)
H12A	0.3599	0.7896	0.3149	0.028*
H12B	0.5096	1.0200	0.3383	0.028*
C13	0.1117 (6)	1.0791 (5)	0.31306 (11)	0.0217 (7)
C14	0.0578 (6)	1.2981 (6)	0.33339 (11)	0.0217 (7)
H14	0.1601	1.3494	0.3638	0.026*
C15	−0.1407 (6)	1.4436 (5)	0.31056 (12)	0.0221 (7)
H15	−0.1761	1.5921	0.3254	0.027*
C16	−0.2894 (6)	1.3701 (5)	0.26528 (11)	0.0204 (6)
C17	−0.2453 (6)	1.1502 (5)	0.24511 (11)	0.0210 (6)
H17	−0.3509	1.0971	0.2152	0.025*
C18	−0.0440 (5)	1.0069 (6)	0.26906 (11)	0.0210 (6)
H18	−0.0125	0.8561	0.2549	0.025*
C19	−0.6412 (6)	1.4591 (6)	0.19967 (12)	0.0287 (7)
H19A	−0.5281	1.4105	0.1722	0.043*
H19B	−0.7582	1.5900	0.1874	0.043*
H19C	−0.7538	1.3265	0.2091	0.043*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0156 (12)	0.0248 (15)	0.0290 (14)	0.0065 (11)	0.0046 (11)	0.0012 (11)
O1	0.0169 (10)	0.0287 (12)	0.0265 (11)	0.0047 (9)	0.0049 (8)	−0.0002 (10)
O2	0.0129 (10)	0.0291 (12)	0.0307 (12)	−0.0004 (10)	0.0046 (8)	0.0016 (9)
O3	0.0198 (11)	0.0253 (12)	0.0304 (11)	0.0054 (9)	−0.0024 (8)	−0.0007 (10)
C1	0.0188 (16)	0.0253 (17)	0.0246 (15)	−0.0002 (13)	0.0040 (12)	−0.0012 (13)
C2	0.0162 (14)	0.0243 (17)	0.0206 (14)	0.0023 (13)	0.0015 (11)	0.0006 (13)
C3	0.0140 (14)	0.0207 (16)	0.0272 (15)	−0.0006 (12)	0.0015 (12)	−0.0025 (12)
C4	0.0179 (15)	0.0259 (18)	0.0256 (15)	0.0010 (13)	0.0031 (12)	−0.0028 (13)
C5	0.0176 (15)	0.0310 (18)	0.0254 (15)	0.0026 (14)	0.0058 (12)	0.0013 (15)
C6	0.0261 (16)	0.0290 (18)	0.0246 (15)	−0.0017 (14)	0.0021 (12)	0.0032 (13)
C7	0.0199 (14)	0.0240 (17)	0.0284 (17)	0.0022 (14)	0.0005 (12)	0.0009 (14)
C8	0.0175 (14)	0.0219 (16)	0.0242 (14)	0.0001 (13)	0.0003 (11)	−0.0003 (13)
C9	0.0137 (14)	0.0213 (16)	0.0239 (15)	−0.0010 (13)	0.0013 (11)	0.0005 (12)
C10	0.0129 (15)	0.0180 (16)	0.0252 (14)	−0.0002 (12)	0.0008 (12)	−0.0033 (12)
N11	0.0122 (11)	0.0266 (14)	0.0248 (12)	0.0015 (11)	0.0048 (9)	0.0018 (11)
C12	0.0164 (14)	0.0278 (17)	0.0256 (16)	0.0026 (13)	0.0072 (12)	0.0040 (13)
C13	0.0154 (14)	0.0266 (18)	0.0238 (15)	0.0003 (13)	0.0050 (12)	0.0031 (13)
C14	0.0157 (14)	0.0258 (17)	0.0236 (15)	−0.0058 (13)	0.0019 (12)	−0.0010 (13)
C15	0.0189 (15)	0.0222 (17)	0.0259 (15)	0.0002 (13)	0.0062 (12)	−0.0008 (13)
C16	0.0161 (14)	0.0222 (16)	0.0236 (15)	−0.0003 (12)	0.0049 (12)	0.0007 (13)
C17	0.0197 (14)	0.0240 (17)	0.0198 (14)	−0.0026 (13)	0.0049 (12)	0.0017 (13)
C18	0.0187 (14)	0.0191 (16)	0.0259 (16)	0.0003 (13)	0.0066 (12)	0.0003 (13)
C19	0.0220 (16)	0.0358 (19)	0.0274 (16)	0.0002 (14)	−0.0035 (13)	0.0005 (15)

Geometric parameters (Å, º)

N1—C1	1.342 (4)	C9—C10	1.539 (4)
N1—C8	1.389 (4)	C10—N11	1.337 (4)
N1—H1N	0.8800	N11—C12	1.466 (4)
O1—C9	1.234 (4)	N11—H11	0.8800
O2—C10	1.235 (3)	C12—C13	1.500 (4)
O3—C16	1.376 (3)	C12—H12A	0.9900
O3—C19	1.428 (3)	C12—H12B	0.9900
C1—C2	1.394 (4)	C13—C14	1.387 (4)
C1—H1	0.9500	C13—C18	1.389 (4)
C2—C9	1.437 (4)	C14—C15	1.381 (4)
C2—C3	1.445 (4)	C14—H14	0.9500
C3—C4	1.398 (4)	C15—C16	1.401 (4)
C3—C8	1.410 (4)	C15—H15	0.9500
C4—C5	1.381 (4)	C16—C17	1.379 (4)
C4—H4	0.9500	C17—C18	1.394 (4)
C5—C6	1.401 (5)	C17—H17	0.9500
C5—H5	0.9500	C18—H18	0.9500
C6—C7	1.379 (4)	C19—H19A	0.9800
C6—H6	0.9500	C19—H19B	0.9800
C7—C8	1.396 (4)	C19—H19C	0.9800
C7—H7	0.9500
C1—N1—C8	109.4 (2)	C10—N11—C12	119.9 (2)
C1—N1—H1N	125.3	C10—N11—H11	120.0
C8—N1—H1N	125.3	C12—N11—H11	120.0
C16—O3—C19	117.1 (2)	N11—C12—C13	112.3 (2)
N1—C1—C2	110.2 (3)	N11—C12—H12A	109.2
N1—C1—H1	124.9	C13—C12—H12A	109.2
C2—C1—H1	124.9	N11—C12—H12B	109.2
C1—C2—C9	127.2 (3)	C13—C12—H12B	109.2
C1—C2—C3	106.3 (3)	H12A—C12—H12B	107.9
C9—C2—C3	126.5 (3)	C14—C13—C18	117.9 (3)
C4—C3—C8	118.7 (3)	C14—C13—C12	120.7 (3)
C4—C3—C2	135.0 (3)	C18—C13—C12	121.3 (3)
C8—C3—C2	106.2 (2)	C15—C14—C13	121.7 (3)
C5—C4—C3	118.5 (3)	C15—C14—H14	119.2
C5—C4—H4	120.8	C13—C14—H14	119.2
C3—C4—H4	120.8	C14—C15—C16	119.3 (3)
C4—C5—C6	121.9 (3)	C14—C15—H15	120.3
C4—C5—H5	119.1	C16—C15—H15	120.3
C6—C5—H5	119.1	O3—C16—C17	124.8 (3)
C7—C6—C5	121.0 (3)	O3—C16—C15	115.1 (3)
C7—C6—H6	119.5	C17—C16—C15	120.1 (3)
C5—C6—H6	119.5	C16—C17—C18	119.2 (3)
C6—C7—C8	117.0 (3)	C16—C17—H17	120.4
C6—C7—H7	121.5	C18—C17—H17	120.4
C8—C7—H7	121.5	C13—C18—C17	121.6 (3)
N1—C8—C7	129.1 (3)	C13—C18—H18	119.2
N1—C8—C3	108.0 (3)	C17—C18—H18	119.2
C7—C8—C3	122.9 (3)	O3—C19—H19A	109.5
O1—C9—C2	124.2 (3)	O3—C19—H19B	109.5
O1—C9—C10	118.8 (3)	H19A—C19—H19B	109.5
C2—C9—C10	117.0 (2)	O3—C19—H19C	109.5
O2—C10—N11	123.2 (3)	H19A—C19—H19C	109.5
O2—C10—C9	121.9 (2)	H19B—C19—H19C	109.5
N11—C10—C9	114.9 (2)
C8—N1—C1—C2	0.7 (3)	C3—C2—C9—C10	−178.6 (3)
N1—C1—C2—C9	−176.5 (3)	O1—C9—C10—O2	144.8 (3)
N1—C1—C2—C3	−0.1 (3)	C2—C9—C10—O2	−36.8 (4)
C1—C2—C3—C4	−178.2 (3)	O1—C9—C10—N11	−35.2 (4)
C9—C2—C3—C4	−1.8 (5)	C2—C9—C10—N11	143.3 (3)
C1—C2—C3—C8	−0.5 (3)	O2—C10—N11—C12	5.5 (4)
C9—C2—C3—C8	176.0 (3)	C9—C10—N11—C12	−174.6 (3)
C8—C3—C4—C5	−0.5 (4)	C10—N11—C12—C13	−163.5 (3)
C2—C3—C4—C5	177.1 (3)	N11—C12—C13—C14	65.6 (3)
C3—C4—C5—C6	0.1 (4)	N11—C12—C13—C18	−116.7 (3)
C4—C5—C6—C7	0.7 (5)	C18—C13—C14—C15	−1.1 (4)
C5—C6—C7—C8	−1.1 (4)	C12—C13—C14—C15	176.8 (3)
C1—N1—C8—C7	178.0 (3)	C13—C14—C15—C16	−0.9 (4)
C1—N1—C8—C3	−0.9 (3)	C19—O3—C16—C17	5.4 (4)
C6—C7—C8—N1	−178.1 (3)	C19—O3—C16—C15	−175.6 (3)
C6—C7—C8—C3	0.7 (4)	C14—C15—C16—O3	−176.3 (3)
C4—C3—C8—N1	179.0 (3)	C14—C15—C16—C17	2.8 (4)
C2—C3—C8—N1	0.8 (3)	O3—C16—C17—C18	176.3 (3)
C4—C3—C8—C7	0.0 (4)	C15—C16—C17—C18	−2.6 (4)
C2—C3—C8—C7	−178.2 (3)	C14—C13—C18—C17	1.2 (4)
C1—C2—C9—O1	175.5 (3)	C12—C13—C18—C17	−176.6 (3)
C3—C2—C9—O1	−0.2 (5)	C16—C17—C18—C13	0.6 (4)
C1—C2—C9—C10	−2.9 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O1^i	0.88	2.08	2.944 (3)	165
N11—H11···O2^ii	0.88	2.04	2.881 (3)	159
N11—H11···O1	0.88	2.49	2.787 (3)	100
C1—H1···O2	0.95	2.36	2.888 (4)	115

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