5-Bromo-1H-pyrrolo­[2,3-b]pyridine

Abstract

In the title compound, C₇H₅BrN₂, fused six-membered pyridine and five-membered pyrrole rings form the essentially planar aza­indole skeleton (r.m.s. deviation = 0.017 Å). In the crystal, pairs of N—H⋯N hydrogen bonds connect the mol­ecules into inversion dimers.

Related literature  

For the structure of 7-aza­indole (C₇H₆N₂), see: Dufour et al. (1990 ▶) and for the structure of 3-iodo-7-aza­indole (C₇H₅IN₂), see: Chou et al. (2000 ▶). For the utilization of the title compound as the N-donor carrier ligand of highly cytotoxic platinum(II) dichlorido complexes, see: Štarha et al. (2012 ▶).

Experimental  

Crystal data  

• C₇H₅BrN₂

• M _r = 197.04

• Monoclinic,

• a = 8.9082 (4) Å

• b = 13.3632 (6) Å

• c = 5.8330 (3) Å

• β = 103.403 (5)°

• V = 675.47 (6) ų

• Z = 4

• Mo Kα radiation

• μ = 6.00 mm⁻¹

• T = 100 K

• 0.24 × 0.24 × 0.12 mm

Data collection  

• Oxford Diffraction Xcalibur Sapphire2 CCD diffractometer

• Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2009 ▶) T _min = 0.327, T _max = 0.533

• 3977 measured reflections

• 1185 independent reflections

• 1047 reflections with I > 2σ(I)

• R _int = 0.022

Refinement  

• R[F ² > 2σ(F ²)] = 0.035

• wR(F ²) = 0.092

• S = 1.13

• 1185 reflections

• 91 parameters

• H-atom parameters constrained

• Δρ_max = 1.69 e Å⁻³

• Δρ_min = −0.33 e Å⁻³

Data collection: CrysAlis CCD (Oxford Diffraction, 2009 ▶); cell refinement: CrysAlis RED (Oxford Diffraction, 2009 ▶); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: DIAMOND (Brandenburg et al., 2011 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯N7i	0.88	2.12	2.960 (5)	159

Symmetry code: (i) .

supplementary crystallographic information

Comment

The title compound 5-bromo-7-azaindole (5BrHaza), which is commercially available, was recently used, together with 3-chloro-7-azaindole and 3-iodo-7-azaindole, for the preparation of the platinum(II) dichlorido and oxalato (ox) complexes of the general formula cis-[PtCl₂(nHaza)₂], and [Pt(ox)(nHaza)₂], respectively (Štarha et al., 2012); nHaza stands for the above-mentioned 7-azaindole halogeno-derivatives. The prepared Pt(II)-dichlorido complexes were found to be highly cytotoxic against the osteosarcoma (HOS), breast carcinoma (MCF7) and prostate carcinoma (LNCaP) human cancer cell lines. Particularly cis-[PtCl₂(5BrHaza)₂] exceeded the clinically applied platinum-based anticancer drug cisplatin, (cis-[PtCl₂(NH₃)₂]), since its IC₅₀ values (the concentration lethal for 50% of the tested cancer cells) equaled 2.5 µM (HOS; 34.2 µM for cisplatin), 2.0 µM (MCF7; 19.6 µM for cisplatin) and 1.5 µM (LNCaP; 3.8 µM for cisplatin).

The discrete molecules (Fig. 1) of the title compound contain fused six-membered pyridine and five-membered pyrrole rings forming the 7-azaindole skeleton. The planes fitted through the atoms of both rings form a dihedral angle of 2.09 (14)° (Fig. 2). The most deviated atoms from the mentioned planes are C6 (-0.012 (4) Å) and C3 (-0.006 (4) Å), respectively, while the most deviated atom from the plane fitted through nonhydrogen atoms of the 7-azaindole moiety is C5 (0.025 (4) Å).

The crystal structure contains the N—H···N hydrogen bonds and C—H···C non-covalent contacts (Fig. 3). Two N1—H1···N7 hydrogen bonds (Table 1) bind together two 5BrHaza molecules into a centrosymmetric dimer. The dimers are connected by C4—H4···C4 and C4—H···C5 non-covalent contacts (see Hydrogen-bond geometry) with four other dimers, which results in the formation of a 2D supramolecular array (Fig. 4).

The molecular structure of the title compound resembles literature precedents: 7-azaindole (Dufour et al., 1990) and 3-iodo-7-azaindole (Chou et al., 2000).

Experimental

The title compound was employed as a starting compound of the syntheses of cis-[PtCl₂(5BrHaza)₂] and [Pt(ox)(5BrHaza)₂].0.75H₂O (Štarha et al., 2012). These complexes were prepared by the reactions of the appropriate platinum(II) salt (K₂[PtCl₄] or K₂[Pt(ox)₂].2H₂O; water solution, 0.5 mmol) with 1.0 mmol of 5BrHaza dissolved in ethanol at 50 °C. Microcrystals obtained as a main product during 2 days of stirring were filtered off and the filtrate was left to crystalize at laboratory temperature in the case of the oxalato-5BrHaza complex. The colourless crystals, which formed as a by-product during a slow evaporation in next 2 weeks, were collected and characterized by elemental analysis, NMR spectroscopy and single-crystal X-ray analysis. ¹H NMR (DMF-d₇, TMS, 298 K, p.p.m.): δ 11.91 (bs, 1H, HN¹), 8.30 (d, J = 2.2 Hz, 1H, HC⁶), 8.20 (d, J = 2.0 Hz, 1H, HC⁴), 7.63 (t, J = 2.8 Hz, 1H, HC²), 6.50 (m, 1H, HC³). ¹³C NMR (DMF-d₇, TMS, 298 K, p.p.m.): δ 147.5 (C⁸), 142.9 (C⁶), 130.3 (C⁴), 128.2 (C²), 122.1 (C⁷), 111.1 (C⁵), 100.0 (C³). ¹⁵N NMR (DMF-d₇, relative to DMF, 298 K, p.p.m.): δ 140.9 [s, 11.93, HN¹; s, 7.63, HC²; s, 6.50, HC³ (N¹)], 277.5 [s, 8.30, HC⁶ (N⁷)]. Analysis calculated for C₇H₆BrN₂: C 42.67, H 2.56, N 14.22%; found: C 42.58, H 2.62, N 14.09%. Elemental analysis (C, H, N) was performed on a Thermo Scientific Flash 2000 CHNO-S Analyzer. The ¹H, ¹³C and ¹⁵N NMR spectra of the DMF-d₇ solutions were collected at 300 K on a Varian 400 spectrometer at 400.00 MHz, 100.58 MHz and 40.53 MHz, respectively. ¹H and ¹³C spectra were calibrated using tetramethylsilane (TMS) as a reference. The ¹⁵N NMR spectrum was measured relative to the DMF signals.

Refinement

Hydrogen atoms were located in difference maps and refined using the riding model with C—H = 0.95 Å and N—H = 0.88 Å, and with U_iso(H) = 1.2U_eq(CH, NH). The maximum and minimum residual electron density peaks of 1.69 and -0.33 eÅ^-3, respectively, were located 1.72 Å and 1.25 Å from the H6 and C6 atoms, respectively.

Figures

Fig. 1.

The molecular structure of the title compound with the non-hydrogen atoms depicted as displacement ellipsoids at the 50% probability level and given with the atom numbering scheme.

Fig. 2.

A view of the title compound showing the mutual orientation of the six-membered pyridine (least-squares plane created through the C4, C5, C6, N7, C8 and C7 atoms; in blue) and five-membered pyrrole rings (least-squares plane created through the N1, C2, C3, C7 and C8 atoms; in green). The planes are nearly coplanar forming the dihedral angle of 2.09 (14)°.

Fig. 3.

Part of the crystal structure of the title compound (ball-and-stick model) showing the N—H···N hydrogen bonds (dashed green lines) and C—H···C non-covalent contacts (dashed orange lines). [Symmetry codes: (i) 1 - x, 1 - y, 1 - z; (ii) x, 0.5 - y, z - 0.5; (iii) x, 0.5 - y, z + 0.5; (iv) 1 - x, y + 0.5, 1.5 - z; (v) 1 - x, y + 0.5, 0.5 - z; (vi) 1 - x, y - 0.5, 0.5 - z; (vii) 1 - x, y - 0.5, 1.5 - z; (viii) x, 1.5 - y, z + 0.5; (ix) x, 1.5 - y, z - 0.5].

Fig. 4.

Part of the crystal structure of the title compound (ball-and-stick model) showing the formation of zigzag chains; dashed green lines indicate the N—H···N hydrogen bonds and dashed orange lines indicate C—H···C non-covalent contacts.

Crystal data

C7H5BrN2	F(000) = 384
Mr = 197.04	Dx = 1.938 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 4062 reflections
a = 8.9082 (4) Å	θ = 3.0–33.1°
b = 13.3632 (6) Å	µ = 6.00 mm−1
c = 5.8330 (3) Å	T = 100 K
β = 103.403 (5)°	Prim, colourless
V = 675.47 (6) Å3	0.24 × 0.24 × 0.12 mm
Z = 4

Data collection

Oxford Diffraction Xcalibur Sapphire2 CCD diffractometer	1185 independent reflections
Radiation source: Enhance (Mo) X-ray Source	1047 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.022
Detector resolution: 8.3611 pixels mm-1	θmax = 25.0°, θmin = 3.1°
ω scans	h = −10→9
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2009)	k = −15→15
Tmin = 0.327, Tmax = 0.533	l = −6→6
3977 measured reflections

Refinement

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)] = 0.035	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.092	H-atom parameters constrained
S = 1.13	w = 1/[σ2(Fo2) + (0.0578P)2 + 1.0071P] where P = (Fo2 + 2Fc2)/3
1185 reflections	(Δ/σ)max < 0.001
91 parameters	Δρmax = 1.69 e Å−3
0 restraints	Δρmin = −0.33 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
Br1	−0.02317 (5)	0.34425 (3)	−0.26611 (7)	0.0188 (2)
N1	0.6033 (4)	0.4228 (3)	0.3167 (6)	0.0151 (7)
H1	0.6364	0.4519	0.4545	0.018*
C2	0.6944 (5)	0.3858 (3)	0.1738 (8)	0.0168 (9)
H2	0.8039	0.3886	0.2096	0.020*
C3	0.6054 (5)	0.3447 (3)	−0.0253 (8)	0.0151 (9)
H3	0.6411	0.3135	−0.1491	0.018*
C4	0.3052 (5)	0.3375 (3)	−0.1574 (7)	0.0143 (9)
H4	0.2942	0.3057	−0.3060	0.017*
C5	0.1780 (5)	0.3665 (3)	−0.0748 (7)	0.0153 (9)
C6	0.1933 (5)	0.4118 (3)	0.1439 (7)	0.0150 (9)
H6	0.1023	0.4281	0.1944	0.018*
N7	0.3299 (4)	0.4335 (2)	0.2865 (6)	0.0153 (7)
C7	0.4494 (5)	0.3572 (3)	−0.0129 (7)	0.0148 (9)
C8	0.4527 (5)	0.4061 (3)	0.2052 (7)	0.0150 (9)

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
Br1	0.0135 (3)	0.0203 (3)	0.0197 (3)	0.00003 (15)	−0.00191 (18)	−0.00174 (16)
N1	0.0141 (19)	0.0143 (16)	0.0167 (18)	−0.0019 (13)	0.0034 (15)	−0.0021 (14)
C2	0.011 (2)	0.015 (2)	0.025 (2)	0.0024 (16)	0.0054 (18)	0.0023 (18)
C3	0.015 (2)	0.013 (2)	0.018 (2)	0.0006 (15)	0.0045 (17)	0.0006 (16)
C4	0.018 (2)	0.010 (2)	0.015 (2)	−0.0014 (15)	0.0040 (18)	0.0003 (15)
C5	0.017 (2)	0.010 (2)	0.018 (2)	−0.0010 (15)	0.0015 (18)	0.0021 (15)
C6	0.014 (2)	0.010 (2)	0.022 (2)	0.0001 (15)	0.0050 (17)	0.0028 (16)
N7	0.0166 (18)	0.0121 (16)	0.0179 (18)	−0.0007 (13)	0.0057 (15)	−0.0016 (14)
C7	0.021 (2)	0.0087 (19)	0.016 (2)	0.0007 (15)	0.0063 (18)	0.0006 (15)
C8	0.014 (2)	0.010 (2)	0.021 (2)	−0.0002 (15)	0.0032 (17)	0.0033 (16)

Geometric parameters (Å, º)

Br1—C5	1.902 (4)	C4—C5	1.385 (6)
N1—C8	1.367 (6)	C4—C7	1.389 (6)
N1—C2	1.383 (5)	C4—H4	0.9500
N1—H1	0.8800	C5—C6	1.390 (6)
C2—C3	1.361 (6)	C6—N7	1.337 (5)
C2—H2	0.9500	C6—H6	0.9500
C3—C7	1.418 (6)	N7—C8	1.339 (5)
C3—H3	0.9500	C7—C8	1.425 (6)
C8—N1—C2	107.6 (4)	C4—C5—Br1	119.2 (3)
C8—N1—H1	126.2	C6—C5—Br1	119.0 (3)
C2—N1—H1	126.2	N7—C6—C5	123.1 (4)
C3—C2—N1	110.6 (4)	N7—C6—H6	118.4
C3—C2—H2	124.7	C5—C6—H6	118.4
N1—C2—H2	124.7	C6—N7—C8	114.9 (3)
C2—C3—C7	107.0 (4)	C4—C7—C3	136.6 (4)
C2—C3—H3	126.5	C4—C7—C8	116.9 (4)
C7—C3—H3	126.5	C3—C7—C8	106.4 (4)
C5—C4—C7	116.9 (4)	N7—C8—N1	125.4 (4)
C5—C4—H4	121.5	N7—C8—C7	126.3 (4)
C7—C4—H4	121.5	N1—C8—C7	108.3 (4)
C4—C5—C6	121.8 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N7i	0.88	2.12	2.960 (5)	159
C4—H4···C4ii	0.95	2.82	3.738 (6)	162
C4—H4···C5ii	0.95	2.84	3.656 (6)	144

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