3-Amino-5-bromo-2-iodo­pyridine

Bunker, K.D.; Sach, N.W.; Nukui, S.; Rheingold, A.L.; Yanovsky, A.

doi:10.1107/S1600536808040452

organic compounds

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Volume 65| Part 1| January 2009| Page o28

doi:10.1107/S1600536808040452

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3-Amino-5-bromo-2-iodopyridine

Kevin D. Bunker,^a Neal W. Sach,^a Seiji Nukui,^a Arnold L. Rheingold ^b and Alex Yanovsky ^a ^*

^aPfizer Global Research and Development, La Jolla Laboratories, 10614 Science Center Drive, San Diego, CA 92122, USA, and ^bDepartment of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
^*Correspondence e-mail: alex.yanovsky@pfizer.com

(Received 27 November 2008; accepted 1 December 2008; online 6 December 2008)

The reaction of 3-amino-5-bromopyridine with N-iodosuccinimide in the presence of acetic acid produces the title compound, C₅H₄BrIN, with an iodo substituent in position 2 of the pyridine ring. The crystal structure features rather weak intermolecular N—H⋯N hydrogen bonds linking the molecules into chains along the z axis of the crystal.

Related literature

For structures of ortho-iodoanilines, see: McWilliam et al. (2001 ); Sandor & Foxman (2000 ); Parkin et al. (2005 ).

Experimental

Crystal data

C₅H₄BrIN₂
M_r = 298.90
Monoclinic, P 2₁ /c
a = 4.0983 (12) Å
b = 15.172 (4) Å
c = 12.038 (3) Å
β = 90.152 (5)°
V = 748.5 (3) Å³
Z = 4
Mo Kα radiation
μ = 9.53 mm⁻¹
T = 100 (2) K
0.40 × 0.33 × 0.04 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2001 ) T_min = 0.234, T_max = 0.557
3783 measured reflections
1251 independent reflections
1086 reflections with I > 2σ(I)
R_int = 0.037

Refinement

R[F² > 2σ(F²)] = 0.032
wR(F²) = 0.082
S = 1.05
1251 reflections
82 parameters
H-atom parameters constrained
Δρ_max = 1.33 e Å⁻³
Δρ_min = −0.92 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2A⋯N1ⁱ	0.88	2.16	3.025 (8)	166
N2—H2B⋯I1	0.88	2.79	3.259 (5)	115
Symmetry code: (i) $[x, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]$ .

Data collection: APEX2 (Bruker, 2007 ); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808040452/rz2275sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808040452/rz2275Isup2.hkl

checkCIF report

Comment top

The reaction of 5-bromo-3-aminopyridine with N-iodosuccinimide in the presence of acetic acid leads to iodo-substitution at position 2 of the pyridine ring, as shown by the X-ray study of the title compound (Fig. 1). To the best of our knowledge, this is the first structure of ortho-iodoaminopyridine derivative. The N2···I1 distance 3.259 (5) Å is typical for ortho-iodoanilines (McWilliam et al., 2001; Sandor & Foxman, 2000; Parkin et al., 2005) and may suggest involvement of the H2B atom in weak intramolecular N2—H2B···I1 interaction (Table 1).

The second `active' H-atom, H2A, participates in the intermolecular H-bond N2—H2A···N1ⁱ (symmetry code (i): x, 1/2 - y, z - 1/2; Table 1), which links the molecules into the chains along the z-axis of the crystal (Fig. 2). There are no strong halogen···halogen interactions in the structure; the shortest intermolecular I···I distances are 4.091 (1) Å and 4.098 (1) Å.

Related literature top

For structures of ortho-iodoanilines, see: McWilliam et al. (2001); Sandor & Foxman (2000); Parkin et al. (2005).

Experimental top

To a solution of 3-amino-5-bromopyridine (100 mg, 0.56 mmol) in acetic acid (0.1 M, 5.61 ml) was added N-iodosuccinimide (133 mg, 0.56 mmol) at rt. After 3 h, the reaction was quenched with sat. sodium bicarbonate and extracted 3 times with EtOAc. The organic layers were combined, dried, filtered, and concentrated. The crude residue was subjected to flash chromatography (silica gel, 0–50% EtOAc/heptane). Isolated 93 mg (55%) of 3-amino-5-bromo-2-iodopyridine, as a brown solid. X-ray quality crystals were obtained by slow evaporation of a concentrated chromatography fraction (approx. 30% EtOAc/heptane). ¹H NMR (400 MHz, DMSO-d₆) (δ p.p.m.) 5.65 (s, 2 H), 7.16 (d, J = 2.27 Hz, 1 H), 7.67 (d, J = 2.01 Hz, 1 H). ¹³C NMR (101 MHz, DMSO-d₆) (δ p.p.m.) 106.10, 120.01, 120.92, 137.97, 147.68.

Computing details top

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

	Fig. 1. Molecular structure of the title compound, showing 50% probability displacement ellipsoids and atom numbering scheme. H atoms are drawn as circles with arbitrary small radius.
	Fig. 2. The crystal packing diagram viewed down the x-axis.

3-Amino-5-bromo-2-iodopyridine top

Crystal data top

C₅H₄BrIN₂	F(000) = 544
M_r = 298.90	D_x = 2.652 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 2536 reflections
a = 4.0983 (12) Å	θ = 2.7–25.3°
b = 15.172 (4) Å	µ = 9.53 mm⁻¹
c = 12.038 (3) Å	T = 100 K
β = 90.152 (5)°	Plate, colourless
V = 748.5 (3) Å³	0.40 × 0.33 × 0.04 mm
Z = 4

Data collection top

Bruker APEXII CCD diffractometer	1251 independent reflections
Radiation source: fine-focus sealed tube	1086 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.037
ϕ and ω scans	θ_max = 25.3°, θ_min = 2.2°
Absorption correction: analytical (SADABS; Bruker, 2001)	h = −4→1
T_min = 0.234, T_max = 0.557	k = −17→18
3783 measured reflections	l = −10→14

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)] = 0.032	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.082	H-atom parameters constrained
S = 1.05	w = 1/[σ²(F_o²) + (0.037P)² + 2.524P] where P = (F_o² + 2F_c²)/3
1251 reflections	(Δ/σ)_max = 0.003
82 parameters	Δρ_max = 1.33 e Å⁻³
0 restraints	Δρ_min = −0.92 e Å⁻³

Crystal data top

C₅H₄BrIN₂	V = 748.5 (3) Å³
M_r = 298.90	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 4.0983 (12) Å	µ = 9.53 mm⁻¹
b = 15.172 (4) Å	T = 100 K
c = 12.038 (3) Å	0.40 × 0.33 × 0.04 mm
β = 90.152 (5)°

Data collection top

Bruker APEXII CCD diffractometer	1251 independent reflections
Absorption correction: analytical (SADABS; Bruker, 2001)	1086 reflections with I > 2σ(I)
T_min = 0.234, T_max = 0.557	R_int = 0.037
3783 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.032	0 restraints
wR(F²) = 0.082	H-atom parameters constrained
S = 1.05	Δρ_max = 1.33 e Å⁻³
1251 reflections	Δρ_min = −0.92 e Å⁻³
82 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
I1	0.18405 (10)	0.37509 (3)	0.48761 (3)	0.02516 (17)
Br1	−0.56202 (16)	0.01782 (4)	0.28399 (5)	0.0266 (2)
N2	−0.0278 (15)	0.3306 (4)	0.2326 (4)	0.0298 (13)
H2A	−0.0808	0.3282	0.1617	0.036*
H2B	0.0760	0.3769	0.2589	0.036*
N1	−0.1133 (14)	0.1994 (4)	0.4858 (4)	0.0264 (13)
C2	−0.2684 (18)	0.1278 (4)	0.4470 (6)	0.0264 (15)
H2	−0.3243	0.0815	0.4965	0.032*
C1	−0.0390 (15)	0.2637 (5)	0.4165 (5)	0.0242 (14)
C5	−0.1071 (15)	0.2622 (5)	0.3019 (5)	0.0227 (14)
C3	−0.3480 (16)	0.1208 (4)	0.3350 (5)	0.0221 (14)
C4	−0.2713 (15)	0.1878 (4)	0.2636 (5)	0.0213 (14)
H4	−0.3303	0.1834	0.1874	0.026*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
I1	0.0244 (3)	0.0324 (3)	0.0187 (3)	−0.00094 (16)	−0.00522 (18)	−0.00340 (17)
Br1	0.0285 (4)	0.0274 (4)	0.0238 (4)	−0.0007 (3)	−0.0039 (3)	−0.0027 (3)
N2	0.044 (4)	0.029 (3)	0.016 (3)	−0.002 (3)	−0.008 (3)	−0.001 (2)
N1	0.035 (3)	0.030 (3)	0.015 (3)	0.002 (2)	−0.005 (2)	0.002 (2)
C2	0.035 (4)	0.024 (4)	0.020 (3)	0.000 (3)	−0.007 (3)	0.002 (3)
C1	0.017 (3)	0.036 (4)	0.020 (3)	0.004 (3)	−0.006 (3)	−0.008 (3)
C5	0.017 (3)	0.035 (4)	0.016 (3)	0.006 (3)	−0.001 (2)	−0.002 (3)
C3	0.021 (4)	0.027 (4)	0.018 (3)	0.005 (3)	−0.001 (3)	−0.001 (3)
C4	0.021 (3)	0.033 (4)	0.011 (3)	0.007 (3)	−0.005 (2)	−0.006 (3)

Geometric parameters (Å, º) top

I1—C1	2.102 (7)	C2—C3	1.390 (9)
Br1—C3	1.894 (7)	C2—H2	0.9500
N2—C5	1.371 (9)	C1—C5	1.407 (9)
N2—H2A	0.8800	C5—C4	1.393 (9)
N2—H2B	0.8800	C3—C4	1.368 (9)
N1—C1	1.320 (9)	C4—H4	0.9500
N1—C2	1.342 (9)

C5—N2—H2A	120.0	N2—C5—C4	121.8 (5)
C5—N2—H2B	120.0	N2—C5—C1	122.6 (6)
H2A—N2—H2B	120.0	C4—C5—C1	115.6 (6)
C1—N1—C2	119.3 (5)	C4—C3—C2	119.9 (6)
N1—C2—C3	120.6 (6)	C4—C3—Br1	121.1 (5)
N1—C2—H2	119.7	C2—C3—Br1	119.0 (5)
C3—C2—H2	119.7	C3—C4—C5	120.4 (6)
N1—C1—C5	124.2 (6)	C3—C4—H4	119.8
N1—C1—I1	116.0 (4)	C5—C4—H4	119.8
C5—C1—I1	119.8 (5)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···N1ⁱ	0.88	2.16	3.025 (8)	166
N2—H2B···I1	0.88	2.79	3.259 (5)	115

Symmetry code: (i) x, −y+1/2, z−1/2.

Experimental details

Crystal data
Chemical formula	C₅H₄BrIN₂
M_r	298.90
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	100
a, b, c (Å)	4.0983 (12), 15.172 (4), 12.038 (3)
β (°)	90.152 (5)
V (Å³)	748.5 (3)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	9.53
Crystal size (mm)	0.40 × 0.33 × 0.04

Data collection
Diffractometer	Bruker APEXII CCD diffractometer
Absorption correction	Analytical (SADABS; Bruker, 2001)
T_min, T_max	0.234, 0.557
No. of measured, independent and observed [I > 2σ(I)] reflections	3783, 1251, 1086
R_int	0.037
(sin θ/λ)_max (Å⁻¹)	0.601

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.032, 0.082, 1.05
No. of reflections	1251
No. of parameters	82
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	1.33, −0.92

Computer programs: APEX2 (Bruker, 2007), SAINT (Bruker, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···N1ⁱ	0.88	2.16	3.025 (8)	166.2
N2—H2B···I1	0.88	2.79	3.259 (5)	115.0

Symmetry code: (i) x, −y+1/2, z−1/2.

References

Bruker (2001). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bruker (2007). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
McWilliam, S. A., Skakle, J. M. S., Low, J. N., Wardell, J. L., Garden, S. J., Pinto, A. C., Torres, J. C. & Glidewell, C. (2001). Acta Cryst. C57, 942–945. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Parkin, A., Spanswick, C. K., Pulham, C. R. & Wilson, C. C. (2005). Acta Cryst. E61, o1087–o1089. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Sandor, R. B. & Foxman, B. M. (2000). Tetrahedron, 56, 6805–6812. Web of Science CSD CrossRef CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar

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CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 65| Part 1| January 2009| Page o28

doi:10.1107/S1600536808040452

Open

access