![](/logos/buttonlogos/cross.png)
![](/logos/buttonlogos/cross.png)
organic compounds
3-Amino-5-bromo-2-iodopyridine
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
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 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
|
Refinement
|
|
Data collection: APEX2 (Bruker, 2007); cell 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
10.1107/S1600536808040452/rz2275sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536808040452/rz2275Isup2.hkl
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 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.
(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 fraction (approx. 30% EtOAc/heptane). 1H NMR (400 MHz, DMSO-d6) (All H atoms were treated as riding with the C—H and N—H distances of 0.95 Å and 0.88 Å respectively; the Uiso(H) were set to 1.2Ueq of the carrying atom.
Data collection: APEX2 (Bruker, 2007); cell
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).C5H4BrIN2 | F(000) = 544 |
Mr = 298.90 | Dx = 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 |
Bruker APEXII CCD diffractometer | 1251 independent reflections |
Radiation source: fine-focus sealed tube | 1086 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.037 |
ϕ and ω scans | θmax = 25.3°, θmin = 2.2° |
Absorption correction: analytical (SADABS; Bruker, 2001) | h = −4→1 |
Tmin = 0.234, Tmax = 0.557 | k = −17→18 |
3783 measured reflections | l = −10→14 |
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(Fo2) + (0.037P)2 + 2.524P] where P = (Fo2 + 2Fc2)/3 |
1251 reflections | (Δ/σ)max = 0.003 |
82 parameters | Δρmax = 1.33 e Å−3 |
0 restraints | Δρmin = −0.92 e Å−3 |
C5H4BrIN2 | V = 748.5 (3) Å3 |
Mr = 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)° |
Bruker APEXII CCD diffractometer | 1251 independent reflections |
Absorption correction: analytical (SADABS; Bruker, 2001) | 1086 reflections with I > 2σ(I) |
Tmin = 0.234, Tmax = 0.557 | Rint = 0.037 |
3783 measured reflections |
R[F2 > 2σ(F2)] = 0.032 | 0 restraints |
wR(F2) = 0.082 | H-atom parameters constrained |
S = 1.05 | Δρmax = 1.33 e Å−3 |
1251 reflections | Δρmin = −0.92 e Å−3 |
82 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
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* |
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) |
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) |
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 |
Mr | 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) |
Tmin, Tmax | 0.234, 0.557 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 3783, 1251, 1086 |
Rint | 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 |
Δρmax, Δρmin (e Å−3) | 1.33, −0.92 |
Computer programs: APEX2 (Bruker, 2007), SAINT (Bruker, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).
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
This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
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.