organic compounds
7-Bromo-2,3-bis[(prop-2-yn-1-yl)sulfanyl]pyrido[2,3-b]pyrazine
aLaboratoire de Chimie Organique Appliquée, Université Sidi Mohamed Ben Abdallah, Faculté des Sciences et Techniques, Route d'Imouzzer, BP 2202, Fez, Morocco, bDepartment of Chemistry, Tulane University, New Orleans, LA 70118, USA, and cLaboratoire de Chimie Organique Hétérocyclique URAC 21, Pôle de Compétence Pharmacochimie, Av. Ibn Battouta, BP 1014, Faculté des Sciences, Université Mohammed V, Rabat, Morocco
*Correspondence e-mail: sikine.meriem@gmail.com
In the title compound, C13H8BrN3S2, one propynyl substituent lies approximately in the plane of the pyridopyrazine ring system, while the other is twisted away from this plane. In the crystal, offset π–π stacking interactions between the pyridine and pyrazine rings with a centroid–centroid distance of 3.740 (1) Å stack the molecules along the a-axis direction. At the conclusion of the initial a significant residual peak remained in the difference map. This suggested an alternate location for the Br atom but at a very low occupancy. Further with Br disordered over two sites yielded a population ratio for the two Br sites of 97:3. As the refined location of the minor Br site leads to unequal C—C—Br angles, we feel that the results indicate a `whole molecule' disorder rather than the presence of a minor amount of an isomer. Unfortunately, the very low amount of the second component of the disorder prevented the location of any of its other atoms.
Keywords: crystal structure; pyridopyrazine; offset π-stacking.
CCDC reference: 1518915
Structure description
Pyrido-pyrazine et al., 2006). Their uses include as antimalarial agents (Shekhar et al., 2014), anti-cancer drugs (Gong et al., 2011), as anti-inflammatories (Hodgetts et al., 2010) and as HIV-1 integrase inhibitors (Wai et al., 2007). They are also used as inhibitors of anaplastic lymphoma kinase (Milkiewicz et al., 2010). As a continuation of our research in the field of substituted pyrido[2,3-b]pyrazine derivatives (Hjouji et al., 2014), we report here the synthesis of a new product by the reaction of propargyl bromide with an excess of pyrido[2,3-b]pyrazine(1H,4H)-2,3-dithiol in dimethyl formamide in the presence of potassium carbonate and a catalytic quantity of tetra-n-butylammonium bromide. The structure of another pyrido [2,3-b]pyrazine derivative has been reported previously (Fun et al., 2011).
are important in organic chemistry and are also known to be important biologically (RichterIn the title compound (Fig. 1), one propynyl substituent lies approximately in the plane of the pyridopyrazine ring system while the other is twisted away from this plane as shown by the C6—S1—C8—C9 [175.29 (17)°] and C7—S2—C11—C12 [76.78 (19)°] torsion angles. In the crystal, the molecules form stacks along the a-axis direction (Fig. 2) through offset π–π-stacking interactions between the pyridine and pyrazine rings (Fig. 3) with a centroid–centroid distance of 3.740 (1) Å and an interplanar separation of 3.440 (1) Å.
Synthesis and crystallization
Propargyl bromide (0.16 ml, 1.82 mmol) was added to a solution of 7-bromopyrido[2,3-b]pyrazine-2,3-dithiol (0.2 g, 0.73 mmol), K2CO3 (0.3 g, 2.19 mmol), tetra-n-butyl ammonium bromide (0.03 g, 0.1 mmol) in DMF (10 ml). The mixture was then stirred for 6 h at room temperature. The solvent was evaporated under reduced pressure and the product isolated by on a silica gel column with ethyl acetate/hexane (1/3) as The compound forms pale yellow columnar crystals in 20% yield and was recrystallized from a solvent mixture (dichloromethane–hexane: 1/2).
Refinement
Crystal data, data collection and structure . At the conclusion of the initial a significant residual peak remained in the difference map at ca 1.85 Å from C4. This suggested an alternate location for Br1 but at a very low occupancy. Further with Br1 disordered over two sites yielded a population ratio for the two Br sites of 97:3. As the refined location of the minor Br site leads to unequal C—C—Br angles, we feel that the results indicate a `whole molecule' disorder rather than the presence of a minor amount of an isomer. Unfortunately, the very low amount of the second component of the disorder prevented the location of any of its other atoms.
details are summarized in Table 1Structural data
CCDC reference: 1518915
https://doi.org/10.1107/S2414314616018812/sj4070sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314616018812/sj4070Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2414314616018812/sj4070Isup3.cml
Data collection: APEX3 (Bruker, 2016); cell
SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: DIAMOND (Brandenburg & Putz, 2012); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).C13H8BrN3S2 | F(000) = 696 |
Mr = 350.25 | Dx = 1.690 Mg m−3 |
Monoclinic, P21/c | Cu Kα radiation, λ = 1.54178 Å |
a = 4.2159 (1) Å | Cell parameters from 9904 reflections |
b = 16.7730 (5) Å | θ = 3.5–72.4° |
c = 19.4656 (5) Å | µ = 6.81 mm−1 |
β = 91.149 (1)° | T = 150 K |
V = 1376.20 (6) Å3 | Column, pale yellow |
Z = 4 | 0.20 × 0.08 × 0.04 mm |
Bruker D8 VENTURE PHOTON 100 CMOS diffractometer | 2726 independent reflections |
Radiation source: INCOATEC IµS micro-focus source | 2513 reflections with I > 2σ(I) |
Mirror monochromator | Rint = 0.035 |
Detector resolution: 10.4167 pixels mm-1 | θmax = 72.4°, θmin = 3.5° |
ω scans | h = −5→5 |
Absorption correction: multi-scan (SADABS; Bruker, 2016) | k = −20→20 |
Tmin = 0.46, Tmax = 0.77 | l = −24→24 |
21387 measured reflections |
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)] = 0.033 | Hydrogen site location: mixed |
wR(F2) = 0.086 | H-atom parameters constrained |
S = 1.05 | w = 1/[σ2(Fo2) + (0.0425P)2 + 1.2838P] where P = (Fo2 + 2Fc2)/3 |
2726 reflections | (Δ/σ)max = 0.001 |
176 parameters | Δρmax = 0.50 e Å−3 |
1 restraint | Δρmin = −0.57 e Å−3 |
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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. H-atoms attached to carbon were placed in calculated positions (C—H = 0.95 - 0.99 Å) and included as riding contributions with isotropic displacement parameters 1.2 times those of the attached atoms. At the conclusion of the initial refinement, a significant residual peak remained the difference map at ca. 1.85 Å from C4. This suggested an alternate location for Br1 but at a very low occupancy. Further refinement with Br1 disordered over two sites yielded a population ratio for the two Br sites of 97:3. Because the refined location of the minor Br site leads to unequal C–C–Br angles, we feel that the results indicate a "whole molecule" disorder rather than the presence of a minor amount of an isomer. Unfortunately, the very low amount of the second component of the disorder prevented location of any of its other atoms. |
x | y | z | Uiso*/Ueq | Occ. (<1) | |
Br1 | 1.33510 (8) | 0.89445 (2) | 0.98676 (2) | 0.05325 (13) | 0.9711 (8) |
C3 | 1.0987 (6) | 0.87110 (17) | 0.90621 (13) | 0.0414 (6) | 0.9711 (8) |
C4 | 0.9795 (7) | 0.93338 (16) | 0.86557 (14) | 0.0438 (6) | 0.9711 (8) |
H4 | 1.0330 | 0.9864 | 0.8784 | 0.053* | 0.9711 (8) |
Br1A | 1.186 (3) | 1.0075 (6) | 0.9223 (5) | 0.05325 (13) | 0.0289 (8) |
C3A | 1.0987 (6) | 0.87110 (17) | 0.90621 (13) | 0.0414 (6) | 0.0289 (8) |
H3A | 1.2202 | 0.8812 | 0.9483 | 0.050* | 0.0289 (8) |
C4A | 0.9795 (7) | 0.93338 (16) | 0.86557 (14) | 0.0438 (6) | 0.0289 (8) |
S1 | 0.21077 (15) | 0.74574 (3) | 0.64709 (3) | 0.03557 (15) | |
S2 | 0.46504 (15) | 0.60113 (3) | 0.72597 (3) | 0.03503 (15) | |
N1 | 0.5283 (5) | 0.83752 (11) | 0.73672 (10) | 0.0324 (4) | |
N2 | 0.7585 (5) | 0.70372 (12) | 0.81113 (10) | 0.0337 (4) | |
N3 | 0.7976 (6) | 0.92284 (12) | 0.81063 (11) | 0.0400 (5) | |
C1 | 0.8373 (6) | 0.78020 (14) | 0.83001 (12) | 0.0330 (5) | |
C2 | 1.0335 (6) | 0.79318 (16) | 0.88808 (13) | 0.0385 (5) | |
H2 | 1.1184 | 0.7499 | 0.9140 | 0.046* | |
C5 | 0.7232 (6) | 0.84662 (14) | 0.79321 (12) | 0.0331 (5) | |
C6 | 0.4557 (6) | 0.76449 (14) | 0.71894 (12) | 0.0313 (5) | |
C7 | 0.5753 (5) | 0.69566 (13) | 0.75688 (12) | 0.0313 (5) | |
C8 | 0.1351 (6) | 0.84778 (14) | 0.61874 (12) | 0.0355 (5) | |
H8A | 0.0153 | 0.8770 | 0.6540 | 0.043* | |
H8B | 0.3383 | 0.8759 | 0.6117 | 0.043* | |
C9 | −0.0480 (6) | 0.84493 (15) | 0.55455 (13) | 0.0378 (5) | |
C10 | −0.1994 (7) | 0.84327 (18) | 0.50324 (14) | 0.0484 (7) | |
H10 | −0.3217 | 0.8419 | 0.4617 | 0.058* | |
C11 | 0.6516 (6) | 0.53851 (14) | 0.79116 (12) | 0.0343 (5) | |
H11A | 0.6691 | 0.4835 | 0.7731 | 0.041* | |
H11B | 0.8691 | 0.5583 | 0.8008 | 0.041* | |
C12 | 0.4780 (6) | 0.53656 (14) | 0.85501 (13) | 0.0355 (5) | |
C13 | 0.3346 (7) | 0.53361 (17) | 0.90614 (15) | 0.0467 (6) | |
H13 | 0.2188 | 0.5312 | 0.9475 | 0.056* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Br1 | 0.0562 (2) | 0.0577 (2) | 0.04545 (19) | −0.01377 (14) | −0.01003 (14) | −0.00496 (13) |
C3 | 0.0422 (14) | 0.0438 (14) | 0.0383 (13) | −0.0088 (11) | 0.0013 (11) | −0.0023 (11) |
C4 | 0.0508 (15) | 0.0350 (13) | 0.0456 (15) | −0.0115 (11) | 0.0034 (12) | −0.0030 (11) |
Br1A | 0.0562 (2) | 0.0577 (2) | 0.04545 (19) | −0.01377 (14) | −0.01003 (14) | −0.00496 (13) |
C3A | 0.0422 (14) | 0.0438 (14) | 0.0383 (13) | −0.0088 (11) | 0.0013 (11) | −0.0023 (11) |
C4A | 0.0508 (15) | 0.0350 (13) | 0.0456 (15) | −0.0115 (11) | 0.0034 (12) | −0.0030 (11) |
S1 | 0.0424 (3) | 0.0295 (3) | 0.0345 (3) | 0.0006 (2) | −0.0039 (2) | 0.0022 (2) |
S2 | 0.0422 (3) | 0.0260 (3) | 0.0367 (3) | −0.0005 (2) | −0.0040 (2) | 0.0007 (2) |
N1 | 0.0370 (10) | 0.0273 (9) | 0.0330 (10) | 0.0003 (8) | 0.0024 (8) | 0.0015 (8) |
N2 | 0.0363 (10) | 0.0287 (9) | 0.0360 (10) | −0.0014 (8) | 0.0004 (8) | 0.0038 (8) |
N3 | 0.0496 (12) | 0.0284 (10) | 0.0420 (12) | −0.0048 (9) | 0.0006 (9) | 0.0001 (9) |
C1 | 0.0354 (12) | 0.0307 (11) | 0.0328 (11) | −0.0044 (9) | 0.0026 (9) | 0.0020 (9) |
C2 | 0.0388 (13) | 0.0399 (13) | 0.0366 (13) | −0.0049 (10) | −0.0018 (10) | 0.0063 (10) |
C5 | 0.0381 (12) | 0.0281 (11) | 0.0333 (11) | −0.0024 (9) | 0.0040 (9) | 0.0022 (9) |
C6 | 0.0330 (11) | 0.0302 (11) | 0.0310 (11) | 0.0008 (9) | 0.0037 (9) | 0.0024 (9) |
C7 | 0.0321 (11) | 0.0279 (11) | 0.0342 (11) | 0.0007 (9) | 0.0040 (9) | 0.0026 (9) |
C8 | 0.0418 (13) | 0.0316 (12) | 0.0332 (12) | 0.0028 (10) | 0.0010 (10) | 0.0029 (9) |
C9 | 0.0415 (13) | 0.0353 (12) | 0.0367 (13) | 0.0063 (10) | 0.0043 (10) | 0.0035 (10) |
C10 | 0.0532 (16) | 0.0515 (16) | 0.0401 (14) | 0.0140 (13) | −0.0056 (12) | −0.0024 (12) |
C11 | 0.0376 (12) | 0.0255 (10) | 0.0397 (12) | 0.0013 (9) | −0.0025 (10) | 0.0013 (9) |
C12 | 0.0365 (12) | 0.0272 (11) | 0.0424 (13) | −0.0034 (9) | −0.0080 (10) | 0.0009 (10) |
C13 | 0.0525 (16) | 0.0452 (15) | 0.0423 (15) | −0.0083 (12) | 0.0004 (12) | −0.0001 (12) |
Br1—C3 | 1.882 (3) | N2—C1 | 1.373 (3) |
C3—C2 | 1.380 (4) | N3—C5 | 1.358 (3) |
C3—C4 | 1.398 (4) | C1—C2 | 1.404 (3) |
C4—N3 | 1.315 (4) | C1—C5 | 1.404 (3) |
C4—H4 | 0.9500 | C2—H2 | 0.9500 |
Br1A—C4A | 1.866 (4) | C6—C7 | 1.455 (3) |
C3A—C2 | 1.380 (4) | C8—C9 | 1.456 (3) |
C3A—C4A | 1.398 (4) | C8—H8A | 0.9900 |
C3A—H3A | 0.9729 | C8—H8B | 0.9900 |
C4A—N3 | 1.315 (4) | C9—C10 | 1.175 (4) |
S1—C6 | 1.750 (2) | C10—H10 | 0.9500 |
S1—C8 | 1.824 (2) | C11—C12 | 1.455 (4) |
S2—C7 | 1.755 (2) | C11—H11A | 0.9900 |
S2—C11 | 1.814 (2) | C11—H11B | 0.9900 |
N1—C6 | 1.307 (3) | C12—C13 | 1.176 (4) |
N1—C5 | 1.368 (3) | C13—H13 | 0.9500 |
N2—C7 | 1.303 (3) | ||
C2—C3—C4 | 119.7 (2) | N3—C5—N1 | 116.0 (2) |
C2—C3—Br1 | 120.6 (2) | N3—C5—C1 | 123.0 (2) |
C4—C3—Br1 | 119.6 (2) | N1—C5—C1 | 121.0 (2) |
N3—C4—C3 | 123.8 (2) | N1—C6—C7 | 122.2 (2) |
N3—C4—H4 | 118.1 | N1—C6—S1 | 120.73 (18) |
C3—C4—H4 | 118.1 | C7—C6—S1 | 117.11 (17) |
C2—C3A—C4A | 119.7 (2) | N2—C7—C6 | 121.5 (2) |
C2—C3A—H3A | 118.6 | N2—C7—S2 | 121.34 (18) |
C4A—C3A—H3A | 121.6 | C6—C7—S2 | 117.14 (17) |
N3—C4A—C3A | 123.8 (2) | C9—C8—S1 | 108.37 (17) |
N3—C4A—Br1A | 145.9 (4) | C9—C8—H8A | 110.0 |
C3A—C4A—Br1A | 90.3 (4) | S1—C8—H8A | 110.0 |
C6—S1—C8 | 99.78 (11) | C9—C8—H8B | 110.0 |
C7—S2—C11 | 100.09 (11) | S1—C8—H8B | 110.0 |
C6—N1—C5 | 116.8 (2) | H8A—C8—H8B | 108.4 |
C7—N2—C1 | 116.8 (2) | C10—C9—C8 | 179.0 (3) |
C4A—N3—C5 | 117.2 (2) | C9—C10—H10 | 180.0 |
C4—N3—C5 | 117.2 (2) | C12—C11—S2 | 113.08 (17) |
N2—C1—C2 | 119.7 (2) | C12—C11—H11A | 109.0 |
N2—C1—C5 | 121.7 (2) | S2—C11—H11A | 109.0 |
C2—C1—C5 | 118.5 (2) | C12—C11—H11B | 109.0 |
C3A—C2—C1 | 117.6 (2) | S2—C11—H11B | 109.0 |
C3—C2—C1 | 117.6 (2) | H11A—C11—H11B | 107.8 |
C3—C2—H2 | 121.2 | C13—C12—C11 | 178.6 (3) |
C1—C2—H2 | 121.2 | C12—C13—H13 | 180.0 |
C2—C3—C4—N3 | 1.9 (4) | C4—N3—C5—C1 | −1.5 (4) |
Br1—C3—C4—N3 | −176.1 (2) | C6—N1—C5—N3 | 179.6 (2) |
C2—C3A—C4A—N3 | 1.9 (4) | C6—N1—C5—C1 | −0.2 (3) |
Br1A—C3A—C4A—N3 | 179.5 (5) | N2—C1—C5—N3 | −179.9 (2) |
C2—C3A—C4A—Br1A | −177.6 (4) | C2—C1—C5—N3 | 1.0 (4) |
C3A—Br1A—C4A—N3 | −179.2 (7) | N2—C1—C5—N1 | −0.1 (4) |
C3A—C4A—N3—C5 | 0.1 (4) | C2—C1—C5—N1 | −179.2 (2) |
Br1A—C4A—N3—C5 | 179.2 (7) | C5—N1—C6—C7 | −0.1 (3) |
C3—C4—N3—C5 | 0.1 (4) | C5—N1—C6—S1 | −179.46 (17) |
C7—N2—C1—C2 | 179.9 (2) | C8—S1—C6—N1 | 0.2 (2) |
C7—N2—C1—C5 | 0.7 (3) | C8—S1—C6—C7 | −179.20 (18) |
C4A—C3A—C2—C1 | −2.3 (4) | C1—N2—C7—C6 | −1.0 (3) |
C4—C3—C2—C1 | −2.3 (4) | C1—N2—C7—S2 | 178.35 (17) |
Br1—C3—C2—C1 | 175.62 (18) | N1—C6—C7—N2 | 0.8 (4) |
N2—C1—C2—C3A | −178.1 (2) | S1—C6—C7—N2 | −179.84 (18) |
C5—C1—C2—C3A | 1.0 (4) | N1—C6—C7—S2 | −178.63 (18) |
N2—C1—C2—C3 | −178.1 (2) | S1—C6—C7—S2 | 0.7 (2) |
C5—C1—C2—C3 | 1.0 (4) | C11—S2—C7—N2 | 3.2 (2) |
C4A—N3—C5—N1 | 178.7 (2) | C11—S2—C7—C6 | −177.38 (18) |
C4—N3—C5—N1 | 178.7 (2) | C6—S1—C8—C9 | 175.29 (17) |
C4A—N3—C5—C1 | −1.5 (4) | C7—S2—C11—C12 | 76.78 (19) |
Acknowledgements
The support of NSF–MRI grant No. 1228232 for the purchase of the diffractometer and Tulane University for support of the Tulane Crystallography Laboratory are gratefully acknowledged.
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