Acta Cryst. (2011). E67, o833 [ doi:10.1107/S160053681100821X ]
The V-shaped title compound, C11H10Br2N4, lies on a crystallographic twofold rotation axis which passes through the central C atom. In the crystal, an infinite tape motif, which propagates in the a-axis direction, is formed by inversion-related N-H
N hydrogen-bonding interactions. The structure confirmed the identity of the compound as a reaction side product.
To a solution of 5-bromopyridin-2-amine 1a (0.58 mmol, 100 mg) in dichloromethane (DCM) (1.5 ml), was added aq. 37% solution of formaldehyde (140 µl, 1.78 mmol) followed by (isocyanomethyl)benzene (75.4 µl, 0.58 mmol) and the solution was stirred for 10 min. DCM was evaporated and the resulting solid was irradiated under microwave at 100° C for 10 min. The crude product was purified through silica gel chromatography to provide 41 mg of 4a in (20% yield). The product was recrystallized from a DCM solution.
All H atoms were located in a difference map and are freely refined, with the exception of an N–H distance restaint of 0.88 (1) Å used on H2N. C–H distances lie in the range 0.92 (2) to 1.01 (2) Å.
The space group was set as I2/a since I2/a results in a smaller beta angle (and slightly shorter c axis).
Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: SHELXTL (Sheldrick, 2008), publCIF (Westrip, 2010) and local programs.
![[Figure 1]](./ng5123fig1thm.gif)
| Fig. 1. Three reaction pathways in the Groebke-Blackburn reaction. |
![[Figure 2]](./ng5123fig2thm.gif)
| Fig. 2. Three possible products in the reaction described herein. |
![[Figure 3]](./ng5123fig3thm.gif)
| Fig. 3. The molecular structure of 4a, with displacement ellipsoids at the 50% probability level. Unlabelled atoms are related to labelled atoms by a twofold rotation (symmetry operator: -x + 3/2, y, -z). |
![[Figure 4]](./ng5123fig4thm.gif)
| Fig. 4. Hydrogen bonding interactions (blue dotted lines; red dotted lines indicate continuation) in the crystal structure of 4a. The long c axis has been truncated. |
| C11H10Br2N4 | F(000) = 696 |
| Mr = 358.05 | Dx = 1.930 Mg m−3 |
| Monoclinic, I2/a | Mo Kα radiation, λ = 0.71073 Å |
| Hall symbol: -I 2ya | Cell parameters from 6689 reflections |
| a = 11.9075 (6) Å | θ = 3.2–30.6° |
| b = 4.0523 (2) Å | µ = 6.56 mm−1 |
| c = 25.8065 (15) Å | T = 100 K |
| β = 98.326 (3)° | Rod, colourless |
| V = 1232.11 (11) Å3 | 0.24 × 0.08 × 0.07 mm |
| Z = 4 |
| Bruker Kappa APEXII DUO CCD diffractometer | 1903 independent reflections |
| Radiation source: fine-focus sealed tube with Miracol optics | 1674 reflections with I > 2σ(I) |
| graphite | Rint = 0.023 |
| φ and ω scans | θmax = 30.7°, θmin = 1.6° |
| Absorption correction: numerical (SADABS; Sheldrick, 1996) | h = −16→17 |
| Tmin = 0.297, Tmax = 0.675 | k = −5→5 |
| 11800 measured reflections | l = −36→37 |
| 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)] = 0.019 | Hydrogen site location: difference Fourier map |
| wR(F2) = 0.051 | H atoms treated by a mixture of independent and constrained refinement |
| S = 1.03 | w = 1/[σ2(Fo2) + (0.0253P)2 + 1.5219P] where P = (Fo2 + 2Fc2)/3 |
| 1903 reflections | (Δ/σ)max = 0.002 |
| 98 parameters | Δρmax = 0.70 e Å−3 |
| 1 restraint | Δρmin = −0.47 e Å−3 |
| C11H10Br2N4 | V = 1232.11 (11) Å3 |
| Mr = 358.05 | Z = 4 |
| Monoclinic, I2/a | Mo Kα radiation |
| a = 11.9075 (6) Å | µ = 6.56 mm−1 |
| b = 4.0523 (2) Å | T = 100 K |
| c = 25.8065 (15) Å | 0.24 × 0.08 × 0.07 mm |
| β = 98.326 (3)° |
| Bruker Kappa APEXII DUO CCD diffractometer | 1903 independent reflections |
| Absorption correction: numerical (SADABS; Sheldrick, 1996) | 1674 reflections with I > 2σ(I) |
| Tmin = 0.297, Tmax = 0.675 | Rint = 0.023 |
| 11800 measured reflections | θmax = 30.7° |
| R[F2 > 2σ(F2)] = 0.019 | H atoms treated by a mixture of independent and constrained refinement |
| wR(F2) = 0.051 | Δρmax = 0.70 e Å−3 |
| S = 1.03 | Δρmin = −0.47 e Å−3 |
| 1903 reflections | Absolute structure: ? |
| 98 parameters | Flack parameter: ? |
| 1 restraint | Rogers parameter: ? |
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 | ||
| Br | 0.596053 (15) | 1.07921 (4) | 0.214841 (6) | 0.02877 (6) | |
| N1 | 0.54707 (10) | 0.7010 (3) | 0.06616 (5) | 0.0220 (2) | |
| N2 | 0.65505 (10) | 0.4435 (3) | 0.01189 (5) | 0.0213 (2) | |
| H2N | 0.5900 (11) | 0.412 (5) | −0.0074 (7) | 0.026 (5)* | |
| C1 | 0.64953 (12) | 0.5832 (4) | 0.05935 (6) | 0.0189 (3) | |
| C2 | 0.74416 (12) | 0.6124 (4) | 0.09880 (6) | 0.0205 (3) | |
| H2 | 0.8137 (17) | 0.536 (5) | 0.0930 (8) | 0.025 (5)* | |
| C3 | 0.73085 (13) | 0.7578 (4) | 0.14580 (6) | 0.0224 (3) | |
| H3 | 0.7917 (16) | 0.776 (5) | 0.1733 (8) | 0.026 (5)* | |
| C4 | 0.62425 (13) | 0.8776 (4) | 0.15222 (6) | 0.0218 (3) | |
| C5 | 0.53646 (13) | 0.8461 (4) | 0.11167 (6) | 0.0231 (3) | |
| H5 | 0.4625 (18) | 0.923 (5) | 0.1152 (9) | 0.030 (6)* | |
| C6 | 0.7500 | 0.2511 (5) | 0.0000 | 0.0207 (4) | |
| H6 | 0.7804 (16) | 0.108 (5) | 0.0309 (8) | 0.024 (5)* |
| U11 | U22 | U33 | U12 | U13 | U23 | |
| Br | 0.04319 (11) | 0.02711 (9) | 0.01784 (8) | −0.00538 (7) | 0.01056 (6) | −0.00376 (6) |
| N1 | 0.0194 (5) | 0.0262 (6) | 0.0208 (6) | −0.0010 (5) | 0.0045 (4) | −0.0038 (5) |
| N2 | 0.0166 (5) | 0.0286 (6) | 0.0188 (6) | −0.0013 (5) | 0.0033 (4) | −0.0050 (5) |
| C1 | 0.0201 (6) | 0.0198 (6) | 0.0175 (6) | −0.0032 (5) | 0.0052 (5) | 0.0006 (5) |
| C2 | 0.0192 (6) | 0.0231 (7) | 0.0192 (6) | −0.0013 (5) | 0.0030 (5) | 0.0023 (5) |
| C3 | 0.0258 (7) | 0.0232 (7) | 0.0176 (6) | −0.0029 (6) | 0.0010 (5) | 0.0026 (6) |
| C4 | 0.0294 (7) | 0.0214 (6) | 0.0159 (6) | −0.0049 (5) | 0.0074 (5) | −0.0013 (5) |
| C5 | 0.0224 (7) | 0.0260 (7) | 0.0219 (7) | −0.0020 (6) | 0.0071 (5) | −0.0032 (6) |
| C6 | 0.0227 (9) | 0.0204 (9) | 0.0199 (9) | 0.000 | 0.0067 (7) | 0.000 |
| Br—C4 | 1.8838 (15) | C2—C3 | 1.378 (2) |
| N1—C1 | 1.3452 (19) | C3—H3 | 0.94 (2) |
| N1—C5 | 1.3356 (19) | C3—C4 | 1.391 (2) |
| N2—H2N | 0.868 (9) | C4—C5 | 1.374 (2) |
| N2—C1 | 1.3596 (18) | C5—H5 | 0.95 (2) |
| N2—C6 | 1.4425 (17) | C6—N2i | 1.4425 (17) |
| C1—C2 | 1.410 (2) | C6—H6 | 1.01 (2) |
| C2—H2 | 0.92 (2) | ||
| C1—N1—C5 | 118.31 (13) | C2—C3—C4 | 118.51 (14) |
| H2N—N2—C1 | 115.0 (14) | H3—C3—C4 | 119.9 (13) |
| H2N—N2—C6 | 117.5 (14) | Br—C4—C3 | 122.18 (11) |
| C1—N2—C6 | 123.94 (11) | Br—C4—C5 | 118.90 (12) |
| N1—C1—N2 | 115.37 (13) | C3—C4—C5 | 118.92 (14) |
| N1—C1—C2 | 121.41 (13) | N1—C5—C4 | 123.52 (14) |
| N2—C1—C2 | 123.20 (13) | N1—C5—H5 | 115.8 (13) |
| C1—C2—H2 | 120.1 (13) | C4—C5—H5 | 120.6 (13) |
| C1—C2—C3 | 119.31 (14) | N2—C6—N2i | 114.56 (18) |
| H2—C2—C3 | 120.6 (13) | N2—C6—H6 | 110.2 (11) |
| C2—C3—H3 | 121.6 (13) | N2i—C6—H6 | 106.1 (11) |
| C5—N1—C1—N2 | −178.95 (14) | C2—C3—C4—Br | 179.74 (11) |
| C5—N1—C1—C2 | −0.4 (2) | C2—C3—C4—C5 | 0.1 (2) |
| C6—N2—C1—N1 | −168.30 (15) | C1—N1—C5—C4 | −0.9 (2) |
| C6—N2—C1—C2 | 13.2 (2) | Br—C4—C5—N1 | −178.55 (12) |
| N1—C1—C2—C3 | 1.6 (2) | C3—C4—C5—N1 | 1.1 (2) |
| N2—C1—C2—C3 | 179.98 (14) | C1—N2—C6—N2i | −80.54 (14) |
| C1—C2—C3—C4 | −1.4 (2) |
| Symmetry codes: (i) −x+3/2, y, −z. |
| D—H···A | D—H | H···A | D···A | D—H···A |
| N2—H2N···N1ii | 0.87 (1) | 2.11 (1) | 2.9645 (18) | 168 (2) |
| Symmetry codes: (ii) −x+1, −y+1, −z. |
| D—H···A | D—H | H···A | D···A | D—H···A |
| N2—H2N···N1i | 0.87 (1) | 2.11 (1) | 2.9645 (18) | 168 (2) |
| Symmetry codes: (i) −x+1, −y+1, −z. |
Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555–1573.
Bienaymé, H. & Bouzid, K. (1998). Angew. Chem. Int. Ed. 37, 2234–2237.
Blackburn, C., Guan, B., Fleming, P., Shiosaki, K. & Tsai, S. (1998). Tetrahedron Lett. 39, 3635–3638.
Bruker (2007). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.
Groebke, K., Weber, L. & Mehlin, F. (1998). Synlett, pp. 661–663.
Mandair, G. S., Light, M., Russell, A., Hursthouse, M. & Bradley, M. (2002). Tetrahedron Lett. 43, 4267–4269.
Parchinsky, V. Z., Schuvalova, O., Ushalova, O., Krachenko, D. V. & Krasavin, M. (2006). Tetrahedron Lett. 47, 947–951.
Sheldrick, G. M. (1996). SADABS. University of Göttingen, Germany.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925.
Wu, H., Zhou, J., Yu, H.-Z., Lu, L.-L., Xu, Z., Yu, K.-B. & Shi, D.-Q. (2004). Acta Cryst. E60, o2085–o2086.
The Groebke-Blackburn reaction is the most popular way to prepare imidazo-azines from 2-aminoazines in a single-step. (Groebke et al., 1998; Bienaymé & Bouzid,1998; Blackburn et al., 1998). The reaction involves addition of 2-aminoazine 1 to the aldehyde in the presence of catalytic amounts of acid to generate the respective Schiff base which undergoes a non-concerted [4 + 1] cycloaddition with an isocyanide to form the imidazoazine 2 (Pathway A, Figure 1). Though imidazoazine 2 remained the major product, it was later found that the reaction also produced the isomeric imidazo[1,2-a]pyrimidine product 3 through an alternative iminium intermediate involving the ring nitrogen of 1 (Pathway B, Figure 1; Parchinsky et al., 2006). Similarly, nucleophilic solvents (for example, methanol) were found to promote interaction of the primary imine intermediate with the second molecule of 2-aminoazine or the solvent itself to give side-products like 4 (Pathway C, Figure 1; Mandair et al., 2002).
We, in one case, decided to synthesize N-benzyl-6-bromoindolizin-3-amine, 3a. Interestingly, the reaction did not yield the expected product 2a or the regioisomer 3a. However, the product which crystallized from a solution of dichloromethane turned out to be N,N'-bis(5-bromopyridin-2-yl)methanediamine, 4a in 20% yield (Figure 2).
The V-shaped structure of 4a is shown in Figure 3. The compound has crystallized with atom C6 on a twofold rotation axis, and has been set in space group I2/a. Molecular dimensions are unexceptional. In the crystal, inversion-related N—H···N hydrogen bonding interactions form an R22(8) graph set motif (Bernstein et al., 1995). As a result, the crystal forms an infinite hydrogen bonded tape of V-shaped molecules, which propagates in the a-axis direction. The tapes are stacked in the b-axis direction, and the separation between each tape is approximately 3.6 Å. The structure of the related compound N,N'-Di-2-pyridylmethylenediamine exhibits the same V-shaped structure, but with a different crystal packing arrangment (Wu et al., 2004).