Pyrazino[2,3-b]indolizine-10-carbo­nitrile

In the crystal structure of the title compound, C₁₁H₆N₄, neighbouring mol­ecules are linked into inversion dimers through pairs of weak C—H⋯N hydrogen bonds, forming an R₂²(10) ring motif. The dimers forming this motif are further linked by π–π inter­actions. With respective average deviations from planarity of 0.004 (2) and 0.004 (1) Å, the pyrazino[2,3-β]indolizine and cyano fragment are oriented at 0.8 (1)° to each other. The mean planes of the pyrazino[2,3-b]indolizine skeleton either lie parallel or are inclined at an angle of 28.7 (2)° in the crystal.

Related literature

For applications of this class of compounds, see: Akiyama et al. (1978); Foks et al. (2005); Kaliszan et al. (1985); Kushner et al. (1952); Mussinan et al. (1973); Petrusewicz et al. (1993, 1995); Seitz et al. (2002). For the synthesis, see: Pilarski & Foks (1981 and 1982). For the analysis of inter­molecular inter­actions, see: Spek (2009). For a description of the Cambridge Structural Database, see: Allen (2002). For hydrogen bonds, see: Steiner (1999).

Experimental

Crystal data

• C₁₁H₆N₄

• M_r = 194.20

• Monoclinic, P 2₁ /c

• a = 3.8515 (5) Å

• b = 14.147 (2) Å

• c = 16.606 (3) Å

• β = 91.260 (14)°

• V = 904.6 (2) ų

• Z = 4

• Mo Kα radiation

• μ = 0.09 mm⁻¹

• T = 295 K

• 0.30 × 0.08 × 0.06 mm

Data collection

• Oxford Diffraction Ruby CCD diffractometer

• Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2008) T_min = 0.992, T_max = 0.999

• 6832 measured reflections

• 1606 independent reflections

• 1186 reflections with I > 2σ(I)

• R_int = 0.032

Refinement

• R[F² > 2σ(F²)] = 0.040

• wR(F²) = 0.111

• S = 1.02

• 1606 reflections

• 137 parameters

• H-atom parameters constrained

• Δρ_max = 0.18 e Å⁻³

• Δρ_min = −0.15 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C2—H2⋯N12^i	0.93	2.61	3.487 (2)	157
Symmetry code: (i) -x+1, -y, -z.

Table 2
π–π interactions (Å, °)

CgI	CgJ	Cg⋯Cg	Dihedral angle	Interplanar distance	Offset
A	B^ii	3.608 (1)	0.6	3.358 (1)	1.320 (1)
Symmetry codes: (ii) -1+x, y, z. Notes: CgA and CgB are the centroids of the N1/C6–C8/C13 and N1/C2–C6 rings, respectively. The dihedral angle is that between the planes of the rings CgI and CgJ. The interplanar distance is the perpendicular distance of CgI from ring J. The offset is the perpendicular distance of ring I from ring J.

Data collection: CrysAlis CCD (Oxford Diffraction, 2008); cell refinement: CrysAlis RED (Oxford Diffraction, 2008); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009).

Supporting information

S1. Comment

Pyrazines play an important role as building block of many pharmaceutical products. They occur in many compounds with pharmaceutical and flavoring applications. Many of them have been found in nature. Pyrazines are responsible for flavour in foodstuffs, e.g. cheese, tea, coffee or cooked meat. (Akiyama et al., 1978; Mussinan et al., 1973). Biological activities of pyrazine derivatives are widely discussed in plentiful scientific publications: antibacterial (Foks et al., 2005), anti-inflammatory (Petrusewicz et al., 1995), chemotherapeutic agent (Kushner et al., 1952), antimycobacterial (Seitz et al., 2002) and antithrombotic (Petrusewicz et al., 1993). Such pharmacological activities in group of pyrazine are possibly the result of their structures. It is known that the pyrazine-acetonitrile shows antiplatelet and analgestic activity (Kaliszan et al., 1985). X-Ray structure of pyrazino[2,3-β]indolizine-10-carbonitrile is subject of the present paper.

In the Cambridge Structural Database (CSD; Version 5.27; Allen, 2002), there are no crystal structures containing the pyrazino[2,3-β]indolizine skeleton.

With average deviations from planarity of 0.004 (2) and 0.004 (1)Å respectively, the pyrazino[2,3-β]indolizine and cyano fragments are oriented at 0.8 (1)° to each other. The mean planes of the pyrazino[2,3-β]indolizine skeleton lie either parallel to or are inclined at an angle of 28.7 (2)° in the lattice.

In the crystal structure, neighbouring molecules are linked through weak C–H···N hydrogen bond forming R₂²(10) ring motif (Table 1 and Fig. 2). Molecules which forming this motif are linked by π–π interactions between the central ring A and the lateral rings B (Table 2 and Fig. 2). All the interactions demonstrated were found by PLATON (Spek, 2009).

Related literature

For applications of this class of compounds, see: Akiyama et al. (1978); Foks et al. (2005); Kaliszan et al. (1985); Kushner et al. (1952); Mussinan et al. (1973); Petrusewicz et al. (1993, 1995); Seitz et al. (2002). For the synthesis, see: Pilarski & Foks (1981 and 1982). For the analysis of intermolecular interactions, see: Spek (2009). For a description of the Cambridge Structural Database, see: Allen (2002). For hydrogen bonds, see: Steiner (1999).

S2. Experimental

Pyrazino[2,3-β]indolizine-10-carbonitrile was obtained by mixing 2,3-dichloropyrazine, 2-pyridylacetonitrile and potassium carbonate in DMSO. The mixture was stirred for 5 h at 333 K. After cooling the reaction mixture to room temperature, water was added. Then mixture was acidified with hydrochloric acid (Pilarski & Foks, 1981 and 1982). The orange-green precipitate was obtained. Single crystals suitable for X-ray analysis were grown in methanol solution (m. p. = 486 K).

S3. Refinement

All H atoms were positioned geometrically and refined using a riding model, with C–H = 0.93Å and U_iso(H) = 1.2U_eq(C).

Computing details

Data collection: CrysAlis CCD (Oxford Diffraction, 2008); cell refinement: CrysAlis RED (Oxford Diffraction, 2008); data reduction: CrysAlis RED (Oxford Diffraction, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures

	Fig. 1. The molecular structure of the title compound showing the atom-labeling scheme. Displacement ellipsoids are drawn at the 25% probability level and H atoms are shown as small spheres of arbitrary radius. CgA and CgB denote the ring centroids.
	Fig. 2. The arrangement of the molecules in the crystal structure viewed approximately along a axis. The C—H···N interactions are represented by dashed lines and the π–π interactions are represented by dotted lines. H atoms not involved in the interactions have been omitted. [Symmetry codes: (i) 1 - x, - y, - z; (ii) -1 + x, y, z.]

Pyrazino[2,3-b]indolizine-10-carbonitrile

Crystal data

C11H6N4	F(000) = 400
Mr = 194.20	Dx = 1.426 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 6832 reflections
a = 3.8515 (5) Å	θ = 3.0–25.0°
b = 14.147 (2) Å	µ = 0.09 mm^−1
c = 16.606 (3) Å	T = 295 K
β = 91.260 (14)°	Needle, orange-green
V = 904.6 (2) Å^3	0.30 × 0.08 × 0.06 mm
Z = 4

Data collection

Oxford Diffraction Ruby CCD diffractometer	1606 independent reflections
Radiation source: Enhance (Mo) X-ray Source	1186 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.032
Detector resolution: 10.4002 pixels mm^-1	θmax = 25.1°, θmin = 3.1°
ω scans	h = −4→4
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2008)	k = −16→15
Tmin = 0.992, Tmax = 0.999	l = −18→19
6832 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.040	H-atom parameters constrained
wR(F^2) = 0.111	w = 1/[σ^2(Fo^2) + (0.0745P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 1.02	(Δ/σ)max < 0.001
1606 reflections	Δρmax = 0.18 e Å^−3
137 parameters	Δρmin = −0.15 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.017 (5)

Special details

Experimental. Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.

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 > 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
N1	0.1906 (3)	0.18749 (8)	0.01142 (7)	0.0395 (3)
C2	0.3590 (4)	0.15549 (12)	−0.05644 (9)	0.0463 (4)
H2	0.4296	0.0928	−0.0597	0.056*
C3	0.4196 (4)	0.21534 (13)	−0.11734 (10)	0.0541 (5)
H3	0.5303	0.1943	−0.1632	0.065*
C4	0.3135 (4)	0.31070 (13)	−0.11094 (11)	0.0554 (5)
H4	0.3574	0.3523	−0.1529	0.066*
C5	0.1475 (4)	0.34299 (12)	−0.04437 (10)	0.0506 (4)
H5	0.0804	0.4060	−0.0415	0.061*
C6	0.0772 (4)	0.28097 (10)	0.02016 (9)	0.0412 (4)
C7	−0.0876 (4)	0.29055 (10)	0.09485 (9)	0.0431 (4)
C8	−0.0708 (4)	0.20124 (11)	0.13408 (9)	0.0410 (4)
N9	−0.1882 (3)	0.17236 (10)	0.20656 (8)	0.0500 (4)
C10	−0.1199 (4)	0.08189 (13)	0.22182 (10)	0.0538 (5)
H10	−0.1906	0.0569	0.2706	0.065*
C11	0.0522 (4)	0.02209 (12)	0.16866 (10)	0.0528 (4)
H11	0.0890	−0.0403	0.1844	0.063*
N12	0.1684 (3)	0.04892 (9)	0.09592 (8)	0.0482 (4)
C13	0.1002 (3)	0.13879 (10)	0.08115 (9)	0.0387 (4)
C14	−0.2351 (4)	0.37523 (12)	0.12502 (10)	0.0528 (5)
N15	−0.3567 (4)	0.44383 (12)	0.14836 (11)	0.0782 (5)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0429 (6)	0.0342 (7)	0.0413 (7)	0.0010 (5)	−0.0001 (5)	−0.0047 (5)
C2	0.0487 (8)	0.0447 (9)	0.0455 (9)	0.0043 (7)	0.0020 (7)	−0.0093 (7)
C3	0.0561 (10)	0.0600 (12)	0.0466 (10)	0.0024 (8)	0.0074 (8)	−0.0039 (8)
C4	0.0558 (9)	0.0571 (11)	0.0533 (11)	−0.0042 (8)	0.0013 (8)	0.0129 (8)
C5	0.0533 (9)	0.0398 (9)	0.0586 (11)	−0.0007 (7)	−0.0023 (8)	0.0044 (8)
C6	0.0401 (7)	0.0331 (8)	0.0501 (10)	−0.0016 (6)	−0.0033 (7)	−0.0045 (7)
C7	0.0463 (8)	0.0351 (9)	0.0479 (9)	0.0010 (6)	0.0007 (7)	−0.0075 (7)
C8	0.0407 (8)	0.0406 (9)	0.0415 (9)	−0.0042 (6)	−0.0013 (6)	−0.0059 (7)
N9	0.0535 (7)	0.0499 (10)	0.0467 (9)	−0.0028 (6)	0.0035 (6)	−0.0017 (6)
C10	0.0568 (9)	0.0560 (12)	0.0485 (10)	−0.0065 (8)	0.0020 (8)	0.0058 (8)
C11	0.0607 (9)	0.0430 (10)	0.0543 (10)	−0.0034 (8)	−0.0049 (8)	0.0086 (8)
N12	0.0545 (7)	0.0373 (8)	0.0525 (8)	0.0030 (6)	−0.0043 (6)	−0.0006 (6)
C13	0.0407 (7)	0.0339 (9)	0.0413 (9)	−0.0012 (6)	−0.0026 (6)	−0.0032 (6)
C14	0.0552 (9)	0.0436 (11)	0.0597 (11)	0.0000 (8)	0.0016 (8)	−0.0123 (8)
N15	0.0841 (11)	0.0517 (11)	0.0992 (13)	0.0092 (8)	0.0080 (10)	−0.0274 (9)

Geometric parameters (Å, º)

N1—C2	1.3883 (19)	C7—C14	1.422 (2)
N1—C13	1.3980 (18)	C7—C8	1.422 (2)
N1—C6	1.4014 (18)	C8—N9	1.3580 (19)
C2—C3	1.343 (2)	C8—C13	1.419 (2)
C2—H2	0.9300	N9—C10	1.330 (2)
C3—C4	1.414 (3)	C10—C11	1.400 (2)
C3—H3	0.9300	C10—H10	0.9300
C4—C5	1.368 (2)	C11—N12	1.352 (2)
C4—H4	0.9300	C11—H11	0.9300
C5—C6	1.416 (2)	N12—C13	1.3201 (19)
C5—H5	0.9300	C14—N15	1.149 (2)
C6—C7	1.412 (2)
C2—N1—C13	129.87 (13)	C6—C7—C14	125.53 (14)
C2—N1—C6	122.96 (13)	C6—C7—C8	107.47 (12)
C13—N1—C6	107.18 (11)	C14—C7—C8	126.98 (15)
C3—C2—N1	119.85 (15)	N9—C8—C13	122.01 (14)
C3—C2—H2	120.1	N9—C8—C7	131.34 (14)
N1—C2—H2	120.1	C13—C8—C7	106.65 (13)
C2—C3—C4	119.29 (15)	C10—N9—C8	112.96 (13)
C2—C3—H3	120.4	N9—C10—C11	123.77 (15)
C4—C3—H3	120.4	N9—C10—H10	118.1
C5—C4—C3	121.36 (16)	C11—C10—H10	118.1
C5—C4—H4	119.3	N12—C11—C10	124.36 (15)
C3—C4—H4	119.3	N12—C11—H11	117.8
C4—C5—C6	120.35 (16)	C10—C11—H11	117.8
C4—C5—H5	119.8	C13—N12—C11	111.60 (13)
C6—C5—H5	119.8	N12—C13—N1	125.19 (13)
N1—C6—C7	109.19 (12)	N12—C13—C8	125.30 (14)
N1—C6—C5	116.18 (13)	N1—C13—C8	109.50 (13)
C7—C6—C5	134.63 (14)	N15—C14—C7	179.0 (2)
C13—N1—C2—C3	179.88 (14)	C6—C7—C8—C13	−0.94 (16)
C6—N1—C2—C3	0.1 (2)	C14—C7—C8—C13	−179.67 (14)
N1—C2—C3—C4	0.6 (2)	C13—C8—N9—C10	1.07 (19)
C2—C3—C4—C5	−0.6 (2)	C7—C8—N9—C10	−179.86 (16)
C3—C4—C5—C6	−0.1 (2)	C8—N9—C10—C11	−0.5 (2)
C2—N1—C6—C7	179.16 (12)	N9—C10—C11—N12	−0.1 (3)
C13—N1—C6—C7	−0.67 (14)	C10—C11—N12—C13	0.2 (2)
C2—N1—C6—C5	−0.79 (19)	C11—N12—C13—N1	179.34 (12)
C13—N1—C6—C5	179.38 (12)	C11—N12—C13—C8	0.4 (2)
C4—C5—C6—N1	0.8 (2)	C2—N1—C13—N12	1.2 (2)
C4—C5—C6—C7	−179.16 (15)	C6—N1—C13—N12	−178.99 (13)
N1—C6—C7—C14	179.76 (14)	C2—N1—C13—C8	−179.75 (12)
C5—C6—C7—C14	−0.3 (3)	C6—N1—C13—C8	0.07 (14)
N1—C6—C7—C8	1.01 (15)	N9—C8—C13—N12	−1.1 (2)
C5—C6—C7—C8	−179.06 (15)	C7—C8—C13—N12	179.60 (14)
C6—C7—C8—N9	179.88 (14)	N9—C8—C13—N1	179.82 (11)
C14—C7—C8—N9	1.2 (3)	C7—C8—C13—N1	0.55 (15)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C2—H2···N12^i	0.93	2.61	3.487 (2)	157

Symmetry code: (i) −x+1, −y, −z.