rac-(2R,3S)-2-Phenyl-3-(3-phenyl-1,2,3,4-tetra­hydro­quinoxalin-2-yl)quinoxaline

Sven Ammermann; Constantin Daniliuc; Peter G Jones; Wolf-Walther du Mont; Hans-Hermann Johannes

doi:10.1107/S1600536808015481

. 2008 Jun 7;64(Pt 7):o1205–o1206. doi: 10.1107/S1600536808015481

rac-(2R,3S)-2-Phenyl-3-(3-phenyl-1,2,3,4-tetrahydroquinoxalin-2-yl)quinoxaline

Sven Ammermann ^a, Constantin Daniliuc ^b, Peter G Jones ^b,^*, Wolf-Walther du Mont ^b, Hans-Hermann Johannes ^a

PMCID: PMC2961777 PMID: 21202845

Abstract

The title compound, C₂₈H₂₂N₄, is the unexpected by-product of the reaction of 2-hydroxyacetophenone and 1,2-diaminobenzene under iodine catalysis, during which a carbon–carbon σ-bond between two quinoxaline units was formed. Although a fully oxidized title compound should sterically be possible, only one quinoxaline ring is fully oxidized while the second ring remains in the reduced form. As expected, the tetrahydroquinoxaline unit is not planar; it adopts a sofa conformation, whereby the atom joining the two heterocyclic systems lies out of the plane of the other atoms. The quinoxaline ring system makes a dihedral angle of 53.61 (4)° with its phenyl ring substituent. The crystal packing is determined by pairs of N—H⋯N, N—H⋯π and weak C—H⋯N hydrogen bonds, forming a chain parallel to the a axis.

Related literature

For related literature, see: Banik et al. (1999 ▶); Chen et al. (2005 ▶); Gazit et al. (1996 ▶); Hwang et al. (2005 ▶); Jones et al. (2006 ▶); Kim et al. (2004 ▶); Kulkarni et al. (2006 ▶); McGovern et al. (2005 ▶); More et al. (2005 ▶); Raw et al. (2004 ▶); Robinson & Taylor (2005 ▶); Shirota & Kageyama (2007 ▶).

Experimental

Crystal data

C₂₈H₂₂N₄
M _r = 414.50
Monoclinic,
a = 11.1601 (6) Å
b = 11.3987 (6) Å
c = 16.4638 (8) Å
β = 93.170 (2)°
V = 2091.17 (19) Å³
Z = 4
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 133 (2) K
0.35 × 0.35 × 0.32 mm

Data collection

Bruker SMART 1000 CCD diffractometer
Absorption correction: none
24311 measured reflections
6364 independent reflections
3306 reflections with I > 2σ(I)
R _int = 0.109

Refinement

R[F ² > 2σ(F ²)] = 0.057
wR(F ²) = 0.152
S = 0.92
6364 reflections
297 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.42 e Å⁻³
Δρ_min = −0.29 e Å⁻³

Data collection: SMART (Bruker, 1998 ▶); cell refinement: SAINT (Bruker, 1998 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: XP (Siemens, 1994 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808015481/su2058sup1.cif

e-64-o1205-sup1.cif^{(24.8KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808015481/su2058Isup2.hkl

e-64-o1205-Isup2.hkl^{(311.5KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N4—H02⋯N2ⁱ	0.84 (2)	2.49 (2)	3.211 (2)	144 (2)
C15—H15⋯N3ⁱⁱ	1.00	2.69	3.499 (2)	138
N3—H01⋯Cent(C23–C28)ⁱⁱ	0.85 (2)	2.63	3.42	157

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

We thank the German Federal Ministry of Education and Research (BMBF) for financial support.

supplementary crystallographic information

Comment

Quinoxalines are a versatile class of heterocyclic compounds. This moiety is found in pharmaceutically and biologically active molecules e.g. as potential antibiotics (Kim et al., 2004), DNA cleavage agents (More et al., 2005) and for inhibition of tumor activity (Gazit et al., 1996). The electron-withdrawing property of quinoxalines leads to their use in electroluminescent devices as electron transporters (Shirota & Kageyama, 2007). Often these transporters are designed as a dipolar unit consisting of an acceptor (quinoxaline) and a donor (e.g. triarylamines) (Chen et al., 2005; Kulkarni et al., 2006). Lately quinoxalines have been used as ligands for metal complexes (Jones et al., 2006) that show efficient electroluminescence (Hwang et al., 2005) in organic light-emitting diodes (OLEDs).

Several routes for the synthesis of quinoxalines are described in the literature. For condensations, starting materials are 1,2-diketones and 1,2-diamines which are reacted in boiling ethanol (Gazit et al., 1996) or at room temperature in acetonitrile with iodine as catalyst (More et al., 2005). For 2-substituted quinoxalines, α-hydroxy ketones and 1,2-diamines are used together with different catalysts such as Pd(OAc)₂/Et₃N (Robinson & Taylor, 2005) or MnO₂ (Raw et al., 2004). These catalysts are necessary to oxidize the alcohol from the a-hydroxy ketones. In the present study a synthesis for 2-phenylquinoxaline was planned under similiar conditions to those used by More et al. (2005) from 2-hydroxyacetophenone, 1,2-diaminobenzene and iodine without the use of an oxidization catalyst. As expected the yield of the reaction was low, but beside the anticipated product (I) the title compound (II) was formed. To the best of our knowledge neither the structure itself nor this type of formation have been described in the literature. Raw et al. (2004) describe the formation of an azobenzene derivative as the by-product. The most striking feature is the formation of a carbon-carbon σ-bond [C1—C15 1.536 (2) Å] between two quinoxaline moieties. Assuming that compound (I) is formed in the first place, either the attack on the C═ N bond or the reaction of (I) as a nucleophile with the starting materials could lead to the formation of a dimer. Subsequent reduction with 2 equivalents of hydrogen would form the title compound (II). Barik et al. (1999) demonstrated that dimeric structures starting from imines can be formed via a samarium-induced iodine-catalyzed reduction. The authors postulate a one electron transfer mechanism across the C═ N bond resulting in two carbon radicals merging in a pinacol type reaction. Even though these conditions cannot be found in our case, it is this reference that is most relevant to the formation of a dimer. The red color of compound (II) is remarkable and the origin is unclear, because the UV/VIS-spectrum shows no significant absorption above a maximum of 320 nm (ε = 9300 in CH₃CN). In comparison McGovern et al. (2005) have shown that an intramolecular charge-transfer causes the red color of 9,14-dihydrodipyridophenazine, which possesses a moiety like the 1',2',3',4'-tetrahydroquinoxaline in the present study. The title compound potentially exists as two different diastereomers, but one of them is formed exclusively, as shown by spectroscopic evidence. We surmise that the other diastereomer is suppressed for steric reasons.

The molecular structure of compound (II) is illustrated in Fig. 1. Bond lengths and angles in the two phenyl rings and in the quinoxaline unit are normal. As expected the tetrahydroquinoxaline unit is not planar; it adopts a sofa conformation, whereby the atom joining the two heterocyclic systems lies out of the plane of the other atoms. Atoms C15 and C16 show sp³hybridization (angles ranged from 107.9° to 113.9°). The relative configurations at atoms C15 and C16 are S,R. The bond length C15—C16 [1.549 (2) Å] indicates a C—C single bond, whereas bond C1—C2 [1.444 (2) Å] shows the aromatic character of an oxidized ring. The phenyl rings subtend interplanar angles of 53.61 (4)° with the quinoxaline ring system [C1, N1, C8, C3, N2 and C2], and 79.01 (4)° with the tetrahydroquinoxaline ring [C16, N4, C17, C22 and N3] (atom C15 lies 0.655 (2) Å out of this plane).

In the crystal structure of (II) the packing of the molecules is determined by weak N4—H02···N2 and C15—H15···N3 hydrogen bonds (Fig 2 and Table 1). Pairs of alternating C—H···N and N—H···N hydrogen bonds are formed across inversion centres. Additionally, there is an N—H···π contact from N3—H01 to the centroid of the phenyl ring [C23–C28]. The overall effect is to form a chain parallel to the a axis.

Experimental

A 100 ml round-bottomed flask was charged with 2-hydroxyacetophenone (3.00 g, 22.034 mmol), 1,2-diaminobenzene (2.86 g, 26.441 mmol), iodine (559 mg, 2.203 mmol), and acetonitrile (30 ml). The reaction was stirred for 23h at room temperature, monitored by thin-layer chromatography and finally concentrated to dryness under reduced pressure. The dark crude product obtained was then subjected to flash column chromatography using silica gel (eluent: 6:1 n-hexane–EtOAc). 630 mg (14%) of 2-phenylquinoxaline, the expected product, and 390 mg (9%) of the unexpected title compound, (II), were obtained. Red crystals of (II) grew overnight from the eluted fractions of the flash column chromatography.