A novel synthesis of 2,5-diphenylpyrazine

Article abstract of DOI:10.1007/s11164-010-0159-9

The compound C₁₆H₁₂N₂ (2,5- diphenylpyrazine) was obtained as the by-product of synthesizing 5H-Imidazol[2,3-b]isoquinoline-1-ethanol-5-one, 1,2,3, 10b-tetrahydro-, β(S)-phenyl-3(S)-phenyl-(compound 2), and its structure was determined by X-ray diffraction. The crystal is monoclinic, P2(1)/c, a = 13.466(5) A, α = 90.00°, b = 5.758(2) A, β = 93.049(9)°, c = 7.713(3) A, γ = 90.00°, V = 597.2(4) A³, Z = 2, Dcalc. = 1.292 mg/m³; the final R factor is R₁ = 0.0592, 771 for reflections with I₀ > 2σ(I₀). Springer Science+Business Media B.V. 2010.

Full text of DOI:10.1007/s11164-010-0159-9

Res Chem Intermed (2010) 36:491–494
DOI 10.1007/s11164-010-0159-9
A novel synthesis of 2,5-diphenylpyrazine
•
Mei Luo Wen Min Pang Hao Yin Ke Liang Hu
•
•
Received: 17 February 2010 / Accepted: 11 June 2010 / Published online: 13 August 2010
Ó Springer Science+Business Media B.V. 2010
Abstract The compound C16H12N2 (2,5-diphenylpyrazine) was obtained as the
by-product of synthesizing 5H-Imidazol[2,3-b]isoquinoline-1-ethanol-5-one,1,2,3,
10b-tetrahydro-, b(S)-phenyl-3(S)-phenyl-(compound 2), and its structure was deter-
˚
mined by X-ray diffraction. The crystal is monoclinic, P2(1)/c, a = 13.466(5) A,
˚
˚
a = 90.008, b = 5.758(2) A, b = 93.049(9)8, c = 7.713(3) A, c = 90.008, V =
3
3
˚
597.2(4) A , Z = 2, Dcalc. = 1.292 mg/m ; the final R factor is R1 = 0.0592, 771
for reflections with I0 [ 2r(I0).
Keywords Crystal structure Á C16H12N2 Á 2,5-Diphenylpyrazine Á
5H-Imidazol[2,3-b]isoquinoline-1-ethanol-5-one Á 1,2,3,10b-Tetrahydro- Á
b(S)-Phenyl-3(S)-phenyl-
Introduction
Pyrazine and derivatives are important medical products [1–3]; for example, they
can be used for treating atherosclerosis, neurological, cardiovascular, and other
diseases, and also used as intermediates for agrochemicals, pharmaceuticals and
perfumes. They are easily prepared from reductive decyanation of pyrazinecarbo-
nitriles, or from ethylenediamine on copper oxide/copper chromite catalysts [4, 5].
In this communication, we report on the crystal structure of 2,5-diphenylpyrazine.
Electronic supplementary material Theonlineversionofthisarticle(doi:10.1007/s11164-010-0159-9)
contains supplementary material, which is available to authorized users.
M. Luo (&)
Hefei University of Technology, Hefei 230009, China
e-mail: lmhh5523385@yahoo.cn
W. M. Pang Á H. Yin Á K. L. Hu
University of Science and Technology of China, Hefei 230009, China
123

492
M. Luo et al.
This compound was first reported in 1975 [6], and it was reported again in 1973 [7],
Our original target was to synthesize the bis-oxazoline, but instead we got the two
products, 5H-Imidazol[2,3-b]isoquinoline-1-ethanol-5-one,1,2,3,10b-tetrahydro-,
b(S)-phenyl-3(S)-phenyl(compound 2), and the by-products, 2,5-diphenylpyrazine
(Scheme 1, Fig. 1).
Experimental
Preparation of 2,5-diphenylpyrazine (1)
An amount of 60 mg of dry ZnCl2, 2-cyanophenyacetonitrile (7.8 mmol)
L-phenylalaninol (22.4 mmol) was added under anhydrous and oxygen-free
condition in a dry 100-mL Schlenk flask. They were dissolved in 30 mL of dry
chlorobenzene, the reaction mixture was refluxed for 72 h. The solvent was
removed under reduced pressure and the residue was dissolved in 15 mL H2O,
extracted with 10 9 3 mL of dichloromethane, the solvent was removed under
vacuum, to give the crude red oil. Further purification was performed by silica gel
(petroleum ether/dichlormethane 4/1), the red crystals of 1 were obtained in the first
component of the collection points.
Structure determination
A red block prismatic crystal of the title compound 1 of approximately 0.347 9
0.211 9 0.056 mm was selected for the data collection on a BRUKER SMART
´
˚
diffractometer with graphite monochromated MoKa radiation (k = 0.7103 A).
A total of 1,103 reflections were collected in the range of 1.51 \ h \ 25.49° by using
OH
Ph
N
CH2OH
ZnCl2
N
N
H N
H
2
2
+
chlorobenzene, reflux
Ph
Ph
O
2
N
N
N
1
Scheme 1 The synthetic route to the 2,5-diphenylpyrazine
123

Novel synthesis of 2,5-diphenylpyrazine
493
Fig. 1 Crystal structure of 1
‘‘phi and omega’’ scan techniques at 293(2) K, C16H12N2, M = 232.28, monoclinic,
˚
˚
P2(1)/c, a = 13.466(5) A, a = 90.008, b = 5.758(2) A, b = 93.049(9)8, c =
3
3
˚
˚
7.713(3) A, c = 90.008, V = 597.2(4) A , Z = 2, Dcalc. = 1.292 mg/m , the final
R factor is R1 = 0.0592, 771 for reflections with I0 [ 2r(I0), Rx = 0.1334 for all
data; largest peak and hole are 0.181 and -0.175eA-3 respectively. The structure were
solved by full-matrix least-squares on F2 using the SHELXTL PROGREM [8–10].
˚
Results and discussion
The synthetic route can be summarized as follows (Scheme 1). We adopted an
efficient, one-pot method to synthesize 5H-Imidazol[2,3-b]isoquinoline-1-ethanol-
5-one,1,2,3,10b-tetrahydro-, b(S)-phenyl-3(S)-phenyl- (2). It was prepared from the
reaction of 2-cyanophenylacetonitrile with L-phenylalaninol in chlorobenzene
under dry, anaerobic conditions. ZnCl2 was dried under vacuum and acted as the
Lewis catalyst in this reaction, but interestingly, in the process of silical gel column
chromatography, we were able to characterize the structure of 2,5-diphenylpyrazine.
From Fig. 1, several interesting observations can be made about the structure.
Compound 1 was composed of two phenyl and 3,6-dihydropyrazine rings. The C(1),
C(2), C(3), C(4), C(5), and C(6) atoms were all coplanar. The C–C distances ranged
˚
from 1.372(3) to 1.397(3) A, and the C–C bond angles ranged from 118.5(2)° to
121.1(10)°. The aromatic ring in the molecule was in agreement with the literature
˚
without any unusual features. The two C=N bonds [N(1) *C(1) = 1.340(3) A,
˚
N(1) *C(2) = 1.334(3) A] were not equal, C(1), C(2), N(1), C(1A), C(2A), N(1A)
atoms formed a pyrazine ring, they were also coplanar, and its bond angles were
nearly 120°.
Conclusions
In summary, we report for the first time a novel method of synthesizing 2,5-
diphenylpyrazine. It was obtained unexpectedly, and the next step of our research is
to put forward a reasonable reaction mechanism.
123

494
M. Luo et al.
References
1. A.E. Erickson, P.E. Spoerri, J. Am. Chem. Soc. 68, 400–402 (1946)
2. C. Charalambos, N. Sotirios, C. Panayotis, J. Chem. Eng. Data 32, 478–479 (1987)
3. B.M. Latha, V. Sadasivam, B. Sivasankar, Catal. Commun. 8, 1070–1073 (2007)
4. J. Albaneze-Walker, M. Zhao, M.D. Baker, P.G. Dormer, J. McNamara, Tetrahedron Lett. 43,
6747–6750 (2002)
5. B. George, G. Jose, J. Org. Chem. 56, 2605–2606 (1991)
6. H. Alper, S. Wollowitz, J. Am. Chem. Soc. 97, 3541–3543 (1975)
7. J. Daniel, D.N. Dhar, Synth. Commun. 23, 2151–2157 (1993)
¨
8. Sheldrick, G. M. SHELXS-97, Program for X-ray Crystal Structure Solution (Gottingen University,
Germany, 1997)
9. Sheldrick, G. M. SHELXL-97, Program for X-ray Crystal Structure Refinement (Gottingen Univer-
¨
sity, Germany, 1997)
10. G.H. Stout, L.H. Jensen, X-Ray Structure Determination: A Practical Guide (MacMillan, New York,
1968)
123