Formation of quinoxalines
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 12, December, 2007 2511
Table 1. Conditions of the reaction and yields of quinoxalines
Apparently, ethanolаmine plays the role of a reducing
agent similarly to ethylenediamine, which is a mild reꢀ
ducing agent.1
Starting
comꢀ
T/°С
τ/h
Proꢀ YIeld
duct (%)
M.p./°С
(lit. data)
The sequence of processes in this synthesis of quinoxꢀ
aline derivatives is not yet studied. It can be supposed that
the enamine is initially formed from ethanolаmine. Conꢀ
version of ethanolamines to enamines upon treatment
with acids was confirmed in Ref. 2. Further attack of
enаmine at the nitrogen atom of the furazan ring leads to
the ring opening followed by the pyrazine ring closure to
form quinoxaline Nꢀoxide similarly to the known "Beirut
reaction".3 NꢀOxide oxygen atom, apparently, is readily
eliminated upon treatment with ethanolаmine, which, as
it was shown above, is a reducing agent (Scheme 3).
The found way for the synthesis of quinoxalines from
benzofurazans can serve as the alternative to the already
existing methods.
pound
1a
1b
1c
1d
1e
1f
150—160
150—160
150—160
165—170
100—120
150—160
165—170
150—160
4
5
4
12
1
4
2a
2b
2c
2d
2e
2f
87
85
72
74
75
89
78
29—30 (30.5)12
Oil (b.p. 248)13
55—57 (57.5)13
93—95 (90)14—16
164—165 *
194—195 *
1g
2e
16
1
2g
3
54—56 (55—57)1
66 144—145 (144—145)12
* Compounds were rеcrystallized from ethanol.
J = 2 Hz). 13C NMR, δ: 149.09; 147.84; 146.94 (CH); 146.02;
144.95 (CH); 135.90; 134.58 (CH); 118.31 (CH).
2ꢀPhenylꢀ2Hꢀtriazolo[4,5ꢀf]quinoxaline (2f). Found (%):
C, 67.90; H, 3.65; N, 28.20. C14H9N5. Calculated (%): C, 68.00;
H, 3.67; N, 28.33. MS, m/z: 247 [M]+. 1H NMR, δ: 7.38 (m,
1 H, Рh); 7.48 (m, 2 H, Ph); 7.85, 8.03 (both d, 1 H each, J =
10 Hz); 8.36 (m, 2 H, Ph); 8.84, 8.86 (both d, 1 H each, J =
2 Hz). 13C NMR, δ: 144.91; 144.56 (CH); 144.07; 143.83 (CH);
141.65; 139.80; 137.76; 129.46 (CH); 129.27 (CH); 128.93 (CH);
121.27 (CH); 120.22 (CH).
Experimental
IR spectra were recorded on a Bruker Vector spectrometer
in KBr pellets (concentration, 0.25%), H and 13C NMR specꢀ
1
tra were recorded on a Bruker AM 400 spectrometer (400.13 and
100.63 MHz, respectively) as 5—10% solutions in CDCl3, sigꢀ
nals of residual protons of the solvent at δ 7.24 (1H) and 76.90
(
13C) relatively to Ме4Si were used as the internal standard.
Mass spectra were recorded on a Finnigan MATꢀ8200 instruꢀ
ment (ionization energy of electrons: 70 eV, direct inlet of a
substance, the source of ions temperature: 180 °C). Monitoring
of the course of the reaction and purity of compounds were
performed by TLC on Sorbfil UVꢀ254 plates with visualization
in the UV light. Melting points were determined on the Kofler
microheating stage.
Benzofurazans 1a,b,e were synthesized according to the proꢀ
cedures described earlier4—6 from the corresponding benzofuroxꢀ
ans by the reaction with triethyl phosphite. Compounds 1c,7
1d,8 and 1f 9 were obtained according to the known procedures.
Compound 1g was synthesized from the corresponding dioxime
by its oxidation to furoxan10 followed by the reduction to furaꢀ
zan with sulfur in ethylene glycol11 in 60% yield. Structures of
quinoxalines obtained were established by comparison of their
melting points, IR and NMR spectra with those published in the
literature.
References
1. T. F. Chung, Y. M. Wu, and C. H. Cheng, J. Org. Chem.,
1984, 49, 1215.
2. S. A. Fine and J. Shreiner, J. Org. Chem., 1974, 39, 1009.
3. L. I. Khmelґnitskii, S. S. Novikov, and T. I. Godovikova,
Khimiya furoksanov. Reaktsii i primenenie [Chemistry of Furoxꢀ
ans. Reactions and Application], Nauka, Moscow, 1983,
142—175 pp. (in Russian).
4. A. S. Bailey and J. M. Evans, J. Chem. Soc., C, 1967, 2105.
5. P. B. Ghosh, B. Ternai, and M. W. Whitehouse, J. Med.
Chem., 1972, 15, 255.
6. A. J. Boulton, A. C. Gripper Gray, and A. R. Katritzky,
J. Chem. Soc., 1965, 5958.
7. R. J. Gaughran, J. P. Picard, and J. V. R. Kaufman, J. Am.
Chem. Soc., 1954, 76, 2233.
Synthesis of quinoxalines 2a—g and 3 (general procedure).
Ethanolаmine (4 mL) and pꢀtoluenesulfonic acid (0.1 g) were
added to benzofurazan 1a—g or 2g (1 g). The mixture was heatꢀ
ed until the starting compound disappeared (TLC monitoring).
The mixture was cooled and poured in brine. The product was
extracted with ethyl acetate (3×30 mL), the extract was washed
with brine (3×30 mL) and dried with MgSO4. The solvent was
evaporated, the residue was subjected to chromatography on
silica gel with chloroform as the eluent. Conditions of the reacꢀ
tion and yields of quinoxalines 2a—g and 3 are given in Table 1.
1,2,5ꢀOxadiazolo[3,4ꢀf]quinoxaline (2e). Found (%):
C, 55.80; H, 2.29; N, 32.60. C8H4N4O. Calculated (%): C, 55.82;
H, 2.34; N, 32.55. MS, m/z: 172 [M]+. 1H NMR, δ: 7.88,
7.96 (both d, 1 H each, J = 10 Hz); 8.93, 8.98 (both d, 1 H each,
8. Pat. RF 1187432; Byul. isobret.[Bull. Inventions], 1993, 48,
197 (in Russian).
9. V. A. Samsonov, L. B. Volodarskii, V. L. Korolev, and G. Kh.
Khisamutdinov, Khim. Geterotsikl. Soedin., 1994, 1432 [Chem.
Heterocycl. Compd., 1994, 30, 1243 (Engl. Transl.)].
10. S. V. Bogdanov and I. N. Koroleva, Zh. Obshch. Khim.,
1956, 26, 264 [J. Gen. Chem. USSR, 1956, 26 (Engl. Transl.)].
11. I. Z. Kondyukov, Yu. V. Karpychev, P. G. Belyaev, G. Kh.
Khisamutdinov, S. I. Valeshnii, S. P. Smirnov, and V. P.
Ilґin, Zh. Org. Khim., 2007, 43, 636 [Russ. J. Org. Chem.,
2007, 43, 635 (Engl. Transl.)].
12. The Sadtler Standard Spectra: Infrared Grating Spectra,
Sadtler Research Lab., Philadelphia, 1966—1990, Vol. 1—99,
N 1K—79000K.
Samsonov
