1200
A. Cuenca, S. Pérez, A. Yepez, L. Paredes, L. Montecinos, L. Llovera, C. Rodríguez.
Vol 45
Table 1.
Thermal and Microwave Irradiation Conditions and Yield of Products.
Compounds
Ar
Time
Yielda
ꢁ, h
MWI, s
ꢁ, %
MWI, %
2a
2b
2c
2d
2e
2f
4-FC6H4
2,3-F2C6H3
2,6-F2C6H3
3-ClC6H4
2-BrC6H4
2-IC6H4
4b
2
30
30
60
20
30
30
30
60
64
63
45
65
68
56
57
76
85
78
70
79
76
86
84
85
2
1.5
4b
2
2g
2h
3-IC6H4
2
5b
4-NCC6H4
[a] Isolated yield. [b] Ref. 6.
microwave oven (2450 MHz) for the appropriate time according
to Table 1. The reaction mixture was allowed to reach room
temperature and poured onto crushed ice. The precipitate was
collected by filtration, washed with water, dried under vacuum
and recrystallized from chloroform to afford the desired
products.
However, no cyclised material was obtained in the
synthesis procedure described here. New 2-substituted
quinoxalines, 2b-d, 2f, 2g, are stable compounds property
which makes them useful substances in drug research. In
all cases, any remaining starting material 2-chloro-
quinoxaline 1 could be easily removed by sublimation.
Five unknown quinoxaline derivatives 2b-d, 2f and 2g
were characterized on the basis of their elemental
analysis, ms, 1H nmr and ir spectral data. The synthesis of
2a, 2e and 2h was earlier reported by us [6] under thermal
conditions and are now prepared under MWI. All
compounds were obtained in high purity as indicated by
TLC and spectral analysis.
2-(2,3-Difluorophenoxy)quinoxaline (2b). This compound
was obtained as a white solid, mp = 139-140 °C; ir (potassium
bromide): 3047, 1576, 1306, 1265, 1211 cm-1; 1H nmr (CDCl3)
ꢀ: 7.15 (m, 3H, 2'-H, 3'-H, 4'-H), 7.69 (m, 2H, 6-H, 7-H), 7.73
(dd, 1H, 5-H, J= 1.8, 8.1 Hz), 8.08 (dd, 1H, 8-H, J = 1.8, 7.7
Hz), 8.77 (s, 1H, 3-H); 13C nmr (CDCl3) ꢀ: 114.5, 119.0, 123.6,
127.0, 127.9, 129.1, 130.7, 138.3, 139.8, 140.0, 141.5, 143.5,
151.0, 155.9; ms: m/z = 258 (M+), 239 (M+-F), 230 (M+-CH2N),
129 (M+- OC6H3 F2), 102 (129-HCN). Anal. Calcd. for
C14H8N2OF2: C, 67.70; H, 3.12; N, 10.85; F, 14.71. Found: C,
67.69 ; H, 3.16; N, 10.80; F, 14.68.
EXPERIMENTAL
2-(2,6-Difluorophenoxy)quinoxaline (2c). This compound
was obtained as a light brown solid, mp = 140-141 °C; ir
(potassium bromide): 3060, 1577, 1501, 1213, 1014 cm-1; 1H nmr
(CDCl3) ꢀ: 7.04 (m, 2H, 3'-H, 5'-H), 7.21 (m, 1H, 4'-H), 7.62 (m,
2H, 6-H, 7-H), 7.70 (m, 1 H, 5-H), 8.07 (m, 1H, 8-H), 8.83 (s, 1H,
3-H); 13C nmr (CDCl3) ꢀ: 112.2, 112.6, 126.2, 127.8, 129.1, 130.6,
138.1, 139.8, 140.1, 154.7, 155.4, 157.2; ms: m/z = 258 (M+), 239
(M+-F), 129 (M+-OC6H3F2), 102 (129-HCN ), 76 (102-CN). Anal.
Calcd. for C14H8N2OF2: C, 67.70; H, 3.12; N, 10.85; F, 14.71.
Found: C, 67.73; H, 3.10; N, 10.81; F, 14.70.
2-Choroquinoxaline 1 was prepared according to the literature
method by Castle and Onda [12]. Ir spectra were obtained on a
Bruker, Tensor 27 instrument. H rmn spectra were recorded at
room temperature on a Jeol Eclipse + 400 NMR spectrometer.
Mass spectra were determined on a Jeol JMS-AX505WA
spectrometer. Melting points (mp) in °C are uncorrected.
1
General Procedure for the Synthesis of Quinoxaline
Derivatives (2a-h) Under Thermal Conditions. A typical
procedure is a follows: 2-chloroquinoxaline 1 (2-4 mmol) and a
catalytic amount of AgNO3 were added to a solution of
equivalent amounts of KOH (2-4 mmol) and the corresponding
phenol derivative in 8 mL of N,N-dimethylformamide (DMF).
The resulting mixture was stirred under reflux condition for the
appropriate time according to Table 1. The progress of the
reaction was monitored by TLC, hexane-ethyl acetate (7:3). The
reaction mixture was cooled to room temperature, filtered, and
the solution poured onto cold water. The resulting solid was
collected by filtration, washed with water, dried in vacuum and
recrystallized from chloroform to yield the desired product.
General Procedure for the Synthesis of Quinoxaline
Derivatives (2a-h) Under Microwave Irradiation. 2-
Chloroquinoxaline 1 (2-3 mmol) was added to a mixture of
equimolar amounts of KOH (2-3 mmol) and the corresponding
phenol previously dissolved in DMF (2 mL). The mixture was
2-(3-Chlorophenoxy)quinoxaline (2d). This compound was
obtained as light yellow solid, mp = 74-75 °C.; ir (potassium
1
bromide): 3070, 1588, 1498, 1135, 1072, 784; H nmr (CDCl3)
ꢀ: 7.19 (m, 1H, 5'-H), 7.26 (m, 1H, 4'-H), 7.35 (m, 2H, 2'-H, 6'-
H), 7.64 (m, 2H, 6-H, 7-H), 7.77 (dd, 1H, 5-H, J = 0.7, 7.7), 8.06
(dd, 1H, 8-H, J = 1.4, 8.4 Hz), 8.69 (s, 1H, 3-H); 13C nmr
(CDCl3) ꢀ: 119.8, 122.1, 125.8, 127.8, 129.1, 130.4, 130.6,
134.9, 139.1, 139.9, 153.3, 156.5; ms: m/z = 256 (M+); 228 (M+-
HCN); 129 (M+-OC6H4Cl); 102 (129-HCN); 76 (102-CN). Anal.
Calcd. for C14H9N2OCl: C,65.51; H, 3.53; N, 10.91. Found: C,
65.52; H, 3.48; N, 10.94.
2-(2-Iodophenoxy)quinoxaline (2f). This compound was
obtained as a brown solid, mp = 83-84 ºC; ir (potassium
bromide): 3058, 1569, 1500, 1224, 1136, 594 cm-1; 1H nmr
(CDCl3) ꢀ: 7.05 (m, 1H, 6'-H), 7.28 (m, 1H, 4'-H), 7.45 (m, 1H,
5'-H), 7.64 (m, 2H, 6-H, 7-H), 7.73 (m, 1H, 3'-H), 7.91 (dd, 1H,
5-H, J = 1.5, 8.0 Hz), 8.07 (m, 1H, 8-H), 8.76 (s, 1H, 3-H); 13C
placed into
intermittently at 20 s intervals at 700 W in
a
pyrex-glass open vessel and irradiated
domestic
a