The Journal of Organic Chemistry
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2H), 7.70 (d, J = 8.24 Hz, 1H) 7.62 (t, J = 7.55 Hz, 1H), 7.54 (d, J =
8.52 Hz, 2H), 7.47 (t, J = 7.55 Hz, 1H), 5.01 (br, 2H). 13C NMR (100
MHz, CDCl3, ppm): δ 150.6, 144.8, 141.4, 138.3, 136.1, 135.6, 130.5,
130.1, 129.7, 129.2, 125.9, 125.7.
Further development of cyanide-based multicomponent
reactions is currently underway in our laboratory.
EXPERIMENTAL SECTION
2-Amino-3-(4-acethylphenyl)-quinoxaline (3e). A yellow solid.
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1
Yield: 51 mg (92%). Rf = 0.2 (EtOAc:hexanes = 1:3). H NMR (300
General. All reactions were carried out in oven- or flame-dried
glassware under an air atmosphere unless otherwise noted. Except as
otherwise indicated, all reactions were magnetically stirred and
monitored by analytical thin layer chromatography (TLC) using
precoated silica gel glass plates (0.25 mm) with F254 indicator.
Visualization was accomplished by UV light (254 nm), with the
combination of phosphomolybdic acid solution as an indicator. Flash
column chromatography was performed according to the method of
Still using silica gel 60 (230−400 mesh). Yields refer to chromato-
graphically and spectrographically pure compounds, unless otherwise
noted. 1,2-Phenylenediamine and other commercial grade reagents
and solvents were purchased from commercial suppliers and were used
without further purification. Liquid aldehydes were freshly distilled
under an atmosphere of dry argon, and solid aldehydes were purified
by flash chromatography on silica gel. 1H NMR spectra were recorded
on 300 and 400 MHz spectrometers and 13C NMR spectra were
recorded on 75 and 100 MHz spectrometers, respectively.
MHz, CDCl3, ppm): δ 8.23 (d, J = 8.24 Hz, 2H), 7.97 (d, J = 8.24 Hz,
1H), 7.90 (d, J = 8.24 Hz, 2H), 7.71 (d, J = 7.97 Hz, 1H), 7.64 (t, J =
8.10 Hz, 1H), 7.48 (t, J = 8.24 Hz, 1H), 5.03 (br, 2H), 3.98 (s, 3H).
13C NMR (100 MHz, CDCl3, ppm): δ 166.6, 150.5, 144.8 141.5,
138.3, 131.3, 130.7, 130.6, 129.3, 128.8, 125.9, 125.8, 52.6. HRMS (EI)
calcd for C16H13N3O2 (M+) 279.1008, found 279.1005.
2-Amino-3-(2-methoxyphenyl)-quinoxaline (3f). A light gray solid.
1
Yield: 46 mg (92%). Rf = 0.3 (EtOAc:hexanes = 1:2). H NMR (300
MHz, CDCl3, ppm): δ 7.97 (d, J = 8.24 Hz, 1H), 7.71 (d, J = 8.24 Hz,
1H), 7.61 (t, J = 7.69 Hz, 1H), 7.43−7.51 (m, 3H), 7.15 (t, J = 7.42
Hz, 1H), 7.05 (d, J = 8.24 Hz, 1H), 4.95 (br, 2H), 3.83 (s, 3H). 13C
NMR (100 MHz, CDCl3, ppm): δ 157.2, 151.6, 145.3, 141.6, 138.0,
131.5, 131.3, 130.1, 129.3, 126.2, 125.9, 125.3, 121.9, 111.7, 56.0.
HRMS (EI) calcd for C15H13N3O (M+) 251.1059, found 251.1054.
2-Amino-3-(2-chlorophenyl)-quinoxaline (3g). A light brown
solid. Yield: 42 mg (82%). Rf = 0.4 (EtOAc:hexanes = 1:3). 1H
NMR (300 MHz, CDCl3, ppm): δ 7.97 (d, J = 8.24 Hz, 1H), 7.73 (d, J
= 7.97 Hz, 1H), 7.65 (t, J = 7.55 Hz, 1H), 7.46−7.58 (m, 5H), 4.84
(br, 2H). 13C NMR (100 MHz, CDCl3, ppm): δ 150.8, 144.6, 141.9,
137.7, 135.7, 133.3, 131.2, 131.1, 130.7, 130.6, 129.3, 128.0, 126.1,
125.6. HRMS (EI) calcd for C14H10ClN3 (M+) 255.0563, found
255.0564.
1
Tetramethylsilane and CDCl3 were used as internal standards for H
NMR (δ: 0.0 ppm) and 13C NMR (δ: 77.16 ppm), respectively. The
proton spectra were reported as follows δ (position of proton,
multiplicity, coupling constant J, number of protons) and the carbon
spectra were reported as only δ (position of carbon). Multiplicities are
indicated by s (singlet), d (doublet), t (triplet), q (quartet), p
(quintet), h (heptet), m (multiplet), and br (broad). High-resolution
mass spectra (HRMS) were obtained using a quadrupole instrument
using either electron ionization (EI) or electospary ionization (ESI) as
the ionization method.
2-Amino-3-(2-hydroxyphenyl)-quinoxaline (3h). A yellow solid.
1
Yield: 32 mg (67%). Rf = 0.3 (EtOAc:hexanes = 1:3). H NMR (300
MHz, CDCl3, ppm): δ 8.03 (d, J = 7.69 Hz, 1H), 7.87 (d, J = 8.24 Hz,
1H), 7.70−7.60 (m, 2H), 7.48 (t, J = 8.24 Hz, 1H), 7.40 (t, J = 8.52
Hz, 1H), 7.16 (d, J = 8.24 Hz, 1H), 7.01 (t, J = 8.24 Hz, 1H), 5.28 (br,
2H). 13C NMR (100 MHz, CDCl3, ppm): δ 158.5, 150.7, 143.8, 140.6,
135.7, 132.3, 130.6, 127.7, 127.2, 126.2, 126.0, 119.8, 119.3, 119.0.
HRMS (ESI) calcd for C14H12N3O ((M + H)+) 238.0980, found
238.0981.
General Procedure for the Synthesis of 3-Substituted 2-Amino-
quinoxalines 3 (Table 2). 1,2-Phenylenediamine 1 (0.20 mmol; 1.0
equiv) and aldehyde 2 (0.22 mmol; 1.1 equiv) and the molecular sieve
(10 mg) were dissolved in DMF (1.0 mL). The reaction mixture was
stirred at 80 °C in an open flask and monitored by TLC. On the
complete consumption of compound 1, NaCN (11 mg; 0.22 mmol;
1.1 equiv) was added to the above reaction mixture. On completion of
the reaction, the reaction mixture was cooled to room temperature and
concentrated under reduced pressure. The crude product was purified
by column chromatography on silica to give the corresponding 2-
aminoquinoxaline product 3.
2-Amino-3-phenylquinoxaline (3a). The spectroscopic data were
in good agreement with the literature.10b A yellow solid. Yield: 38 mg
(86%). Rf = 0.4 (EtOAc:hexanes = 1:3). 1H NMR (300 MHz, CDCl3,
ppm): δ.7.98 (d, J = 8.24 Hz, 1H), 7.79 (d, J = 6.32 Hz, 2H), 7.71 (d, J
= 8.24 Hz, 1H), 7.44−7.65 (m, 5H), 5.24 (br, 2H). 13C NMR (100
MHz, CDCl3, ppm): δ 150.9, 146.1, 141.4, 138.2, 137.2, 130.2, 129.9,
129.5, 129.3, 128.6, 125.7, 125.4.
2-Amino-3-(1-naphthyl)-quinoxaline (3i). A light brown solid.
1
Yield: 40 mg (73%). Rf = 0.4 (EtOAc:hexanes = 1:3). H NMR (300
MHz, CDCl3, ppm): δ 7.99 (t, J = 7.04 Hz, 2H), 7.94 (d, J = 8.22 Hz,
1H), 7.75 (d, J = 8.61 Hz, 1H), 7.65 (t, J = 7.04 Hz, 2H), 7.61 (d, J =
6.65 Hz, 2H), 7.54 (t, J = 7.04 Hz, 1H), 7.43−7.50 (m, 2H), 4.82 (br,
2H). 13C NMR (100 MHz, CDCl3, ppm): δ 151.5, 145.9, 141.8, 138.0,
134.2, 133.9, 131.1, 130.5, 130.2, 129.4, 128.9, 127.4, 127.3, 126.8,
126.0, 125.9, 125.5, 125.2. HRMS (ESI) calcd for C18H14N3 ((M +
H)+) 272.1188, found 272.1190.
2-Amino-3-(2-naphthyl)-quinoxaline (3j). A light yellow solid.
1
Yield: 49 mg (90%). Rf = 0.4 (EtOAc:hexanes = 1:3). H NMR (300
MHz, CDCl3, ppm): δ 8.29 (s, 1H), 7.86−8.03 (m, 5H), 7.71 (d, J =
8.22 Hz, 1H), 7.61 (t, J = 7.44 Hz, 1H), 7.55−7.57 (m, 2H), 7.46 (t, J
= 7.44 Hz, 1H), 5.14 (br, 2H). 13C NMR (100 MHz, CDCl3, ppm): δ
150.9, 146.0, 141.4, 138.4, 134.5, 133.9, 133.5, 130.3, 129.4, 129.3,
128.7, 128.3, 128.1, 127.4, 127.0, 125.9, 125.8, 125.6. HRMS (ESI)
calcd for C18H14N3 ((M + H)+) 272.1188, found 272.1186.
2-Amino-3-(4-methoxyphenyl)-quinoxaline (3b). A light brown
1
solid. Yield: 40 mg (80%). Rf = 0.3 (EtOAc:hexanes = 1:2). H NMR
(300 MHz, CDCl3, ppm): δ.7.95 (d, J = 8.24 Hz, 1H), 7.76 (d, J =
8.52 Hz, 2H), 7.68 (d, J = 8.24 Hz, 1H), 7.59 (t, J = 7.97 Hz, 1H), 7.44
(t, J = 7.97 Hz, 1H)), 7.06 (d, J = 8.52 Hz, 2H), 5.11 (br, 2H), 3.88 (s,
3H). 13C NMR (100 MHz, CDCl3, ppm): δ 161.0, 150.9, 145.9, 141.2,
138.4, 130.1, 129.9, 129.5, 129.1, 125.8, 125.4, 114.8, 55.7. HRMS (EI)
calcd for C15H13N3O (M+) 251.1059, found 251.1054.
2-Amino-3-(2-furyl)-quinoxaline (3k). A brown solid. Yield: 38 mg
(90%). Rf = 0.4 (EtOAc:hexanes = 1:2). 1H NMR (300 MHz, CDCl3,
ppm): δ 7.90 (d, J = 8.24 Hz, 1H), 7.62−7.66 (m, 2H), 7.56 (t, J =
7.55 Hz, 1H), 7.39−7.46 (m, 2H), 6.67 (dd, J = 3.30, 1.63 Hz, 1H),
6.89 (br, 2H). 13C NMR (100 MHz, CDCl3, ppm): δ 152.6, 149.4,
143.9, 140.9, 137.6, 134.6, 130.1, 128.9, 125.6, 125.6, 113.0, 112.7.
HRMS (EI) calcd for C12H9N3O (M+) 211.0746, found 211.0739.
2-Amino-3-(2-thienyl)-quinoxaline (3l). A light yellow solid. Yield:
2-Amino-3-(4-methylphenyl)-quinoxaline (3c). A yellow solid.
1
Yield: 6 mg (77%). Rf = 0.4 (EtOAc:hexanes = 1:3). H NMR (300
MHz, CDCl3, ppm): δ 7.96 (d, J = 8.24 Hz, 1H), 7.69 (d, J = 8.24 Hz,
3H), 7.60 (t, J = 8.24 Hz, 1H), 7.45 (t, J = 8.24 Hz, 1H), 7.36 (d, J =
7.97 Hz, 2H), 5.07 (br, 2H), 2.45 (s, 3H). 13C NMR (100 MHz,
CDCl3, ppm): δ 150.8, 146.2, 141.3, 140.1, 138.4, 134.3, 130.1, 130.1,
129.2, 128.5, 125.8, 125.4, 21.7. HRMS (EI) calcd for C15H13N3 (M+)
235.1109, found 235.1107.
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29 mg (64%). Rf = 0.3 (EtOAc:hexanes = 1:3). H NMR (300 MHz,
CDCl3, ppm): δ 7.94 (d, J = 8.24 Hz, 1H), 7.77 (d, J = 3.57 Hz, 1H),
7.67 (d, J = 8.24 Hz, 1H), 7.56−7.62 (m, 2H), 7.46 (t, J = 8.24 Hz,
1H), 7.21 (dd, J = 3.85, 1.10 Hz, 1H), 5.27 (br, 2H). 13C NMR (100
MHz, CDCl3, ppm): δ 150.1, 141.2, 140.8, 139.6, 138.1, 130.2, 129.4,
129.0, 128.2, 127.3, 125.8, 125.7. HRMS (ESI) calcd for C12H10N3S
((M + H)+) 227.0595, found 228.0596.
2-Amino-3-(4-chlorophenyl)-quinoxaline (3d). The spectroscopic
data were in good agreement with the literature.19 A yellow solid.
1
Yield: 48 mg (93%). Rf = 0.4 (EtOAc:hexanes = 1:3). H NMR (300
MHz, CDCl3, ppm): δ 7.95 (d, J = 8.24 Hz, 1H), 7.77 (d, J = 8.52 Hz,
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dx.doi.org/10.1021/jo4021908 | J. Org. Chem. XXXX, XXX, XXX−XXX