6596
H. Ge et al. / Tetrahedron 69 (2013) 6591e6597
3. Conclusion
m/z¼244 [M]þ; HRMS: m/z calcd for C14H16N2O2þHþ: 245.13
[MþH]þ; found: 245.1362.
In conclusion, a novel, direct, and efficient method has been
successfully described for the synthesis of 2-oxazines and
2-oxazolines under thermal and microwave conditions. The features
of this procedure are S/Co(NO3)2 cascade catalysis, high conversions,
the mild reaction conditions, and solvent-free. In addition, this
general procedure showed high selectivity for the synthesis of
mono- and bis-oxazines and oxazolines and afforded a broad scope
of 2-oxazines and 2-oxazolines in moderate to excellent yields. Es-
pecially, a new method of synthesizing the bis-oxazines is proposed
and four heterocyclic compounds are reported for the first time.
4.2.3. 1,3-Bis (5,6-dihydro-4H-1,3-oxazin-2-yl)benzene (3o). Silica
gel chromatography (ethyl acetate, Rf¼0.24); white solid (104.9 mg,
86% yield); 1H NMR (400 MHz, CDCl3):
d¼8.39 (s, 1H), 7.96 (dd,
J¼7.8, 17 Hz, 2H), 7.39 (t, J¼7.8 Hz, 1H), 4.39 (t, J¼5.4 Hz, 4H), 3.63 (t,
J¼5.8 Hz, 4H), 2.02e1.96 (m, 4H); 13C NMR (100 MHz, CDCl3):
d
¼155.3 (C), 134.0 (C), 128.7 (CH), 127.8 (CH), 125.3 (CH), 65.1 (CH2),
42.7 (CH2), 21.9 ppm (CH2); IR (KBr):
n
¼2926, 2887, 2857, 1652,
1581, 1472, 1434, 1127, 1100, 816, 793, 699 cmꢁ1; MS (EI): m/z¼244
[M]þ; HRMS: m/z calcd for C14H16N2O2þHþ: 245.13 [MþH]þ; found:
245.1358.
4. Experimental section
4.1. General remarks
4.2.4. 2-(Pyrimidin-2-yl)-5,6-dihydro-4H-1,3-oxazine (3r). Silica gel
chromatography (ethyl acetate/methyl alcohol¼3:1, Rf¼0.27); yel-
low oil (67.6 mg, 83% yield); 1H NMR (400 MHz, CDCl3):
d¼8.90 (d,
1H NMR (400 MHz), 13C NMR (100 MHz) spectra were recorded
on 400 MHz spectrometers. Chemical shifts for 1H NMR spectra are
reported in parts per million downfield from TMS, chemical shifts
for 13C NMR spectra are reported in ppm relative to internal chlo-
roform. Infrared spectra (IR) were recorded with KBr pellets. Silica
gel (200e300 mesh) was used for column chromatography. Mass
spectra were obtained using EI. High-resolution mass spectra were
obtained using ESI.
J¼4.9 Hz, 2H), 7.48 (t, J¼4.9 Hz, 1H), 3.75e3.66 (m, 4H), 1.86 (dt,
J¼11.6, 5.9 Hz, 2H); 13C NMR (100 MHz, CDCl3):
¼163.3 (C), 157.5
d
(CH),157.3 (C),122.7 (CH), 59.4 (CH2), 36.8 (CH2), 32.1 ppm (CH2); IR
(KBr):
n
¼2947, 2880, 1673, 1567, 1538, 1414, 1202, 1061, 840 cmꢁ1
;
MS (EI): m/z¼163 [M]þ; HRMS: m/z calcd for C8H9N3OþHþ: 164.08
[MþH]þ; found: 164.0840.
4.3. Typical procedure for the synthesis of 2-oxazolines
(5aer), respectively, under thermal conditions and microwave
irradiation
4.2. Typical procedure for the synthesis of 2-oxazines (3aer),
respectively, under thermal conditions and microwave
irradiation
A mixture of nitrile (0.5 mmol), 2-aminoethanol (4) (0.65 mmol,
0.040 g), Co(NO3)2 (0.02 mmol, 0.036 g), and sulfur (0.05 mmol,
0.0016 g) was stirred at 90 ꢀC or subjected to microwave irradiation
(90 ꢀC, 800 W) for appropriate time. For the synthesis of mono-
oxazolines, dicyanobenzene (0.5 mmol), 2-aminoethanol (4)
(0.65 mmol, 0.040 g), Co(NO3)2 (0.02 mmol, 0.036 g), and sulfur
(0.05 mmol, 0.0016 g) was stirred at 90 ꢀC for 3 h or subjected to
microwave irradiation (90 ꢀC, 800 W) for 3 min. For the synthesis of
bis-oxazoline, dicyanobenzene (0.5 mmol), 2-aminoethanol (4)
(2.6 mmol, 0.159 g), Co(NO3)2 (0.02 mmol, 0.036 g), and sulfur
(0.05 mmol, 0.0016 g) was stirred at 110 ꢀC for 10 h or subjected to
microwave irradiation (110 ꢀC, 800 W) for 8 min. After completion
of the reaction (detected by TLC), the reaction mixture was cooled
to room temperature, ethyl acetate (6 mL) was added and the
catalyst was separated by the filtration. Following concentration
under reduced pressure, the residue was purified by silica gel
chromatography to give pure product (5aer).
A
mixture of nitrile (0.5 mmol), 3-amino-1-propanol (2)
(1.3 mmol, 0.098 g), Co(NO3)2 (0.02 mmol, 0.036 g), and sulfur
(0.05 mmol, 0.0016 g) was stirred at 90 ꢀC or subjected to micro-
wave irradiation (90 ꢀC, 800 W) for appropriate time. For the syn-
thesis of mono-oxazines, dicyanobenzene (0.5 mmol), 3-amino-1-
pro-panol (2) (0.65 mmol, 0.049 g), Co(NO3)2 (0.02 mmol,
0.036 g), and sulfur (0.05 mmol, 0.0016 g) was stirred at 90 ꢀC for
2 h or subjected to microwave irradiation (90 ꢀC, 800 W) for 2 min.
For the synthesis of bis-oxazines, dicyanobenzene (0.5 mmol),
3-amino-1-propanol (2) (2.6 mmol, 0.196 g), Co(NO3)2 (0.02 mmol,
0.036 g), and sulfur (0.05 mmol, 0.0016 g) was stirred at 110 ꢀC for
6 h or 7h or subjected to microwave irradiation (110 ꢀC, 800 W) for
6 min. After completion of the reaction (detected by TLC), the re-
action mixture was cooled to room temperature, ethyl acetate
(6 mL) was added, and the catalyst was separated by the filtration.
Following concentration under reduced pressure, the residue was
purified by silica gel chromatography to give pure product (3aer).
4.3.1. 2-(Pyrimidin-2-yl)-4,5-dihydrooxazole (5r). Silica gel chro-
matography (ethyl acetate/methyl alcohol¼3:1, Rf¼0.40); while
solid (59.6 mg, 80% yield), mp: 106e108 ꢀC; 1H NMR (400 MHz,
4.2.1. 2-(Pyridin-2-yl)-5, 6-dihydro-4H-1,3-oxazine (3b). Silica gel
chromatography (petroleum ether/ethyl acetate¼1:1, Rf¼0.30);
CDCl3):
d
¼8.89 (s, 2H), 7.46 (t, J¼4.6 Hz, 1H), 3.89 (t, J¼5.0 Hz, 2H),
yellow oil (73.7 mg, 91% yield); 1H NMR (400 MHz, CDCl3):
d
¼8.58
3.71 (dd, J¼10.2, 5.4 Hz, 2H); 13C NMR (100 MHz, CDCl3):
¼163.1
d
(d, J¼4.7 Hz, 1H), 8.22 (d, J¼7.8 Hz, 1H), 7.90 (td, J¼7.7, 1.5 Hz, 1H),
7.51e7.45 (m, 1H), 3.71e3.63 (m, 4H), 1.83 (dt, J¼11.6, 5.9 Hz, 2H);
(C), 157.5 (C), 157.4 (CH), 122.7 (CH), 61.5 (CH2), 42.6 ppm (CH2); IR
(KBr):
n
¼2980, 1650, 1610, 1514, 1357, 1257, 1100, 940, 829,
13C NMR (100 MHz, CDCl3):
d
¼165.3, 149.3, 148.0, 137.7, 126.3, 121.7,
728 cmꢁ1
;
MS (EI): m/z¼149 [M]þ. HRMS: m/z calcd for
58.8, 35.9, 31.8 ppm; IR (KBr):
n
¼2946, 2879, 1662, 1592, 1571, 1538,
C7H7N3OþHþ: 150.0662 [MþH]þ; found: 150.0662.
1467, 1436, 1249, 1063, 900, 823, 752, 695 cmꢁ1; MS (EI): m/z¼162
[M]þ; HRMS: m/z calcd for C9H10N2OþHþ: 163.0871 [MþH]þ;
found: 163.0875.
Acknowledgements
The project was supported by the National Natural Science
Foundation of China (NSFC 20972124; 21272184; 21143010), the
Shaanxi Provincial Natural Science Fund Project (No. 2012JQ2007),
the Shaanxi Science and Technology Coordination Innovation En-
gineering Project (No. 2011K12-77), the Special Science Research
Foundation of Education Committee in Shaanxi Province
(No. 12JK0584), and the Chinese National Innovation Experiment
Program for University Students (No. 201210697011).
4.2.2. 1,4-Bis (5,6-dihydro-4H-1,3-oxazin-2-yl)benzene (3m). Silica
gel chromatography (petroleum ether/ethyl acetate¼1:1, Rf¼0.20);
white solid (109.7 mg, 90% yield); 1H NMR (400 MHz, CDCl3):
d
¼8.00 (d, J¼12.0 Hz, 4H), 4.44 (dd, J¼9.1, 3.7 Hz, 4H), 3.71e3.63 (m,
4H), 2.10e1.98 (m, 4H); 13C NMR (100 MHz, CDCl3):
d
¼155.4 (C),
135.6 (C), 126.5 (CH), 65.2 (CH2), 42.6 (CH2), 21.7 ppm (CH2); IR
(KBr):
n
¼2965, 2888, 2854, 1650, 1128, 1099, 862 cmꢁ1; MS (EI):