L. Cecchi, F. De Sarlo, F. Machetti
FULL PAPER
Isoxazoline 5d: Hexane/diethyl ether, 3:1, Rf = 0.23. White powder.
vessel (Schlenk) heated at 60 °C. The solvent was then removed,
Yield 59 mg, 50%. M.p. 85–86 °C (Ref.[55] 85–86 °C). 1H NMR and the residue was dissolved in diethyl ether (15 mL), washed with
(400 MHz, CDCl3): δ = 1.04–1.10 (m, 1 H, Norb-H), 1.20–1.28 (m, water (3×15 mL), NaOH (1 , 3×15 mL) and then brine
2 H, Norb-H), 1.33–1.39 (m, 1 H, Norb-H),1.48–1.60 (m, 2 H,
Norb-H), 2.57 (m, 1 H, Norb-H), 2.74 (m, 1 H, Norb-H), 3.42 (d,
J = 8.4 Hz, 1 H, CHC=N), 4.68 (d, J = 8.4 Hz, 1 H, CHON), 7.54–
7.60 (m, 2 H, Ph-H), 7.65–7.70 (m, 1 H, Ph-Hpara), 7.94–7.99 (m,
2 H, Ph-H) ppm. 13C NMR (100.58 MHz, CDCl3): δ = 22.4 (t,
Norb-C), 26.8 (t, Norb-C), 32.4 (t, Norb-C), 39.5 (d, Norb-C), 42.7
(d, Norb-C), 55.6 (d, CC=N), 91.6 (d, CON), 128.8 (d, 2 C, Ph-
C), 129.3 (d, 2 C, Ph-C), 134.6 (d, Ph-C), 138.2 (s, Ph-C), 160.7 (s,
C=N) ppm. MS (EI): m/z (%) = 277 (5) [M]+, 221, (9), 210 (4), 141
(60) [SO2Ph]+, 125 (13), 108 (28), 77 (100) [Ph]+, 67 (84). IR
(3×15 mL). The organic layer was dried (sodium sulfate) and con-
centrated to afford the final product.
Isoxazoline 5e: Colourless crystals. Yield 82 mg, 100%. M.p. 123–
124 °C. 1H NMR (400 MHz, CDCl3): δ = 1.02–1.12 (m, 1 H, Norb-
H), 1.20–1.36 (m, 1 H, Norb-H), 1.22–1.38 (m, 2 H, Norb-H),
1.44–1.59 (m, 2 H, Norb-H), 2.53 (m, 1 H, Norb-H), 2.60 (s, 1 H,
Norb-H), 2.85 (d, J = 5.2 Hz, 3 H, CH3), 3.33 (d, J = 8.4 Hz, 1 H,
CHC=N), 4.58 (d, J = 8.4 Hz, 1 H, CHON), 6.57 (br. s, N–H)
ppm. 13C NMR (100.58 MHz, CDCl3): δ = 22.6 (t, Norb-C), 25.9
(NHCH3), 27.1 (t, Norb-C), 32.2 (t, Norb-C), 39.2 (d, Norb-C),
42.9 (d, Norb-C), 55.7 (d, CC=N), 89.7 (d, CON), 154.2 (s, C-3),
160.4 (s, C=O) ppm. MS (EI): m/z (%) = 194 (6) [M]+, 165 (4), 127
(CHCl ): ν = 2968, 2878, 1326, 1166 cm–1. C H NO S (277.34):
˜
3
14 15
3
calcd. C 60.63, H 5.45, N 5.05; found C 60.70, H 5.66, N 4.95.
(8), 81 (77), 58 (100) [CH NCO]+. IR (KBr): ν = 3435 (NH), 2968,
Isoxazoline 6d: Hexane/diethyl ether, 4:1, Rf = 0.1. Column
chromatography monitored by TLC with different eluent (hexane/
diethyl ether, 3:2, Rf = 0.37). Clear oil. Yield 11 mg, 10%. 1H NMR
(400 MHz, CDCl3): δ = 3.32 (dd, J = 9.0 and 17.3 Hz, 1 H, 4-H),
3.72 (dd, J = 11.4 and 17.3 Hz, 1 H, 4-H), 5.78 (dd, J = 9.0 and
11.4 Hz, 1 H, 5-H), 7.14–7.42 (m, 5 H, Ph-H), 7.55–7.80 (m, 3 H,
Ph-H), 7.98–8.08 (m, 2 H, Ph-H) ppm. 13C NMR (100.58 MHz,
CDCl3): δ = 40.3 (t, C-4), 86.0 (d, C-5), 125.8 (d, 2 C, Ph-C), 128.8
(d, 2 C, Ph-C), 128.9, (d, Ph-C), 129.0 (d, 2 C, Ph-C), 129.3 (d, 2
C, Ph-C), 134.7 (d, Ph-C), 137.2 (s, Ph-C), 138.2, (s, Ph-C), 159.6
(s, C-3) ppm. MS (EI): m/z (%) = 287 (11) [M]+, 146 (44), 128 (72),
˜
3
1676 (C=O), 1588, 1542 cm–1. C10H14N2O2 (194.23): calcd. C
61.84, H 7.26, N 14.42; found C 61.55, H 7.27, N 14.28.
Isoxazoline 6e: White solid. Yield 60 mg, 70%. M.p. 111 °C. 1H
NMR (400 MHz, CDCl3): δ = 2.92 (d, J = 5.1 Hz, 3 H, NCH3),
3.25 (dd, J = 18.0 and 8.8 Hz, 1 H, 4-H), 3.64 (dd, J = 18.0 and
11.3 Hz,1 H, 4-H), 5.71 (dd, J = 11.4 and 8.8 Hz, 1 H, 5-H), 6.64
(br. s, 1 H, NH), 7.28–7.40 (m, 5 H, Ph-H), ppm. 13C NMR
(100.58 MHz, CDCl3): δ = 26.1 (q, NCH3), 41.2 (t, C-4), 84.7 (d,
C-5), 125.9 (d, 2 C, Ph-C), 128.6 (d, Ph-C), 128.8 (d, 2 C, Ph-C),
139.6 (s, Ph-C), 153.6 (s, C-3), 160.1 (s, C=O) ppm. MS (EI): m/z
(%) = 204 (36) [M]+, 203 (60),187 (33), 105 (21), 104 (61), 58 (100)
115 (31), 104 (39), 77 (100) [Ph]+. IR (CHCl ): ν = 1448, 1328 cm–1.
˜
3
C15H13NO3S (287.34): calcd. C 62.70, H 4.56, N 4.87; found C
62.84, H 4.36, N 4.94.
[CH NCO]+. IR (CHCl ): ν = 3453 (NH), 1679 (C=O), 1596,
˜
3
3
1541 cm–1. C11H12NO2 (204.23): calcd. C 64.69, H 5.92, N 13.72;
Isoxazole 7d: Hexane/diethyl ether, 3:1, Rf = 0.27. Yellowish solid.
Yield 24 mg, 20%. M.p. 120–121 °C. 1H NMR (400 MHz, CDCl3):
δ = 6.89 (s, 1 H, 4-H), 7.40–7.80 (m, 8 H, Ph-H), 8.02–8.18 (m, 2
H, Ph-H) ppm. 13C NMR (100.58 MHz, CDCl3): δ = 97.9 (d, C-
4), 126.0 (s, Ph-C),126.1 (d, 2 C, Ph-C), 128.7 (d, 2 C, Ph-C), 129.2
(d, 2 C, Ph-C), 129.5 (d, 2 C, Ph-C), 131.4 (d, Ph-C), 134.7 (d, Ph-
C), 138.7 (s, Ph-C), 166.3 (s, C-3), 172.6 (s, C-5) ppm. MS (EI):
m/z (%) = 285 (4) [M]+, 141 (44) [SO2Ph]+, 105 (6), 77 (77) [Ph]+.
found C 64.30, H 5.88, N 13.78.
Isoxazole 7e: White solid. Yield 35 mg, 41%. M.p. 198–199 °C
1
(Ref.[57] 199–200 °C). H NMR (400 MHz, CDCl3): δ = 3.01 (d, J
= 4.8 Hz, 3 H, NCH3), 6.95(s, 1 H, 4-H), 7.42–7.50 (m, 3 H, Ph-H),
7.74–7.80 (m, 2 H, Ph-H) ppm. 13C NMR (100.58 MHz, CDCl3): δ
= 26.1 (q, NCH3), 99.0 (d, C-4), 125.9 (d, 2 C, Ph-Cortho), 126.8 (s,
Ph-Cipso), 129.1 (d, 2 C, Ph-Cmeta), 130.7 (d, Ph-Cpara), 159.1 (s, C-
3)*, 159.6 (s, C=O)*, 171.7 (s, C-5), ppm, *may be exchanged. MS
(EI): m/z (%) = 202 (38) [M]+, 172 (34) [M – NHCH]+, 145 (20),
105 (56) [PhCO]+, 77 (44) [Ph]+, 58 (100) [CONHMe]+. IR
IR (CHCl ): ν = 1449, 1432, 1345, 1334 cm–1. C H NO S
˜
3
15 11
3
(285.32): calcd. C 63.14, H 3.89, N 4.91; found C 62.89, H 3.89, N
4.89.
(CHCl ): ν = 3433, 1685 (C=O), 1551, 1447 cm–1. C H N O
˜
3
11 10
2
2
Preparation of N-Methylnitroacetamide (1e): Ethyl nitroacetate (1a,
1.33 g, 10.0 mmol) was treated with methylamine (40% water solu-
tion, 7.8 mL), and the mixture stirred at room temperature for 3 d.
A stream of N2 was bubbled through the mixture and then HCl
(5%) was added (12 mL, pH = 1–2). The aqueous solution was
then concentrated to dryness, and the yellow solid residue was
mixed with CH2Cl2 (100 mL). The obtained suspension was vigor-
ously stirred at room temperature for 2 h. After filtration, the sol-
vent was removed under reduced pressure to afford 1e as a white
solid. Yield 1.08 g, 92%. M.p. 68–69 °C (Ref.[56] 67–69 °C). 1H
NMR (400 MHz, CDCl3): δ = 2.90 (d, J = 4.8 Hz, 3 H, CH3), 5.08
(s, 2 H, CH2), 6.48 (br. s, 1 H, NH) ppm. 13C NMR (100.58 MHz,
CDCl3): δ = 26.7 (q, CH3), 77.8 (t, CH2), 160.7 (s, C=O) ppm. MS
(EI): m/z (%) = 118 (5) [M]+, 88 (1), 72 (82), 58 (100) [CH3-
(202.21): calcd. C 65.34, H 4.98, N 13.85; found C 65.59, H 5.03,
N 13.81.
Preparation of Phenylnitromethane (1f): Crude compound 1f (8 g,
97%) was obtained according to a previously described procedure
from benzyl bromide (10.3 g, 60.0 mmol), sodium nitrite 6.21 g,
(90.0 mmol) and urea (7.09 g), in DMF (90 mL).[58] The workup
was slightly modified, diethyl ether was used as the solvent for the
extraction instead of dichloromethane. Freshly pure 1f was pre-
pared immediately prior to use through chromatography: pentane/
diethyl ether, 10:1 Rf = 0.3. 1H NMR and 13C NMR spectroscopic
data are identical to those reported in the literature.[59,60]
General Method for the Reaction of Phenylnitromethane (1f) with
Dipolarophiles
NCO]+. IR (CDCl ): ν = 3433 (NH), 1696 (C=O), 1563, 1533,
˜
3
A
solution of 1f (146 mg, 1.06 mmol), DABCO (24 mg,
1416, 1374 cm–1. C3H6N2O3 (118.08): calcd. C 30.51, H 5.12, N
0.212 mmol) and the dipolarophile (0.424 mmol) in anhydrous and
ethanol-free chloroform (1.4 mL) was stirred for 20 h (norbornene)
or 40 h (styrene and phenylacetylene) in a sealed vessel (Schlenk)
heated at 60 °C. The solvent was then removed; the residue was
dissolved in diethyl ether (15 mL) and washed with water
(3×15 mL), NaOH (1 , 3×15 mL) and then brine (3×15 mL por-
tions). The organic layer was dried (sodium sulfate) and concen-
23.72; found C 30.47, H 5.21, N 23.56.
General Method for the Reactions of N-Methylnitroacetamide (1e)
with Dipolarophiles
A
solution of 1e (125 mg, 1.06 mmol), DABCO (24 mg,
0.212 mmol) and the dipolarophile (0.424 mmol) in anhydrous and
ethanol-free chloroform (1.4 mL) was stirred for 20 h in a sealed
4858
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 4852–4860