N, 11.1. C12H16N2O4 requires C, 57.13; H, 6.39; N, 11.10%);
νmax(neat)/cmϪ1 2977, 1764, 1532, 1353, 1204, 1094, 998, 897,
810 and 736; δH (+20 ЊC) 1.23 (6 H, d, J 6.0), 1.86 (3 H, s), 2.99
(1 H, hept, J 6.0), 4.10 (2 H, s) and 7.47–8.35 (4 H, m);
δH (Ϫ50 ЊC) 1.27 (6 H, broad), 1.92 (3 H, s), 3.33 (1 H, hept,
J 7.0), 4.01 (1 H, d, J 13.0), 4.26 (1 H, d, J 13.0) and 7.55–8.39
(4 H, m); mass spectrum: m/z 252 (M+ 5%).
O-Acetyl-N-m-bromobenzyl-N-isopropylhydroxylamine 15h.
Compound 15h was a colourless liquid (Found: C, 50.2;
H, 5.6; N, 4.9. C12H16NO2Br requires C, 50.37; H, 5.64; N,
4.89%); νmax(neat)/cmϪ1 2972, 2862, 1765, 1571, 1472, 1371,
1204, 1070, 998, 906 and 778; δH (+24 ЊC) 1.22 (6 H, d, J 7.0),
1.90 (3 H, s), 3.24 (1 H, hept, J 7.0), 3.98 (2 H, s) and 7.17–7.65
(4 H, m).
O-Acetyl-N-p-bromobenzyl-N-isopropylhydroxylamine 15i.
Compound 15i formed colourless crystals, mp 34–36 ЊC (diethyl
ether–hexane) (Found: C, 50.15; H, 5.6; N, 4.9. C12H16NO2Br
requires C, 50.37; H, 5.64; N, 4.89%); νmax(KBr)/cmϪ1 3000,
1765, 1490, 1368, 1210, 1174, 1070, 1013, 906 and 799;
δH (+24 ЊC) 1.20 (6 H, d, J 7.0), 1.84 (3 H, s), 3.21 (1 H, hept, J
7.0), 3.95 (2 H, s), 7.31 (2 H, d, J 10.0) and 7.49 (2 H, d, J 10.0).
O-Acetyl-N-2,4,5-trimethoxybenzyl-N-isopropylhydroxyl-
amine 15j. Compound 15j formed white crystals, mp 40–41 ЊC
(diethyl ether–hexane) (Found: C, 60.35; H, 7.8; N, 4.7.
C15H23NO5 requires C, 60.59; H, 7.80; N, 4.71%); νmax(KBr)/
cmϪ1 2975, 2925, 2825, 1768, 1615, 1517, 1466, 1434, 1311,
1257, 1216, 1129, 1046, 989, 903, 861, 837, 810 and 751;
δH (+23 ЊC) 1.21 (6 H, d, J 6.0), 1.88 (3 H, s), 3.22 (1 H, hept,
J 6.0), 3.84 (3 H, s), 3.86 (3 H, s), 3.91 (3 H, s), 4.03 (2 H, s),
6.57 (1 H, s) and 7.26 (1 H, s).
m), 3.17 (1 H, m), 3.48 (1 H, dq, J 7.0, J 9.5), 3.75 (1 H, dq,
J 7.0, J 9.5), 3.97 (1 H, d, J 14.0), 4.10 (1 H, d, J 14.0), 5.22 (1 H,
dd, J 2.0, J 5.5) and 7.35 (4 H, m); mass spectrum: m/z 243
(M+ 24).
2-(p-Methoxybenzyl)-5-ethoxyisoxazolidine 17d. Compound
17d was purified by chromatography using 1:1 hexane–diethyl
ether mixture as eluent. Colourless liquid (32% yield);
νmax(neat)/cmϪ1 2977, 2909, 1517, 1249, 1103, 1034, 984 and 820
(Found: C, 65.6; H, 8.05; N, 5.9. C13H19NO3 requires C, 65.80;
H, 8.07; N, 5.90%); δH (Ϫ30 ЊC) 1.24 (0.60 × 3 H, t, J 7.0), 1.29
(0.40 × 3 H, t, J 7.0), 2.13–2.69 (2.40 × 1 H, m), 3.09 (0.40 × 1
H, app. q, J 8.0), 3.21–3.59 (2.20 × 1 H, m), 3.81 (1 H, m), 3.85 (3
H, s), 3.91 (0.60 × 1 H, d, J 12.5), 4.01 (0.40 × 1 H, d, J 12.5),
4.09 (0.60 × 1 H, d, J 12.5), 4.24 (0.40 × 1 H, d, J 12.5), 5.25 (1
H, broad m), 6.95 (2 H, m) and 7.37 (2 H, m); δH (+50 ЊC) 1.22
(3 H, t, J 7.0), 2.15–2.51 (2 H, m), 2.89 (1 H, m), 3.13 (1 H, m),
3.49 (1 H, dq, J 7.0, J 10.0), 3.77 (1 H, m), 3.79 (3 H, s), 4.02 (2
H, broad s), 5.22 (1 H, dd, J 2.0, J 5.5), 6.90 (2 H, d, J 10.0)
and 7.34 (2 H, d, J 10.0); mass spectrum: m/z 237 (M+ 9%).
2-(p-Methylbenzyl)-5-ethoxyisoxazolidine 17e. Compound
17e was purified by chromatography using 4:1 hexane–diethyl
ether mixture as eluent. Colourless liquid (33% yield);
νmax(neat)/cmϪ1 2977, 2932, 1517, 1109, 1076, 1004, 935 and 802
(Found: C, 70.6; H, 8.7; N, 6.5. C13H19NO2 requires C, 70.56;
H, 8.65; N, 6.33%); δH (Ϫ40 ЊC) 1.26 (0.59 × 3 H, t, J 7.0), 1.31
(0.41 × 3 H, t, J 7.0), 2.12–2.72 (2.41 × 1 H, m), 2.39 (3 H, s),
3.18 (0.41 × 1 H, app. q, J 8.0), 3.22–3.58 (2.18 × 1 H, m), 3.86
(1 H, m), 3.94 (0.59 × 1 H, d, J 13.5), 4.04 (0.41 × 1 H, d, J
12.5), 4.11 (0.59 × 1 H, d, J 13.5), 4.26 (0.41 × 1 H, d, J 12.5),
5.26 (1 H, broad m), 7.26 (2 H, m) and 7.38 (2 H, m); δH (+50 ЊC)
1.22 (3 H, t, J 7.0), 2.16–2.52 (2 H, m), 2.34 (3 H, s), 2.92 (1 H,
m), 3.14 (1 H, m), 3.50 (1 H, dq, J 7.0, J 10.0), 3.80 (1 H, dq,
J 7.0, J 10.0), 4.05 (2 H, broad s), 5.22 (1 H, dd, J 2.0, J 5.25),
7.16 (2 H, d, J 8.0) and 7.32 (2 H, d, J 8.0); mass spectrum: m/z
221 (M+ 52).
2-(p-N,N-dimethylbenzyl)-5-ethoxyisoxazolidine 17f. Com-
pound 17f was purified by chromatography using 4:1 hexane–
diethyl ether mixture as eluent. Colourless liquid (37% yield);
νmax(neat)/cmϪ1 2961, 2884, 1615, 1523, 1344, 1105, 1079, 1010,
984, 951 and 808 (Found: C, 67.25; H, 8.8; N, 11.1. C14H22N2O2
requires C, 67.17; H, 8.86; N, 11.19); δH (Ϫ40 ЊC) 1.26 (0.62 × 3
H, t, J 7.0), 1.31 (0.38 × 3 H, t, J 7.0), 2.12–2.71 (2.38 × 1 H,
m), 2.94 (6 H, s), 3.06 (0.38 H, m), 3.27 (1.24 × H, m), 3.47 (1
H, m), 3.90 (1 H, m), 3.79 (0.62 × 1 H, d, J 12.5), 3.96 (0.38 × 1
H, d, J 12.5), 4.13 (0.62 × 1 H, d, J 12.5), 4.25 (0.38 × 1 H, d, J
12.5), 5.28 (1 H, broad m), 6.81 (2 H, m) and 7.33 (2 H, m);
δH (+50 ЊC) 1.13 (3 H, t, J 7.0), 2.12–2.52 (2 H, m), 2.86 (1 H, s),
2.94 (6 H, s), 3.08 (1 H, m), 3.52 (1 H, dq, J 7.0, J 10.0), 3.84
(1 H, dq, J 7.0, J 10.0), 4.02 (2 H, broad s), 5.24 (1 H, dd, J 2.0,
J 5.25), 7.11 (2 H, d, J 10.0), 7.65 (2 H, d, J 10.0).
General procedure for the synthesis of isoxazolidines 17
To a solution of the hydroxylamine 8 (3.0 mmol) in CH2Cl2
(10 cm3) at 0 ЊC was added yellow HgO (2.60 g, 12 mmol).
The reaction mixture was stirred at Ϫ10 ЊC until the formation
of the N-oxide and the disappearance of the hydroxylamine
were complete (ca. 2 h) as indicated by TLC (silica, diethyl
ether). After passing through a bed of MgSO4 and washing the
bed with CH2Cl2 the resultant solution was concentrated to ca.
10 cm3 and ethyl vinyl ether (3 cm3) was added to it. After stir-
ring the mixture at 30 ЊC for 48 h, the solvent and excess alkane
were removed and the residual mixture was chromatographed
over silica gel using appropriate eluent as detailed below.
2-(p-Nitrobenzyl)-5-ethoxyisoxazolidine 17b. Compound 17b
was purified by chromatography using 4:1 hexane–diethyl ether
mixture as eluent. Colourless liquid (18% yield); νmax(neat)/
cmϪ1 2971, 2906, 1520, 1350, 1106, 1101, 935 and 745 (Found:
C, 57.1; H, 6.3; N, 11.1. C12H16N2O4 requires C, 57,13; H, 6.39;
N, 11.10%); δH (Ϫ30.0 ЊC) 1.25 (0.60 × 3 H, t, J 7.0), 1.29
(0.40 × 3 H, t, J 7.0), 2.22–2.80 (2.60 × 1 H, m), 3.18–3.32
(0.40 × 1 H, m), 3.34–3.60 (2 H, m), 3.77 (1 H, dq, J 7.0, J 10.0),
4.05 (0.60 × 1 H, d, J 15.0), 4.17 (0.40 × 1 H, d, J 14.0), 4.25
(0.60 × 1 H, d, J 15.0), 4.41 (0.40 × 1 H, d, J 14.0), 5.28 (1 H,
broad m), 7.69 (2 H, two overlapping doublets, J 9.0) and 8.33
(2 H, two overlapping doublets, J 9.0); δH (+50 ЊC) 1.22 (3 H,
t, J 7.0), 2.44 (2 H, m), 3.0 (1 H, m), 3.27 (1 H, m), 3.50 (1 H,
dq, J 7.0, J 10.0), 3.73 (1 H, dq, J 7.0, J 10.0), 4.07 (1 H, d,
J 14.0), 4.27 (1 H, d, J 14.0), 5.24 (1 H, dd, J 2.3, J 5.75), 7.66
(2 H, d, J 10.0) and 8.27 (2 H, d, J 10.0).
2-p-(Chlorobenzyl)-5-ethoxyisoxazolidine 17c. Compound
17c was purified by chromatography using 4:1 hexane–diethyl
ether mixture as eluent. Colourless liquid (25% yield);
νmax(neat)/cmϪ1 2977, 2909, 1493, 1103, 1016, 933 and 811
(Found: C, 59.5; H, 6.7; N, 5.8. C12H16NO2Cl requires C, 59.62;
H, 6.67; N, 5.79%); δH (Ϫ40 ЊC) 1.24 (0.58 × 3 H, t, J 7.0), 1.29
(0.42 × 3 H, t, J 7.0), 2.17–2.71 (2.42 × 1 H, m), 3.11 (0.42 × 1
H, app. q, J 8.0), 3.41 (2.16 × 1 H, m), 3.81 (1 H, m), 4.02
(0.58 × 2 H, AB, J 13.8), 4.05 (0.42 × 1 H, d, J 12.5), 4.25
(0.42 × 1 H, d, J 12.5), 5.25 (1 H, broad m) and 7.38 (4 H, s);
δH (+50 ЊC) 1.19 (3 H, t, J 7.0), 2.18–2.56 (2 H, m), 2.91 (1 H,
2-(m-Nitrobenzyl)-5-ethoxyisoxazolidine 17g. Compound 17g
was purified by chromatography using 4:1 hexane–diethyl ether
mixture as eluent. Colourless liquid (12% yield); νmax(neat)/cmϪ1
2977, 2909, 1532, 1350, 1103, 1001, 948, 814, 730 and 677
(Found: C, 57.0; H, 6.3; N, 11.2. C12H16N2O4 requires C, 57.13;
H, 6.39; N, 11.10%); δH (Ϫ40 ЊC) 1.29 (0.63 × 3 H, t, J 7.0), 1.33
(0.37 × 3 H, t, J 7.0), 2.23–3.13 (2.37 × 1 H, m), 3.21 (0.37 × 1
H, app. q, J 8.0), 3.50 (2.26 × 1 H, m), 3.82 (1 H, m), 4.06
(0.63 × 1 H, d, J 15.5), 4.17 (0.37 × 1 H, d, J 13.8), 4.27
(0.63 × 1 H, d, J 15.5), 4.39 (0.37 × 1 H, d, J 13.8), 5.28 (1 H,
broad m), 7.63 (1 H, m), 7.86 (1 H, m), 8.27 (1 H, m) and 8.41
(1 H, m); δH (+50 ЊC) 1.21 (3 H, t, J 7.0), 2.21–2.63 (2 H, m),
2.98 (1 H, m), 3.27 (1 H, m), 3.50 (1 H, dq, J 7.0, J 10.0), 3.76
(1 H, dq, J 7.0, J 10.0), 4.07 (1 H, d, J 15.5), 4.27 (1 H, d, J
15.5), 5.24 (1 H, dd, J 2.20, J 5.5), 7.55 (1 H, t, J 8.0), 7.81 (1 H,
d, J 8.0), 8.19 (1 H, d, J 8.0) and 8.36 (1 H, s); mass spectrum:
m/z 252 (M+ 54%).
2-(o-Hydroxybenzyl)-5-ethoxyisoxazolidine 17h. Compound
17h was purified by chromatography using 4:1 hexane–diethyl
ether mixture as eluent. White crystal, mp 47–49 ЊC (diethyl
J. Chem. Soc., Perkin Trans. 2, 1997
417