2080 J . Org. Chem., Vol. 67, No. 7, 2002
Dejaegher et al.
(1H, d, J ) 2.97 Hz, NCH(H)), 3.15 and 3.38 (2 × OMe), 7.27-
7.37 and 7.50-7.55 (5H, 2 × m, C6H5); 13C NMR (CDCl3) δ
25.0, 25.1, 25.9 and 32.3 (C5H10), 30.3 (NCH2), 44.8 (NCHCq),
49.3 and 49.5 (2 × OMe), 70.0 (NCH), 99.9 (C(OMe)2), 127.2
and 127.7 (Co, Cm), 127.9 (Cp), 140.5 (Cq); IR (NaCl) 2929, 2854,
(1H, septet, J ) 6.27 Hz, CHMe2), 1.79 (1H, d × d, J ) 6.6
Hz, J ) 2 Hz, NCH(H)), 2.29 (1H, d × d, J ) 3, 2 Hz, NCH-
(H)), 2.94 (1H, d × d, J ) 6.6, 3 Hz, NCHCdO), 7.34-7.61
and 8.05-8.09 (5H, m, C6H5); 13C NMR (CDCl3) δ 21.8 and
22.2 (2 × Me2CH), 36.5 (NCH2), 40.3 (NCHCdO), 61.7 (CHMe2),
128.2 and 128.6 (Co, Cm), 133.2 (Cp), 136.9 (Cq), 196.3 (CdO);
IR (NaCl) 1682 cm-1 (CdO); MS m/z 189 (M+, 13), 174 (18),
146 (30), 133 (64), 105 (100), 91 (50), 84 (54), 77 (67), 57 (23),
42 (66). Flash chromatography: CH2Cl2/MeOH 98/2, Rf ) 0.41.
Anal. Calcd for C12H15NO: C, 76.16; H, 7.99; N, 7.40. Found:
C, 76.25; H, 8.09; N, 7.32.
1489, 1449, 1369, 1249, 1197, 1175, 1102, 1073, 1051 cm-1
;
MS m/z no M+, 245 (4), 230 (55), 162 (4), 151 (8), 147 (16), 105
(16), 91 (11), 86 (35), 84 (54), 49 (10). Anal. Calcd for C17H25
-
NO2: C, 74.14; H, 9.15; N, 5.09. Found: C, 74.28; H, 9.30; N,
4.94.
2-[Dim eth oxy(4-m eth ylph en yl)m eth yl]-1-isopr opylazir -
id in e (5c): 1H NMR (CDCl3) δ 0.59 and 1.06 (2 × 3H, 2 × d,
J ) 6.27 Hz, Me2CH), 1.24 (1H, septet, J ) 6.27 Hz, CHMe2),
1.28 (1H, d, broad, J ) 6.5 Hz, NCH(H)), 1.46 (1H, d × d, J )
6.5, 3 Hz, NCHCq), 2.20 (1H, d, J ) 3 Hz, NCH(H)), 2.34 (3H,
s, CqCH3), 3.15 and 3.37 (2 × OMe), 7.15 and 7.42 (4H, 2 × d,
J ) 8 Hz, C6H4); 13C NMR (CDCl3) δ 21.1 (CqCH3), 21.8 and
21.9 (2 × Me2CH), 30.8 (NCH2), 45.5 (NCHCq), 49.2 and 49.4
(2 × OMe), 61.8 (CHMe2), 99.8 (C(OMe)2), 127.1 and 128.4 (Co,
Cm), 137.2 and 137.5 (2 × Cq); IR (NaCl) 2967, 2831, 1511,
1455, 1382, 1367, 1340, 1249, 1196, 1136, 1107 cm-1; MS m/z
249 (M+, 0.22), 234 (M+ - Me, 0.61), 219 (M+ - 2 × Me, 5),
218 (M+ - OMe, 12), 204 (42), 165 (100), 144 (6), 119 (24),
105 (12), 91 (11). Anal. Calcd for C15H23NO2: C, 72.25; H, 9.30;
N, 5.62. Found: C, 72.39; H, 9.43; N, 5.50.
2-[Dim eth oxy(4-flu or op h en yl)m eth yl]-1-isop r op yla zir -
id in e (5d ): 1H NMR (CDCl3) δ 0.55 and 1.06 (2 × 3H, 2 × d,
J ) 6.27 Hz, Me2CH), 1.24 (1H, septet, J ) 6.27 Hz, CHMe2),
1.30 (1H, d × d, J ) 6.5, 0.7 Hz, NCH(H)), 1.45 (1H, d × d, J
) 6.5 Hz, J ) 3.3 Hz, NCHCq), 2.22 (1H, d, J ) 3.3 Hz, NCH-
(H)), 3.12 and 3.39 (2 × OMe), 7.03 and 7.51 (4H, 2 × t, J )
8.91 Hz, C6H4); 13C NMR (CDCl3) δ 21.8 and 21.9 (2 × Me2-
CH), 31.1 (NCH2), 45.3 (NCHCq), 49.3 and 49.4 (2 × OMe),
61.7 (CHMe2), 99.6 (C(OMe)2), 114.5 and 129.1 (Co, Cm, 2 × d,
J ) 20.7, 8.6 Hz), 136.4 (Cq, d, J ) 3.6 Hz), 162.5 (FCq, d, J )
246.6 Hz); IR (NaCl) 3062, 2968, 2833, 1604, 1508, 1455, 1382,
1367, 1340, 1294, 1252, 1223, 1196, 1156, 1137 cm-1; MS m/z
no M+, 234 (2), 222 (5), 209 (20), 208 (30), 169 (100), 123 (38),
109 (13), 95 (15), 42 (13). Anal. Calcd for C14H20FNO2: C, 66.38;
H, 7.96; N, 5.53. Found: C, 66.51; H, 8.09; N, 5.40.
1-Cycloh exyl-2-ben zoylazir idin e (13b): 1H NMR (CDCl3)
δ 1.01-1.86 (12H, m, C6H11 and NCH(H)), 2.29 (1H, d, broad,
J ) 1.65 Hz, NCH(H)), 2.94 (1H, d × d, J ) 6, 3 Hz, NCHCd
O), 7.45-7.61 and 8.05-8.08 (5H, m, C6H5); 13C NMR (CDCl3)
δ 24.7, 24.8, 25.9, 32.3 and 32.7 (C5H10), 35.8 (NCH2), 39.6
(NCHCdO), 69.5 (NCH), 128.2 and 128.5 (Co, Cm), 133.0 (Cp),
136.9 (Cq), 196.4 (CdO); IR (NaCl) 1682 cm-1 (CdO); MS m/z
229 (M+, 38), 228 (16), 186 (11), 177 (14), 147 (14), 146 (44),
133 (87), 124 (100), 110 (35), 109 (33), 105 (84), 97 (31), 96
(25), 91 (43), 77 (60), 55 (52), 54 (14), 51 (13). Flash chroma-
tography: CH2Cl2/MeOH 98/2, Rf ) 0.34. Anal. Calcd for
C15H19NO: C, 78.56; H, 8.35; N, 6.11. Found: C, 78.69; H, 8.46;
N, 6.03.
1-Isopr opyl-2-(4-m eth ylben zoyl)azir idin e (13c): 1H NMR
(CDCl3) δ 1.18 and 1.21 (2 × 3H, 2 × d, J ) 6.27 Hz, Me2CH),
1.67 (1H, septet, J ) 6.27 Hz, CHMe2), 1.77 (1H, d × d, J )
6.6, 2 Hz, NCH(H)), 2.29 (1H, d × d, J ) 3, 2 Hz, NCH(H)),
2.42 (3H, s, CH3Cq), 2.92 (1H, d × d, J ) 6.6, 3 Hz, NCHCd
O), 7.28 and 7.97 (4H, 2 × d, J ) 7.92 Hz, C6H4); 13C NMR
(CDCl3) δ 21.7 (CH3Cq), 21.9 and 22.2 (2 × Me2CH), 36.4
(NCH2), 40.2 (NCHCdO), 61.7 (CHMe2), 128.4 and 129.3 (Co,
Cm), 134.5 (Cp), 144.1 (Cq), 195.8 (CdO); IR (NaCl) 1679 cm-1
(CdO); MS m/z 203 (M+, 17), 188 (11), 160 (25), 147 (55), 119
(100), 105 (54), 91 (55), 84 (49), 65 (26), 57 (22), 55 (19), 43
(27); flash chromatography CH2Cl2/MeOH 98/2, Rf ) 0.13.
Anal. Calcd for C13H17NO: C, 76.81; H, 8.43; N, 6.89. Found:
C, 76.89; H, 8.38; N, 6.95.
1-Isopr opyl-2-(4-flu or oben zoyl)azir idin e (13d): 1H NMR
(CDCl3) δ 1.19 and 1.21 (2 × 3H, 2 × d, J ) 6.27 Hz, Me2CH),
1.68 (1H, septet, J ) 6.27 Hz, CHMe2), 1.79 (1H, d × d, J ) 6,
2 Hz, NCH(H)), 2.29 (1H, m, NCH(H)), 2.88 (1H, d × d, J ) 6,
3 Hz, NCHCdO), 7.12-7.28 and 8.05-8.15 (4H, 2 × m, C6H4);
13C NMR (CDCl3) δ 21.9 and 22.2 (2 × Me2CH), 36.5 (NCH2),
40.5 (NCHCdO), 61.8 (CHMe2), 115.8 and 131.0 (Co, Cm, 2 ×
d, J ) 22.0, 9.8 Hz), 133.3 (Cp, d, J ) 2.5 Hz), 165.8 (FCq, d,
J ) 253.9 Hz), 194.8 (CdO); IR (NaCl) 1683 cm-1 (CdO); MS
m/z 207 (M+, 8), 192 (11), 164 (18), 152 (43), 124 (99), 110 (38),
96 (56), 85 (70), 75 (16), 58 (16), 43 (100); flash chromatography
CH2Cl2/MeOH 98/2, Rf ) 0.36. Anal. Calcd for C12H14FNO: C,
69.55; H, 6.81; N, 6.76. Found: C, 69.66; H, 6.90; N, 6.70.
1-Isop r op yl-2-(4-m eth oxyben zoyl)a zir id in e (13e): mp
2-[Dim eth oxy(4-m eth oxyp h en yl)m eth yl]-1-isop r op yl-
a zir id in e (5e): 1H NMR (CDCl3) δ 0.59 and 1.06 (2 × 3H, 2
× d, J ) 6.27 Hz, Me2CH), 1.24 (1H, septet, J ) 6.27 Hz,
CHMe2), 1.26 (1H, d, broad, J ) 6.27 Hz, NCH(H)), 1.46 (1H,
d × d, J ) 6.27 Hz, J ) 3.3 Hz, NCHCq), 2.20 (1H, d, J ) 3.3
Hz, NCH(H)), 3.13, 3.37 and 3.79 (3 × OMe), 6.87 and 7.46
(4H, 2 × d, J ) 8.91 Hz, C6H4); 13C NMR (CDCl3) δ 21.9 (2 ×
Me2CH), 30.9 (NCH2), 45.5 (NCHCq), 49.2, 49.4 and 55.1 (3 ×
OMe), 61.8 (CHMe2), 99.8 (C(OMe)2), 113.0 and 128.4 (Co, Cm),
132.8 and 159.2 (2 × Cq); IR (NaCl) 2966, 2833, 1612, 1583,
1511, 1464, 1381, 1366, 1340, 1301, 1247, 1196, 1136, 1107,
1042 cm-1; MS m/z 265 (M+, 2), 250 (M+ - Me, 2), 235 (M+
-
2 × Me, 13), 234 (M+ - OMe, 5), 220 (83), 203 (2), 181 (65),
135 (100), 122 (11), 121 (13), 86 (17), 84 (28), 77 (18), 49 (28),
47 (13). Anal. Calcd for C15H23NO3: C, 67.90; H, 8.74; N, 5.28.
Found: C, 68.06; H, 8.89; N, 5.11.
81.4-82.4 °C; H NMR (CDCl3) δ 1.18 and 1.20 (2 × 3H, 2 ×
1
d, J ) 6.27 Hz, Me2CH), 1.66 (1H, septet, J ) 6.27 Hz, CHMe2),
1.76 (1H, d × d, J ) 6.6, 1.65 Hz, NCH(H)), 2.27 (1H, d, broad,
J ) 1.65 Hz, NCH(H)), 2.89 (1H, d × d, J ) 6.6, 3 Hz, NCHCd
O), 3.87 (OMe), 6.95 and 8.07 (4H, 2 × d, J ) 8.91 Hz, C6H4);
13C NMR (CDCl3) δ 21.9 and 22.2 (2 × Me2CH), 36.2 (NCH2),
40.1 (NCHCdO), 55.5 (OMe), 61.7 (CHMe2), 113.8 and 130.6
(Co, Cm), 129.8 (Cp), 163.6 (Cq), 194.6 (CdO); IR (KBr) 1672
cm-1 (CdO); MS m/z 219 (M+, 14), 176 (11), 163 (48), 135 (100),
121 (36), 107 (11), 92 (14), 84 (45), 77 (16), 57 (13), 42 (29);
flash chromatography CH2Cl2/MeOH 98/2, Rf ) 0.28. Anal.
Calcd for C13H17NO2: C, 71.21; H, 7.81; N, 6.39. Found: C,
71.33; H, 7.87; N, 6.29.
Syn th esis of 1-Alk yl-2-a r oyla zir id in es 13. The synthesis
of 1-isopropyl-2-benzoylaziridine (13a ) is representative for the
synthesis of these compounds. Sodium hydride (0.33 g; 8.25
mmol, 60% dispersion in oil) was washed two times with 5
mL of pentane and evaporated to dryness. Dry DMSO (6 mL)
was added, and the mixture was stirred for 15 min at room
temperature to generate dimsylsodium. Subsequently, 1.00 g
(4.1 mmol) of 3,3-dichloro-1-isopropyl-2-phenylazetidine 4,
dissolved in 6 mL of dry DMSO, was added dropwise at room
temperature. After the addition was completed, the mixture
was kept at 80 °C for 2 h. After cooling, 20 mL of water was
added and the water phase was extracted three times with 10
mL of diethyl ether. The combined organic phases were dried
over magnesium sulfate and after filtration and evaporation
of the solvent, the crude 1-isopropyl-2-benzoylaziridine (13a )
was obtained. Further purification was performed by flash
chromatography to yield 0.36 g (46%) of the pure compound.
1-Isop r op yl-2-ben zoyla zir id in e (13a ): 1H NMR (CDCl3)
δ 1.18 and 1.21 (2 × 3H, 2 × d, J ) 6.27 Hz, Me2CH), 1.68
Syn th esis of 1-Alk yl-2-a r oyla zir id in es 13 by Hyd r oly-
sis of Azir id in es 5. The synthesis of 1-isopropyl-2-(4-meth-
oxybenzoyl)aziridine (13e) is representative for the synthesis
of these aziridines 13. To a solution of 0.11 g (0.4 mmol) of
2-[dimethoxy(4-methoxyphenyl)methyl]-1-isopropylaziridine (5e)
in 1 mL of acetonitrile was added 0.09 g (0.6 mmol) sodium
iodide at room temperature. To this stirred solution was added
dropwise 0.08 mL (0.6 mmol) of boron trifluoride etherate. The
resulting mixture was kept under reflux for 2 h and subse-
quently poured into a saturated sodium bicarbonate solution.