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13
Synthesis of 2-(Bromomethyl)-1-isobutylaziridine (
3c).
To a solution of isobutanal (5c, 0.14 g, 2 mmol) in CH2Cl2 (10 mL) was added 2,3-dibromo-1-propylammonium bromide (0.60 g, 2 mmol, 1 equiv), MgSO4 (0.5 g) and Et3N (0.20 g, 2 mmol, 1 equiv) at 0 °C, and the mixture was heated under reflux for 2 h. After evaporation of the solvent, dry Et2O (20 mL) was added, the resulting precipitate was filtered and the solvent evaporated, affording the corresponding dibromoimine in 94% yield. This imine was used as such in the next step due to its lability. To a solution of N-(isobutylidene)-2,3-dibromopropylamine (0.54 g, 2 mmol) in MeOH (2 mL) was added NaBH4 (0.15 g, 4 mmol, 2 equiv) in small portions at 0 °C, and the mixture was heated under reflux for 3 h. Extraction with CH2Cl2 (2 × 10 mL), drying (MgSO4) and filtration afforded 2-(bromo-methyl)-1-isobutylaziridine (3c, 0.33 g, 87%), which was purified by distillation (65-69 °C/11-12 mmHg); colorless liquid, bp 65-69 °C/11-12 mmHg. 1H NMR (300 MHz, CDCl3): δ = 0.92 and 1.01 [6 H, 2 d, J = 6.6 Hz, (CH3)2], 1.47 [1 H, d, J = 6.1 Hz, (H
cis
CH)N], 1.68-1.76 (1 H, m, CHMe2), 1.75 [1 H, d, J = 3.0 Hz, (HCH
trans
)N], 1.80-1.93 (1 H, m, CHN), 2.05 and 2.17 [2 H, 2 dd, J = 5.8, 8.1, 11.6 Hz, N(HCH)CHMe2], 3.27 and 3.36 [2 H, 2 dd, J = 5.4, 7.3, 10.3 Hz, (HCH)Br]. 13C NMR (75 MHz, CDCl3): δ = 20.80 and 20.92 [(CH3)2], 28.99 (CHMe2), 35.77 and 36.00 (NCH2CH and CH2Br), 40.03 (NCH2
CH), 69.18 (NCH2
i-Pr). IR (NaCl): ν = 3040, 1469, 1383, 1364, 1238, 1220 cm-1. MS (70 eV): m/z (%) = 191/193 (1) [M+], 148/150 (20), 119/121 (18), 112 (100), 70 (7), 68 (5), 57 (41), 56 (77), 42 (73), 41 (45). Anal. Calcd for C7H14BrN (%): C, 43.77; H, 7.35; N, 7.29. Found: C, 43.94; H, 7.55; N, 7.17.
14 As a representative example, the synthesis of 2-ethyl-1-(phenylmethyl)aziridine (6a) is described. To a suspension of CuI (1.52 g, 8 mmol, 2 equiv) in dry Et2O (40 mL) was added slowly MeLi (10 mL, 4 equiv, 1.6 M in Et2O) via a syringe at -78 °C under nitrogen atmosphere. After stirring for 30 min at -78 °C, a solution of 1-benzyl-2-(bromo-methyl)aziridine (3a, 0.90g, 4 mmol) in Et2O (10 mL) was added at -78 °C, and the resulting suspension was further stirred for 6 h at r.t. The reaction mixture was quenched with a sat. solution of NH4Cl (20 mL), filtered over Celite® and washed with Et2O (2 × 20 mL). The filtrate was poured into H2O (100 mL), extracted with Et2O (2 × 75 mL), and the combined organic extracts were washed with sat. NH4Cl (50 mL) and brine (50 mL). Drying (MgSO4), filtration and evaporation of the solvent afforded 2-ethyl-1-(phenyl-methyl)aziridine (6a), which was purified by means of column chromatography on silica gel (EtOAc-hexane, 1:4).
Spectroscopic data of, e.g. 1-(phenylmethyl)-2-pentyl-aziridine (6b): yield 54%, colorless liquid. Flash chromato-graphy on silica gel: EtOAc-hexane, 1:4, R
f
= 0.32. 1H NMR (270 MHz, CDCl3): δ = 0.84 (3 H, t, J = 6.2 Hz, CH3), 1.22-1.47 [10 H, m, (H
cis
CH)N, CHN and (CH
2)4CH3], 1.60 [1 H, d, J = 2.9 Hz, (HCH
trans
)N], 3.30 and 3.49 [2 H, 2 d, J = 13.2 Hz, (HCH)C6H4], 7.22-7.35 (5 H, m, C6H5). 13C NMR (68 MHz, CDCl3): δ = 14.00 (CH3), 22.62, 27.12, 31.57 and 32.96 [(CH2)4CH3], 34.07 (NCH2CH), 39.82 (NCH2
CH), 65.00 (CH2C6H4), 126.95 (HCpara), 128.17 and 128.26 (2 HCortho and 2 HCmeta), 139.40 (Carom,quat). IR (NaCl): ν = 1607, 1496, 1454 cm-1. MS (70 eV): m/z (%) = 203 (6) [M+], 202 (9), 174 (11), 173 (20), 161 (26), 160 (51), 147 (19), 146 (39), 121 (23), 112 (22), 92 (56), 91 (100), 65 (13). Anal. Calcd for C14H21N (%): C, 82.70; H, 10.41; N, 6.89. Found: C, 82.84; H, 10.55; N, 6.74.
Spectroscopic data of aziridines 6a,c-f,j,k are available upon request.
