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Synlett 2005(6): 0931-0934  
DOI: 10.1055/s-2005-864801
LETTER
© Georg Thieme Verlag Stuttgart · New York

Coupling of 1-Alkyl-2-(bromomethyl)aziridines with Lithium Dialkylcuprates towards 1,2-Dialkylaziridines

Matthias D’hooghe, Mario Rottiers, Robrecht Jolie, Norbert De Kimpe*
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
Fax: +32(9)2646243; e-Mail: norbert.dekimpe@UGent.be;
Further Information

Publication History

Received 6 December 2004
Publication Date:
23 March 2005 (online)

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Abstract

The reactivity of 1-alkyl-2-(bromomethyl)aziridines with respect to lithium dialkylcuprates (Gilman reagents) has been evaluated for the first time, pointing to the conclusion that these substrates can be applied successfully as synthetic equivalents for the aziridinylmethyl cation synthon towards, e.g. 2-ethyl-, 2-pentyl- and 2-(phenylmethyl)aziridines in good yields.

Key words

2-(bromomethyl)aziridines - organometallics - nucleophilic substitution - 1,2-dialkylaziridines

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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.

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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.