912
A. Cruz et al. / Tetrahedron: Asymmetry 21 (2010) 909–913
129.71 (Co), 129.71 (Cm), 62.98 (C1), 58.93 (C2), 29.84 (N–CH3);
4.7. cis-(2S,3R)-1,2-Dimethyl-3-phenylaziridine 9a
13.59 (C2–CH3).
(1S,2S)-Chlorodeoxypseudoephedrine hydrochloride 3a (1.0 g,
4.54 mmol) and K2CO3 (1.88 g, 13.64 mmol) were dissolved in
5 mL of anhydrous ethanol and refluxed during 72 h, the resulted
KHCO3 and KCl in suspension were filtered off and ethanol was
evaporated. The resulting mixture was dissolved in CHCl3. From
this solution compound 10a precipitated and was filtered off as a
white solid (0.1 g). Chloroform was eliminated to give the corre-
sponding aziridine 9a as viscous liquid (0.53 g, 80% yield):
4.3. (1R,2R)-Chlorodeoxynorpseudoephedrine hydrochloride 3b
Synthesized as 3a, (1R,2R)-(+)-norpseudoephedrine hydrochlo-
ride 2b (1.0 g, 5.33 mmol) to get 3b as a white solid (0.82 g, 74%),
mp 205–207 °C; ½a D33
ꢂ
¼ ꢁ10:4 (c 0.1, H2O); 1H NMR [d, ppm,
DMSO-d6]: 8.68 (br, 3H, +NH3), 7.45 (m, 5H, Ph), 5.26 (d, 1H,
3J = 9.7 Hz, C1-H), 3.83 (dq, 1H, J = 9.7, 6.7 Hz, C2-H), 1.03 (d, 3H,
3J = 6.7 Hz, C2–CH3). 13C NMR [d, ppm, DMSO-d6]: 138.08 (Ci),
129.9 (Cp), 129.65 (Co), 128.51 (Cm), 65.0 (C1), 52.92 (C2), 16.91
½
a 2D0
ꢂ
¼ ꢁ131 (c 0.8, EtOH) 1H NMR [d, ppm, CDCl3]: 7.25 (m, 5H,
Ph), 2.50 (s, 3H, N–CH3), 2.44 (d, 1H, 3J = 6.7 Hz, C2-H), 1.68 (dq,
1H, J = 6.7, 5.9 Hz, C2-H), 0.92 (d, 3H, 3J = 5.9 Hz, C2–CH3). 13C
NMR [d, ppm, CDCl3]: 137.76 (Ci), 128.11 (Co), 127.96 (Cm),
126.7 (Cp), 47.82 (C2), 47.71 (C3), 43.14 (N–CH3); 12.85 C3–CH3.
z/e (%): 146 (100), 147 (16), 148 (2).
C2–CH3; IR (KBr, m
max/cmꢁ1): 3420 (NH3), 3058, 3014 (Ar), 2996,
2974, 2958 (CH, CH3), 716, 692 (Cl); Elemental Anal. Calcd: C,
52.4461; H, 6.3570; N, 6.7956. Found: C, 53.1263; H, 6.4989; N,
7.5554.
4.4. (1R,2S)-Chlorodeoxyephedrine hydrochloride 4a
4.8. Threo-(1S,2S)-ephedrinylethylether hydrochloride 10a
Synthesized as 3a, (1R,2S)-(+)-ephedrine hydrochloride 1a
(1.0 g, 4.96 mmol) at room temperature to get 0.96 g (88%) of a
mixture of chlorodeoxy stereoisomers 4a/3a (40:60 erythro/threo).
The erythro chlorodeoxy hydrochloride 4a was separated from the
threo isomer 3a by a fractional crystallization from ethanol as a
white solid (0.2 g). 1H NMR [d, ppm, DMSO-d6]: 9.45 (br, 2H,
+NH2Me), 7.35 (m, 5H, Ph), 5.93 (d, 1H, 3J = 3.2 Hz, C1-H), 3.70
(dq, 1H, J = 3.2, 6.4 Hz, C2-H), 2.60 (s, 3H, N–CH3), 1.13 (d, 3H,
3J = 6.4 Hz, C2–CH3). 13C NMR [d, ppm, DMSO-d6]: 137.15 (Ci),
128.80 (Cp), 129.32 (Co), 128.04 (Cm), 63.45 (C1), 59.58 (C2),
31.19 (N–CH3); 10.63 (C2–CH3).
1H NMR [d, ppm, CDCl3]: 7.3 (m, 5H, Ph), 4.40 (d, 1H, 3J = 9.7 Hz,
C1-H), 3.31 (dq, J = 19.1, 7.0 Hz, 2H, O–CH2), 3.17 (dq, 1H, J = 9.7,
6.7 Hz, C2-H), 1.16 (t, J = 7.0 Hz, 3H, CH2CH3), 1.08 (d, 3H,
3J = 6.7 Hz, C2–CH3). 13C NMR [d, ppm, CDCl3]: 137.80 (Ci), 129.0
(Co), 128.99 (Cm), 127.82 (Cp), 82.65 (C1), 64.71 (C2), 60.59 (O–
CH2), 31.52 (N–CH3), 15.36 (CH2CH3), 13.72 (C2–CH3). z/e (%): 58
(100), 77 (9.6), 194 (18.4).
4.9. cis-(2R,3S)-2-Methyl-3-phenylaziridine 9b
Synthesized as 10a, (1R,2R)-chlorodeoxynorpseudo-ephedrine
hydrochloride 3b (1.0 g, 4.85 mmol) and K2CO3 (2.0 g,
14.55 mmol), aziridine 9b precipitate as white solid (0.62 g, 96%
4.5. (1S,2R)-Chlorodeoxynorephedrine hydrochloride 4b
yield): mp 61 °C, (lit.10 68 °C); ½a D20
ꢂ
¼ þ69:1 (c 4.43 ꢃ 10ꢁ3, CHCl3),
This compound was identified when the threo chlorodeoxy
hydrochloride 3b in DMSO-d6 solution is heated (80–90 °C) for five
hours in the NMR tube to get a 60:40 mixture of the 3b/4b
stereoisomers.
{lit.10
½
a 2D5
ꢂ
¼ ꢁ74 (c 3, EtOH)}; IR (KBr) 3218, 1600 cmꢁ1
;
1H NMR
[d, ppm, CDCl3]: 7.26 (m, 5H, Ph), 3.18 (d, 1H, 3J = 6.4 Hz, C2-H),
2.34 (dq, 1H, C2-H, 3J = 6.4, 5.6 Hz), 0.88 (d, 3H, 3J = 5.6 Hz, C2–
CH3). 13C NMR [d, ppm, CDCl3]: 137.86 (Ci), 128.11 (Co), 128.02
(Cm), 126.83 (Cp), 37.33 (C2), 32.39 (C3), 13.83 C3–CH3. z/e (%):
1H NMR [d, ppm, DMSO-d6]: 8.8 (br, 3H, +NH3), 7.45 (m, 5H, Ph),
5.65 (d, 1H, 3J = 4.4 Hz, C1-H), 3.70 (dq, 1H, J = 4.4, 6.4 Hz, C2-H),
1.17 (d, 3H, 3J = 6.4 Hz, C2–CH3). 13C NMR [d, ppm, DMSO-d6]:
135.63 (Ci), 129.93 (Cp), 129.65 (Co), 128.51 (Cm), 64.76 (C1),
52.51 (C2), 13.72, (C2–CH3).
132 (100), 133 (12), 77 (19.25), 28 (53.2). IR (KBr,
m
max/cmꢁ1):
3308 (NH), 3060, 3026 (Ar), 2992, 2958, 2926 (CH, CH3); Elemental
Anal. Calcd: C, 81.1600; H, 8.3239; N, 10.5161. Found: C, 81.0615;
H, 8.3238; N, 11.1770.
4.6.
4.10. Erythro-(1R,2S)-ephedrinylethylether 10ae
The isochlorodeoxy-derivatives 8a and 8b were identified as
intermediates in a solid mixture with the corresponding chlorode-
oxy-derivatives 3a and 3b when the reactions of the corresponding
chlorodeoxy-hydrochlorides 3a or 3b were reacted with two molar
equivalents of K2CO3 in refluxing chloroform for 72 h.
Sythesized as 10a, (1R,2S)-chlorodeoxyephedrine hydrochloride
4a (0.2 g, 0.11 mmol) and K2CO3 (0.046 g, 0.33 mmol) to get ether
10ae as white solid (0.2 g, 96% yield): mp = 185–186 °C;
½
a 2D0
ꢂ
¼ ꢁ68:5 (c 3.08 ꢃ 10ꢁ3, EtOH) 1H NMR [d, ppm, CDCl3]: 7.30
(m, 5H, Ph), 4.98 (d, 1H, 3J = 2.9 Hz, C1-H), 3.51 (dq, J = 7.0,
4.7 Hz, 2H, O–CH2), 3.27 (dq, 1H, J = 2.9, 6.7 Hz, C2-H), 1.26 (t,
J = 7.0 Hz, 3H, CH2CH3), 1.21 (d, 3H, 3J = 6.7 Hz, C2–CH3). 13C NMR
[d, ppm, CDCl3]: 137.82 (Ci), 128.86 (Co), 126.83 (Cm), 128.37
(Cp), 79.78 (C1), 65.41 (C2), 59.77 (O–CH2), 30.75 (N–CH3), 15.52
(CH2–CH3), 9.81 (C2–CH3). z/e (%): 58 (100), 77 (11.2), 194 (6.2).
4.6.1. (1R,2R)-Isochlorodeoxypseudoephedrine hydrochloride
8a
1H NMR [d, ppm, DMSO-d6]: 9.35 (br, 2H, +NH2CH3), 7.5 (m, 5H,
Ph), 4.76 (dq, 1H, 8.5, 6.4 Hz, C2-H), 4.49 (d, 1H, 3J = 8.5 Hz, C1-H),
2.59 (s, 3H, N–CH3), 1.26 (d, 3H, 3J = 6.4 Hz, C2–CH3). 13C NMR [d,
ppm, DMSO-d6]: 132.61 (Ci), 130.34 (Cp), 130.00 (Co), 129.83
(Cm), 68.45 (C1), 58.07 (C2), 32.08 (N–CH3); 22.44 (C2–CH3).
4.10.1. Crystal data
Formula, C12H20NOCl; formula weight, 229.74; crystal system,
monoclinic; space group, P21 (No. 4); a, b, c [Å], 14.1041(19),
4.6.2. (1S,2S)-Isochlorodeoxynorpseudoephedrine
hydrochloride 8b
7.1403(10), 14.642(2); a, b, c
[°], 90, 113.044(2), 90; V [°3],
1356.9(3); Z, 4; D(calcd) [g/cm3], 1.125; Mu(MoKa) [mm ], 0.260;
F(0 0 0), 496; crystal size [mm], 0.35 ꢃ 0.30 ꢃ 0.20.
1H NMR [d, ppm, DMSO-d6]: 7.65–7.40 (m, 5H, Ph), 4.63 (dq, 1H,
J = 9.7, 6.6 Hz, C2-H), 4.47 (d, 1H, 3J = 9.7 Hz, C1-H), 1.26 (d, 3H,
3J = 6.6 Hz, C4–CH3). 13C NMR [d, ppm, DMSO-d6]: 137.29 (Ci),
129.82 (Cp), 129.48 (Co), 127.96 (Cm), 60.91 (C1), 59.41 (C2),
22.35 (C2–CH3).
4.10.2. Data collection
Temperature (K), 293; radiation [Å], MoKa 0.71073; Theta Min–
Max [Deg], 1.5–25.0; dataset: ꢁ16:16; ꢁ8:8; ꢁ17:17; Tot., Uniq.