ꢀ
F. Martınez Lagos et al. / Tetrahedron: Asymmetry 15 (2004) 763–770
768
the chemical shift values expressed in ppm, using TMS
as the internal standard. Optical rotations were mea-
sured with a Perkin Elmer 241 polarimeter. Optical
density was measured on a Cecil 1021 spectrophoto-
meter at 600 nm. Gas chromatographic analysis was
performed using a Hewlett Packard Model 5890A GC
equipped with a flame ionization detector and a TR-
WAX X 60 m 0,25 mm, 0,25 lm capillary column from
SUGELABOR (Spain). The oven temperature was
programmed from 155 ꢁC (1 min isotherm) to 175 ꢁC at
4.0 ꢁC minꢀ1 and then held at the upper limit for 6.5 min,
with the final chromatogram time being 12.5 min. The
column pressure was 40 psi, the flow rate of the carrier
gas (helium) was 2.1 mL minꢀ1 (auxiliary gas was not
necessary), and the split flow ratio was 20:1.
5.2.4. (RS)-1-Chloro-3-phthalimide propan-2-ol 4. A
mixture of potassium phthalimide (0.054 mol), and epi-
chlorohydrin (0.27 mol) in EtOH/CH2Cl2 (1:1) (50 mL)
was stirred at room temperature for 8 h. Then, the un-
reacted epichlorohydrin was removed under vacuum.
The mixture was cooled and HCCl3 (20 mL) and 6 mL of
HCl 35% then added, and the mixture stirred for 1 h at
0–5 ꢁC. Afterwards, 10 mL of water were added and the
organic phase removed and washed again with 10 mL of
water. The organic phase was dried over anhydrous
CaCl2 and concentrated at vacuum. Halohydrin was
obtained in 89% yield after the usual work-up followed
by chromatography (eluant CH2Cl2). 1H NMR (CDCl3,
250 MHz) d: 2.86 (d, 1H, OH), 3.62 (m, 2H, CH2–N),
3.90 (m, 2H, CH2–Cl), 4.16 (m, 1H, CH–OH), 7.72 (m,
2H, Ar–H), 7.85 (m, 2H, Ar–H), ppm; 13C NMR
(CDCl3) d: 41.6 (CH2–N), 47.3 (CH2–Cl), 69.8 (CH–
OH), 123.6 (2CH, Ar), 131.9 (2C, Ar), 134.4 (2CH, Ar),
168.7 (2CO–N), ppm. Elemental Anal. Calcd for
C11H10ClNO3: C, 55.12; H, 4.22; N, 5.80. Found: C,
55.30; H, 4.38; N, 5.91.
5.2. Preparation of racemic halohydrins 3
5.2.1. Preparation of racemic 1-aryloxy-3-halopropan-2-
ols 3a–f. A mixture of phenol (0.02 mol), epichlorohy-
drin (0.1 mol) and pyridine (0.002 mol) was stirred at
room temperature for 24 h. Then, the unreacted epi-
chlorohydrin and pyridine were removed under vacuum.
The mixture was cooled at which point CHCl3 (10 mL)
and 5 mL of HCl 35% were added and the mixture was
stirred for 1 h at room temperature. Afterwards, 10 mL
of water were added and the organic phase removed and
washed again with 10 mL of water. The organic phase
was dried over anhydrous CaCl2 and concentrated
under vacuum. Preparation of halohydrins 3a–d has
been previously described.12;13
5.2.5. Preparation of 1-aryloxy-3-halopropan-2-one 1 a–f
and 1-chloro-3-phthalimide propan-2-one 2. The synthesis
of haloketones 1a–d has already been described.12;13 The
alcohols 3e,f and for 2 were oxidized as follows: A
mixture of pyridinium chlororochromate (4.83 mmol)
and CH2Cl2 (20 mL) was stirred for 10 min at room
temperature. Alcohol (3.22 mmol) in CH2Cl2 (10 mL)
was then added. The solution was stirred for 24 h for 3e
and 3f, and for 48 h 2. The solution was decanted and
washed with three portions of ether. The combined
organic solution was passed through celite, the solvent
removed and the product subjected to chromatography
on silica gel.
5.2.2. (RS)-1-Chloro-3-(p-nitrophenyloxy)propan-2-ol 3e.
Prepared as described above. Halohydrin was obtained
in 77% yield after the usual work-up followed by chro-
matography (eluant CH2Cl2). 1H NMR (CDCl3,
250 MHz) d: 2.52 (d, 1H, OH), 3.74 (m, 2H, CH2–Cl),
4.13 (m, 2H, CH2–O), 4.37 (m, 1H, CH), 6.92 (d, 2H,
Ar–H), 8.22 (d, 2H, Ar–H) ppm; 13C NMR (CDCl3) d:
45.8 (CH2–Cl), 69.2 (CH–OH), 69.6 (CH2–O), 114.6 (C2,
C6, Ar), 126.1 (C3, C5, Ar), 142.0 (C1, Ar), 163.0 (C4,
Ar), ppm. Elemental Anal. Calcd for C9H10ClNO4: C,
46.72; H, 4.45; N, 6.03. Found: C, 46.70; H, 4.46; N
6.05.
5.2.6. 1-Chloro-3-(p-nitrophenyloxy)propan-2-one 1e.
Prepared as described above. Haloketone was obtained
in 70% yield after the usual work-up followed by chro-
matography (eluant CHCl3). 1H NMR (CDCl3,
250 MHz) d: 4.34 (s, 2H, CH2–Cl), 4.93 (s, 2H, CH2–O),
6.97 (d, 2H, Ar–H), 8.23 (d, 2H, Ar–H) ppm; 13C NMR
(CDCl3) d: 46.7 (CH2–Cl), 71.2 (CH2–O), 114.6 (C2, C6,
Ar), 126.0 (C3, C5, Ar), 142.0 (C1, Ar), 161.9 (C4, Ar),
197.0 (CO) ppm. Elemental Anal. Calcd for
C9H8ClNO4: C, 47.12; H, 3.51; N, 6.10. Found: C,
47.60; H, 3.29; N 5.85.
5.2.3. (RS)-1-Chloro-3-(2,5-dimethyl-phenyloxy)propan-
2-ol 3f. Prepared as described above. Halohydrin was
obtained in 70% yield after the usual work-up followed
by chromatography (eluant hexane/ethyl acetate 9:1).
1H NMR (CDCl3, 250 MHz) d: 2.16 (s, 3H, CH3), 2.30
(s, 3H, CH3), 2.56 (d, 1H, OH), 3.77 (m, 2H, CH2–Cl),
4.06 (m, 2H, CH2–O), 4.21 (m, 1H, CH), 6.64 (s, 1H,
Ar–H), 6.99 (d, 1H, Ar–H), 7.01 (d, 1H, Ar–H), ppm;
13C NMR (CDCl3): 15.9 (CH3), 21.4 (CH3), 46.2
(CH2–Cl), 68.4 (CH–OH), 70.1 (CH2–O), 112.3 (C6, Ar),
121.7 (C4, Ar), 123.6 (C2, Ar), 130.6 (C3, Ar), 136.9 (C5,
Ar), 156.1 (C1, Ar), ppm. Elemental Anal. Calcd
for C11H15ClO2: C, 61.53; H, 7.04. Found: C, 61.55; H,
7.06.
5.2.7. 1-Chloro-3-(2,5-dimthyl-phenyloxy)propan-2-one
1f. Prepared as described above. Haloketone was
obtained in 63% yield after the usual work-up followed
by chromatography (CH2Cl2). 1H NMR (CDCl3,
250 MHz) d: 2.22 (s, 3H, CH3), 2.29 (s, 3H, CH3), 4.47
(s, 2H, CH2–Cl), 4.70 (s, 2H, CH2–O), 6.48 (s, 1H, Ar–
H), 6.72 (d, 1H, Ar–H), 7.02 (d, 1H, Ar–H) ppm; 13C
NMR (CDCl3) d: 15.9 (CH3), 21.4 (CH3), 47.1 (CH2–
Cl), 71.8 (CH2–O), 111.7 (C6, Ar), 122.5 (C4, Ar), 123.6
(C2, Ar), 131.0 (C3, Ar), 137.1 (C5, Ar), 153.3 (C1, Ar),
199.5 (CO) ppm. Elemental Anal. Calcd for
C11H13ClO2: C, 62.12; H, 6.26. Found: C, 62.34; H, 6.30.