98
D. Yang et al. / Journal of Molecular Structure 929 (2009) 97–104
400 MHz with TMS as an internal standard. The IR spectra were ob-
tained from KBr discs in the range 4000–400 cmꢁ1 on a Nicolet
5DXFT-IR spectrophotometer. Elemental analyses were performed
with a Perkin-Elmer 2400 instrument and melting points were
determined by an RK1 microscopic melting apparatus. The mass
spectra were measured on a TRACE MS 2000 mass spectrometer.
3c: Yield 62.4%; m.p. 228–230 °C. C20H26ClNO(331.9): Anal.
Calc. for 3c: C 72.31, H 7.83, N 4.22%; Found: C 72.33, H 7.86, N
4.25%. IR (KBr, cmꢁ1
) m: 3321.68 (O–H,stretching), 2921.23 (C–H,
stretching), 2573.89 (N+–H, stretching), 1489.3 cmꢁ1 (Ar, stretch-
ing). 1H NMR (400 MHz in DMSO-d6,) d: 1.78–1.81 (m, 2H, CH2,
piperidine), 2.26 (s, 3H, CH3), 2.32–2.37 (m, 2H, CH2, piperidine),
3.17–3.20 (m, 4H, N–CH2, piperidine), 3.14–3.38 (m, 2H, ph–CH2),
3.20–3.42 (m, 2H, N–CH2), 5.41 (s, 1H, OH), 7.16–7.37 (m, 10H,
Ar–H), 10.71 (s, 1H, N+–H). MS m/z (%): 295.4 ([M–HCl]+,9.41),
204.2 (100), 90.8 (31.42), 55.8 (53.32), 42.0 (82.65).
2.2. Synthesis of 1-phenethyl-4-hydroxy-4-substituted piperidinium
hydrochlorides, 3a–3d
The synthesis of the title compounds 3a–3d are presented in
Scheme 1. Phenethylamine (1) was converted to the intermediate
of 4-(2-phenethyl)-piperidone (2) according to the procedure gi-
ven in the literature [3,4].
3d: Yield 51.3%; m.p. 203–205 °C. C19H30ClNO(323.8). Anal.
Calc. for 3d: C 70.41, H 9.26, N 4.32%; Found: C 70.44, H 9.27, N
4.35%. IR (KBr, cmꢁ1
) m: 3348.72 (O–H, stretching), 2926.38(C–H,
stretching), 2569.32(N+–H, stretching), 1461 cmꢁ1 (Ar, stretching).
1H NMR (400 MHz in DMSO-d6,) d: 0.91–1.81 (m, 11H, 5CH2, CH,
cyclohexanyl), 1.86–1.90 (m, 2H, CH2 piperidine), 2.46–2.57 (m,
2H, CH2, piperidine), 3.02–3.37 (m, 4H, N–CH2, piperidine), 3.21–
3.36(m, 2H, ph–CH2), 3.23–3.42 (m, 2H, N–CH2), 5.31 (s, 1H, OH),
7.38–7.47 (m, 5H, Ar–H), 10.42 (s, 1H, N+–H). MS m/z (%): 287.3
([M–HCl]+, 5.04), 196.3 (12.32), 91.1 (100), 60.1 (57.42), 42.2
(85.31).
A solution of 2.732 g (0.016 mol) 3-bromofluorobene in 8 mL dry
tetrahydrofuran was added dropwise, with stirring, to a stirred solu-
tion of 0.384 g magnesium and a little of iodine in 5 mL dry tetrahy-
drofuran, which was protected by N2, with a speed of 3 mL/min
under 60 °C. The mixture was heated under refluxing for 2 h, and
added a solution of 1-phenethyl-4-piperidone (2) 4.06 g (0.02 mol)
in dry tetrahydrofuran (10 mL) over a period of 20 min at 65 °C after
the solid of Mg disappeared. It was cooled to 0–5 °C and 15 mL water
was slowly added, concentrated hydrochloric acid was added drop-
wise with stirring to pH = 4. The mixture was extracted into CH2Cl2
(40 mL) and washed with concentrated salt solution (15 mL ꢂ 3).
After drying with MgSO4 (5 g) and removal of CH2Cl2, the residue
was crystallized from acetone (30 mL) to get a white solid 4.187 g
of the title compound 3a.
2.3. X-ray crystallography
The colorless crystal of the title compound 3a (grown from a
mixed solution of petroleum dichloromethane) having approxi-
mate dimensions of 0.30 ꢂ 0.10 ꢂ 0.10 mm was mounted on a
glass fiber in a random orientation. The data were collected by a
Bruker Smart Apex CCD diffractometer with a graphite-monochro-
The syntheses of 3b–3d were carried out by the similar method.
The analytical data for all the compounds 3a–3d are summarized
as follow:
mated Mo K radiation (k = 0.71073 Å) by using a u–
x scan mode
a
in the range of 1.57 6 h 6 25.00° at 293(2) K. Empirical absorption
correction was applied. A total of 16,531 reflections including 7065
unique ones (Rint = 0.0622) were measured. The structure was
solved by direct methods and refined by full-matrix least-squares
techniques on F2 using the SHELXTL program package [5] on a leg-
end Pentium (IV) computer. All the non-hydrogen atoms were re-
fined anisotropically, and hydrogen atoms were located at their
idealized positions. The final R = 0.0687, wR = 0.1452 (w = 1/
3a: Yield 64.3%; m.p. 192–194 °C. C19H23ClFNO(335.8). Anal.
Calc. for 3a: C 67.90, H 6.87, N 4.17%; Found: C 67.93, H 6.84, N
4.19%. IR (KBr, cmꢁ1
) m: 3318.37 (O–H,stretching), 2921.2 (C–H,
stretching), 2586.1 (N+–H, stretching), 1429.14 cmꢁ1 (Ar, stretch-
ing). 1H NMR (400 MHz in DMSO-d6,) d: 1.81–1.84 (m, 2H, CH2,
piperidine), 2.37–2.43 (m, 2H, CH2, piperidine), 3.15–3.23 (m, 4H,
N–CH2, piperidine), 3.18–3.33 (m, 2H, ph–CH2), 3.26–3.52 (m, 2H,
N–CH2), 5.64 (s, 1H, OH), 7.09–7.46 (m, 10H, Ar–H), 10.67 (s, 1H,
N+–H). MS m/z (%): 299.3 ([M–HCl]+,5.37), 207.5 (100), 90.9
(30.67), 55.9 (54.01), 42.0 (84.72).
[
(
r
D
2(F2o) + (0.0284P)2 + 3.5000P], where P = (Fo2 þ 2F2c )/3), S = 1.096,
/r)
max = 0.020, (
D
q
)
max = 0.447 and (
D
q
)
min = ꢁ0.495 e/Å3. The
structural plots were drawn with SHELXTL-97 software package.
Details of the data collection and refinement parameters are given
in Table 1. Atomic coordinates and equivalent displacement
parameters are list in Table 2. Other details of the structure have
been deposited with the Cambridge Crystallographic Data Centre
No. CCDC713410.
3b: Yield 60.1%; m.p. 190–193 °C. C20H26ClNO2(347.9). Anal.
Calc. for 3b: C 68.99, H 7.47, N 4.02%; Found: C 69.02, H 7.48, N
4.04%. IR (KBr, cmꢁ1
) m: 3317.39 (O–H,stretching), 2929.40 (C–H,
stretching), 2561.33 (N+–H, stretching), 1512.34 cmꢁ1 (Ar, stretch-
ing). 1H NMR (400 MHz in DMSO-d6,) d: 1.80–1.83 (m, 2H, CH2,
piperidine), 2.35–2.39 (m, 2H, CH2, piperidine), 3.14–3.21 (m, 4H,
N–CH2, piperidine), 3.19–3.35 (m, 2H, ph–CH2), 3.24–3.47 (m, 2H,
N–CH2), 3.73 (s, 3H, OCH3) 5.33 (s, 1H, OH), 6.91–7.53 (m, 10H,
Ar–H), 10.68 (s, 1H, N+–H). MS m/z (%): 311.4 ([M–HCl]+, 10.52),
220.3 (100), 90.7 (35.53), 55.7 (52.30), 41.8 (83.23).
2.4. B3LYP calculation
The B3LYP [6,7] calculations with a 6-31G (d, p) [8] basis set
were performed using the GAUSSION-O3 package [9].
Scheme 1. Structure and synthesis of 1-phenethyl-4-hydroxy-4-substituted piperidinium hydrochlorides.