- 7.67 (m, 4H, Ar-H); 13C NMR (126 MHz, CDCl3) δ 47.8, 67.1,
127.3, 128.8, 130.3, 133.2; HRMS (FAB, calcd for C16H20N (M+)
226.1596, found 226.1599.
Syntheses of Deuterated Compounds 8 and 9. CD3CN was
subjected to method B as described above and the title compound
was isolated by preparative thin-layer chromatography. Compound
1
Syntheses of Deuterated Compound 3. NaH (60% dispersion
in oil, 20 mg, 0.5 mmol) was added to a vigorously stirred solution
of benzyl bromide (70 µL, 0.6 mmol) in DMF-d6 (0.7 mL) in an
ice-water bath and was stirred for 16 h. The solution was mixed
with hexanes and the top hexanes layer was removed. The DMF
layer was analyzed by NMR. The sample was purified by
recrystallization from chloroform. Compound 3-D: 1H NMR (500
MHz, DMF-d6) δ 5.24 (s, 4H), 7.43-7.52 (m, 6H), 7.73-7.80 (m,
4H); 13C NMR (126 M Hz, DMF-d6) δ 46.5 (m), 65.8, 128.9, 130.3,
133.5, 139.5; HRMS (FAB) calcd for C16H14D6N (M+) 232.1972,
found 232.1980.
Syntheses of Compounds 7-9. Two methods were used.
Method A: NaH (60% dispersion on oil, 0.2 g, 5 mmol) was
added to a vigorously stirred solution of benzyl bromide (0.7 mL,
6 mmol) in anhydrous acetonitrile (7 mL) in three portions over a
period of 5 h in an ice-water bath under a nitrogen atmosphere.
The mixture was stirred overnight, then it was filtered through layers
of silica gel and Celite and washed with acetonitrile. The combined
filtrate was mixed with hexanes and the top hexanes layer was
removed. The acetonitrile layer was evaporated to an oil, which
was distilled (130 °C/20 mmHg) to yield compound 8 as a major
product (55%). The 1H NMR spectrum of this sample matched that
of the authentic 3-phenylpropanenitrile purchased from Sigma-
Aldrich.
Method B: Benzyl bromide (0.7 mL, 6 mmol) was added to a
vigorously stirred suspension of NaH (60% dispersion on oil, 0.2 g,
5 mmol) in anhydrous acetonitrile (7 mL) in three portions over a
period of 5 h in an ice-water bath under a nitrogen atmosphere.
The mixture was stirred overnight and the resulting suspension was
filtered through layers of silica gel and Celite and washed with
acetonitrile. The combined filtrate was mixed with hexanes and
the top hexanes layer was removed. The bottom acetonitrile layer
was evaporated under reduced pressure and the resulting oil was
subjected to vacuum distillation to remove compound 8 from the
crude reaction mixture. The remaining oil was dissolved in a
mixture of ethyl acetate and hexanes (5 mL). Slow evaporation of
solvent overnight gave colorless crystals of compound 7. 1H NMR
(500 M Hz, CDCl3) δ 1.20 (d, J ) 6.8 Hz, 3H), 2.36 (dd, J )
16.7, 6.8 Hz, 1H), 2.56 (dd, J ) 16.7, 7.8 Hz, 1H), 3.24 (sxt, J )
6.9 Hz, 1H), 3.54 (d, J ) 13.8 Hz, 2H), 3.69 (d, J ) 13.8 Hz, 2H),
7.06-7.58 (m, 10H); 13C NMR (126 M Hz, CDCl3) δ 13.9, 21.9,
50.3, 53.3, 118.7, 127.1, 128.4, 128.6, 139.1; HRMS (FAB) calcd
for C18H21N2 (M + H+) 265.1705, found 265.1703.
8-D: H NMR (500 MHz, CDCl3) δ 2.95 (s, 2H), 7.22-7.43 (m,
5H); 13C NMR (126 M Hz, CDCl3) δ 18.6 (m), 31.1, 119.0, 127.0,
128.1, 128.2, 128.6, 137.9; HRMS (FAB) calcd for C9H7D2N (M+)
133.0861, found 133.0879.
1
Compound 9-D: H NMR (300 M Hz, CDCl3) δ 1.36 (br s,
1H), 2.99 (s, 1H), 3.76 (s, 2H), 7.13-7.34 (m, 5H); 13C NMR (151
MHz, CDCl3) δ 19.6 (m), 24.4 (m), 48.9, 51.1, 118.0, 127.2, 127.9,
128.5, 139.6; HRMS (FAB) calcd for C11H10D5N2 (M + H+)
180.1549, found 180.1533.
Crystal Growth and Analysis. Repeated recrystallization from
chloroform afforded colorless crystals of compound 3 suitable for
X-ray diffraction analysis. For compound 7, crystals of suitable
size for single-crystal X-ray diffraction analysis were obtained by
diffusion of diethyl ether into the CH2Cl2 solution at room
temperature overnight.
Crystals were examined under Infineum V8512 oil and placed
on a MiTeGen mount, then transferred to the 100 K N2 stream of
a Bruker SMART Apex CCD diffractometer. Unit cell parameters
were determined from reflections with I > 10σ(I) harvested from
three orthogonal sets of 30 0.5° ω scans. Data collection strategy
was calculated with use of COSMO, included in the Apex2 suite
of programs14 to maximize coverage of reciprocal space in a
minimum amount of time. Average 4-fold redundancy of measure-
ments was sought. Data were corrected for Lorentz and polarization
effects, as well as for absorption.
Structure solution and refinement utilized the programs of the
SHELXTL software package.15 Full details of the X-ray structure
determinations are in the CIF files included as Supporting Informa-
tion.
Previously, the structure of compound 3 was determined by X-ray
powder diffraction2 and later by X-ray single crystal diffraction
with an R value of 0.0637.16 Our data reported herein are of higher
quality, with an R value of 0.0215.
Acknowledgment. This work was supported by the National
Institutes of Health.
Supporting Information Available: Compound character-
ization data, including copies of 1D NMR spectra (1H, 13C NMR,
and Dept) and 2D NMR spectra (H-H COSY and H-C Hetcor)
of compounds 3, 3-D, 7, 9, 8-D, and 9-D and crystallographic
information files (CIFs) of compounds 3 and 7. This material
The mother liquor was evaporated and subjected to preparative
thin-layer column chromatography to furnish compound 9. 1H NMR
(500 MHz, CDCl3) δ 1.29 (d, J ) 6.6 Hz, 3H), 2.34 (s, 1H), 2.48
(d, J ) 5.6 Hz, 2H), 3.09 (m, 1H), 3.83 (s, 2H), 7.12-7.48 (m,
5H); 13C NMR (126 MHz, CDCl3) δ 20.2, 24.8, 49.3, 51.0, 117.8,
127.4, 128.1, 128.6, 139.4; HRMS (FAB) calcd for C11H15N2 (M
+ H+) 175.1235, found 175.1256.
JO802706D
(14) COSMO; Bruker-AXS: Madison, WI, 2008; Vol. 58.
(15) Sheldrick, G. M. Acta Crystallogr. A 2008, 64, 112–122.
(16) Busi, S.; Lahtinen, M.; Ropponen, J.; Valkonen, J.; Rissanen, K. J. Solid
State Chem. 2004, 177, 3757–3767.
2570 J. Org. Chem. Vol. 74, No. 6, 2009