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839
ture was filtered using a membrane filter (Millipore, Millex-LH®, 0.45 mm),
3H), 4.70—4.67 (m, 1H), 2.87 (br s, 1H), 2.72—2.65 (m, 2H), 2.04—1.98
and the filtrate was concentrated to give the product. A mixture of methyl 4- (m, 2H). 13C-NMR d: 150.3, 141.0, 131.9, 128.2, 128.1, 126.3, 125.8, 118.6,
cyanobenzoate,21) 4-methoxycarbonylbenzylamine21) and bis(4-methoxycar- 110.6, 40.4, 31.6. MS (EI) m/z: 237 (Mꢀ), 219, 132, 105, 92. Anal. Calcd for
bonylbenzyl)amine22) was obtained. The ratio of the product was determined
by 1H-NMR.
C16H15NO: C, 80.73; H, 6.39; N, 5.93. Found: C, 80.98; H, 6.37; N, 5.90.
General Procedure for the Hydrogenation to Various Benzonitrile De- References and Notes
rivatives Using 5% Pd/C(en) or 5% Pd/C in THF (Table 3) After two
vacuum/H2 cycles to replace air inside the reaction tube with hydrogen, the
mixture of substrate (1.0 mmol, commercially available) and 5% Pd/C (en)
or 5% Pd/C (10 wt% of the substrate) in THF (1.0 ml) was vigorously stirred
at room temperature (ca. 20 °C) under 1 atm of hydrogen for 24 h. The reac-
tion mixture was filtered using a membrane filter (Millipore, Millex-LH®,
0.45 mm), and the filtrate was concentrated to give the product. A mixture of
a benzylamine derivative and a dibenzylamine derivative were obtained. The
ratio of the products was determined by 1H-NMR. All of the compounds are
commercially available except for dibenzylamine derivatives (3) in entries 2
and 4. The secondary amine (3) in entries 2 and 4 were known products in
the literature; see references 27 and 28.
1) Kleemann A., Engel J., Kutscher B., Reichert D., “Pharmaceutical
Substances Syntheses, Patents, Applications,” 4th ed., Georg Thieme,
Stuttgart, 2001.
2) Larock R. C., “Comprehensive Organic Transformations,” 2nd ed.,
John Wiely & Sons, New York, 1999.
3) Nishimura S., “Handbook of Heterogeneous Catalytic Hydrogenation
for Organic Synthesis,” Wiley-Interscience, New York, 2001.
4) Rylander P. N., “Hydrogenation Methods,” Academic Press, New
York, 1985.
5) Sajiki H., Tetrahedron Lett., 36, 3465—3468 (1995).
6) Sajiki H., Ong K. Y., Tetrahedron, 52, 14507—14514 (1996).
7) Sajiki H., Kuno H., Hirota K., Tetrahedron Lett., 38, 399—402 (1997).
8) Sajiki H., Kuno H., Hirota K., Tetrahedron Lett., 39, 7127—7130
(1998).
General Procedure for the Chemoselective Hydrogenation (Table 4)
After two vacuum/H2 cycles to replace air inside the reaction tube with hy-
drogen, the mixture of the substrate (1.0 mmol) and 5% Pd/C(en) (10 wt% of
9) Sajiki H., Hirota K., Tetrahedron, 54, 13981—13996 (1998).
the substrate) in THF (1.0 ml) was vigorously stirred at room temperature 10) Sajiki H., Hirota K., Chem. Pharm. Bull., 51, 320—324 (2003).
(ca. 20 °C) under 1 atm of hydrogen for 24 h. The reaction mixture was fil- 11) Mori A., Miyakawa Y., Ohashi E., Haga T., Maegawa T., Sajiki H.,
tered using a membrane filter (Millipore, Millex-LH®, 0.45 mm), and the fil-
Org. Lett., 8, 3279—3281 (2006), and references cited therein.
trate was concentrated to give the product. All of the starting materials and 12) Sajiki H., Hattori K., Hirota K., J. Org. Chem., 63, 7990—7992
products are reported in literature except for 1-(4-cyanophenyl)-3-phenyl-2-
propyn-1-ol and 1-(4-cyanophenyl)-3-phenylpropan-1-ol in entry 5.
1-(4-Cyanophenyl)-3-phenyl-2-propyn-1-ol To a diethyl ether (70 ml)
solution of phenylacetylene (2.88 g, 28.2 mmol) and triethylamine (2.85 g,
28.2 mmol) were added a diethyl ether (70 ml) solution of InBr3 (10.0 g,
28.2 mmol) and the reaction mixture was stirred for 1 h at room temperature
(1998).
13) Sajiki H., Hattori K., Hirota K., J. Chem. Soc., Perkin Trans. 1, 1998,
4043—4044 (1998).
14) Sajiki H., Hattori K., Hirota K., Chem. Eur. J., 6, 2200—2204 (2000).
15) Hattori K., Sajiki H., Hirota K., Tetrahedron, 56, 8433—8441 (2000).
16) Hattori K., Sajiki H., Hirota K., Tetrahedron, 57, 4817—4824 (2001).
(ca. 20 °C) under argon. To the solution benzaldehyde (1.85 g, 14.1 mmol) 17) Sajiki H., Ikawa T., Hirota K., Org. Lett., 6, 4977—4980 (2004).
was added dropwise. The mixture was stirred for 2 h at room temperature
(ca. 20 °C). To the reaction mixture dichloromethane (150 ml) was added,
the solution was washed with 1 N HCl (175 ml) and water (120 ml). The
organic layer was dried over MgSO4, filtered, concentrated under reduced
pressure. The crude product was purified by recrystallization (n-hexane and
ethyl acetate) to afford 1-(4-cyanophenyl)-3-phenyl-2-propyn-1-ol (2.55 g,
18) Ikawa T., Hattori K., Sajiki H., Hirota K., Tetrahedron, 60, 6901—
6911 (2004).
19) A mixture of the starting material (3,4,5-trimethoxybenzonitrile (1),
3,4,5-trimethoxybenzylamine (2) and bis(3,4,5-trimethoxybenzyl)-
amine (3) was obtained for even shorter reaction time (6 h, 1 : 2ꢀ3ꢁ
68 : 32).
20) A mixture of 4-hydroxybenzonitrile (A), 4-methylphenol (B) and 4-hy-
droxybenzylamine (C) was obtained (A : B : Cꢁ15 : 68 : 17) by the use
of 5% Pd/C as a catalyst.
1
78% yield) as a pale yellow solid. mp 91.0—92.0 °C. H-NMR (400 MHz,
CDCl3) d 7.71 (d, Jꢁ8.1 Hz, 2H), 7.65 (d, Jꢁ8.1 Hz, 2H), 7.45—7.43 (m,
2H), 7.35—7.29 (m, 3H), 5.73 (s, 1H), 2.98 (br s, 1H). 13C-NMR d: 145.5,
132.3, 131.6, 128.8, 128.3, 127.1, 121.7, 118.5, 111.8, 87.5, 87.4, 64.1. MS 21) Commercially available.
(EI) m/z: 233 (Mꢀ), 216, 204, 102. Anal. Calcd for C16H11NO: C, 82.61; H, 22) Ashton P. R., Clink P. T., Stoddart J. F., Tasker P. A., White A. J. P.,
4.96; N, 6.02. Found: C, 82.38; H, 4.75; N, 6.00.
Williams D. J., Chem. Eur. J., 2, 729—736 (1996).
1-(4-Cyanophenyl)-3-phenylpropan-1-ol To a round-bottom flask with
23) Andrieux C. P., J. Chem. Soc. Perkin Trans. 2, 2002, 985—990 (2002).
a stir bar were added 1-(4-cyanophenyl)-3-phenyl-2-propyn-1-ol (233.2 mg, 24) Huo S., Org. Lett., 5, 423—425 (2003).
1.00 mmol), 5% Pd/C(en) (23 mg, 10 wt% of the substrate), and THF
(1.00 ml). The air in the flask was replaced with hydrogen by two vacuum/H2
cycles and the mixture was vigorously stirred at room temperature (ca.
25) Cheng G., Mirafzal G. A., Woo L. K., Organometalics, 22, 1468—
1474 (2003).
26) Jensen A. E., Kneisel F., Knochel P., Org. Synth., 79, 35—42 (2003).
20 °C) under ambient pressure of hydrogen (balloon). The reaction mixture 27) Anastasi C., Hantz O., Clercq E. D., Pannecouque C., Clayette P.,
was filtered through a filter paper and the filtrate was concentrated under re-
duced pressure to afford 1-(4-cyanophenyl)-3-phenylpropan-1-ol (196.4 mg,
Dereuddre-Bosquet N., Dormont D., Gondois-Rey F., Hirsch I., Kraus
J.-L., J. Med. Chem., 47, 1183—1192 (2004).
83% yield) as a pale yellow oil. 1H-NMR (400 MHz, CDCl3) d: 7.53 (d, 28) Donetti A., Bellora E., J. Org. Chem., 37, 3352—3353 (1972).
Jꢁ8.1 Hz, 2H), 7.40 (d, Jꢁ8.1 Hz, 2H), 7.27—7.24 (m, 2H), 7.19—7.14 (m,