2704 J . Org. Chem., Vol. 67, No. 8, 2002
Notes
Sa len Sch iff Ba se Liga n d 1. In dry ethanol (10 mL), 1.50 g
(5.72 mmol) of 3,5-di-tert-pentylsalicylaldehyde and 0.360 g (3.14
mmol) of (1R,2R)-(-)-1,2-diaminocyclohexane were stirred under
nitrogen atmosphere at room temperature for 8 h. The ethanol
was reduced and cooled in an ice bath. The solid Schiff base was
filtered and washed with cold ethanol. The yellow product was
purified by recrystallization in hexane to afford salen Schiff base
(-)-4-Meth yl-r-h yd r oxyp h en yla ceton itr ile 2c.29 Colorless
oil, [R]22 -48.5 (c ) 0.5, CHCl3); IR (neat) νmax 3415.7 (OH),
D
2246.9 (CN) cm-1
;
1H NMR (400 MHz, CDCl3) δ 2.31 (s, 3H),
2.58 (s, 1H), 5.42 (s, 1H), 7.18 (d, J ) 7.79 Hz, 2H), 7.34 (d, J )
8.09 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 21.67, 63.95, 119.32,
127.10, 130.27, 132.81, 140.45. MS of TFA ester: 243 (M+).
(-)-4-Eth yl-r-h yd r oxyp h en yla ceton itr ile 2d . Colorless oil,
ligand 1 (1.53 g, 89%). IR (KBr) νmax 1629.8 (CdN) cm-1
;
1H
[R]22 -15.6 (c ) 0.9, CHCl3); IR (neat) νmax 3423.45 (OH),
D
NMR (400 MHz, CDCl3) δ 13.53 (br s, 2H), 8.17 (s, 2H), 7.08 (d,
J ) 2.4 Hz, 2H), 6.80 (d, J ) 2.4 Hz, 2H), 3.20-3.23 (m, 2H),
1.88-1.92 (m, 2H), 1.75-1.86 (m, 6H), 1.44 (m, 8H), 1.27 (s,
12H), 1.10 (s, 12H), 0.55 (t, J ) 7.40 Hz, 6H), 0.52 (t, J ) 7.42
Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 166.40, 158.34, 138.36,
134.99, 129.05, 127.16, 118.08, 72.92, 39.05, 37.52, 37.20, 33.57,
33.11, 28.86, 28.70, 27.84, 27.79, 24.74, 9.86, 9.47. Anal. Calcd
for C40H62N2O2 C: 79.68, H: 10.37, N: 4.64. Found: C: 79.50,
H: 10.31, N: 4.59.
2248.87 (CN) cm-1
;
1H NMR (400 MHz, CDCl3) δ 1.16 (t, J )
7.61 Hz, 3H), 2.60 (q, J ) 7.60 Hz, 2H), 2.81(s, 1H), δ5.40 (d, J
) 6.74 Hz, 1H), 7.19 (d, 2H), 7.35 (d, 2H); 13C NMR (100 MHz,
CDCl3) δ 15.80, 29.01, 64.07, 119.17, 127.18, 129.15, 133.06,
146.82. MS of TFA ester: 257 (M+).
(-)-4-Isop r op yl-r-h yd r oxyp h en yla ceton itr ile 2e.29 Color-
less oil, [R]22 -51.5 (c ) 1.0, CHCl3); IR (neat) νmax 3425.38
D
(OH), 2250.80 (CN) cm-1; 1H NMR (400 MHz, CDCl3) δ 1.18 (d,
J ) 6.84 Hz, 6H), 2.85 (m, J ) 6.92 Hz, 1H), 2.89 (s, 1H), 5.40
(d, J ) 6.6 Hz, 1H), 7.22 (d, J ) 8.19 Hz, 2H), 7.36 (d, J ) 8.16
Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 24.24, 34.35, 119.3,
127.21, 127.72, 133.15, 151.38. MS of TFA ester: 271 (M+).
(-)-4-ter t-Bu tyl-r-h yd r oxyp h en yla ceton itr ile 2f. Color-
less oil, [R]22D -25.0 (c ) 0.8, CHCl3); IR (neat) νmax 3421.5 (OH)
A Typ ica l P r oced u r e for Cya n a tion of Ben za ld eh yd e.
Schiff base ligand 1 (15 mg, 0.0248 mmol), Ti(iOPr)4 (7 mg,
0.0246 mmol), and 2 mL of dry CH2Cl2 were added to a 50 mL
round-bottom flask and were stirred at room temperature for 1
h. The solvent was then evaporated under vacuum, and 1 mL
of freshly dried CH2Cl2 was added and evaporated under vacuum
again. A 1 mL amount of freshly dried CH2Cl2 and 53 mg (0.5
mmol) of benzaldehyde were added. The reaction mixture was
cooled to -78 °C, and 100 mg (1.0 mmol) of Me3SiCN in 1 mL of
dry CH2Cl2 was added dropwise to the reaction flask. The
reaction was stirred for 12 h at -78 °C and then allowed to rise
to room temperature for 6 h. The reaction mixture was purified
through silica gel with 4:1 hexane:EtOAc solvent. The solvent
was evaporated, and 10 mL of CH2Cl2 was added to the residue
along with 10 mL of 1 N HCl. The resulting mixture was stirred
at room-temperature overnight to yield the cyanohydrin. The
organic layer was washed several times with water and then
dried with Na2SO4. The cyanohydrin was then further purified
with silica gel using 10:1 (v/v) hexane:EtOAc as the solvent.
Der iva tiza tion of Cya n oh yd r in s. In methylene chloride,
10 mg of cyanohydrin was allowed to react with an excess of
trifluoroacetic anhydride for 1 h. The solution was cooled in an
ice bath, and an aqueous solution of 5% sodium bicarbonate was
added dropwise until the solution was neutralized. The organic
layer was separated and washed several times with water and
dried with anhydrous sodium sulfate. The organic layer was then
analyzed by GC.
2248.9 (CN) cm-1 1H NMR (400 MHz, CDCl3) δ 1.26 (s, 9H),
;
2.88 (s, 1H), 5.42 (s, 1H), 7.35 (m, 4H); 13C NMR (100 MHz,
CDCl3) δ 31.63, 35.18, 63.75, 119.46, 126.55, 126.94, 132.79,
153.54. MS of TFA ester: 285 (M+).
(-)-4-Ch lor o-r-h yd r oxyp h en yla ceton itr ile 2g.29 Colorless
oil, [R]22 -39.4 (c ) 0.5, CHCl3); IR (neat) νmax 3417.66 (OH),
D
2250.80 (CN) cm-1; 1H NMR (CDCl3) δ 3.17 (s, 1H), 5.45 (s, 1H),
7.37 (d, 2H), 7.34 (d, 2H); 13C NMR (100 MHz, CDCl3) δ 63.33,
118.87, 128.44, 129.84, 134.04, 136.37. MS of TFA ester: 263
(M+).
(-)-3-Ch lor o-r-h yd r oxyp h en yla ceton itr ile 2h .29 Colorless
oil, [R]22 -54.4 (c ) 0.8, CHCl3); IR (neat) νmax 3504.5 (OH),
D
2239.2 (CN) cm-1
;
1H NMR (400 MHz, CDCl3) δ 2.75 (s, 1H),
5.46 (s, 1H), 7.33 (m, 3H), 7.46 (s, 1H); 13C NMR (CDCl3) δ 63.20,
118.73, 125.04, 127.17, 130.39, 130.85, 135.55, 137.34. MS of
TFA ester: 263 (M+).
(-)-4-F lu or o-r-h yd r oxyp h en yla cet on it r ile 2i. Colorless
oil, [R]22 -36.4 (c ) 0.8, CHCl3); IR (neat) νmax 3417.7 (OH),
D
2250.8 (CN) cm-1
;
1H NMR (400 MHz, CDCl3) δ 2.57 (d, J )
6.74 Hz, 1H), 5.46 (d, J ) 6.63 Hz, 1H), 7.06 (m, 2H), 7.46 (m,
2H); 13C NMR (100 MHz, CDCl3) δ 63.26, 116.54, 116.76, 119.14,
129.10, 131.51, 162.59, 165.07. MS of TFA ester: 247 (M+).
(-)-2-(r-Hyd r oxya ceton itr ile)n a p h th a len e 2j.29 Light yel-
(S)-(-)-Ma n d elon itr ile 2a . The TFA ester of mandelonitrile
was compared to converted TFA ester of commercial (R)-(+)-
low solid, [R]22 -14.5 (c ) 1.0, CHCl3); IR (neat) νmax 3469.74
D
mandelonitrile. IR (neat) νmax 3417.7 (OH), 2248.9 (CN) cm-1
;
(OH), 2243.08 (CN) cm-1; 1H NMR (400 MHz, CDCl3) δ 2.67 (d,
J ) 6.83 Hz, 1H), 5.63 (d, J ) 6.50 Hz, 1H), 7.49 (m, 3H), 7.83
(m, 3H), 7.94 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 64.37, 119.02,
124.04, 126.65, 127.43, 127.71, 128.23, 128.75, 129.86, 132.85,
133.38, 134.15. MS of TFA ester: 279 (M+).
1H NMR (400 MHz, CDCl3) δ 3.25 (br, 1H), 5.44 (s, 1H), 7.34-
7.45 (5H, m); 13C NMR (100 MHz, CDCl3) δ 64.01, 119.26, 127.07,
129.61, 130.25, 135.69.
(-)-3-Meth yl-r-h yd r oxyp h en yla ceton itr ile 2b.29 Colorless
oil, [R]22 -41.3 (c ) 0.5, CHCl3); IR (neat) νmax 3423.4 (OH),
D
2248.9 (CdN) cm-1; H NMR (400 MHz, CDCl3) δ 2.22 (s, 3H),
1
4.28 (s, 1H), 5.27 (s, 1H), 7.12 (m, 4H); 13C NMR (100 MHz,
CDCl3) δ 20.23, 62.22, 118.16, 122.68, 126.24, 127.95, 129.39,
134.14, 137.99. MS of TFA ester: 243 (M+).
Ack n ow led gm en t . Financial support by NIH/
NIGMS (S06GM08247 and R25GM604 14) as well as
NASA (NCC3-552) are gratefully acknowledged.
(29) Mathews, B. R.; J ackson, W. R.; J ayatilake, G. S.; Wilshire,
C.; J acobs, H. A. Aust. J . Chem. 1988, 41, 1697.
J O0161779