1472 J . Org. Chem., Vol. 61, No. 4, 1996
Krohn et al.
Ta ble 4. Ra tes a t t ) 0 a n d Rea ction Tim es for 50%
Con ver sion (t1/2) of th e Deh yd r ogen a tion of Selected
P r im a r y a n d Secon d a r y Alcoh ols
Ta ble 6. Com p a r ision of th e Kin etic Da ta of th e
Deh yd r ogen a tion by Zr (O-n -P r )4 a n d Zr (O-t-Bu )4
-d(c/c0)/dt
observ
t1/2 [min] T [°C] time [min]
-d(c/c0)
observ
time [min]
substr
Zr(OR)4
[min-1
]
substra
(t ) 0) [min-1
]
t1/2 [min]
T [°C]
7
7
22
22
23
23
R ) n-Pr
R ) t-Bu
R ) n-Pr
R ) t-Bu
R ) n-Pr
R ) t-Bu
0.029
0.748
0.040
0.440
0.025
0.384
24
0.9
327
1.7
135
1.9
20
20
0
0
0
180
180
180
180
240
240
1
2
4
6
7
0.009
0.006
0.011
0.009
0.029
0.006
0.017
0.040
0.025
0.186
20
20
20
20
20
20
20
0
120
240
495
210
180
345
240
420
240
270
296
73
24
66
46
327
135
13
0
8
addition of Zr(O-n-Pr)4 (1 M in CH2Cl2, 0.2 mL, 0.2 mmol).
The conversion was monitored for 6.5 h.
Finally, the efficiency of the catalysts Zr(O-n-Pr)4 and Zr-
(O-t-Bu)4 was compared quantitatively as shown in Table 6.
10/11
22
23
24
0
0
Ca ta lytic Oxid a tion of Ster oid s (a lcoh ols 14-17).
A
a
Catalyst Zr(O-n-Pr)4, solvent CCl4.
solution of the steroid (0.5 mmol) in CH2Cl2 (3 mL) was treated
with TBHP (solution in CH2Cl2, 1.25 mmol) and Zr(O-n-Pr)4
(1 M in CH2Cl2, 0.1 mL, 0.1 mmol) at 20 °C as described in
the general procedure for homogenous catalysis. After 90 min
the same amounts of TBHP and catalyst were added a second
time. The reactions were monitored by TLC (ethyl acetate:
CH2Cl2 ) 1:1) and worked up (procedure A) after the times
indicated in Table 1. If necessary, the crude products were
Ta ble 5. Kin etic Da ta for th e Com p etitive Oxid a tion of
1 a n d 5
time [min]
convn 1 [%]a
convn 2 [%]a
c1/c2
0
15
30
0
8.3
0
1
12.2
20.3
35.9
65.3
91.7
94.9
1.05
1.09
1.16
1.74
6.00
8.40
13.7
26.2
39.5
51.6
57.9
purified by column chromatography (ethyl acetate:CH2Cl2
1:1) and crystallization from ethyl acetate/cyclohexane.
)
60
120
210
270
Oxid a tion of 17R-h yd r oxy-19-n or a n d r ost-4-en -3-on e
(14) to 19-n or a n d r ost-4-en e-3,17-d ion e: mp 162.5-163 °C;
lit.35 mp 162-164 °C; 13C NMR δ ) 14.04 (q, 18-C), 21.87 (t),
25.91 (t), 26.84 (t), 30.12 (t, 7-C), 31.57 (t), 35.47 (t), 35.95 (t),
36.70 (t), 40.00 (d, 8-C), 42.58 (d, 9-C), 47.88 (s, 13-C), 49.72
(d, 14-C), 50.31 (d, 10-C), 124.93 (d, 4-C), 166.30 (s, 5-C), 199.73
(s, 3-C), 220.43 (s, 17-C).
Oxid a tion of 17R-h yd r oxyestr a -4,9-d ien -3-on e (16) to
estr a -4,9-d ien e-3,17-d ion e: mp 125.2-126.5 °C; lit.36 mp
130-131 °C; lit.37 mp 119-121 °C; 13C NMR δ ) 13.45 (q, 18-
C), 22.15 (t), 25.42 (t), 26.12 (t), 26.76 (t), 30.94 (t), 31.71 (t),
36.11 (t), 37.26 (t), 38.96 (d, 14-C), 47.74 (s, 13-C), 51.39 (d,
8-C), 122.65 (d, 4-C), 126.42 (s, 10-C), 145.23 (s), 157.07 (s),
199.78 (s, 3-C), 219.95 (s, 17-C).
Oxid a tion of 11â-h yd r oxy-19-n or a n d r ost-4-en e-3,17-
d ion e (15) to 19-n or a n d r ost-4-en e-3,11,17-tr ion e: mp
192-194 °C; lit.38 mp 185-190 °C; 13C NMR δ ) 14.86 (q, 18-
C), 21.44 (t), 28.54 (t), 29.84 (t), 34.79 (t), 36.20 (d, 8-C), 36.30
(t), 37.14 (t), 40.56 (d, 14-C), 49.45 (d, 10-C), 49.85 (t), 51.78
(s, 13-C), 60.43 (d, 9-C), 126.52 (d, 4-C), 164.75 (s, 5-C), 200.13
(s, 3-C), 208.71 (s, 11-C), 216.83 (s, 17-C).
a
c1 ) concentration of 1-octanol, c2 ) concentration of 2-octanol.
a pad of Celite, the drying agents were washed carefully with
CH2Cl2 (3 × 10 mL), and workup was continued as described
under A.
Gen er a l P r oced u r e for th e Heter ogen ou s Ca ta lysis.
To a mixture of alcohol (1.5 mmol), CCl4 (5 mL), TBHP
(solution in CH2Cl2, 3 mmol), and powdered, activated 3 Å
molecular sieves (300 mg) was added the silica gel-supported
zirconium catalyst (see ref 30) at 20 °C. The reaction mixture
was heated to 80 °C, and the conversion was monitored by
TLC and/or GC. The catalyst and the molecular sieves were
separated by filtration, the solvent was removed under reduced
pressure, and the crude product was purified by bulb-to-bulb
distillation, column chromatography, or crystallization and
analyzed by GC and NMR spectroscopy.
Gen er a l An a lytic P r oced u r es a n d Kin etics. All reac-
tions were monitored by TLC and/or GC (examples in the
tables are the result of at least two experiments). For GC,
samples of 0.01 mL were taken from the reaction mixtures,
diluted with CH2Cl2 (1.25 mL), washed with H2O (0.5 mL),
and dried with Na2SO4. Special care was taken to keep the
temperature constant (20 °C). The aldehydes and ketones
obtained by oxidation were identified by comparison of their
1H and 13C NMR data or their retention times/Rf values with
authentic samples.
The nature of the catalyst changed continuously during the
reaction time, and rate orders or constants were difficult to
determine. Instead, the rate v at t ) 0 (d(c/c0)/dt for t ) 0)
and the time at 50% conversion (t1/2) were determined to
compare the reactions quantitatively. The kinetic data were
fitted using TechPlot for Windows,34 and the d(c/c0)/dt values
were calculated for t ) 0 from the functions resulting from
the fit. The square of the correlation coefficient r2 ranged
between 0.98 and 1.00. Selected examples are shown in Table
4, demonstrating the increased rate at t ) 0 for primary,
secondary, and benzylic alcohols.
Oxid a tion of 17r-h yd r oxy-3,3-(2,2-d im eth yltr im eth yl-
en e-1.3-d ioxy) 5(10),9(11)-estr a d ien e (17) to (2,2-d im eth -
yltr im eth ylen e-1,3-dioxy)-5(10),9(11)-estr adien -17-on e: mp
1
129-133 °C (n-hexane), lit.39 139-140 °C; H NMR δ ) 0.78
(18- CH3), 0.79 and 0.98 (2 s, 2 × 3 H, 2 × dioxolane CH3),
1.1-2.4 (m, 18 H), 3.2-3.6 (m, 4 H, dioxolane CH2), 5.45 (s,
broad, 1 H, 11-H); 13C NMR δ ) 15.11 (q, 18-C), 22.71 (q,
dioxolane CH3), 23.21 (q, dioxolane CH3), 23.94 (t), 27.11 (t),
27.23 (t), 30.50 (s, dioxolane-C), 31.16 (t), 33.99 (t), 36.36 (t),
37.83 (d, 14-C), 41.73 (t), 46.52 (s, 13-C), 47.80 (d, 8-C), 70.57
(t, 2 dioxolane CH2), 97.48 (s, 3-C), 116.92 (d, 11-C), 126.41
(s), 130.02 (s), 137.30 (s), 221.88 (s, 17-C).
Ack n ow led gm en t. We thank the Deutsche Fors-
chungsgemeinschaft for financial support, Dr. O. Petrov,
Schering AG, Berlin, for a gift of steroidal alcohols, and
Dr. W. Zeiss, Peroxid Chemie GmbH, Munich, for peroxo
compounds.
J O9518720
Com p etitive Oxid a tion of 1-Octa n ol a n d 2-Octa n ol. A
mixture of 1-octanol (1 mmol) and 2-octanol (1 mmol) was
dissolved in CCl4 (3 mL) (Table 5). TBHP (solution in CH2-
Cl2, 4 mmol) and powdered, activated 3 Å molecular sieves
(0.6 g) were added at 20 °C, and the reaction was started by
(35) French Patent (CIBA, Ltd.) No. 1356548, 1962 (Chem. Abstr.
1964, 61, 10747b).
(36) Perelman, M.; Farkas, E.; Fornefeld, E. J .; Kraay, R. J .; Rapala,
R. T. J . Am. Chem. Soc. 1960, 82, 2402-2403.
(37) Alvarze, F. S.; Watt, A. N. J . Org. Chem. 1972, 37, 3725-3730.
(38) Daniewski, A. R.; Guzewska, M.; Koco´r, M. J . Org. Chem. 1975,
40, 3131-3136.
(34) Dittrich, R. Computer software: Techplot: Braunschweig, 1994.
(39) Hook, C.; Kasch, H. J . Prakt. Chem. 1995, 337, 358-362.