8584 J . Org. Chem., Vol. 63, No. 23, 1998
Notes
6H-dibenzo[a,c]cyclohepten-6-one5 and diethyl ketone.7
Story et al.1 argue that the hexaoxonane is the kinetically
controlled product that is subsequently converted to the
thermodynamically favored tetraoxane. This interpreta-
tion is disputed by McCullough et al.5 who note that while
tetraoxanes are more thermodynamically stable than
hexaoxonanes, which of these is kinetically preferred
depends on the relative rates of the multiple equilibria
between starting material ketone and products. More
specifically, Hardy and Whalen16 suggest that intramo-
lecular ring closure of the penultimate precursors for the
hexaoxonane and tetraoxane is considerably less hin-
dered for the hexaoxonane than for the tetraoxane. At
this point, a preference for tetraoxane versus hexaoxo-
nane formation cannot easily be predicted and is a subject
of our ongoing investigations.
Ad a m a n ta n e-2-sp ir o-3′-1′,2′,4′,5′-tetr a oxa n e-6′-sp ir o-2′′-
a d a m a n ta n e (2a ). Yield, 49%; colorless solid, mp 167 °C dec
1
(CH3CN) (lit.14 mp 172 °C); H NMR 1.50-2.10 (m, 26H), 3.20
(br s, 2H); 13C NMR 27.10, 30.23 (br s), 33.20, 34.25 (br s), 37.00,
110.10.
Nor b or n a n e-2-sp ir o-3′-1′,2′,4′,5′-t et r a oxa n e-6′-sp ir o-2′′-
n or bor n a n e (2b). Yield, 20%; colorless solid, mp 149-151 °C
dec (pentane); 1H NMR 1.05-1.90 (m, 16H), 2.28 (s, 2H), 3.30
(s, 2H); 13C NMR 22.08, 28.09, 35.01, 37.41, 41.89, 42.22, 117.51.
Anal. Calcd for C14H20O4: C, 66.65; H, 7.99. Found: C, 66.79;
H, 7.79.
3,12-D i m e t h y l-7,8,15,16-t e t r a o x a d i s p i r o [5.2.5.2]-
h exa d eca n e (2c). Yield, 19%; colorless solid, mp 71-72 °C
(CH3CN) (lit.4a mp 71-72 °C); 1H NMR 0.94 (d, J ) 6.5 Hz, 6H),
1.09-1.38 (m, 4H), 1.39-1.99 (m, 12H), 3.05 (br s, 2H); 13C NMR
21.47, 28.99 (br), 29.93 (br), 30.45 (br), 31.35 (br), 31.64, 31.74,
108.15, 108.19. VPO MW (CHCl3) 257; calcd MW 256.
3,12-Di-t er t -b u t yl-7,8,15,16-t e t r a oxa d isp ir o[5.2.5.2]-
h exa d eca n e (2d ). Yield, 17%; colorless solid, mp 196-198 °C
dec (CH3CN) (lit.4a mp 90-95 °C, mixture of tetraoxane and
hexaoxonane); 1H NMR 0.88 (s, 18H), 0.99-1.58 (m, 10H), 1.59-
2.00 (m, 6H), 3.19 (br s, 2H); 13C NMR 22.74 (br), 23.13 (br),
27.57, 27.61, 29.70 (br), 31.98 (br), 32.32, 47.37, 47.52, 108.14.
Anal. Calcd for C20H36O4: C, 70.55; H, 10.66. Found: C, 70.70;
H, 10.56. VPO MW (CHCl3) 323; calcd MW 341.
In summary, this work reveals that ozonolysis of
O-methyl oximes can be extended to the preparation of
dispiro-1,2,4,5-tetraoxanes, some of which are inacces-
sible by acid-catalyzed peroxidation methods. In com-
parison with ozonolysis of enol ethers to form tetraox-
anes9 (yields of 11-37%) this method has the advantage
of using the more easily accessible O-methyl oximes
despite their lower reactivities toward ozone. As the
current most reliable method used to differentiate tet-
raoxanes from hexaoxonanes is VPO MW analysis,17 we
also note that ozonolysis of O-methyl oximes can be used
as an independent means of tetraoxane structural veri-
fication, since only tetraoxanes, not hexaoxonanes, are
formed. Finally, this ozonolysis procedure is an attrac-
tive alternative method for tetraoxane synthesis, as many
acid-catalyzed peroxidation methods4b,5 apparently re-
quire commercially unavailable highly concentrated H2O2
to proceed efficiently.
1,10-Di-t er t -b u t yl-7,8,15,16-t e t r a oxa d isp ir o[5.2.5.2]-
h exa d eca n e (2e). Yield, 2%; colorless solid, mp 128 °C dec
1
(ethanol); H NMR 1.05 (s, 18H), 0.80-1.95 (m, 16H), 3.38 (br
s, 2H); 13C NMR 22.34, 24.87, 26.45, 30.28, 33.82, 34.08, 55.78,
113.80. Anal. Calcd for C20H36O4: C, 70.55; H, 10.66. Found:
C, 70.80; H, 10.51.
3,7,8,12,15,16-H exa oxa d isp ir o[5.2.5.2]h exa d eca n e (2f).
Yield, 6%; colorless solid, mp 158-159 °C (CH3OH) (lit.6 mp
1
157-158 °C); H NMR 1.74 (br s, 4H), 2.48 (br s, 4H), 3.75 (br
s, 4H), 3.78 (br s, 4H); 13C NMR 30.83 (br), 32.29 (br), 63.28 (br),
64.62 (br), 106.12.
Gen er a l P r oced u r e for th e P er oxid a tion of Keton es.5
A solution of a cycloalkanone (10 mmol) in acetonitrile (2 mL)
[or in 1:1 acetonitrile/CH2Cl2 (4 mL) for 2-adamantanone] was
added dropwise to a stirred, cold (-30 °C) solution of 50%
hydrogen peroxide (0.60 mL, 11 mmol) and concentrated sulfuric
acid (1.0 mL) in acetonitrile (4.0 mL). After being stirred for
another 1 h at -30 to -20 °C, the solution was kept at -20 °C
overnight.
Ad a m a n ta n e-2-sp ir o-3′-1′,2′,4′,5′-tetr a oxa n e-6′-sp ir o-2′′-
a d a m a n ta n e (2a ). From the precipitated crude product, tet-
raoxane 2a was isolated by flash chromatography using silica
gel and petroleum ether/ether in a ratio of 97:3. Yield, 4%; data
are identical to that reported above.
Exp er im en ta l Section
The melting points are uncorrected. 1H (300 MHz) and 13C
(75 MHz) NMR spectra were recorded on a Varian XL-300
spectrometer using CDCl3 as a solvent. All chemical shifts are
reported in parts per million (ppm) and are relative to internal
(CH3)4Si for 1H and CDCl3 (77.0 ppm) for 13C NMR. Microanaly-
ses were performed by M-H-W-laboratories, Phoenix, AZ. Mo-
lecular weights were determined via the vapor pressure osmom-
etry (VPO) method by Galbraith Laboratories, Inc., Knoxville,
TN.
3,7,8,12,15,16,20,23,24-N o n a o x a t r is p ir o [5.2.5.2.5.2]-
tetr a cosa n e (3). Hexaoxonane 3 was obtained by addition of
water to the reaction mixture to induce precipitation, followed
by filtration and successive recrystallizations from methanol and
All ketones were purchased from Aldrich Chemical Co.
O-Methyl oximes were prepared according to a slightly modified
published method.12 Ozone was generated using an OREC
model 03V5-0 ozonator (percent volt amperes 60; oxygen flow
rate 0.6 L/min).
1
pentane. Yield, 12%; colorless solid, mp 137-139 °C; H NMR
1.75-2.25 (m, 12H), 3.50-4.10 (m, 12H); 13C NMR 31.28, 64.58,
105.53. Anal. Calcd for C15H24O9: C, 51.72; H, 6.94. Found:
C, 51.68; H, 6.85. VPO MW (CHCl3) 342; calcd MW 348.
Gen er a l P r oced u r e for Syn th esis of Disp ir o Tetr a ox-
a n es. A solution of an O-methyl oxime (20 mmol) in 100 mL of
dichloromethane was treated with ozone at -75 or -40 °C (1f)
until the O-methyl oxime was consumed. The solution was
flushed with oxygen and then concentrated in vacuo at room
temperature. From the residue, tetraoxanes 2a -d were isolated
by flash chromatography using silica gel and petroleum ether/
ether in a ratio of 97:3, and tetraoxanes 2e and 2f were purified
by crystallization from ethanol.
3,12,20-T r im e t h y l-7,8,15,16,23,24-h e x a o x a t r is p ir o -
[5.2.5.2.5.2]tetr a cosa n e (4). Hexaoxonane 4 was isolated by
filtration and was purified by recrystallization from aceto-
nitrile. Yield, 21%; colorless solid, mp 106-107 °C (CH3CN)
1
(lit.18 mp 107-109 °C); H NMR 0.80-1.03 (m, 9H), 1.04-1.80
(m, 21H), 2.05-2.37 (m, 6H); 13C NMR 21.54, 21.62, 21.66, 28.51,
28.57, 30.78, 30.94, 30.97, 31.06, 31.11, 31.16, 31.67, 31.74, 31.77,
31.83, 107.54, 107.60, 107.74. VPO (CHCl3) MW 374; calcd MW
385.
3,12,20-Tr i-ter t-b u t yl-7,8,15,16,23,24-h exa oxa t r isp ir o-
[5.2.5.2.5.2]tetr a cosa n e (5). Hexaoxonane 5 was isolated by
filtration and was purified by recrystallization from aceto-
nitrile. Yield, 37%; colorless solid, mp 195-196 °C (CHCl3)
(lit.18 mp 216-218 °C); 1H NMR 0.87 (s, 27H), 0.95-1.85 (m,
21H), 2.15-2.45 (m, 6H); 13C NMR 23.31, 23.50, 23.63, 23.66,
(16) Harding, M. J . C.; Whalen, D. M. Ind. Eng. Chem. Prod. Res.
Dev. 1975, 14, 232-239.
(17) Bertrand, M.; Flisza´r, S.; Rousseau, Y. J . J . Org. Chem. 1968,
33, 1931-1934. Although these investigators were able to get a small
molecular ion for the dispiro-1,2,4,5-tetraoxane of cyclohexanone using
EI-MS, the intensity was very low (0.2% of the total ionic current).
We have also found MS (even FAB-MS) to be an inconsistent method
for MW assignment as the molecular ions are not always present. When
the M+ peak was observed, it was uniformly of very low intensity.
(18) Sanderson, J . R.; Paul, K.; Story, P. R. Synthesis 1975, 275-
276.