Ozonolysis of 1,4-Cyclohexadienes in the Presence of Methanol and Acid
B part of AB system, J ) 18.5, 4.2 Hz, 1H); 13C NMR (CDCl3,
400 MHz) δ 201.6, 171.6, 167.4, 167.3, 133.9, 132.3, 129.0,
127.6, 53.3, 52.9, 49.2, 49.0, 44.7. Anal. Calcd for C15H17NO6:
C, 58.63; H, 5.58; N, 4.56. Found: C, 58.38; H, 5.74; N, 4.17.
P r ep a r a tion of Dim eth yl S-N-(9-F lu or en ylm eth oxy-
ca r bon yl)-2-a m in o-4-oxoa d ip a te (4b) by Ozon olysis of
Meth yl S-N-(9-F lu or en ylm eth oxyca r bon yl)-3-(1,4-cyclo-
h exa d ien -1-yl)a la n in a te. Methyl S-N-(9-fluorenylmethoxy-
carbonyl)-3-(1,4-cyclohexadien-1-yl)alaninate, which was pre-
pared by the Birch reduction of L-phenylalanine, followed by
reaction with N-(9-fluorenylmethoxycarbonyl)succinimide and
esterification2,3 (0.5 g, 1.2 mmol) was dissolved in dichlo-
romethane (20 mL). p-Toluenesulfonic acid (0.1 g, 0.5 mmol),
3 mL of methanol, and a drop of a methanolic solution of Sudan
III indicator were added. The dilution of the indicator solution
was adjusted so that the reaction mixture will have a very
slight pink color. The solution was cooled and treated as above.
Upon elution with petroleum ether-ethyl acetate gradient the
keto ester dimethyl S-N-(9-fluorenylmethoxycarbonyl)-2-amino-
viewing the spots by immersion of either KI solution or
ethanolic anisaldehyde (1% aldehyde and 1% H2SO4), on
different plates. The KI solution detected the hydroperoxides
(brown-yellow coloration), but upon standing at room temper-
ature yellow stains of the hydroxydioxolanes were observed
as well. The anisaldehyde solution was used to detect hydroxy-
dioxolanes and carbonylic compounds (blue and red coloration).
Elution was carried out with petroleum ether-ethyl acetate
gradient, and the NMR spectra were taken immediately.
Gen er a l P r oced u r e for Tr ea tm en t of 1,4-Cycloh exa -
d ien es w ith Ozon e in th e P r esen ce of Meth a n ol a n d
p-Tolu en esu lfon ic Acid in Dich lor om eth a n e. A 1,4-cyclo-
hexadiene (0.42 g, 4 mmol) was dissolved in dichloromethane
(10 mL), and 1.5 mL (40 mmol) of methanol, p-toluenesulfonic
acid (0.05 g, 0.3 mmol), and a drop of a methanolic solution of
Sudan III indicator were added. The dilution of the indicator
solution was adjusted so that the reaction mixture had a very
slight pink color. The solution was cooled on an acetone-dry
ice bath (-78 °C), and a mixture of ozone and oxygen was
passed carefully until the light pink color faded. The solvent
was evaporated to a small volume (1 mL) and loaded on a silica
gel column. Identification of fractions was performed on TLC,
as above. All products gave color with the anisaldehyde
solution. Dimethoxyoxolanes gave yellow color with KI solu-
tion, only after it was immersed in 1% ethanolic H2SO4. Elution
was carried out with petroleum ether-ethyl acetate gradient,
and the NMR spectra were taken immediately.
4-oxoadipate (4b) was obtained: mp 123 °C; yield 0.3 g (58%);
1
[R]25 ) -30.2 (CHCl3, c ) 8); H NMR (CDCl3, 300 MHz) δ
D
7.76 (d, J ) 7.4 Hz, 2H), 7.59 (d, J ) 7.3 Hz, 2H), 7.4-7.2 (m,
4H), 5.80 (d, J ) 8.4 Hz, 1H), 4.6 (dd, J ) 8.5, 4.3 Hz, 1H),
4.38 (m, 2H), 4.22 (t, J ) 7.0 Hz, 1H), 3.74 (s, 3H), 3.72 (s,
3H), 3.44 (s, 1H), 3.16 (dd A part of AB system, J ) 18.4, 4.3
Hz, 2H) 3.32 (dd B part of AB system, J ) 18.4, 4.3 Hz, 1H).
13C NMR (CDCl3, 300 MHz) δ 201.2, 171.6, 167.4, 156.4,
144.23, 144.1, 141.7, 128.2, 127.5, 125.6, 120.4, 67.7, 53.3, 52.9,
50.2, 49.3, 47.5, 45.0. Anal. Calcd for C23H23NO7: C, 64.93; H,
5.45; N, 3.29. Found: C, 65.07; H, 5.48; N, 3.11.
Gen er a l P r oced u r e for Tr ea tm en t of 1,4-Cycloh exa -
d ien es w ith Ozon e in th e P r esen ce of Meth a n ol in
CDCl3. A 1,4-cyclohexadiene (0.1 g, 1 mmol) was dissolved in
CDCl3 (2 mL), and 0.35 mL (10 mmol) of methanol, and a drop
of a methanolic solution of Sudan III indicator were added.
The indicator solution was adjusted so that the reaction
mixture had a very slight pink color. The solution was cooled
on an acetone-dry ice bath (-78 °C), and a mixture of ozone
and oxygen was passed carefully until the light pink color
faded. The reaction mixture was thus ready for taking the
NMR spectrum.
P r ep a r a tion of Ra cem ic Dim eth yl N-Ben zoyl-3-oxo-
glu ta m a te (5) by Ozon olysis of Meth yl R-N-Ben zoyl-2-
(1,4-cycloh exa d ien -1-yl)glycin a te. Methyl R-N-benzoyl-2-
(1,4-cyclohexadien-1-yl)glycinate, which was prepared by the
Birch reduction of d-phenylglycine, followed by N-benzoylation
and esterification2,3 (1.0 g, 3.7 mmol) was dissolved in dichlo-
romethane (25 mL). p-Toluenesulfonic acid (0.2 g, 1.1 mmol),
5 mL of methanol, and a drop of a methanolic solution of Sudan
III indicator were added. The dilution of the indicator solution
was adjusted so that the reaction mixture had a very slight
pink color. The solution was cooled and treated as above. Upon
elution with petroleum ether-ethyl acetate gradient the keto
Gen er a l P r oced u r e for Tr ea tm en t of 1,4-Cycloh exa -
d ien es w ith Ozon e in th e P r esen ce of Meth a n ol a n d
p-Tolu en esu lfon ic Acid in CDCl3. A 1,4-cyclohexadiene (0.1
g, 1 mmol) was dissolved in CDCl3 (2 mL), and 0.35 mL (10
mmol) of methanol, p-toluenesulfonic acid (0.01 g, 0.06 mmol),
and a drop of a methanolic solution of Sudan III indicator were
added. The indicator solution was adjusted so that the reaction
mixture had a very slight pink color. The solution was cooled
on an acetone-dry ice bath (-78 °C), and a mixture of ozone
and oxygen was passed carefully until the light pink color
faded. The reaction mixture was thus ready for taking the
NMR spectrum.
ester dimethyl N-benzoyl-3-oxoglutamate (5) was obtained:
1
yield 0.43 g (40%); mp 96 °C; [R]25 ) ∼0; H NMR (CDCl3,
D
400 MHz) δ: 7.84 (d, J ) 7.5 Hz, 2H), 7.53 (t, J ) 7.5 Hz, 1H),
7.42 (t, J ) 7.5 Hz, 2H), 5.63 (d, J ) 6.7 Hz, 1H), 3.80 (s, 3H),
3.79 (s, 3H), 3.70 (s, 2H); 13C NMR (CDCl3, 400 MHz) δ 194.5,
169.2, 167.4, 167.1, 166.6, 134.0, 133.1, 129.1, 127.7, 56.11,
53.8, 53.0, 47.0. Anal. Calcd for C14H15NO6: C, 57.34; H, 5.16;
N, 4.78. Found: C, 57.46; H, 5.31; N, 4.80.
Gen er a l P r oced u r e for Tr ea tm en t of 1,4-Cycloh exa -
d ien es w ith Ozon e in th e P r esen ce of Meth a n ol in
Dich lor om eth a n e. A 1,4-cyclohexadiene (0.42 g, 4 mmol) was
dissolved in dichloromethane (10 mL), and 1.5 mL (40 mmol)
of methanol, 0.08 g of NaHCO3, and a drop of a methanolic
solution of Sudan III indicator were added. The indicator
solution was adjusted so that the reaction mixture had a very
slight pink color. The solution was cooled on an acetone-dry
ice bath (-78 °C), and a mixture of ozone and oxygen was
passed carefully until the light pink color faded. The solvent
was evaporated to a small volume (1 mL) and loaded on a silica
gel column. Identification of fractions was performed on TLC,
Su p p or tin g In for m a tion Ava ila ble: A report on im-
proved Birch reduction of xylenes, the description of the
ozonolysis of methyl S-N-benzoyl-3-(1,4-cyclohexadien-1-yl)-
alaninate (2) in the presence of methanol and base, copies of
the 1H NMR spectra of mixtures and partly isolated dioxolanes,
and copies of 1H and 13C NMR spectra of 4a ,b and 5. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O049731Y
J . Org. Chem, Vol. 69, No. 12, 2004 4139