Terent’ev et al.
ketones or benzaldehydes;1f,2d,j,7-14 the trimethylsilyl trifluo-
romethanesulfonate (TMSOTf)-catalyzed cyclocondensation of
bis(trimethylsilyl) peroxides with carbonyl compounds;2a,15 the
ozonolysis of olefins,10,16 enol ethers,17 and O-alkyl oximes;18-20
the BF3-catalyzed rearrangement of dioxetanes;21 and the
rearrangement of ozonides in the presence of catalytic amounts
of SbC15 or ClSO3H.22
and the BF3-catalyzed reaction of acetals with alicyclic gem-
bishydroperoxides.25
In the present study, we report the synthesis of bridged
1,2,4,5-tetraoxanes by the acid-catalyzed reaction of ꢀ-diketones
with hydrogen peroxide. Attempts to prepare tetraoxane from
the simplest ꢀ-diketone (acetylacetone) have been made earlier.
In the study,26 the corresponding tetraoxane was synthesized
in a total yield of 18.5% in two steps involving the reaction of
acetylacetone with hydrogen peroxide in a neutral medium
giving rise to 5-hydroperoxy-3,5-dimethyl-1,2-dioxolan-3-ol
followed by the intramolecular cyclization of the latter com-
pound in the presence of P2O5 in diethyl ether. It was also noted
that this tetraoxane is formed in trace amounts in the course of
the sulfuric acid catalyzed synthesis of 3,5-dihydroperoxy-3,5-
dimethyl-1,2-dioxolane from acetylacetone and hydrogen per-
oxide. Tetraoxane derived from acetylacetone was prepared by
heating the presynthesized 5-hydroperoxy-3,5-dimethyl-1,2-
dioxolan-3-ol in acetic acid (the yield was not reported).27 In
some other studies of the reactions of ꢀ-diketones with hydrogen
peroxide, the formation of tetraoxanes was not documented.28
In the study,29 presumably bis-tetraoxane was synthesized in
high yield from tetraketone (1,1,3,3-tetraacetylpropane) by the
sulfuric acid catalyzed reaction with hydrogen peroxide in water
at elevated temperature (80 °C). This result is apparently
attributed to the specific reactivity of this tetraketone, its good
solubility in water, and the relatively high thermal stability of
the resulting peroxide.
Because unsymmetrical tetraoxanes are of great interest for
the design of antimalarial drugs, methods for their preparation
have attracted more attention. The synthesis of these peroxides
is based on the cyclocondensation of ketones or aldehydes with
steroid2j,4f,g,23 or alicyclic gem-bishydroperoxides (in the pres-
ence of H2SO4 as the catalyst24), with aliphatic or alicyclic gem-
bishydroperoxides (in the presence of the MeRhO3-HBF4
system2h or HBF45a as the catalyst), the reaction of ketones with
gem-bis(trimethylsilyldioxy)alkanes (TMSOTf2a as the catalyst),
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Therefore, despite the results of investigations on the reactions
of ꢀ-diketones with hydrogen peroxide, appropriate conditions
for the selective synthesis of bridged 1,2,4,5-tetraoxanes have
not been found hitherto.
Results and Discussion
We succeeded in finding the conditions for the one-pot
synthesis of bridged 1,2,4,5-tetraoxanes 2a-l from ꢀ-diketones
1a-l (Scheme 1) in yields from moderate to good (44-77%).
These results were achieved with the use of large amounts
of strong acids (H2SO4, HClO4, HBF4, or BF3), which act as
the catalyst and simultaneously serve as the cosolvent. Unex-
pectedly, the amount of the acid was found to influence both
the formation of tetraoxanes 2 and stability of these peroxides
during experiments. It is known that peroxides can be involved
in the Baeyer-Villiger,30 Criegee,31 and Hock32 reactions in
an acidic medium; these reactions are accompanied by the O-O
bond cleavage. Under the proposed conditions, these reactions
did not proceed.
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