J . Org. Chem. 1997, 62, 2505-2511
2505
Ap p lica tion s of High -Tem p er a tu r e Aqu eou s Med ia for Syn th etic
Or ga n ic Rea ction s
J ingyi An,† Laurence Bagnell, Teresa Cablewski, Christopher R. Strauss,* and
Robert W. Trainor‡
CSIRO Division of Chemicals and Polymers, Private Bag 10, Clayton South MDC,
Victoria 3169, Australia
Received November 12, 1996X
Preparative organic synthesis was investigated in aqueous media at temperatures up to 300 °C.
Experiments were conducted with a recently disclosed pressurized microwave batch reactor (MBR)
or in conventionally heated autoclaves. Thirty-six examples are presented. Among these, methods
were developed for a Fischer synthesis, an intramolecular aldol condensation that was scaled up,
decarboxylation of indole-2-carboxylic acid, Rupe rearrangement of 1-ethynyl-1-cyclohexanol,
isomerization of carvone to carvacrol, and conversion of phenylacetylene to acetophenone. The
applicability of high-temperature water was also demonstrated for biomimetic processes important
in food, flavor, and aroma chemistry and for tandem reactions such as formation of 2-methyl-2,3-
dihydrobenzofuran from allyl phenyl ether. When addition of acid or base was necessary, less
agent was usually required for high-temperature processes than for those at and below boiling,
and the reactions often proceeded more selectively. In some instances the requirement was orders
of magnitude lower, with obvious consequences for safe, economic processing and for lowering costs
of effluent disposal. The diversity of reactions indicates that high-temperature aqueous media
could play an increasingly important role in the development of new preparative processes.
In tr od u ction
conducted extensive studies4-25 and found that super-
heated water not only was an effective solvent for organic
reactions but also could react.
The past decade has seen increasing use of water as a
medium for nonenzymatic organic reactions.1 Synthetic
procedures developed by several groups have employed
temperatures at and below boiling.2 On the other hand,
conditions near supercritical (Tc water ) 374 °C) have
been investigated mainly for production of liquid and
gaseous fuels from biomass,3 for geochemical modeling,4-25
and for the destruction of waste and hazardous organic
materials.3-5 J ointly, the groups of Katritzky and Siskin
With temperature rise from ambient toward the critical
point, the dielectric constant of water decreases substan-
tially, yet the ionic product increases by 3 orders of
magnitude.4,26 These properties appear anomalous, the
former implying a decrease in polarity with temperature
rise, and the latter, an increase due to higher dissocia-
tion. This behavior suggests that the role of water may
be complex and could vary with temperature of organic
reactions in aqueous media. To support this interpreta-
tion, we have observed that for some reactions optimal
† On study leave from Institute of Photographic Chemistry, Aca-
demica Sinica, Beijing, China 100101.
‡ Present address: Institute of Drug Technology, 45 Wadhurst Drive,
Boronia, Victoria 3155, Australia.
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4, 506.
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4, 510.
X Abstract published in Advance ACS Abstracts, March 15, 1997.
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