Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
9140
G. Ferguson, A. Nait Ajjou / Tetrahedron Letters 44 (2003) 9139–9142
H2O2 (30%), sodium percarbonate or sodium perborate
gave no reaction. Increasing the quantity of TBHP to 2
and 3 equiv. afforded acetophenone with 85 and 100%
conversion respectively (Table 1, entries 15 and 16).
Recently, we developed catalytic transformations in
water including the hydration of nitriles to the corre-
sponding amides,6 and Oppenauer-type oxidation of
secondary alcohols.5a In this paper we wish to report a
selective, clean and cheap solvent-free oxidation of
secondary benzylic, allylic and propargylic alcohols to
the corresponding ketones, with aqueous t-butyl
hydroperoxide under phase-transfer catalysis condi-
tions. The catalytic system composed of CuCl2 and
BQC (2,2%-biquinoline-4,4%-dicarboxylic acid dipotas-
sium salt), catalyzes also the oxidation of aliphatic
alcohols. The system is stable and can be easily recov-
ered and recycled several times without loss of activity.
As we aimed the quantitative recovery and recycling of
the catalyst, it is important to select judiciously a
proper solvent for the extraction of the products with-
out leaching of the catalyst to the organic phase. The
aqueous phase containing CuCl2/BQC/Na2CO3 is
green–blue-coloured, and became purple when TBHP
was added to the mixture. Examination of different
solvents, under the oxidation conditions showed that
TBHP and TBAC allowed the leaching of the catalyst
from the aqueous phase to the organic one in the case
of CH2Cl2, ClCH2CH2Cl and PhCN which became
purple, and in the case of PhNO2 which strangely
turned yellow. Based on the UV–visible absorptions
CH2Cl2 extracts almost quantitatively the catalyst from
the aqueous phase which became clearer. This solvent
has been shown to be an excellent media for the
oxidations with TBHP.3a,j When we performed the oxi-
dation of 1-phenylethanol using CuCl2 as the catalyst
and CH2Cl2 as the solvent, acetophenone was obtained
with a conversion of 39% (Table 1, entry 17). In the
light of these results, and considering the toxicity and
the cost of methylene chloride, it is largely more advan-
tageous to use our process based on CuCl2/BQC which
is cheap and environmentally friendly. Other solvents,
namely ethyl acetate, toluene and diethylether, allow
the extraction of acetophenone without leaching of the
catalyst as they remained clear solutions and as demon-
strated by UV–visible absorption measurements.
AcOEt was then chosen as the solvent for the extrac-
tion procedure due to its inertness to the oxidation
media. After the separation of the organic layer, the
aqueous phase of the reaction mixture was reused.10
The results obtained (Table 2) demonstrate the stability
and recyclability of the catalytic system which gave
excellent conversions up to six cycles.
In our preliminary experiments we investigated the
oxidation of 1-phenylethanol, chosen as model sub-
strate, under various conditions. When neat 1-
phenylethanol (2 mmol) was treated with aqueous
t-butyl hydroperoxide (TBHP) (1 equiv., 2 mmol) in the
presence of CuCl2 (0.02 mmol), BQC (0.02 mmol) and
Na2CO3 (1 mmol) in distilled water, acetophenone was
obtained with 20% conversion (Table 1, entry 1). No
reaction was observed in the absence of CuCl2 or
TBHP.
In
aqueous
organometallic
catalysis,
surfactants7 and modified cyclodextrins8 as well as
polar solvents such as alcohols9 were added to enhance
the reaction rates. Thus, when the oxidation of 1-
phenylethanol was repeated with added phase transfer
catalysts or co-solvents, conversions ranging from 35%
to 60% were obtained (Table 1, entries 2–8). The best
results were achieved using b-cyclodextrin (58%) and
tetrabutylammonium chloride (TBAC) (60%). In this
process sodium carbonate can be used only in catalytic
amounts (Table 1, entry 9), and its absence is prejudi-
cial to the process leading to low conversion (Table 1,
entry 10). The role of Na2CO3 is to keep the ligand
BQC in its basic form. Indeed, CuCl2 in distilled water
generates an acidic solution where BQC is transformed
by protonation to water insoluble 2,2%-biquinoline-4,4%-
dicarboxylic acid (BQCH). When the reaction was per-
formed without Na2CO3, green water insoluble copper
complex (Cu/BQCH) was formed. Under these condi-
tions, there is not enough contact between the catalyst
and the substrate, which accounts for the poor yield
obtained (entry 10). The advantage of using BQC is
clearly demonstrated, since the use of copper chloride
alone, or in combination with sodium carbonate, as the
catalyst resulted in very low activities (Table 1, entries
11 and 12). When Pd(OAc)2 was used as the catalyst in
stead of CuCl2, a conversion of 51% was obtained,
while CrO3 failed to catalyze the oxidation (Table 1,
entries 13 and 14). Also, the substitution of TBHP with
The synthetic utility and limits of our catalytic system
were illustrated by various alcohols (Table 3).11 Sec-
ondary benzylic alcohols afforded selectively the corre-
sponding ketones with full conversions (Table 3, entries
1–8). When the oxidation of 1-phenylethanol was per-
formed with an alcohol:TBHP:CuCl2:BQC:TBAC:
Na2CO3 ratio of 1250:3750:1:1:3:7, a turn over number
(defined as mols of the product per mol of Cu) of 750
was obtained. Allylic and propargylic alcohols under-
went chemoselective oxidations leading to the corre-
sponding unsaturated ketones (Table 3, entries 9–11).
In the case of 1-octen-3-ol no other products from
epoxidation (1,2-epoxyoctan-3-ol and 1,2-epoxyoctan-
3-one), or rearrangement12 (2-octenal) reactions were
detected. The catalytic system proved also to be able to
catalyze the oxidation of aliphatic alcohols, albeit low
yields (Table 3, entries 12–14). 2-Indanol and 1-phenyl-
2-propanol were converted respectively with 27 and
20% conversions, while the oxidation of a mixture of
4-t-butylcyclohexanols (trans/cis=4.9) led to 4-t-butyl-
cyclohexanone with 39% conversion. The cis isomer
was found to be more reactive than trans one as the ratio
Table 2. Reuse of the aqueous phase containing the cata-
lyst for the oxidation of 1-phenylethanol10
Cycle
Conversion (%)
Cycle
Conversion (%)
1
2
3
4
98
97
100
100
5
6
7
8
100
100
64
40