One Pot Condensation Reactions between Ketones and Aromatic Alcohols
acetophenone afforded a 81% yield of chalcone after 18
the condensation reaction in the benzyl alcohol/acetone
reaction. Ketones react with the intermediate of the al-
cohol/CrO3 oxidation reaction rather than with the al-
dehydes under the reaction conditions. Therefore, a
probable mechanism is proposed in Scheme 2. Accord-
ing to the well accepted mechanism for CrO3/alcohol
oxidation reactions,13 the intermediate of the
CrO3/alcohol reaction is the ester of chromic acid (1,
10
h at 80 ℃ in DMF in the presence of Zn(bpy)(OAc)2
and a 75% yield after 24 h at 120 ℃ using bamboo
char sulfonic acid as catalyst,11 whereas the present
study afforded a much higher yield of 91% (Entry 2,
Table 2) for chalcone from the benzyl alcohol/aceto-
phenone condensation reaction at 56 ℃ for 10 h.
We noted that in literature,3 CrO3 was used for oxi-
dizing hydroxyl groups to carbonyl compounds in rela-
tively high yields. In most of the oxidation reactions,
CrO3 pyridine complex [such as PDC (pyridium di-
chromate) or PCC (pyridium chlorochromate) regents
which are thought as the most reliable oxidation re-
agents for alcohols4], rather than CrO3 alone, was used.
The reaction temperature is 20 ℃ or below, rarely us-
ing ketones as the solvents.12 Briefly speaking, we have
not found a single example in the literature in which all
the conditions and requirements for the alcohol/ketone
condensations were met. Therefore, only the oxidation
products were obtained from the reported systems of
oxidizing alcohols by CrO3.
-
Scheme 2); HCrO4 is produced in the system by the
reaction between CrO3 firstly with trace water in the
environment and subsequently with the water either
from the environment or from the oxidation reaction
-
and the condensation reaction. Then HCrO4 reacts
with alcohol, forming the ester.13 The intermediate 1 is
attacked by the enol form of acetone because the CrO3H
group, a strong electron deficient Lewis acid, increased
the electrophilicity of and thus activated the carbon
atom C*, forming cation 2. In this way, the intermediate
1 reacted with acetone directly rather than was trans-
ferred to aldehydes. The cation 2, which is also the in-
termediate of aldehyde/ketone condensation reaction to
produce α,β-unsaturated carbonyl compounds, was
prompt to eliminate H2O to produce benzalacetone 3,
according to the largely reported mechanism for the
aldehyde/ketone condensation reactions.14 In the pro-
posed mechanism, CrO3 acts as a catalyst and an oxi-
dant.
It is known that CrO3 can oxidize primary alcohols
into aldehydes. Is it possible that the aldehydes pro-
duced from the oxidation reaction of the alcohols re-
acted with ketone to produce corresponding
α,β-unsaturated carbonyl compounds? This possibility is
excluded by the results of our control experiments. In
the control experiments, we heated benzaldehyde with
acetone in the presence of 1.2 equiv. of CrO3 with or
without small amount of water (See Supporting Infor-
mation, S1) at 56 ℃ for 10 h. However, the total
products yields of benzalacetone/dibenzalacetone ob-
tained in the repeated control experiments were less
than 10%. As mentioned above, in the present study,
when reacting benzyl alcohol instead of benzaldehyde
with acetone at 56 ℃ in the presence of CrO3 for 10 h,
condensation products were produced in the yield of
86%. The large difference in the yields suggests that
there is a synergy between the oxidation reaction and
Conclusions
In summary, we reported a new, effective and simple
method for the preparation of α,β-unsaturated carbonyl
compounds directly from ketones and aromatic alcohols
in the presence of CrO3. The procedure is simple and
the yields can be high up to 98%. A probable mecha-
nism is proposed. The process represents a step towards
wider range of available substrates and reduced cost of
production, and has the potential to be adapted to indus-
trial production of benzalacetones and chalcones.
Scheme 2 Probable mechanism for the benzyl alcohol/acetone condensation reaction
-
HCrO4
+
H+
H2O + CrO3
CH2OCrO3H
CH2OH
+
+ H2O
H+
-
+
HCrO4
1
OH+2
H
O
OH OH+
CH3
H
*
O
CrO3H
+
O
C
H
- H2O
- H+
O
CH3
CH3
-
HCrO3
H2C
CH3
+
3
2
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
2089