A.F. Begum, K.K. Balasubramanian and B. Shanmugasundaram
Tetrahedron Letters xxx (xxxx) xxx
as stoichiometric amount or more of the reagents, inert conditions,
poor atom economy and problems of waste disposal as well
mounting the cost. The use of CH3SO3H and TFA reagents involve
tedious workup and are not suitable for large scale reactions either
because of cumbersome work up or due to its corrosive nature.
Also, some of the reagents used for the cyclisation cannot be easily
reused or recovered. This intramolecular acylation reaction is
found to be inefficient and quite challenging for substrates in
which the phenyl ring contains electronegative groups resulting
in yields as low as 10%.[15] These considerations motivated us to
explore the use of modified inexpensive heterogeneous catalysts
for the cyclisation of 3- aryloxypropionic acids which would exhi-
bit good substrate scope and which can be recovered and reused.
no significant effect (Table 1, Entry 4). Heating the acid 3a with
TiO2 and ZrOCl2 too were not successful as it led to only mixture
of products (Table 1, Entry 5–7). Mont.K-10 and Nafion-H were
completely inert when the cyclisation was done at room tempera-
ture (Table 1, Entry 1,3). Based on these findings, we chose mont-
morillonite K-10 for further investigation focussing our attention
to improve its catalytic efficiency by treating it with sulphuric acid.
For convenience, all AA mentioned further stands for ‘‘Acid
Activated”.
Literature reports reveal that Bronsted acid treated clays exhibit
significant enhancement in the catalytic activity due to their
increased acidity.[26] To increase the acidity of the Mont.K-10,
H2SO4 and HCl were employed. Acidification of the Mont.K-10 clay
was carried out with 0.5 N, 5 N and 36 N (conc.) of H2SO4 as per
known method.[27] Intramolecular cyclisation of 3a with the cat-
alyst prepared from 36 N afforded the corresponding chromanone
4a in just 30 min and in good yields (Table 1, Entry 10), whilst the
AA.Mont.K-10 prepared from 0.5 N and 5 N sulphuric acid solution
behaved similar to the thermally activated Mont.K-10 showing
only a slight increase in the reaction conversion rate. It is found
that this acid treated clay should be washed with water until the
pH of the washing is ~ 2–3 as excessive washing of the clay reduces
its acidity. Drying of AA.Mont.K-10 at three different temperatures
i.e. 100 °C, 250 °C and 500 °C for 6 h when examined, it is found
that the AA.Mont.K-10 dried at 100 °C gave quantitative yields of
the chromanone 4a upon cyclization of the acid 3a; whilst the
AA.Mont.K-10 dried at higher temperature (250 °C & 500 °C) did
not lead to any product formation.
Performing this reaction under neat conditions without the use
of any solvents were also not satisfactory as it required longer time
and the yields was also not reproducible (Table 1, Entry 8 & 11). It
was interesting to observe that conc. HCl treated clay was equally
efficient for this intramolecular cyclisation of the acid 3a (Table 1,
Entry 13). The desired chromanone 4a could also be obtained in
few minutes by refluxing the acid 3a at higher temperatures with
high boiling solvents like nitrobenzene and decalin (Table 1, Entry
14–15), but isolation of the chromanone 4a with these high boiling
solvents posed problems of purification by vacuum distillation or
chromatographic separation, and hence this was not pursued
further.
Montmorillonite K-10 (Mont.K-10) is
a well-known green
heterogeneous reusable catalyst for a wide range of organic reac-
tions due to its ease of work-up, in-expensive and milder reaction
conditions.[16] Acid activated montmorillonite clays are also found
to be much more effective than the commercially available clays.
[17] Although Mont.K-10 has been used in various acylation reac-
tions,[18] its utility has not yet been explored towards the synthe-
sis of 4-chromanones. In this report, we describe the use of acid
activated Mont.K-10 for the intramolecular cyclisation of 3-ary-
loxypropionic acids towards the synthesis of 4-chromanones.
3-Aryloxypropionic acids 3a-3o can be synthesised in two steps
from the respective phenols (Scheme 1) according to literature
reports. Oxa-Michael addition of phenols 1a-o to acrylonitrile in
the presence of sodium yielded the 3-aryloxypropane nitrile 2a-
o.[19] Subsequent hydrolysis of the crude 3-aryloxypropane nitrile
with conc.HCl afforded the desired 3-aryloxypropionic acids 3a-o
in moderate to very good yields.[20]
Our initial work on the intramolecular cyclization reaction of 3-
aryloxypropionic acids using TfOH/TFA[11] & PPA[21] led to chro-
manones;[11] but in very low yields; especially with electron
withdrawing substituents 3i, 3f and disubstituents 3h. Hence, we
turned our attention to explore the use of acidic heterogeneous
catalysts like Mont.K-10,[22] Nafion-H,[23] TiO2[24] and
ZrOCl2[25] for this transformation as these catalysts are known
to bring about aromatic acylation reactions. It is to be noted that
although Friedel-Crafts acylation reactions are known using
Mont.K-10, its application towards synthesis of chromanone has
not been reported so far.
Subsequently, use of microwaves in the presence of the AA.
Mont.K-10 was explored for the cyclisation of the acid 3a. Cyclisa-
tion of 3a with the thermally activated commercial Mont.K-10
under microwave irradiation at 120 °C led to the formation chro-
manone 4a, but the reaction was incomplete (Table 2, Entry 1).
Once again, the use of excess of the AA.Mont.K-10 and irradiating
for longer time leads to only decomposition. Interestingly the
cyclization reaction was successful and went to completion in
5 min when irradiated at 200 °C using the thermally activated
Mont.K-10 (Table 2, Entry 2). It is also observed that the H2SO4
treated Mont.K-10 and HCl treated Mont.K-10 under microwave
irradiation led to facile cyclization of the acid 3a to 4a (Table 2,
Entry 3–4) in just 30 s at 200 °C. Strangely, microwave irradiation
of 3a using the acid treated Mont.K-10 when carried out at 120 °C
(Table 2, Entry 5–6) did afford the chromanone 4a, but in low
yields due to incomplete reaction. Performing the reaction with
increasing the irradiation time at 120 °C led to only charring of
the reaction mass and hence microwave reactions were not satis-
factory for this AA.Mont.K-10 promoted transformation. These
experiments reveal that the temperature is one of the crucial fac-
tors like that of acidity for this intramolecular cyclization of the
aryloxypropionic acids.
To begin with, we screened the above-mentioned heteroge-
neous catalysts for the intramolecular cyclisation of 3-phe-
noxypropionic acid 3a varying the reaction conditions and the
results are summarised in Table 1. Treatment of the 3-phenoxypro-
pionic acid 3a with thermally activated Mont.K-10 in toluene
afforded the corresponding chromanone 4a albeit in very low
yields (Table 1, Entry 2) and with only 50% conversion. Heating
it for longer time and increasing the quantity of the Mont.K-10 cat-
alyst were not fruitful. Cyclisation with Nafion-H films did afford
the product, but here again the reaction was incomplete and
further heating it longer time with additional catalyst also had
From our optimisation studies, the amount of the AA.Mont.K-10
required for the cyclization of 3a to 4a was found to be 300–500%
by weight. Use of lesser quantity of the AA.clay i.e. 100–200% by
weight considerably slowed the rate of reaction requiring longer
Scheme 1. Synthesis of 3-aryloxypropionic acids 3a-o.
2