An efficient biomaterial supported bifunctional organocatalyst (ES-SO 3- C5H5NH+) for the synthesis of β-amino carbonyls

Article abstract of DOI:10.1039/c0ob00965b

A biomaterial supported organocatalyst, readily synthesized by the reaction of chemically modified sulfonic group containing expanded corn starch with pyridine exhibited excellent catalytic activity for the synthesis of β-amino carbonyls in excellent yields via aza-Michael addition of amines to electron deficient alkenes. A remarkable enhancement in the reaction rates was observed with the prepared bifunctional organocatalyst in comparison to the either starch grafted sulfonic acid or the corresponding homogeneous pyridinium p-toluenesulfonate.

Full text of DOI:10.1039/c0ob00965b

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Organic &
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PAPER
An efficient biomaterial supported bifunctional organocatalyst
-
(ES-SO3 C5H5NH+) for the synthesis of b-amino carbonyls
Sanny Verma, Suman L. Jain* and Bir Sain*
Received 1st November 2010, Accepted 14th December 2010
DOI: 10.1039/c0ob00965b
A biomaterial supported organocatalyst, readily synthesized by the reaction of chemically modified
sulfonic group containing expanded corn starch with pyridine exhibited excellent catalytic activity for
the synthesis of b-amino carbonyls in excellent yields via aza-Michael addition of amines to electron
deficient alkenes. A remarkable enhancement in the reaction rates was observed with the prepared
bifunctional organocatalyst in comparison to the either starch grafted sulfonic acid or the
corresponding homogeneous pyridinium p-toluenesulfonate.
conjunction with Cu(acac)2,10 quaternary ammonium salt,11 b-
Introduction
cyclodextrin in H2O,12 PEG13 and H2O,14 the organocatalytic
version of this reaction are relatively less explored. Since, most
of the known organocatalysts are based on the secondary amines,
resembling to the nucleophiles in the aza-Michael addition and
therefore make the reaction of less synthetic importance. Recently,
few reports dealing with the use of tributylphosphine,15 nano-
organocatalysts,16 bifunctional thioureas17 have been reported for
this reaction. However, the major limitations of these methods
such as homogeneous nature, longer reaction times and moderate
yield of the products, leaving the scope for further development
in this area. Therefore we decided to develop an environmentally
benign, economical, easily recoverable, and reusable bifunctional
organocatalyst to further extend the area of organocatalytic aza-
Michael reactions.
In the present paper we report a cost effective, environ-
mentally benign, easily accessible, recyclable and highly effi-
cient pyridinium-based organocatalyst grafted to the chemically
modified expanded starch (Scheme 1) for the synthesis of b-
aminocarbonyls by aza-Michael reaction of amines to electron
deficient alkenes under mild reaction conditions (Scheme 2).
A remarkable enhancement in the reaction rates could be ob-
served than the corresponding pyridinium-based homogeneous
pyridinium p-toluenesulfonate
Our future challenges in resources, environmental and economical
sustainability need the development of more efficient and atom
economic technologies in chemical industry. Presently, the con-
siderable depletion in the availability of non-renewable organic
feedstocks is continuously focusing our attention towards the
utilization of renewable resources for the sustainable development
of our society.1 Expanded corn starches due to their high
surface area and pore volumes have emerged to be promising
materials and their uses in catalysis is a key enabling area for
the development of new and improved processes for chemical
reactions.2 Organocatalysis, which involves the use of small organic
molecules to catalyze organic reactions, is another step forward
towards developing the green chemical synthesis.3 In contrast
to the conventional catalysts, these organic catalysts are easily
available, more stable to air and water, easy to handle, less toxic,
and can promote an organic reaction by several activation modes.
On the other hand, immobilization of these organic molecules,
which allows the advantages of being their facile recovery and
their repeated use with retaining their catalytic activity, is gaining
ever increasing interest in current years.4 In this context, a variety
of organic and inorganic materials have been widely used as
supports for the immobilization,5 whereas, to the best of our
knowledge there is no report on the use of biomaterial supported
organocatalysts for organic transformations. Among the known
reactions, the formation of new carbon-heteroatom bonds via
aza-Michael addition is one of the important transformations
in organic chemistry. These aza-Michael adducts are versatile
synthetic intermediates and have been widely used in the syn-
thesis of a variety of biologically active natural products, chiral
auxiliaries, antibiotics, and other nitrogen containing molecules.6
In contrast to the many improved protocols using metal based
Lewis acids,7 boric acid/H2O,8 ionic liquids either alone9 or in
Scheme 1 Synthetic approach of organocatalyst 3.
Results and discussion
Initially, we synthesized the expanded starch by following
a literature procedure with some modifications.2a For the
Chemical Sciences Division, Indian Institute of Petroleum, Mohkampur,
Dehradun-248005, India. E-mail: suman@iip.res.in, birsain@iip.res.in
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Table 1 Results of various optimization experimentsa
Entry
Reaction time (min)
Yields (%)b
c
1
2
3
4
5
6
7
8
9
60
35
50
35
35
30
25
20
35
—
Scheme 2 Organocatalytic aza-Michael addition.
65d
35e
72f
84f
85f
92f
96g
68h
expansion process, normal corn starch was initially heated in
water under reflux for 5–6 h followed by continuing the stirring
at room temperature overnight. The resulting gel was separated
by centrifugation and washed several times with ethanol. Finally,
the obtained solid was stirred at room temperature in ethanol
for 5–6 h. The white solid was filtered off and dried at room
temperature. The surface area of the expanded material was found
to be 105 m2 g-1. The resulting expanded starch (ES) was utilized
for further chemical modifications to synthesize the desired starch
supportedpyridinium-basedorganocatalystas showninScheme1.
The drop-wise addition of chlorosulfonic acid into the stirred
suspension of expanded starch (ES) 1 in at 0 ◦C, resulting in
the formation of the sulfonated starch material (ES-SO3H) 2.
The presence of sulfonic acid group was confirmed by the IR
spectroscopy as it revealed characteristic bands at 3420–3242 (b,
OH) and 1096 cm-1 (S O). Further the remarkable decrease in
the values of BET surface area from 105 m2 g-1 to 30 m2 g-1,
established the high loading of the sulfonic acid groups to the
support. The loading of the acidic H+ was determined by acid–
base titration and was found to be 0.89 mmol g-1. In the next
step, the obtained support 2 was treated with pyridine in dry
THF to obtain the desired bifunctional organocatalyst 3. The
presence of characteristic bands such as (3384; NH), 1641, 1520,
1491 (aromatic C–C), 1154, 1081 (S O) cm-1 in the IR spectrum
revealed the successful formation of the catalyst 3. Further, the
loading of the organanocatalyst was found to be 0.82 mmol g-1 as
determined by the value of nitrogen content in elemental analysis.
The thermal stability of the prepared organocatalyst 3 was found
to be good and it did not show any decomposition up to 250 ◦C
in TGA analysis.
a Conditions: substrate (1 mmol), nucleophile (1.2 mmol), catalyst
(1 mol%). b Isolated yields. c Without catalyst. d Using expanded starch
supported SO3H as catalyst (10 mol%). e By using pyridine as catalyst.
f Catalyst was prepared by varying the concentration of pyridine from
10, 20, 40, 60% to SO3H. g By using 3 (1 mol%) as catalyst. h By using
homogeneous pyridinium-p-toluenesulfonate as catalyst.
shown in the Table 1, entry 2–3. Further, to see the effect of
the pyridine in accelerating the reaction rates, we prepared a
series of organocatalysts by varying the amount of pyridine from
10%, 20%, 40%, 60% relative to the SO3H group in the reaction
mixture containing supported sulfonated expanded starch (ES-
SO3H). We then studied the catalytic efficiency of the prepared
catalysts for the reaction between dibenzyl amine and acrylonitrile
under similar reaction conditions. Results of these experiments are
summarized in Table 1 (entries 4–7). The rate of the reaction was
found to increase as the amount of the pyridine increases, the use
of 1 : 1 molar ratio of SO3H and pyridine provided best results
(Table 1, entry 8), however, excess use of pyridine did not improve
the reaction to any significant extend. Similarly, in case of the
homogeneous pyridinium salt of p-toluenesulfonic acid (PTTS),
the reaction proceeded slowly and provided moderate yield of the
desired product (Table 1, entry 9).
Next, we extended the scope of the reaction by using a variety
of primary and secondary amines with various a,b-unsaturated
compounds such as acrylamide, methyl acrylate, acrylonitrile etc.
under the described reaction condition to afford corresponding b-
amino carbonyl compounds. These results are presented in Table 2.
All the reactants were efficiently converted to the corresponding
b-amino carbonyl in excellent yields within 20–35 min. The
method also worked well with substituted olefins such as methyl
methacrylate, ethyl 2-methylacrylate, methyl 3-methoxyacrylate
(Table 2, entries 4–6) and dimethyl fumerate (Table 2, entry 7) and
afforded high product yields under described reaction conditions.
However, the reaction was found to be very slow in case of
trimethylsilyl 3,3-dimethylacrylate (Table 2, entry 8) and gave
trace amount of the corresponding addition product, perhaps
the steric factors are responsible for this reactivity. Among the
various amines studied, secondary amines in general were found to
be more reactive than primary amines. However, primary amines
yielded mono-addition products selectively without any evidence
for the formation of bis products as mentioned in several existing
procedures. Aromatic amines such as aniline and p-anisidine were
found to be less reactive and afforded poor product yield in longer
reaction times (Table 2, entries 26–27). All the products were
Thecatalytic potential of the prepared catalyst 3 was tested for
aza-Michael addition reaction as shown in Scheme 2.
In a typical experimental procedure, a mixture containing
dibenzyl amine (1 mmol), acrylonitrile (1.2 mmol) and 3 (1 mol%)
in dry THF (2 ml) was stirred for 20 min at room temperature.
After completion, the catalyst was recovered by decantation,
washed with THF, dried at room temperature and reused as such
for subsequent runs. The combined organic layer was concen-
trated and the obtained crude product was purified by column
chromatography. Next we compared the catalytic efficiency of
the supported catalyst 3 with its corresponding mono-functional
biomaterial supported sulfonic acid, pyridine and also with the
homogeneous bifunctional catalyst pyridinium p-toluenesulfonate
(PTTS) under similar reaction conditions. The results of these
experiments are presented in Table 1. In the absence of catalyst,
no reaction occurred under the described reaction conditions
(Table 1, entry 1). It is worthy to mention that in the presence
of either sulfonated expanded starch (ES-SO3H) or pyridine
alone, the reaction between dibenzyl amine and acrylonitrile
was found to be very slow and did not reach completion as
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Table 2 Aza-Michael addition of amines to a, b-unsaturated
Table 2 (Contd.)
compoundsa
Entry Amine
23
Michael acceptor Reaction time (min) Yields (%)b
Entry Amine
1
Michael acceptor Reaction time (min) Yields (%)b
25
95
20
30
30
60
96
95
92
90
24
30
91
2
3
4
25
26
27
35
92
65
70
180
160
5
6
7
60
45
20
87
92
96
a Conditions: amine (1 mmol), a,b-unsaturated compound (1.2 mmol),
catalyst (1 mol%), THF (2 ml) at room temperature. b Isolated yields.
8
90
trace
analyzed by GCMS and characterized by comparing their physical
and spectral data (IR & 1H NMR) with authentic compounds.
To check the recycling of the prepared material 3, we studied
the reaction of dibenzyl amine and acrylonitrile under described
reaction conditions. After completion of the reaction, the catalyst
could easily be recovered by decantation, washed successively with
THF and dried. The recovered catalyst was used for the subsequent
experiments (6 runs). The results of these experiments are shown
in the Table 3. As shown in the results, no significant difference was
obtained in the yield of the product and reaction time, establishing
the efficient recycling of the synthesized catalyst. As suggested
by one of the Referees, we repeated the recycling experiments
by stopping the reactions after 5 min and recovered the catalyst
by filtration. The conversion was determined by GCMS, these
results are summarized in Table 3. In all cases we obtained 50–
60% conversion in five minutes, indicating the consistent catalytic
efficiency of the catalyst during recycling. Similarly, to check the
leaching of the active sites from the catalyst support, we stirred
the catalyst 3 for 5–6 h in dichloromethane and then catalyst was
filtered off. The filtrate was charged with substrates and allowed
the reaction under described reaction conditions. The reaction did
not occur clearly indicating that there was no leaching occurred
and the reaction is truly heterogeneous in nature.
9
25
35
30
94
95
94
10
11
12
13
25
35
92
94
14
15
nBuNH2
nBuNH2
30
35
96
90
16
30
89
17
35
86
18
19
25
35
95
87
Table 3 Results of recycling experiments using dibenzyl amine and
acrylonitrile as substratesa
Run
Time (min)
Yield (%)b
Conv. (%)c
1
2
3
4
5
6
20
20
20
20
20
20
96
96
95
95
95
95
60
60
52
52
55
50
20
21
22
25
30
20
95
82
96
a Conditions as mentioned in the text. b Isolated yield. c Conversion was
determined by GCMS after stopping the reaction in 5 min.
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The exact mechanism of the reaction is not clear; we assume
that the probable mechanism of the reaction may involving the
activation of both a,b-unsaturated carbonyl compound and amine
via hydrogen bonding with acidic site and basic site of the catalyst
respectively.18 This activation increases the electrophilic character
of the b-carbon, which is subsequently attacked by the nucleophilic
amine. The dual activation, resulting through the interaction of
unsaturated carbonyl compound and amine with acidic and basic
sites of the catalyst may be facilitating the reaction and enhancing
the reaction rates (Scheme 3).
was stirred for 3–4 h at room temperature. The obtained solid
was filtered off and thoroughly washed with dichloromethane
(3 ¥ 30 ml) and dried at room temperature to obtain sulfonated
expanded starch 2 as a white powder (5.2 g). The loading of the
sulfonic acid groups or H+ sites were determined by acid–base
titration and was found to be 0.89 mmol g-1. In the next step, the
suspended mixture containing sulfonated expanded starch (ES-
SO3H) (5 g) in dry THF (20 ml) with dry pyridine (0.39 g, 5 mmol)
and the resulting mixture was stirred for 2 h. The solid thus
obtained was separated by filtration, washed with THF and dried
first at room temperature and then under vacuum. The expanded
-
starch supported (ES-SO3 ·C5H5NH+) bifunctional catalyst 3 was
obtained as a white solid in yield (94%, 4.3 g). The loading of
the organic moiety to the support was calculated by nitrogen
content as determined in elemental analysis and was found to
be 0.82 mmol g-1. IR (cm-1): 3384, 2925, 1641, 1419, 1154, 1081,
931
Representative experimental procedure for aza-Michael addition
A reaction mixture containing amine (1 mmol), a,b unsaturated
compound (1.2 mmol) and catalyst 3 (1 mol%) in dry THF
(2 ml) was stirred at room temperature for the time as given in
Table 2. The completion of the reaction was monitored by TLC
(SiO2). After completion, the catalyst was separated by filtration,
thoroughly washed with THF, dried and reused for recycling
experiments. The combined organic layer was concentrated under
reduced pressure and the obtained crude product was purified
by column chromatography using ethyl acetate/hexane (6 : 4) as
eluent.
Scheme 3 The proposed role of catalyst via dual activation.
Conclusions
In summary, we have developed for the first time a cost effec-
tive, environmentally benign, biodegradable, highly efficient and
recyclable biomaterial grafted pyridinium-based organocatalyst
in a very simple manner for the synthesis of b-amino carbonyl
compounds via aza-Michael reaction. The immobilized catalyst is
found to be efficient with remarkable enhancement in reaction
rates than the corresponding homogeneous pyridinium salt as
well as starch immobilized monofunctional catalyst. Further, the
biodegradable nature of the support, the recycling/reusability of
the catalyst and the faster reaction rates make the method more
environmentally friendly and will open a wide scope in developing
sustainable chemistry.
Acknowledgements
We are thankful to the Director, IIP for his kind permission to
publish these results. SV acknowledges CSIR, New Delhi, for his
Research Fellowship. We kindly acknowledge Dr J. K. Gupta for
TGA analysis, Analytical Division, for IR, elemental analysis and
GCMS analysis and Dr A. K. Sinha for providing surface area
analysis.
Experimental section
General Experimental
Notes and references
All the solvents were commercially available and used as obtained.
All the substrates were purchased from Aldrich and used as re-
ceived. Chlorosulfonic acid was purchased from Acros Chemicals
and used the fresh sample. Dichloromethane was distilled and
dried before use. Pyridine was distilled and dried over KOH pellets
before use. Pyridinium p-toulenesulfonate (PPTS) was purchased
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