Fermented baker's yeast: An efficient catalyst for the synthesis of pyran derivatives in water at room temperature

Article abstract of DOI:10.1080/00397911.2012.665559

An environmentally friendly, one-pot synthesis of biologically important pyran derivatives in water is described herein. The advantages of this method are its simplicity, cost-effectiveness, and environmental friendliness. Water was exploited both as reac

Full text of DOI:10.1080/00397911.2012.665559

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Fermented Baker's Yeast: An Efficient
Catalyst for the Synthesis of Pyran
Derivatives in Water at Room
Temperature
a
a
M. Saha & A. K. Pal
a
Department of Chemistry, North Eastern Hill University, Mawlai
Campus, Shillong, India
Accepted author version posted online: 08 Aug 2012.Version of
record first published: 06 Mar 2013.
To cite this article: M. Saha & A. K. Pal (2013): Fermented Baker's Yeast: An Efficient Catalyst for
the Synthesis of Pyran Derivatives in Water at Room Temperature, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 43:12, 1708-1713
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1
Synthetic Communications , 43: 1708–1713, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2012.665559
FERMENTED BAKER’S YEAST: AN EFFICIENT
CATALYST FOR THE SYNTHESIS OF PYRAN
DERIVATIVES IN WATER AT ROOM TEMPERATURE
M. Saha and A. K. Pal
Department of Chemistry, North Eastern Hill University, Mawlai Campus,
Shillong, India
GRAPHICAL ABSTRACT
Abstract An environmentally friendly, one-pot synthesis of biologically important pyran
derivatives in water is described herein. The advantages of this method are its simplicity,
cost-effectiveness, and environmental friendliness. Water was exploited both as reaction
media as well as activator of catalyst (fermentation of bakers’ yeast). Compared with other
methods for synthesis of pyran derivatives, satisfactory results were obtained with good
yields under simple experimental procedure.
Keywords Bakers’ yeast; dimedone; 4-hydroxy coumarin
INTRODUCTION
To face current environmental concerns, the development of green organic
synthesis is necessary and an environmentally benign protocol appears essential.
In these respects, multicomponent reactions (MCRs), particularly those performed
[1]
in=on aqueous media, have become increasingly useful tools for the synthesis of
chemically and biologically important compounds because of their environmentally
[
friendly atom economy and green characteristics. Thus MCRs are perfectly suited
2]
Received December 16, 2011.
Address correspondence to A. K. Pal, Department of Chemistry, North Eastern Hill University,
Mawlai Campus, Shillong 793022, India. E-mail: amartya_pal22@yahoo.com
1
708

FERMENTED BAKER’S YEAST
1709
for combinatorial library syntheses and are finding increasing use in discovery
[
3]
processes for new drugs and agrochemicals.
Pyran derivatives are an important class of compounds, being the main com-
[
ponents of many naturally occurring products, and have been of interest in recent
4]
[
years because of their useful biological and pharmacological aspects. These include
5]
[
6]
anticoagulant, anticancer, diuretic, spasmolytic, and anti-anaphylactin activities.
They can be used as cognitive enhancers for the treatment of Alzheimer’s disease,
Huntington’s disease, amyoprophic lateral sclerosis, Parkinson’s disease, AIDS-
associated dementia, and Down syndrome as well as for thetreatment of schizo-
[7]
phrenia and myoclonus. These heterocycles are also used as cosmetics, pigments,
[
8]
and biodegradable agrochemicals and photoactive materials.
Therefore, several methods have been reported for the synthesis of pyran
derivatives using various catalysts and methods such as hexadecyltrimethyl
[
9]
[10]
ammonium bromide (HTMAB), benzyltriethylammonium chloride (TEBA),
[
11]
[12]
[13]
piperidine,
N-methylimidazole,
dodecylbenzene sulfonic acid (DBSA),
(D,L)-proline,
sodium
KF-alumina,
carbonate
[
14]
[15]
[16]
(Na CO ),
nophthalimide (DAPH),
dianili-
[21]
1,8-
2
3
[17]
[18]
[19]
[20]
I ,
2
microwave,
ultrasound,
ionic liquid,
[22]
[23]
diazabicyclo[5.4.0]undec-7-ene (DBU), potassium phosphate (K PO ), magnes-
3
4
[24]
[25]
ium oxide (MgO), and sodium dodecyl sulfate (SDS). Although most of these
processes offer distinct advantages, at the same time they suffer from certain draw-
backs such as longer reaction times, unsatisfactory yields, high costs, harsh reaction
conditions, use of a large quantity of volatile organic solvents, expensive metal precur-
sors, and environmentally toxic catalysts. Considering these reports, the development
of new, simple, and efficient synthetic methods for the preparation of heterocycles
containing pyran ring fragments will be beneficial and an interesting challenge.
Bakers’ yeast has the ability to catalyze different type of organic transform-
[
26 27]
ation.
,
It is also used in the formation of C=C double bonds via acyloin conden-
[
28,29]
[30]
sation,
bakers’ yeast is gaining much importance in organic synthesis.
As a part of our current studies on the development of efficient methods for the
and Michael addition reaction.
Because of this important aspect,
[
31]
[32]
synthesis of heterocyclic compounds,
we herein report an environmentally
friendly and straightforward protocol for the synthesis of pyran derivatives by using
a biocatalyst (bakers’ yeast) in water at room temperature.
RESULTS AND DISCUSSION
[
33]
A number of reactions including Knoevenagel
condensation have been
carried out in aqueous media. Water is environmentally friendly, safe, and easily
available in nature. Therefore we explored the use of water as a solvent for our
present work. Accordingly, domino Knoevenagel and Michael addition reaction
of dimedone 1 with aryl aldehydes 2 and malononitrile 3 was carried out in an
aqueous medium in the presence of biocatalyst (bakers’ yeast) at room tempera-
ture. As a model reaction, we selected 1 equiv. of dimedone (1), 1 equiv. of
benzaldehyde (2a), 1 equiv. of malononitrile (3), and fermented bakers’ yeast in
water at room temperature and obtained a white solid (4a) in 89% yield
(Scheme 1, Table 1). The structure of the compound was determined by the
analysis of analytical and spectral data.

1710
M. SAHA AND A. K. PAL
Scheme 1. (i) Reagents and conditions: Fermented bakers’ yeast, rt, stirred, 45–60 min.
Scheme 2. (i) Reagents and conditions: Fermented bakers’ yeast, rt, stirred, 0.3–3 h.
In evaluating the effect of catalyst on the model reaction, initially the reaction
was carried out without bakers’ yeast and D-glucose and, in another attempt, in the
presence of only D-glucose. In both cases, yield of the desired product was very low
(23%). A slightly better yield was observed in the presence of bakers’ yeast and
Table 1. Synthesis of compounds 4a–k catalyzed by bakers’ yeast at room temperature in water
a
ꢀ
Entry
Ar
3
Product
Time (min)
Yield (%)
Mp ( C)
1
2
3
4
5
6
7
8
9
C
6
H
5
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
2
2
2
2
2
2
2
2
2
2
2
(CN)
(CN)
(CN)
(CN)
(CN)
(CN)
(CN)
(CN)
(CN)
(CN)
(CN)
2
2
2
2
2
2
2
2
2
2
2
4a
4b
4c
4d
4e
4f
45
55
55
45
45
50
60
50
50
55
60
89
84
87
88
92
90
81
89
90
82
86
230–232
215–217
196–198
189–191
174–176
195–197
198–199
213–215
223–225
212–213
210–211
4-CH
4-CH
3
6 4
C H
3
O C
6
H
4
6 4
4-F C H
2 6 4
4-NO C H
6 4
4-Br C H
4N(CH
4-Cl-C
4-CNC
2-ClC
3
)
2
C
6
H
4
4g
4h
4i
6
H
4
6
H
4
1
1
0
1
6
H
4
4j
4k
C
10
H
9
a
The yields refer to isolated yields.

FERMENTED BAKER’S YEAST
1711
Table 2. Synthesis of compounds 6a–e and 7a–e catalyzed by bakers’ yeast at room temperature in water
a
ꢀ
Entry
Ar
3
Product
Time (h)
Yield (%)
Mp ( C)
1
2
3
4
5
6
7
8
9
C
6
H
5
CH
CH
CH
CH
CH
2
2
2
2
2
(CN)
(CN)
(CN)
(CN)
(CN)
2
2
2
2
2
6a
6b
6c
6d
6e
7a
7b
7c
7d
7e
2.3
3
82
80
85
80
81
87
88
90
86
85
255–256
255–257
250–251
227–229
225–227
228–229
230–232
265–266
245–247
268–270
4-CH
4-NO
4-CH
4-CNC
3 6 4
C H
2
C
6
H
4
2
3
OC
6
H
4
2.3
2.3
0.4
0.3
0.4
0.4
0.3
6
H
4
C
4-NO
6
H
5
—
—
—
—
—
2
C
6
H
4
4-CH
4-CH
3
C
6 4
H
3 6 4
OC H
1
0
4-BrC
6 4
H
a
The yields refer to isolated yields.
D-glucose. To improve the yield of the desired product, the reaction was carried out
at room temperature by mixing bakers’ yeast and D-glucose in water at pH 7.0.
Unfortunately it afforded the desired product 4a in only 39% yield even after
prolonged reaction time. On the other hand, the use of fermented bakers’ yeast under
the same reaction condition showed a significant improvement of yield as well as
reaction time compared to unfermented bakers’ yeast. The best result was achieved
by stirring the reaction mixture for 45 min at room temperature using fermented
bakers’ yeast. Fermentation was done by stirring a mixture of bakers’ yeast
(200 mg) and D-glucose (300 mg) in 5 ml phosphate buffer (pH 7.0) overnight. We next
investigated the substrate scope of this domino reaction by subjecting a series of aryl
aldehydes 2b–k to the reaction with dimedone 1 and malononitrile 3 in the presence of
fermented bakers’ yeast under the optimal condition (Scheme 1). As shown in Table 1,
aromatic aldehydes carrying either electron-donating or electron-withdrawing substi-
tuents worked well, giving excellent yields of the products with high purity.
Encouraged by initial results, we tried to extend the scope of the present
protocol for the synthesis of 3,4-dihydropyran[c]chromene derivatives (6a–e). The
desired compounds were obtained 81–85% yields by condensation of 1 equiv. of
4
(
-hydroxycoumarin (5), 1 equiv. of aryl aldehydes (2a), and 1 equiv. of malononitrile
3) in the presence of fermented bakers’ yeast in water at room temperature. The
results are listed in Table 2. The results clearly indicate that the reaction can tolerate
a wide range of differently substituted aryl aldehydes.
All products were characterized by elemental analysis, and spectroscopic and
1
2,21,25
physical data (mp) were compared with those reported in literature.
CONCLUSION
In summary, we have developed a novel, mild, and efficient strategy for the
synthesis of pyran derivatives and bis-coumarol from dimedone or 4-hydroxy cou-
marin, aryl aldehydes, and malononitrile via Knoevenagel condensation followed
by Michael addition reaction using fermented bakers’ yeast in water at room
temperature. The methodology is environmentally friendly, simple, rapid, and inex-
pensive, affording good to excellent yields with operational simplicity.

1712
M. SAHA AND A. K. PAL
EXPERIMENTAL
Melting points were determined in open capillaries and are uncorrected. Infra-
red (IR) spectra were recorded on Spectrum BX Fourier transform (FT)–IR and
À1
1
13
Perkin-Elmer (tmax in cm ) instruments on KBr disks. H NMR and C NMR
400 and 100 MHz respectively) spectra were recorded on Bruker Avance II-400
(
spectrometer. Mass spectra were recorded on Waters ZQ-4000. CHN were recorded
on CHN-OS analyzer (Perkin-Elmer 2400, series II). Silica gel G (E-mark, India) was
used for thin-layer chromatography (TLC). Hexane refers to the fraction boiling
ꢀ
between 60 and 80 C. Mili-Q-grade water was used for the preparation of phosphate
buffer.
Typical Procedure for the Synthesis of Compounds 4a–k and 6a–e
A mixture of bakers’ yeast (200 mg), D-glucose (300 mg), and phosphate buffer
5
ml (pH 7.0) was taken in a flask and stirred for 24 h at room temperature. Dime-
done 1 (200 mg, 1 mmol) or 4-hydroxy coumarin (162 mg, 1 mmol), aryl aldehyde
1 mmol), and malonitrile 3 (66 mg, 1 mmol) were added to it, and the reaction
(
was continued for the time mentioned in Tables 1 and 2. After completion (TLC),
the reaction mixture was diluted with water, extracted with ethyl acetate (10 ml  3),
washed with brine (10 ml), and dried over anhydrous sodium sulfate. The solvent was
removed in vacuum, and the crude product was purified by column chromatography
over silica gel using ethyl acetate–hexane (2:8) as eluent.
Typical Procedure for the Synthesis of Compounds 7a–e
A mixture of bakers’ yeast (200 mg), D-glucose (300 mg), and phosphate buffer
ml (pH 7.0) was taken in a flask and stirred for 24 h at room temperature.
-Hydroxy coumarin (324 mg, 2 mmol) and aryl aldehyde (1 mmol) were added to
5
4
it, and the reaction was stirred for another 30–40 min. After completion (TLC),
the reaction mixture was diluted with water, extracted with ethyl acetate (10 ml  3),
washed with brine (10 ml), and dried (Na SO ). The solvent was removed in vacuum,
2
4
and the crude product was purified by simple recrystallization from ethanol.
ACKNOWLEDGMENTS
We thank to the University Grants Commission–Funding for Infrastructure in
Science and Technology and Department of Science and Technology–SAP, Depart-
ment of Chemistry, North Eastern Hill University.
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