International Journal of Organic Chemistry, 2011, 1, 125-131
doi:10.4236/ijoc.2011.13019 Published Online September 2011 (http://www.SciRP.org/journal/ijoc)
Pineapple Juice as a Natural Catalyst:
An Excellent Catalyst for Biginelli Reaction
Suresh Patil*, Swati D. Jadhav, Sanjeevani Y. Mane
Organic Research Laboratory, Department of Chemistry, P.D.V.P. College, Tasgaon, India
Received May 8, 2011; revised June 23, 2011; accepted July 5, 2011
Abstract
An efficient and greener synthesis of a series of dihydropyrimidinone (DHPMs) derivatives were accom-
plished via three-component one-pot cyclocondensation between substituted aryl aldehydes, diketone/ke-
toester and urea. This solvent free approach is totally nonpolluting having several advantages such as shorter
reaction time, mild reaction conditions, simple workup and reduced environmental impact.
Keywords: Biginelli, Natural Catalyst, Pineapple Juice, Dihydropyrimidinone.
1. Introduction
Among the challenges for chemists include discovery
and development of non-hazardous and simple environ-
mentally safe chemical processes for selective synthesis
by identifying alternative reaction conditions and sol-
vents for much improved selectivity, energy conservation
and even less hazardous waste generation are not desir-
able and inherently safer chemical products. Therefore,
to address depletion of natural resources and preservation
of ecosystem it is just urgent to adopt so called “greener
technologies” to make chemical agents for well being of
human health. Due to acidic nature (pH = 3.7) pineapple
juice as a natural catalyst has been found to be a suitable
replacement for various homogeneous acid catalysts.
In literature number organic reactions are reported in
which natural catalyst like clay [1-3], phosphates [4,5],
gold [5], animal bone [6] etc. are employed. In continua-
tion of our research work in application of natural acids
as catalyst, here, we report a solvent free one pot cyclo-
condensation reactio n of substituted aryl aldehydes, dike-
tone/ketoester and urea (Scheme 1) with good yields.
Pineapple (Ananas comosus) is sometimes called the
King of Fruit [7]. Pineapple is grown extensively in Ha-
waii, Philippines, Caribbean area, Malaysia, Taiwan,
Thailand, Australia, Mexico, Kenya and South Africa.
Pineapple has long been one of the most popular of the
non-citrus tropical and subtropical fruits, largely because
of its attractive flavour and refreshing sugar-acid bal-
ance [8]. For the present work, we have used extract of
pineapple as natural catalyst for synthesis of dihydro-
pyrimidinone (DHPMs). The main ingredients of 100 g
pineapple contain 47 - 52 calories, water (85.3 - 87.0 g),
protein (0.4 - 0.7 g), fat (0.2 - 0.3 g), total carbohydrate
(11.6 - 13.7 g), fiber (0.4 - 0.5 g), ash (0.3 - 0.4 g), cal-
cium (17 - 18 mg), pho sphoru s (8 - 12 mg), iron (0.5 mg),
sodium (1 - 2 mg) and potassium (125 - 146 mg) [9]. It
also contains 12% - 15% sugars of which two-third is in
the form of sucrose and the rest are glucose and fructose
and 0.6% - 1.2% acid of which 87% is citric acid and
13% is malic acid [10,11]. The composition of the juice
varies with geographical, cultural and seasonal harvest-
ing and processing.
N
N
O
R
H
H
R'
O
RCHO R'
O O
NH2NH2
O
++Pineapple Juice
Stirr, RT
R' = OEt, Me
1-22
R = -H, -Ph, o-ClC6H4, p-ClC6H4,p-OHC6H4,o-OHC6H4, p-OCH3C6H4, p-OH m-OCH3C6H3,
-CH=CHC6H4, o-NO2C6H4, -C4H3O(furfural)
Scheme 1. Synthesis of dihydr opyrimidinones.

S. PATIL ET AL.
126
als (Table 1).
nthesis of DHPMs us-
. Conclusions
We have developed an eco-friendly and economic proc-
. Experimental Section
4.1 General Process for Preparation of Pineapple
Fresh pineapple (Ananas comosus) was procured lo cally.
Table 1. Comparison for different catalysts used for syn-
EntryCatalyst Time Temperature Yield (%)
The extract of pineapple is acidic having pH 3.7 and
the acidity percentage is 53.5% and hence it will be
worked as acid catalyst for cyclocondensation. Therefore,
we have used this extract as natural catalyst for synthesis
of DHPMs.
The Italian chemist Pietro Biginelli (1893, University
of Florence) for the first time reported on the acid-cata-
lyzed cyclocondensation reaction of ethyl acetoacetate,
benzaldehyde, and urea [12]. The three components re-
action mixture in ethanol was simply heated with a cata-
lytic amount of HCl at reflux temperature and the prod-
uct that precipitated on cooling the reaction mixture was
identified as 3,4-dihydropyrimidin-2(1H)-one. This reac-
tion is nowadays referred to as the Biginelli reaction,
Biginelli condensation or as the Biginelli dihydropy-
rimidine synthesis. However, this method is suffered
from drawbacks of the longer reaction time and lower
yields, hence reaction remained unfocused in the last
century. But due to important biological properties of
DHPMs, the interest in their synthesis has been increased
in the last two decades. Much effort has been made re-
cently to improve and modify this reaction. This gave
inspiration to organic chemists to find out more suitable
protocol and simpler methods for the synthesis of
DHPMs.
DHPM and its derivatives are found in a large family
of natural products with broad biological activities, due
to which they become important classes of organic com-
pounds. They generally possess intriguing therapeutic and
pharmacological properties [13-15]. Several of their
functionalized derivatives are used as calcium channel
modu- lators [13-16], Ca-antagonists [16-18] and vaso-
dilative, antihyp ertensive [19].
For Biginelli reaction, large number of methods have
been reported to synthesize DHPMs by altering catalyst.
Of them various homogeneous catalysts such as
Mg(NO3)2 [20], Pb(NO3)2 [21], LaCl3·7H2O [22], P2O5
[23]. Recently Lewis acids like DDQ [24], InBr3 [25],
CaCl2 [26], Y(OAc)3 [27], ZnCl2 [28], RuCl3 [29], Metal
triflimides Ni(NTf2)2 [30] etc. have been extensively re-
ported in the literature Biginelli reactions. Apart from
these, the Bronsted acids such as p-TSA [31], almost
neutral catalyst Zn(BF4)2 [32] also reported. Heterogene-
ous catalysts such as E4a [33], SiO2-Cl [34], AMA [35],
KSF(montmorillonite) [36], zeolites like HZSM-5, HY,
MCM-41 [37] have also been employed. Synthesis of
DHPMs can also be catalyzed by ionic liquids [38].
The limitation s in using the above mentioned catalysts
were such as long reaction time, elevated reaction tem-
perature, harsh reaction conditions, use of expensive re-
agents, moderate yields of the products, use of harmful
organic solvents and toxic and hazardous transition met-
2. Results and Discussion
Herein, we, report a single step sy
ing a pineapple juice as natural catalyst under solvent-
free conditions. As per literature survey, there are no
earlier reports of pineapple juice as catalyst for Biginelli
reaction. In addition to its clean and simplicity, this
catalyst resulted in higher yields for different aromatic
aldehydes (Table 2).
3
ess for the synthesis of DHPMs by pineapple juice as a
catalyst with good yields. This solvent free approach is
totally nonpollu ting and th ere no any use of tox ic materi-
als, quantifying it as a green approach to this cyclocon
densation reaction. In addition to this, it involved mild.
4
Juice
The crown and stem portions were removed and the skin
reaction conditions and simple workup was peeled using
thesis of DHPMs (R = p-OCH3C6H4).
1 p-TSA [31] 1 hr Refluxed in EtOH90
2 RuCl3 [29] 4.5 hr Reflux in N2 atm82
3 Zn(BF)4 [32] 4 hr Stirring at RT 71
4 Y(OAC)3 [27]4.5 hr 115˚C 89
5 Mg(NO3)2 [20] 45 min Refluxed
Ref
P] 1
SA & SSA [39]
3
Ya Aq. ˚C
Pineapple
90
6 CaCl2 [26] 2 hr luxed in EtOH98
7 InBr3 [25] 7 hr Refluxed in EtOH97
8 b(NO3)2 [218 0 min Refluxed in CH3CN89
9 P2O5 [23] 1.5 hr Refluxed at 100˚C94
1010 min Reflux 120˚C 86
11E4a [33 ] 8 hr Heated at 80˚C 91
12AMA [35] 5 min Heated at 60˚C
in EtOH
CH3CN 60
96
13 attria-Zirconi
Lewis acid [40]
Silica chloride
6 hr 92
14 [34] 3 hr Heated at 80˚C 90
153.5 hr Stirring at RT 82

S. PATIL ET AL. 127
apple catalyzed synthesis of DHPM s.
M.P.
Table 2. Pinee Juic
Entry R R Time (hours) Yield (%) Found Reported
1
1 H OEt 3.5 60 232 -
2 OEt 2.5 82 207 202 [32]
3
Cl
OEt 3.5 81 216 218 [27]
4
Cl
OEt 4.5 85 213 215 [32]
5
OH
OEt 2 86 222 226 [32]
6
OH
OEt 3.5 79 202 201 [32]
7
MeO
OEt 3.5 82 203 203 [32]
8 OH
OMe
OEt 2.5 85 215 215 [41]
9 OEt 2 89 230 232 [32]
10 NO2 OEt 3.5 87 209 208 [32]
11 O OEt 5 88 204 203 - 205 [21]
12 H Me 3.5 61 230 --
13
Me 3.5 90 232 233 [32]
14
Cl
Me 3 92 240 -
15
Cl
Me 5.5 93 277 -
16
OH
Me 3 90 256 -
17
OH
Me 4 88 220 -
18
MeO
Me 3 93 172 166 [32]

S. PATIL ET AL.
128
19 OH
OMe
Me 2 92 232 -
20 Me 5 89 243 -
21 NO2
Me 2.5 91 230 234 - 236 [21]
22 O
Me 4.5 90 197 -
kn. Then the fruit was sliced the fslices
prfruit juicer r one to two minutes tet the
misolid mass which was th en filtered through co tton to
enyl)-3,4-dihydropyrimidin-2(1H)-one
oxy d
as a reptities of
to fine yellow crystals of 5-ethoxycarbony6-methyl-
4-(4-ethoxyphenyl)-3,4-dihydropyrimidin-2(1H)-one.
The formation of the compound was confirmed by IR,
4.
yl)-3,4-dih
ydro )-one (Com poun d 7 Table 2):
(CHCl3, cm): max 3230, 1720, 1690 cm–1.
2CH3),
5.r-H),
7.
ife
essed in a d anruit o gfo
se
get liqui d pineapple j ui c e.
4.2 General Procedure for Synthesis of
5-Ethoxycarbonyl-6-methyl-4-(4-methoxyph
The synthesis of 5-ethoxycarbonyl-6-methyl-4-(4-meth-
phenyl)-3,4-dihydropyrimidin-2(1H)-one is describe
resentative example : The equ imolar quan
p-metho-xy- benzaldehyde (1.36 g, 10 mmol), ethyl ace-
toacetate, (1.30 g, 10 mmol) and urea (0.6 g, 10 mmol) in
1 ml pineapple juice were stirred for 3.5 hours at room
temperature with monitoring by TLC. Then the reaction
mixture was filtered, washed with little water. The yel-
low solid obtained was then recrystallized with ethanol
get
ml-
NMR and its melting point.
This procedure is followed for the synthesis of all the
DHPMs listed in Table 2.
3 Spectral Data for Representative
Compounds
5-ethoxycarbonyl-6-methyl-4-(4-methoxyphen
pyrimidin-2(1H
–1
IR
1H NMR (CDCl3): 1.14 (s, 3H, -OCH2CH3), 2.32 (s,
3H, -CH3), 3.78 (s, 3H, -OCH3), 4.05 (s, 2H, -OCH
34 (s, 1H,-NH), 5.90 (s, 1H,-NH), 6.84 (s, 2H, A
21 (s, 2H, Ar-H), 8.42 (s , 1 H, -C H) (Figure 1).
Figure 1. NMR Spectrum (1).

129 S. PATIL ET AL.
Figure 2. NMR Spectrum (2).
-acetyl-6-methyl-4-(4-methoxyphenyl)-3,4-dihydropyri
midin-2(1H)-one (Compound 18 Table 2)
IR (CHCl3, cm–1): max 3235, 1721, 1692 cm–1.
1H NMR (CDCl3): 2.09 (s, 3H, -CH3), 2.32 (s, 3H,
-CH3), 3.77 (s, 3H, -OCH3), 5.37 (s, 1H, -NH), 6.10 (s,
1H, -NH), 6.85 (s, 2H, Ar-H), 7.21 (s, 2H, Ar-H), 8.52 (s,
1H, -CH) (Figure 2).
5. Acknowledgements
Authors gratefully acknowledge the financial support
from the UGC, New Delhi.
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