Sulfamic acid as a green, reusable catalyst for stepwise, tandem & one-pot solvent-free synthesis of pyrazole derivatives

Article abstract of DOI:10.1016/j.cclet.2017.02.005

Sulfamic acid (SA) is a bi-functional, cost-effective and reusable green catalyst for the synthesis of 4-(pyrazol-4-yl)methylenepyrazol-5(4H)-one derivatives by one-pot, three-component condensation of pyrazol-4-carbaxaldehydes, β-ketoesters and phenyl hydrazine (Route-I). In addition to this method, another simple condensation of pyrazol-4-carbaxaldehydes with pyrazolone in the presence of SA under the solvent-free condition in good yield is reported. The merits of these protocols are mild conditions, non-aqueous workup, high yields, easy availability of the catalyst, no chromatographic separation and inexpensive solid acid catalyst. Furthermore, SA could be recycled and reused for five times without losing its catalytic activity.

Full text of DOI:10.1016/j.cclet.2017.02.005

Accepted Manuscript
Title: Sulfamic acid as a green, reusable catalyst for stepwise,
tandem and one-pot solvent-free synthesis of pyrazole
derivatives
Authors: Veera Swamy Konkala, Pramod Kumar Dubey
PII:
S1001-8417(17)30061-X
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.cclet.2017.02.005
CCLET 3978
To appear in:
Chinese Chemical Letters
Received date:
Revised date:
Accepted date:
7-11-2016
23-1-2017
13-2-2017
Please cite this article as: Veera Swamy Konkala, Pramod Kumar Dubey,
Sulfamic acid as a green, reusable catalyst for stepwise, tandem and one-
pot solvent-free synthesis of pyrazole derivatives, Chinese Chemical Letters
http://dx.doi.org/10.1016/j.cclet.2017.02.005
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Original article
Sulfamic acid as a green, reusable catalyst for stepwise, tandem & one-pot solvent-
free synthesis of pyrazole derivatives
Veera Swamy Konkala, Pramod Kumar Dubey *
Department of Chemistry, Jawaharlal Nehru Technological University Hyderabad, College of Engineering, Kukatpally 500085, India
 Corresponding author.
E-mail address: veeruchem06@gmail.com
ABSTRACT
Sulfamic acid (SA) is a bi-functional, cost-effective and reusable green catalyst for the synthesis of 4-(pyrazol-4-yl)methylenepyrazol-5(4H)-one
derivatives by one-pot, three-component condensation of pyrazol-4-carbaxaldehydes, β-ketoesters and phenyl hydrazine (Route-I). In addition to
this method, another simple condensation of pyrazol-4-carbaxaldehydes with pyrazolone in the presence of SA under the solvent-free condition in
good yield is reported. The merits of these protocols are mild conditions, non-aqueous workup, high yields, easy availability of the catalyst, no
chromatographic separation and inexpensive solid acid catalyst. Furthermore, SA could be recycled and reused for five times without losing its
catalytic activity.
Keywords:
Pyrazol-4-carbaxaldehydes
Knoevenagel condensation
Sulfamic acid
Multicomponent reaction
Physical grinding.
1. Introduction
Pyrazole derivatives are well known for their broad range of biological properties [1-8]. Thus, it is attracting the scientists towards
their preparation [9, 10]. Pyrazolones are structurally closed to pyrazoles, which are also associated with wide spectrum of biological
activities [11-16]. Inspired by their importance, many research groups have reported different protocols for the synthesis of 4-
pyrazolylmethylenepyrazol-5-(4H)-ones through two-component condensation of pyrazolone and pyrazole-4-carbaxaldehyde in the
presence of different catalysts [17-20]. However, some of the above reported methods suffer from one or more drawbacks like use of
unfavourable conditions, non-eco-friendly catalysts, solvents, prolonged reaction times, high catalyst loading and the use of
expensive ionic liquids.
Literature survey reveals that, the multicomponent reactions (MCRs) have been recently discovered as a powerful tool in the field
of medicinal chemistry and synthetic organic chemistry [21-24]. Moreover, MCRs are having huge applications like short reaction
time, avoiding of intermediate isolation, diversity in reaction, atom‐ economy, environmental benign and substantial minimization of
waste.
Organic transformations under the solvent-free conditions have also gained attention particularly from the view point of green
strategy [25]. Physical grinding is one of the techniques which have increased in the use of organic synthesis rather than other
traditional methods [26, 27]. This method offers many advantages interims of green protocol by avoiding of hazardous solvents, cost
efficiency and product yields.

Sulfamic acid has been found to be a promising solid, proton donor catalyst. It is insoluble in almost all organic solvents, relatively
stable, non-volatile, non-hygroscopic, non-corrosive and economically cheaper. This catalyst could be easily recycled and reused due
to its very high immiscibility with most organic solvents. It acts as a solid acid catalyst for so many organic transformations as
witnessed by many reports published in the past [28-34]. Mohan et al. reported the synthesis of pyrazolone with phenyl hydrazine and
ethyl acetoacetate in the presence of sulfamic acid [35]. Thus, we decided to explore the capability of sulfamic acid to perform multi
component reactions.
Here, we report a simple, convenient and eco-friendly method for the synthesis of 4-(pyrazol-4-yl)methylenepyrazol-5(4H)-one
6(a-n) by using 3-diphenyl-1H-pyrazol-4-carboxaldehyde 4(a-h) and pyrazolone 9(a, b) (Scheme 1) and one-pot, three component
reaction of 3-diphenyl-1H-pyrazol-4-carboxaldehyde 4(a-h), β-ketoesters 5(a, b) and phenyl hydrazine 2 in the presence of sulfamic
acid and has not been reported elsewhere on its use for the synthesis of 4-(pyrazol-4-yl)methylenepyrazol-5(4H)-one.
2. Results and discussion
The starting materials consumed in the present study, 3-diphenylpyrazol-4-carboxaldehyde 4(a-h) were prepared in accordance
with literature procedure. The reaction of substituted acetophenones 1(a-h) with phenyl hydrazine (2) in ethanol containing catalytic
amount of acetic acid yields acetophenone phenyl hydrazones 3(a-h). The latter undergoes Vilsmeier-Haack reaction to give 4-(1H-
pyrazol-4-yl) methylenepyrazol-5(4H)-one 4(a-h) in good yield (Scheme 1).
To optimise the reaction conditions, we have chosen 3-diphenyl-1H-pyrazol-4-carboxaldehyde (4a), ethyl acetoacetate (5a) and
phenyl hydrazine (2) as model substrates (Scheme 2). Initially, we have focused to find out the best catalyst for the synthesis of 4-
(pyrazol-4-yl) methylenepyrazol-5(4H)-one 6(a-n) by employing variety catalysts under different conditions (Table 1).
It is obvious from Table 1 that the best results were obtained in the presence of 20 mol% sulfamic acid under solvent-free grinding
conditions (Table 1, entry 8). The other catalysts such as L-proline, InCl3, montmorillonite-K10 and amberlyst-15 (Table 1, entries 2-
5) afforded moderate to good yields. From the view of cost and performance of the catalyst SA was found as the best catalyst for the
synthesis of 6a through one-pot, three component reaction. The model reaction was also checked under catalyst-free conditions in
which the reaction did not proceed even after 100 min (Table 1, entry 1). From these observations, it can be confirmed the crucial role
played by SA to yield the desired product 6a. The influence of various amounts of the catalyst was also examined on the model
reaction. It is confirmed that, 20 mol% of sulfamic acid (Table 1, entry 8) is enough to get good yields in a shortest reaction time (35
min). Excess amount of sulfamic acid did not effect on reaction time and yields (Table 1, entry 9). Further, we thought of scrutinising
with various solvents and the role played by them on the reaction time and yields. It was found that protic solvents like ethanol and
methanol (Table 1, entries 11, 12) were effective than non-protic solvents (Table 1, entries 13-15). It is confirmed from Table 1, the
best optimised reaction conditions are observed when the model reaction is carried out in the presence of 20 mol% sulfamic acid
under solvent-free conditions.
After optimising the reaction conditions, formation of undesired side products was also examined under the similar conditions by
carrying a set of reactions. Primarily, Knoevenagel condensation was carried out with 3-diphenyl-1H-pyrazol-4-carboxaldehyde (4a)
and ethyl acetoacetate (5a) in the presence of sulfamic acid, under solvent-free grinding conditions. It does not yield condensation
product even after 60 min (Scheme 3).
In another set of reactions, formation of hydrazones was tested by using 4a and phenyl hydrazine 2 under the above similar
conditions. It results in the formation of hydrazone 8a in 50 min (Scheme 4).
Finally, pyrazolone 9a was prepared as per literature procedure [35] (Scheme 4) by the condensation of ethyl acetoacetate 5a with
phenyl hydrazine 2 in the presence of sulfamic acid under solvent-free conditions for 30 min.
As it is clear from the above sets of reactions, in three-component reaction between 4a, 5a and 2 initially, it results in the formation
of the pyrazolone as intermediate which further undergoes Knoevenagel condensation with 4a. Hence, there is no side products
formation in multicomponent reaction.
The compound 6a can also be synthesized through tandem method as well as stepwise method. In stepwise manner, 9a was
prepared from 5a, 2 and sulfamic acid were ground together for 30 min under solvent-free conditions [35]. Further, the compound 9a
was condensed with 4a under the same conditions for 10 min. It results in the formation of 6a in good yield (Scheme 5).

To compare the capability and efficiency of our methodology with respect to the reported catalysts for the preparation of 6a, the
results of these catalysts for the synthesis of 6a were tabulated in Table 2.
It is clear from Table 2, our methodology is more efficient than previous reports because sulfamic acid is cheap when compared
with other catalysts like Ionic liquids, B2O3-ZrO2, easily handling eco-friendly nature.
The optimised reaction conditions were applied for the synthesis of other derivatives such as 6(b-h). Results of this study were
presented in Table 3 and it concluded that the substitution on pyrazole ring does not exert any effect on the efficiency of the reaction.
Further, we have also examined recycling of the catalyst for model reaction (Scheme 2) under optimised conditions and the results
are tabulated in Table 4. Sulfamic acid was insoluble in many organic solvents hence it can be easily separated from the reaction
mixture. After completion of reaction, ethyl acetate was added to extract the product and the insoluble catalyst was separated by
simple separating technique. The separated catalyst was reused for five times with fresh starting materials without losing its catalytic
activity and slight reduction of products yields. This might be due to loss of small amount of catalyst during handling.
To find the structure of recovered catalyst, the IR spectra of fresh sulfamic acid were compared with 1st and 5th time recovered
sulfamic acid (Fig.1). It is observed that there are no differences in the IR spectra. Hence, it can be concluded that the structure of
recovered sulfamic acid is stable under the applied conditions even after 5th time recovery and reuse.
The plausible mechanism of this reaction is explained by the following sequence of reactions (Scheme 6). It consist two steps, in
the first step ethylacetoacetate 5a gets protonated in the presence of sulfamic acid. The protonated ethyl acetoacetate reacts with
phenyl hydrazine 2 with subsequent cyclisation to form compound 9a. Knoevenagel condensation involves in the second step of
mechanism. In this step, 4a undergoes protonation with sulfamic acid, which reacts with 9a to form alcohol intermediate. The latter
undergoes protonation followed by elimination of water molecule to yield desire product 6a.
3. Conclusions
In summary, we have reported a bi-functional, efficient, and green methodology for the multi component reaction using sulfamic
acid as solid acid catalyst. This method offers many advantages, like eco-friendly, economically cheaper, avoiding of hazardous
organic solvents, short reaction time, without isolation of intermediates and high yields.
4. Experimental
4.1 Material and methods
All the chemicals sulfamic acid, derivatives of acetophenones, phenyl hydrazine and β-ketoesters were obtained from commercial
sources & are used without purification. Melting points were determined in open capillary tubes on Cintex melting point apparatus
and are uncorrected. Pre-coated TLC silica gel plates (Kieselgel 60 F254, Merck) were used for monitoring reactions and the spots are
visualized under UV lamp (254 nm). IR spectra were recorded using Perkin-Elmer spectrum version 10.03.02 instrument in KBr
1
Pellets. H NMR and 13C NMR spectra were recorded in CDCl3/DMSO-d6 on a Bruker (400 MHz) or Varian Mercury 400 MHz
spectrometer. Proton chemical shifts are presented in δ ppm with reference to TMS. Mass spectra were recorded on an Agilent LC-
MS instrument giving only M+ values.
4.2. Synthesis of 4-((1, 3-diphenyl-1H-pyrazol-4-yl) methylene)-1-phenyl pyrazolin-5(4H)-one 6(a-n)
One-pot synthesis of 6(a-n): A mixture of appropriate 1,3-diphenylpyrazolin-5-(4H)-4-carbaldehyde 4(a-h) (5 mmol), β-ketoesters
5(a, b) (5 mmol), phenyl hydrazine 2 (5 mmol) and sulfamic acid (20 mol%) was thoroughly grind with pestle in an open mortar at
room temperature. Reaction progress was monitored by TLC. Upon completion of the reaction ethyl acetate (5 mL×3) was added to
the mixture, shaked well and insoluble catalyst was separated by simple separating methods. The combined organic layers were
concentrated under reduced pressure to get the clean products 6(a-n). Purification of the crude products was done by recrystallization
from suitable solvent, which afforded respective 4-(1H-pyrazol-4-yl) methylene-1H-pyrazol-5(4H)-ones 6(a-n). All the synthesized
products are stable, coloured solids and authenticity of these compounds was established based on their melting points and spectral
analysis (IR, 1H NMR and LC-MS).
Stepwise synthesis: A mixture of appropriate 1,3-diphenylpyrazolin-5-(4H)-4-carbaldehyde 4(a-h) (5 mmol), pyrazolones 9(a, b)
(5 mmol) and sulfamic acid (20 mol%) was thoroughly grind with pestle in an open mortar at room temperature. Reaction progress

was monitored by TLC. Upon completion of the reaction, isolation and purification of the crude products 6(a-n) was carried out by
using above methodology. All the synthesized products are stable, coloured solids and authenticity of these compounds was
established based on their melting points and spectral analysis (IR, 1H NMR and LC-MS).
Spectral data for compound 6(a-n):
(Z)-3-Methyl-1-phenyl-4-(1-phenyl-3-p-tolyl-1H-pyrazol-4-yl)methylene)-1H-pyrazol-5(4H)-one (6a): IR (KBr, cm-1): 3125.7,
1
2982, 1675; H NMR (400 MHz, DMSO-d6/TMS): δ 2.42 (s, 3H, -CH3), 7.38-7.99 (m, 15H, aromatic protons and 1H olefinic
proton), 10.88 (s, 1H pyrazole ring proton); LC-MS: m/z 405 (Q+1).
(Z)-3-Methyl-4-((3-(3-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-1-phenyl-1H-pyrazol-5(4H)-one (6b): IR (KBr, cm-1):
1
3539, 312, 3152, 1625, 1590, 778; H NMR (400 MHz, DMSO-d6/TMS): δ 2.30 (s, 3H, -CH3), 7.18-7.96 (m, 14H, aromatic protons
and 1H olefinic proton), 10.60 (s, 1H, pyrazole ring proton); LC-MS: m/z 450 (Q+1).
(Z)-4-((3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (6c): IR (KBr, cm-1):
1
3108, 3072, 2902, 1624, 1573,743; H NMR (400 MHz, DMSO-d6/TMS): δ 2.39 (s, 3H, CH3), 7.20-8.48 (m, 14H, aromatic protons
and 1H olefinic proton), 10.66 (s, 1H, pyrazole ring proton); LC-MS: m/z 439 (Q+1).
(Z)-3-Methyl-1-phenyl-4-((1-phenyl-3-(p-tolyl)-1H-pyrazol-4-yl)methylene)-1H-pyrazol-5(4H)-one (6d): IR (KBr cm-1): 3128.7,
2985, 1670; 1H NMR (400 MHz, DMSO-d6/TMS): δ 2.30 (s, 3H, -CH3), 3.41(s, 3H, -CH3), 7.26-7.71 (m, 15H, aromatic protons and
1H olefinic proton), 9.22 (s, 1H, pyrazole ring proton); LC-MS: m/z 419 (Q+1).
(Z)-4-((3-(4-Bromophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (6e): IR (KBr cm-1):
3125.7, 2982, 1675; 1H NMR (400 MHz, DMSO-d6/TMS): δ 2.34 (s, 3H, -CH3), 7.18-7.14 (m, 14H, aromatic protons and 1H olefinic
proton), 9.25 (s, 1H, pyrazole ring proton); LC-MS: m/z 494 (Q+1).
(Z)-4-((3-(4-Methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (6f): IR (KBr, cm-
1): 3325, 3158, 1620, 1574, 1435; 1H NMR (400 MHz, DMSO-d6/TMS): δ 2.33 (s, 3H, CH3), 3.62 (s, 3H, OCH3), 7.26-7.72 (m, 15H,
aromatic protons and 1H olefinic proton), 9.63 (s,1H pyrazole ring proton); LC-MS: m/z 435 (Q+1).
(Z)-4-((3-(3-Nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-1,3-diphenyl-1H-pyrazol-5(4H)-one (6h): IR (KBr, cm-1): 1625,
1
1590, 778; H NMR (400 MHz, DMSO-d6/TMS): δ 7.28-7.71 (m, 20H, aromatic protons and 1H olefinic proton), 9.44 (s, 1H,
pyrazole ring proton); LC-MS: m/z 512 (Q+1).
(Z)-4-((3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-1,3-diphenyl-1H-pyrazol-5(4H)-one (6i): IR (KBr, cm-1): 1625,
1
1590, 778; H NMR (400 MHz, DMSO-d6/TMS): δ 7.25-7.91 (m, 20H, aromatic protons and 1H olefinic proton), 9.42 (s, 1H,
pyrazole ring proton); LC-MS: m/z 499 (Q-1).
(Z)-1,3-diphenyl-4-((1-phenyl-3-(p-tolyl)-1H-pyrazol-4-yl)methylene)-1H-pyrazol-5(4H)-one (6j): IR (KBr, cm-1): 3325, 3158,
1620, 1574, 1435 ; 1H NMR (400 MHz, DMSO-d6/TMS): δ 2.33 (s, 3H, -CH3), 7.25-7.91 (m, 20H, aromatic protons and 1H olefinic
proton), 7.27 (s, 1H, pyrazole ring proton); LC-MS: m/z 481 (Q+1).
(Z)-Ethyl-4-((3-methyl-5-oxo-1-phenyl-1H-pyrazol-4(5H)-ylidene)methyl)-1-phenyl-1H-pyrazole-3-carboxylate (6m): IR (KBr,
1
cm-1): 1720, 1625,1354, 792; H NMR (400 MHz, DMSO-d6/TMS): δ 1.4 (s, 3H, -CH3), 2.4 (s,3H, -CH3), 4.4(s,2H, -CH2), 7.2-7.2
(m, 10H, aromatic protons and 1H olefinic proton), 10.1 (s, 1H, pyrazole ring proton); LC-MS: m/z 399 (Q-1).
(Z)-4-((3-Methyl-5-oxo-1-phenyl-1H-pyrazol-4(5H)-ylidene)methyl)-1-phenyl-1H-pyrazole-3-carboxylic acid (6n): IR (KBr, cm-
1): 3353,1756, 1625,1342, 778; 1H NMR (400 MHz, DMSO-d6/TMS): δ 2.18(s, 3H, -CH3), 7.23-7.84 (m, 11H, aromatic protons and
1H olefinic proton), 10.31 (s, 1H, pyrazole ring proton), 13.10 (s, br, 1H, -COOH D2O exangeble); LC-MS: m/z 371 (Q-1).
Acknowledgement
The authors are very thankful to authorities of Jawaharlal Nehru Technological University for providing laboratory facilities and
they are indebted to University Grants Commission, Govt. of India for providing financial support to one of them (K.V.S) in form of
UGC-SRF scheme.
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B. Zakerinasab, M.A. Nasseri1, H. Hassani, M.M. Samieadel, Application of Fe3O4@SiO2@sulfamic acid magneticnanoparticles as recyclable
heterogeneous catalystfor the synthesis of imine and pyrazole derivativesin aqueous medium, Res. Chem. Intermed. 42 (2016) 3169-3181.
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M.R. Shetty, S.D. Shriniwas, Sulfamic acid (H2NSO3H): a low-cost, mild, and efficient catalyst for the synthesis of substituted n-phenylpyrazoles under
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Fig. 1. IR spectra of sulfamic acid.

Scheme 1. Synthesis of 1, 3-diphenylpyrazolin-5-(4H)-4-carbaldehyde 4(a-h).

Scheme 2. One-pot synthesis of 4-((1,3-diphenyl-1H-pyrazol-4-yl) methylene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-ones 6a.

Scheme 3. Condensation of 4a, 5a in the presence of SA under solvent-free conditions.

Scheme 4. Synthesis of hydrazone 8a and pyrazolones 9a.

Scheme 5. Stepwise synthesis of compound 6a.

Scheme 6. Plausible mechanism for the synthesis of 6a

Table 1
Optimisation of reaction conditions for the synthesis of 6a.a
Entry
1
2
3
4
5
6
7
Catalyst
Catalyst-free/Solvent-free
Proline/Solvent free
InCl3/Solvent free
Montmorillonite K10/Solvent free
Amberelyst-15/Solvent free
Sulfamic acid (5 mol%) /Solvent free
Sulfamic acid (10 mol%) /Solvent free
Sulfamic acid (20 mol%) /Solvent free
Sulfamic acid (30 mol%) /Solvent free
Sulfamic acid (20 mol%)/Water
Sulfamic acid (20 mol%)/Ethanol
Sulfamic acid (20 mol%)/Methanol
Sulfamic acid (20 mol%)/DMF
Time (min)
100b
60 b
Yields (%)c
Nil
62
88
68
80
74
78
92
92
Nil
86
80
Nil
Nil
Nil
40 b
50 b
70 b
40 b
35 b
8
9
35 b
35 b
10
11
12
13
14
15
180
90
90
180
Sulfamic acid (20 mol%)/Tetrahydrofuran 180
Sulfamic acid (20 mol%)/Chloroform 180
a Reaction conditions: One-pot reaction of 4a (5 mmol, 1.24 g), 5a (5 mmol, 0.6 mL) and 2 (5 mmol, 0.5 mL) were reacted in the presence of
various catalysts under different conditions.
b Reaction carried out under solvent-free physical grinding conditions.
c isolated yields.

Table 2
Comparing the catalytic activity of sulfamic acid for the synthesis of 6a with reported catalysts
No. Catalyst/ conditions
Time
Yields Ref.
(%)
1
2
3
4
5
Methanol/ Piperidine/Reflux
Ionic liquid / RT
AcONa/PEG-400/60 °C
B2O3-ZrO2/H2O/reflux
Sulfamic acid / solvent free
12h
20 min
12 h
25 min
35min
74
78
78
70
92a
17
18
19
20
Present
work
Present
work
6
Sulfamic acid / solvent free
10 min
96b
a One-pot synthesis of compound 6a.
b Stepwise synthesis of compound 6a.

Table 3
One-pot synthesis of 4-pyrazolylmethylene pyrazol-5(4H)-ones 6(a-n).a
Entry R1
R2
Product
One-pot
Time (min)
Step wise
Time (min)
mp. (°C) (Lit.)
Yield (%)b
Yield (%)b
1
2
3
4
5
6
7
8
Ph-
3-NO2-Ph-
4-Cl-Ph-
4-CH3-Ph-
4-Br-Ph-
4-OCH3-Ph-
Ph-
3-NO2-Ph-
4-Cl-Ph-
4-CH3-Ph-
4-Br-Ph-
4-OCH3-Ph-
-COOC2H5
-COOH
CH3
CH3
CH3
CH3
CH3
CH3
Ph
Ph
Ph
Ph
Ph
35
40
38
36
38
40
36
37
43
40
40
45
38
38
92
90
89
90
89
85
89
90
90
89
88
90
92
92
10
12
10
10
11
15
11
14
13
10
13
15
15
15
96
92
95
95
95
94
95
95
92
94
92
94
92
92
212-214 (212) [18]
242-244 (242) [18]
240-242 (238) [20]
232-234 (235) [20]
228-230 (228) [18]
168-170 (167-169) [19]
186-188
244-248
202-204
208-210
194-196
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
9
10
11
12
13
14
Ph
CH3
CH3
204
226-228
>250
a Reaction conditions: One-pot reaction of 4a (5 mmol, 1.24 g), 5a (5 mmol, 0.6 mL) and 2 (5 mmol, 0.5 mL) were ground in the presence 20
mol% SA under solvent-free conditions.
b Refer to the yields of crude product.

Table 4
Recyclability of the catalysta
No. of cycles Fresh Run 1 Run 2 Run 3 Run 4
Yield (%)b
92
35
92
35
90
37
88
40
85
42
Time (min)
a Reaction conditions: One-pot reaction of 4a (5 mmol, 1.24g), 5a (5 mmol, 0.6 mL) and 2 (5 mmol, 0.5 mL) were ground in the presence 20
mol% SA under solvent-free conditions.
b Refer to the yields of crude product.