A modular approach for multicomponent synthesis of amidines using modified Scolecite

Article abstract of DOI:10.1016/j.apcata.2015.11.010

Copper exchanged Scolecite was successfully synthesized and used as an efficient, mild and recyclable catalyst for promoting multi-component synthesis of amidines from 4-toluenesulfonyl azide, phenyl acetylene and variety of substituted amines in THF at ambient temperature in good yields within short reaction time.

Full text of DOI:10.1016/j.apcata.2015.11.010

Accepted Manuscript
Title: A modular approach for multicomponent synthesis of
amidines using modified Scolecite
Author: Megha Jagadale Pallavi Bhange Rajashri Salunkhe
Deu Bhange Mohan Rajmane Gajanan Rashinkar
PII:
S0926-860X(15)30239-8
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.apcata.2015.11.010
APCATA 15637
To appear in:
Applied Catalysis A: General
Received date:
Revised date:
Accepted date:
17-9-2015
4-11-2015
6-11-2015
Please cite this article as: Megha Jagadale, Pallavi Bhange, Rajashri Salunkhe, Deu
Bhange, Mohan Rajmane, Gajanan Rashinkar, A modular approach for multicomponent
synthesis of amidines using modified Scolecite, Applied Catalysis A, General
http://dx.doi.org/10.1016/j.apcata.2015.11.010
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A modular approach for multicomponent synthesis of amidines using modified Scolecite
Megha Jagadalea , Pallavi Bhangea, Rajashri Salunkhea, Deu Bhangea, Mohan Rajmaneb, Gajanan
Rashinkara*
aDepartment of Chemistry, Shivaji University, Kolhapur, 416004, M.S., India
bSadguru Gadge Maharaj College, Karad, 415110, M.S., India
E-mail: gsr_chem@unishivaji.ac.in
∗Corresponding author. Tel.: +91 231 260 9169; fax: +91 231 2692333.

Highlights:
 Copper exchanged Scolecite(Cu-Scolecite)was prepared by ion exchange method.
 Thecatalytic activity of Cu-Scolecite was evaluated for multi-component synthesis of
amidines.
 High yields with easy recovery and reusability of catalyst were observed.

Graphical Abstract

Abstract
Copper exchanged Scolecite was successfully synthesized and used as an efficient, mild and
recyclable catalyst for promoting multi-component synthesis of amidines from 4-toluenesulfonyl
azide, phenyl acetylene and variety of substituted amines in THF at ambient temperature in good
yields within short reaction time.
Keywords: Scolecite, N- Sulfonyl amidines, Multi-component synthesis, Reusability.

1. Introduction
Scolecite is a subclass of zeolites, which is crystalline, fibrous aggregation of an aluminum
silicate that occurs in nature and manufactured by synthetic methods [1]. They have orderly pore
structure within aluminosilicate framework which comprises interchangeable alkali and alkaline
earth metal cations accompanied by water [2]. By virtue of their Lewis and Bronsted acidic sites,
Scolecites have been extensively used as heterogeneous catalyst in the preparation of
polyhydroquinolines by Hantzsch synthesis [3] and 3, 4 dihydropyrimidin-2(1H)-ones (DHPMs)
by Biginelli reaction [4]. They have also been successfully employed in the synthesis of
bioactive benzimidazoles and 2, 4, 5-triarylimidazoles [5, 6]. In addition, Scolecites are widely
used as adsorbents for removal of heavy and toxic metal from waste water [2].
A unique characteristic feature of zeolites is their micropores of molecular size, which
give them adsorption and ion exchange characteristic properties of paramount importance. These
properties enable the introduction of transition metal cations in the porous framework of zeolites.
Zeolites render a unique ligand system, which provides multiple types for coordination of the
cation, thus providing active sites for catalyzing a variety of reactions. It is now well established
that cation-exchanged zeolites offer unique and high catalytic activity for a wide variety of
important reactions. The cation exchanged zeolites have been widely used in the study of new
applications related to process intensification [7], green chemistry [8], hybrid materials [9],
medicine [10], animal food [11], optical and electrical based applications [12], reactions [13],
sensing [14] and nanotechnology [15]. The Scolecites, like zeolites, also possess micropores that
can be exchanged with transition metals. The scrutiny of the literature reveals that there are
scarce reports on transition metal exchanged Scolecites [16]. To tap the barely exploited
potential of transition metal exchanged Scolecites in catalysis, we sought to exchange alkali

metal ions in the Scolecite network by copper envisioning that such process could lead to a new
composite with interesting catalytic properties.
Amidines are structural motifs in numerous natural products and biologically active
molecules [17]. They have fascinating chemical properties and have profound applications in
medicinal chemistry, synthetic chemistry, supramolecular chemistry, and coordination chemistry
[17a, 18-20]. N-Sulfonyl amidines constitute an important class of amidines that has received
much attention due to their wide range of pharmaceutical and biological properties [17], and also
serves as useful synthetic intermediates [21] as well as efficient coordinating ligands [20].
Consequently, the construction of these molecules represents a significant area in organic
synthesis. A plethora of distinct protocols have been developed for the synthesis of N-sulfonyl
amidines. Some of the most prominent methods include Cu-catalyzed multi-component coupling
of terminal alkyne, sulfonyl azide and amine [22], oxidative dehydrogenation of a tertiary amine
followed by 1, 3-dipolar cycloaddition of sulfonyl azide [23], chlorophosphite-mediated
Beckmann ligation of oximes and p-toluenesulfonyl azide [24], palladium catalyzed sulfonyl
ynamide rearrangement in the presence of an amine [25], aerobic oxidative three-component
coupling of a terminal alkyne, secondary amine and sulfonamide [22e], NaI-catalyzed
condensation of sulfonamide and formamide [26], and direct condensation of sulfonamide
derivatives with N, N-dimethylformamide dimethyl acetal (DMF-DMA) [27]. Amongst these,
Cu-catalyzed multi-component coupling between p-toluenesulfonyl azide, phenyl acetylene and
amines represents most elegant protocol due to wide substrate scope, mild reaction conditions,
and potential synthetic utility. A variety of catalytic systems have been reported to improve the
efficiency of this protocol [22]. However, there is a still scope for improvement especially
toward developing a green procedure using heterogeneous catalyst.

In continuation of our studies related to heterogeneous catalysis [28-29], we report herein
synthesis of modified Scolecite and its application in the synthesis of N-sulfonyl amidines.
2. Experimental
2.1. General remarks
Infrared spectra were recorded on a Perkin-Elmer FTIR spectrometer. X-Ray Diffraction (XRD)
pattern was taken by using Brucker D2 Phaser. Elemental analyses were performed on EURO
EA3000 vectro model. Surface area and pore volume were determined by N2-physisorption using
the Quantachrome Nova Station instrument. Surface areas were calculated by using the BET
model with micro- and macropores described by Barrett-Joyner-Halenda (BJH) model. The
thermal gravimetric analysis (TGA) curves were obtained using the instrument TA SDT Q600 in
the presence of static air at a linear heating rate of 10 °C min−1 from 25 °C to 1000 °C. Copper
loadings were determined by Atomic Absorption Spectroscopy (AAS) using a VARIAN Spectra
AA-20 instrument. SEM was recorded using JSM-6701F, Japan. The elemental composition of
materials was analyzed by an energy-dispersive X-ray spectra (EDS) attached to the field
1
emission scanning electron microscope (FE-SEM, Model Hitachi S 4800, Japan). H NMR and
1
13
13C NMR spectra were recorded on a Brucker AC (300 MHz for H NMR and 75 MHz for C
NMR) spectrometer using CDCl3 as solvent and tetramethylsilane (TMS) as an internal standard.
Chemical shifts (δ) are expressed in parts per million (ppm) values with tetramethylsilane (TMS)
as the internal reference and coupling constants are expressed in hertz (Hz). Mass spectra were
recorded on a Shimadzu QP2010 GCMS and all other chemicals (Spectrochem) were used as
received. Melting points were determined in an open capillary and are uncorrected. All reactions
were carried out under air atmosphere in dried glasswares. X-ray diffraction data of compound
4e was collected at T = 298 and 293 K on a Bruker APEXII CCD and Crys Alis PRO Oxford
diffractometer with graphite monochromated Mo Ka (k = 0.71073 A °) radiation. Table 4 shows

the unit cell parameters and other crystallographic details. Table 5 shows specified hydrogen
bonding in packing diagram of 4e. The determination of cell refinement and data reduction were
performed with program SAINT and Crys Alis PRO [30]. The structure was solved using the
direct methods of program SHELXS97 and refined anisotropically by full-matix least-square on
F2 was carried out with the program SHELXL97 [31].
2.2. Preparation of Cu-Scolecite
Scolecite (10 g) was exchanged three times with 1M aqueous Cu(NO3)2 solution. Each exchange
0
was performed at 80 C for 24 h. Following exchange, the material was separated by gently
decanting mother liquor and the blue colored solid was thoroughly washed with deionized water
and dried overnight at 373 K to give Cu-Scolecite.
2.3. General procedure for the synthesis of N-sulfonyl amidine
A mixture of phenyl acetylene (1 mmol), p-toluenesulfonyl azide (1 mmol), amine (1.2 mmol)
and Cu-Scolecite (150 mg) in THF (5 mL) were added to a dried round bottom flask. The
reaction mixture was magnetically stirred at ambient temperature and progress was monitored by
thin layer chromatography (TLC). After completion of reaction, the reaction mixture was filtered
to isolate insoluble Cu-Scolecite. The evaporation of solvent in vacuuo afforded crude product
which was purified by column chromatography over silica gel using petroleum ether/ethyl
acetate (85:15 v/v).
2.4. Spectroscopic data
N1, N1-Diisopropyl-2-phenyl-N2-tosylacetamidine (Table 3, product entry 4a): White
solid; mp 146-147 °C (lit., 147.5-148.5 °C)22d; IR (KBr): υ = 2973, 1541, 1457, 1375, 1263,

1
1137, 1084, 802, 755, 716, 546 cm-1; H NMR (300 MHz, CDCl3): δ 0.89 (d, J = 6.6 Hz, 6H),
1.40 (d, J = 6.9 Hz, 6H), 2.40 (s, 3H), 3.46 (t, 1H), 4.02 (q, 1H), 4.42 (s, 2H), 7.19-7.32 (m, 7H),
7.84 (d, J = 8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3): 19.8, 21.4, 38.7, 48.0, 50.3, 126.2, 126.7,
127.9, 128.8, 129.0, 134.9, 141.5, 163.4; MS (EI): m/z 373 (M+H)+; Anal. Calcd. for
C21H28N2O2S (372.524): C, 71.17; H, 8.63; N, 7.02. Found: C, 71.21; H, 8.69; N, 6.90.
N1, N1-Dimethyl-2-phenyl-N2-tosylacetamidine (Table 3, product entry 4b): Colourless
solid; mp 127 °C (lit., 126.5-128.0 °C)32; IR (KBr): υ = 3054, 3037, 2945, 2920, 2299, 1938,
1
1856, 1750, 1625, 1579, 518, 494 cm-1; H NMR (300 MHz, CDCl3): δ 2.37 (s, 3H), 2.56 (s,
13
8H), 7.27-7.34 (m, 5H), 7.45 (d, J = 7.5 Hz, 2H), 7.61 (d, J = 7.7 Hz, 2H); C NMR (75 MHz,
CDCl3): 21.4, 21.8, 40.7, 63.3, 124.4, 127.5, 128.4, 129.1, 130.0, 136.2, 140.4, 142.4, 144.2,
164.2; MS (EI): m/z 317 (M+H)+; Anal. Calcd. for C17H20N2O2S (316.417): C, 64.53; H, 6.37; N,
8.85. Found: C, 64.01; H, 6.89; N, 8.32.
N1, N1-Diethyl-2-phenyl-N2-tosylacetamidine (Table 3, product entry 4c): White solid;
mp 138 °C (lit., 136-139 °C)22a; IR (KBr): υ = 2980, 1552, 1471, 1363, 1274, 1142, 1076, 827,
1
593 cm-1; H NMR (300 MHz, CDCl3): δ 0.97 (t, 3H), 1.17 (t, 3H), 2.38 (s, 3H), 3.23 (q, 2H),
13
3.52 (q, 2H), 4.40 (s, 2H), 7.11-7.30 (m, 7H), 7.79 (d, J = 8.1 Hz, 2H); C NMR (75 MHz,
CDCl3): 11.9, 13.4, 21.4, 22.4, 36.5, 43.2, 43.3, 126.2, 126.7, 127.8, 128.8, 128.9, 141.3, 141.6,
164.5; MS (EI): m/z 345 (M+H)+; Anal. Calcd. for C19H24N2O2S (344.471): C, 66.25; H, 7.02; N,
8.13. Found: C, 66.02; H, 7.18; N, 7.69.
N1, N1-Dibutyl-2-phenyl-N2-tosylacetamidine (Table 3, product entry 4d): White solid;
mp 65 °C (lit., 66-67 °C)22e; IR (KBr): υ = 3066, 3016, 2965, 2927, 2852, 1584, 1542, 1469,
1477, 1371, 1286, 1264, 1192, 1172, 1134, 1088, 1025, 950, 902, 844, 813, 722, 692, 652, 592,
1
539, 506 cm-1; H NMR (300 MHz, CDCl3): δ 0.80-0.90 (m, 6H), 1.12-1.38 (m, 8H), 2.39 (s,

13
3H), 3.12 (t, 2H), 3.42 (t, 2H), 4.40 (s, 2H), 7.14-7.30 (m, 7H), 7.79 (d, J = 8.4 Hz, 2H); C
NMR (75 MHz, CDCl3): 13.5, 13.6, 19.9, 20.2, 21.3, 28.7, 30.4, 36.9, 48.7, 49.0, 126.2, 126.7,
127.9, 128.8, 128.9, 134.5, 141.5, 141.5, 164.6; MS (EI): m/z 401 (M+H)+; Anal. Calcd. for
C23H32N2O2S (400.577): C, 68.96; H, 8.05; N, 6.99. Found: C, 68.38; H, 8.23; N, 7.06.
N1, N1-Dipropyl-2-phenyl-N2-tosylacetamidine (Table 3, product entry 4e): White solid;
mp 86 °C(lit., 84-85 °C)22e; IR (KBr): υ = 2965, 2929, 2879, 1539, 1471, 1377, 1252, 1132,
1
1090, 954, 853, 691, 597 cm-1; H NMR (300 MHz, CDCl3): δ 0.77 (t, 3H), 0.87 (t, 3H), 1.25-
1.49 (m, 2H), 1.58-1.66 (m, 2H), 2.39 (s, 3H), 3.10 (t, 2H), 3.38-3.43 (m, 2H), 4.40 (s, 2H), 7.23
(m, 7H), 7.78 (d, J = 8.1 Hz, 2H); 13C NMR (75 MHz, CDCl3): 11.0, 11.4, 20.0, 21.4, 21.6, 36.8,
50.6, 50.8, 126.1, 126.7, 127.9, 128.8, 128.9, 134.5, 141.6, 164.8; MS (EI): m/z 373 (M+H)+;
Anal. Calcd. for C21H28N2O2S (372.524): C, 67.71; H, 7.58; N, 7.52. Found: C, 67.89; H, 7.46;
N, 7.71.
N1, N1-Dinonyl-2-phenyl-N2-tosylacetamidine (Table 3, product entry 4f)22b: colorless
solid; mp 91 °C; IR (KBr): υ = 3032, 2956, 2937, 2845, 1725, 1606, 1555, 1496, 1468, 1458,
1369, 1388, 1276, 1155, 1087, 1016, 965, 886, 767, 745, 689, 594, 587, 545 cm-1; 1H NMR (300
MHz, CDCl3): δ 0.77-0.85 (m, 6H), 1.16-1.49 (m, 28H), 2.32 (s, 3H), 3.01 (t, 2H), 3.34 (t, 2H),
13
4.41 (s, 2H), 7.09-7.19 (m, 7H), 7.81 (d, J = 7.7 Hz, 2H); C NMR (75 MHz, CDCl3): 14.4,
21.1, 22.4, 26.4, 26.9, 28.3, 29.0, 29.6, 31.4, 31.8, 36.5, 48.9, 49.5, 125.8, 126.5, 127.7, 128.7,
128.9, 133.7, 141.5, 141.7, 164.7; MS (EI): m/z 541 (M+H)+; Anal. Calcd. for C33H52N2O2S
(540.843): C, 73.28; H, 9.69; N, 5.18. Found: C, 73.25; H, 9.72; N, 5.16.
N1, N1-Diphenyl-2-phenyl-N2-tosylacetamidine (Table 3, product entry 4g)22c: White
solid; mp 147 °C; IR (KBr): υ = 3068, 3015, 2915, 1587, 1519, 1427, 1387, 1137, 1078, 979,
819, 750, 673, 546, 529 cm-1; 1H NMR (300 MHz, CDCl3): δ 2.31 (s, 3H), 4.27 (s, 2H), 6.89 (d,

J = 3.5 Hz, 4H), 7.17-7.27 (m, 13H), 7.55 (d, J = 8.0 Hz, 2H); 13C NMR (75 MHz, CDCl3): 21.1,
37.3, 126.1, 126.8, 128.4, 128.5, 128.9, 129.3, 134.4, 140.0, 141.8, 164.7; MS (EI): m/z 441
(M+H)+; Anal. Calcd. for C27H24N2O2S (440.556): C, 73.61; H, 5.49; N, 6.36. Found: C, 73.64;
H, 7.51; N, 6.34.
N1-Methyl-N1-phenyl-N2-(4-methylbenzensulfonyl)-2-phenylacetamidine
(Table
3,
product entry 4h): White solid; mp 132 °C (lit., 131.5-133.5 °C) 22d; IR (KBr): υ = 3055, 1525,
1
1459, 1288, 1142, 1070, 754, 710, 676, 542 cm-1; H NMR (300 MHz, CDCl3): δ 2.26 (s, 3H),
3.29 (s, 3H), 4.20 (s, 2H), 6.65-6.75 (m, 4H), 7.00-7.25 (m, 3H), 7.27-7.36 (m, 5H), 7.86 (d, J =
13
7.8 Hz, 2H); C NMR (75 MHz, CDCl3): 20.4, 35.7, 41.4, 126.5, 126.7, 127.3, 128.1, 128.6,
129.0, 129.4, 133.9, 141.2, 142.1, 142.5, 166.2; MS (EI): m/z 379 (M+H)+; Anal. Calcd. for
C22H22N2O2S (378.487): C, 69.81; H, 5.86; N, 7.40. Found: C, 69.69; H, 5.68; N, 7.32.
N1-Benzyl-N2-(4-methylbenzenesulfonyl)-2-phenylacetamidine (Table 3, product entry
4i): White solid; mp 112 °C (lit., 110-111 °C) 22d; IR (KBr): υ = 3301, 3027, 2909, 1587, 1565,
1267, 1132, 1067, 720, 780, 658 cm-1; 1H NMR (300 MHz, CDCl3): δ 2.40 (s, 3H), 4.32 (s, 2H),
4.41 (d, J = 5.6 Hz, 2H), 5.52 (s, 1H), 7.07 (m, 2H), 7.20-7.40 (m, 10H), 7.70 (d, J = 8.1 Hz, 2H);
13C NMR (75 MHz, CDCl3): 20.1, 39.6, 44.1, 126.1, 127.3, 127.9, 128.2, 128.7, 129.2, 129.6,
130.1, 131.6, 135.9, 139.2, 141.4, 165.7; MS (EI): m/z 379 (M+H)+; Anal. Calcd. for
C22H22N2O2S (378.487): C, 69.81; H, 5.86; N, 7.40. Found: C, 69.62; H, 5.54; N, 7.63.
N1-Isopropyl-N2-(4-methylbenzensulfonyl)-2-phenylacetamidine (Table 3, product entry
4j): White solid; mp 112 °C (lit., 110-111 °C)22d; IR (KBr): υ = 3305, 2999, 1566, 1261, 1163,
1070, 722, 689, 557, 522 cm-1; 1H NMR (300 MHz, CDCl3): δ 0.95 (d, J = 6.5 Hz, 6H), 2.35 (s,
3H), 4.02 (m, 1H), 4.25 (s, 2H), 5.25 (s, 1H), 7.09 (d, J = 7.8 Hz, 2H), 7.20 (d, J = 8.1 Hz, 2H),
13
7.35-7.46 (m, 3H), 7.82 (d, J = 7.8 Hz, 2H); C NMR (75 MHz, CDCl3): 21.1, 21.6, 39.2, 42.8,

126.2, 127.6, 129.1, 129.4, 130.0, 133.4, 140.6, 141.7, 165.6; MS (EI): m/z 331 (M+H)+; Anal.
Calcd. for C18H22N2O2S (330.444): C, 65.42; H, 6.71; N, 8.48. Found: C, 65.19; H, 6.39; N, 8.70.
N1-4-Fluro benzyl-N2-(4-methylbenzensulfonyl)-2-phenylacetamidine (Table 3, product
entry 4k): White solid; mp 91 °C; IR (KBr): υ = 3383, 2924, 1602, 1513, 1226, 1158, 1074, 845,
770, 697, 542 cm-1; 1H NMR (300 MHz, CDCl3): δ 1.27 (s, 3H), 2.42 (s, 4H), 5.45 (s, 1H), 6.89-
13
7.06 (m, 3H), 7.20-7.35 (m, 6H), 7.75 (s, 4H); C NMR (75 MHz, CDCl3): 21.4, 39.6, 45.1,
2
115.3 (d, JC-F = 21 Hz), 126.3, 128.1, 128.6, 128.9, 129.1, 130.0, 139.3, 140.4, 142.3, 143.3,
1
160.5 (d, JC-F = 244 Hz), 166.4; MS (EI): m/z 397 (M+H)+; Anal. Calcd. for C22H21FN2O2S
(396.477): C, 65.65; H, 5.34; N, 7.07. Found: C, 65.87; H, 5.23; N, 7.15.
N1, N1-Dicyclohexyl-2-phenyl-N2-tosylacetamidine (Table 3, product entry 4l): White
solid; mp 160 °C; IR (KBr): υ = 2934, 2861, 1542, 1450, 1392, 1268, 1192, 1140, 1084, 947,
1
785, 694, 547 cm-1; H NMR (300 MHz, CDCl3): δ 0.96-1.73 (m, 20H), 2.41 (s, 3H), 2.96 (s,
13
1H), 3.59 (t, 1H), 4.41 (s, 2H), 7.27 (t, 7H), 7.87 (d, J = 7.5 Hz, 2H); C NMR (75 MHz,
CDCl3): 21.4, 24.9, 28.5, 30.2, 39.3, 58.6, 126.2, 126.7, 128.2, 128.7, 128.9, 135.3, 141.5, 141.6,
163.7; MS (EI): m/z 453 (M+H)+; Anal. Calcd. for C27H36N2O2S (452.651): C, 71.64; H, 8.02; N,
6.19. Found: C, 71.51; H, 8.15; N, 6.41.
3. Result and Discussion
Our initial efforts were directed toward the synthesis of modified Scolecite acronymed as Cu-
Scolecite. The Cu2+ ions were entrapped into Scolecite matrix (Ca8[Al16Si24O80]·24H2O) via
heating mixture of Cu(NO3)2 and Scolecite following standard ion exchange technique. The Ca+2
ions in Scolecite were replaced by Cu+2 ions with the equilibrium established as

Ca2+
(aq.)
Cu2+
(s)
Cu2+
(aq.)
Ca2+
(s)
The resultant Cu-Scolecite was characterized by FTIR spectroscopy. The FTIR spectrum
displayed internal and external silanol group characteristic bands at 3740 and 3725 cm-1. In
addition, bands at 1652 cm-1 (bending mode of water), 1105 and 987 cm-1 (antisymmetric
stretching modes of alumino-silicate tetrahedral), 719 cm-1 (symmetric stretching vibrations of
Al-Si-O bonds) and 504 cm-1 (liberation mode of water) were observed. A weak diagnostic peak
at 820 cm-1 attributed to the formation of Si-O-Cu bond confirmed entrapment of Cu in the
Scolecite framework. This is further supported by the fact that the peak at 1013 cm-1 (asymmetric
stretching vibrations of Si-Al-O group) of pristine Scolecite is shifted to 1019 cm-1 in Cu-
Scolecite revealing the interaction of the Scolecite network with the Cu atoms. The
quantification of Cu in modified Scolecite was done by energy Dispersive X-Ray (EDX)
spectroscopy. The analysis revealed the presence of 1.76 wt % of Cu.
The Cu-Scolecite had a BET surface area of around 3.710 m2/g with a micropore volume
of about 0.014 mL/g, which is less in comparison with the parent Scolecite (13.638 m2/g, 0.051
mL/g, respectively). The minute decrease in surface area is due to sorption of copper ions
through the pores of Scolecite.
The powder XRD pattern of Cu-Scolecite is shown in the fig. 1. All the reflections in the
powder XRD pattern of Cu-Scolecite are successfully indexed to monoclinic structure of
Scolecite with space group C1c1 [33] except one line marked by asterisk in the fig. 1 appearing
at 2θ = 12.80°. This line, in our view, is because of 220 hkl reflection from Cu-exchanged phase
of Scolecite. As the cationic radius of Cu2+ is smaller than the Ca2+, if there is any cation
exchange in Scolecite, the position of 220 reflection has to be shifted towards higher 2θ values.

However, in the present study, the peak is shifted towards lower 2θ values which can be
rationalized on the basis that although the ionic size of Cu2+ is smaller, it may have strong
hydration sphere which would expand the channel size in greater strength as compared to Ca2+
analogue. The similar results have been observed for Mg2+ exchanged Scolecite. It is evident
from XRD results that Ca in the channels of Scolecite is exchanged by Cu, although partially but
significantly. We have further indexed the powder XRD pattern to obtain the information
regarding unit cell parameters from the model-less Le bail fitting, which were found to be nearly
similar to that of natural Scolecite analogue.
The SEM images of Scolecite and Cu-Scolecite are shown in the fig. 2. The SEM image
of modified Scolecite reveals that particles are irregular in size and comparatively less spherical
but not aggregated. The particle size of Scolecite is about 2-8 μm and that of Cu-Scolecite is
about 8-15 μm respectively.
The thermal profile of Cu-Scolecite was studied by TGA and is shown in fig. 3. The
thermogram shows that the initial weight loss due to dehydration does not occur in single step
but is step wise. This is in contrast to the recently reported thermal behavior of pure Scolecite,
which shows two step dehydration mechanism in the 100-250 °C and from 250-400 °C [34]. The
Cu-Scolecite shows three step dehydration mechanism plausibly due to the slight alteration of
the channel cation composition. These channel cations have crucial impact on the dehydration
profile as they are directly interacting with the water molecules present in the channels. Thus, the
altered TGA profile of Cu-Scolecite can be taken as additional evidence that the Cu is exchanged
partially in the Scolecite channels. The initial weight loss of 5.3% can be attributed to the loss of
approximately 10 molecules from the channels of Scolecite. The further weight loss of 2.4%
suggests that the four more molecules are expelled from the channels of Scolecite. The third step

of water loss occurs at a slightly elevated temperature and eliminates 10 more water molecules
from channels of Scolecite, thus leaving behind the dehydrated form of Cu-Scolecite.
In order to evaluate the catalytic activity of Cu-Scolecite in the synthesis of N-sulfonyl
amidines, the multi-component reaction of phenyl acetylene (1), 4-toluenesulfonyl azide (2) and
diisopropyl amine (3) was chosen as model reaction in order to optimize different parameters.
Initial studies to examine the effect of catalyst loading were carried out on model reaction
between 1 (1mmol), 2 (1 mmol) and 3 (1.2 mmol) in THF (5 mL) using different quantities of
Cu-Scolecite at ambient temperature. We observed that the amount of catalyst had a significant
impact on the reaction course. When the quantity of Cu-Scolecite was increased from 50 mg
(1.39 mol %) to 150 mg (4.17 mol%), the yield of corresponding product N1, N1-diisopropyl-2-
phenyl-N2-tosylacetamidine (4a) elevated significantly (from 50% to 90%; Table 1, entries 1−3).
The further increase in catalyst quantity beyond 150 mg did not have a profound influence on
yield of the product (Table 1, entry 4).
Subsequently, the solvent effect on the reaction was examined. An array of solvents was
employed for this purpose. The model reaction afforded moderate yields in polar protic solvents
such as ethanol and methanol (Table 2, entries 1-2). Better yields were achieved in polar aprotic
solvents like DCM and THF (Table 2, entries 3-4) while lower yields were acquired in non-polar
solvents such as toluene, chloroform and 1, 4-dioxane (Table 2, entries 5-7). Among all the
screened solvents, THF was found to furnish excellent yield of product in short reaction time
(Table 2, entry 4).
After the optimization of reaction conditions, the generality of the protocol was studied
by reacting structurally diverse amines with 4-toluenesulfonyl azide and phenyl acetylene. The
results are summarized in Table 3. In all cases, the reactions proceeded smoothly affording the

corresponding N-sulfonyl amidines in a short reaction time. The reactions were clean and high
yielding without any side products. In general, aliphatic secondary amines (Table 3, entry a-f)
offered better yields of corresponding products than aromatic secondary amines (Table 3, entry
g, h). The aliphatic primary amines (Table 3, entry i-k) also reacted efficiently providing the
desired products in relatively good yields. Moreover, alicyclic amine such as dicyclohexyl amine
also furnished high yield of anticipated product highlighting the general applicability of the
protocol (Table 3, entry l). The use of heterogeneous catalyst and the choice of a low-boiling
solvent such as THF greatly simplified and speed-up the isolation procedure. Indeed, it was only
necessary to filter off the spent solid at the end of the reaction, wash it with a few portions of
THF, and evaporate the resulting filtrate to obtain a final product.
1
13
The molecular structure of all products 4a-l were elucidated from the FTIR, H and C
NMR spectroscopy as well as mass spectrometry as described for 4e. The mass spectrum of 4e
displayed the molecular ion peak at m/z = 373 (M+H+), which is in agreement with the proposed
structure. The FTIR spectrum of 4e displayed C=N stretching band at 1539 cm-1 and coupled
vibration bands of sulfonyl group at 1377, 1132 cm-1 indicating the most significant functional
groups of the product. The 1HNMR spectrum of 4e exhibit two sharp singlets at δ 2.39 ppm and
4.40 ppm for methyl and methylene groups attached to phenyl rings. The propyl group could be
readily recognized on the basis of two triplets at δ 0. 87 and 3.10 ppm and a multiplet at 3.40
ppm. The nine aromatic protons appeared as multiplets in the region δ 7.10-7.80 ppm. The
proton decoupled 13C NMR spectrum of 4e displayed 16 distinct signals which are in agreement
with the proposed structure. The final confirmation for the formation of product was derived
from X-ray analysis as shown in the fig. 4 and the packing arrangement of molecules was shown
in the fig. 5. The C=N bond of N-sulfonyl amidines has E configuration.

A plausible mechanism for the formation of sulfonyl amidines is shown in Scheme 2. The
initial interaction between alkyne and Cu-Scolecite forms copper acetylide intermediate (I). The
reaction of sulfonyl azide with (I) generates copper-triazolyl intermediate (II) that eliminates
nitrogen to form ketenimine intermediate (III). Further nucleophilic attack of amine on (III)
furnishes the desired N-sulfonyl amidine.22e
The heterogeneity of Cu-Scolecite was assessed by leaching studies and hot filtration test.
Initially, leaching of Cu from Cu-Scolecite was investigated using atomic absorption
spectroscopy (AAS). There was negligible leaching of the copper (0.0038%) as evidenced by
AAS indicating that most of copper ions were held strongly in the Scolecite matrix. Using the
same amount of copper (in the form of copper nitrate) as that leached out, the model reaction
could not be initiated even after prolonged reaction time (12h). The heterogeneity of Cu-
Scolecite was also investigated by hot filtration test for the stated model reaction. After 50 %
completion of the reaction (gas chromatography), the Cu-Scolecite was removed by simple hot-
filtration method and the filtrate (without the catalyst) was subjected to further reaction under the
optimized reaction conditions. There was no further increase in the yield of product even after 3
hours. These results suggest that the catalysis take place exclusively under heterogeneous
conditions.
Reusability is representative characteristic of heterogeneous catalysts to determine their
dynamic lifespan. The reusability of the Cu-Scolecite was tested by repeating model reaction for
the synthesis of 4a (Fig. 6). After accomplishment of the reaction, the catalyst was recovered by
simple filtration, washed thoroughly with THF and then dried under vacuum. The catalyst
showed a substantial recyclability as the corresponding yields started at 90% and reached 70% at
the seventh run. The reduction in conversion observed on successive recycles is due to attrition

during filtration that disallowed quantitative recovery of the catalyst. It was also observed from
FTIR studies that there is no change in the nature of catalyst even after seventh cycle.
To show the merit of Cu-Scolecite in comparison with other reported catalysts, we have
summarized some of previous reports for the preparation of N1, N1-diisopropyl-2-phenyl-N2-
tosylacetamidine in Table 6. The comparison of results clearly proves that Cu-Scolecite is a good
catalyst in terms of reaction time and yields of product than the other reported catalysts.
4. Conclusion
In summary, a simple, efficient and facile protocol for the synthesis of N-sulfonyl amidines using
Cu-Scolecite has been described. The notable features of this novel procedure are mild reaction
conditions, higher yields, and simplicity in operation and reusable catalyst.
Supplementary material for X-ray analysis
Crystallographic data for the structural analyses of compound 4e has been deposited with the
Cambridge Crystallographic Data Centre as supplementary publication numbers CCDC
1039420. A copy of this information may be obtained free of charge from the Director, CCDC,
12 Union Road, Cambridge, CBZ 1EZ, UK (fax: +44 1223 336 033; e-mail:
deposit@ccdc.cam.ac.uk or www: http://www.ccdc.cam.ac.uk).
Acknowledgement
The authors thank Indian Institute of Sciences (IISc), Bengaluru and Sophisticated Analytical
Instrumental Facility, Indian Institute of Technology, Madras (IITM) for providing spectral
facilities and Shivaji University Kolhapur for providing DRF fellowship.

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24000
16000
8000
0
*
10
20
30
40
50
2 Theta (Degree)
Fig. 1: XRD of Cu-Scolecite

B
A
Fig.2: Scanning electron micrographs of (A) Scolecite and (B) Cu-Scolecite

Fig. 3: TGA curve of Cu-Scolecite

Fig. 4: Single crystal structure of N1, N1-dipropyl-2-phenyl-N2-tosylacetamidine (4e)

Fig.5: The packing diagram of 4e compound, viewed down Y axis. The packing
arrangement of molecules viewed along the b axis. The dashed lines show intermolecular
C–H…O hydrogen bonds.

90%
86%
82%
79%
80
60
40
20
0
75%
73%
70%
0
1
2
3
No. of cycles
4
5
6
Fig. 6: Reusability of Cu-Scolecite in synthesis of N-sulfonyl amidines

Scheme 1: Synthesis of Cu-Scolecite by ion exchange process