Novel bio-based core-shell organic-inorganic nanohybrid from embedding aspartic acid-guanine ionic liquid on the hydroxylated nano silica surface (nano [(Asp-Gua) IL?PEG-SiO2]): A versatile nanostructure for the synthesis of bis(2,3-dihydroquinazolin-4(1H)-one) derivatives and tricarboxamides under green media

Article abstract of DOI:10.1016/j.poly.2020.114361

A new multi-layered nano structure has been prepared using hydroxylated nano silica (as core) and novel guaninium aspartate ionic liquid (as shell) (nano [(Asp-Gua) IL?PEG-SiO₂]). It characterized by FT-IR, ¹H NMR, FESEM, EDAX, XRD, TGA/ DTG, and BET analysis. This bio-based organic-inorganic hybrid catalyzed synthesis of peptide-like tricarboxamides though the pseudo five-component condensation of aromatic aldehydes, aromatic amines, tert-butyl isocyanide, and Meldrum's acid under green solventless conditions at room temperature successfully. Its efficacy affirmed in the preparation of bis(2,3-dihydroquinazolin-4(1H)-one) derivatives via one-pot pseudo five-component reaction of aldehydes, amines, and isatoic anhydride in 70 °C aqueous media. The protocol contains several advantages such as relatively short reaction times, simple work-up procedure, economic and environmentally-friend because of performing the two class of MCRs under green media, utilizing wide-range of substrates, and reusability and recoverability of the core-shell nano-promoter for 3 runs without significant activity loss.

Full text of DOI:10.1016/j.poly.2020.114361

Journal Pre-proofs
Novel bio-based core-shell organic-inorganic nanohybrid from embedding as-
partic acid-guanine ionic liquid on the hydroxylated nano silica surface (nano
[(Asp-Gua) IL@PEG-SiO2]): A versatile nanostructure for the synthesis of
bis(2,3-dihydroquinazolin-4(1H)-one) derivatives and tricarboxamides under
green media
Kobra Nikoofar, Fatemeh Shahriyari
PII:
S0277-5387(20)30018-8
DOI:
https://doi.org/10.1016/j.poly.2020.114361
POLY 114361
Reference:
Polyhedron
To appear in:
Received Date:
Revised Date:
Accepted Date:
1 September 2019
8 January 2020
11 January 2020
Please cite this article as: K. Nikoofar, F. Shahriyari, Novel bio-based core-shell organic-inorganic nanohybrid from
embedding aspartic acid-guanine ionic liquid on the hydroxylated nano silica surface (nano [(Asp-Gua) IL@PEG-
SiO2]): A versatile nanostructure for the synthesis of bis(2,3-dihydroquinazolin-4(1H)-one) derivatives and
tricarboxamides under green media, Polyhedron (2020), doi: https://doi.org/10.1016/j.poly.2020.114361
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Novel bio-based core-shell organic-inorganic nanohybrid from embedding aspartic
acid-guanine ionic liquid on the hydroxylated nano silica surface (nano [(Asp-Gua)
IL@PEG-SiO2]): A versatile nanostructure for the synthesis of bis(2,3-
dihydroquinazolin-4(1H)-one) derivatives and tricarboxamides under green media
Kobra Nikoofar*, Fatemeh Shahriyari
Department of Chemistry, Faculty of Physics& Chemistry, Alzahra University, Tehran, Iran
*Corresponding author Tel.: +98-21-85692601; fax: +98-21-88041344; e-mail:
kobranikoofar@yahoo.com, k.nikoofar@alzahra.ac.ir
ABSTRACT
A new multi-layered nano structure has been prepared using hydroxylated nano silica (as core)
and novel guaninium aspartate ionic liquid (as shell) (nano [(Asp-Gua) IL@PEG-SiO2]). It
characterized by FT-IR, 1H NMR, FESEM, EDAX, XRD, TGA/ DTG, and BET analysis. This
bio-based organic-inorganic hybrid catalyzed synthesis of peptide-like tricarboxamides though
the pseudo five-component condensation of aromatic aldehydes, aromatic amines, tert-butyl
isocyanide, and Meldrum's acid under green solventless conditions at room temperature
successfully. Its efficacy affirmed in the preparation of bis(2,3-dihydroquinazolin-4(1H)-one)
derivatives via one-pot pseudo five-component reaction of aldehydes, amines, and isatoic
anhydride in 70 °C aqueous media. The protocol contains several advantages such as relatively
short reaction times, simple work-up procedure, economic and environmentally-friend because
of performing the two class of MCRs under green media, utilizing wide-range of substrates,
and reusability and recoverability of the core-shell nano-promoter for 3 runs without significant
activity loss.

Keywords: Tricarboxamide; Dihydroquinazolinone; Aspartic acid; Guanine; Ionic liquid;
Nano silica; Core-shell nanostructure; Green chemistry
1. Introduction
Ionic liquids (ILs) illustrate many special properties which are environmental benignity,
good thermal and chemical stabilities, low vapor pressure, low toxicity, high ion density and
ionic conductivity, non-flammability, variable viscosity, and extended solvation nature [1-3].
In recent years, many task-specific ionic liquids (TSILs), possess various class of cationic and
anionic parts, were designed and utilized for accelerating various organic transformations [4,5].
In general ILs play multiple roles as solvent, chiral additives, and excellent promoter in
reactions. They also may cause high product yields, excellent selectivity, very high catalytic
activity, lower reaction times, and simple work-up procedures. In addition most of them could
easily be recycled and reused for several times without noticeably reducing catalytic activity.
So, the biological properties of a synthesized IL can be adjusted by selecting convenient of
anion and cation structures [6,7].
Amino acids, building blocks of proteins, involve a carboxylic acid functional group and
an also an amino group on the alpha (α) carbon with a diverse side part. These bio-compounds
ha paly critical vast roles in various (a)symmetric catalytic transformations [8]. They could be
used in the preparation of some chiral TSILs [9]. Aspartic acid (asp), 2-aminobutanedioic acid,
an non-essential amino used for the proteins biosynthesis [10] that also has pharmacological
activity at some glutamate receptors [11], is our cationic-part candidate to prepare a novel IL.
Besides the all promising properties of ILs, amino acid-derived ILs possess special properties
for example low cost, high hydrogen bonding ability, good thermal stability, multi-
functionality, chirality, biodegradability and biocompatibility [12].
Guanine (Gua), with the IUPAC name of 2-amino-9H-purin-6(1H)-one, is one of the four
main nucleobases found in the nucleic acids DNA and RNA. Actually it is a derivative of

purine, consisting of a fused pyrimidine-imidazole ring system with conjugated double bonds
[13]. In 2012 a guanine-based organocatalyst has been utilized for conjugate addition of
1,3‐dicarbonyl compounds to nitroolefins [14]. Although some multi-layered catalysts and
composites has been prepared that consist of guanine in recent years [15,16], but its utility in
catalytic organic transformations is not wide-spread.
Nanocatalysts offer some special proprieties that elevated their catalytic activity which are
high surface-to-volume ratio (large surface area), high selectivity, good stability (thermal
and/or mechanical), atom efficacy, easy separating process (efficient recovery characteristics),
time economic exploitation, clean energy production, environmentally-friend, minimum
chemical waste generation (green technology), and permanence or recycling potential [17-20].
Multicomponent reactions (MCRs) are favored one-pot processes, which preferred to other
kinds of processes (such as tandem, cascade, and zipper) because they include sequential
combinations of at least three reagents in the same pot. They could afforded diverse organic
structures and small‐molecule libraries, that are potentially applicable in medicinal and/or
pharmaceutical chemistry [21,22]. The main advantages of MCRs include depressed costs,
quick times of the reactions, atom-economy, energy protection (environmentally friend),
prevention of time consuming product purification, facile performance, and anticipation of by-
products appearance [23,24]. Because the significance of MCRs in organic/ medicinal
chemistry, varies procedures led to carbon-carbon and carbon-heteroatom formation has been
accomplished recently [24-27].
Tricarboxamides are a class of organic compounds that contains three peptide-like bonds.
Recently these hetero-organics obtained via the pseudo five-component condensation reaction
of aldehydes, Meldrum’s acid, isocyanides, and amines (1:1:1:2 molar ratio) [29,30]. The
organics consist of carboxamide functional possessed different range of properties such as
cardiovascular [31], antitumor [32], antimalarial [33], fluorescence [34], anticancer [35], and

apoptotic (DNA intercalation and topoisomerase-II inhibition) [36] that introduce them as
potent compounds in medicinal chemistry and industry.
2,3-Dihydroquinazolin-4(1H)-ones are important group of nitrogen-containing
heterocycles that exhibit various pharmacological and therapeutic properties such as
antimicrobial [37], hypolipidemic [38], and anticancer (as potent fluorescent tubulin inhibitors)
[39]. Some class of dihydroquinazolin-4(1H)-ones showed antioxidative and electrochemically
redox properties [40].
According to our research group interest to preparation/characterization of new
nanostructures and examining their catalytic activities in heterocycles synthesis via MCRs [41-
44], herein we repot preparation of a novel bio-based core-shell organic-inorganic nanohybrid
form embedding aspartic acid-guanine ionic liquid on the hydroxylated nano silica surface
(nano [(Asp-Gua) IL@PEG-SiO2]) via simple procedure. The obtained nanostructure has been
characterized by FT-IR, 1H NMR, FESEM, EDAX, TGA/ DTG, and BET techniques. In the
next step the obtained nano [(Asp-Gua) IL@PEG-SiO2] catalyzed synthesis of bis(2,3-
dihydroquinazolin-4(1H)-one) derivatives via the pseudo five-component condensation of
isatoic anhydride, aldehydes, amines in water at 70 °C in green aqueous media. The extensive
application of the bio-based nano core-shell has also approved to prepare tricarboxamides
through pseudo five-component condensation of isocyanides, aromatic aldehydes, Meldrum’s
acid, and aromatic amines at room temperature under solvent-free conditions. Recovery and
recyclability of the nanostructure within 3 runs without activity loss, in combination with green
reaction media, and high yields of the products, obtaining various range of novel heterocycles
under economic and eco-friendly situations, absence of any by-products formation in two class
of pseudo five- comment reactions are some highlighted points of the reported research.
2. Experimental
2.1. General

Chemicals and solvents purchased from the Sigma-Aldrich and Merck companies and used
without purification. The commercial amorphous nano silica (average particle size of 20-30
nm, surface area of 180-270 m2/g) purchased form Tecnan Company. Melting points
determined in capillary tubes on Electrothermal 9200 melting point apparatus and are
uncorrected. FT-IR spectrum recorded on Bruker FT-IR, Tensor 27 spectrometer on KBr discs.
Morphology and size of the nanostructures visualized by Field Emission Scanning electron
microscope (FESM, VEGA//TESCAN-LMU). The Energy dispersive X-ray spectroscopy
(EDAX) has been done by VEGA3 TESCAN machine. Centrifuge machine (UNIVERSAL
1
320, 1000 W) with 10000-12000 rpm used for preparation process of nanocatalyst. The H
NMR and 13C NMR spectra were obtained on Bruker drx (300 MHz and 75 MHz) spectrometer
in DMSO-d6 as solvent. The mass spectra were recorded on a GC-Mass (5973 Network Mass
Selective Detector, GC 6690 Agilent) and also (Mass l 5973 Network Mass Selective Detector,
Agilent Technology (HP) Agilent) instruments. The Brunauer–Emmett–Teller (BET) surface
area measurements done by Belsorp mini Jipan, Finetec 40 pointe apparatus. Homogenization
performed in an ultrasonic bath Chrom Tech, UP-1200. The absorbance of samples, done with
a UV-VIS, Lambda 35, PerkinEler apparatus. Thermal gravimetric analysis (TGA) was
recorded by TGA1 METTLER TOLEDO. X-ray diffraction (XRD) was taken on a Philips
X’Pert MPD apparatus with using Co radiation (λ = 1.78897 Å) operating at 40 kV and 40 mA
with scan the range of 5–80◦ 2θ (Step Size: 0.02°/s).
2.2. Preparation of nano [(Asp-Gua) IL@PEG-SiO2]
2.2.1. Preparation (Asp-Gua) IL
Aspartic acid (Asp, 1 g) and guanine (Gua, 1 g) in deionized water (5 ml) stirred vigorously
at 30 °C for 3 h and homogenized through putting into an ultrasonic bath for 20 min. The solid
centrifuged and washed with EtOH-H2O (1:1) mixture. Drying in an oven at 60 °C for 7 h gave

1
a white powder. M.P = 298-300 °C. H NMR (300 MHz, D2O): δ (ppm) 2.82-2.98 (m, 2H),
3.98 (dd, J = 6.49 & 4.81 Hz, 1H) 5.71 (d, J = 7.68 Hz, 1H), 7.44 (d, J = 7.44 Hz, 1H).
2.2.2. Preparation of PEG-SiO2
A mixture of nano SiO2 (1 g), PEG-4000 (1 g), and hydrazine hydrate (1 g) stirred
vigorously at 60 °C for 10 min. Then NaOH solution (1 M, 30 ml) added (pH = 12) and stirred
at 65 °C for 30 min. The solid centrifuged and washed with EtOH-H2O (1:1) until to be natural.
The white solid dried at 60 °C for 8 h.
2.2.3. Embedding the (Asp-Gua) IL on the surface of PEG-SiO2 (nano [(Asp-Gua)
IL@PEG-SiO2])
A mixture of (Asp-Gua) IL (1 g) and PEG-SiO2 (0.5 g) in EtOH (10 ml) stirred for 1 h at
room temperature followed by sonication for 30 min. The obtained solid separated through
centrifugation and washing with EtOH (2 × 10 ml). Drying in oven at 60 °C for 6 h gave the
desired nanostructure.
2.3. General procedure for the synthesis of bis(2,3-dihydroquinazolin-4(1H)-one) derivatives
by nano [(Asp-Gua) IL@PEG-SiO2]
In a round bottom flask equipped with condenser, a mixture of diamines 1 (1 mmol), isatoic
°
anhydride 2 (2 mmol), aldehydes 3 (2 mmol) in deionized water (5 ml) stirred at 70 C for the
appropriate time monitored by TLC (n-hexne:EtOAc, 5:3). After completion, MeOH (15 ml)
added to the mixture and the catalyst separated through filtration. The pure 3,3'-(1,4-
phenylene)bis(2-aryl-2,3-dihydroquinazolin-4(1H)-one) 4a-n obtained by recrystallization form a
mixture of MeOH:CHCl3 (1:1). In the case of 2,2'-(1,4-phenylene)bis(3-aryl-2,3-
dihydroquinazolin-4(1H)-one) derivatives 4n-x, the substrates are amines 1, isatoic anhydride 2,
and dialdehydes 3 used in a 2:2:1 molar ratio.

2.3.1. Spectral data of new compounds
3,3'-(1,4-Phenylene)bis(2-(1H-indol-3-yl)-2,3-dihydroquinazolin-4(1H)-one) (4g)
Yellow solid; m.p. 126-128 °C. IR (KBr): 3372, 3228, 1642, 1610 cm–1. 1H NMR (DMSO-
d6): 6.72-6.77 (m, 3H, 2CH & 1Ar), 7.01-7.07 (m, 2H, Ar), 7.12-7.16 (m, 1H, Ar), 7.19-7.29
(m, 8H, 6Ar & 2NH), 7.37-7.40 (m, 1H, Ar), 7.43-7.46 (m, 1H, Ar), 7.48-7.50 (m, 1H, Ar),
7.53-7.55 (m, 3H, Ar), 7.99-8.09 (m, 2H, Ar), 8.26-8.27 (m, 1H, Ar), 8.33-8.39 (m, 1H, Ar),
8.66 (brs, 1H, Ar), 8.78 (m, 1H, Ar), 10.96 (brs, 2H, NH).
3,3'-(Ethane-1,2-diyl)bis(2-(5-bromo-2-hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one)
(4l)
°
1
Yellow solid; m.p. 76-78 C. IR (KBr): 3425, 3113, 1639, 1453, 1234 cm–1. H NMR
(DMSO-d6): 2.05 (s, 1H, CH), 2.33-2.41 (m, 1H, CH), 2.59-2.71 (m, 1H, CH), 5.41 (s, 2H,
NH), 5.44 (s, 2 H, OH), 6.33-6.46 (m, 1H, CH), 6.63-6.68 (m, 2H, CH & Ar), 6.70-6.81 (m,
1H, Ar), 7.11-7.20 (m, 3H, Ar), 7.34-7.42 (m, 8H, Ar), 7.64-7.68 (m, 1H, Ar).
3,3'-(Hexane-1,6-diyl)bis(2-(4-chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one) (4m)
White solid; m.p. 117-120 °C. IR (KBr): 3362, 3062, 1651, 1511 cm–1. 1H NMR (DMSO-
d6): 3.22-3.24 (m, 1H, CH), 3.49-3.74 (m, 2H, CH2), 4.32-4.42 (m, 2H, CH2), 4.55-4.63 (m,
2H, CH2), 4.88-4.96 (m, 1H, CH), 5.75-5.85 (m, 1H, CH), 6.27 (brs, 1H, CH), 6.57-6.76 (m,
2H, Ar), 6.88-6.98 (m, 3H, 2NH & Ar), 7.18-7.38 (m, 5H, Ar), 7.42-7.48 (m, 1H, Ar), 7.62 (d,
1H, J = 8.49 Hz, Ar), 7.66 (d, 1H, J = 8.18 Hz, Ar), 7.68-7.74 (m, 2H, Ar), 7.92 (d, 1H, J =
8.32 Hz, Ar), 8.02-8.16 (m, 1H, Ar), 8.37-8.50 (m, 1H, Ar).
2,2'-(1,4-Phenylene)bis(3-(4-hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one) (4r)
°
1
Black solid; m.p. 192-194 C. IR (KBr): 3474, 3373, 1697, 1453, 1384 cm–1. H NMR
(DMSO-d6): 6.58-6.66 (m, 7H, 3Ar, 2OH & 2CH), 6.81-6.83 (m, 2H, Ar), 7.16-7.26 (m, 9H,

Ar), 7.32 (d, 2H, J = 8.6 Hz, Ar), 7.40-7.43 (m, 1H, Ar), 7.57-7.59 (m, 1H, Ar), 7.68-7.87 (m,
2H, Ar), 7.95 (brs, 1H, NH), 8.09 (s, 1H, NH). 13C NMR (DMSO-d6): 107.55, 114.97, 115.10,
115.79, 116.68, 117.38, 122.10, 122.91, 127.95, 128.07, 129.05, 130.93, 131.05, 134.81,
134.86, 138.41, 152.19, 160.07, 161.34, 166.04, 173.49, 174.59.
2,2'-(1,4-Phenylene)bis(3-(2-(1H-indol-3-yl)ethyl)-2,3-dihydroquinazolin-4(1H)-one) (4t)
Yellow solid; m.p. 115-117 °C. IR (KBr): 3420, 3064, 1650, 1608 cm–1. 1H NMR (DMSO-
d6): 2.82-2.93 (m, 2H, CH2), 2.96-3.04 (m, 4H, 2CH2), 3.47-3.56 (m, 1H, CH), 5.90-5.98 (m,
2H, CH), 6.52 (t, 1H, J = 7.31 Hz, Ar), 6.63-6.78 (m, 3H, 2NH & Ar), 6.92-7.05 (m, 5H, Ar),
7.14-7.20 (m, 2H, Ar), 7.33-7.38 (m, 4H, Ar), 7.39-7.43 (m, 3H, Ar), 7.48-7.49 (m, 2H, Ar),
7.61-7.72 (m, 3H, Ar), 8.23-8.34 (m, 1H, Ar), 10.81-10.84 (brs, 2H, NH). 13C NMR (DMSO-
d6): 13.96, 22.09, 23.62, 70.62, 111.27, 111.36, 112.05,114.28, 114.58, 114.90, 116.36, 117.17,
118.27, 120.94, 122.74, 126.57, 127.09, 127.34, 127.50, 128.05, 133.21, 136.21, 141.46,
146.38, 162.30.
2,2'-(1,4-Phenylene)bis(3-(1H-1,2,4-triazol-3-yl)-2,3-dihydroquinazolin-4(1H)-one) (4u)
Yellow solid; m.p. 187-190 °C. IR (KBr): 3249, 3065, 1611, 1450 cm–1. 1H NMR (DMSO-
d6): 5.90-6.50 (brs, 2H, 2CH), 6.75–6.82 (m, 3H, 2NH & Ar), 7.15-7.30 (m, 5H, Ar), 7.49 (m,
2H, Ar), 7.57 (d, 1H, J = 7.14 Hz Ar), 7.70-7.74 (m, 1H, Ar), 8.00-8.03 (m, 1H, Ar), 8.05-8.09
(m, 1H, Ar), 8.16-8.19 (m, 1H, Ar), 8.35-8.57 (m, 1H, Ar), 9.16 (brs, 1H, NH), 9.32 (brs, 1H,
NH).
2.4. General procedure for the preparation of tricarboxamides by nano [(Asp-Gua) IL@PEG-
SiO2]
A mixture of amines 1 (2 mmol), aldehydes 3 (1 mmol), tert-butyl isocyanide 5 (1 mmol),
and Meldrum's acid 6 (1 mmol) stirred at room temperature in the absence of any solvent. The

progress of the reaction monitored by TLC (n-hexne:EtOAc, 7:3). After completion, MeOH (15
ml) added to the mixture and the catalyst separated through filtration. The pure tricarboxamides
7a-f obtained from recrystallization form methanol.
2.4.1. Spectral data of new compounds
N2-(tert-butyl)-2-(2-chlorophenyl)-N1,N'1-bis(3-hydroxyphenyl)ethane-1,1,2-
tricarboxamide (7a)
Dark yellow solid; m.p. 67-69 oC. FT- IR (KBr): 3371, 2925, 1604, 1603, 1518, 815 cm-1.
1H NMR (DMSO-d6): 1.24 (s, 9H, 3CH3), 2.79-2.93 (m, 2H, CH), 5.64 (brs, 1H, Ar), 5.93 (d,
1H, J = 8.00 Hz, Ar), 5.98-6.01 (m, 2H, Ar), 6.32-6.47 (m, 1H, Ar), 6.62 (s, 1H, Ar), 6.76 (t,
1H, J = 7.77 Hz, Ar), 6.67-6.73 (m, 1H, Ar), 6.88-6.91 (m, 1H, Ar), 6.97-7.00 (m, 1H, Ar),
7.10-7.24 (m, 2H, Ar), 7.85-8.23 (brs, 2H, OH), 9.80 (brs, 1H, NH), 10.18 (bs, 2H, NH). 13C
NMR (DMSO-d6): 27.16, 29.09, 37.00, 51.02, 101.05, 103.40, 105.45, 109.70, 115.02, 127.62,
128.50, 128.90, 129.44, 129.78, 139.47, 139.86, 149.73, 158.10. MS (EI) (m/z): 510 [M+], 474
[M+]-Cl, 433 [M+]-phenyl, 416 [M+]-3-hydroxyphenyl, 380 [M+]-3-hydroxyphenyl, -Cl, 363
[M+]-3-hydroxyphenyl, -Cl, -Me, 308 [M+]-3-hydroxyphenyl, -Cl, -NHC(Me)3, 291 [M+]-3-
hydroxyphenyl, -Cl, -NHC(Me)3, -OH, 273 [M+]-2(3-hydroxyphenyl), -Cl, -Me, 198 [M+]-2(3-
hydroxyphenyl), -chlorophenyl, -Me, 192 [(NH2CO)2CCH2CONH2]+, 109 [hydroxyaniline]+,
90 [hyrdoxyphenyl]+.
N2-(tert-butyl)-2-(2-hydroxy-3-methoxyphenyl)-N1,N'1-bis(2-nitrophenyl)ethane-1,1,2-
tricarboxamide (7b)
1
Black Viscos liquid. FT-IR (KBr): 3360, 2965, 1601, 1515, 1490, 1512, 1336, 1304. H
NMR (DMSO-d6): 1.15 (s, 3H, CH3),, 1.24 (s, 6H, 2CH3), 1.97 (s, 3H, OCH3), 3.34 (brs, 1H,
CH), 4.01 (d, 1H, J = 4.59 Hz, CH), 5.92-6.01 (m, 5H, 4Ar & OH), 6.21-6.47 (m, 2H, Ar),
13
6.65-6.76 (m, 2H, Ar), 6.89-7.31 (m, 4H, Ar), 9.81 (brs, 1H, NH), 10.19 (brs, 2H, NH). C

NMR (DMSO-d6): 14.14, 27.47, 59.85, 101.06, 103.42, 105.50, 129.48, 149.82, 155.20,
158.14. MS (EI) (m/z): 579 [M+], 529 [M+]-OMe, -OH, 491 [M+]-OMe, -OH, -NH, 459 [M+]-
nitrophenyl, 431 [M+]-CONHCMe3, -OH, -OMe, 140 [nitroaniline]+, 120 [nitrophenyl]+.
N2-(tert-butyl)-2-(naphthalen-2-yl)-N1,N'1-di-p-tolylethane-1,1,2-tricarboxamide (7c)
Pale yellow solid; m.p. 62-64 oC. FT- IR (KBr): 3427, 2922, 1722 1619, 1370, 1164, 1034
cm-1. 1H NMR (DMSO-d6): 1.25 (s, 6H, 2CH3), 2.1 (s, 3H, CH3), 2.22 (s, 3H, CH3), 2.29 (s,
3H, CH3), 3.1 (brs, 1H, CH), 3.37 (brs, 1H, CH), 6.50 (d, 2H, J = 6.03 Hz, Ar), 6.80 (m, 2H,
Ar), 6.97 (d, 1H, J = 8.22 Hz, Ar), 7.07 (m, 2H, Ar), 7.23-7.29 (m, 2H, Ar), 7.47 (m, 3H, Ar),
7.84 (d, 1H, J = 8.37, Ar), 7.71 (m, 2H, Ar), 8.42 (brs, 2H, NH), 9.56 (brs, 1H, NH). 13C NMR
(DMSO-d6): 20.13, 20.45, 20.59, 27.16, 28.34, 41.00, 114.24, 119.09, 108.36, 120.21, 123.33,
123.33, 124.20, 126.57, 128.01, 128.97, 129.11, 129.27, 129.79, 130.08, 133.21, 136.68,
141.10, 145.86, 154.51, 169.71, 170.90. MS (EI) (m/z): 521 [M+], 451 [M+]-Me, -NHCMe3,
378 [M+]-naphthyl, -Me, 333 [M+]-naphthyl, -4Me, 260 [M+]-p-tolylNHCO, -naphthyl, 217
[M+]-p-tolylNHCO, -naphthyl, -3Me, 189 [M+]-p-tolylNHCO, -naphthyl, -NHCMe3, 140 [2-
methylnaphthyl]+, 91 [p-tolyl]+.
N2-(tert-butyl)-N1,N'1-bis(3-hydroxyphenyl)-2-(1H-pyrrol-2-yl)ethane-1,1,2-tricarboxamide
(7d)
o
Glossy black solid; m.p. 79-81 C. FT- IR (KBr): 3367, 2967, 1660, 1605, 1583, 1494,
1224 cm-1. 1H NMR (DMSO-d6):1.17-1.29 (brs, 9H, 3CH3), 4.8 (brs, 2H, OH), 5.90 (brs, 1H,
CH), 5.91 (brs, 1H, CH), 5.97-5.99 (m, 3H, Ar), 6.40-6.47 (m, 1H, Ar), 6.69-6.89 (m, 3H, Ar),
7.00-7.07 (m, 1H, Ar), 7.19 (m, 1H, Ar), 7.83 (m, 1H, Ar), 8.25-8.30 (m, 1H, Ar), 8.90 (brs,
3H, NH), 10.07 (brs, 1H, NH). 13C NMR (DMSO-d6): 158.13, 151.2, 149.88, 129.47, 105.44,
103.33, 100.99, 28.52, 27.23. MS (EI) (m/z): 464 [M+], 449 [M+]-OH, 449 [M+]-2OH, 413
[M+]-2OH, -Me, 393[M+]-NHCMe3, 354 [M+]-4-hydroxynaphthyl, -OH, 321 [M+]-4-

hydroxynaphthyl, -OH, -2Me, 293 [M+]-4-hydroxynaphthyl, -OH, -CMe3, 13840 [4-
hydroxyanilyl]+, 95 [p-hydroxyphenyl]+.
N2-(tert-butyl)-2-(1H-indol-3-yl)-N1,N'1-bis(5-methyl-1H-pyrazol-3-yl)ethane-1,1,2-
tricarboxamide (7e)
Dark yellow solid; m.p. 199-201 oC. FT- IR (KBr): 3392, 3323, 3216, 2923, 1616, 1463,
1
1150 cm-1. H NMR (DMSO-d6): 1.16-1.32 (brs, 9H, 3CH3), 1.36-1.46 (brs, 3H, CH3), 1.81
(brs, 1H, CH3), 3.41-3.46 (m, 1H, CH), 5.19 (d, 1H, J = 6.08 Hz, CH), 6.87 (s, 1H, Ar), 6.89-
6.95 (m, 1H, Ar), 6.98-7,04 (m, 2H, Ar), 7.18 (d, 1H, J = 7.66 Hz, Ar), 7.30-7.36 (m, 1H, Ar),
7.59-7.85 (m, 2H, Ar), 8.16 (brs, 1H, NH), 8.47 (brs, 1H, NH), 10.17 (brs, 1H, NH), 10.27 (brs,
1H, NH), 10.72 (brs, 1H, NH), 10.82 (brs, 1H, NH). 13C NMR (DMSO-d6): 10.24, 11.43, 12.24,
18.60, 26.34, 27.19, 28.05, 28.30, 28.60, 51.08, 56.13, 90.54, 103.74, 114.03, 115.34, 115.41,
116.82, 118.28, 121.17, 123.28, 123.48, 127.67, 128.50, 129.06, 130.82, 136.86, 137.07,
140.07, 145.90, 151. 153.67, 170.02, 68, 170.40. MS (EI) (m/z): 474 [M+], 429 [M+]-3Me, 415
[M+]-4Me, 379 [M+]-3-methylpyrazolyl, -Me, 112 [CH2CONHCMe3]+.
2,2'-(1,4-Phenylene)bis(N1,N'1-bis(4-bromophenyl)-N2-(tert-butyl)ethane-1,1,2-
tricarboxamide) (7f)
Pale yellow solid; m.p. 90-92 oC. FT- IR (KBr): 3371, 2963, 1723, 1665, 1487, 762 cm-1.
1H NMR (DMSO-d6): 1.26 (brs, 9H, 3CH3), 2.48-2.67 (m, 1H, CH), 3.36-3.75 (m, 1H, CH),
6.07 (brs, 1H, Ar), 6.50 (brs, 2H, Ar), 7.09 (brs, 3H, Ar), 7.32-7.54 (m, 3H, Ar), 7.78-7.79 (m,
1H, Ar), 8.04 (brs, 1H, NH), 8.45 (brs, 2H, NH). 13C NMR (DMSO-d6): 27.13, 28.97, 49.47,
106.10, 111.93, 115.80, 119.27, 123.13, 123.30, 128.79, 131.30, 132.05, 140.10, 148.03,
154.21. MS (EI) (m/z): 346 [M+]/2-bromophrnyl, -CMe3, 327 [M+]/2-2Br, -CMe3, 237 [M+]/2-
bromophrnyl, -CMe3, -NH, -Br, 171 [4-bromoaniline]+, 157 [4-bromophenyl]+, 117
[Me3CNHCOMe]+, 92 [tolyl]+.

3. Results and discussion
The schematic simple and 3-stage synthetic procedure and proposed structure of the novel
bio-based core-shell organic-inorganic nanohybrid which gained form embedding aspartic
acid-guanine ionic liquid part on the surface of hydroxylated nano silica (nano [(Asp-Gua)
IL@PEG-SiO2]) illustrated in Scheme 1.
HO
OH
OH
OH
HO
Nano
SiO2
PEG (4000)
Nano
SiO2
HO
HO
OH
PEG-SiO2
O
O-
+H3N
NH2
H
N
N
NH2
OH
HN
H2O, 30 C
HO2C
O
+
H2N
HN
HO2C
O
N
N
H
Aspartic acid
Guanine
O
(ASP-Gua) IL
HO
OH
HO
HO
HO
Nano
H2O, 30 C
OH
OH
(ASP-Gua) IL
PEG-SiO2
SiO2
+
OH
nano [(Asp-Gua) IL@PEG-SiO2]
Scheme 1. Schematic synthetic route of nano [(Asp-Gua) IL@PEG-SiO2.
After preparation the nano [(Asp-Gua) IL@PEG-SiO2], as light-cream powder, it has been
characterized through FT-IR, 1H NMR, EDAX, FESEM, XRD, TGA/ DTG, and BET analysis.
The step by step FT-IR spectra respective to final nanostructure synthesis illustrated in Fig. 1.

As demonstrated in parts a & b, the stretching vibrations of Si-O-Si bond at 1043-1077 Cm-1,
stretching vibration of the OH group in silanol at 3446 Cm-1, and stretching Si-O-H bond in
1121 Cm-1 are the fingerprints. The broad peak in 3115-2446 Cm-1 due to stretching vibration
+
of NH3 group and NH functional of the guaninium anion, bending vibrations of NH band in
1535 Cm-1 and 812 Cm-1, the asymmetric and symmetric stretching of COO- group at 1674 Cm-1
and 1628 Cm-1, the aliphatic C-C stretching bands at 2845 Cm-1, in addition with the peaks at
1470 Cm-1 , 1375 Cm-1 and 1245 Cm-1 for C=C, C=N and C-N bonds confirmed the successful
preparation of the ionic liquid. The nano [(Asp-Gua) IL@PEG-SiO2] in Fig. 1d contains the all
the mentioned bands related to the pervious layers.
d
c
b
a
Fig. 1. The FT-IR spectra of a) nano SiO2, b) PEG-SiO2, c) (Asp-Gua) IL, and d) nano [(Asp-
Gua) IL@PEG-SiO2].
The FESEM images of PEG-SiO2 (top) and nano [(Asp-Gua) IL@PEG-SiO2] (down) are
shown in Fig. 2. The average size of the nanoparticles in hydroxylated nano silica with PEG is
about 70 -100 nm and the average diameter for the final core-shell nanostructure is between 25
to 50 nm. The morphology of PEG-SiO2 is spherical, the same as the nano silica core, but the

final nanostructure did not show any special nano shape. In addition the final nano [(Asp-Gua)
IL@PEG-SiO2] possess coarse nanoparticles with condensed texture.
Fig. 2. FESEM images of PEG-SiO2 (top) and nano [(Asp-Gua) IL@PEG-SiO2] (down).
The Fig. 3 demonstrated The EDAX patterns of PEG-SiO2 (top) and nano [(Asp-Gua)
IL@PEG-SiO2] (middle). The analysis affirmed presentation of some elements such as C
(36.21%), N (27.33%), Si (2.24%), and O (35.68%) in final nanostructure that proved its
successful preparation. The presentation of Na (1.78%) and N (20.16%) in PEG-SiO2 is due to
sodium hydroxide and hydrazine hydrate utilized in the manufacturing of this segment process.
The EDAX of the catalyst after recovery and reusability also shown at the bottom of the Fig.

3. As it is obvious, the main element on the nanocatalyst structure remained intact that
confirmed that the catalyst structured is indissoluble under reaction conditions.
3000
C K
2500
O K
2000
1500
N K
NaK
1000
SiK
500
keV
6.743
0
0

Fig. 3. The EDAX analysis of PEG-SiO2 (top), nano [(Asp-Gua) IL@PEG-SiO2 (middle),
and reused nano [(Asp-Gua) IL@PEG-SiO2 (bottom).
TGA/ DTG analysis of PEG-SiO2 (top) and nano [(Asp-Gua) IL@PEG-SiO2 (down), have
been presented in Fig. 4 respectively. As could be seen the endothermic degradation PEG-SiO2
(Fig. 4, top) happened in two stages. The first occurred at 200-250 °C (about 20% weight loss)
and the second weight loss of about 45% at 600-680 °C belongs to total decay of the structure.
In the case of nano [(Asp-Gua) IL@PEG-SiO2 (down), degradation occurred in a multistep
endothermic stapes in the range of 150-600 °C (about 12% weight loss). This data affirmed
that the multi-layered organic –inorganic hybrid is very heat-resistance even up to 600 °C.

Fig. 4. TGA/ DTG curves of PEG-SiO2 (top) and nano [(Asp-Gua) IL@PEG-SiO2 (down).
The N2 adsorption/desorption isotherm (top) and pore size distribution diagram (down) of
the nano [(Asp-Gua) IL@PEG-SiO2 demonstrated in Fig. 5 that could be classified as a type
III isotherm that exhibited hysteresis loop of type H3. The physicochemical properties of the

nanostructure is: BET surface area (SBET) = 8.3912 m2g-1), total pore volume = 0.3018 cm3g-1,
and average pore diameter = 15.147 nm.
Fig. 5. Nitrogen adsorption/ desorption isotherms (top) and pore size distribution (down) of
nano [(Asp-Gua) IL@PEG-SiO2.
The XRD patterns of the nano [(Asp-Gua) IL@PEG-SiO2 (top) and the recycled and
reused nano [(Asp-Gua) IL@PEG-SiO2 after 3 runs (bottom) has been illustrated in Fig. 6. As
could be seen in top, the broad peak at around 2θ = 22° characterized the amorphous SiO2 [45].
The pattern exhibits peaks at 12.31°, 16.39°, 20.13°, 37.35°, and 47.45° which are

representative of guanine (JCPDS no. 04-0557). The peaks at 25.23°, 26.49°, 29.75°, 30.51°,
32.57°, 36.39°, 43.67°, and 46.29° (JCPDS no. 39-1523) affirmed presentation of aspartic acid
in the nan catalyst structure. At the bottom diagram of Fig. 6 the XRD pattern of the nano
[(Asp-Gua) IL@PEG-SiO2], was taken after 3 cycles of recovery and reusability. Again the
broad peak around 2θ = 22° confirmed that the amorphous nano silica in the structure remained
intact. The peaks at 16.39°, 20.93°, and 32.49 ° which belong to guanine and also the peak at
26.37°(related to aspartic acid), affirmed that (Asp-Gua) IL part is also persist in the recycled
nano catalyst. It must be mentioned that the board peak of amorphous SiO2 covered some peaks
of aspartic acid in the 2θ range between 18-35°.
700
600
500
400
300
200
100
0
80 75 70 65 60 55 50 45 40 35 30 25 20 15 10
5
2θ/ degree
350
300
250
200
150
100
50
0
80 75 70 65 60 55 50 45 40 35 30 25 20 15 10
5
2θ/ degree

Fig. 6. XRD pattern of nano [(Asp-Gua) IL@PEG-SiO2 (top) and recycled nano [(Asp-Gua)
IL@PEG-SiO2 (bottom).
After preparation/ characterization of novel nano [(Asp-Gua) IL@PEG-SiO2, its catalytic
efficacy examined in the synthesis of 2,3-dihydroquinazolin-4(1H)ones. For this purpose the
pseudo five-component reaction of p-phenylenediamine (1), isatoic anhydride (2), and 4-
chlorobenzaldehyde (3), in 1:2:2 molar ratio, chosen as the model. In order to get the optimized
condition various parameters checked due to the data on Table 1. As could be seen, the
temperature effect investigated in entries 1-4. The best results belonged to 70 °C (entry 3).
Surprisingly elevating temperature up to 90 °C (entry 4) decreased the yield and elongated the
time compared to 70 °C. The catalyst amount studies (entries 5 & 6) revealed that the best
amount is 0.028 g. The solvent and media was another variable that investigated. The model
MCR performed in different solvents, as well as solvent-free media. The best medium was
aqua (entries 7-10). Consequently, based on Table 1, the optimized condition was heated
aqueous medium (70 °C) in the presence of 0.028 g of nano [(Asp-Gua) IL@PEG-SiO2.(entry
3). It is noticeable that performing the organic transformations in water contains environmental
benefits and aqua concerned as green and economic media.
Table 1
Optimization the reaction condition for the synthesis of 3,3'-(1,4-phenylene)bis(2-(4-
chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one) 4
CHO
Cl
H
N
O
H
N
NH2
N
O
O
Cl
O
N
CHO
NH2
H
N
O
N
1
H
Cl
4
O
Cl
3
2
Yielda
(%)
-
Entry
Solvent (5 ml)/ temperature (°C) Catalyst (g)
Time (min)
1
2
H2O/ rt
0.028
0.028
180
150
H2O/ 50
85

3
4
5
6
7
8
9
10
H2O/ 70
H2O/ 90
H2O/ 70
H2O/ 70
EtOH/ 70
CH3CN/ 70
-/ rt
0.028
0.028
0.02
0.032
0.028
0.028
0.028
0.028
100
150
150
100
240
180
140
140
90
74
81
89
86
73
70
84
-/ 70
a Isolated yield.
Next, the generality of the procedure surveyed by preparing various 2 3,3'-(1,4-
phenylene)bis(2-aryl-2,3-dihydroquinazolin-4(1H)-one) derivatives respecting different
substituted benzaldehydes. The results demonstrated in Table 2 (4a-f). Indole-3-carbaldehdye,
as a heterocyclic sterically-hindered aldehyde, also gave the corresponding 3,3'-(1,4-
phenylene)bis(2-(1H-indol-3-yl)-2,3-dihydroquinazolin-4(1H)-one) 4g well. In order to affirm
the efficacy of the method, pseudo five-component cyclocondensation examined in the
presence of 1,2-ethylenediamine, as an aliphatic candidate, successfully (4h-l). 1,6-
Hexyldiamine, as a long chain aliphatic model also achieved the correspondence 3,3'-(hexane-
1,6-diyl)bis(2-(4-chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one) 4m in good yield. In the
next stage to extend the proficiency of the protocol, terephthalaldehyde, isatoic anhydride, and
different anilines, in 1:2:2 molar ratio, accomplished successfully to obtain 2,2'-(1,4-
phenylene)bis(3-aryl-2,3-dihydroquinazolin-4(1H)-one) derivatives (Table 2, 4n-r). This
experiment also repeated using 2-naphthyl amine, as bicyclic hindered aliphatic amine to get
the 4s successfully. An interesting resultant of the procedure is due to utilizing 4-amino
pyridine, tryptamine, and 3-amino-1,2,4-triazole, as potent pharmaceutical motifs, that
performed the condensation with terephthalaldehyde and isatoic anhydride easily (4t-u). 2,2'-
(1,4-phenylene)bis(3-benzyl-2,3-dihydroquinazolin-4(1H)-one) 4v obtained using benzyl
amine. Oxalaldehyde, an aliphatic dialdehyde also implied the condensation with 4-
chloroaniline, and benzylamine to obtain 4w-x respectively.

Table 2
Nano [(Asp-Gua) IL@PEG-SiO2.catalyzed the Synthesis of bis-(2,3-dihydroquinazolin-
4(1H)-one) derivatives in 70 °C aqua
Cl
Cl
H
N
H
H
N
N
N
N
N
O
O
O
O
O
O
N
N
N
N
N
N
H
H
H
Cl
Cl
4a
4c
45 min, 93%
4b
60 min, 90%a
100 min, 90%
NO2
O2N
NO2
H
H
N
N
O
H
N
N
N
O
O
N
O
O
N
N
O
N
N
N
O2N
N
H
H
H
O2N
NO2
4d
45 min, 93%
4f
4e
75 min, 91%
75 min, 95%
H
NH
Cl
N
H
N
O
H
N
O
N
O
N
N
O
N
N
N
O
Cl
O
N
N
N
HN
H
H
H
4h
4i
75 min, 96%
75 min, 91%
4g
60 min, 90%
126-128 °C (new)
HO
H
N
NO2
H
N
O
Me
Br
H
N
N
O
O
O
N
N
N
OH
N
N
O
O
N
N
N
H
H
H
O2N
Me
4k
4j
Br
4l
60 min, 91%
60 min, 85%
45 min, 91%
76-78 °C (new)

Cl
N
O
O
Cl
H
N
N
N
O
N
N
H
N
H
N
H
H
N
O
N
N
H
N
Cl
4m
60 min, 92%
117-120 °C (new)
O
O
Cl
4n
4o
75 min, 81%
60 min, 92%
OH
O
Me
Br
O
O
N
N
N
N
H
N
N
H
H
H
N
H
H
N
N
N
N
N
O
O
O
HO
Br
Me
4r
60 min, 95%
4p
4q
60 min, 89%
45 min, 91%
192-194 °C (new)
NH
O
N
O
NH
O
N
N
N
N
N
N
H
H
N
N
H
H
H
N
H
N
N
N
N
HN
N
O
O
HN
O
N
4u
4t
45 min, 95%
115-117 °C (new)
100 min, 89%
187-190 °C (new)
4s
75 min, 93%
O
N
N
Cl
O
O
N
N
H
H
N
N
N
H
H
N
H
N
H
N
N
N
O
O
O
Cl
4w
120 min, 90%
4x
4v
120 min, 95%
90 min, 95%
a Isolated yields.
b The compounds 4g, 4l, 4m, 4r,4t, and 4u are new. The others are known and characterized
with their data with previously reported authentic samples [40,46,47].

In the next part, in order to investigate the proficiency of the nano [(Asp-Gua) IL@PEG-
SiO2, the pseudo five-component reaction of amines 1, aldehydes 3, tert-butyl isocyanide 5,
and Meldrum's acid 6, in a 2:1:1:1 molar ratio, in order to gain novel peptide-like
tricarboxamides (7a-f) examined in the absence of solvent at room temperature successfully
(Scheme 2). The results are summarized in Table 3.
O
Ar
NH
O
O
O
NC
O
Nano [(Asp-Gua) IL@PEG-SiO2] (0.02 g)
Ar1CHO
2 ArNH2
+
+
+
O
O
Solvent-free, rt
HN
7a-f
NH
Ar
1
3
5
Ar
6
Ar = 4-BrC6H4, 4-MeC6H4, 3-OHC6H4, 2-NO2C6H4, 3-amino-5methyl-pyrazolyl
Ar1 = 2-ClC6H4, 2-OH-3-MeC6H3, 4-CHOC6H4, 2-naphthyl, 2-pyrolyl, 3-indolyl
Scheme 2. Synthesis of novel tricarboxamides catalyzed by nano [(Asp-Gua) IL@PEG-SiO2.
As it is represented, various (hetero)aromatic aldehydes and amines utilized to preparer
different tricarboxamies. High-hindered 2-naphthaldehyde gave the corresponding N2-(tert-
butyl)-2-(naphthalen-2-yl)-N1,N'1-di-p-tolylethane-1,1,2-tricarboxamide 7c successfully. N2-
(tert-butyl)-2-(1H-indol-3-yl)-N1,N'1-bis(5-methyl-1H-pyrazol-3-yl)ethane-1,1,2-
tricarboxamide 7e, is an interesting heterocycle possessing many pharmaceutic potent motifs.
Another noteworthy property of the protocol belongs to its regioselectivity. As illustrated in
Table 3, p-phenylene-bistricarboxamide 7f obtained via the reaction of terephthalaldehyde, 4-
bromoaniline, tert-butyl isocyanide, and Meldrum's acid, in a 1:4:2:2 molar ratio in the
presence of nano [(Asp-Gua) IL@PEG-SiO2 (0.04 g). It means the condensation occurred in
both aldehydic moiety of the terephthalaldehyde and no N1,N'1-bis(4-bromophenyl)-N2-(tert-
butyl)-2-(4-formylphenyl)ethane-1,1,2-tricarboxamide, as by-product didn’t obtained. The
mentioned reaction repeated two times first by 0.02 g of the nanostructure. In this case no by-
product observed bnt the yield was less than utilizing 0.04 g of the catalyst. Secondly try
performed by terephthalaldehyde, 4-bromoaniline, tert-butyl isocyanide, and Meldrum's acid,
in a 1:2:1:1 molar ratio, in the presence of 0.02 g of nano [(Asp-Gua) IL@PEG-SiO2.

Surprisingly no by-product achieved and 7f was the only product. So, the high regioselectivity
of the procedure affirmed.
Table 3
Synthesis of novel tricarboxamides by nano [(Asp-Gua) IL@PEG-SiO2
OMe
O
Cl
O
OH
O
NH
O
NH
O
NH
O
O
O
O
HN
NH
HN
NH
NO2
O2N
OH
HN
NH
HO
Me
Me
7a
7c
60 min, 94%a
7b
120 min, 95%
Viscose (new)
60 min, 94%
62-64°C (new)
67-69 °C (new)
Br
H
N
O
HN
O
O
O
NH
O
N
H
NH
O
NH
O
O
O
O
HN
O
NH
O
HN
NH
HN
NH
OH
HO
Me
Br
HN
NH
N
Me
N
N
N
H
H
7d
7e
90 min, 94%
199-201 °C (new)
Br
Br
60 min, 95%
79-81 °C (new)
7f
120 min, 90%
90-92°C (new)
a Isolated yields.
In order to affirm the formation of tricarboxamides, the UV study of 7e, as an example,
has been done. According to Fig. 7, the spectra of 3-amino-5-methylpyrazol (a), indole-3-
carbaldehyde (b), and the final tricarboxamide 7e (c) recorded in a 0.001 gl-1 of their ethanolic
solution. The results demonstrated a bathochromic shift in the product 7e in comparison to its
substrates that is due to conjugation enhancement.

Fig. 7. UV spectrum of 3-amino-5-methylpyrazol (a), indole-3-carbaldehyde (b), and N2-
(tert-butyl)-2-(1H-indol-3-yl)-N1,N'1-bis(5-methyl-1H-pyrazol-3-yl)ethane-1,1,2-
tricarboxamide 7e (c) (c = 0.001 gl-1, EtOH)
Finally, for perfection the catalyst properties in line with economical green chemistry, the
recovery and reusability of the nanostructure examined for the synthesis of 7e as a model. After
completion of the reaction, the nano [(Asp-Gua) IL@PEG-SiO2, separated by adding methanol
to the reaction mixture and further simple filtration followed by air-drying. The recovered
nanostructure used for 2 more cycles without significant activity loss (Fig. 8).
Fig. 8. Recovery and reusability diagram of nano [(Asp-Gua) IL@PEG-SiO2 in the synthesis
of 7e.

4. Conclusion
In this research a novel multi-layered bio based organic- inorganic nanohybrid
synthesized simply and characterized by different techniques. Its catalytic activity examined
for the synthesis of two class of interesting heterocycles that are bis(2,3-dihydroquinazolin-
4(1H)-one) derivatives and tricarboxamides through pseudo five-component condensations in
aqueous heated and solvent and heat free media, respectively. Performing the reaction under
green media, obtaining the desired products without any by-product formation, simple work-
up procedure, high yields, short reaction times, in addition with preparing a vast range of
potentially pharmaceutically-active heterocycles, and recovery and reusability of the products
without loss of activity are some highlighted features of the reported protocol.
Acknowledgments
The authors express their gratitude for financial support from Alzahra University.
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