Green and efficient one-pot synthesis of 2,3-dihydroquinazolin-4(1H)-ones and their anthelmintic studies

Article abstract of DOI:10.1080/00397911.2019.1639754

A facile and highly efficient one-pot synthesis of 2,3-dihydroquinazolin-4(1H)-ones derivatives has been developed by the condensation of anthranilamide with aldehydes using sulfonic acid functionalized l-Proline?Fe₃O₄ nanoparticles as a catalyst. The advantages of this protocol are easy recovery and reusability of the catalyst besides simple work-up procedure and short reaction time. In addition, the anthelmintic activities of some selective compounds were investigated and it was found that 2-phenyl-2,3-dihydroquinazolin-4(1H)-one exhibited profound anthelmintic activity against two helminth models.

Full text of DOI:10.1080/00397911.2019.1639754

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: https://www.tandfonline.com/loi/lsyc20
Green and efficient one-pot synthesis of
2,3-dihydroquinazolin-4(1H)-ones and their
anthelmintic studies
George Kupar Kharmawlong, Ridaphun Nongrum, Bhusan Chhetri, Jims
World Star Rani, Noimur Rahman, Arun Kumar Yadav & Rishanlang
Nongkhlaw
To cite this article: George Kupar Kharmawlong, Ridaphun Nongrum, Bhusan Chhetri, Jims
World Star Rani, Noimur Rahman, Arun Kumar Yadav & Rishanlang Nongkhlaw (2019): Green
and efficient one-pot synthesis of 2,3-dihydroquinazolin-4(1H)-ones and their anthelmintic studies,
Synthetic Communications, DOI: 10.1080/00397911.2019.1639754
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https://doi.org/10.1080/00397911.2019.1639754
Green and efficient one-pot synthesis of
2,3-dihydroquinazolin-4(1H)-ones and their
anthelmintic studies
George Kupar Kharmawlonga, Ridaphun Nongruma, Bhusan Chhetrib,
Jims World Star Rania, Noimur Rahmana, Arun Kumar Yadavb, and
Rishanlang Nongkhlawa
aDepartment of Chemistry, Centre for Advances Studies, North-Eastern Hill University, Shillong, India;
bDepartment of Zoology, North-Eastern Hill University, Shillong, India
ABSTRACT
ARTICLE HISTORY
Received 13 April 2019
A facile and highly efficient one-pot synthesis of 2,3-dihydroquinazo-
lin-4(1H)-ones derivatives has been developed by the condensation
of anthranilamide with aldehydes using sulfonic acid functionalized
L-Proline@Fe3O4 nanoparticles as a catalyst. The advantages of this
protocol are easy recovery and reusability of the catalyst besides
simple work-up procedure and short reaction time. In addition, the
anthelmintic activities of some selective compounds were investi-
gated and it was found that 2-phenyl-2,3-dihydroquinazolin-4(1H)-
one exhibited profound anthelmintic activity against two helminth
models.
KEYWORDS
2,3-Dihydroquinazolin-
4(1H)-ones; anthranilamide;
chlorosulfonic acid;
functionalized organo-
nanocatalyst; magnetic
nanocatalyst
GRAPHICAL ABSTRACT
CONTACT Rishanlang Nongkhlaw
rlnongkhlaw@nehu.ac.in
Department of Chemistry, Centre for Advances
Studies, North-Eastern Hill University, Umshing, Mawlai, Shillong 793022, India.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
Supplemental data for this article can be accessed on the publisher’s website.
ß 2019 Taylor & Francis Group, LLC

2
G. K. KHARMAWLONG ET AL.
Introduction
The development of a simple, efficient, and environmentally benign process in organic syn-
thesis is in great demand, in recent years. Multicomponent reactions (MCRs) have emerged
as an attractive strategy for synthetic chemists, due to the fact that products can be easily
obtained in a single step, thereby, reducing the consumption of solvents, catalysts, and
energy besides minimizing the generation of waste. In addition, the utilization of a catalyst
having high recyclability feature promotes a more economical and environmental friendly
benign protocol.
Quinazolinones constitute a very important heterocyclic core in various organic mole-
cules having diverse biological activities. 2,3-dihydroquinazolin-4(1H)-ones, in particu-
lar, have received notable attention because of their wide range of biological
and pharmaceutical activities, such as antifungal,[1] anti-inflamatory,[2] antimicrobial,[3]
anticonvulsant,[4] analgesic,[5] antibacterial,[6] anticancer,[7] and diuretic.[8] Some bio-
logically active compounds are shown below, in which (E)-3-(4-(3-(4-chlorophenyl)acry-
loyl)phenyl)-1-methyl-2,3-dihydroquinazolin-4(1H)-one exhibited ulcerogenic activity[9]
and 3-(2-(4-(4-fluorobenzoyl)piperidin-1-yl)ethyl)quinazoline-2,4(1H,3H)-dione (ketan-
serin) showed a positive serotonergic activity.[10]
Biologically active 2,3-dihydroquinazolin-4(1H)-ones
Taking into account their biological significance, several strategies have been reported
for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones. Generally, the simplest and effi-
cient methods for their synthesis involves the cyclo-condensation of 2-aminobenzamide
with aromatic aldehydes in presence of various salts such as CuCl2,[11] InCl3,[12]
ZrCl4,[13] TiCl4/Zn,[14] NH4Cl,[15] and acids such as trichloroacetic acid,[16] succini-
mide-N-sulfonic acid,[17] 2-morpholinoethanesulfonic acid,[18] and p-toluenesulfonic
acid[19] as catalysts.
For green and sustainable approaches, ionic liquids,[20–22] nanocrystalline sulfated zir-
conia[23] and PEG-400[24] have been employed for the preparation of these derivatives.
Organo-catalysts such as L-proline,[25] chiral organo-catalyst,[26] etc. have also been
reported for the synthesis of a wide range of 2,3-dihydroquinazolin-4(1H)-ones. Lately,
organic compound encapsulated on magnetic nanoparticles have received paramount
attention, due to the various advantages it offers. Earlier, we have reported the synthesis
of magnetic nanoparticles Fe2O3@SiO2 encapsulated with thiamine hydrochloride[27–29]
and employed it as an efficient catalyst for the synthesis of benzo[b]pyran and spiro
compounds. Similarly, a novel basic catalyst 3-methylaminopropyl-functionalized Fe3O4
nanoparticles (Fe3O4@MAP nanoparticles) was also prepared and utilized for the

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Scheme 1. Synthetic pathway for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones.
synthesis of [1,3]oxazines compounds,[30] In continuation, with our on-going work, we
report herein the synthesis of 2,3-dihydroquinazolin-4(1H)-ones using L-Proline N-
Sulfonic acid functionalized magnetic nanoparticles as a green and efficient organo-
nanocatalyst.
Results and discussion
A two-component condensation reaction, consisting of anthranilamide and aromatic
aldehydes, was carried out in the presence of a catalytic amount of sulfonic acid func-
tionalized L-Proline@Fe3O4 in ethanol to effectively yield 2,3-dihydroquinazolin-4(1H)-
ones (Scheme 1).
First, the L-proline coated Fe3O4 nanoparticles (Fe3O4@L-proline) was synthesized by
chemical co-precipitation of ferric and ferrous salt solution in the presence of L-proline
using ammonium hydroxide as a precipitating agent. The Fe3O4@L-proline thus
obtained was further functionalized by condensing it with chlorosulfonic acid. The
resultant product, i.e., L-proline sulfonic acid functionalized nanoparticles (Fe3O4@L-
proline-SO3H) was then characterized using Fourier transform infrared (FT-IR) spec-
troscopy, powder X-ray diffraction (XRD), transmission electron microscope (TEM),
field emission scanning electron microscope (FE-SEM), energy-dispersive X-ray spec-
troscopy (EDS), thermogravimetric analysis (TGA), and vibrating sample magnetometry
(VSM). The FT-IR spectrum of L-proline, Fe3O4@L-proline, and Fe3O4@L-proline-SO3H
is given in Figure 1. The peaks observed at 1124 cmꢀ1 and 655 cmꢀ1 in L-proline (a)
corresponds to the twisting and rocking mode of N–H and CH2 of the pyrrolidine ring,
respectively. A peak at 1155 cmꢀ1 in Fe3O4@L-proline (b) indicates the presence of the
organic moiety (L-proline) embedded on Fe3O4 nanoparticles. The L-proline N-sulfonic
acid functionalized magnetic nanoparticles (c) showed a peak at 1628 cmꢀ1, 1108 cmꢀ1
and 602 cmꢀ1 corresponding to the C¼O, S¼O, and Fe–O stretching frequencies,
respectively, indicating the immobilization of the organic moiety on the magnetic nano-
particles. The powder XRD data of Fe3O4@L-Proline (a) and Fe3O4@L-Proline-SO3H (b)
is given in Figure 2. The peaks obtained at 2h ¼ 30.1ꢁ, 35.6ꢁ, 43.3ꢁ, 53.6ꢁ, 57.4ꢁ, 63.1ꢁ
corresponding to (220), (311), (400), (422), (511), (440) planes, respectively, reveals that
the crystalline structure of the Fe3O4 nanoparticles are retained in both a and b.
The size of the sulfonic acid functionalized Fe3O4@L-proline nanoparticles were calcu-
lated using Debye Scherrer equation and the average size was found to be 17.44 nm.
Transmission electron microscopy (TEM) images of the prepared catalyst reveals that
the size of the particles ranges between 5 and 20 nm (Figure 3), which further substanti-
ates the calculated size. The surface morphology of the catalyst was characterized using

4
G. K. KHARMAWLONG ET AL.
Figure 1. FT-IR spectra of (a) L-proline, (b) Fe3O4@L-proline, and (c) Fe3O4@L-proline-SO3H.
311
220
440
b
400
400
511
422
311
220
30
440
422 511
a
20
40
50
60
70
2q (degree)
Figure 2. Powder-XRD of (a) Fe3O4@L-proline and (b) Fe3O4@L-proline-SO3H.
field emission scanning electron microscopy (FE-SEM) technique, and it was observed
that the nanoparticles are non-uniform in nature (Figure 4). The energy-dispersive X-
ray spectroscopy (EDS) of the nanoparticles displayed the presence of Fe, S besides C
and O which confirmed the formation of the target catalyst (supplementary).
To ascertain the stability of the catalyst, a thermal gravimetric analysis (TGA) of the
catalyst was performed and it was found that the catalyst was stable up to 240 ꢁC,
beyond which, the proline moiety starts to decompose (Figure 5). The weight loss
occurring up to 240 ꢁC may be attributed to the elimination of the adsorbed water and
other solvents from the surface of the catalyst. Similarly, the weight loss observed within

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Figure 3. TEM images of Fe3O4@L-proline-SO3H at (a) lower and (b) higher magnification.
Figure 4. FE-SEM images of Fe3O4@L-proline-SO3H at (a) lower and (b) higher magnification.
Figure 5. TGA graph of Fe3O4@L-proline-SO3H.

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G. K. KHARMAWLONG ET AL.
60
50
a
b
c
40
30
20
10
0
−10
−20
−30
−40
−50
−60
−15000 −10000 −5000
0
5000 10000 15000
Applied field (Oe)
Figure 6. VSM curve of (a) Fe3O4, (b) Fe3O4@L-proline, and (c) Fe3O4@L-proline-SO3H.
Table 1. Optimization of catalyst loading in the reaction.
Sl. No
Amount of catalyst (mg)
Time (min)
Yielda (%)
1
2
3
4
5
6
7
8
–
2
4
6
8
10
12
14
40
30
30
20
15
10
10
10
Trace
50
80
93
95
96
96
96
aIsolated yield.
Bold represents the optimized parameter with maximum yield of the products.
300–600 ꢁC corresponds to the decomposition of the organic moiety (L-proline-N-sul-
fonic acid) of the prepared catalyst.
Vibrating-sample magnetometer (VSM) analysis (Figure 6) of the Fe3O4 nanoparticles
(a), Fe3O4@L-proline (b), and Fe3O4@L-proline-SO3H (c) showed a saturation magnet-
ization value of 55.12, 43.63, and 37.66 emu/g, respectively. The decrease in the mag-
netic properties of the sulfonic acid functionalized Fe3O4@L-proline may be associated
with the presence of organo-coated layer on the Fe3O4 nanoparticles.
The catalytic activity of nano-Fe3O4@L-proline-SO3H was explored for the synthesis
of 2,3-dihydroquinazolin-4(1H)-ones. Initially, a model reaction comprising of benzalde-
hyde (1.0 mmol) and 2-aminobenzamide (1.0 mmol) was studied for the optimization of
the amount of catalyst and solvent. The results are represented in Table 1. It was found
that only trace of the product was obtained in the absence of the catalyst. However, on
addition of the catalyst, the yield of the product increased considerably, and it was
found out that 10 mg of the catalyst gave the best yield in minimum reaction time.
Further, increase in the amount of the catalyst did not show any significant change in
the yield of the products.

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Table 2. Optimization of reaction condition using different catalysts and solvents.
Sl. No
Catalyst
Solvent
Yielda (%)
Time (min)
1
2
3
4
5
6
7
8
–
EtOH
EtOH
EtOH
EtOH
H2O
EtOH
EtOH/H2O
MeOH
CH3CN
Toluene
Trace
45
60
56
90
96
90
90
68
40
30
25
25
15
10
20
22
40
30
L-proline
Fe3O4
Fe3O4@SiO2
Fe3O4@L-proline-SO3H
Fe3O4@L-proline-SO3H
Fe3O4@L-proline-SO3H
Fe3O4@L-proline-SO3H
Fe3O4@L-proline-SO3H
Fe3O4@L-proline-SO3H
9
10
20
aIsolated yield.
Bold represents the optimized parameter with maximum yield of the products.
100
90
80
70
60
50
40
30
20
20
30
40
50
60
70
Temperature (°C)
Figure 7. Effect of temperature on the synthesis of 2,3-dihydroquinazolin-4(1H)-ones.
Using the optimized amount of the catalyst, the model reaction was investigated in
different solvents such as water, ethanol, methanol, water–ethanol (1:1) mixture, aceto-
nitrile, and toluene to select a suitable reaction media (Table 2). The results indicated
that optimum yield of the product was obtained with ethanol, at a shorter reaction
time. It was also observed that with the increase of temperature, the yield of the product
also increases and the optimum yield was obtained at 50 ꢁC (Figure 7).
To increase the scope of the reaction, various substituted aromatic aldehydes were
used (Table 3). It was observed that, with electron withdrawing substituents, the reac-
tion was completed within a shorter reaction time as compared to those with electron
donating substituents. On completion of the reaction (monitored by TLC), the catalyst
was separated from the reaction mixture with the help of an external magnet. It was
then washed with ethanol followed by acetone and dried in the oven at 60 ꢁC before
reusing for the next reaction. The recycled catalyst did not show much alteration in its
activity even after five runs (Table 4). Studies were also carried out by replacing the aro-
matic aldehyde with aliphatic aldehydes under similar reaction condition. However, it
was observed that only traces of the corresponding products were formed even at higher
temperature.

8
G. K. KHARMAWLONG ET AL.
Table 3. Fe3O4@L-proline-SO3H catalyzed one-pot synthesis of 2,3-dihydroquinazolin-4(1H)-ones.
Entry
(R)
Product
Time (min)
Yield (%)a
1
2
3
4
5
6
7
8
H
4-OH
4-Br
4-F
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
10
15
20
10
10
12
15
10
10
8
10
15
10
15
15
12
96
92
96
96
96
95
90
92
94
95
96
92
96
96
96
95
4-Cl
4-OEt
4-CH3
4-OCH3
4-NO2
3-Cl
3-Br
4-OH,3-OMe
2-Cl
9
10
11
12
13
14
15
16
1-Napthaldehyde
3,4-OCH3
4-NMe2
aIsolated yield.
Table 4. Reusability of the catalyst.
Amount of catalyst
after recycled (mg)
No. of runs
Product
Time (min)
Yielda (%)
1st
3a
3a
3a
3a
3a
10
9
8
8
6
10
10
10
10
10
96
93
93
92
87
2nd
3rd
4th
5th
aIsolated yield.
The plausible reaction pathway for the formation of 2,3-dihydroquinazolin-4(1H)-
ones can be rationalized via the activation of the carbonyl carbon of benzaldehyde by
protonation from the sulfonic acid proton of the catalyst, thereby enhancing the nucleo-
philic attack by nitrogen lone pair. The conjugate base then abstracts the nitrogen pro-
ton which eventually leads to the removal of water via the E1cB mechanism. Further,
cyclization leads to the formation of C–N bond, thereby leading to a fused six-mem-
bered ring product (Scheme 2).
Anthelmintic studies
The prevalence of intestinal helminth infection remains staggeringly high in tropical
and sub-tropical condition. Helminth infections are not normally fatal, but heavy worm
burden may result in severe adverse effects, like malnutrition, anorexia, anemia, and
retarded growth.[31] Children are most affected with worm burden, over 267 million
preschool age and over 568 million school-age children are in need of treatment and
preventive interventions.[32] Rise in report of anthelmintic resistance from all over the
world has alarmed new drug development programs. More importantly, reduced efficacy
of broad spectrum anthelmintic albendazole against intestinal helminth, Ascaris lumbri-
coides in school children has raised deep concern.[33]
Anthelmintic screening of six dihydroquinazolinones derivatives was carried out and
it was found that one of the derivative namely 2-phenyl-2,3-dihydroquinazolin-4(1H)-
one exhibited activity at all test concentrations against both Raillietina and Syphacia

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Scheme 2. Mechanistic pathway proposed for the synthesis of compounds 3(a–p).
obvelata helminths species (Table 5). 2-phenyl-2,3-dihydroquinazolin-4(1H)-one treated
against Raillietina sp. at 800 mg/mL showed mortality at 5.78 0.36 h as compared with
1 mg/mL praziquantel (PZQ) at 6.51 0.24 h and for S. obvelata 11.14 0.23 h compared
with 1 mg/mL albendazole (ALZ) at 16.56 0.18 h. Bromo substituted derivatives were
more efficacious than fluoro or chloro substituent and dimethoxy derivative was more
effective as compared to dimethyl amino substituted. At 800 mg/mL, all derivatives have
significant mortality; however, at 200 mg/mL, much reduced mortality was recorded and
dose dependence predominates, though it varies with derivatives and helminth test
models. Interestingly the nature of substituent (electron donating or withdrawing) and
the positions of substituent were vital to achieve desired efficacy.[34,35]
Experimental
Experimental reagents and solvents were obtained from Merck, Alfa aesar and sigma
Aldrich and were used without further purification. Infrared spectra of the compounds
and catalyst were recorded in Perkin Elmer FT-IR 550 spectrophotometer using KBr
1
disk. H and 13C NMR spectra were recorded in Bruker Avance II DRX 400 spectrom-
eter. Mass spectra were recorded on WATERS (ZQ-4000) mass spectrometer. Powder
XRD of the catalyst was recorded in Explorer-GNR. All the melting points were
recorded in Optics Technology digital melting point apparatus and are uncorrected. A
transmission electron microscopic (TEM) image of the catalyst was recorded on trans-
mission electron microscopic make JEOL, model: JEM 2100. FE-SEM images of the
nanoparticles were recorded on Field Emission Scanning Electron Microscope make
Zeiss, Model: Sigma. All reactions were monitored by using a 0.2 mm thickness pre-alu-
minum sheet thin-layer chromatography (TLC).
General procedure for the synthesis of Fe3O4@L-proline
Fe3O4@L-proline was prepared as reported[36] with minor modification. Briefly, 5 mmol
of FeCl3.6H2O and 2.5 mmol of FeSO4 were dissolved separately in 50 mL deionized

10
G. K. KHARMAWLONG ET AL.
Table 5. Anthelmintic activity of 2,3-dihydroquinazolin-4(1H)-ones at different test concentration.
Syphacia obvelata
mean
Syphacia obvelata
mean
Raillietina sp. mean Raillietina sp. mean
Compounds Concentration
paralysis SEM
mortality SEM
paralysis SEM
mortality SEM
3a
3e
3d
3k
3o
3p
200 mg
400 mg
800 mg
200 mg
400 mg
800 mg
200 mg
400 mg
800 mg
200 mg
400 mg
800 mg
200 mg
400 mg
800 mg
200 mg
400 mg
800 mg
1 mg/ mL
1 mg/ mL
–
8.98 0.50
6.87 0.34
5.06 0.41
14.02 0.36
12.43 0.29
9.88 0.37
10.74 0.18
9.26 0.36
7.96 0.34
10.39 0.49
8.36 0.19
7.51 0.53
10.76 0.45
8.93 0.44
8.38 0.24
13.06 0.47
11.26 0.44
10.16 0.28
–
10.31 0.50
7.81 0.46
5.78 0.36
15.69 0.42
13.89 0.40
11.16 0.32
12.34 0.27
10.43 0.51
8.76 0.26
11.91 0.48
9.54 0.10
8.63 0.54
12.49 0.39
10.49 0.50
9.26 0.29
15.01 0.59
13.46 0.47
11.01 0.37
–
17.23 0.22
11.78 0.21
9.81 0.18
21.39 0.27
18.75 0.23
15.91 0.20
18.91 0.16
15.44 0.20
12.86 0.19
18.33 0.22
14.77 0.16
12.51 0.16
19.85 0.17
17.61 0.24
14.36 20.22
21.40 0.20
19.97 0.16
17.63 0.14
15.27 0.20
–
20.03 0.18
13.36 0.20
11.14 0.23
24.04 0.35
20.85 0.23
18.06 0.24
21.73 0.22
17.76 0.26
14.76 0.19
20.98 0.28
16.99 0.14
14.64 0.18
22.53 0.29
20.22 0.29
16.12 0.23
24.20 0.16
22.73 0.22
19.66 0.26
16.56 0.18
–
ALZ
PZQ
CONTROL
4.96 0.23
26.08 0.37
6.51 0.24
31.68 0.48
41.55 0.67
45.88 0.61
water and then mixed together with vigorous stirring at room temperature. 2 mmol of
L-proline and NH4OH (25%, 15 mL) were added until a black suspension appears and
the pH was raised to 11. The mixture was reflux at 100 ꢁC for 6 h under stirring condi-
tion. The black suspension was removed by magnetic decantation, washed with water
and methanol several times and then finally with ethanol. The solid product was dried
in the oven at 60 ꢁC.
General procedure for the synthesis of Fe3O4@L-proline-SO3H
1.0 g of Fe3O4@L-proline was ultra-sonicated in 10 mL of dry hexane for 30 min and
then stirred at room temperature. 0.2 mL of chlorosulfonic acid was added drop-wise
and the reaction mixture was further stirred for 1 h for the complete removal of the
HCl gas. The Fe3O4@L-proline-N-sulfonic acid nanoparticles were separated by an exter-
nal magnet and then washed several times with toluene and deionized water. The coated
nanoparticles was dried in the oven at 60 ꢁC.[37]
General procedure for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones
To a mixture of 2-aminobenzamide (1 mmol) and aromatic aldehyde (1 mmol) in 10 mL
of ethanol, 0.010 g of the catalyst was added. The reaction mixture was stirred at 50 ꢁC
for appropriate time. When the reaction has completed (monitored by TLC), the cata-
lyst was removed by an external magnet and the product was filtered and recrystallized
from hot ethanol. The recovered catalyst was washed and dried in the oven at 60 ꢁC
before reusing for the next reaction.

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2-phenyl-2,3-dihydroquinazolin-4(1H)-one: 3a
White solid, melting point: 220-222 ꢁC [Lit.[38] 217-219 ꢁC]. FT-IR (KBr): ꢀmax 3305,
1
3187, 3064, 1655, 1614, 1587, 1453 cmꢀ1. H-NMR (400 MHz, DMSO-d6): d 8.30 (s,
1 H), 7.60–7.23 (m, 7 H), 7.12 (s, 1 H), 6.72–6.68 (m, 2 H), 5.74 (s, 1 H). 13C-NMR
(100 MHz, DMSO-d6): d 163.57, 147.84, 141.54, 133.30, 128.43, 128.29, 127.32, 126.82,
117.04, 114.89, 114.35, 66.50. calc. MS (ESI) m/z: 224. Found MS (ESI) m/z:
225 [M þ 1]þ.
Methods for anthelmintic studies
2,3-dihydroquinazolin-4(1H)-ones and its derivatives are freshly prepared and were
screened for anthelmintic activity against Raillietina echinobothridia a fowl cestode and
S. obvelata a pin worm nematode in mice. Derivatives were selected on the basis of side
chain with electron donating (dimethoxy and dimethylamino) and electron withdrawing
(Cl, F, and Br) groups.[39,40] Raillietina echinobothridia were collected from intestine of
freshly slaughtered domestic chicken and adult S. obvelata obtain from cecum of nec-
ropsied mice. The collected worms were washed with warm 0.9% phosphate-buffered
saline (PBS) and further maintained at 37 1 ꢁC. Test parasite was divided into five
groups (5 in each) in triplicates, helminths incubated in PBS serve as control whereas
praziquental and albendazole at 1 mg/mL as a standard group for cestode and nema-
tode, respectively. 2,3-dihydroquinazolin-4(1H)-one derivatives at a concentration of
200, 400, and 800 mg were selected for in vitro studies.[41] Each group was dissolved
with a minimum amount of 1% DMSO (dimethyl sulfoxide) and the volume was
adjusted to 5 mL. Helminth viability was determined through physical mobility test,
body movement was recorded in regular interval under a light microscope to determine
paralysis and mortality time.[42]
Statistical analysis
All data are represented as mean standard error of mean (SEM). Data were analyzed
using one-way ANOVA at significance level of p ˂ 0.05.
Conclusions
We have successfully developed a green and efficient protocol for the synthesis of 2,3-
dihydroquinazolin-4(1H)-ones, starting from aldehydes and 2-aminobenzamide using
Fe3O4@L-proline-SO3H as the reusable catalyst. The notable features of the protocol
include shorter reaction time, excellent yield of the products, easy separation and recyc-
lability of the catalyst. The in vitro study of 2,3-dihydroquinazolin-4(1H)-ones revealed
that 2-phenyl-2,3-dihydroquinazolin-4(1H)-one showed a positive result for the treat-
ment of helminths against Railietina sp. and S. obvelata when compared with stand-
ard drugs.
Full experimental detail can be found via the “Supplementary Content” section of
this article.

12
G. K. KHARMAWLONG ET AL.
Acknowledgments
The authors acknowledge SAIF-NEHU, Department of chemistry, NEHU, Dr L. Robindro Singh,
Department of Nanotechnology for Powder XRD data analysis. The authors also acknowledge the
CIF, IIT Guwahati for VSM and FE-SEM analysis.
Funding
The authors acknowledge the financial support from DST-SERB [sanctioned no.: EEQ/
2016/000646].
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