Superfast synthesis, antibacterial and antifungal studies of halo-aryl and heterocyclic tagged 2,3-dihydro-1H-inden-1-one candidates

Article abstract of DOI:10.1007/s00706-021-02772-0

We describe a successful synthesis of halo-aryl and heterocyclic labelled 2,3-dihydro-1H-inden-1-one derivatives, as well as their antibacterial and antifungal properties. A total of 15 derivatives from 2,3-dihydro-1H-inden-1-one were synthesized by grind

Full text of DOI:10.1007/s00706-021-02772-0

Monatshefte für Chemie - Chemical Monthly
https://doi.org/10.1007/s00706-021-02772-0
ORIGINAL PAPER
Superfast synthesis, antibacterial and antifungal studies of halo‑aryl
and heterocyclic tagged 2,3‑dihydro‑1H‑inden‑1‑one candidates
Rahul A. Shinde1 · Vishnu A. Adole1 · Bapu S. Jagdale1 · Thansing B. Pawar2
Received: 18 May 2020 / Accepted: 20 April 2021
© Springer-Verlag GmbH Austria, part of Springer Nature 2021
Abstract
We describe a successful synthesis of halo-aryl and heterocyclic labelled 2,3-dihydro-1H-inden-1-one derivatives, as well
as their antibacterial and antifungal properties. A total of 15 derivatives from 2,3-dihydro-1H-inden-1-one were synthesized
by grinding, stirring, and ultrasound irradiation methods. The fndings revealed that the ultrasound technique is increasingly
satisfactory in terms of time and synthetic performance. The synthesized compounds have been tested for their antimicrobial
activities against two Gram-positive (Staphylococcus aureus and Bacillus subtilis) and two Gram-negative bacteria (Escheri-
chia coli and Proteus vulgaris), and also two fungal agents (Aspergillus niger and Candida albicans). Most of the compounds
were found to exert potent antibacterial action with broad-spectrum antibacterial activity. Likewise, few compounds were
revealed to have potent antifungal properties against A. niger and C. albicans. The synthesized compounds were character-
ized by FT-IR, 1H NMR, 13C NMR, and HRMS spectral techniques.
Graphic abstract
Keywords 2,3-Dihydro-1H-inden-1-one · Antibacterial · Antifungal · Ultrasound irradiation
Introduction
ensure their long-term survival. The worldwide problem
of antimicrobial resistance is rapidly becoming a major
health problem [1–4]. It has been postulated that the
resistance of microbes to current antimicrobials could
be overcome by developing new synthetic organic com-
pounds by updating the current antimicrobial concept,
and discovering new agents with promising activity and
structure [5–7]. 2,3-Dihydro-1H-inden-1-one is a fused
molecule containing cyclopentanone and a benzene ring.
A literature survey reveals that compounds containing a
2,3-dihydro-1H-inden-1-one structure exhibit the great
profle of pharmacological properties [8]. Some noticeable
examples include activities like anticancer [9, 10], anti-
infammatory [11, 12], antioxidant [13], anti-Alzheimer
disease [14], etc. Likewise, the presence of a halogen atom
Microorganisms are living things that have ability to rep-
licate, fourish, and spread rapidly and productively. They
can adjust to their environments and evolve in ways that
* Bapu S. Jagdale
dr.jagdalebs@gmail.com
1
Department of Chemistry, Mahatma Gandhi Vidyamandir’s
Arts, Science and Commerce College, Manmad, (Afliated
to Savitribai Phule Pune University, Pune), Nashik 423 104,
India
2
Department of Chemistry, Mahatma Gandhi Vidyamandir’s
Loknete Vyankatrao Hiray Arts, Science and Commerce
College Panchavati, (Afliated to Savitribai Phule Pune
University, Pune), Nashik 422 003, India
Vol.:(0123456789)
1 3

R. A. Shinde et al.
in the drug molecule can change its properties dramati-
cally. Especially, fuorinated compounds possess a broad
range of medicinal properties. Some examples of biologi-
cally active compounds containing above said properties
are depicted in Fig. 1. The excellent activities shown by
them are anticancer, anaesthetics, antibacterial, antiviral,
antimalarial, antidepressants, and many more [15, 16]. On
the other hand, the applications of heterocyclic compounds
have been expanded in the last decade. Heterocyclic com-
pounds are known to display tremendous therapeutic appli-
cations [17, 18].
vulgaris), and two fungal agents (Aspergillus niger and
Candida albicans).
Results and discussion
Chemistry
We began our investigation to determine the most efec-
tive method for synthesizing the titled compounds. Three
environmentalfriendly synthetic methods were addressed;
grinding, stirring, and ultrasound irradiation. The reaction
of 2,3-dihydro-1H-inden-1-one with thiophene-2-carbalde-
hyde was selected as a standard reaction for the explora-
tion of the better synthetic method. Ethanol and KOH were
chosen as solvent and base, respectively. We performed
three parallel reactions; grinding, stirring, and ultrasound
strategies. To our credit, all three reactions yielded the
corresponding (E)-2-(thiophen-2-ylmethylene)-2,3-dihy-
dro-1H-inden-1-one in excellent yield within 15 minutes.
More importantly, the ultrasound irradiation required less
reaction time and furnished more yield of the product as
compared to the other two methods. Then, we shifted our
emphasis on solvent comparison (Table 1). For that, we
varied the solvents from non-polar to polar solvents. The
outcome revealed that the polar protic solvents are bet-
ter at giving more yield and that with less reaction time
except water (Table 1). The non-polar solvents required
long reaction run and also resulted in lesser yields as com-
pared to polar aprotic and polar protic solvents. To mark
the importance of KOH as a base, we performed same
Green chemistry has carved out a distinct niche for
itself in synthetic organic chemistry. The green chemistry
felds like microwave [19, 20], ultrasound [21–24], grind-
stone chemistry [25, 26], benign reaction media [27–31],
nanochemistry [32–37], and ionic liquids [38, 39] are
tremendously used to develop environmental-friendly
approaches. Antimicrobial agents become very interest-
ing to research when looking at these important aspects
of modern times. In light of all these crucial points, we
would like to report the expeditious synthesis, antibacte-
rial, and antifungal studies of halo-aryl and heterocyclic
tagged 2,3-dihydro-1H-inden-1-one derivatives. To the
best of our knowledge, this is the frst report on combined
investigation on green synthesis, antibacterial and anti-
fungal screening of 2-arylideneindanones. In the present
investigation, synthesized compounds have been tested
for their biological activities against two Gram positive
(Staphylococcus aureus and Bacillus subtilis) and two
Gram negative bacteria (Escherichia coli and Proteus
Fig. 1 Some biologically important intermediates and medicinal agents
1 3

Superfast synthesis, antibacterial and antifungal studies of halo-aryl and heterocyclic…
Table 1 Solvent study for the synthesis of 3aa
Entry
Solvent
Grinding
Time/min
Stirring
Ultrasonic irradiation
Yield/%b
Time/min
Yield/%b
Time/min
Yield/%b
1
2
3
4
5
6
7
8
9
10
PhCH3
MeCN
CH2Cl2
THF
CHCl3
H2O
50
35
40
45
40
65
45
18
25
15
60
70
70
65
72
45
65
80
60
85
45
32
42
38
40
50
40
15
25
10
60
75
72
68
76
48
70
82
62
86
40
30
38
40
30
50
30
12
24
09
62
75
75
70
78
50
74
88
62
97
CCl4
MeOH
AcOH
EtOH
aReaction conditions: dihydro-1H-inden-1-one (10 mmol), thiophene-2-carbaldehyde (10 mmol), KOH (10 mmol), 5 cm3 solvent at r.t
bIsolated yield of pure product
Table 2 Base study for the synthesis of 3aa
Entry
Base
Grinding
Time/min
Stirring
Ultrasonic
irradiation
Yield/%b
Time/min
Yield/%b
Time/min
Yield/%b
1
2
3
4
K2CO3
Piperidine
NaOH
45
50
20
15
60
65
85
85
40
50
20
10
60
67
85
86
38
40
15
09
70
70
94
97
KOH
aReaction conditions: dihydro-1H-inden-1-one (10 mmol), thiophene-2-carbaldehyde (10 mmol), base (10 mmol), 5 cm3 ethanol, at r.t
bIsolated yield of pure product
reaction using NaOH, piperidine, and K2CO3 (Table 2).
However, none of the used bases could compete with KOH
in terms of synthetic efciency. Only NaOH came close to
matching KOH’s synthetic results, but KOH outperformed
NaOH in terms of yield and reaction time. This afrmed
that the best solvent is none other than ethanol and base
as KOH. As all three methods were afording product for-
mation within 15 minutes, we tested all three methods for
all remaining reactions in ethanol solvent and KOH as a
base. The scope and validity of the synthetic methods were
tested for variety of heterocyclic and halogenated aromatic
aldehydes (Table 3). All three methods were best at their
task. In all instances the product yield was greater than
80%. The highest yield was recorded for the compounds
3g and 3h under ultrasound irradiation conditions. The
ultrasound approach was more accomplished in terms of
1 3

R. A. Shinde et al.
Table 3 Substrate scope and physicochemical data of the synthesized compounds and comparison between grinding, stirring, and ultrasonic
irradiationa
Entry
Het/Ar
Grinding
Time/min
Stirring
Ultrasonic irradiation
M.p. /°C
Yield/%b
85
Time/min
Yield/%b
86
Time/min
9
Yield/%b
3a
3b
15
17
10
12
97
93
122–124
118–120
93
93
10
3c
20
22
92
90
17
13
92
92
15
10
92
92
110–112
126–128
3d
3e
3f
12
13
91
93
10
11
90
92
08
10
95
95
153–155
182–184
3g
3h
15
12
95
96
08
08
96
92
08
08
97
97
154–158
163–166
3i
13
90
13
91
12
94
132–134
3j
22
15
92
85
13
10
94
87
10
07
96
88
152–154
163–165
3k
3l
12
13
83
89
10
11
85
92
08
10
86
94
186–188
162–164
3m
3n
3o
18
15
81
90
10
10
80
91
08
10
85
94
184–186
120–122
aReaction conditions: dihydro-1H-inden-1-one (10 mmol), thiophene-2-carbaldehyde (10 mmol), KOH (10 mmol), 5 cm3 ethanol, at r.t
bIsolated yield of pure product
1 3

Superfast synthesis, antibacterial and antifungal studies of halo-aryl and heterocyclic…
reaction yield and time by examining all reactions under
three reaction conditions (Table 3).
by the metabolically active live cells. If blue color does not
change, it indicates the absence of metabolically live cells.
The MIC values of synthesized compounds were evaluated
and the results are depicted in Table 5 which clearly stresses
the diferential sensitivity pathogens toward the synthesized
compounds. The MIC results are expressed as the mean val-
ues of three independent experiments.
Biological studies
Disc difusion assay
Disc difusion method were employed for the screening of
the antibacterial and antifungal activities and the results are
summarized in Table 4. The synthesized compounds were
tested for their biological activities against two Gram-posi-
tive (S. aureus and B. subtilis) and two Gram-negative bac-
teria (E. coli and P. vulgaris), and also two fungal agents (A.
niger and C. albicans). The compounds 3c, 3d, 3f, and 3o
were found to apply strong antibacterial action with broad-
spectrum antibacterial activity. The compounds 3b and 3g
were exerted strong antifungal action against A. niger and C.
albicans. Besides, other compounds have additionally shown
great antimicrobial potential. The assays were performed
in triplicate using Chloramphenicol and Amphotericin-B as
standards. The compounds 3h, 3l, and 3n have been found to
exert null efect on both bacterial and fungal agents.
Structure–activity relationship studies
The various aromatic and hetero-aromatic aldehydes were
exactly chosen to present diverse electronic condition to
the molecules (Fig. 2 and Table 3). Therefore, various fve
membered and six membered hetero-aromatic aldehydes
containing oxygen, nitrogen, and sulfur atoms were precisely
selected. Besides, aromatic aldehydes containing chloro and
fuoro substituents were also selected to test their antimi-
crobial action. Most of the synthesized compounds were
exhibited wide range of antibacterial and antifungal activity.
Amongst heterocyclic linked synthesized compounds; those
containing sulfur and nitrogen atoms were exerted better
antimicrobial activity. The compounds 3c, 3d, 3f, and 3o
were found as strong antibacterial agents with broad-spec-
trum antibacterial activity. Especially the compound bearing
4-pyridyl ring (3f) was linked with the stronger antibacterial
activity. It has exerted broad-spectrum antibacterial poten-
tial. Other compound which has exhibited nearly same anti-
bacterial action is compound 3d which contains thiazole
system. The compound 3a was active against three bacterial
agents and inactive against E. coli. The heterocyclic linked
Resazurin microtiter plate assay
The resazurin microtiter plate assay (REMA) was used for
checking the minimum inhibitory concentration (MIC) [29].
The REMA is a simple and inexpensive which is a routine
method for checking cellular viability. The oxidation–reduc-
tion mechanism involves the reduction of blue color to pink
Table 4 Antibacterial
Entry
E. coli
P. vulgaris
S. aureus
B. subtilis
A. niger
C. albicans
and antifungal activity of
synthesized compounds 3a–3o
3a
–
–
+++
+++
+++
++++
+++
++++
++
+++
–
+++
+++
+++
++
++
+++
++
++++
++
–
++
++
++
–
++
+++
–
–
–
–
3b
+++
–
–
–
3c
+++
++++
+++
++++
–
–
–
++
–
–
+
–
3d
3e
–
3f
+++
–
–
–
++
–
–
–
–
++
+++++
NA
–
–
3g
+++
–
–
++
+++
–
++
–
+++
–
–
–
–
–
++
–
–
3h
–
–
3i
3j
+++
–
–
+
–
+++
+++++
NA
3k
3l
3m
+
–
3n
3o
++
+++++
NA
++
+++++
NA
+++
NA
++++
Chloramphenicol
Amphotericin-B
NA
++++
+ ≤5 mm zone, ++=5–10 mm zone, +++≥10–15 mm zone, ++++≥15–20 mm, +++++≥20 mm,
–=No inhibition, NA=Not applicable
1 3

R. A. Shinde et al.
Table 5 Minimum inhibitory
concentration (MIC) of
Compounds
E. coli
P. vulgaris
S. aureus
B. subtilis
A. niger
C. albicans
synthesized compounds 3a–3o
3a
>250
>250
62.5
62.5
62.5
31.25
>250
>250
>250
>250
>250
>250
250
62.5
62.5
62.5
31.25
62.5
31.25
125
>250
>250
>250
>250
>250
250
>250
62.25
1.95
62.5
>250
125
62.5
125
125
31.25
62.5
62.5
125
>250
125
125
62.5
>250
125
>250
>250
>250
>250
62.5
>250
>250
>250
>250
>250
125
>250
>250
NA
3b
3c
>250
>250
>250
>250
31.25
>250
>250
>250
31.25
>250
250
3d
62.5
3e
>250
31.25
>250
>250
>250
>250
>250
>250
>250
>250
125
3f
3g
3h
3i
3j
125
3k
62.5
>250
250
>250
62.5
3.9
3l
3m
3n
>250
125
1.95
>250
31.25
NA
3o
Chloramphenicol
Amphotericin-B
1.95
NA
NA
NA
NA
1.95
1.95
Three synthetic methods grinding, stirring, and ultra-
sound method have been deliberately employed in which
ultrasound irradiation method has been found to be more
superior in terms of yield and reaction time. The ample
substrate scope, simple reaction conditions, excellent
yields, and high purity of the products are the key high-
lights of the present synthetic strategies. The antibacte-
rial potential of the synthesized compounds was screened
against against two Gram-positive bacteria namely S.
aureus and B. subtilis and two Gram-negative bacteria
namely E. coli and P. vulgaris whereas antifungal activity
against two fungal agents namely A. niger and C. albi-
cans. Most of the synthesized compounds were found as
good antibacterial and antifungal agents. Especially, the
compounds 3c, 3d, 3f, and 3o were found to apply strong
antibacterial activity with a wide range of antibacterial
action. On the other hand, the compounds 3b and 3g were
applied solid antifungal activity against A. niger and C.
albicans.
Fig. 2 General structures (A and B) for synthesized compounds
indanones were found to be less potent antifungal agents
than simple aromatic linked indanones. On the contrary,
former were more potent antibacterial agents than latter.
Amongst aromatic aldehydes, the compound 3g has exerted
strong antifungal action against both fungal agents A. niger
and C. albicans. The only heterocyclic linked synthesized
compound to be active against both fungal agents was com-
pound 3b. The compounds containing chorine and fuorine
atoms (3g and 3k) were good against both fungal agents.
Comparing the compounds 3j and 3o, the compound 3o was
far better in terms of antibacterial and antifungal activity.
The presence of methyl group is linked with reduction in
antimicrobial potential. The chorine substituents are pow-
erful antibacterial and antifungal at C-2 and C-3 positions.
Experimental
The chemicals (Make—Sigma Aldrich, SD Fine Chemicals,
and Avra synthesis) were purchased from Sigma laboratory,
Nashik with a high purity and were used as such without
any purifcation. The NMR experiment was performed on
sophisticated multinuclear FT-NMR spectrometer model
Advance-II (Bruker). The compounds were dissolved in
chloroform-d or DMSO-d6 and the chemical shifts were
reported in ppm relative to tetramethylsilane (TMS). The
reactions were monitored by thin-layer chromatography
Conclusion
In summary, we presented eco-friendly synthesis and
antimicrobial screening of fifteen halo-aryl and hetero-
cyclic labelled 2,3-dihydro-1H-inden-1-one derivatives.
1 3

Superfast synthesis, antibacterial and antifungal studies of halo-aryl and heterocyclic…
using Merck Aluminum TLC plate, silica gel coated with
fuorescent indicator F254. All the glass apparatus were
cleaned and dried in oven prior to use.
of KOH. The alkaline mixture was exposed to ultrasound
irradiation at room temperature until the formation of prod-
ucts (checked by TLC). The reaction mass was allowed to
cool at room temperature, then added into beaker containing
ice-cold water, acidifed, fltered, dried and recrystallized
using ethanol solvent.
Procedures for the synthesis of compounds 3a–3o
The general scheme for the synthesis of compounds 3a–3o
(Note: In all three methods, the reaction mixture was not
acidifed when one of the reactant was either 2-pyridinecar-
boxaldehyde or 4-pyridinecarboxaldehyde.)
is depicted in Scheme 1.
Grinding method
(E)‑2‑(Thiophen‑2‑ylmethylene)‑2,3‑dihydro‑1H‑in‑
den‑1‑one (3a, C14H10OS) Pale yellow colour; yield 97%;
m.p.: 122–124 °C; FT-IR (KBr): ꢀ = 3059.10, 2873.94,
1672.28, 1469.76 1415.75, 1371.39, 1251.80, 1201.65,
1099.43, 1029.99, 952.84, 908.47, 831.32, 781.17, 725.23,
663.51, 524.64, 472.56, 424.34, 358.76 cm−1; 1H NMR (500
MHz, CDCl3): δ=3.97–3.93 (m, 2H), 7.18 (dd, J=5.0, 3.7
Hz, 1H), 7.47–7.40 (m, 2H), 7.61–7.55 (m, 2H), 7.66–7.61
(m, 1H), 7.92–7.87 (m, 2H) ppm; 13C NMR (126 MHz,
CDCl3): δ=193.89, 149.07, 139.92, 138.56, 134.58, 133.16,
132.76, 130.57, 128.23, 126.62, 127.69, 126.26, 124.34,
32.35 ppm; HRMS (ESI): m/z calcd. 227.0530 ([M+H]+),
found 227.0531.
A mixture of 2,3-dihydro-1H-inden-1-one (1, 10 mmol), and
hetero-aromatic/aromatic aldehyde (2, 10 mmol), 0.5 cm3
ethanol were taken in a mortar and pestle. To this reaction
mixture, equimolar amount of KOH was added. The colour
of the solution turned into dark yellow/brown after addition
of KOH. The alkaline mixture was grinded at room tem-
perature until the formation of products (checked by TLC).
The reaction mass was allowed to cool at room temperature,
then added into beaker containing ice-cold water, acidifed,
fltered, dried, and recrystallized using ethanol solvent.
Stirring method
(E)‑2‑(Thiophen‑3‑ylmethylene)‑2,3‑dihydro‑1H‑in‑
den‑1‑one (3b, C14H10OS) Pale yellow colour; yield 93%;
m.p.: 118–120 °C; FT-IR (KBr): ꢀ = 3059.10, 2941.44,
1660.71, 1591.27, 1415.75, 1367.53 1313.52, 1244.09,
1199.72, 1109.07, 1068.56, 985.62, 904.61, 825.53, 775.38,
661.58, 570.93, 516.92, 385.76, 368.40 cm−1; 1H NMR (500
MHz, CDCl3): δ=4.03–3.93 (m, 2H), 7.47–7.34 (m, 3H),
7.56 (td, J=7.4, 1.2 Hz, 1H), 7.62 (td, J=7.4, 1.2 Hz, 1H),
7.70 (m, 2H), 7.93–7.88 (m, 1H) ppm; 13C NMR (126 MHz,
CDCl3): δ=194.44, 149.27, 138.43, 137.76, 134.58, 133.40,
129.64, 128.32, 127.70, 127.37, 126.70, 126.22, 124.37,
32.38 ppm.
A mixture of 2,3-dihydro-1H-inden-1-one (1, 10 mmol),
and hetero-aromatic/aromatic aldehyde (2, 10 mmol), 5 cm3
ethanol were taken in a 25 cm3 Pyrex fask. To this reaction
mixture, equimolar amount of KOH was added. The colour
of the solution turned into dark yellow/brown after addi-
tion of KOH. The alkaline mixture was stirred on magnetic
stirrer at room temperature until the formation of products
(checked by TLC). The reaction mass was allowed to cool
at room temperature, then added into beaker containing ice-
cold water, acidifed, fltered, dried and recrystallized using
ethanol solvent.
Ultrasound method
(E)‑2‑[(3‑Methylthiophen‑2‑yl)methylene]‑2,3‑dihy‑
dro‑1H‑inden‑1‑one (3c, C15H12OS) Yellow colour; yield
92%; m.p.: 110–112 °C; FT-IR (KBr): ꢀ =3059.10, 1662.64,
1593.20, 1413.82, 1367.53, 1313.52, 1242.16, 1199.72,
1109.07, 1066.64, 983.70, 904.61, 825.53, 775.38, 719.45,
661.58, 570.93, 518.85, 381.91 cm−1; 1H NMR (500 MHz,
CDCl3): δ=2.48 (s, 3H), 3.96–3.90 (m, 2H), 7.00 (d, J=5.1
A mixture of 2,3-dihydro-1H-inden-1-one (1, 10 mmol),
and hetero-aromatic/aromatic aldehyde (2, 10 mmol), 5 cm3
ethanol were taken in a 25 cm3 Pyrex fask. To this reaction
mixture, equimolar amount of KOH was added. The colour
of the solution turned into dark yellow/brown after addition
Scheme 1
1 3

R. A. Shinde et al.
Hz, 1H), 7.46–7.39 (m, 1H), 7.50 (d, J=5.1 Hz, 1H), 7.65–
7.54 (m, 2H), 7.90 (m, 1H), 7.97 (m, 1H) ppm; 13C NMR
(126 MHz, CDCl3): δ = 193.96, 149.14, 143.20, 138.67,
134.38, 133.90, 131.68, 131.06, 129.12, 127.58, 126.20,
124.96, 124.27, 32.45, 14.58 ppm; HRMS (ESI): m/z calcd.
241.0687 ([M+H]+), found 241.0682.
163–166 °C; FT-IR (KBr): ꢀ =3059.10, 3008.95, 1662.64,
1593.20, 1413.82, 1369.46, 1315.45, 1242.16, 1199.72,
1109.07, 1068.56, 1020.34, 983.70, 906.54, 825.53, 777.31,
1
719.45, 661.58, 570.93, 516.92, 426.27, 383.83 cm−1; H
NMR (500 MHz, CDCl3): δ = 4.03 (d, J = 2.2 Hz, 2H),
7.47–7.42 (m, 1H), 7.49 (t, J=2.2 Hz, 1H), 7.63–7.51 (m,
3H), 7.65 (dd, J=7.6, 2.0 Hz, 1H), 7.75 (d, J=2.0 Hz, 1H),
7.92 (d, J=7.6 Hz, 1H) ppm; 13C NMR (126 MHz, CDCl3):
δ=193.89, 149.33, 137.70, 136.30, 135.41, 135.04, 133.69,
133.25, 131.81, 131.14, 130.93, 129.73, 127.94, 126.25,
124.63, 32.24 ppm; HRMS (ESI): m/z calcd. 289.0186
([M+H]+), found 289.0179.
(E)‑2‑[(4‑Methylthiazol‑5‑yl)methylene]‑2,3‑dihydro‑1H‑in‑
den‑1‑one (3d, C14H11NOS) Pale yellow colour; yield 92%;
m.p.: 122–128 °C; FT-IR (KBr): ꢀ = 3057.21, 1668.98,
1610.51, 1413.82, 1387.45, 1319.51, 1267.53, 1202.70,
1135.50, 1064.99, 987.42, 906.13, 835.50, 782.35, 729.55,
663.51, 535.50, 466.71, 352.70 cm−1; 1H NMR (500 MHz,
CDCl3): δ = 8.89 (s, 1H), 7.94–7.88 (m, 2H), 7.64 (m,
J=7.6, 1.2 Hz, 1H), 7.57 (dt, J=7.6, 1.2 Hz, 1H), 7.48–7.41
(m, 1H), 3.91–3.87 (m, 2H), 2.70 (s, 3H) ppm; 13C NMR
(126 MHz, CDCl3): δ = 188.52, 152.87, 149.31, 144.03,
133.68, 130.06, 129.82, 123.25, 123.11, 121.53, 119.77,
118.45, 27.37, 11.25 ppm.
(E)‑2‑[(2,3‑Dihydrobenzofuran‑5‑yl)methylene]‑2,3‑dihy‑
dro‑1H‑inden‑1‑one (3i, C18H14O2) Bright yellow colour;
yield 94%; m.p.: 132–134 °C; FT-IR (KBr): ꢀ = 3059.10,
1662.64, 1593.20, 1413.82, 1369.46, 1315.45, 1201.65,
1111.00, 1066.64, 983.70, 906.54, 825.53, 777.31, 719.45,
661.58, 379.98 cm−1; 1H NMR (500 MHz, CDCl3): δ=3.28
(t, J=8.7 Hz, 2H), 3.99 (d, J=2.1 Hz, 2H), 4.65 (t, J=8.7
Hz, 2H), 6.86 (d, J=8.3 Hz, 1H), 7.47–7.38 (m, 1H), 7.48
(dd, J = 8.3, 1.9 Hz, 1H), 7.58–7.51 (m, 2H), 7.60 (td,
J=7.3, 1.2 Hz, 1H), 7.64 (t, J=2.1 Hz, 1H), 7.90 (m, 1H)
ppm; 13C NMR (126 MHz, CDCl3): δ = 194.45, 161.81,
149.48, 138.33, 134.39, 134.29, 132.25, 131.76, 128.28,
128.19, 127.58, 127.54, 126.09, 124.28, 109.97, 71.95,
32.63, 29.40 ppm.
(E)‑2‑(Pyridin‑2‑ylmethylene)‑2,3‑dihydro‑1H‑inden‑1‑one
(3e, C15H11NO) White colour; yield 95%; m.p.: 153–155
°C; FT-IR (KBr): ꢀ =3094.74, 1669.64, 1596.27, 1417.46,
1367.26, 1317.38, 1245.74, 1215.75, 1117.38, 1069.46,
1026.64, 985.21, 956.64, 915.75, 817.38, 782.27, 729.24,
663.51, 527.46, 472.27, 370.63 cm−1; 1H NMR (500 MHz,
CDCl3): δ=8.59–8.55 (m, 1H), 7.78–7.76 (m, 1H), 7.57 (m,
1H), 7.44 (m, 2H), 7.38 (td, J=7.7, 1.9 Hz, 2H), 7.23 (m,
1H), 7.16 (m, 1H), 4.11–4.15 (m, 2H) ppm.
(E)‑2‑[(5‑Methylfuran‑2‑yl)methylene]‑2,3‑dihydro‑1H‑in‑
den‑1‑one (3j, C15H12O2) Yellow colour; yield 96%; m.p.:
152–154 °C; FT-IR (KBr): ꢀ =3315.63, 3059.10, 2949.16,
1670.35, 1598.99, 1492.90, 1465.90, 1415.75, 1369.46,
1317.38, 1280.73, 1249.87, 1201.65, 1105.21, 1070.49,
1029.99, 981.77, 952.84, 908.47, 829.39, 781.17, 721.38,
663.51, 522.71, 470.63, 405.05 cm−1; 1H NMR (500 MHz,
CDCl3): δ=7.88 (d, J=7.6 Hz, 1H), 7.60 (m, 1H), 7.55 (m,
1H), 7.43–7.41 (m, 1H), 7.41–7.39 (m, 1H), 6.69 (d, J=3.4
Hz, 1H), 6.17 (d, J=3.4 Hz, 1H), 4.03–3.99 (m, 2H), 2.43 (s,
3H) ppm; 13C NMR (126 MHz, CDCl3): δ=194.05, 156.27,
150.93, 149.76, 138.74, 134.20, 131.00, 127.37, 126.13,
124.12, 120.26, 118.50, 109.36, 32.40, 14.20 ppm; HRMS
(ESI): m/z calcd. 225.0915 ([M+H]+), found 225.0916.
(E)‑2‑(Pyridin‑4‑ylmethylene)‑2,3‑dihydro‑1H‑inden‑1‑one
(3f, C15H11NO) White colour; yield 95%; m.p.: 182–184
°C; FT-IR (KBr): ꢀ =3101.65, 1673.59, 1602.75, 1473.56,
1415.75, 1378.09, 1269.89, 1201.65, 1109.43, 1034.95,
950.84, 912.41, 839.32, 783.53, 731.33, 667.51, 531.34,
481.17, 425.23, 353.51 cm−1; 1H NMR (500 MHz, CDCl3):
δ = 8.48–8.41 (m, 2H), 8.41–8.35 (m, 2H), 7.80 (m, 1H),
7.62 (m, 1H), 7.52 (td, J=7.5, 1.3 Hz, 1H), 7.45 (m, 1H),
7.33 (m, 1H), 4.06–4.08 (m, 2H) ppm.
(E)‑2‑(2,3‑Dichlorobenzylidene)‑2,3‑dihydro‑1H‑inden‑1‑one
(3 g, C16H10Cl2O) Yellow colour; yield 97%; m.p.: 154–158
°C; FT-IR (KBr): ꢀ =3248.13, 1676.88, 1612.49, 1417.68,
1257.59, 1163.08, 1097.50, 972.12, 810.10, 732.95, 582.50,
534.28, 464.84, 441.70 cm−1; 1H NMR (500 MHz, CDCl3):
δ = 3.94 (d, J = 2.3 Hz, 2H), 7.29 (m, 1H), 7.69–7.38 (m,
5H), 7.92 (m, 1H), 7.99 (t, J=2.3 Hz, 1H) ppm; 13C NMR
(126 MHz, CDCl3): δ = 193.56, 149.55, 137.96, 137.83,
135.92, 134.99, 134.10, 134.03, 130.85, 129.88, 127.92,
127.88, 127.16, 126.21, 124.68, 31.69 ppm.
(E)‑2‑(4‑Fluorobenzylidene)‑2,3‑dihydro‑1H‑inden‑1‑one
(3 k,C16H11FO) Yellow colour; yield 88%; m.p.: 190–194
°C; FT-IR (KBr): ꢀ =3057.17, 1666.50, 1597.06, 1415.75,
1369.46, 1317.38, 1247.94, 1201.65, 1105.21, 1066.64,
1022.27, 981.77, 952.84, 906.54, 827.46, 779.24, 719.45,
663.51, 520.78, 470.63, 366.48 cm−1; 1H NMR (500 MHz,
CDCl3): δ=4.06–4.01 (m, 2H), 7.20–7.12 (m, 2H), 7.48–
7.41 (m, 1H), 7.57 (m, 1H), 7.76–7.60 (m, 4H), 7.92 (m,
1H) ppm; 13C NMR (126 MHz, CDCl3): δ=194.26, 164.35,
162.35, 149.49, 137.97, 134.71, 134.29, 134.27, 132.71,
(E)‑2‑(3,4‑Dichlorobenzylidene)‑2,3‑dihydro‑1H‑inden‑1‑one
(3 h, C16H10Cl2O) Pale yellow colour; yield 97%; m.p.:
1 3

Superfast synthesis, antibacterial and antifungal studies of halo-aryl and heterocyclic…
132.66, 132.60, 131.70, 131.67, 127.79, 126.19, 124.51,
116.25, 116.07, 32.34 ppm.
(m, 1H), 6.78 (m, 1H), 6.56 (m, 1H), 4.06 (d, J = 2.1 Hz,
2H) ppm; 13C NMR (126 MHz, CDCl3): δ=194.02, 152.32,
149.80, 145.38, 138.50, 134.46, 132.58, 127.49, 126.20,
124.25, 120.07, 116.64, 112.67, 32.36 ppm; HRMS (ESI):
m/z calcd. 211.0759 ([M+H]+), found 211.0761.
(E)‑2‑[(1‑Methyl‑1H‑pyrrol‑2‑yl)methylene]‑2,3‑dihy‑
dro‑1H‑inden‑1‑one (3l, C15H13NO) Yellow colour; yield
86%; m.p.: 186–188 °C; FT-IR (KBr): ꢀ = 3057.17,
1672.28, 1415.75, 1371.39, 1249.87, 1201.65, 1101.35,
1029.99, 950.91, 908.47, 831.32, 781.17, 723.31, 663.51,
522.71, 470.63, 381.91 cm−1; 1H NMR (500 MHz, CDCl3):
δ = 7.88 (d, J = 7.8 Hz, 1H), 7.65 (m, 1H), 7.60–7.57 (m,
1H), 7.55 (m, 1H), 7.41 (m, 1H), 6.87 (m, 1H), 6.76 (m, 1H),
6.36–6.29 (m, 1H), 3.87–3.84 (m, 2H), 3.81 (s, 3H) ppm;
13C NMR (126 MHz, CDCl3): δ=193.97, 149.03, 139.00,
134.02, 129.95, 129.93, 127.44, 126.08, 124.04, 120.90,
114.94, 110.06, 34.45, 32.76 ppm; HRMS (ESI): m/z calcd.
224.1075 ([M+H]+), found 224.1072.
Biological methods
Disk difusion assay
The antibacterial and antifungal potential of synthesized
compounds was evaluated as per the previous reported
method. Briefy, each compound dried paper disk (What-
man flter paper No.1) contained synthesized compounds
50 mm3 (0.001 mM) [29]. Each disk was then placed on the
surface of the sterile solidifed agar which was spread with
inoculums of bacterial and fungal cultures (0.5 McFarland
Standard). Chloramphenicol and Amphotericin-B was used
as standard (0.001 mM) for antibacterial and antifungal
activities respectively. The plates were kept in refrigerator
for difusion for 1 h and then transferred to the incubator
at 37 °C for 24 h. After incubation, the zones around the
discs were measured by the zone scale (Himedia Pvt. Ltd.
Mumbai).
(E)‑2‑[4‑(Pyrrolidin‑1‑yl)benzylidene]‑2,3‑dihydro‑1H‑in‑
den‑1‑one (3m, C20H19NO) Yellow colour; yield 94%; m.p.:
162–164 °C; FT-IR (KBr): ꢀ =3057.17, 1670.35, 1467.83,
1415.75, 1371.39, 1317.38, 1249.87, 1201.65, 1103.28,
1029.99, 952.84, 908.47, 829.39, 781.17, 723.31, 663.51,
522.71, 470.63, 358.76 cm−1; 1H NMR (500 MHz, CDCl3):
δ = 7.90 (d, J = 7.6 Hz, 1H), 7.65 (m, 1H), 7.63–7.51 (m,
4H), 7.44–7.37 (m, 1H), 6.61 (m, 2H), 4.00 (d, J=1.9 Hz,
2H), 3.41–3.33 (m, 4H), 2.10–2.01 (m, 4H) ppm; 13C NMR
(126 MHz, CDCl3): δ = 194.33, 149.38, 148.79, 138.89,
135.36, 133.71, 133.01, 129.27, 127.35, 125.96, 124.05,
122.68, 111.89, 47.56, 32.80, 25.48 ppm; HRMS (ESI): m/z
calcd. 290.1544 ([M+H]+), found 290.1544.
Resazurin microtiter assay
The resazurin microtiter assay (REMA) plate assay was car-
ried out as described elsewhere [29]. Briefy, 100 mm3 of
7H9-S (containing 0.1% casitone, and 0.5% glycerol and
supplemented with oleic acid, albumin, dextrose, and cata-
lase) broth was dispensed in each well of a sterile fat-bottom
96-well plate, and serial twofold dilutions of each synthe-
sized compounds were prepared directly in the plate. One
hundred micro liters of inoculums was added to each well.
Sterile cold water was added to all perimeter wells to avoid
evaporation during the incubation. The plate was covered,
sealed in a plastic bag, and incubated at 37 °C for 24 h. After
incubation, 30 mm3 of resazurin solution (0.01% in sterile
deionized water) was added to each well, and the plate was
re-incubated for 4 h. A change in color from blue to pink
indicated the growth of bacteria, and the MIC was defned as
the lowest concentration of drug that prevented this change
in color. The drug concentration ranges used were as fol-
lows: for synthesized compounds, 0.048–500 µg/cm3 and for
Chloramphenicol and Amphotericin-B, 0.048–500 µg/cm3.
(E)‑2‑[(1H‑Pyrrol‑2‑yl)methylene]‑2,3‑dihydro‑1H‑in‑
den‑1‑one (3n, C14H11NO) Yellow color; yield 85%; m.p.:
184–186 °C; FT-IR (KBr): ꢀ =3059.10, 1668.43, 1597.06,
1415.75, 1369.46, 1317.38, 1247.94, 1201.65, 1107.14,
1068.56, 1026.13, 981.77, 908.47, 827.46, 779.24, 721.38,
663.51, 520.78, 470.63, 381.91 cm−1; 1H NMR (500 MHz,
CDCl3): δ=9.05 (s, 1H), 7.89 (ddd, J=7.7, 1.3, 0.7 Hz, 1H),
7.67 (m, 1H), 7.63–7.53 (m, 2H), 7.47–7.39 (m, 1H), 7.08
(m, 1H), 6.76 (s, 1H), 6.46–6.40 (m, 1H), 3.92–3.88 (m,
2H) ppm; 13C NMR (126 MHz, CDCl3): δ=194.06, 148.87,
138.94, 134.14, 129.38, 129.25, 127.56, 126.11, 124.06,
123.66, 122.91, 114.89, 111.99, 32.37 ppm.
(E)‑2‑(Furan‑2‑ylmethylene)‑2,3‑dihydro‑1H‑inden‑1‑one
(3o, C14H10O2) Yellow color; yield 94%; m.p.: 120–122
°C; FT-IR (KBr): ꢀ =3776.62, 3059.10, 2947.23, 1668.43,
1598.99, 1492.90, 1465.90, 1415.75, 1369.46, 1319.31,
1247.94, 1201.65, 1107.14, 1068.56, 1028.06, 981.77,
952.84, 908.47, 829.39, 781.17, 721.38, 663.51, 522.71,
472.56, 403.12, 360.69 cm−1; 1H NMR (500 MHz, CDCl3):
δ=7.89 (dt, J=7.6, 1.0 Hz, 1H), 7.63 (m, 1H), 7.62–7.58
(m, 1H), 7.55 (m, 1H), 7.46 (t, J=2.1 Hz, 1H), 7.44–7.38
Supplementary Information The online version contains supplemen-
tary material available at https://doi.org/10.1007/s00706-021-02772-0.
Acknowledgements Authors acknowledge central instrumentation
1
facility, Savitribai Phule Pune University, Pune for H NMR, 13C
NMR and HRMS spectral analyses, and central instrumentation center,
1 3

R. A. Shinde et al.
KTHM College for FT-IR spectral analysis. Authors are thankful to
Arts, Science and Commerce College, Manmad for providing neces-
sary research facilities. The authors are grateful to Mr. Mahesh Patil
for providing antimicrobial results. The authors gratefully acknowledge
Dr. Aapoorva P. Hiray for his motivation for the research.
19. Dudley GB, Richert R, Stiegman AE (2015) Chem Sci 6:2144
20. Bose AK, Manhas MS, Ghosh M, Shah M, Raju VS, Bari SS,
Newaz SN, Banik BK, Chaudhary AG, Barakat KJ (1991) J Org
Chem 56:6968
21. Adole VA, Jagdale BS, Pawar TB, Sagane AA (2020) S Afr J
Chem 73:35
22. Rao SS, Reddy CV, Dubey PK (2014) Org Chem Int Article ID
403803:5 pages
References
23. Crawford DE (2017) Beilstein J Org Chem 13:1850
24. Cravotto G, Cintas P (2006) Chem Soc Rev 35:180
25. Khaskel A, Gogoi P, Barman P, Bandyopadhyay B (2014) RSC
Adv 4:35559
1. Ventola CL (2015) Pharm Ther 40:277
2. Prestinaci F, Pezzotti P, Pantosti A (2015) Pathog Glob Health
109:309
26. Thangamani A (2017) J Appl Adv Res 2:78
27. Gawande MB, Bonifácio VD, Luque R, Branco PS, Varma RS
(2013) Chem Soc Rev 42:5522
3. Ayukekbong JA, Ntemgwa M, Atabe AN (2017) Antimicrob
Resist Infect Control 6:47
28. Adole VA, Pawar TB, Jagdale BS (2020) J Chin Chem Soc 67:306
29. Adole VA, More RA, Jagdale BS, Pawar TB, Chobe SS (2020)
ChemistrySelect 5:2778
4. Qu J, Huang Y, Lv X (2019) Front Microbiol 10:2240
5. Li B, Webster TJ (2018) J Orthop Res 36:22
6. Jackson N, Czaplewski L, Piddock LJ (2018) J Antimicrob Chem-
other 73:1452
30. Chaturvedi D (2011) Curr Org Synth 8:438
31. Varma RS (2014) Green Chem 16:2027
7. Podolsky SH (2018) Palgrave Commun 4:1
8. Jung HJ, Noh SG, Park Y, Kang D, Chun P, Chung HY, Moon HR
(2019) Comput Struct Biotechnol J 17:1255
32. Satheesh A, Usha H, Visalakshi M, Rambabu T, Srinivas CV,
Kumar YV, Douglas SP (2017) Int J Eng Res & Tech 6:730
33. Naikwade A, Jagadale M, Kale D, Gajare S, Rashinkar G (2018)
Catal Lett 148:3178
9. Chanda D, Bhushan S, Guru SK, Shanker K, Wani ZA, Rah BA,
Luqman S, Mondhe DM, Pal A, Negi AS (2012) Eur J Pharm Sci
47:988
34. Vibhute SP, Mhaldar PM, Shejwal RV, Rashinkar GS, Pore DM
(2020) Tetrahedron Lett 61:151801
10. Hu J, Yan J, Chen J, Pang Y, Huang L, Li X (2015) MedChem-
Comm 6:1318
35. Sheng W, Yang Q, Weng J (2011) Curr Org Chem 15:3692
36. Adole VA, Pawar TB, Koli PB, Jagdale BS (2019) J Nanostruct
Chem 9:61
11. Shrestha A, Oh HJ, Kim MJ, Pun NT, Magar TB, Bist G, Choi H,
Park PH, Lee ES (2017) Eur J Med Chem 133:121
12. Xiao S, Zhang W, Chen H, Fang B, Qiu Y, Chen X, Chen L, Shu
S, Zhang Y, Zhao Y, Liu Z, Liang G (2018) Drug Des Dev Ther
12:887
37. Lim CW, Lee IS (2010) Nano Today 5:412
38. Kurane R, Jadhav J, Khanapure S, Salunkhe R, Rashinkar G
(2013) Green Chem 15:1849
39. Khanapure S, Jagadale M, Kale D, Gajare S, Rashinkar G (2019)
Aust J Chem 72:513
13. Tang CM, Zhong C, Liu ZY, Peng P, Liu XH, Sun X (2016) Eur
J Med Chem 113:63
14. Rampa A, Mancini F, De Simone A, Falchi F, Belluti F, Di Mar-
tino RM, Gobbi S, Andrisano V, Tarozzi A, Bartolini M, Cavalli
A (2015) Bioorg Med Chem Lett 25:2804
Publisher’s Note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional afliations.
15. Park BK, Kitteringham NR, O’Neill PM (2001) Annu Rev Phar-
macol Toxicol 41:443
16. Inoue M, Sumii Y, Shibata N (2020) ACS Omega 5:10633
17. Mendgen T, Steuer C, Klein CD (2012) J Med Chem 55:743
18. Dua R, Shrivastava S, Sonwane SK, Srivastava SK (2011) Adv
Biol Res 5:120
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