Synthesis and antimicrobial activities of chalcones and indole derived from acetyl pyridines

Article abstract of DOI:10.14233/ajchem.2018.21124

In the present study, chalcones and indole bearing nitrogen containing heterocyclic ring such as pyridine ring have been synthesized and characterized by elemental analysis and spectral studies. Attempts were made to prepare chacones via condensation of 2-acetyl pyridines/ 3-acetyl pyridines/4-acetyl pyridines with substituted benzaldehydes in presence of a number of different inorganic and organic bases. Out of different bases methanolic sodium hydroxide was found best both in terms of rate of reaction and percentage of yield. Synthesized chalcones and indoles were purified by flash column chromatography under nitrogen pressure. Purity of the isolated compounds was checked by HPLC. Compounds with HPLC purity of more than 98 % have been characterized and reported. Synthesized chalcones were tested against the bacteria strains Staphylococcus aureus and E. coli with reference to the standard drug ciprofloxacin at the concentration 1 μg/mL. Synthesized chalcones were further tested against the fungal strains Aspergillus Niger and Penicillium funiculosum with reference to the standard ketoconazole at the concentration 1 μg/mL.

Full text of DOI:10.14233/ajchem.2018.21124

Asian Journal of Chemistry; Vol. 30, No. 4 (2018), 883-888
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2018.21124
Synthesis and Antimicrobial Activities of Chalcones and Indole Derived from Acetyl Pyridines
1,*
1
2
S. SANTRA , B. JAT and P.K. SANTRA
1Department of Chemistry, JECRC University, Jaipur-303 905, India
2Therachem Research Medilab (India) Pvt. Ltd., Sitapura, Jaipur-302 022, India
*Corresponding author: E-mail: swapna.santra@jecrcu.edu.in
Received: 8 November 2017;
Accepted: 31 January 2018;
Published online: 28 February 2018;
AJC-18804
In the present study, chalcones and indole bearing nitrogen containing heterocyclic ring such as pyridine ring have been synthesized and
characterized by elemental analysis and spectral studies. Attempts were made to prepare chacones via condensation of 2-acetyl pyridines/
3-acetyl pyridines/4-acetyl pyridines with substituted benzaldehydes in presence of a number of different inorganic and organic bases.
Out of different bases methanolic sodium hydroxide was found best both in terms of rate of reaction and percentage of yield. Synthesized
chalcones and indoles were purified by flash column chromatography under nitrogen pressure. Purity of the isolated compounds was
checked by HPLC. Compounds with HPLC purity of more than 98 % have been characterized and reported. Synthesized chalcones were
tested against the bacteria strains Staphylococcus aureus and E. coli with reference to the standard drug ciprofloxacin at the concentration
1 µg/mL. Synthesized chalcones were further tested against the fungal strains Aspergillus niger and Penicillium funiculosum with reference
to the standard ketoconazole at the concentration 1 µg/mL.
Keywords: Acetyl pyridine, Benzaldehyde, Chalcone, Indole, Antibacterial activity, Antifungal activity.
INTRODUCTION
EXPERIMENTAL
Chalcones due to its diverse biological and pharmacological
activities have generated extensive scientific studies throughout
the world. Chalcones having substitution on two aryl rings
exhibit anticancer, antioxidant, anti-inflammatory, antimicro-
bial, antiulcer, antimalaria and many other activities [1-9].
Chalcones and their derivatives have also been seen to find
applications in large varieties of diverse areas such as artificial
sweeteners [10], scintillator [11], stabilizer against heat,
visible light, ultraviolet light and aging [12,13]. In agriculture,
chalcones are used to destroy phytopathogenic organisms [14].
Similarly in industry chalcones are also used in anti-sunburn
oil [15].
Indole nucleus is a biologically accepted pharmacophore
in medicinal compounds. Compounds bearing indole nucleus
exhibit wide spectrum of biological activities such as anti-
fungal, antimicrobial, antiviral, antitubercular, anticancer etc.
[16,17]. In the present study, it was thus been decided to
synthesize and characterize chalcones and indole bearing
nitrogen containing heterocyclic ring such as pyridine ring
with substitutions selected from -F, -NO2, -NH2 and to screen
the antibacterial and antifungal activity of the synthesized
compounds.
The organic solvents of spectral grade were used without
further purification.All key raw materials and the reagents used
in the synthesis were of LR grade and were procured from
standard sources. Reactions were monitored by TLC using
pre-coated TLC plates and by determining the mass of mole-
cular ion of desired molecule in the reaction mass. Silica gel
of mesh size 230-400 was used for purification by flash column
chromatography under nitrogen pressure. IR spectra were
recorded on Perkin-Elmer FT-IR Spectrum 2 using KBr pellets
and the values are presented in cm-1. The 1H NMR spectra of
the compounds were recorded on Bruker DPX 300 NMR spec-
trophotometer using TMS as an internal standard and the values
are expressed in δ ppm. The mass spectra of the compounds
were recorded on Agilent G1946 MSD Mass Spectrometer
using both positive and negative modes. Elemental analysis
(C, H and N) was carried out on a Perkin-Elmer 2400 CHN
analyzer. Purity was checked in Agilent 1260 series HPLC.
Synthesis of chalcones and indole
3-(4-Fluoro-3-nitro-phenyl)-1-pyridin-2-yl-prop-2-en-
1-one (1): To a stirred solution of 2-acetylpyridine (2.00 g,
16.52 mmol) in methanol (80 mL) was added 4-fluro-3-nitro-

884 Santra et al.
Asian J. Chem.
benzaldehyde (2.79 g, 16.52 mmol) at 0 °C followed by
addition of 3.30 mL of 1 N NaOH (0.13 g, 3.30 mmol). The
resultant reaction mixture was stirred for 12 h at room tempe-
rature. The progress of the reaction was monitored by TLC
(mobile phase: 70 % EtOAc in hexane). The reaction mixture
was cooled to 0 °C. 10 mL of 1 N HCl was added slowly to the
reaction mixture. The reaction mixture was further diluted
with distilled water (80 mL) and was stirred for 1 h. Desired
compound 3-(4-fluoro-3-nitro-phenyl)-1-pyridin-2-yl-prop-2-
en-1-one was slowly precipitated out. The compound was
filtered and isolated as an off white solid (yield 3.5 g, 77.88
0 °C followed by addition of 3.30 mL of 1 N NaOH (0.13 g,
3.30 mmol) solution. The resultant reaction mixture was stirred
for 12 h at 0 °C to room temperature. Progress of the reaction
was monitored by TLC (mobile phase: 80 % EtOAc in hexane).
The reaction mixture was cooled to 0 °C. 10 mL 1 N HCl was
added to the reaction mixture. The reaction mixture was diluted
with 80 mL distilled water. Reaction mixture was stirred for
1 h. 3-(2-Nitro-phenyl)-1-pyridin-4-yl-prop-2-en-1-one was
precipitated out as a reddish brown solid which was filtered
and dried under vacuum (yield 1.60 g, 38.09 %). Mass: 255.3
(M+1), 1H NMR in CDCl3 (value in δ): 8.76 (t, J = 3.00 Hz,
1H), 8.75-8.18 (m, 3H), 7.93-7.83 (m, 3H), 7.54-7.49 (m, 1H),
7.26 (s, 1H), 7.19 (t, J = 3.27 Hz, 1H).
%). HPLC purity: 99.11 %, Mass: 271.1 (M–1). IR (KBr, νmax
,
cm-1): 1698 (C=O), 1590 (C=N), 1532 (C=C quadrant of Ar),
1419 (CH=CH); 1H NMR in DMSO-d6 (value in δ): 8.80 (d, J
= 6.00 Hz, 1H), 8.39 (d, J = 2.10 Hz, 1H), 8.25 (d, J = 16.20
Hz, 1H), 8.18-8.02 (m, 3H), 7.86 (d, J = 15.90 Hz, 1H), 7.73-
7.67 (m, 1H), 7.45 (d, J = 9.00 Hz, 1H).
To stirred a solution of 3-(2-nitro-phenyl)-1-pyridin-4-
yl-prop-2-en-1-one (0.50 g, 1.97 mmol) in ethanol (20 mL)
was added iron dust (0.44 g, 7.87 mmol) at room temperature.
4 mL of 10 N HCl was added to the reaction mixture. The
resultant reaction mixture was heated and stirred for 12 h at
70 °C. The progress of the reaction was monitored by TLC
(mobile phase: 100 % EtOAc). The reaction mixture was allowed
to cool to room temperature and pH of reaction mixture was
adjusted to 9 by aqueous NH3. The reaction mixture was diluted
with distilled water (10 mL). The reaction mixture was extracted
with ethyl acetate (2 × 50 mL). Combined organic extract was
concentrated to afford a brown subject compound 1H-indol-
2-yl)-pyridine-4-yl-methanone (yield 0.4 g, 91 %). HPLC purity:
99.06 %, Mass: 221.1 (M–1), IR (KBr, νmax, cm-1): 3414 (C-NH),
1620 (C=O), 1594 (C=N), 1490 (C=C quadrant of Ar), 1424
3-(4-Fluoro-3-nitro-phenyl)-1-pyridin-3-yl-prop-2-en-
1-one (2): To a stirred solution of 3-acetylpyridine (1.50 g,
12.93 mmol) in 60 mL methanol was added 4-fluoro-3-nitro-
benzaldehyde (2.09 g, 12.39 mmol) at 0 °C, followed by addition
of 1 N NaOH (0.09 g, 2.47 mmol). The resultant reaction
mixture was stirred for 12 h at 0 °C to room temperature. Reac-
tion was monitored by TLC (mobile phase: 80 % EtOAc in
hexane). The reaction mixture was cooled to 0 °C, added slowly
1 N HCl (10 mL) and finally diluted with 80 mL distilled
water. After stirring of 1 h the compound 3-(4-fluoro-3-nitro-
phenyl)-1-pyridin-3-yl-prop-2-en-1-one was precipitated out
which was filtered and isolated as a pale yellow solid (yield
2.1 g, 62.29 %). HPLC purity: 99.06 %, Mass: 271.1 (M–1),
IR (KBr, νmax, cm-1): 1698 (C=O), 1582 (C=N), 1532 (C=C
quadrant of Ar), 1410 (CH=CH), 1H NMR in DMSO-d6: 9.15
(dd, J = 2.40 Hz, 0.90 Hz, 1H), 8.79 (dd, J = 4.80 Hz, 1.80
Hz, 1H), 8.32 (dt, J = 9.00 Hz, 1.80 Hz, 1H), 8.22 (dd, J =
7.50 Hz, 2.40 Hz, 1H), 7.91-7.85 (m, 1H), 7.60-7.58 (m, 2H),
5.80 (d, J = 4.80 Hz, 1H), 5.27 (t, J = 4.20 Hz, 1H).
3-(4-Fluoro-3-nitro-phenyl)-1-pyridin-4-yl-prop-2-en-
1-one (3): To a stirred solution of 4-acetylpyridines (2.0 g,
16.52 mmol) in methanol (80 mL) was added 4-fluro-3-nitro-
benzaldehyde (2.79 g, 16.52 mmol) at 0 °C followed by addi-
tion of 3.30 mL of 1 N NaOH (0.13 g, 3.30 mmol). The resultant
reaction mixture was stirred for 12 h at 0 °C to room tempe-
rature. The progress of the reaction was monitored by TLC
(mobile phase: 70 % EtOAc in hexane). The reaction mixture
was cooled to 0 °C. 10 mL of 1 N HCl was added slowly to the
reaction mixture. The reaction mixture was diluted by distilled
water (80 mL). The reaction mixture was stirred for 1 h. Subject
compound was slowly precipitated out as an off white solid.
Subject compound 3-(4-fluoro-3-nitro-phenyl)-1-pyridin-4-yl-
prop-2-en-1-one was filtered and isolated as an off white solid
(yield 3.80 g, 84.82 %). HPLC purity: 99.35 %, Mass: 271.1
(M–1), IR (KBr, νmax, cm-1): 1694 (C=O), 1592 (C=N), 1532
(C=C quadrant ofAr), 1428 (CH=CH), 1H NMR in DMSO-d6
(value in δ): 8.80 (d, J = 3.00 Hz, 2H), 8.21 (dd, J = 7.20 Hz,
2.10 Hz, 1H), 7.89-7.84 (m, 3H), 7.57 (dd, J = 11.40 Hz, 8.70
Hz, 1H), 5.81 (d, J = 4.80 Hz, 1H), 5.26 (t, J = 4.20 Hz, 1H).
(1H-Indol-2-yl)-pyridin-4-yl-methanone (4): To a stirred
solution of 4-acetylpyrdine (2 g, 16.52 mmol) in 60 mL metha-
nol was added 2-nitro-benzaldehyde (2.49 g, 16.52 mmol) at
1
(CH=CH), H NMR in DMSO-d6 (value in δ): 8.78 (d, J =
5.70 Hz, 2H), 8.57 (d, J = 8.70 Hz, 1H), 8.37-8.28 (m, 3H),
8.16-8.05 (m, 2H), 7.84 (t, J = 7.59 Hz, 1H), 7.67 (t, J = 7.87
Hz, 1H).
3-(2-Amino-phenyl)-1-pyridin-4-yl-propan-1-one (5):
To stirred a solution of 3-(-2-nitro-phenyl)-1-pyridin-4-yl-
prop-2-en-1-one (0.50 g, 1.97 mmol) as prepared above in
methanol (20 mL) was added Pd/C (0.42 g) at room tempe-
rature. Reaction mixture was stirred overnight at room tempe-
rature. The progress of the reaction was monitored by TLC
(mobile phase: 5 % MeOH in DCM). The reaction mixture
was filtered through celite bed and washed twice with MeOH.
The filtrate was concentrated and crude thus obtained was
purified by flash column chromatography (mobile phase: 0-
80 % EtOAc in n-hexane). Subject compound 3-(2-amino-
phenyl)-1-pyridin-4-yl-propan-1-one was isolated as a red
solid (yield: 0.12 g, 26.96 %). HPLC purity: 99.23 % Mass:
227 (M+1), IR (KBr, νmax, cm-1): 3373 (C-NH2), 1669 (C=O),
1604 (C=N), 1491 (C=C quadrant of Ar), 1414 (CH=CH), 1H
NMR in DMSO-d6 (value in δ): 8.95-8.90 (m, , 2H), 8.02-
7.99 (m, 2H), 7.42-7.37 (m, 3H), 6.45 (d, J = 6.01 Hz, 1H), 5.23
(br, s, 2H), 2.75 (t, J = 5.98 Hz, 2H), 2.13 (t, J = 8.99 Hz, 2H).
3-(2-Nitro-phenyl)-1-pyridin-4-yl-prop-2-en-1-ol (6):
To stirred a solution of 3-(2-nitro-phenyl)-1-pyridin-4-yl-prop-
2-en-1-one (0.50 g, 1.97 mmol) in methanol (20 mL) was
added NaBH4 (0.74 g, 19.68 mmol) at room temperature.
Reaction mixture was stirred overnight at room temperature.
The progress of the reaction was monitored by TLC (mobile
phase: 5 % MeOH in DCM). The reaction mixture was quenched
with water and was extracted with EtOAc (2 × 100 mL).
Combined organic extract was washed with brine, dried on

Vol. 30, No. 4 (2018)
Synthesis and Antimicrobial Activities of Chalcones and Indole Derived from Acetyl Pyridines 885
Na2SO4 and concentrated to get crude. Compound was purified
by flash column chromatography (mobile phase: 0-80 % EtOAc
in n-hexane). Desired compound 3-(2-nitro-phenyl)-1-pyridin-
4-yl-prop-2-en-1-ol was isolated as a brown solid (yield 0.10 g,
19.86 %). HPLC purity: 99.03 %, Mass: 257.3 (M+1), IR (KBr,
purity: 99.03 %, Mass: 257.3 (M+1), IR (KBr, νmax, cm-1): 3425
(O-H), 1610 (C=N), 1513 (C=C quadrant ofAr), 1424 (CH=CH),
1349 (N-O), 1H NMR in DMSO-d6 (value in δ): 8.63 (s, 1H),
8.48 (dd, J = 4.80 Hz, 1.50 Hz, 1H), 7.96-7.89 (m, 1H), 7.82-
7.77 (m, 2H), 7.66 (t, J = 7.35 Hz, 1H), 7.51 (t, J = 7.65 Hz,
1H), 7.42-7.37 (m, 1H), 7.00 (d, J = 14.76 Hz, 1H), 6.55 (dd,
J = 16.5 Hz, 5.70 Hz, 1H), 5.41 (d, 5.40 Hz, 1H), 1.98 (s, 1H).
3-(3-((2-Chloropyrrolo[2,1-f][1,2,4]triazin-4-yl)amino)-
phenyl)-1-(pyridin-2-yl)propan-1-ol (9): To a stirred solution
of 3-(3-aminophenyl)-1-(pyridin-2-yl)propan-1-ol ((0.2 g, 0.87
mmol) in 20 mL ethanol were added 2,4-dichloropyrrolo[2,1-
f][1,2,4]triazine (0.197 g, 1.05 mmol) and DIPEA (0.339 g,
2.62 mmol) at room temperature. The reaction mixture was
stirred for 12 h at room temperature. The progress of the reaction
was monitored by TLC (mobile phase: 5 % MeOH in DCM).
The reaction mixture was concentrated and crude thus obtained
was purified by flash column chromatography (mobile phase:
5 % MeOH in DCM). Subject compound 3-(3-((2-chloropyrrolo-
[2,1-f][1,2,4]triazin-4-yl)amino)phenyl)-1-(pyridin-2-yl)-
propan-1-ol (180 mg, 54.21 %) was isolated as a yellow solid.
ν
max, cm-1): 3435 (O-H), 1582 (C=N), 1357 (N-O), 1H NMR
in DMSO-d6 (value in δ): 8.82-8.97 (m, 1H), 8.40-8.37 (m,
3H), 7.95-7.90 (m, 3H), 7.45=7.41 (m, 1H), 7.23 (d, J = 14.99 Hz,
1H), 6.28 (d, J = 15.10 Hz, 1H), 5.21 (s, 1H), 2.12 (s, 1H).
3-(2-Nitro-phenyl)-1-pyridin-4-yl-propane-1-ol (7): To
stirred a solution of 3-(-2-nitro-phenyl)-1-pyridin-4-yl-prop-
2-en-1-one (0.50 g, 1.97 mmol) in methanol (20 mL) was added
NaBH4 (0.74 g, 19.68 mmol) at room temperature. Reaction
mixture was stirred for overnight at reflux temperature. The
progress of the reaction was monitored by TLC (mobile phase:
5 % MeOH in DCM). The reaction mixture was quenched
with water and was extracted with EtOAc (2 × 100 mL). Com-
bined organic extract was washed with brine, dried on Na2SO4
and concentrated to get crude. Crude was purified by flash
column chromatography (mobile phase: 100 % EtOAc). Desired
compound 3-(2-nitro-phenyl)-1-pyridin-4-yl-propane-1-ol was
isolated as a brown solid (yield: 0.32 g, 63.01 %). HPLC purity:
99.01 %, Mass: 259.3 (M+1), IR (KBr, νmax, cm-1): 3373 (O-
H), 1564 (C=N), 1524 (C-C quadrant of Ar), 1348 (N-O), 1H
NMR in DMSO-d6 (value in δ): 8.84-8.79 (m, 1H), 8.42-8.39
(m, 2H), 7.93-7.88 (m, 2H), 7.43-7.40 (m, 1H), 7.20-7.17 (m,
2H), 2.72 (t, J = 5.96 Hz, 2H), 2.19 (t, J = 5.95 Hz, 2H), 2, 10
(s, 1H).
HPLC purity: 99.12 %, Mass: 378.1 (M–1), IR (KBr, νmax
,
cm-1): 3322 (N-H), 1610 (C=N), 1609 (C=C), 3322 (N-H),
1350 (C-N), 1H NMR in DMSO-d6 (value in δ): 10.23 (s, 1H),
8.60-8.31 (m, 1H), 7.90-7.76 (m, 2H), 7.68 (d, J = 8.1 Hz,
1H), 7.53 (dd, J = 5.4, 2.7 Hz, 2H), 7.33 (t, J = 7.8 Hz, 1H),
7.29-7.14 (m, 2H), 7.04 (d, J = 7.5 Hz, 1H), 6.75 (dd, J = 4.5,
2.6 Hz, 1H), 5.51 (d, J = 5.1 Hz, 1H), 4.81-4.38 (m, 1H), 2.70
(t, J = 7.9 Hz, 2H), 2.18-1.75 (m, 2H).
3-(2-Nitro-phenyl)-1-pyridin-3-yl-prop-2-en-1-ol (8):
To a stirred solution of 3-acetylpyridine (2.00 g, 16.50 mmol)
in 60 mL methanol was added 2-nitro-benzaldehyde (2.49 g,
16.47 mmol) at 0 °C followed by addition of 3.3 mL of 1 N
NaOH (0.13 g, 3.25 mmol) solution. Reaction mixture was
stirred for 12 h at 0 °C to room temperature. Progress of the
reaction was monitored by TLC (mobile phase: 80 % EtOAc
in n-hexane). The reaction mixture was cooled to 0 °C. 10 mL
of 1 N HCl was added to the reaction mixture. The reaction
mixture was further diluted with 80 mL with distilled water.
Reaction mixture was stirred for 1 h. Reddish brown compound
was precipitated out and it was filtered. 1.60 g of 3-(2-nitro-
phenyl)-1-pyridin-3-yl-prop-2-en-1-one was isolated as a
reddish brown solid (yield 1.60 g, 47.55 %). Mass: 255.3
(M+1), 1H NMR in DMSO-d6 (value in δ): 9.35 (d, J = 1.50
Hz, 1H), 8.86 (dd, J = 4.65 Hz, 1.50 Hz, 1H), 8.49 (dt, J =
8.10 Hz, 1.80 Hz, 1H), 8.23 (d, J = 7.20 Hz, 1H), 8.14-8.00
(m, 1H), 7.99-7.82 (m, 2H), 7.73 (t, J = 7.50 Hz, 1H), 7.67-
7.60 (m, 1H)), 6.65-6.50 (m, 1H).
To a stirred solution of 3-(2-nitro-phenyl)-1-pyridin-3-
yl-prop-2-en-1-one (0.20 g, 0.79 mmol) in 30 mL methanol
and 30 mL THF was added NaBH4 (0.089 g, 2.362 mmol) at
room temperature. Reaction mixture was stirred over night at
room temperature. Reaction was monitored by TLC (mobile
phase: 5 % MeOH in DCM)). After completion of reaction,
reaction mixture was quenched by water and extracted twice
with ethyl acetate (2 × 100 mL). Combined organic extract
was washed with brine and concentrated to get crude. Crude
was purified by flush chromatography (mobile phase: 0-100
% EtOAc in n-hexane) to give 3-(2-nitro-phenyl)-1-pyridin-
3-yl-prop-2-en-1-ol as brown solid (yield 0.11 g, 56 %). HPLC
3-(3-((2-Chloropyrrolo[2,1-f][1,2,4]triazin-4-yl)-
amino)phenyl)-1-(pyridin-3-yl)propan-1-one (10):To a stirred
solution of 3-(3-aminophenyl)-1-(pyridin-3-yl)propan-1-one
((0.2 g, 0.88 mmol) in 20 mL ethanol were added 2,4-dichloro-
pyrrolo[2,1-f][1,2,4]triazine (0.21 g, 1.05 mmol) and DIPEA
(0.34 g, 2.64 mmol) at room temperature. The reaction mixture
was stirred 12 h at room temperature. The progress of the
reaction was monitored by TLC (mobile phase: 5 % MeOH in
DCM). The reaction mixture was concentrated and crude thus
obtained was purified by flash column chromatography
(mobile phase: 5 % MeOH in DCM). Subject compound 3-
(3-((2-chloropyrrolo[2,1-f][1,2,4]triazin-4-yl)amino)phenyl)-
1-(pyridin-3-yl)propan-1-one (200 mg, 60.24 %) was isolated
as a yellow solid. HPLC purity: 99.51 %, Mass: 376.0 (M–1),
IR (KBr, νmax, cm-1): 1621 (C=O), 1682 (C=N), 3359 (N-H),
1174 (C-Cl), 1679 (C=N), 1352 (C-N), 1H NMR in DMSO-d6
(value in δ): 10.28 (s, 1H), 9.17 (dd, J = 2.3, 0.9 Hz, 1H), 8.79
(dd, J = 4.8, 1.7 Hz, 1H), 8.33 (dt, J = 8.1, 1.9 Hz, 1H), 7.78 (dd,
J = 2.6, 1.5 Hz, 1H), 7.69-7.59 (m, 2H), 7.57-7.52 (m, 1H),
7.35 (t, J = 7.7 Hz, 1H), 7.28-7.09 (m, 2H), 6.75 (dd, J = 4.5,
2.6 Hz, 1H), 3.49 (t, J = 7.3 Hz, 2H), 3.00 (t, J = 7.3 Hz, 2H).
3-(3-((2-Chlorothieno[3,2-d]pyrimidin-4-yl)amino)-
phenyl)-1-(pyridin-3-yl)propan-1-one (11): To a stirred solution
of 3-(3-aminophenyl)-1-(pyridin-3-yl)propan-1-one (0.3 g,
1.32 mmol) in 20 mL ethanol were added 2,4-dichlorothieno[3,
2-d]pyrimidine (0.326 g, 1.58 mmol) and DIPEA (0.511 g,
3.96 mmol) at room temperature. The reaction mixture was
stirred for 12 h at room temperature. The progress of the reaction
was monitored by TLC (mobile phase: 5 % MeOH in DCM).
The reaction mixture was concentrated and crude thus obtained
was purified by flash column chromatography (mobile phase

886 Santra et al.
Asian J. Chem.
5 % MeOH in DCM). Subject compound 3-(3-((2-chlorothieno-
[3,2-d]pyrimidin-4-yl)amino)phenyl)-1-(pyridin-3-yl)propan-
1-one (250 mg, 47.70 %) was isolated as a brown solid. HPLC
purity: 99.22 %, Mass: 393.9 (M–1), IR (KBr, νmax, cm-1): 3230
(N-H), 695 (C-S), 1308 (C=N), 1161 (C-Cl), 1686 (C=O), 1H
NMR in DMSO-d6 (value in δ): 9.95 (s, 1H), 8.94 (d, J = 2.2
Hz, 1H), 8.57 (dd, J = 4.8, 1.7 Hz, 1H), 8.27-7.91 (m, 2H),
7.34 (dd, J = 7.8, 4.2 Hz, 2H), 7.30-7.06 (m, 3H), 6.94 (d, J =
7.6 Hz, 1H), 3.27 (t, J = 7.4 Hz, 2H), 2.78 (t, J = 7.4 Hz, 2H)),
3-(3-((2-Chlorothieno[3,2-d]pyrimidin-4-yl)amino)-
phenyl)-1-(pyridin-3-yl)propan-1-ol (12):To a stirred solution
of 3-(3-aminophenyl)-1-(pyridin-3-yl)propan-1-ol (0.2 g, 0.876
mmol) in 20 mL ethanol were added 2,4-dichlorothieno[3,2-
d]pyrimidine (0.215 g, 1.051 mmol) and DIPEA (0.339 g, 2.62
mmol) at room temperature. The reaction mixture was stirred
for 12 h at room temperature. The progress of the reaction
was monitored by TLC (mobile phase: 5 % MeOH in DCM).
The reaction mixture was concentrated and crude thus obtained
was purified by flash column chromatography (mobile phase:
5 % MeOH in DCM). Subject compound 3-(3-((2-chlorothieno-
[3,2-d]pyrimidin-4-yl)amino)phenyl)-1-(pyridin-3-yl)propan-
1-one (250 mg, 72.25 %) was isolated as an off white solid.
against bacterial strains by the agar well diffusion method [18].
Mueller Hinton agar no.2 (Hi Media, India) was used as the
bacteriological medium. The extracts were diluted in 100 %
dimethyl sulphoxide at the concentrations of 5 mg/mL. The
Mueller Hinton agar was melted and cooled to 48-50 °C and
standardized inoculums (1.5 × 108 CFU/mL, 0.5 McFarland)
was then added aseptically to the molten agar and poured into
sterile petri dishes to give a solid plate. Wells were prepared
in the seeded agar plates. The test compound (100 µL) was
introduced in the well (6 mm). The plates were incubated over-
night at 37 °C. The antimicrobial spectrum of the extract was
determined for the bacterial species in terms of zone sizes
around each well. The diameters of zone of inhibition produced
by the agent were compared with standard ciprofloxacin. For
each bacterial strain controls were maintained where pure
solvents were used instead of the extract. The control zones
were subtracted from the test zones and the resulting zone
diameter was measured with antibiotic zone reader to nearest
mm. The experiments were performed in triplicate.
Determination of antifungal assay: Antifungal activity
of the synthesized compounds was investigated by agar well
diffusion method [19]. Suspensions of fungal spores were
prepared in sterile PBS and adjusted to a concentration of 106
cells/mL by dipping a sterile swab into the fungal suspension
and rolled on the surface of the agar medium. The plates were
dried at room temperature for 15 min. Wells of 10 mm diameter
and about 7 mm apart were punctured in the culture media
using sterile glass tube. 0.1 mL of several dilutions of fresh
solutions was administered to fullness for each well. Plates
were incubated at 37 °C.After incubation of 24 h bioactivities
were determined by measuring the diameter of inhibition zone
(in mm). All experiments were performed in triplicate.
HPLC purity: 99.29 %, Mass: 396.0 (M–1), IR (KBr, νmax
,
cm-1): 3240 (N-H), 693 (C-S), 1350 (C=N), 1191 (C-Cl), 1078
(C-N), 946 (O-H), 1H NMR in DMSO-d6 (value in δ): 10.12
(s, 1H), 8.48 (ddd, J = 4.8, 1.8, 1.0 Hz, 1H), 8.26 (d, J = 5.4
Hz, 1H), 7.79 (td, J = 7.7, 1.9 Hz, 1H), 7.61-7.50 (m, 2H),
7.47 (t, J = 1.9 Hz, 1H), 7.40 (d, J = 5.4 Hz, 1H), 7.32 (t, J =
7.8 Hz, 1H), 7.24 (ddt, J = 8.1, 4.9, 1.7 Hz, 1H), 7.05 (d, J =
7.5 Hz, 1H), 5.46 (dd, J = 23.0, 5.1 Hz, 1H), 4.62 (dt, J = 8.9,
4.6 Hz, 1H), 2.70 (t, J = 7.9 Hz, 2H), 2.24-1.55 (m, 2H).
Antibacterial and antifungal activities: The synthesized
compounds were screened for antibacterial activity against
the bacteria Staphylococcus aureus, E. coli and Bacillus
sphaericus. Antifungal activities of the synthesized compounds
were studied against the fungus Aspergillus niger, Penicillium
funiculosum and Fusarium oxysporum.
RESULTS AND DISCUSSION
Purity of the chalcones was determined by HPLC. Chalcones
with purity more than 98 % were submitted for spectral analysis.
The structures of the product were deduced from elemental
analysis and spectral analysis. HPLC purity of synthesized
chalcones are given in Table-1.
Determination of antibacterial assay: In vitro anti-
bacterial activity of the crude methanol solution was studied
O
O
O
O
N
N
N
N
(3)
(2)
H
F
F
F
(1)
(4)
NO2
NO2
NO2
N
OH
OH
OH
O
N
(8)
(7)
N
N
(5)
(6)
N
NO2
NH2
NO2
NO2
N
N
HN
N
HN
N
HN
HN
OH
O
O
OH
S
S
N
N
N
N
N
N
N
Cl
Cl
N
N
Cl
Cl
N
(12)
(10)
)
(11
(9)
Structure of synthesized compounds 1-12

Vol. 30, No. 4 (2018)
Synthesis and Antimicrobial Activities of Chalcones and Indole Derived from Acetyl Pyridines 887
The mass spectrum are recorded both in positive and
negative mode. Mass spectrum revealed mainly the [M+H]
and [M-H] ions without much fragmentation and supported
the molecular weight corresponding to the molecular formula
suggested for synthesized chalcones and indole. The elemental
analysis of the reported compounds supported the suggested
molecular formulae. Elemental analysis and molecular ions
observed in Mass spectrum are presented in Table-1.
protons. NMR data of synthesized compounds are presented
with their respective synthesis.
The synthesized chalcones were screened for antibacterial
activity against the bacteria Staphylococcus aureus, E. coli
and Bacillus sphaericus. Antifungal activities of the synthesized
compounds were studied against the fungus Apergillus niger,
Penicillium funiculosum and Fusarium oxysporum. Significant
antibacterial activities were observed with compounds 4, 5,
11 and 12. Antibacterial activities of different synthesized
compounds have been presented in Table-2. Again significant
antifungal activities were observed with compound 4, 5, 6, 8,
9, 10, 11 and 12. Antifungal activities of different synthesized
compounds have been presented in Table-2.
All the synthesized chalcones exhibited characteristic
absorption bands in the IR spectra from 1656-1650 cm-1 for
(C=O), 1507-1503 cm-1 for (C=C quadrant of Ar), 1467-1461
cm-1 for (CH=CH) and at other regions of the spectrum depen-
ding upon the specific substitutions present in the chalcones
and indole. IR frequencies observed for different compounds
are presented with their respective synthesis.
Conclusion
1
Novel chalcones and indole derivatives (1-12) were synthe-
sized and tested against the bacteria strains Staphylococcus
aureus, E. coli and Bacillus sphaericus with reference to the
standard drug Ciprofloxacin at the concentration 1 µg/mL.
Again synthesized compounds were tested against the fungal
strains Apergillus niger, Penicillium funiculosum and Fusarium
oxysporum with reference to the standard ketoconazole at the
The H NMR spectrum of the synthesized chalcones
exhibited signals for aromatic proton in between 8.69 to 7.10
regions. Number of peaks and their relative intensity comply
with the molecular formula and predicted structure of the
reported molecules. The 1H NMR spectra of different chalcones
also exhibited two doublets with high J value around 9-15 Hz
indicating the trans relationship of =CH-Ar and –CO-CH=
TABLE-1
ELEMENTAL ANALYSIS AND MOLECULAR MASS IONS OF SYNTHESIZED COMPOUNDS
Elemental analysis (%): Found (calcd.)
Compd.
No.
Molecular
mass
HPLC
purity (%)
m.f.
m.w.
Appearance
C
H
N
C14H9N2O3F
C14H9N2O3F
C14H9N2O3F
C14H10N2O
272.23
272.23
272.23
222.24
226.27
256.26
258.10
256.26
379.85
377.83
394.88
396.89
Off white solid
Pale yellow solid
Off white solid
Brown solid
Red solid
Brown solid
Brown solid
Brown solid
Yellow solid
Yellow solid
Brown solid
Off white
271.1 (M–1)
271.1 (M–1)
271.1 (M–1)
221.1 (M–1
227.0 (M+1)
257.3 (M+1)
259.3 (M+1)
257.3 (M+1)
378.1 (M–1)
376.0 (M–1)
393.9 (M–1)
396.0 (M–1)
99.11
99.06
99.35
99.06
99.23
99.03
99.01
99.03
99.12
99.51
99.22
99.29
61.79 (61.75)
61.78 (61.75)
61.78 (61.75)
75.68 (75.66)
74.36 (74.30)
65.66 (65.60)
65.10 (65.09)
65.65 (65.60)
63.65 (63.35)
63.57 (63.64)
60.90 (60.83)
60.52 (60.53)
3.37 (3.34)
3.36 (3.34)
3.37 (3.34)
4.56 (4.54)
6.27 (6.25)
4.74 (4.73)
5.48 (5.47)
4.74 (4.73)
4.79 (4.78)
4.27 (4.24)
3.80 (3.83)
4.30 (4.32)
10.31 (10.29)
10.32 (10.29)
10.33 (10.29)
12.63 (12.60)
12.40 (12.38)
10.95 (10.93)
10.86 (10.84)
10.96 (10.93)
18.44 (18.46)
18.54 (18.56)
14.21 (14.19)
14.10 (14.12)
1
2
3
4
5
6
7
8
9
C14H14N2O
C14H12N2O3
C14H14N2O3
C14H12N2O3
C20H18N5OCl
C20H16N5OCl
C20H15N4OSCl
C20H17N4OSCl
10
11
12
TABLE-2
MICROBIAL ACTIVITIES OF SYNTHESIZED COMPOUNDS
Diameter of inhibition zone (mm)
Antibacterial activity
Antifungal activity
Compound No.
Escherichia
coli
Staphylococcus
aureus
Bacillus
sphaericus
Aspergillus
niger
Fusarium
oxysporum
Penicillium
funiculosum
NIL
NIL
NIL
NIL
NIL
NIL
NIL
NIL
–
–
–
–
1
2
NIL
NIL
NIL
NIL
–
–
3
A: 22; B: 26
A: 18; B: 24
A: 10; B: 12
NIL
A: 06; B: 06
A: 28; B: 28
A: 32; B: 34
A: 6; B: 6
NIL
A: NIL; B: 16
A-12; B: 16
NIL
A: 14; B: 16
–
–
–
–
–
–
–
–
4
5
6
7
8
9
10
11
12
NIL
NIL
NIL
NIL
–
–
–
–
–
NIL
NIL
NIL
NIL
NIL
NIL
NIL
–
–
A: 12; B: 14
A: 8; B: 10
A: 6; B: 16
A: 10; B: 14
–
–
–
–
–
–
NIL
NIL
–
A: 4; B: 11
A: 4; B: 10
–
A: 16; B: 18
A: 8; B: 10
22
NIL
NIL
22
Ciprofloxacin standard
Ketoconazole standard
22
22
–
–
–
Stock solution: 1 mg/mL (DMSO) A = 40 µL, B = 80 µL

888 Santra et al.
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ACKNOWLEDGEMENTS
https://doi.org/10.1016/S0960-894X(00)00409-1.
The authors are thankful to the Management of Therachem
Research Medilab (India) Pvt. Ltd. for providing the equipped
synthetic laboratory with SciFinder and sophisticated analytical
instrumentation facilities.
10. G.A. Crosby, P.C. Wang and R.E. Wingard Jr., 4-(Dihydroxyhexoxy)-
dihydrochalcone Sweeteners, US Patent 4204007A (1980).
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