Synthesis and In vitro antimicrobial, anthelmintic and insecticidal activities study of 4(4'-bromophenyl)-6-substituted-aryl-1-acetyl pyrimidine-2-thiols

Article abstract of DOI:10.1155/2010/927601

A new series of 4(4'-bromophenyl)-6-substituted aryl-1-acetyl pyrimidine-2-thiol derivatives were synthesized by heating chalcones with thiourea, in the presence of ethanolic potassium hydroxide, followed by treatment with acetyl chloride. The structure of the compounds was characterized by IR and H¹ NMR spectral study and elemental analysis. The compounds were screened for their antimicrobial, anthelmintic and insecticidal activities. All the compounds exhibited significant to moderate biological activities.

Full text of DOI:10.1155/2010/927601

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
2010, 7(3), 935-941
http://www.e-journals.net
Synthesis and In Vitro Antimicrobial,
Anthelmintic and Insecticidal Activities Study of
4(4'-Bromophenyl)-6-substituted-aryl-1-acetyl
pyrimidine-2-thiols
RITA BAMNELA* and S. P. SHRIVASTAVA
*Department of Chemistry, Govt. P.G. College,
Damoh, M.P. -470 661, India.
Synthetic Organic Laboratory, Department of Chemistry,
Dr. Hari Singh Gour, University, Sagar - 470 003, M.P, India.
ritabamnela@gmail.com
Received 7 January 2010; Accepted 5 March 2010
Abstract: A new series of 4(4'-bromophenyl)-6-substituted aryl-1-acetyl
pyrimidine-2-thiol derivatives were synthesized by heating chalcones with
thiourea, in the presence of ethanolic potassium hydroxide, followed by
treatment with acetyl chloride. The structure of the compounds was
characterized by IR and H1 NMR spectral study and elemental analysis. The
compounds were screened for their antimicrobial, anthelmintic and
insecticidal activities. All the compounds exhibited significant to moderate
biological activities.
Keywords:Pyrimidine-2-thiols, Antimicrobial, Anthelmintic,Insecticidal activity.
Introduction
Heterocyclic system containing pyrimidine ring, constitute an important class of potentially
bio-active compounds. The earlier workers reported that, pyrimidine derivatives are associated
with a wide spectrum of biological activities viz. antimicrobial1-4, anthelmintic5-7, anticancer8-9, anti-
tumer10, anti-inflammatory11-12, anti-HIV agents13, calcium-channel-blocker14 and insecticidal
agents15 and this significance led us to synthesize the titled compounds.
In the present communication, we have reported, the synthesis of a new series of 4(4'-
bromophenyl)-6-substituted aryl-1-acetyl pyrimidine-2-thiols (Scheme 1) and evaluated for
their antimicrobial, anthelmintic and insecticidal activities.

936
RITA BAMNELA et al.
Ethanol +KOH
[3] (a-j)
[2]
Where - R1 = Bromo, R2 = 4-O-CH3, 4-OH-3-OCH3, H, 4-Cl, 2-Cl, 4-N(CH3)2, 2-NO2, 3-
NO2, Furyl, 2-OH.
Scheme 1
Experimental
The melting points were recorded by open capillary method and are uncorrected. IR
spectra (
ν
max in cm-1) were recorded on a Shimadzu FTIR 8300 spectrophotometer, using
KBr pellets. The H1 NMR spectra were recorded on a DRX-300 (300 MHz) instrument
using CDCl3 as solvent (Chemical Shift in δ ppm), using TMS as internal standard. The
completion of reactions was monitored by TLC.
General procedure
Synthesis of 4-bromochalcones (1a-j)
4-Bromoacetophenone (0.01 mol) and anisaldehyde (0.01 mol) were stirred in ethanol (20 mL) and to
it 10 mL of 40% NaOH solution was added. The mixture was kept overnight at room
temperature. The contents were then poured on crushed ice and acidified with dil. HCl. The solid
was filtered, dried and recrystallised from ethanol. The other chalcones were prepared with the
same procedure using different aromatic aldehydes.
4(4'-Bromophenyl)-6-substituted phenyl-1, 5, 5, 6-tetrahydropyrimidine-2-thiones (2a-j)
The chalcones (0.01 mol), thiourea (0.01 mol) and KOH (1.0 g) in ethanol (20 mL) was refluxed
on water bath for 6 h and completion of reaction was monitored by TLC. After keeping in ice-
cold condition, the solid was collected and recrystallised from ethanol.
Yield 71%, m.p. 206 ºC, m.wt.374.9, (% of C : found 54.38 - calculated 54.41), (% of
H: found 03.98, calculated 4.00), (% of N: found 7.40, calculated 7.46), IR (KBr) in cm-1 :
536-600 (Ar-Br str), 1595-1560 (C=N str), 1220-1200 (C=S str.), 820-740 (Ar-H def.
pyrimidine ring breath), 3351-3300 (N-H Str). The other derivatives were prepared with
different chalcones, applying the same procedure.
4(4'-Bromophenyl)-6-substitutedphenyl-1-acetyl-5, 6-dihydropyrimidine-2-thiols (3a-j)
The different thiones (2a-j), (0.005 mol) and acetyl chloride (16 mL) were heated at 30-40 ºC,
under reflux on water bath for 2 h, completion of reaction was monitored by TLC. Excess of
acetyl chloride was evaporated and the oily product obtained, was treated with pet ether. The
solid obtained was filtered off, dried and recrystallised from ethanol. The physical and
spectral data of all the synthesized compounds described as follows:

Synthesis and In Vitro Antimicrobial Activities Study
Table 1. Physical data of compounds 3a-j.
937
Elemental Analysis %
M.P.
ºC
R2
M.F.
M.wt.
C
H
N
found 54.62 4.05 6.69
calc. 54.68 4.07 6.71
found 52.65 3.90 6.42
calc. 52.66 3.92 6.46
found 55.80 3.82 7.20
calc. 55.82 3.87 7.23
found 51.21 3.30 6.61
calc. 51.25 3.32 6.64
found 51.20 3.30 6.60
calc. 51.25 3.32 6.64
found 55.80 4.61 9.72
calc. 55.82 4.65 9.76
found 49.99 3.21 9.70
calc. 50.01 3.24 9.72
found 50.00 3.20 9.69
calc. 50.01 3.24 9.72
found 50.90 3.40 7.40
calc. 50.94 3.44 7.42
found 53.58 3.70 6.90
calc. 53.61 3.72 6.94
4-O-CH3
4-OH-3-OCH3
H
C19H17O2N2SBr
C19H17O3N2SBr
C18H15N2 OSBr
C18H14N2OSClBr
C18H14N2OSClBr
C20H20N3OSBr
C18H14N3O3SBr
C18H14N3O3SBr
C16H13N2O2SBr
C18H15N2O2SBr
416.9 215 85
432.9 185 86
386.9 218 65
421.4 194 75
421.4 220 70
429.9 200 72
431.9 190 72
431.9 180 84
376.9 176 85
402.9 205 60
3a
3b
3c
3d
3e
3f
4-Cl
2-Cl
4-N(CH3)2
2-NO2
3g
3h
3i
3-NO2
6-Furyl
2-OH
3j
Spectral data of compounds (3a-j)
4(4'-Bromophenyl)-6-(4''-methoxyphenyl)-1-acetyl- 5, 6-dihydropyrimidine-2-thiol (3a)
IR (KBr) in cm-1: 2550.11(S-H str), 1681.98 (N-C=O str), 1606.76 (C=C str), 1581.68(C=N
str), 582.52 (Ar-Br str), 1114.89 (C-O-C str.); H1NMR (CDCl3) δ (ppm) : 1.50 (δ, 1H, S-H),
2.03 (δ, 3H, N-CO-CH3), 5.51 (d, 1H, H-C6-pyrimidine), 6.73(d, 1H, H-C5-pyrimidine),
7.17-7.66 (m, 8H, Ar-H).
4(4'-Bromophenyl)-6-(4"-hydroxy-3-methoxy-phenyl)-1-acetyl-5,6-dihydropyrimidine-
2-thiol (3b)
IR (KBr) in cm-1: 2540.28 (S-H str), 3450.25 (O-H str), 1712.85 (N-C=O str), 1589.40
(C=N str), 1599.04 (C=C str), 594.10 (Ar-Br str), 1074.39 (C-O-C str), H1 NMR
(CDCl3) δ (ppm); 1.52(ꢀ, 1H, S-H), 2.03 (ꢀ, 3H, NCOCH3), 2.11 (ꢀ, 3H, C-O-CH3),
4.90 (ꢀ, 1H, Ar-OH), 5.52 (d, 1H, H-C6 pyrimidine), 6.74 (d, 1H, H-C5 pyrimidine),
7.12-7.66 (m, 7H, Ar-H)
4(4'-Bromophenyl)-6-phenyl-1-acetyl,5,6-dihydro-pyrimidine-2-thiol (3c)
IR (KBr) in cm-1 : 2565.44 (S-H str), 1689.97 (N-C=O str), 1606.76 (C=C str), 1585.64
(C=N str), 590.24 (Ar-Br); H1 NMR (CDCl3) δ (ppm) : 1.50 (ꢀ, 1H, S-H), 2.04 (ꢀ, 3H,
NCOCH3), 5.50 (d, 1H, H-C6 pyrimidine), 6.72 (d, 1H, H-C5 pyrimidine), 7.11-7.50
(m, 9H, Ar-H).

938
RITA BAMNELA et al.
4(4'-Bromophenyl)-6-(4''-chlorophenyl)-1-acetyl 5,6- dihydropyrimidine-2-thiol (3d)
IR (KBr) in cm-1 : 2542.38 (S-H str), 1703.20 (N-C=O str), 1587.47 (C=C str), 1576.89
(C=N str), 619.17 (Ar-Br str), 750.01 (Ar-Cl str); H1 NMR (CDCl3) δ (ppm) : 1.54 (ꢀ, 1H, S-H),
2.06 (ꢀ, 3H, N-CO-CH3), 5.53 (d, 1H, H-C6 pyrimidine), 6.72 (d, 1H, H-C5 pyrimidine),
7.15 - 7.60 (m, 8H, Ar-H).
4(4'-Bromophenyl)-6-(2'-chlorophenyl)-1-acetyl, 5,6-dihydropyrimidine-2-thiol (3e)
IR (KBr) in cm-1 : 2596.27 (S-H str), 1681.98 (N-C=O str), 1583.61 (C=C str), 1568.18
(C=N str), 513.08 (Ar-Br str), 702.11 (Ar-Cl str). H1 NMR (CDCl3) δ(ppm) : 1.56 (ꢀ, 1H, S-H),
2.08 (ꢀ 3H, N-CO-CH3), 5.55 (d, 1H, H-C6 pyrimidine), 6.73 (d, 1H, H-C5 pyrimidine),
7.16 - 7.62 (m, 8H, Ar-H).
4(4'-Bromophenyl)-6-(4''-dimethylaminophenyl)-1-acetyl-5,6-dihydropyrimidine-2-thiol (3f)
IR (KBr) in cm-1 : 2548.05 (S-H str), 1680.99 (N-C=O str), 1583.61 (C=C str), 1508.38 (C=N str).
H1NMR (CDCl3) δ(ppm) : 1.57 (ꢀ, 1H, S-H), 2.08 (δ, 3H, N-COCH3), 3.03 (ꢀ, 6H, N(CH3)2), 5.54
(d, 1H, H-C6 pyrimidine), 6.74 (d, 1H, H-C5 pyrimidine), 7.19-7.68 (m, 8H, Ar-H).
4(4'-Bromophenyl)-6-(2'-nitrophenyl)-1-acetyl-5, 6-dihydropyrimidine-2-thiol (3g)
IR (KBr) in cm-1 : 2580.77 (S-H str), 1680.98 (N-C=O str), 1605.09 (C=C str), 1560.08
(C=N str), 560.02 (Ar-Br str), 1590.25 (Ar-NO2 Asym str), 1340.22 (Ar-NO2 sym str).
H1NMR (CDCl3) δ(ppm) : 1.60 (ꢀ, 1H, S-H), 2.10 (ꢀ, 3H, N-COCH3), 5.60 (d, 1H, H-C6
pyrimidine), 6.78 (d, 1H, H-C5 pyrimidine), 7.20-8.10 (m, 8H, Ar-H).
4(4'-Bromophenyl)-6-(3'-nitrophenyl)-1-acetyl- 5,6 - dihydropyrimidine-2- thiol (3h)
IR (KBr) in cm-1 : 2580.77 (S-H str), 1680.90 (N-C=O str), 1605.08 (C=C str), 1560.04
(C=N str), 560.00 (Ar-Br str), 1540.00 (Ar-NO2 Asym. str), 1320.99 (Ar-NO2 sym. str).
H1NMR (CDCl3) δ (ppm) : 1.52 (ꢀ, 1H, S-H), 2.05 (ꢀ, 3H, N-COCH3), 5.58 (d, 1H, H-C6
pyrimidine), 6.74 (d, 1H, H-C5 pyrimidine), 7.27-8.12 (m, 8H, Ar-H).
4(4'-Bromophenyl)-6-furyl-1-acetyl-5,6-dihydro- pyrimidine- 2-thiol (3i)
IR (KBr) in cm-1 : 2569.27 (S-H str), 1683.91 (N-C=O str), 1585.54 (C=C str), 1489.01
(C=N str), 569.02 (Ar-Br str), 1072.46 (Furyl ring C-O-C str), 2980.04 (C-H str), H1 NMR
(CDCl3) δ (ppm) : 1.61 (ꢀ, 1H, S-H), 2.10 (ꢀ, 3H, N-COCH3), 5.59 (d, 1H, H-C6
pyrimidine), 6.76 (d, 1H, H-C5 pyrimidine), 7.20-7.78 (m, 7H, Ar-H).
4(4'-Bromophenyl)-6-(2'-hydroxyphenyl)-1-acetyl- 5,6-dihydropyrmidine-2-thiol (3j)
IR(KBr) in cm-1 : 2600.01 (S-H str), 1680.88 (N-C=O str), 1585.55 (C=C str), 1568.18 (C=N
str), 599.88 (Ar-Br str), 3400.01 (Ar-OH), H1NMR (CDCl3) δ (ppm) : 1.61 (ꢀ, 1H, S-H), 2.09 (ꢀ,
3H, N-COCH3), 4.99 (ꢀ, 1H, Ar-OH), 5.61 (d, 1H, H-C6 pyrimidine), 6.75 (d, 1H, H-C5
pyrimidine), 7.18-7.78 (m, 8H, Ar-H).
Antimicrobial activity
The synthesized compounds (3a-j) were screened for their in vitro antimicrobial activity
against, Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae and Staphylococcus
aureus and antifungal activity against, Aspergillus niger, Aspergillus flavus, Trichoderma
viride, Candida albicans by measuring the zone of inhibition in mm. The antimicrobial
activity was performed by standard filter paper disc diffusion method16-17 and zone of
inhibition is reported in the Table 3. Streptomycin and nystatin were used as standard drug
for antibacterial and antifungal activities respectively. Nutrient agar was employed as culture
medium and DMSO, was used as solvent.

Synthesis and In Vitro Antimicrobial Activities Study
Table 2. Antimicrobial data of compounds 3a-j.
939
Antibacterial
Antifungal
Compounds
1.
2.
++
++
+++ ++
+++
++ ++++
++
++
++
+
++
-
+++
+
++
++
-
3a
3b
3c
3d
3e
3f
++
++
-
3.
++
++++
+
++
++
++
+++
++
+
+
++
++
++
++
4.
+
+
5.
+
++
++
+
++
-
6.
+++ +++ ++ ++++
+
7.
8.
++
+++
+
++
-
++
+
+++ +++ +++ +++
3g
3h
3i
+++
+++
+
+++
++
+
++
+++ +++ +++
++
+++
9.
10.
+++ +++ ++
+++ ++
+
++
-
+++
-
++
-
3j
Std. Streptomycin ++++ +++ +++ ++++
drug Nystatin
-
-
-
-
-
++++ +++ ++++ +++
Zone of inhibition was measured in mm.++++ : Strong activity, +++ : good activity, ++ : moderate
activity, + : poor activity, - : inactive.
In vitro anthelmintic activity18
In vitro anthelmintic screening studies of compounds 3a-j were performed by the Watkins
technique, against common Indian earthworm 'P. posthuma’. For this purpose 4% and 2%
solutions of the synthesized pyrimidine derivatives and standard drug piperazine
hydrochloride in ethylene glycol were used for experiment. The experiments were
performed in duplicate and average values of paralytic time and lethal time in minutes have
given in the Table 3.
Table 3. Anthelmintic activity of compounds 3a-j (in minutes).
Concentration, %
S.
No.
4%
2%
Paralytic time
Compounds
Paralytic time Lethal time
Lethal time
1.
2.
7
8
15
17
18
17
14
16
15
17
15
14
13
9
8
18
20
21
17
17
16
20
18
17
18
15
3a
3b
3.
10
9
6
10
9
7
3c
3d
3e
4.
5.
6.
8
7
3f
3g
7.
9
10
9
8.
9
3h
3i
9.
8
9
10.
11.
7
6
10
7
3j
Std. drug

940
RITA BAMNELA et al.
Insecticidal activity19-20
Adult cockroaches (P. americana) were selected for the testing of, in vitro insecticidal
activity. 4% solutions of synthesized pyrimidine derivatives and standard drug cypermethrin
(w/v), in acetone were used for experiment. The time of death of cockroaches was noted, on
an average and denoted as KD (Knock Down) value in minutes. For each sample three
replication were performed and same experiments were performed with standard drug.
Table 4. Insecticidal activity of compounds 3a-j (in minutes).
S. No.
1.
Compounds
R2
4-O-CH3
4-OH-3-OCH3
H
K.D. Value, min
9
9
3a
3b
2.
3.
10
12
8
3c
3d
4.
4-Cl
2-Cl
5.
3e
6.
4-N(CH3)2
2-NO2
3-NO2
8
3f
3g
7.
7
8.
9
3h
3i
9.
6-Furyl
2-OH
Cypermethrin
7
10.
11.
9
3j
Std. drug
8
Conclusion
All the synthesized pyrimidine-2-thiols 3(a-j) have given appreciable yield with satisfactory
elemental analysis. It is inferred from the Table 2, 3 & 4, that synthesized compounds 3a-j,
have shown significant antibacterial activity, good to moderate antifungal activity and
significant anthelmintic and insecticidal activities, due to the presence of thio group, which
enhance the respective activities with varied substituent groups, against selected pathogens
and organisms.
Acknowledgment
Authors wish to express their thanks & gratitude to the Head of the Department, Chemistry,
Dr. H.S. Gour University, Sagar, for providing necessary facilities, Prof. Archna Mehta &
Prof. P. Mehta, Dept. of Botany, Prof. M. Bhide Dept. of Zoology, for their help and
guidance to carry out biological activities and Director, CDRI, Lucknow, for providing
spectral data.
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