Synthesis and biological activity of some 3,4-dihydro-4-(4-substituted aryl)-6-(naptho[2,1-b]furan-2-yl pyrimidine-2(1H)-one derivatives

Article abstract of DOI:10.1155/2012/258672

A series of new oxopyrimidine were prepared by cyclocondensation route with various substituted chalcones in presence of alcoholic solution of potassium hydroxide at reflux temperature. The synthesized oxopyrimidine derivatives were characterized by means

Full text of DOI:10.1155/2012/258672

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
2012, 9(1), 175-180
http://www.e-journals.net
Synthesis and Biological Activity of Some
3,4-Dihydro-4-(4-substituted aryl)-6-(naptho
[2,1-b]furan-2-yl pyrimidine-2(1H)-one Derivatives
SANJEEVAN S. GAIKWAD, VENKAT S. SURYAWANSHI§*,
KISHAN S. LOHAR, DHANAJI V. JADHAV# and NARAYAN D. SHINDE§
Dept. of Chemistry, Shrikrishna College, Gunjoti
Tal-Omerga, Dist-Osmanabad, Maharashtra-413613, India
§Dept. of Chemistry, PG studies and Research Center
Shri Chattrapati Shivaji College, Omerga, Maharashtra-413 606, India
#Dept. of Chemistry, Y. C. Arts & Science College, Mangrulpir
Dist-Washim, Maharashtra-444 403, India
venkatesh1@sify.com
Received 25 June 2011; Accepted 13 August 2011
Abstract: A series of new oxopyrimidine were prepared by cyclocondensation
route with various substituted chalcones in presence of alcoholic solution of
potassium hydroxide at reflux temperature. The synthesized oxopyrimidine
1
derivatives were characterized by means of their IR, H NMR, mass spectral
data and elemental analysis. The synthesized oxopyrimidines derivatives were
evaluated for antibacterial and antifungal activities, some of them were found to
possess significant activity.
Keywords: Naphthofuran, Chalcone, Oxopyrimidines, Synthesis, Biological activities
Introduction
The search for new potent anti-microbial agents with reduced toxicity and lower side effects
is of continuous process. One of the most frequently encountered groups of organic
compound in medicinal chemistry is oxopyrimidine and their derivatives. Pyrimidines1 have
occupied unique place in the field of medicinal chemistry. Some antibacterial2-7 and
antimalerial8-10 drug is constituted by pyrimidine derivatives. Certain pyrimidine derivatives
are known to display as analgesic11, anthelmintic12- 13, antitumor14, antifungal15, antiviral16-18
,
anticancer19, insecticidal20 and diuretic & anti-inflammatory21-22 activities. Keeping in view
of the biological importance23 and chemotherapeutic properties of oxopyrimidine and
naphthofuran derivatives, attempts has been made to synthesize some new oxopyrimidine
derivatives linked with naphthofuran and aryl group with the hope that they might display
antimicrobial activity.

176
V. S. SURYAWANSHI et al.
Experimental
Melting points were determined on an open capillary melting point apparatus and are
1
uncorrected. IR spectra were recorded on Brucker FT-IR (Alpha-P) spectrometer, H NMR
spectra were recorded in CDCl3 on Bruker “AVANCE 400” MHz spectrometer using TMS
as an internal standard and Mass spectrum on Shimadzu GCMS QP 5050A,mode-
DI,operating at 70eV. Progress of reaction was monitored by TLC. Naphthaldehyde,
chloroacetone, Urea, aromatic aldehydes were purchased from Merk, India. All compounds
have been recrystallized in ethanol.
Synthesis of 2-acetylnaphtho [2, 1-b] furan (1)
In a 250 mL four necked round bottom flask fitted with overhead mechanical stirrer, a
dropping funnel, a thermometer and condenser with child water circulation, 2-hydroxy-1-
naphthaldehyde (0.1 mole), chloroacetone (0.11 mole) and anhydrous potassium carbonate
(15gm) were refluxed in dry acetone (75 mL) for 12 h. Potassium salts were filtered off, the
filtrate on removal of solvent and on trituration with ethanol gave the pale yellow crystals of
2-acetylnaphtho [2, 1-b] furan (1). The sample was purified by recrystallized from absolute
ethanol. MP = 96 °C, Yield = 60%
Typical synthesis of 3-(4-hydroxyphenyl)-1 (naphtho [2,1-b]furan-2 yl) prop-2-en-
1-one (2c)
A
mixture of 2-acetylnaphtho [2,1-b] furan (1) (0.02 mole) and p-hydroxy
benzaldehyde (0.022 mole) was stirred in ethanol (50 mL) and then in aqueous solution
of potassium hydroxide (50%) (10 mL) was added to it portion wise, keeping the
temperature below 10 °C throughout the addition. The mixture was kept for 36 h and it
was acidified with conc. HCl. The reaction mixture was poured into crushed ice and the
solid obtained was filtered under vaccum. It was washed firstly with sodium carbonate
solution and then with water, dried and the product was recrystalized from ethanol. Same
procedure is extended for other compounds of this series. (2a-e) were synthesized by using
appropriate aldehyde. The physical data of chalcones were shown in Table 1.
Table 1. Physical data of the synthesized compounds
Elements %
H
C
N
Cl
Calcd
Found
Compound Molecular
Molecular Yield M.P.
0C
Calcd. Calcd Calcd
Found Found Found
No.
Formula
C21H14O2
C22H16O2
C21H14O3
C23H16O3
C21H13ClO2
Weight
%
84.53
84.55
84.58
84.57
80.25
80.24
81.17
81.11
75.74
75.73
4.69
4.7
-
-
-
-
-
-
-
-
-
-
-
298.1
312.1
314.0
340.0
332.7
60
66
65
72
55
132
151
172
135
143
2a
2b
2c
2d
2e
-
5.12
5.10
4.45
4.44
4.70
4.69
3.90
4.00
-
-
-
-
-
-
10.67
10.61

Synthesis and Biological Activity of Some Derivatives 177
Synthesis of 3, 4-dihydro-6-(naphtho [2,1-b]furan-2-yl)4-phenyl pyrimidine-2(1H)-
one (3a-e)
A mixture of 1-(naphtho [2, 1-b] furan-2-yl)-3-phenyl prop-2-en-1-one (2a) (0.01 mole) and
urea (0.02 mole) dissolved in ethanol (50 mL) under stirring. To this an alcoholic potassium
hydroxide 50% (10 mL) was added and refluxed for 10 h. After completion of reaction, it
was cooled and poured in ice cold water and neutralized by acetic acid. The solid product
was filtered washed with water and recrystallized from absolute ethanol. Compounds (3b-e)
were prepared similarly from (2b-e). The physical data of oxopyrimidine derivatives are
given in Table 2.
Table 2. Physical data of the synthesized compounds
Elements %
H
Molecular
Formula
Molecular Yield M.P.
0C
C
N
Cl
Compound
Weight
%
Calcd. Calcd Calcd Calcd
Found Found Found Found
C22H16N2O2
C23H18N2O2
C22H16N2O3
C23H18N2O3
77.57
77.56
77.87
77.81
74.13
74.19
74.57
74.49
70.43
70.10
4.7
4.7
8.22
8.21
7.90
7.89
7.86
7.86
7.56
7.55
7.47
7.46
-
340.3
354.4
52
55
56
52
50
235
247
297
260
258
3a
3b
3c
3d
3e
-
5.07
5.00
4.49
4.48
4.86
4.85
4.0
-
-
-
-
-
356.12
370.1
-
C22H15
ClN2O2
9.47
9.49
374.08
4.04
Purification
Crude product was dissolved in 10 mL absolute ethanol and heated up to 70 °C to get clear
solution and cooled slowly up to 10 °C, filtered, sucked and dried in vacuum to offered pure
compound. Under similar condition, a compound of this series has been carried out. Results
are summarized in Table 1 & 2. Good to excellent yields and perfect selectivity was
obtained in all cases.
Spectral Discussion
Compound 2c
IR (KBr, λmax): 3310 cm-1 (Ar-O- H str.), 3058 cm-1 (-CH str. of Ar), 1644 cm-1 (C=O str. in
ketone), 1586 cm-1 (C=C), 1515 cm-1 (C=C str. in Ar), 1443 & 1359 cm-1 (CH3 def.), 1153 &
1
1167 cm-1 (C-O-C str.), 830 cm-1 (-CH str.), 747 cm-1 (Ar-H opb.) H NMR (CDCl3 in
ꢀppm) 6.35 (d, 1H, -CO-CH=), 6.95 (d, 1H, C=CH), 7.21-8.24 (complex m, Ar. Proton
11H), 10.32 (s, 1H, phenolic -OH) proton. Mass (m/z): 314 [M] +, 221, 195, 147, 119, 118,
91, 69, 65, 43.
Compound 3a
IR (KBr, λmax.): 3300-3400 cm-1 (C-H str. in Ar), 1659 cm-1 (C=O str. in N-CO-N),
1
1541 cm-1 (-C-O-C- in Ar), 1262 cm-1 (C-O-C str.) H NMR (CDCl3 in ꢀppm) 5.46
(d, 1H, H-4), 5.68 (s, 1H, N-H-3), 5.84(d, 1H, H-5), 6.01(s, 1H, N-H-1), 6.71-7.80 (m,
+
12H, Ar-H) Mass (m/z): 340[M] , 297, 296, 220, 198, 197, 194, 105, 104, 103, 102,
101, 91, 77, 70.

178
V. S. SURYAWANSHI et al.
Reaction Scheme
O
CH3
O
R
KOH /
EtOH
10°C
O
H
O
O
R
2a - 2e
NH2CONH 2
Reflux
KOH / C 2H5OH
O
R
NH
HN
O
3a - 3e
Scheme 1
R = Substituted group R = a = 4 - H, R = b = 4 - CH3, R = c = 4 – OH, R = d = 4 – OCH3, R = e = 4 – Cl.
Antimicrobial activity
The antimicrobial activity was determined by cup-plate method24-25. In vitro antimicrobial
activity was carried out against 24 h. culture of four bacteria and four fungi. The bacteria
used were Escherichia coli, Salmonua typhi, Staphylococcus aureus and Bacillus substilis.
While the fungi used were Aspergillus niger, Penicillium chrysogenum, Fusirium
moneliforme and Candida albicans. The compounds were tested at a (20 mg) dissolved in
dimethyl sulphoxide (5 mL) against all organisms. Penicillin and griseofulvin were used as
standards for comparison of antibacterial and antifungal activities respectively. The zone of
inhibition was compared with the standard drug after 24 h. incubation at 37 °C for
antibacterial activity & 48 h. at 28-30 °C for antifungal activity. The results are reported in
Table 3.

Synthesis and Biological Activity of Some Derivatives 179
Table 3. Antimicrobial activity of synthesized compounds
Antibacterial activity
Antifungal activity
zone of inhibition
Compound
B.sub
stilis
-ve
11
P.
Chrysogen. Moneli Albicans
F.
C.
E.coli S.typi S.aureus
A.niger
-ve
-ve
-ve
-ve
-ve
18
-
-ve
-ve
-ve
-ve
-ve
20
-
13
14
13
12
15
32
-
-ve
+ve
-ve
+ve
-ve
-
-ve
-ve
+ve
+ve
+ve
-
-ve
+ve
-ve
-ve
+ve
-
3a
+ve
-ve
+ve
-ve
-ve
-
3b
3c
11
-ve
15
3d
3e
penicillin
Griseofulvin
28
-
+ve
+ve
+ve
+ve
Penicillin & Griseofulvin were used as standards for antibacterial & antifungal activities respectively.
Control (DMSO) –ve no activity
Results and Discussion
Compounds (3a-e) showed significant antibacterial activity at 0.02 mL (20 mg)
concentration level when compared with standard drug penicillin. However the
oxopyrimidine 3b, 3c & 3e were found to be more potent on all the bacteria strains.
Compounds (3a-e) also showed significant antifungal activity at 0.02 mL (20 mg)
concentration levels when compared with standard drug griseofulvin compound 3a, 3b, 3c,
3d & 3e showed maximum antifungal activity.
Acknowledgment
The authors are thankful to Dr.C.H.Gill, Dr. M.S.Shingare, Dr. R.A.Mane Dept.of
chemistry, Dr.D.R.Mane, Dean, Faculty of Science, Dr. B.A.M. University, Aurangabad for
providing necessary facilities and helpful suggestions.
References
1.
Maria T C, Cenzo Congiu, Antonio Maccioni and Valentina Onnis, J Het Chem.,
2009, 31(2), 329.
2.
3.
4.
Mahadevan K M and Vaidya V P, Indian J Pharm Sci., 2003, 65, 128.
Burger A, Medicinal Chemistry, Wiley Inter Science., New York, 1961.
Vagdevi H.M, Latha K P, Vaidya V P and Vijay Kumar M.L, Indian J Pharm Sci..,
2001, 63(4), 286.
5.
6.
Foye W O, Principles of Medicinal Chemistry, Lea and Febiger, Philadelphia, 1981.
Pershin G N, Sherbakova L I and Zykova T N., Sakolova Farmakol aksikol, 1972, 35,
466-471, Chem Abstr., 1972, 77, 1555802.
7.
8.
Kodihalli C R, Hosadu M V and Vijayvithal P V, ARKIVOC, 2008, XI, 1-10.
Steck E A, Chemotherapy of protozoan Diseases; Walter Reed, Army Institute of
Res., Washington D.C., 1971.
9.
Thompson P E and Werbal L M, Antibacterial Agents Chemistry Pharmacology,
Academic press, New York, 1972.
Falco E A and Brit J Pharmacol., 1961, 6, 185.
10
11
Pemmisin M, Lue-Due C, Hoguet F and Gaultier C, Narcisse J, Eur J Chem., 1988,
23, 534.
Ram V J, Pak J Chem., 1989, 331, 893.
12

180
V. S. SURYAWANSHI et al.
13
14
15
Ram V J, Haque N and Guru P Y, Eur J Med Chem., 1992, 27, 851-855.
Suguira K, Schimid M M and Brown FG, Cancer Chemother Rep., 1973, 2, 231-233.
Basavraj P, Vaidya V P and Vijay Kumar M L, Indian J Heterocycl Chem., 2002, 12,
89-94.
16
17
18
19
Balzarini J and McGuigan C, J Antimicrob Chemothr., 2002, 50(1), 5-9.
Mercer F L, Lindhorst L E and Commoner B, Science, 1953, 117, 558.
Nasr M.N and Gineinah M M, Arch Pharm., 2002, 335, 289-295.
EI-Gaby M S, Abdel-Hamide S G and Ghorab M M and El-Sayed S M, Acta Pharm.,
1999, 49, 149.
20
21
Cheng C C, Progr Med Chem., 1969, 6, 67-134.
Kumarswamy M N, Prathima Matthias D A, Chandrasekhar C and Vaidya V P,
Indian J Pharm Sci., 2006, 68(6), 731-736.
22
23
24
Nega S, Aionso J, Diazj A and Junquere F, J Het Chem., 1990, 27, 269.
Sondhi S M, Johar M, Rajvanshi S, Dastidar S G, Australian J Chem., 2001, 54, 69-74.
Banty A L, Antimicrobial susceptibility tests: Principle and practice; Edited by Illus,
Lea and Febiger, Philadelphia, PA: USA, 1976,180.
25
Saundane A R, Rudresh K, Satyanarayan N D and Hiremath S.P, Indian J Pharm Sci.,
1998, 60(6), 379-383.

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