Novel synthesis and characterization of some pyrimidine derivatives of oxadiazoles, triazole and 1,3,4-thiadiazoles

Article abstract of DOI:10.14233/ajchem.2013.13320

In the present investigation, synthetic methods of 4-aryl-6-methyl-2-oxo-1, 2,3,4-tetrahydro pyrimidine-(5)-1,3,4-thiadiazole-2-amine (3) and 4-aryl-6-methyl-2-oxo-1,2,3,4-tetrahydro pyrimidine-(5)-1,3,4-oxadiazole-2-amine (3a) and 4-aryl-6-methyl-2-oxo-1

Full text of DOI:10.14233/ajchem.2013.13320

Asian Journal of Chemistry; Vol. 25, No. 4 (2013), 2070-2072
http://dx.doi.org/10.14233/ajchem.2013.13320
Novel Synthesis and Characterization of Some Pyrimidine
Derivatives of Oxadiazoles, Triazole and 1,3,4-Thiadiazoles
*
B. ANDREWS and MANSUR AHMED
Department of Chemistry, Islamiah College, Vaniyambadi-635 751, India
*Corresponding author: E-mail: bandrews2006@yahoo.com
(Received: 23 December 2011;
Accepted: 12 October 2012)
AJC-12281
In the present investigation, synthetic methods of 4-aryl-6-methyl-2-oxo-1,2,3,4-tetrahydro pyrimidine-(5)-1,3,4-thiadiazole-2-amine (3)
and 4-aryl-6-methyl-2-oxo-1,2,3,4-tetrahydro pyrimidine-(5)-1,3,4-oxadiazole-2-amine (3a) and 4-aryl-6-methyl-2-oxo-1,2,3,4-tetrahydro
pyrimidine-(5)-1,3,4-triazole-2-thiol derivative (3b) are described. Compound 1 is converted to carbothiamide 2 by the reaction with
ethyl ester followed by thiosemicarbazide. Compound 2 acts as key intermediate for all series of the final compounds. In one pathway, 2
is converted to corresponding thiadiazole 3 by treatment with conc. H2SO4 and NH3 and compound 3a by treatment with I2 followed by
KI and NaOH and compound 3b by treatment with 10 % of NaOH to furnish the final compound. Structural elucidation is accomplished
by IR, 1H NMR and mass spectral data of the synthesized compounds.
Key Words: Pyrimidine, Thiadiazole, Oxadiazole, Triazole, Carbothiamide, Thiosemicarbazide.
1 (0.01 mol) and thiosemicarbazide (0.01 mol) in acetone was
refluxed for 8-10 h and allow to cool and yellow solid was
recrystallized was carried out from alcohol (Scheme-I). m.p.
of the compound is 146 ºC yield 75 %. IR (KBr, νmax, cm-1):
3242, 3115 (N-H str.), 2978 (C-H str, Ar-H), 1724 (C=O Str,
CONH), 1647 (C=N str.), 1313 (C-N str.), 1090 (C=S str.). 1H
NMR (acetone, δ): 8.34 (1H, br,s), 7.82-7.80 (1H, m), 6.92(1H,
br, s), 5.38 (5H, d), 2.10-1.99 (3H, m), 1.17-1.15 (3H, s). Mass
spectra: m/z = 305 M+ (base peak).
INTRODUCTION
Literature survey revealed the importance of pyrimidine
derivatives and antimicrobial agent1, which are found to be
associated with variety of biological activities such as insecticidal,
antimicrobial, antiviral etc., pyrimidine derivatives2-5 are also
known to possess antiinflammatory activity. Moreover incorpo-
ration of pyrimidine ester6-8 with thiosemicarbazide compound
has produced new organic compound9,10 motivated by the
above mentioned facts herein is reported. The synthesis of
new compound and their characterization of new pyrimidine
series conjugated with 1,3,4-thiadiazole11, 1,3,4-oxadiazole12
and 1,3,4-triazole13,14 rings, respectively.
4-Aryl-6-methyl-2-oxo-1,2,3,4-tetrahydro pyrimidine-
(5)-1,3,4-thiadiazole-2-amine 3: Carbothioamide 2. (0.01
mol) was dissolved in 5 mL conc. H2SO4. This solution was
stirred at room temperature for a few minutes and left overnight.
It was then poured on crushed ice. The resulting suspension
was kept in ammonical water for 2 h filtered and recrystallized
from alcohol as white crystals (Scheme-II). m.p. 120 ºC, yield
82 %. IR (KBr, νmax, cm-1): 3328, 3173 (N-H str.), 3105 (C-H
str. Ar-H), 2979 (C-H str. CH2), 1669 (C=O str. CONH), 1574
(C=N str.), 1118 (C-S str.). 1H NMR (acetone, δ): 9.24 (1H,
s), 8.69 (1H, s), 7.30-7.27 (1H, m), 5.43 (1H, d, J = 3.0 Hz),
4.11-4.01 (2H, m), 2.45 (3H, s). Mass spectra: m/z = 287 M+
(base peak).
EXPERIMENTAL
Melting points of all the synthesized compounds were
taken in open capillaries and are uncorrected. IR spectra (KBr)
were recorded on a Perkin-Elmer 1300 FT IR spectrometer
and 1H NMR were determined on a Bruker WM-500 (500 MHz
FT NMR) spectrometer using TMS as internal standard, mass
spectra were recorded on GCMS spectrometer-Jeol GC mate
spectrometer.All compounds gave satisfactory micro analytical
results.
4-Aryl-6-methyl-2-oxo-1,2,3,4-tetrahydro pyrimidine-
(5)-1,3,4-oxadiazole-2-amine 3a: Compound 2. (0.01 mol)
was added into 10 mL of 10 % NaOH with cooling and shaking
iodine solution in KI (10 %) was added gradually and shaking
until the iodine colour persisted. Heating was continued for
Purity of the synthesized compound was checked by TLC
using Silica gel-G Plates using water-benzene as a solvent.
Pyrimidine 1 were prepared by reported methods.
4-Aryl-6-methyl-2 oxo-1,2,3,4-tetrahydro pyrimidine-
(5)-carbothioamide 2: An equimolar mixture of compound

Vol. 25, No. 4 (2013)
Novel Synthesis of Some Pyrimidine Derivatives of Oxadiazoles, Triazole and 1,3,4-Thiadiazoles 2071
1H NMR (acetone, δ): 8.40 (1H, br), 7.42-7.3 (5H, m), 7.32-
7.40 (1H, m), 6.95 (1H, br), 5.39 (1H, d, J = 3.5 Hz), 2.40
(3H, s). Mass spectra: m/z = 271 M+ (base peak).
O
4-Aryl-6-methyl-2-oxo-1,2,3,4-tetrahydro pyrimidine-
(5)-1,3,4-triazole-2-thiol (3b): To the aqueous solution of
sodium hydroxide (10 %, 40 mL) was added in carbothioamide
2. (0.01 mol) and the reaction mixture refluxed gently for 2 h.
The resulting solution was treated with charcoal, cooled and
filtered. The filtrate was acidified with 10 % HCl and adjusted
pH 5-6. The solid mass was precipitated, filtered, washed with
ice-cold water and re-crystallized from alcohol as white crystals
(Scheme-II). m.p. 205 ºC, yield 80 %. IR (KBr, νmax, cm-1):
3328, 3173 (N-H str.), 3105 (C-H str. Ar-H), 2979 (C-H str.
CH2), 1669 (C=O str. CONH), 1574 (C=N str.), 1118 (C-S
H3CH2CO
H3C
NH
N
X
H
compound-1
S
S
Reflux
Reflux 8-10 h
8-10 hrs
H2
C NH2
H2N HNN NCH NH2
Acetone
1
str.). H NMR (acetone, δ): 9.24 (1H, s), 8.69 (1H, s), 7.30-
7.27 (1H, m), 5.43 (1H, d, J = 3.0 Hz), 4.11-4.01 (2H, m),
2.45 (3H, s). Mass spectra: m/z = 287 M+ (base peak).
O
H
H2N
N
N
H
NH
RESULTS AND DISCUSSION
S
H3C
N
H
X
The key intermediate used for the synthesis of all series
of the final compounds was 4-aryl-6-methyl-2-oxo-1,2,3,4
tetrahydro pyrimidine-(5)-3-carbothioamide 2, which in turn
was prepared by the reaction of 4-aryl-6-methyl-2-oxo-1,2,3,4-
tetrahydro pyrimidine-(5)-carboxylic acid ethyl ester-1 with
thiosemicarbazide in presences of acetone. Formation of 2 was
confirmed by the presence of N-H stretching peaks at 3328
and 3173 cm-1 and C=O stretching peaks at 1669 cm-1 in IR
and multiplet at 8.34 cm-1 for NH.NH.C=S.NH2 group in 1H
Scheme-I: Synthesis and reaction of 4-aryl-6-methyl pyrimidine derivatives
5-6 h and cooled and poured onto ice-cold water. The solution
was filtered washed with cold water and little amount of carbon
disulphide was added. The product was recrysta-llized from
alcohol (Scheme-II). m.p. 160 ºC, yield 85 %. IR (KBr, νmax
,
cm-1): 3245, 3117 (N-H str.), 3060 (C-H str. Ar-H), 2979 (C-H
Str, CH2), 1649 (C=N str.), 1420 (C-O-C str.), 1699 (C=O str.).
N
N
H2N
(3)
S
NH
Conc.H2SO4
H3C
N
H
X
NH3
O
H
N
H2N
N
N
I2 / KI
NaOH
N
H
NH
(3a)
H2N
S
O
NH
H3C
N
H
X
H3C
N
H
X
Compound-2
NaOH
N
N
HS
(3b)
N
H
NH
H3C
N
H
X
Scheme-II: Synthesis and reaction of 4-aryl-6-methyl pyrimidine derivatives

2072 Andrews et al.
Asian J. Chem.
TABLE-1
PHYSICAL AND ANALYTICAL DATA OF COMPOUNDS 2, 3, 3A AND 3B
Calcd. (%)
Compounds
m.f.
m.w.
Yield (%)
m.p. (ºC)
Time (h)
C
N
C13H15N5O2S1
C13H13N5O1S1
C13H13N5O2
305
287
271
287
75
82
85
80
146
120
160
205
8-10
–
(51.35)
(54.59)
(57.82)
(54.59)
(23.03)
(24.48)
(25.93)
(24.48)
2
3
5-6
3a
3b
C13H13N5O1S1
2-2.5
NMR spectra. Treatment of compound 2 with conc. H2SO4
and NH3, furnished 4-aryl-6-methyl-2-oxo-1,2,3,4-tetrahydro
pyrimidine-(5)-1,3,4-thiadiazole-2-amine (3). The structure of
3 was elucidated on the basis of C-S-C linkage in the thiadiazol
ring, which caused a sharp absorption band at 1102 cm-1 in its
IR spectrum.
1H NMR spectrum showed a fine singlet at δ 4.11 due to
NH2 functionality confirmations of their structure were
obtained through spectral and analytical data (physical and
analytical data are given in Table-1). IR and 1H NMR spectral
data revealed carbonyl absorption band at 1725 cm-1 of
NH-CO-NH group, N-O stretching band at 1355 cm-1 aliphatic
C-H and aromatic C-H stretching at 2979 and 3105 cm-1 group
of pyrimidine moiety 3. Mass spectrum also supported the
proposed structure by viewing molecular ion peak at m/z =
287 M+.
C-H stretching at 2979 and 3105 cm-1 group of pyrimidine
moiety 3b. Mass spectrum also supported the proposed structure
by viewing molecular ion peak at m/z = 287 M+.
Conclusion
A novel method for the synthesis of 1,3,4-oxadiazole,
1,3,4-triazole and 1,3,4-thiadiazole tetrahydro pyrimidine
derivatives by modified compound 2 using conc. H2SO4 and
NH3 for compound 3 and I2 followed by KI and NaOH for
compound 3a and NaOH for compound 3b was developed for
the first time and the yields are excellent. The mildness of the
method together with ease of operation should largely extend
the scope of this as an alternate substituted compound systems.
These condition will tolerate the presence of different consti-
tuents on aromatic ring.
ACKNOWLEDGEMENTS
In another pathway, 2 underwent ready heterocyclization
upon its reaction with I2 followed by KI and added 10 % NaOH
with cooling and shaking to afford 4-aryl-6-methyl-2-oxo-
1,2,3,4-tetrahydro pyrimidine-(5)-1,3,4-oxadiazole-2-amine
3a. In IR spectrum, bands in the range of 1735 and 1699 cm-1
were obtained due to carbonyl stretching and C-O-C stretching
The authors are thankful to Principal and HOD of
Chemistry, Islamiah College,Vaniyambadi, India for constant
encouragement and providing necessary research facilities.
REFERENCES
1
range from 1420 and 1465 cm-1. In the H NMR spectrum,
1. C.O. Kape, Tetrahedron, 49, 6937 (1993).
2. C.O. Kape, Eur. J. Med. Chem., 35, 1043 (2000).
3. A. Manjula, B.V. Rao and P. Neelakantam, Synth. Commun., 34, 2665
(2004).
signal were found at δ 5.39 which showed the presence of
oxo-diazol and NH2 group in ring.
The assigned structure of 3a was based on the obtained
analytical and spectral data. The mass spectrum also supported
the proposed structure by viewing molecular ion peak at m/z
= 271 M+.
4. A.J. Zych, H.-J. Wang and S.A. Sakwa, Tetrahedron Lett., 51, 5103
(2010).
5. Garima, V.P. Srivastava and L.D.S. Yadav, Tetrahedron Lett., 51, 6436
(2010).
6. M.B. Moore and R.T. Rapela, J. Am. Chem. Soc., 68, 1657 (1946).
7. R.O. Atkinson, J. Chem. Soc., 1329 (1954).
8. R.S. Varma, J. Indian Chem. Soc., 81, 627 (2004).
9. M. Kidwai, R. Venkataramanan and B. Dave, J. Heterocycl. Chem., 39,
1045 (2002).
In another path way treatment of compound 2 with NaOH
furnished 4-aryl-6-methyl-2-oxo-1,2,3,4-tetrahydro pyrimidine-
(5)-1,3,4-triazole-2-thiol (3b). The structure of 3b was eluci-
dated on the basis of C-N-C linkage in the triazole ring, which
caused a sharp absorption band at 1102 cm-1 in its IR spectrum.
1H NMR spectrum showed a fine singlet at δ 4.11 due to
SH functionality confirmations of their structure were obtained
through spectral and analytical data. (Physical and analytical
data are given in Table-1) IR and 1H NMR spectral data revealed
carbonyl absorption band at 1725 cm-1 of NH-CO-NH group,
N-O stretching band at 1355 cm-1 aliphatic C-H and aromatic
10. N.A. Ross and R.A. Burtsch, J. Heterocycl. Chem., 38, 1255 (2001).
11. V. Singh, V. Sapehiyia and G.L. Kad, Synthesis, 198 (2003).
12. X. Zou and G. Jin, J. Heterocycl. Chem., 38, 993 (2001).
13. N.A. Ross and R.A. Burtsch, J. Heterocycl. Chem., 38, 1255 (2001).
14. S.G. Jagadhani, S.B. Kale, N.R. Dalvi, M.S. More and B.K. Karale,
Indian J. Heterocycl. Chem., 15, 335 (2006).