1074
O. Prakash et al. / European Journal of Medicinal Chemistry 39 (2004) 1073–1077
4.1.1.1. Characterization data of new hydrazones are gi-
ven. 2a: m.p. 84–86 °C, yield 95.93%. IR cm–1 3239.8 N-
Hstr.; 1HNMR.d 2.24 (s, 6H, C4–CH3, C6–CH3), 6.51 (s, 1H,
–N=C–H), 7.31–7.41 (d, 2H, C2′–H, C3′–H), 7.62–7.71 (d,
2H, C5′–H, C6′–H), 8.00 (s, 1H, C5–H).
2b:m.p. 182–184 °C, yield 51.93%. IR cm–1 3215.8 N-
Hstr.; 1HNMR. d 2.33 (s, 6H, C4–CH3, C6–CH3), 6.50 (s, 1H,
–N=C–H), 7.17–7.21 (1H, m, C5′–H), 7.25–7.29 (2H, m,
C4′–H, C6′–H), 8.13–8.16 (1H, dd, J = 1.8, 7.8 Hz, C3′–H).
2c:m.p. 170–172 °C, yield 46.66%. IR cm–1 3257.9 N-
Hstr.; 1HNMR. d 2.24 (s, 6H, C4–CH3, C6–CH3), 2.10 (s, 3H,
C4′–CH3), 6.46 (s, 1H, –N=C–H), 7.10–7.13 (d, 2H, C2′–H,
C3′–H), 7.56–7.59 (d, 2H, C5′–H, C6′–H), 8.00 (s, 1H,
C5–H).
2d: m.p. Ref. [18]; m.p. 166–167/170–172 °C, yield
78.51%.
2e:m.p. 199–201 °C, yield 87.66%. IR cm–1 3185.6 N-
Hstr.; 1HNMR d 2.37 (s, 6H, C4–CH3, C6–CH3), 6.54 (s, 1H,
–N=C–H), 8.45 (s, 1H, C5–H), 7.42–7.43 (1H, m, C5′–H),
7.55–7.57 (m, 1H, C4′–H), 7.94–7.96 (1H, m, C6′–H), 8.28–
8.31 (m, 1H, C3′–H).
Scheme 1
.
reby illustrating the generality of our previous I(III) mediated
approach.
2f:m.p. 180–181 °C, yield 31.46%. IR cm–1 3213.8 N-
Hstr.; 1HNMR. d 2.35 (s, 6H, C4–CH3, C6–CH3), 3.86 (s, 3H,
C4–OCH3), 6.46 (s, 1H, –N=C–H), 3.91(s, 3H, C3′–OCH3),
7.43–7.44 (d, 1H, C5′–H), 6.77–6.80 (d, 1H, C2′–H), 7.17–
7.20 (dd, 1H, C6′–H), 7.6 (s, 1H, C5–H).
3. Biological investigation and results
2g:m.p. 170–172 °C, yield 56.78%. IR cm–1 3565.6 N-
Hstr.; 1HNMR d 2.10 (s, 6H, C4–CH3, C6–CH3), 6.47 (s, 1H,
–N=C–H), 8.5 (s, 1H, C5–H), 3.85 (s, 3H, C4′–OCH3), 3.86
(s, 6H, C3′–OCH3, C5′–OCH3), 7.02 (s, 2H, C2′–H, C6′–H).
2h:m.p. 123–125 °C, yield 54.29%. IR cm–1 3203.7 N-
Hstr.; 1HNMR d 2.10 (s, 6H, C4–CH3, C6–CH3), 6.47 (s, 1H,
–N=C–H), 8.71(s, 1H, C5–H), 7.04–7.07 (m, 1H, C4′–H),
7.27–7.29 (d, 1H, C5′–H, J = 5.1 Hz), 7.35–7.36 (d, 1H,
C3′–H, J = 3.6 Hz).
Compounds 3b–g and 3i–k were tested in vitro for their
antibacterial activity against Bacillus subtilis, Escherichia
coli, Staphylococcus aureus and Salmonella typhi. 3-(4′-
Pyridyl)-5,7-dimethyl-1,2,4-triazolo[4,3-a]pyrimidine (3k)
and 3-(3′,4′-dimethoxyphenyl)-5,7-dimethyl-1,2,4-triazolo-
[4,3-a]pyrimidine (3f) were associated with substantially hi-
gher antibacterial activity than some commercial antibiotics
2i:m.p. 108–110 °C, yield 45.27%. IR cm–1 3172.8 N-
Hstr.; 1HNMR d 2.10 (s, 6H, C4–CH3, C6–CH3), 6.52 (s, 1H,
–N=C–H), 7.93 (s, 1H, C5–H), 7.25–8.10 (m, 4H, C3′–H,
C4′–H, C5′–H C6′–H).
4. Experimental
4.1. Chemical synthesis
2j:m.p. 152–153 °C, yield 65.60%. IR cm–1 3179.5 N-
Hstr.; 1HNMR d 2.36 (s, 6H, C4–CH3, C6–CH3), 6.51(s, 1H,
–N=C–H), 7.83 (s, 1H, C5–H), 7.23–7.27 (dd, 1H, C5′–H,
J = 4.8, 8.1 Hz), 8.14–8.18 (dd, 1H, C4′–H, J = 2.1, 6.0 Hz),
8.48–8.50 (distorted doublet, 2H, C2′–H, C6′–H).
2k:m.p. 171–172°C, yield 67.40%. IR cm–1 3179.5 N-
Hstr.; 1HNMR d 2.37 (s, 6H, C4–CH3, C6–CH3), 6.54 (s, 1H,
–N=C–H), 7.76 (s, 1H, C5–H), 7.54–7.56 (dd, 2H, C3′–H,
C5′–H, J = 2.1, 5.1 Hz), 8.54–8.56 (dd, 2H, C2′–H, C6′–H,
J = 1.5, 4.5 Hz).
Melting points were determined in open capillaries in
electrical melting point apparatus and are uncorrected. The
IR (KBr) and 1HNMR spectra were recorded on Buck Scien-
tific IR M-500 and Bruker (300 MHz) spectrometers, respec-
tively. All the new compounds gave satisfactory analytical
results (within 0.4 of the theoretical values).
4,6-Dimethyl-2-hydrazinopyrimidine 1 was synthesized
according to the literature procedure commencing with urea
4.1.1. Hydrazones 2a–k
4.1.2. 3-Aryl-5,7-dimethyl-1,2,4-triazolo [4,3-a]
The hydrazones 2 required for the oxidative cyclization
were prepared by the condensation of 2-hydrazino-4,6-
dimethylpyrimidine 1 with different aromatic and heteroaro-
matic aldehydes in ethanol with a trace of glacial acetic acid
pyrimidines 3a–k
4.1.2.1. General procedure. To a stirred solution of pyrimi-
dinylhydrazones 2 (0.01 mol) in DCM (25 ml) at room
temperature, IBD (0.01 mol) was added in four to five por-