Synthesis and fungicidal activities of new 1,2,4-triazolo[1,5-a]pyrimidines

Article abstract of DOI:10.1002/cbdv.200800168

A series of new acetohydrazone-containing 1,2,4-triazolo[1,5-a]pyrimidine derivatives were designed and synthesized for the purpose of searching for novel agrochemicals with higher fungicidal activity. Their in vitro fungicidal activities against Rhizocto

Full text of DOI:10.1002/cbdv.200800168

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Synthesis and Fungicidal Activities of New 1,2,4-Triazolo[1,5-a]pyrimidines
by Qiong Chen, Zu-Ming Liu, Chao-Nan Chen, Li-Li Jiang, and Guang-Fu Yang*
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central
China Normal University, Wuhan 430079, P. R. China
(phone: þ86-27-67867800; fax: þ86-27-67867141; e-mail: gfyang@mail.ccnu.edu.cn)
A series of new acetohydrazone-containing 1,2,4-triazolo[1,5-a]pyrimidine derivatives were designed
and synthesized for the purpose of searching for novel agrochemicals with higher fungicidal activity.
Their in vitro fungicidal activities against Rhizoctonia solani were evaluated, and the most promising
compound, 2-[(5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-2’-[(2-hydroxyphenyl)methyli-
dene]acetohydrazide (2-17), showed a lower EC50 value (5.34 mg mlꢀ1) than that of commercial
carbendazim (EC50 ¼7.62 mg mlꢀ1). Additionally, compound 2-17 was also found to display broad-
spectrum fungicidal activities, and its EC50 value (4.56 mg mlꢀ1) against Botrytis cinereapers was very
similar to that of carbendazim. Qualitative structure–activity relationships (QSARs) of the synthesized
compounds were also discussed.
1. Introduction. – Triazolo[1,5-a]pyrimidine derivatives have attracted a lot of
attention from medicinal and agricultural chemists due to their broad-spectrum
biological activities [1–9], i.e., as cardiovascular vasodilators [1], calcium channel-
blocking agents, and potassium-channel inhibitors and openers. Some triazolopyrimi-
dine-2-sulfonamide derivatives, such as metosulam [6], flumetsulam [7], and florasu-
lam [8], have also been used as herbicides for many years [9]. Recently, many
triazolopyrimidine derivatives have been patented for their fungicidal activities [10].
To search for new triazolopyrimidines with potent fungicidal activities, we previously
designed and synthesized a series of 1,3,4-oxadiazole-containing compounds 1, some of
which were found to display good fungicidal activity against Rhizoctonia solani.
However, these compounds displayed a narrow fungicidal spectrum. Keeping in mind
that the acetohydrazone derivatives always displayed interesting biological activities
[11][12], we designed and synthesized a series of new 1,2,4-triazolo[1,5-a]pyrimidine
derivatives, 2 and 3, by incorporating the pharmacophore of acetohydrazone with the
aim of discovery of new lead compounds with more potent and broad-spectrum
fungicidal activities.
2. Results and Discussion. – 2.1. Chemistry. The target compounds 2 and 3 were
synthesized by a multiple-step procedure as shown in the Scheme. In Route A, the
starting material 4, prepared according to our previously described procedures [12],
reacted with various benzaldehydes to afford the target compounds 2-1–2-40 in yields
of 57–97%. In Route B, 6-chloro-5,7-dimethyl-2-(methylsulfanyl)-1,2,4-triazolo[1,5-
a]pyrimidine (5), easily prepared by the cyclization reaction of 3-amino-5-(methyl-
ꢀ 2009 Verlag Helvetica Chimica Acta AG, Zꢁrich

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sulfanyl)-1,2,4-triazole with 3-chloropentane-2,4-dione, was oxidized by H2O2 in AcOH
to give 6-chloro-5,7-dimethyl-(2-methylsulfonyl)-1,2,4-triazolo[1,5-a]pyrimidine (6) in
a yield of 91%. Then, 6 was reacted with ethyl 2-hydroxyacetate under basic conditions
Scheme
a) EtOH, r.t. b) H2O2, AcOH, 608. c) HOCH2COOEt, NaH, toluene, reflux. d) NH2NH2 ·H2O, EtOH,
reflux. e) Substituted benzaldehyde, EtOH, r.t.

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to afford ethyl 2-[(6-chloro-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidin-2-yl)oxy]ace-
tate (7), which reacted subsequently with 1 equiv. of NH2NH2 ·H2O to afford 2-[(6-
chloro-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidin-2-yl)oxy]acetohydrazide (8) in 82%
yield. Finally, the desired hydrazides 3-1–3-9 were obtained in 60–80% yields by the
reaction of compound 8 with various benzaldehydes. The experimental results
indicated that the reactivity of the benzaldehyde determined the reaction time and
the yields of compounds 2 and 3. The reaction of benzaldehydes bearing an electron-
withdrawing group proceeded more smoothly than those bearing an electron-donating
group. The structures of all of the new compounds were characterized by 1H-NMR, MS,
and elemental analyses. In addition, the crystal structure of 2-3 was determined by X-
ray diffraction analysis (Fig.).
Figure. ORTEP Plot [13] of compound 2-3. Displacement ellipsoids are drawn at the 30% probability
level.
2.2. Fungicidal Activity and SAR. The EC50 values against R. solani of compounds 2,
3, and carbendazim were listed in Table 1. For the sake of clarity, according to the
substitution patterns at the triazolopyrimidine ring, compounds 2-1–2-20, 2-21–2-40,
and 3-1–3-9 will be named monosubstituted (MS), disubstituted (DS), and trisub-
stituted (TS) derivatives, respectively, through the text. As indicated in Table 1,
compound 2-17 (EC50 ¼5.34 mg mlꢀ1) exhibited the highest fungicidal activity against
R. solani, which is higher than that of carbendazim (EC50 ¼7.62 mg mlꢀ1). In addition,
some compounds, such as 2-5 (EC50 ¼8.01 mg mlꢀ1), 2-6 (EC50 ¼7.28 mg mlꢀ1), 2-22
(EC50 ¼7.62 mg mlꢀ1), and 2-32 (EC50 ¼7.30 mg mlꢀ1), were found to display
comparable fungicidal activity as carbendazim. Although it is difficult to derive
quantitative structure–activity relationships (QSARs), some interesting phenomena
could be deduced from Table 1. For example, halogenated MS derivatives always
displayed higher activity than the corresponding halogenated TS derivatives (2-1>3-1,
2-3>3-2, and 2-6>2-14), TS Derivatives bearing an electron-donating substituent
always displayed higher activity than the corresponding MS and DS derivatives (3-5>
2-36>2-19 and 3-6>2-35>2-13). Of the phenyl-substitution patterns investigated
within the DS and TS derivatives bearing two electron-donating substituents, 2,5-
disubstitution (i.e., 2-32, 2-33, and 2-34) displayed higher activity than 2,4-disubstitu-
tion (i.e., 2-31) and 3,4-disubstitution (i.e., 2-39). However, 2,4-disubstitution (i.e., 3-7)

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displayed higher activity than 2,5-disubstitution (i.e., 3-8 and 3-9) within the TS
derivatives bearing electron-donating groups. With respect to the substituents of
investigated MS derivatives, the order of increasing fungicidal activity could be
summarized as follows: OH (2-17)ꢂCl (2-1)>NO2 (2-10)>F (2-7) at position 2, NO2
(2-11)>Br (2-9)>Cl (2-2) at position 3, F (2-6)>Cl (2-3)>Me (2-19)>MeO (2-13)ꢃ
Me2N (2-18)>NO2 (2-12)>OH (2-15) at position 4.
In addition, the EC50 values against Fusarium oxysporium, Botrytis cinereapers,
Gibberella zeae, Dothiorella gregaria, and Colletotrichum gossypii of highly active
compounds 2-5, 2-6, 2-17, 2-22, 2-32, and carbendazim were collected in Table 2. All
compounds except 2-22 displayed the most potent fungicidal activity against B.
cinereapers among the five tested fungi. Fortunately, compound 2-17 was found to
display fungicidal activity comparable with that of carbendazim against B. cinereapers.
Table 2. Fungicidal Spectrum (EC50 in mg mlꢀ1) of Some Representative Compounds
Compound
F. oxysporium
B. cinereaper
G. zeae
D. gregaria
C. gossypii
2-5
2-6
2-17
2-22
2-32
Carbendazim
9.6ꢁ0.4
9.7ꢁ0.4
12.8ꢁ0.5
8.5ꢁ0.3
15.0ꢁ0.7
2.0ꢁ0.1
5.8ꢁ0.3
5.3ꢁ0.3
4.6ꢁ0.2
14.6ꢁ0.5
8.9ꢁ0.3
3.6ꢁ0.1
13.8ꢁ0.5
13.3ꢁ0.4
14.7ꢁ0.4
17.2ꢁ0.4
15.5ꢁ0.5
0.9ꢁ0.1
18.8ꢁ0.4
13.1ꢁ0.4
20.1ꢁ0.5
18.7ꢁ0.4
16.7ꢁ0.4
0.8ꢁ0.1
13.7ꢁ0.4
18.5ꢁ0.8
16.0ꢁ0.4
16.4ꢁ0.4
22.6ꢁ0.6
1.2ꢁ0.1
3. Conclusions. – In summary, a series of new 1,2,4-triazolo[1,5-a]pyrimidine
derivatives with fungicidal activity were designed and synthesized by incorporating the
pharmacophore of acetohydrazone within the scaffold of triazolo[1,5-a]pyrimidine.
Two compounds, 2-17 and 2-32, were found to display higher fungicidal activities than
carbendazim against R. solani, while compound 2-17 displayed fungicidal activity
comparable with that of carbendazim against B. cinereapers. Further structural
optimizations are underway.
The present work was supported by the National Natural Science Foundation of China (No. 20702018
and 20432010) and the National Basic Research Program of China (No. 2003CB114400).
Experimental Part
General. All chemical reagents were commercially available and treated according to standard
methods before use. Solvents were dried in a routine way and redistilled. Intermediates were prepared
according to previously reported methods [12][14][15]. Rhizoctonia solani, Fusarium oxysporium,
Botrytis cinereapers, Gibberella zeae, Dothiorella gregaria, and Colletotrichum gossypii were provided
through the courtesy of the Center for Bioassay, The Environment and Plant Protection Institute of
Chinese Academy of Tropical Agricultural Sciences. M.p.: Electrothermal digital melting-point
1
apparatus; uncorrected. H-NMR Spectra: Varian Mercury spectrometer, at 300 MHz, in (D6)DMSO;
d in ppm rel. to TMS, J in Hz. MS: Finnigan Trace MS organic mass spectrometer; in m/z. Elemental
analysis: Vario EL III instrument.
2-[(5-Methyl-1,2,4-triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]acetohydrazide (X¼H, R1 ¼H; 4a). A
mixture of 12.6 g (0.05 mol) of 2-[(5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]acetate and

CHEMISTRY & BIODIVERSITY – Vol. 6 (2009)
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2.94 g (0.05 mol) of 85% NH2NH2 ·H2O in 200 ml of EtOH was heated at 608 for 4 h. The mixture was
cooled to r.t., and the precipitate was filtered and recrystallized from MeOH to give pure 4a (8.09 g,
1
68%). White crystals. M.p. 170–1728. H-NMR (400 MHz): 9.36 (s, 1 H); 9.12 (d, J¼6.8, 1 H); 7.20 (d,
J¼6.4, 1 H); 4.33 (s, 2 H); 3.95 (s, 2 H); 2.60 (s, 3 H).
2-[(5,7-Dimethyl-1,2,4-triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]propanohydrazide (X¼Me, R1 ¼Me;
4b). A mixture of 14.0 g (0.05 mol) of 2-[(5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]pro-
panoate and 20.6 g (0.35 mol) of 85% NH2NH2 ·H2O in 200 ml of EtOH was refluxed for 7 h. The mixture
was cooled to r.t., and the precipitate was filtered and recrystallized from MeOH to give pure 4b (10.51 g,
1
79%). White crystals. M.p. 104–1068. H-NMR (400 MHz): 9.47 (s, 1 H); 7.13 (s, 1 H); 4.50 (q, J¼6.8,
1 H); 4.35 (s, 2 H); 2.68 (s, 3 H); 2.56 (s, 3 H); 1.56 (d, J¼7.2, 3 H).
6-Chloro-5,7-dimethyl-2-(methylsulfanyl)-1,2,4-triazolo[1,5-a]pyrimidine (5). A soln. of 6.50 g
(0.05 mol) of 3-amino-5-(methylsulfanyl)-1,2,4-triazole and 6.75 g (0.05 mol) of 3-chloropentane-2,4-
dione in 25 ml of glacial AcOH was heated at reflux for 18 h and poured into 150 ml of ice-H2O. The
precipitate was filtered and recrystallized from EtOH to give pure 5 (10.49 g, 92%). White crystals. M.p.
155–1578. 1H-NMR (400 MHz): 2.89 (s, 3 H); 2.74 (s, 3 H); 2.72 (s, 3 H).
6-Chloro-5,7-dimethyl-2-(methanesulfonyl)-1,2,4-triazolo[1,5-a]pyrimidine (6). To a soln. of 2.29 g
(10 mmol) of 5 dissolved in 20 ml of anh. CH2Cl2 was slowly added 1.73 g (10 mmol) of m-
chloroperbenzoic acid (mCPBA), maintaining the temp. of the mixture below 08. Stirring was continued
at r.t., until the reaction was complete (TLC, acetone/petroleum ether (PE) 2 :1). Then, 50 ml of H2O
was added, the mixture was extracted with CH2Cl2 (3ꢄ10 ml), the org. phase was washed with sat.
NaHCO3 soln. and H2O, and the separated org. phase was dried (anh. Mg2SO4). After the filtrate had
been evaporated, the residue was recrystallized from EtOH to give pure 6 (2.37 g, 91%). White solid.
1
M.p. 178–1798. H-NMR (400 MHz): 3.42 (s, 3 H); 3.02 (s, 3 H); 2.85 (s, 3 H).
Ethyl [6-Chloro-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidin-2-yl)oxy]acetate (7). A mixture of 4.38 g
(0.04 mol) of ethyl hydroxyacetate and 1.80 g (0.045 mol) of NaH (60%) in 150 ml of anh. toluene was
stirred at 55–608 for 1 h, then 5.2 g (0.02 mol) of 6 was added, and the mixture was refluxed, until the
reaction was complete (TLC, acetone/PE 2 :1). The mixture was cooled to r.t., and, after diatomite
filtration, the solvent was removed under reduced pressure. The residue was recrystallized from acetone/
PE 1:3 to give pure 7 (4.54 g, 80%). White solid. M.p. 96–988. 1H-NMR (400 MHz): 5.03 (s, 2 H); 4.25 (q,
J¼7.2, 2 H); 2.87 (s, 3 H); 2.72 (s, 3 H); 1.29 (t, J¼7.2, 3 H).
2-[(6-Chloro-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidin-2-yl)oxy]acetohydrazide (8). A mixture of
2.85 g (0.01 mol) of 7 and 4.12 g (0.07 mol) of 85% NH2NH2 ·H2O in 55 ml of EtOH was refluxed for 7 h.
The mixture was cooled to r.t., and the precipitate was filtered and recrystallized from EtOH to give pure
8 (2.21 g, 82%). White crystals. M.p. 174–1768. 1H-NMR (400 MHz): 9.38 (s, 1 H); 4.83 (s, 2 H); 4.33 (s,
2 H); 2.77 (s, 3 H); 2.66 (s, 3 H).
General Procedure for the Synthesis of the Target Compounds 2 and 3. A mixture of intermediate 4 or
8 (5 mmol) dissolved in 30 ml of EtOH and 6 mmol of substituted benzaldehyde was refluxed until the
reaction was complete (TLC, acetone/PE 2 :1). Then, the mixture was cooled to r.t., and the precipitate
was filtered and recrystallized from DMF/EtOH to give pure products 2 or 3 in yields of 60–97%.
2’-[(2-Chlorophenyl)methylidene]-2-[(5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]aceto-
hydrazide (2-1). Yield 94%. White solid. M.p. 168–1698. 1H-NMR: 11.89, 12.07 (2s, NH); 9.17 (d, J¼7.2,
CH); 8.44, 8.64 (2s, CH); 7.45–8.02 (m, 4 arom. H); 7.21 (d, J¼7.2, CH); 4.15, 4.58 (2s, CH2S); 2.61 (s,
Me). EI-MS: 360.9 (Mþ ). Anal. calc. for C15H13ClN6OS (360.82): C 49.93, H 3.63, N 23.29; found: C
50.07, H 3.42, N 23.50.
2’-[(3-Chlorophenyl)methylidene]-2-[(5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]aceto-
hydrazide (2-2). Yield 91%. White solid. M.p. 218–2208. 1H-NMR: 11.70, 11.82 (2s, NH); 9.11 (d, J¼7.2,
CH); 8.02, 8.22 (2s, CH); 7.46–7.74 (m, 4 arom. H); 7.18 (d, J¼7.2, CH); 4.14, 4.54 (2s, CH2S); 2.60 (s,
Me). EI-MS: 360.7 (Mþ ). Anal. calc. for C15H13ClN6OS (360.82): C 49.93, H 3.63, N 23.29; found: C
50.20, H 3.47, N 22.91.
2’-[(4-Chlorophenyl)methylidene]-2-[(5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]aceto-
hydrazide (2-3). Yield 83%. White solid. M.p. 232–2348. 1H-NMR: 11.72, 11.83 (2s, NH); 9.14 (d, J¼7.2,
CH); 8.05, 8.24 (2s, CH); 7.51–7.55 (m, 4 arom. H); 7.20 (d, J¼7.2, CH); 4.14, 4.55 (2s, CH2S); 2.61 (s,

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Me). EI-MS: 360.75 (Mþ ). Anal. calc. for C15H13ClN6OS (360.82): C 49.93, H 3.63, N 23.29; found: C
50.18, H 3.82, N 23.47.
2’-[(2,4-Dichlorophenyl)methylidene]-2-[(5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-
acetohydrazide (2-4). Yield 94%. Yellowy solid. M.p. 237–2398. 1H-NMR: 11.93, 12.05 (2s, NH); 9.13 (d,
J¼6.6, CH); 8.04, 8.25 (2s, CH); 7.50–8.01 (m, 3 arom. H); 7.19 (d, J¼6.6, CH); 4.16, 4.57 (2s, CH2S);
2.62 (s, Me). EI-MS: 395.3 (Mþ ). Anal. calc. for C15H12Cl2N6OS (395.27): C 45.58, H 3.06, N 21.26;
found: C 45.84, H 2.90, N 21.50.
2’-[(3,4-Dichlorophenyl)methylidene]-2-[(5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-
acetohydrazide (2-5). Yield 97%. Yellowy solid. M.p. 222–2248. 1H-NMR: 11.81, 11.96 (2s, NH); 9.12 (d,
J¼6.6, CH); 8.02, 8.22 (2s, CH); 7.70–7.93 (m, 3 arom. H); 7.20 (d, J¼6.6, CH); 4.17, 4.57 (2s, CH2S);
2.61 (s, Me). EI-MS: 394.9 (Mþ ). Anal. calc. for C15H12Cl2N6OS (395.27): C 45.58, H 3.06, N 21.26;
found: C 45.23, H 3.40, N 21.53.
2’-[(4-Fluorophenyl)methylidene]-2-[(5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]aceto-
hydrazide (2-6). Yield 94%. White solid. M.p. 228–2308. 1H-NMR: 11.68, 11.79 (2s, NH); 9.14 (d, J¼6.9,
CH); 8.03, 8.22 (2s, CH); 7.21–7.79 (m, 4 arom. H); 7.19 (d, J¼6.9, CH); 4.13, 4.55 (2s, CH2S); 2.60 (s,
Me). EI-MS: 344.4 (Mþ ). Anal. calc. for C15H13FN6OS (344.33): C 52.32, H 3.81, N 24.40; found: C 52.60,
H 4.02, N 24.69.
2’-[(2-Fluorophenyl)methylidene]-2-[(5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]aceto-
hydrazide (2-7). Yield 88%. White solid. M.p. 171–1738. 1H-NMR: 11.75, 11.96 (2s, NH); 9.12 (d, J¼7.2,
CH); 8.24, 8.46 (2s, CH); 7.19–7.92 (m, 4 arom. H); 7.17 (d, J¼7.2, CH); 4.14, 4.55 (2s, CH2S); 2.60 (s,
Me). EI-MS: 344.5 (Mþ ). Anal. calc. for C15H13FN6OS (344.37): C 52.32, H 3.81, N 24.40; found: C 52.07,
H 3.53, N 20.71.
2’-[(2-Chloro-6-fluorophenyl)methylidene]-2-[(5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfa-
nyl]acetohydrazide (2-8). Yield 92%. White solid. M.p. 198–2018. 1H-NMR: 11.86, 12.00 (2s, NH); 9.13
(d, J¼6.9, CH); 8.30, 8.48 (2s, CH); 7.31–7.51 (m, 3 arom. H); 7.19 (d, J¼6.9, CH); 4.16, 4.50 (2s, CH2S);
2.60 (s, Me). EI-MS: 379.1 (Mþ ). Anal. calc. for C15H12ClFN6OS (378.81): C 45.58, H 3.06, N 21.26;
found: C 45.42, H 3.40, N 21.50.
2’-[(3-Bromophenyl)methylidene]-2-[(5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]aceto-
hydrazide (2-9). Yield 95%. White solid. M.p. 224–2278. 1H-NMR: 11.76, 11.90 (2s, NH); 9.14 (d, J¼6.9,
CH); 8.02, 8.21 (2s, CH); 7.39–7.90 (m, 4 arom. H); 7.19 (d, J¼6.9, CH); 4.15, 4.56 (2s, CH2S); 2.61 (s,
Me). EI-MS: 404.8 (Mþ ). Anal. calc. for C15H13BrN6OS (405.27): C 44.45, H 3.23, N 20.74; found: C
44.20, H 3.50, N 21.01.
2-[(5-Methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-2’-[(2-nitrophenyl)methylidene]acetohy-
drazide (2-10). Yield 90%. Yellowy solid. M.p. 199–2008. 1H-NMR: 11.64, 11.83 (2s, NH); 8.64 (d, J¼6.6,
CH); 8.40, 8.61 (2s, CH); 7.56–8.30 (m, 4 arom. H); 7.03 (d, J¼6.6, CH); 3.98, 4.61 (2s, CH2S); 2.69 (s,
Me). EI-MS: 371.6 (Mþ ). Anal. calc. for C15H13N7O3S (371.37): C 48.51, H 3.53, N 26.40; found: C 48.72,
H 3.75, N 26.12.
2-[(5-Methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-2’-[(3-nitrophenyl)methylidene]acetohy-
drazide (2-11). Yield 83%. Yellowy solid. M.p. 215–2178. 1H-NMR: 11.88, 12.02 (2s, NH); 9.11 (d, J¼6.6,
CH); 8.17, 8.37 (2s, CH); 7.71–8.52 (m, 4 arom. H); 7.20 (d, J¼6.6, CH); 4.19, 4.60 (2s, CH2S); 2.61 (s,
Me). EI-MS: 371.7 (Mþ ). Anal. calc. for C15H13N7O3S (371.37): C 48.51, H 3.53, N 26.40; found: C 48.61,
H 3.29, N 26.58.
2-[(5-Methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-2’-[(4-nitrophenyl)methylidene]acetohy-
drazide (2-12). Yield 73%. Yellowy solid. M.p. 250–2518. 1H-NMR: 11.94, 12.06 (2s, NH); 9.13 (d, J¼6.9,
CH); 8.15, 8.35 (2s, CH); 7.96–8.30 (m, 4 arom. H); 7.20 (d, J¼6.9, CH); 4.17, 4.58 (2s, CH2S); 2.60 (s,
Me). EI-MS: 371.1 (Mþ ). Anal. calc. for C15H13N7O3S (371.37): C 48.51, H 3.53, N 26.40; found: C 48.69,
H 3.19, N 26.22.
2’-[(4-Methoxyphenyl)methylidene]-2-[(5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]ace-
tohydrazide (2-13). Yield 84%. White solid. M.p. 198–2018. 1H-NMR: 11.53, 11.63 (2s, NH); 9.13 (d, J¼
6.9, CH); 7.99, 8.18 (2s, CH); 6.99–7.65 (m, 4 arom. H); 7.20 (d, J¼6.9, CH); 4.17, 4.58 (2s, CH2S); 3.81 (s,
MeO); 2.61 (s, Me). EI-MS: 356.1 (Mþ ). Anal. calc. for C16H16N6O2S (356.40): C 53.92, H 4.52, N 23.58;
found: C 54.14, H 4.79, N 23.19.

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2’-[(4-Hydroxy-3-methoxyphenyl)methylidene]-2-[(5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-
sulfanyl]acetohydrazide (2-14). Yield 88%. White solid. M.p. 154–1578. 1H-NMR: 11.49, 11.59 (2s, NH);
9.53 (s, OH); 9.10 (d, J¼5.7, CH); 7.89, 8.04 (2s, CH); 7.06–7.24 (m, 3 arom. H); 6.79 (d, J¼5.7, CH);
4.09, 4.50 (2s, CH2S); 3.79 (s, MeO); 2.57 (s, Me). EI-MS: 372.8 (Mþ ). Anal. calc. for C16H16N6O3S
(372.40): C 51.60, H 4.33, N 22.57; found: C 51.31, H 4.05, N 22.82.
2’-[(4-Hydroxyphenyl)methylidene]-2-[(5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]ace-
1
tohydrazide (2-15). Yield 82%. Yellowy solid. M.p. 237–2398. H-NMR: 11.45, 11.55 (2s, NH); 9.89 (s,
OH); 9.15 (d, J¼6.9, CH); 7.89, 8.04 (2s, CH); 7.19 (d, J¼6.9, CH); 6.81–7.54 (m, 4 arom. H); 4.11, 4.52
(2s, CH2S); 2.61 (s, Me). EI-MS: 342.2 (Mþ ). Anal. calc. for C15H14N6O2S (342.38): C 52.62, H 4.12, N
24.55; found: C 52.89, H 3.97, N 24.32.
2’-[(2,4-Dihydroxyphenyl)methylidene]-2-[(5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-
1
acetohydrazide (2-16). Yield 80%. Yellowy solid. M.p. 236–2378. H-NMR: 11.77 (s, OH); 11.16, 11.39
(2s, NH); 9.92 (s, OH); 9.11 (d, J¼6.3, CH); 8.21, 8.30 (2s, CH); 7.18 (d, J¼6.3, CH); 6.30–7.47 (m, 3
arom. H); 4.12, 4.49 (2s, CH2S); 2.60 (s, Me). EI-MS: 358.5 (Mþ ). Anal. calc. for C15H14N6O3S (358.38):
C 50.27, H 3.94, N 23.45; found: C 49.98, H 4.09, N 23.70.
2’-[(2-Hydroxyphenyl)methylidene]-2-[(5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]ace-
tohydrazide (2-17). Yield 73%. Yellowy solid. M.p. 222–2258. 1H-NMR: 11.61, 11.99 (2s, NH); 10.07 (s,
OH); 9.12 (d, J¼6.6, CH); 8.36, 8.46 (2s, CH); 7.20 (d, J¼6.6, CH); 6.84–7.71 (m, 4 arom. H); 4.17, 4.55
(2s, CH2S); 2.61 (s, Me). EI-MS: 341.9 (Mþ ). Anal. calc. for C15H14N6O2S (342.38): C 52.62, H 4.12, N
24.55; found: C 52.36, H 4.50, N 24.80.
2’-{[4-(Dimethylamino)phenyl]methylidene}-2-[(5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfa-
nyl]acetohydrazide (2-18). Yield 86%. Yellowy solid. M.p. 107–1108. 1H-NMR: 9.26, 10.71 (2s, NH); 8.58
(d, J¼6.9, CH); 7.66, 7.96 (2s, CH); 6.62–7.61 (m, 4 arom. H); 6.90 (d, J¼6.9, CH); 3.96, 4.59 (2s, CH2S);
3.01 (s, Me2N); 2.73 (s, Me). EI-MS: 369.3 (Mþ ). Anal. calc. for C17H19N7OS (369.44): C 55.27, H 5.18, N
26.54; found: C 55.01, H 4.96, N 26.81.
2’-[(4-Methylphenyl)methylidene]-2-[(5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]aceto-
hydrazide (2-19). Yield 87%. White solid. M.p. 196–1988. 1H-NMR: 11.59, 11.70 (2s, NH); 9.14 (d, J¼7.2,
CH); 8.02, 8.20 (2s, CH); 7.21–7.61 (m, 4 arom. H); 7.19 (d, J¼7.2, CH); 4.14, 4.54 (2s, CH2S); 2.61 (s,
Me); 2.35 (s, MeC6H4). EI-MS: 340.2 (Mþ ). Anal. calc. for C16H16N6OS (340.40): C 56.45, H 4.74, N
24.69; found: C 56.23, H 5.00, N 24.45.
2-[(5-Methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-2’-(phenylmethylidene)acetohydrazide
1
(2-20). Yield 77%. White solid. M.p. 186–1888. H-NMR: 11.63, 11.74 (2s, NH); 9.12 (d, J¼6.6, CH);
8.04, 8.22 (2s, CH); 7.42–7.68 (m, 5 arom. H); 7.18 (d, J¼6.6, CH); 4.13, 4.54 (2s, CH2S); 2.60 (s, Me). EI-
MS: 326.5 (Mþ ). Anal. calc. for C15H14N6OS (326.38): C 55.20, H 4.32, N 25.75; found: C 49.96, H 4.09, N
25.86.
2’-[(4-Chlorophenyl)methylidene]-2-[(5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-
propanohydrazide (2-21). Yield 83%. White solid. M.p. 167–169, 1H-NMR: 11.66, 11.93 (2s, NH); 8.01,
8.23 (2s, CH); 7.41–7.74 (m, 4 arom. H); 7.11, 7.14 (2s, 6-CH); 4.63, 5.49 (2q, J¼6.8, CHS); 2.63, 2.68 (2s,
MeꢀC(7)); 2.56 (s, MeꢀC(5)); 1.64 (d, J¼7.6, Me). EI-MS: 389.1 (Mþ ). Anal. calc. for: C17H17ClN6OS
(388.87): C 52.51, H 4.41, N 21.61; found: C 52.16, H 4.56, N 21.89.
2’-[(3-Chlorophenyl)methylidene]-2-[(5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-
propanohydrazide (2-22). Yield 87%. White solid. M.p. 159–1618. 1H-NMR: 11.45 (s, NH); 8.10 (s, CH);
7.22–7.80 (m, 4 arom. H); 6.84 (s, HꢀC(6)); 4.47 (q, J¼7.5, CHS); 2.76 (s, MeꢀC(7)); 2.71 (s,
MeꢀC(5)); 1.71 (d, J¼7.5, Me). EI-MS: 388.9 (Mþ ). Anal. calc. for C17H17ClN6OS (388.87): C 52.51, H
4.41, N 21.61; found: C 52.65, H 4.68, N 21.24.
2’-[(2-Chlorophenyl)methylidene]-2-[(5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-
propanohydrazide (2-23). Yield 81%. White solid. M.p. 196–1988. 1H-NMR: 11.52 (s, NH); 8.52 (s, CH);
7.20–8.13 (m, 4 arom. H); 6.81 (s, HꢀC(6)); 4.47 (q, J¼7.5, CHS); 2.75 (s, MeꢀC(7)); 2.70 (s,
MeꢀC(5)); 1.71 (d, J¼7.2, Me). EI-MS: 388.6 (Mþ ). Anal. calc. for C17H17ClN6OS (388.87): C 52.51, H
4.41, N 21.61; found: C 52.45, H 4.58, N 21.78.
2’-[(3,4-Dichlorophenyl)methylidene]-2-[(5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfa-
nyl]propanohydrazide (2-24). Yield 87%. White solid. M.p. 189–1918. 1H-NMR: 11.77, 12.05 (2s, NH);
7.98, 8.21 (2s, CH); 7.59–7.94 (m, 3 arom. H); 7.11, 7.14 (2s, HꢀC(6)); 4.64, 5.49 (2q, J¼6.8, CHS); 2.64,

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CHEMISTRY & BIODIVERSITY – Vol. 6 (2009)
2.68 (2s, MeꢀC(7)); 2.55 (s, MeꢀC(5)); 1.64 (d, J¼6.8, Me). EI-MS: 423.5 (Mþ ). Anal. calc. for
C17H16Cl2N6OS (423.32): C 48.23, H 3.81, N 19.85; found: C 48.01, H 4.08, N 19.56.
2’-[(2-Chloro-6-fluorophenyl)methylidene]-2-[(5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sul-
fanyl]propanohydrazide (2-25). Yield 89%. White solid. M.p. 230–2328. 1H-NMR: 11.82, 12.10 (2s, NH);
8.29, 8.49 (2s, CH); 7.29–7.49 (m, 3 arom. H); 7.08, 7.14 (2s, HꢀC(6)); 4.62, 5.43 (2q, J¼6.8, CHS); 2.64,
2.69 (2s, MeꢀC(7)); 2.56 (s, MeꢀC(5)); 1.65 (d, J¼6.8, Me). EI-MS: 407.2 (Mþ ). Anal. calc. for
C17H16ClFN6OS (406.86): C 50.18, H 3.96, N 20.66; found: C 50.32, H 4.09, N 20.39.
2-[(5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-2’-[(2-fluorophenyl)methylidene]-
propanohydrazide (2-26). Yield 78%. White solid. M.p. 181–1838. 1H-NMR: 11.71, 12.00 (2s, NH); 8.23,
8.46 (2s, CH); 7.12–7.88 (m, 4 arom. H); 7.11, 7.14 (2s, HꢀC(6)); 4.60, 5.51 (2q, J¼6.8, CHS); 2.64, 2.68
(2s, MeꢀC(7)); 2.56 (s, MeꢀC(5)); 1.65 (d, J¼7.6, Me). EI-MS: 372.7 (Mþ ). Anal. calc. for
C17H17FN6OS (372.42): C 54.83, H 4.60, N 22.57; found: C 54.68, H 4.43, N 22.36.
2-[(5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-2’-[(3-fluorophenyl)methylidene]-
propanohydrazide (2-27). Yield 74%. White solid. M.p. 153–1558. 1H-NMR: 11.71, 11.98 (2s, NH); 8.01,
8.25 (2s, CH); 7.12–7.56 (m, 4 arom. H); 7.10, 7.13 (2s, HꢀC(6)); 4.65, 5.54 (2q, J¼6.8, CHS); 2.65, 2.68
(2s, MeꢀC(7)); 2.56 (s, MeꢀC(5)); 1.66 (d, J¼7.2, Me). EI-MS: 372.1 (Mþ ). Anal. calc. for
C17H17FN6OS (372.42): C 54.83, H 4.60, N 22.57; found: C 55.02, H 4.87, N 22.29.
2-[(5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-2’-[(2-nitrophenyl)methylidene]pro-
panohydrazide (2-28). Yield 84%. Yellowy solid. M.p. 223–2248. 1H-NMR: 11.88, 12.21 (2s, NH); 8.42,
8.66 (2s, CH); 7.62–8.10 (m, 4 arom. H); 7.09, 7.14 (2s, HꢀC(6)); 4.63, 5.48 (2q, J¼6.8, CHS); 2.62, 2.69
(2s, MeꢀC(7)); 2.56 (s, MeꢀC(5)); 1.64 (d, J¼7.2, Me). EI-MS: 399.8 (Mþ ). Anal. calc. for C17H17N7O3S
(399.43): C 51.12, H 4.29, N 24.55; found: C 52.39, H 4.51, N 24.19.
2-[(5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-2’-[(3-nitrophenyl)methylidene]pro-
1
panohydrazide (2-29). Yield 81%. Yellowy solid. M.p. 213–2148. H-NMR: 11.85, 12.12 (2s, NH); 8.37,
8.53 (2s, CH); 7.63–8.40 (m, 4 arom. H); 7.10, 7.14 (2s, HꢀC(6)); 4.67, 5.53 (2q, J¼7.2, CHS); 2.64, 2.69
(2s, MeꢀC(7)); 2.56 (s, MeꢀC(5)); 1.67 (d, J¼7.2, Me). EI-MS: 399.1 (Mþ ). Anal. calc. for C17H17N7O3S
(399.43): C 51.12, H 4.29, N 24.55; found: C 51.35, H 4.58, N 24.24.
2-[(5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-2’-[(4-nitrophenyl)methylidene]pro-
1
panohydrazide (2-30). Yield 87%. Yellowy solid. M.p. 200–2018. H-NMR: 11.90, 12.16 (2s, NH); 8.11,
8.35 (2s, CH); 7.87–8.31 (m, 4 arom. H); 7.11, 7.14 (2s, HꢀC(6)); 4.65, 5.54 (2q, J¼6.8, CHS); 2.62, 2.68
(2s, MeꢀC(7)); 2.56 (s, MeꢀC(5)); 1.65 (d, J¼7.2, Me). EI-MS: 399.0 (Mþ ). Anal. calc. for C17H17N7O3S
(399.43): C 51.12, H 4.29, N 24.55; found: C 50.96, H 4.60, N 24.82.
2-[(5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-2’-[(2-hydroxy-4-methoxyphenyl)meth-
1
ylidene]propanohydrazide (2-31). Yield 57%. Yellowy solid. M.p. 184–1868. H-NMR: 11.42, 11.96 (2s,
NH); 10.14, 11.28 (2s, OH); 8.23, 8.36 (2s, CH); 6.41–7.48 (m, 3 arom. H); 7.11, 7.14 (2s, HꢀC(6)); 4.61,
5.41 (2q, J¼7.2, CHS); 3.73, 3.77 (2s, MeO); 2.65, 2.68 (2s, MeꢀC(7)); 2.56 (s, MeꢀC(5)); 1.65 (d, J¼7.2,
Me). EI-MS: 400.5 (Mþ ). Anal. calc. for C18H20N6O3S (400.45): C 53.99, H 5.03, N 20.99; found: C 54.13,
H 4.86, N 21.23.
2’-[(2-Hydroxy-5-methoxyphenyl)methylidene]-2-[(5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-
1
yl)sulfanyl]propanohydrazide (2-32). Yield 66%. Yellowy solid. M.p. 212–2138. H-NMR: 11.55, 12.04
(2s, NH); 9.58, 10.39 (2s, OH); 8.29, 8.44 (2s, CH); 6.80–7.13 (m, 3 arom. H); 7.10, 7.14 (2s, HꢀC(6));
4.62, 5.43 (2q, J¼7.2, CHS); 3.58, 3.72 (2s, MeO); 2.65, 2.68 (2s, MeꢀC(7)); 2.56 (s, MeꢀC(5)); 1.65 (d,
J¼7.2, Me). EI-MS: 400.3 (Mþ ). Anal. calc. for C18H20N6O3S (400.45): C 53.99, H 5.03, N 20.99; found: C
53.78, H 5.31, N 20.86.
2’-[(5-Bromo-2-hydroxyphenyl)methylidene]-2-[(5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-
1
sulfanyl]propanohydrazide (2-33). Yield 66%. White solid. M.p. 230–2328. H-NMR: 11.61, 12.14 (2s,
NH); 10.37, 11.03 (2s, OH); 8.25, 8.42 (2s, CH); 6.82–7.77 (m, 3 arom. H); 7.10, 7.14 (2s, HꢀC(6)); 4.61,
5.47 (2q, J¼6.8, CHS); 2.66, 2.68 (2s, MeꢀC(7)); 2.55, 2.56 (2s, MeꢀC(5)); 1.64 (d, J¼7.2, Me). EI-MS:
449.6 (Mþ ). Anal. calc. for C17H17BrN6O2S (449.32): C 45.44, H 3.81, N 18.70; found: C 45.23, H 3.90, N
18.67.
2’-[(5-Chloro-2-hydroxyphenyl)methylidene]-2-[(5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-
1
sulfanyl]propanohydrazide (2-34). Yield 77%. White solid. M.p. 216–2178. H-NMR: 11.61, 12.14 (2s,
NH); 10.34, 11.01 (2s, OH); 8.25, 8.42 (2s, CH); 6.86–7.64 (m, 3 arom. H); 7.11, 7.14 (2s, HꢀC(6)); 4.61,

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5.48 (2q, J¼7.2, CHS); 2.66, 2.68 (2s, MeꢀC(7)); 2.54, 2.56 (2s, MeꢀC(5)); 1.64 (d, J¼7.2, Me). EI-MS:
404.6 (Mþ ). Anal. calc. for C17H17ClN6O2S (404.87): C 50.43, H 4.23, N 20.76; found: C 50.27, H 4.10, N
20.57.
2-[(5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-2’-[(4-methoxyphenyl)methylidene]-
propanohydrazide (2-35). Yield 74%. White solid. M.p.169–1718. 1H-NMR: 11.48, 11.73 (2s, NH); 7.97,
8.18 (2s, CH); 6.90–7.65 (m, 4 arom. H); 7.11, 7.13 (2s, HꢀC(6)); 4.62, 5.51 (2q, J¼6.0, CHS); 3.78, 3.81
(2s, MeO); 2.65, 2.68 (2s, MeꢀC(7)); 2.56 (s, MeꢀC(5)); 1.65 (d, J¼5.6, Me). EI-MS: 384.3 (Mþ ). Anal.
calc. for C18H20N6O2S (384.46): C 56.23, H 5.24, N 21.86; found: C 56.46, H 5.48, N 21.58.
2-[(5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-2’-[(4-methylphenyl)methylidene]-
propanohydrazide (2-36). Yield 72%. White solid. M.p. 190–1928. 1H-NMR: 11.53, 11.79 (2s, NH); 7.98,
8.19 (2s, CH); 7.16–7.60 (m, 4 arom. H); 7.11, 7.14 (2s, HꢀC(6)); 4.62, 5.51 (2q, J¼6.8, CHS); 2.64, 2.68
(2s, MeꢀC(7)); 2.56 (s, MeꢀC(5)); 2.31, 2.38 (2s, Me); 1.65 (d, J¼6.8, Me). EI-MS: 368.2 (Mþ ). Anal.
calc. for C18H20N6OS (368.46): C 58.68, H 5.47, N 22.81; found: C 58.96, H 5.23, N 22.97.
2-[(5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-2’-[(4-hydroxyphenyl)methylidene]-
propanohydrazide (2-37). Yield 75%. White solid. M.p. 158–1598. 1H-NMR: 11.40, 11.66 (2s, NH); 9.90,
9.95 (2s, OH); 7.92, 8.12 (2s, CH); 6.73–7.53 (m, 4 arom. H); 7.11, 7.14 (2s, HꢀC(6)); 4.61, 5.49 (2q, J¼6.8,
CHS); 2.65, 2.68 (2s, MeꢀC(7)); 2.57 (s, MeꢀC(5)); 1.64 (d, J¼6.4, Me). EI-MS: 370.5 (Mþ ). Anal.
calc. for C17H18N6O2S (370.43): C 55.12, H 4.90, N 22.69; found: C 55.23, H 4.76, N 22.57.
2’-{[4-(Dimethylamino)phenyl]methylidene}-2-[(5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-
1
sulfanyl]propanohydrazide (2-38). Yield 71%. Yellow solid. M.p. 129–1318. H-NMR: 11.31, 11.55 (2s,
NH); 7.88, 8.07 (2s, CH); 7.63–7.51 (m, 4 arom. H); 7.11, 7.13 (2s, HꢀC(6)); 4.60, 5.49 (2q, J¼6.8, CHS);
2.95, 2.97 (2s, Me2N); 2.64, 2.68 (2s, MeꢀC(7)); 2.56 (s, MeꢀC(5)); 1.64 (d, J¼6.4, Me). EI-MS: 397.3
(Mþ ). Anal. calc. for C19H23N7OS (397.50): C 57.41, H 5.83, N 24.67; found: C 57.56, H 5.71, N 24.29.
2-[(5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-2’-[(4-hydroxy-3-methoxyphenyl)me-
1
thylidene]propanohydrazide (2-39). Yield 73%. White solid. M.p. 147–1498. H-NMR: 11.43, 11.66 (2s,
NH); 9.48, 9.55 (2s, OH); 7.89, 8.10 (2s, CH); 6.73–7.26 (m, 3 arom. H); 7.10, 7.14 (2s, HꢀC(6)); 4.60, 5.41
(2q, J¼6.8, CHS); 3.70, 3.81 (2s, MeO); 2.65, 2.68 (2s, MeꢀC(7)); 2.56 (s, MeꢀC(5)); 1.64 (d, J¼6.8,
Me). EI-MS: 400.1 (Mþ ). Anal. calc. for C18H20N6O3S (400.45): C 53.99, H 5.03, N 20.99; found: C 54.24,
H 5.14, N 20.65.
2-[(5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-2’-(phenylmethylidene)propanohy-
1
drazide (2-40). Yield 74%. White solid. M.p. 190–1918. H-NMR: 11.62, 11.87 (2s, NH); 8.03, 8.25 (2s,
CH); 7.34–7.71 (m, 5 arom. H); 7.10, 7.12 (2s, HꢀC(6)); 4.65, 5.53 (2q, J¼6.8, CHS); 2.64, 2.68 (2s,
MeꢀC(7)); 2.56 (s, MeꢀC(5)); 1.66 (d, J¼6.8, Me). EI-MS: 354.3 (Mþ ). Anal. calc. for C17H18N6OS
(354.43): C 57.61, H 5.12, N 23.71; found: C 57.35, H 5.24, N 23.58.
2-[(6-Chloro-5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)oxy]-2’-[(2-chlorophenyl)methylide-
ne]acetohydrazide (3-1). Yield 85%. White solid. M.p. 237–2398. 1H-NMR: 11.86, 12.02 (2s, NH); 8.41,
8.68 (2s, CH); 7.42–8.01 (m, 4 arom. H); 5.01, 5.48 (2s, CH2O); 2.77, 2.78 (2s, MeꢀC(7)); 2.62 (s,
MeꢀC(5)). EI-MS: 393.1 (Mþ ). Anal. calc. for C16H14Cl2N6O2 (393.23): C 48.87, H 3.59, N 21.37; found:
C 49.10, H 3.68, N 21.18.
2-[(6-Chloro-5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)oxy]-2’-[(4-chlorophenyl)methylide-
ne]acetohydrazide (3-2). Yield 86%. White solid. M.p. 235–2378. 1H-NMR: 11.73, 11.81 (2s, NH); 8.02,
8.27 (2s, CH); 7.50–7.75 (m, 4 arom. H); 5.00, 5.46 (2s, CH2O); 2.77 (s, MeꢀC(7)); 2.63 (s, MeꢀC(5)).
EI-MS: 393.4 (Mþ ). Anal. calc. for C16H14Cl2N6O2 (393.23): C 48.87, H 3.59, N 21.37; found: C 48.75, H
3.76, N 21.68.
2-[(6-Chloro-5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)oxy]-2’-[(3-fluorophenyl)methylide-
ne]acetohydrazide (3-3). Yield 84%. White solid. M.p. 239–2408. 1H-NMR: 11.77, 11.86 (2s, NH); 8.02,
8.28 (2s, CH); 7.27–7.58 (m, 4 arom. H); 5.01, 5.47 (2s, CH2O); 2.77, 2.78 (2s, MeꢀC(7)); 2.63 (s,
MeꢀC(5)). EI-MS: 377.1 (Mþ ). Anal. calc. for C16H14ClFN6O2 (376.77): C 51.00, H 3.75, N 22.31; found:
C 50.86, H 4.02, N 22.14.
2-[(6-Chloro-5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)oxy]-2’-[(4-fluorophenyl)methylide-
ne]acetohydrazide (3-4). Yield 87%. White solid. M.p. 227–2298. 1H-NMR: 11.68, 11.76 (2s, NH); 8.02,
8.28 (2s, CH); 7.27–7.80 (m, 4 arom. H); 5.00, 5.45 (2s, CH2O); 2.77, 2.78 (2s, MeꢀC(7)); 2.62 (s,

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CHEMISTRY & BIODIVERSITY – Vol. 6 (2009)
MeꢀC(5)). EI-MS: 376.9 (Mþ ). Anal. calc. for C16H14ClFN6O2 (376.77): C 51.00, H 3.75, N 22.31; found:
C 51.13, H 3.89, N 22.17.
2-[(6-Chloro-5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)oxy]-2’-[(4-methylphenyl)methylide-
ne]acetohydrazide (3-5). Yield 75%. White solid. M.p. 226–2288. 1H-NMR: 11.62, 11.71 (2s, NH); 7.99,
8.22 (2s, CH); 7.25–7.61 (m, 4 arom. H); 4.99, 5.44 (2s, CH2O); 2.77, 2.78 (2s, MeꢀC(7)); 2.62 (s,
MeꢀC(5)); 2.34 (s, Me). EI-MS: 372.9 (Mþ ). Anal. calc. for C17H17ClN6O2 (372.81): C 54.77, H 4.60, N
22.54; found: C 54.89, H 4.45, N 22.75.
2-[(6-Chloro-5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)oxy]-2’-[(4-methoxyphenyl)methyli-
dene]acetohydrazide (3-6). Yield 78%. White solid. M.p. 209–2118. 1H-NMR: 11.54, 11.63 (2s, NH); 7.96,
8.21 (2s, CH); 6.99–7.66 (m, 4 arom. H); 4.98, 5.43 (2s, CH2O); 3.80 (s, MeO); 2.77, 2.78 (2s, MeꢀC(7));
2.62 (s, MeꢀC(5)). EI-MS: 388.6 (Mþ ). Anal. calc. for C17H17ClN6O3 (388.81): C 52.51, H 4.41, N 21.61;
found: C 52.76, H 4.57, N 21.28.
2-[(6-Chloro-5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)oxy]-2’-[(2-hydroxy-4-methoxyphe-
1
nyl)methylidene]acetohydrazide (3-7). Yield 65%. White solid. M.p. 244–2468. H-NMR: 11.46, 11.87
(2s, NH); 10.16, 11.30 (2s, OH); 7.95, 8.40 (2s, CH); 6.45–8.23 (m, 3 arom. H); 5.00, 5.40 (2s, CH2O); 3.75,
3.76 (2s, MeO); 2.77, 2.78 (2s, MeꢀC(7)); 2.62 (s, MeꢀC(5)). EI-MS: 405.1 (Mþ ). Anal. calc. for
C17H17ClN6O4 (404.81): C 50.44, H 4.23, N 20.76; found: C 50.70, H 4.01, N 20.96.
2-[(6-Chloro-5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)oxy]-2’-[(2-hydroxy-5-methoxyphe-
1
nyl)methylidene]acetohydrazide (3-8). Yield 60%. White solid. M.p. 249–2518. H-NMR: 11.59, 11.96
(2s, NH); 9.62, 10.41 (2s, OH); 7.95, 8.47 (2s, CH); 6.83–8.29 (m, 3 arom. H); 5.01, 5.40 (2s, CH2O); 3.71
(s, MeO); 2.77, 2.78 (2s, MeꢀC(7)); 2.63 (s, MeꢀC(5)). EI-MS: 404.6 (Mþ ). Anal. calc. for
C17H17ClN6O4 (404.81): C 50.44, H 4.23, N 20.76; found: C 50.65, H 4.51, N 20.85.
2’-[(5-Bromo-2-hydroxyphenyl)methylidene]-2-[(6-chloro-5,7-dimethyl[1,2,4]triazolo[1,5-a]pyri-
midin-2-yl)oxy]acetohydrazide (3-9). Yield 76%. White solid. M.p. 265–2678. 1H-NMR: 11.66, 12.06 (2s,
NH); 10.41, 11.05 (2s, OH); 7.83, 8.46 (2s, CH); 6.87–8.26 (m, 3 arom. H); 5.02, 5.45 (2s, CH2O); 2.77,
2.78 (2s, MeꢀC(7)); 2.63 (s, MeꢀC(5)). EI-MS: 454.1 (Mþ ). Anal. calc. for C16H14BrClN6O3 (453.68): C
42.36, H 3.11, N 18.52; found: C 42.14, H 2.98, N 18.75.
X-Ray Crystal Structure of 2-3. Crystals of 2-3 were grown by slow evaporation of a DMF/EtOH soln.
at r.t. Colorless blocks of 2-3 (0.30ꢄ0.20ꢄ0.10 mm) were mounted on a quartz fiber with protection oil.
Cell dimensions and intensities were measured at 298ꢁ2 K on a Bruker SMART CCD area detector
diffractometer with graphite-monochromated MoKa radiation (l 0.71073 ꢂ). Crystal data for 2-3:
C15H13ClN6OS, Mr 360.82, monoclinic, space group C2/c; a¼17.602(4), b¼15.423(3), c¼13.818(3) ꢂ;
b¼119.06 (4)8, V¼3278.9(12) ꢂ3, Z¼8, Dcalc. ¼1.462 g/cm3. A total of 3885 reflections were measured in
the range of 1.878ꢅqꢅ25.098; 2729 independent reflections (Rint ¼0.0152). Data were corrected for
Lorentz and polarization effects and for absorption (Tmin ¼0.8956; Tmax ¼0.9634). The structure was
solved by direct methods using SHELXS-97 and refined using SHELXS-97; all other calculations were
performed with Bruker SMART system and Bruker SMART programs [16–19]. Full-matrix least-
squares refinement based on F2 using the weight of 1/[s2(Fo2)þ(0.1013P)2 þ0.8599P] (P¼(Fo2 þ2Fc2)/3)
gave final values of R¼0.0468, wR¼0.1655, and GOF(F)¼1.083 for 218 variables and 2729 contributing
reflections. Maximum shift/error 0.000, max/min residual electron density 0.297/ꢀ0.306 e ꢂꢀ3. All H-
atoms bonded to C-atoms were positioned geometrically, with CꢀH¼0.93, 0.97, and 0.96 ꢂ for arom. H-
atoms, CH2, and Me groups, resp., and their displacement parameters were set 1.2 times that of their
carried atoms. H(2a) was found from the difference map and refined with a distance restraint of NꢀH¼
0.86(1) ꢂ, Uiso(H)¼1.2Ueq(N). The crystallographic data of 2-3 have been deposited with the Cambridge
Crystallographic Data Centre with the deposition No. CCDC-665799. Copies of the data can be obtained
free of charge via http://www.ccdc.cam.ac.uk/data request/cif.
Bioassays of Fungicidal Activities. The fungicidal activities were tested according to our previous
methods [12][14][15]. The tested samples were dissolved in 0.5 ml of DMF at a concentration of 500 mg/
l. The solns. (1 ml) were mixed rapidly with thawed potato glucose agar culture medium (9 ml) at 508.
The mixtures were poured into Petri dishes. After the dishes were cooled, the solidified plates were
incubated with 4-mm mycelium disks, inverted, and incubated at 288 for 48 h. The mixed medium without
sample was used as the blank control. Three replicates of each test were carried out. The mycelial
elongation radius (mm) of fungi settlements was measured after 48 h of culture. The growth inhibition

CHEMISTRY & BIODIVERSITY – Vol. 6 (2009)
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rates were calculated with the following equation: I¼[(CꢀT)/C]ꢄ100%, where I is the growth
inhibition rate [%], C is the control settlement radius (mm), and T is the treatment group fungi
settlement radius (mm). From a concentration–inhibition ranking relationship, the concentration to give
50% inhibition effect was defined as EC50 [20].
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Received May 6, 2008