Synthesis and bioactivity of novel triazolo [1,5-a]pyrimidine derivatives[3]

Article abstract of DOI:10.1002/hc.1075

In an attempt to discover novel compounds with high herbicidal activity and low toxicity, a series of novel 1,2,4-triazolo[1,5-a]pyrimidine derivatives, α-(5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-thio)acetamides 3 and α-(5,7-dimethyl-1,2, 4-triazol

Full text of DOI:10.1002/hc.1075

Heteroatom Chemistry
Volume 12, Number 6, 2001
Synthesis and Bioactivity of Novel
Triazolo [1,5-a]Pyrimidine Derivatives[3]
Guangfu Yang, Li Xu, and Aihong Lu
Institute of Organic Synthesis, Central China Normal University, Wuhan 430079, P. R. China;
gfyang@ccnu.edu.cn
Received 8 November 2000; revised 28 February 2001
A recent review [1] discusses the synthesis and
ABSTRACT: In an attempt to discover novel com-
properties of 1,2,4-triazolo[1,5-a]pyrimidine deriva-
pounds with high herbicidal activity and low toxicity,
tives. The 1,2,4-triazolo[1,5-a]pyrimidine-2-sulfon-
a series of novel 1,2,4-triazolo[1,5-a]pyrimidine der-
amide derivatives have shown excellent herbicidal
ivatives, -(5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimi-
and plant growth regulation activity [2–4]. Recently,
dine-2-thio)acetamides 3 and -(5,7-dimethyl-1,2,
we became interested in the syntheses of novel 1,2,4-
4-triazolo[1,5-a]pyrimidine-2-sul-fonyl)acetamides 4,
triazolo[1,5-a]pyrimidines. Some of the compounds
have been designed and synthesized by a three-step
we synthesized have shown potential herbicidal
synthetic route. The structures of all compounds pre-
and fungicidal activities [3–6]. As a continuation
pared were confirmed by elemental analyses and by
of our research, we wish to report herein the
1H NMR and mass spectroscopy. The results of pre-
preparation of -(5,7-di-methyl-1,2,4-triazolo[1,5-a]
liminary bioassay indicate that the title compounds
pyrimidine-2-thio)acetamides 3a–n and -(5,7-dim-
possess good herbicidal activity against rape (Bras-
ethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonyl)ac-
sica campestris L.) and barnyardgrass (Echinochloca
etamides 4a–g. The purpose of the present work
C
crusgalli L.) 2001 John Wiley & Sons, Inc. Heteroatom
Chem 12:491–496, 2001
is to find novel compounds with good biological
activity, such as herbicidal activity.
INTRODUCTION
RESULTS AND DISCUSSION
The chemistry of 1,2,4-triazolo[1,5-a]pyrimidine
derivatives has been of considerable interest for
many years. In 1935, 5-methyl-7-hydroxy-1,2,4-
triazolo[1,5-a]pyrimidine was found to be an ex-
cellent stabilizer for photographic emulsions. Since
then, various derivatives of 1,2,4-triazolo-[1,5-a]
pyrimidine have found applications in pharmaceu-
tical, agricultural, and other areas.
Synthesis and Structure Characterization
of the Title Compounds
The title compounds were synthesized via two differ-
ent routes outlined in Schemes 1 and 2, respectively.
In method A, as shown in Scheme 1, -(5,7-
dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-thio)ac-
etic acids 2a–b were synthesized by treating 2-
mercapto-5,7-dimethyl-1,2,4-triazolo[1,5- a]pyrimi-
dine 1 with ClCH2COOH or CH3CHBrCOOH in the
presence of sodium hydroxide. In the presence of
dicyclohexylcarbodiimide (DCC), these compounds
were reacted with various aromatic amines in dime-
thylformamide (DMF) at room temperature to aff-
ord -(5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-
Correspondence to: Guangfu Yang.
Contract Grant Sponsor: National Natural Science Foundation
of China.
Contract Grant Sponsor: Ministry of Education of China, Foun-
dation for University Key Teachers.
c
2001 John Wiley & Sons, Inc.
491

492 Yang, Xu, and Lu
CH3
reaction temperature, the yield of sulfone increa-
ses. The best yield (67.5%) was obtained when the re-
action was carried out at ca. 55–60 C in the pre-
sence of sodium tungstate dihydrate as catalyst [5].
In summary, the optimum conditions for the oxida-
tion reaction of -(5,7-dimethyl-1,2,4-triazolo[1,5-
a]-pyrimidine-2-thio)acetamides to the correspond-
ing sulfone 4 were ca. 55–60 C and included the
presence of sodium tungstate dihydrate as catalyst.
CH3
N
N
N
N
XCHRCOOH
NaOH
CH3
SCHCOOH
R
N
N
CH3
SH
N
N
2
R = H
a
1
2
R = CH
3
b
H2NAr / DCC
CH3
N
CH3
N
N
N
N
H2O2 / HOAc
CH3
SO2CHCONHAr
R
CH3
N
SCHCONHAr
R
Attempted coupling reactions of
-(5,7-di-
N
N
R = H
methyl-1,2,4-triazolo[1,5-a]pyrimidine-2-thio)acetic
acids 2a–b with heterocyclic amines in DMF in
the presence of DCC were unsuccessful. However,
the convenient synthetic route depicted in Scheme
2 gave fruitful results. Thus, chloroacetyl chlo-
ride was reacted with heterocyclic amines to give
chloroacetamides 5a–c, which were then treated
with 2-mercapto-5,7-dimethyl-1,2,4-triazolo[1,5-a]
pyrimidine 1 in the presence of sodium hydrox-
ide to obtain the target compounds 3l–n in good
yields.
3
3
4
4
R = H
R = CH
3
a~e
f~k
a~b
c~g
R = CH
3
SCHEME 1 (Method A)
+
H2NHet
ClCH2COCl
ClCH2CONHHet
5
a~c
CH3
NaOH
N
N
1
+ 5
a~c
All the products 3 and 4 were purified by re-
crystallization from ethanol. The structures of the
products 3 and 4 were confirmed by 1H NMR, mass
spectral, and elemental analyses. The experimental
data for 3 and 4 are listed in Tables 2 and 3. The
1H NMR spectrum of 3h, a representative example
in this series, shows the presence of a doublet and
a quartet at 1.70 and 4.60 due to the presence
of -CH3 and methyne protons with J = 7.98. The
NH protons appeared as a broad peak at 10.20.
The singlets at 2.71, 2.80, and 6.90 were due
to 5-methyl, 7-methyl, and 6-methyne protons, re-
spectively. The aromatic protons displayed a multi-
CH3
SCH2CONHHet
N
N
3
l~n
SCHEME 2 (Method B)
2-thio)acetamides 3a–k. In view of the stability of
the amide group, the H2O2/HOAc system was sel-
ected as the oxidizing reagent to transform -(5,7-
dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-thio)ac-
etamides 3 to the corresponding sulfones. A repre-
sentative example, 3c, has been taken to study
the influence of the reaction temperature and the
catalyst on the oxidation reaction of -(5,7-dimethyl-
1,2,4-triazolo[1,5-a]pyrimidine-2-thio)acetamides
to the corresponding sulfones, and the results are
summarized in Table 1. With an increase in the
1
plet at 7.20–7.60. In the H NMR spectra of 4, the
chemical shifts of the methylene and the methyne
protons linked with sulfonyl were shifted to lower
field due to the strong inductive effect of the sulfonyl
group and appeared in the range of 4.65–4.80. The
proton of NH of each compound 4 showed broad
1
peaks at 9.15–10.70. The H NMR resonances of
the protons in the heterocycle moiety and aromatic
ring moiety have a similar regularity to 3 and can
be clearly assigned. In addition, the EI-MS spectra
of 3 and 4 exhibited the anticipated molecular ion
peaks. All the fragmentation ions were consistent
with their structures and can be clearly assigned.
For example, compound 3h, under electron impact,
gave the molecular ion peak m/z (%): 361(23.9), and
the other conspicuous peaks: 235(100), 208(83.70),
175(96.90), 149(84.30), 108(11.00), 107(32.40), and
67(22.20), while 4b gave the molecular ion peak m/z
(%): 379(26.40), and other major fragmentation ion
peaks: 315(9.90), 273(100), 253(73.70), 190(24.10),
and 162(59.80).
TABLE 1 The Influence of Reaction Conditions on the
Oxidation of 3c
Reaction
Reaction Time
(hours)
No. Temperature ( C) Catalyst a
Yield(%)
1
2
3
4
5
6
7
8
25–30
25–30
35–40
45–50
55–60
55–60
65–70
75–80
No
Yes
Yes
Yes
Yes
No
5
5
5
5
5
5
5
5
No reaction
23.8
47.6
51.3
67.5
58.7
49.5
Complex
Yes
Yes
aNaWO4 2H2O as a catalyst.

Triazolo[1,5-a] Pyrimidine Derivatives 493
TABLE 2 Physical Constants of Compounds 3 and 4
Analysis (%) Calcd/Found
H
No.
Ar (Het)
R
m.p. ( C)
Yields (%)
C
N
3a
3b
3c
3d
3e
3f
3g
3h
3i
2,6-Cl2C6H3
2-ClC6H4
H
H
H
H
197–199
172–174
195–198
165–166
193–195
174–176
175–176
163–165
153–155
126–128
134–136
233–235
197–198
192–194
182–184
186–188
184–187
170–171
160–161
188–190
186–187
70.2
69.4
65.4
47.6
83.6
80.0
77.9
81.5
67.9
67.6
82.8
85.7
82.4
80.0
32.0
57.0
41.0
60.0
67.5
62.6
70.2
47.12/47.14
51.79/51.96
58.71/58.43
47.12/47.46
55.97/55.69
59.82/60.13
59.82/59.74
53.11/53.35
53.11/52.98
59.82/60.13
53.11/53.38
48.00/48.23
51.89/51.64
52.47/52.75
47.43/47.71
47.43/47.65
53.48/53.15
47.43/47.15
53.48/53.67
48.79/48.53
54.69/54.83
3.40/3.19
4.02/4.37
5.19/4.87
3.40/3.12
4.95/4.78
5.57/5.19
5.57/5.79
4.42/4.68
4.42/4.59
5.57/5.34
4.42/4.71
4.53/4.35
3.78/3.99
4.95/4.78
3.68/3.45
3.68/3.84
4.73/4.97
3.68/3.47
4.73/4.95
4.06/3.87
5.09/5.36
18.32/18.23
20.14/20.55
21.40/21.71
18.32/18.66
20.40/20.74
20.52/20.87
20.52/20.73
19.36/19.71
19.36/19.67
20.52/20.77
19.36/19.57
26.13/26.39
22.70/22.98
28.57/28.79
18.44/18.72
18.44/18.59
19.49/19.64
18.44/18.71
19.49/19.81
17.78/17.96
18.76/19.04
2-CH3C6H4
3,4-Cl2C6H3
3-CH3OC6H4
2-CH3C6H4
4-CH3C6H4
4-ClC6H4
H
CH3
CH3
CH3
CH3
CH3
CH3
H
H
H
H
H
H
H
H
CH3
CH3
2-ClC6H4
3j
3k
3l
3-CH3C6H4
3-ClC6H4
4,6-CH3OPm-2-a
Ben-2-b
3m
3n
4a
4b
4c
4d
4e
4f
4,6-CH3Pm-2-c
2-ClC6H4
4-ClC6H4
4-CH3C6H4
3-ClC6H4
2-CH3C6H4
4-ClC6H4
4-CH3C6H4
4g
a4,6-Dimethoxylpyrimidinyl-2-.
bBenzothiazolyl-2-.
c4,6-Dimethylpyrimidinyl-2-.
and the inhibitory rate of compounds 3b, 3j, 3k, and
3l to rape exceeded 90%. In addition, the herbici-
dal activity of compounds 4 is much weaker than
that of compounds 3. Further studies on the struc-
ture activity relationships of these compounds are
underway.
Biological Studies
The herbicidal activity of some compounds 3 and
4 against rape (Brassica campestris L.) and barn-
yard grass (Echinochloca crusgalli L.) was measured
according to the modified method described previ-
ously [7]. A set amount of each sample was dis-
solved in acetone into which a drop of an emulsi-
fier, Sorpol-144, was added. Then, the solution was
diluted with water until it reached the concentra-
tion required (100 ppm). The amounts of acetone
and the emulsifier were set as low as possible but
were still sufficient to make a uniform emulsion even
at high concentrations. Biological assays were car-
ried out in vials (8 = 3.5 cm) containing 4 mL of so-
lution. Five seeds of rape (or barnyard grass) were
placed in the solution. The vials were kept at 25 C,
with light of 42,000 lux for 12 hours each day. Af-
ter incubation for 72 hours, the shoot length was
measured for the five seeds in each vial and aver-
aged and used as an index of herbicidal activity on
a 0–100 rating scale. The scale is based on measure-
ment of shoot length as compared to an untreated
control. With this scale, 0 represents no inhibition
and 100 represents complete inhibition. The herbi-
cidal activity of some compounds 3 and 4 are listed
in Table 4. The herbicidal activities given in Table 4
indicate most of the compounds showed an inhibi-
tion effect (>50%) against rape and barnyardgrass,
EXPERIMENTAL
Instruments
Melting points were determined with a Yanaco
MT-500 apparatus and are uncorrected. 1H NMR
spectra were taken on a BRUKER AC-P200 spec-
trometer using CDCl3 as solvent and tetramethyl-
silane (TMS) as internal standard. Mass spectra
were recorded on a Hewlett-Packard 5988 instru-
ment. Elemental analyses were carried out on a Yana
MT-3 instrument. All solvents and materials were
reagent grade and purified as required. 2-Mercapto-
5,7-dimethyl-1,2,4-triazolo-[1,5-a]pyrimidine 1 was
prepared as described in a published procedure [8].
General Procedure for the Syntheses of
-(5,7-dimethyl-1,2,4-triazolo[1,5-a]
pyrimidine-2-thio) acetic acids 2a–b
A solution of 9 g (0.05mol) of 2-mercapto-5,7-
dimethyl-1,2,4-triazolo[1,5-a]pyrimidine 1 and 4 g

494 Yang, Xu, and Lu
TABLE 3 Spectral and Analytical Data of Compounds 3 and 4a
1
No.
HNMR (TMS, CDCl , or DMSO-d , , ppm)
MS (m/z, %)
3
6
3a [a] 2.52 (s, 3H, CH3), 2.64 (s, 3H, CH3), 4.20 (s, 2H, SCH2),
7.05 (s, 1H, 6-H), 7.14–7.56 (m, 3H, C6H3), 10.27
(s, 1H, NH).
3b [b] 2.61 (s, 3H, CH3), 2.70 (s, 3H, CH3), 4.08 (s, 2H, SCH2),
6.78–8.40 (m, 5H, 6-H + C6H3), 9.57 (s, 1H, NH).
3c [b] 2.19 (s, 3H, CH3), 2.61 (s, 3H, CH3), 2.70 (s, 3H, CH3),
3.99 (s, 2H, SCH2), 7.05 (s, 1H, 6-H), 7.20–7.89
(m, 4H, C6H4), (s, 1H, NH).
382(M+, 2.9), 194 (100), 193 (31.5), 180 (5.4),
149 (40.8), 108 (34.4), 107 (25.1), 67 (36.4)
347(M+, 12.8), 221 (59.8), 194 (100), 193 (46.3),
180 (7.2), 149 (64.9), 108 (38.6), 107 (28.1), 67 (27.5)
327 (M+, 49.4), 221 (56.5), 194 (100), 193 (55.2),
9.30 180 (7.9), 149 (86.7), 108 (52.8), 107 (60.7),
67 (41.8)
3d [b] 2.64 (s, 3H, CH3), 2.67 (s, 3H, CH3), 3.93 (s, 2H, SCH2),
6.81 (s, 1H, 6-H), 7.42–7.83 (m, 3H, C6H3), 10.14
(s, 1H, NH).
382 (M+, 16.0), 221 (78.5), 194 (100), 193 (57.9),
180 (11.6), 149 (77.3), 108 (49.6), 107 (41.1), 67 (36.9)
3e [a] 2.49 (s, 3H, CH3), 2.61 (s, 3H, CH3), 3.69 (s, 3H, OCH3),
4.20(s, 2H, SCH2), 7.02 (s,1H,6-H), 6.48–7.32
(m,4H,C6H4), 10.29 (s, 1H, NH).
343 (M+, 54.7), 221 (100), 194 (75.5), 193 (65.7),
180 (12.6), 149 (90.6), 108 (59.2), 107 (59.1), 67 (35.7)
3f [a] 1.70 (d, 3H, -CH3), 2.30 (s, 3H, CH3), 2.65 (s, 3H, CH3), 341 (M+, 14.7), 279 (33.2), 278 (100), 235 (32.2),
2.75 (s,3H, CH3), 4.70 (q, 1H, SCH), 6.88 (s, 1H, 6-H),
7.00–8.00 (m, 4H, C6H4), 9.40 (s, 1H, NH).
208 (38.2), 207 (28.0), 180 (10.8), 175 (53.2),
149 (39.0), 107 (24.1), 77 (67.1), 67 (11.2)
3g [a] 1.70 (d, 3H, -CH3), 2.30 (s, 3H, CH3), 2.65 (s, 3H, CH3), 341 (M+, 21.1), 235 (100), 208 (44.4), 207 (55.0),
2.75 (s, 3H, CH3), 4.55 (q, 1H, SCH), 6.80 (s, 1H, 6-H),
7.30 (2d, 4H, C6H4), 9.80 (s, 1H, NH).
180 (12.4), 175 (77.4), 149 (57.4), 108 (8.9),
107 (35.9), 67 (14.1)
3h [a] 1.70 (d, 3H, -CH3), 2.71 (s, 3H, CH3), 2.80 (s, 3H, CH3), 361 (M+, 23.9), 235 (100), 208 (83.7), 207 (69.5),
4.60 (q, 1H, SCH), 6.90 (s, 1H, 6-H), 7.40 (2d, 4H,
C6H4), 10.20 (s, 1H, NH).
175 (96.9), 149 (84.3), 108 (11.0), 107 (32.4), 67 (22.2)
3i [a] 1.64 (d, 3H, -CH3), 2.68 (s, 3H, CH3), 2.73 (s, 3H, CH3), 361 (M+, 3.1), 234 (68.1), 208 (14.1), 207 (99.7),
4.71 (q, 1H, SCH), 6.72 (s, 1H, 6-H), 6.80–8.40 (m, 4H,
C6H4), 9.51 (s, 1H, NH).
180 (20.7), 179 (20.4), 175 (11.3), 174 (100), 149 (8.3),
148 (89.3), 107 (15.0), 67 (11.1)
3j [a] 1.65 (d, 3H, -CH3), 2.25 (s, 3H, CH3), 2.61 (s, 3H, CH3), 341 (M+, 1.5), 234 (89.8), 208 (9.8), 207 (67.4),
2.67 (s, 3H, CH3), 4.71 (q, 1H, SCH), 6.74 (s, 1H, 6-H),
6.81–7.50 (m, 4H, C6H4), 9.81 (s, 1H, NH).
206 (47.3), 180 (7.6), 179 (17.3), 175 (10.9), 174 (100),
148 (90.9), 67 (12.1)
3k [a] 1.65 (d, 3H, -CH3), 2.67 (s, 3H, CH3), 2.73 (s, 3H, CH3), 361 (M+, 5.88), 234 (49.9), 208 (11.4), 207 (90.6),
4.47 (q, 1H, SCH), 6.75 (s, 1H, 6-H), 6.84–7.74
(m, 4H, C6H4), 10.20 (s, 1H, NH).
206 (36.4), 180 (6.7), 179 (21.3), 175 (11.6), 174 (100),
148 (95.7), 106 (42.0), 67 (11.6)
3l [b] 3.90 (s, 6H, 2 OCH3), 2.52 (s, 3H, CH3), 2.67 (s, 3H, CH3), 375 (M+, 54.6), 302 (42.1), 221 (13.4), 220 (58.5),
4.59 (s, 2H, SCH2), 5.88 (s, 1H, Py-H), 7.15 (s, 1H, 6-H),
10.65 (s, 1H, NH).
3m [b] 2.58 (s, 3H, CH3), 2.64 (s, 3H, CH3), 4.22 (s, 2H, SCH2),
7.14 (s, 1H, 6-H), 7.26–8.08 (m, 4H, C6H4), 12.80
(s, 1H, NH).
194 (100), 193 (46.4), 180 (11.6), 149 (72.5),
108 (92.5), 107 (64.0), 67 (78.7)
370 (M+, 17.4), 297 (5.3), 221 (22.8), 194 (100),
193 (42.0), 149 (52.4), 108 (52.8), 107 (26.7), 67 (19.9)
3n [b] 2.30 (s, 6H, 2 CH3), 2.70 (s, 3H, CH3), 2.75 (s, 3H, CH3), [c]
4.50 (s, 2H, SCH2), 7.00 (s, 1H, Py-H), 7.16 (s, 1H, 6-H),
10.92 (s, 1H, NH).
4a [b] 2.70 (s, 3H, CH3), 2.85 (s, 3H, CH3), 4.70 (s, 2H, SCH2),
7.05 (s, 1H, 6-H), 7.10–8.25 (m, 4H, C6H4), 9.15
(s, 1H, NH).
4b [b] 2.60 (s, 3H, CH3), 2.75 (s, 3H, CH3), 4.80 (s, 2H, SCH2),
7.30 (s, 1H, 6-H), 7.50 (2d, 4H, C6H4), 10.70 (s, 1H, NH).
4c [b] 2.22 (s, 3H, CH3), 2.61 (s, 3H, CH3), 2.73 (s, 3H, CH3),
4.65 (s, 2H, SCH2), 6.90–7.50 (m, 5H, 6-H + C6H4),
10.29 (s, 1H, NH).
4d [b] 2.64 (s, 3H, CH3), 2.74 (s, 3H, CH3), 4.71 (s, 2H, SCH2),
7.30 (s, 1H, 6-H), 7.40–7.70 (m, 4H, C6H4),
10.59 (s, 1H, NH).
4e [b] 2.16 (s, 3H, CH3), 2.67 (s, 3H, CH3), 2.73 (s, 3H, CH3),
4.80 (s, 2H, SCH2), 6.90–7.44 (m, 5H, 6-H + C6H4),
9.60 (s, 1H, NH).
379 (M+, 12.8), 344 (39.9), 273 (88.2), 253 (56.6),
238 (100), 190 (18.3), 162 (33.2), 149 (4.91),
127 (24.5), 108 (11.0), 107 (15.3), 67 (29.0)
379 (M+, 26.4), 315 (9.90), 273 (100), 253 (73.7),
190 (24.1), 162 (59.8), 127 (34.7), 67 (33.0)
359 (M+, 2.51), 253 (4.3), 252 (31.1), 189 (11.0),
161 (64.3), 106 (100), 66 (40.9)
379 (M+, 2.4), 272 (23.9), 252 (25.9), 189 (28.6),
162 (10.9), 161 (100), 126 (22.2), 66 (41.4)
359 (M+, 2.2), 344 (100), 225 (93.0), 190 (4.2),
162 (9.0), 67 (11.0)
4f [b] 1.56 (d, 3H, -CH3), 2.64 (s, 3H, CH3), 2.70 (s, 3H, CH3), 393 (M+, 17.5), 273 (79.1), 190 (31.9), 176 (45.1),
4.68 (q, 1H, SCH), 7.20–7.62 (2d, 4H, C6H4),
7.38 (s, 1H, 6-H), 10.58(s, 1H, NH).
148 (16.1), 108 (12.6), 107 (51.8), 67 (100)
4g [b] 1.56 (d, 3H, -CH3), 2.22 (s, 3H, CH3), 2.64 (s, 3H, CH3), 373 (M+, 11.6), 266 (12.4), 253 (12.9), 176 (44.2),
2.70 (s, 3H, CH3), 4.68 (q, 1H, SCH), 6.90–7.50 (m, 5H,
175 (41.9), 108 (16.0), 107 (100), 106 (66.8), 77 (30.9),
67(82.0)
6-H + C6H4), 10.32 (s, 1H, NH).
a[a] CDCl3, [b] DMSO-d6, [c] undetected.

Triazolo[1,5-a] Pyrimidine Derivatives 495
TABLE 4 Herbicidal Activity of Some Compounds 3 and 4
Compounds No.
3a
3b
3c
3f
3g
3h
3i
3j
3k
100
3l
4a
100
4b
4c
4d
Concentration (ppm) 100
100
100
100
100
100
100
100
100
100
100
100
Rape
Barnyard
48.4 94.0 64.4 69.0 72.9 48.9 87.2 96.0 92.7 100
50.4 65.7 62.7 68.0 60.0 39.0 76.4 89.4 78.0 81.5 65.2 52.8 48.4 48.4
61.5 43.1 38.8 41.5
(0.1 mol) of NaOH in 200 mL of water was heated
at reflux for 0.5 hour. Then, 4.7 g (0.05 mol) of
ClCH2COOH (or CH3BrCHCOOH) was added, and
the resulting mixture was refluxed for 5 hours. The
reaction mixture was cooled to room temperature,
adjusted to pH = 2–3 using aq. HCl, and filtered.
The filter cake was recrystallized from DMF to af-
ford the pure products as white needles. 2a: Yield
90%, m.p. 248–250 C. 1H NMR (CDCl3) 2.66 (s, 3H,
CH3), 2.72 (s, 3H, CH3), 3.96(s, 2H, CH2), 6.80(s, 1H,
CH), 12.31(s, 1H, COOH). 2b: yield 91%, m.p. 232–
General Procedure for the Syntheses of N-4,6-
Dimethoxypyrimidinyl-2-chloroacetamide 5a
and N-Benzothiazolyl-2-chloroacetamide 5b
To a stirred, cold (0 C) solution of 3.1 g (0.02 mol)
of 2-amino-4,6-dimethoxypyrimidine (or 2-amino-
benzothiazole) in 20 mL of dichloromethane was
added dropwise a solution of 2 mL of chloroacetyl
chloride in 5 mL of dichloromethane at 0 C with stir-
ring. The resulting mixture was stirred at room tem-
perature for 3 hours. The mixture was filtered, and
the filter cake was washed with water and recrys-
tallized from ethanol to give the pure products. 5a:
yield 70.4%, white solid, m.p. 240–241 C. Anal. calcd
for C8H10N3O3Cl (231.5): C, 41.46; H, 4.32; N, 18.14.
Found: C, 41.73; H, 4.11; N, 18.51. 5b: yield 71.7%,
slight yellow solid, m.p. 161–162 C. Anal. calcd for
C9H7N2OSCl (226.5): C, 47.68; H, 3.09; N, 12.36.
Found: C, 47.42; H, 3.37; N, 12.72.
1
233 C. H NMR (CDCl3) 1.68 (d, 3H, CH3), 2.68 (s,
3H, CH3), 2.73 (s, 3H, CH3), 4.61(q, 1H, CH), 6.83(s,
1H, CH), 12.50 (s, 1H, COOH).
General Procedure for the Syntheses of
-(5,7-Dimethyl-1,2,4-triazolo[1,5-a]
pyrimidine-2-thio) Acetamides 3a–k (Method A)
Procedure for the Syntheses of N-4,6-Dimethyl-
pyrimidinyl-2-chloroacetamide 5c
A mixture of 5 mmol of 2, 5 mmol of aromatic
amine, and 1 g of DCC in 20 mL of DMF was
stirred at room temperature for 5–6 hours. The
mixture was filtered, and the filter cake was washed
with water and recrystallized from ethanol to af-
ford the pure products as white crystals. The
physical data for compounds 3a–k are listed in
Table 2.
To a solution of 12.3 g (0.1 mol) of 2-amino-4,6-dime-
thylpyrimidine and 9 g (0.11 mol) of CH3COONa
in 100 mL of acetone, a solution of 8.1 mL (0.1
mol) of chloroacetyl chloride in 5 mL of acetone was
added dropwise at 0 C with stirring. The resultant
mixture was refluxed for 2 hours and poured into 400
mL of saturated NaCl solution. After extraction with
chloroform three times (3 50 mL), the separated or-
ganic phase was washed with water and dried. After
the filtrate had been evaporated under reduced pres-
sure, the residue was recrystallized from an ethyl ac-
etate/petroleum ether mixture (1:1) to give the pure
products as a slight yellow solid, yield 43%, m.p. 112–
113 C. Anal. calcd for C8H10N3OCl (199.5): C, 48.12;
H, 5.01; N, 21.05. Found: C, 48.47; H, 4.89; N, 21.42.
General Procedure for the Syntheses of
-(5,7-Dimethyl-1,2,4-triazolo[1,5-a]
pyrimidine-2-sulfonyl)acetamides 4a–g
To a vigorously stirred mixture of 4.41 mmol of 3, 20
mL of acetic acid, and 0.04 g (0.13 mmol) of sodium
tungstate dihydrate, was slowly added 1.5 g (13.23
mmol) of hydrogen peroxide as a 30% aqueous so-
lution, maintaining the reaction mixture temperture
at 35–40 C. Stirring was continued at 55–60 C for
an additional 5 hours. The excess hydrogen peroxide
was destroyed by the addition of an aqueous solu-
tion of sodium sulfite, the resulting mixture was fil-
tered, and the filter cake recrystallized from ethanol
to give the pure products as colorless crystals. The
physical data for compounds 4a–g are listed in
Table 2.
General Procedure for the Syntheses of
-(5,7-dimethyl-1,2,4-triazolo[1,5-a]
pyrimidine-2-thio)acetamides 3l–n (Method B)
A mixture of 1.8 g (0.01 mol) of 1, 0.4 g (0.01 mol) of
NaOH, and 0.01 mol of 5 in 10 mL of DMF was stirred
at room temperature for 2 hours. Then, the reaction
mixture was filtered, and the solid was recrystallized

496 Yang, Xu, and Lu
(e) Kleschick, W. A.; Gerwick, B. C.; Carson, C. M.;
Monte, W. T.; Snider, S. W., J Agric Food Chem
1992, 40, 1083–1085.
from ethanol to give the pure product. The physical
data for compounds 3l–n are also listed in Table 2.
[3] Yang, G. F.; Yang, H. Z. Chem J Chinese Univ 1998,
19 (Suppl), 214–215.
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