Synthesis and herbicidal activity of 5-Alkyl(aryl)-3-[(3-trifluoromethyl) anilino]-4,5-dihydro-1H-pyrazolo[4,3-d]pyrimidin-4-imines

Article abstract of DOI:10.1002/jhet.1501

A series of novel 5-alkyl(aryl)-3-[(3-trifluoromethyl)anilino]-4,5-dihydro- 1H-pyrazolo[4,3-d]pyrimidin-4-imines were designed and synthesized by the multistep reactions. 1 reacted with 3-(trifluoromethyl)aniline to obtain N,S-acetals 2 in the presence of 10 mol% DBU. 2 reacted with hydrazine to form 5-amino-3-[(3-trifluoromethyl)anilino]-1H-pyrazol-4- nitrile 3, the target compounds 5a, 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 5j, 5k, 5l, 5m were obtained by the reaction of 3 with triethyl orthoformate followed by the cyclization of 4 with various amines. Their structures were confirmed by IR, ¹H NMR, EI-MS, and elemental analyses. The preliminary bioassay indicated that some of them displayed moderate herbicidal activity against dicotyledonous weed Brassica campestris L at the concentration of 100 mg/L. For example, compounds 5f, 5g, 5h, and 5j possessed 60.1%, 63.4%, 67.1%, and 61.3% inhibition against Brassica campestris L at the concentration of 100 mg/L.

Full text of DOI:10.1002/jhet.1501

656
Synthesis and Herbicidal Activity of 5-Alkyl(aryl)-3-[(3-trifluoromethyl)
Vol 51
anilino]-4,5-dihydro-1H-pyrazolo[4,3-d]pyrimidin-4-imines
*
Hai-Bo Li and De-Qing Shi
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal
University, Wuhan 430079, People’s Republic of China
*
E-mail: chshidq@mail.ccnu.edu.cn
Received June 24, 2011
DOI 10.1002/jhet.1501
Published online 2 December 2013 in Wiley Online Library (wileyonlinelibrary.com).
CF3
NC
NC
SMe
HN
CN
NC
NC
SMe
SMe
DBU
NH2NH2.H2O
CH3OH
NH
N
NH2
+
1,4-Dioxane
F3C
NH2
F3C
N
H
1
2
3
HN
R
CN
RNH2
NH
N
N
NH
N
CH(OC2H5)3
CHOC2H5
F3C
N
N
F3C
N
H
N
H
4
5a~5m
A series of novel 5-alkyl(aryl)-3-[(3-trifluoromethyl)anilino]-4,5-dihydro-1H-pyrazolo[4,3-d]pyrimidin-4-imines
were designed and synthesized by the multistep reactions. 1 reacted with 3-(trifluoromethyl)aniline to obtain N,
S-acetals 2 in the presence of 10mol% DBU. 2 reacted with hydrazine to form 5-amino-3-[(3-trifluoromethyl)
anilino]-1H-pyrazol-4- nitrile 3, the target compounds 5a~ 5m were obtained by the reaction of 3 with triethyl
1
orthoformate followed by the cyclization of 4 with various amines. Their structures were confirmed by IR, H
NMR, EI-MS, and elemental analyses. The preliminary bioassay indicated that some of them displayed moderate
herbicidal activity against dicotyledonous weed Brassica campestris L at the concentration of 100 mg/L. For
example, compounds 5f, 5g, 5h, and 5j possessed 60.1%, 63.4%, 67.1%, and 61.3% inhibition against Brassica
campestris L at the concentration of 100 mg/L.
J. Heterocyclic Chem., 51, 656 (2014).
INTRODUCTION
pyrimidine derivatives possessed a wide range of phar-
maceutical activities, which can be used as PDE1 and
PDE5 cGMP phosphodiesterase inhibitors [6], adenosine
A3 receptor antagonists [7], EGF-R tyrosine kinase
inhibitors [8], antiviral/antitumor activities [9], some of
them exhibited good fungicidal, and herbicidal activities
[10–12]. In order to find novel lead compound with
good herbicidal activity, we designed and synthesized
Phytoene desaturase (PDS) is a key enzyme for photosyn-
thetic apparatus of green plants. A lack of carotenoid synthe-
sis, when PDS is inhibited by its inhibitor, may lead to
typical bleaching symptoms in plants. So, the PDS inhibitors
are developed as important bleaching herbicides in
plant protection. Among them, Norflurazon, Fluridone
Fluorochloridone, Diflufenican, and Picolinafen are
commercially PDS herbicides (Fig. 1). PDS inhibitors pos-
sess a central five-membered or six-membered heterocycle
containing one or two substituted phenyl rings in which a
3-trifluoromethylphenyl group is a common structure in all
compounds [1–5]. On the other hand, pyrazolo[4,3-d]
a
series of novel pyrazolo[4,3-d]pyrimidin-4-imine
derivatives 5 by introducing 3-trifluoromethylphenyl
moiety into the pyrazolo[4,3-d]pyrimidine molecular
skeleton. Herein, we would like to report the synthesis
and herbicidal activities of the title compounds 5 in this
paper (Scheme 1).
O
O
Cl
Cl
N
O
N
NH
F
F
N
NHMe
N
O
F3C
Cl
MeHN
flurtamone
F3C
F3C
O
O
F3C
norflurazon
fluorochloridone
diflufenican
Figure 1. Some commercially PDS inhibitors.
© 2013 HeteroCorporation

May 2014
5-Alkyl(aryl)-3-[(3-trifluoromethyl)anilino]-4,5-dihydro-1H-pyrazolo[4,3-d]pyrimidin-4-imines
657
Scheme 1. Synthetic route of target compounds 5a – 5m.
CF3
NC
NC
SMe
HN
CN
NC
NC
SMe
SMe
DBU
NH2NH2.H2O
CH3OH
NH
N
NH2
+
1,4-Dioxane
F3C
NH2
F3C
N
H
1
2
3
HN
R
CN
RNH2
NH
N
N
NH
N
CH(OC2H5)3
CHOC2H5
F3C
N
N
F3C
N
H
N
H
4
5a~5m
1
RESULTS AND DISCUSSION
to C = C absorption bands of aromatic rings. In the H
NMR spectra of 5h, the two amino protons showed as
two singlets at d 3.37 and 12.16, respectively, whereas
the imino protons displayed as a singlet at d 8.96; the
pyrimidine proton also exhibited as a singlet at d 8.15.
The mass spectrum of 5h shows strong molecular ion peak
at m/z 350 with 100% abundance and anticipated fragmen-
tation ion peaks.
N,S-acetal 2 was prepared by the substitution of 1 with
3-(trifluoromethyl)aniline in the basic condition. Because
of its weak nucleophilicity of 3-(trifluoromethyl)aniline,
the substituted reaction is difficult to undergo. We explored
the reaction conditions for the synthesis of 2. Firstly, the
yields of 2 are very low without the addition of a base even
at higher temperature for a long time (see Table 1, Entries
1, 3, 4, 5). Secondly, when 10 mol% DBU was added and
the mixture was refluxed for 36 h, the yield was raised to
43% (Entry 2). Finally, the yield was raised to 65% using
10 mol% DBU under refluxing in 1,4-dioxane for 12 h. 2
reacted with 85% hydrazine hydrate to give 5-amino-3-
(3-trifluoromethylanilino)-4-cyano-1H-pyrazole 3 in 90%
yield. 3 reacted with excess triethyl orthoformate in the
presence of a catalytic amount of acetic anhydride to give
corresponding imidate 4, which cyclized with various
amines to obtain the target compounds 5 at room tempera-
ture or under reflux in 81–95% yields.
Herbicidal activity.
The preliminary herbicidal
activities of compounds 5 were evaluated, against two
representative targets, oil rape, and barnyard grass, at
concentrations of 100 and 10 mg/L according to a
literature method [13]. The results are listed in Table 2
and show that these compounds have moderate herbicidal
activity against oil rape at the concentration of 100 mg/L.
For example, compounds 5f, 5g, 5h, and 5j possessed
60.1%, 63.4%, 67.1%, and 61.3% inhibition against
Brassica campestris L. As for the preliminary structure-
activity relationships, those compounds when R is ethyl,
Their structures were deduced from their spectral data
1
(IR, H NMR, and EI-MS) and elemental analyses, which
Table 2
were listed in the experimental part. For example, the IR
spectra of 5k revealed OH and NH at 3385 and 3211 cm-
1, respectively. The signal 1636 cm-1 is attributed to
C = N absorption, and 1581 and 1475 cm-1 are attributed
Herbicide activity of componds 5a – 5m (growth inhibition rate %).
Brassica campestris
Echinochloa crus-galli cup
root test
test
Compound
10 mg/
100 mg/
10 mg/
100 mg/
mL
mL
mL
mL
Table 1
Optimization of reaction conditions for the synthesis of 2.
5a
5b
5c
5d
7.2
0
0
37.8
49.7
13.5
9.3
0
0
0
0
0
10.0
Temp.
(ꢀC)
Time
(h)
Yield
(%)
Entry
Solvent
Catalyst
0
0
10.0
15.0
5.0
5e
5f
5g
5h
5i
5j
5k
5l
0
0
16.4
23.9
0
0
0
0
0
6.4
0
0
5.0
0
15.0
10.0
5.0
5.0
10.0
30.0
1
2
EtOH
EtOH
70–80
70–80
—
DBU
(10%)
—
—
—
36
36
31
43
60.1
63.4
67.1
21.8
61.3
20.5
50.5
53.4
35.0
15.0
0
3
4
5
DMF
DMF
1,4-
dioxane
1,4-
dioxane
80–90
120
100
12
12
12
Trace
41
Trace
20.0
15.0
20.0
15.0
20.0
35.0
6
100
DBU
(10%)
12
65
5m
Sulcotrione
0
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

658
H.-B. Li and D.-Q. Shi
Vol 51
(monitored by TLC). After the solvent was concentrated under
vacuum, 3 was obtained as colorless crystals in 90% yield. mp
143~144ꢀC; 1H NMR (DMSO-d6, 600 MHz) d: 3.38 (s, 2H,
NH2), 6.38 (s, 1H, NH), 7.09 (d, J = 7.8 Hz, 1H, ArH), 7.40
(t, J = 8.1 Hz, 1H, ArH), 7.69 (d, J = 7.8Hz, 1H, ArH), 8.01
(s, 1H, ArH); ESI-MS m/z (%): 300 (M + Na-1, 10), 268 (M+, 100).
Anal. calcd for C11H9F3N5: C 49.44, H 3.02, N 26.21; found C,
49.73; H, 3.24; N, 26.07.
Synthesis of 5-(ethoxymethyleneamino)-3-(3-trifluoro-
methylanilino)-4-cyano-1H-pyrazole4. 3 (2.67 g, 10 mmol),
triethyl orthoformate (10 mL) and several drops of acetic
anhydride were added to a 50-mL three-necked flask, and the
mixture was refluxed for 2 h while ethanol formed was
removed until no ethanol was evaporated; after cooling, excess
triethyl orthoformate was removed under a reduced pressure,
the crude product was recrystallized from ethanol to give 4 as
light yellow crystals in 75% yield. mp 147~148ꢀC; 1H NMR
(DMSO-d6, 600 MHz) d: 1.33 (t, J = 7.2 Hz, 3H, CH3), 4.33
(q, J = 7.2 Hz, 2H, CH2), 7.14 (d, J = 6.6 Hz, 1H, ArH), 7.45
(t, J = 7.2 Hz, 1H, ArH), 7.73 (d, J = 6.0 Hz, 1H, ArH), 8.01
(s, 1H, ArH), 8.44 (s, 1H, N = CH). Anal. calcd for
C14H12F3N5O: C 52.01, H 3.74, N 21.66; found C, 52.27; H,
3.97; N, 3.40.
General procedure for the synthesis of 5-alkyl(aryl)-
3-[(3-trifluoromethyl)anilino]-4,5-dihydro-1H-pyrazolo[4,3-
d]pyrimidin-4-imines 5. 4 (1.0 mmol), aliphatic or aromatic
amine (1.0 mmol), and THF (10 mL) were added to a 50-mL
three-necked flask, and the mixture was allowed to be stirred
at room temperature for 1–3 h (for aliphatic amine) or under
refluxed for 3–7 h (for aromatic amine; monitored by TLC).
After the solvent was removed under a reduced pressure, the
crude product was recrystallized from ethanol to give 5 in
81–95% yields.
butyl, i-butyl, and allyl exhibited better activity. So,
compounds 5 when R is aliphatic substitutes showed
better activities than those when R is aromatic group did.
Further exploring of structure-activity relationships needs
more experimental results to support. Further biological
activity (in vivo) investigations are on the way.
In conclusion, a series of novel 5-alkyl(aryl)-3-[(3-tri-
fluoromethyl)anilino]-4,5-dihydro-1H-pyrazolo[4,3-d]pyr-
imidin-4-imines were designed and synthesized by the
multistep reactions. Their structures were confirmed
by IR, 1H NMR, EI-MS, and elemental analyses. The
preliminary bioassay indicated that some of them displayed
moderate herbicidal activity against dicotyledonous weed
Brassica campestris L at the concentration of 100 mg/L.
EXPERIMENTAL
Melting points were determined with a WRS-1B digital
melting point apparatus (Wuhan, China) and are uncorrected.
1H NMR spectra was recorded with a Varian Mercury PLUS
600 (600 MHz) spectrometer (USA) with TMS as the internal
reference and CDCl3 or DMSO-d6 as the solvent, whereas
mass spectra were measured on a Finnigan Trace MS 2000
spectrometer (USA) at 70 eV by using EI method or Applied
Biosystems API 2000 LC/MS/MS (ESI-MS) spectrometer
(USA). IR spectra were measured by the use of a Nicolet
NEXUS470 spectrometer (USA). Elemental analyses were
performed with an Elementar Vario ELШ CHNSO elemental
analyzer (Germany). 1 can be prepared according to a
reported method [14]. All of the solvents and materials were
reagent grade (Sinopharm Chemical Reagent Co. Ltd., China,
or Acros Organics, Beijing, China) and purified as required.
Synthesis of 2-[methylthio-(3-trifluoromethylanilino)-
5a.
(R = 4-ClC6H4): yellow solid, yield: 89%, mp
218~220ꢀC; 1H NMR (DMSO-d6, 600 MHz) d: 7.23
(d, J = 7.8 Hz, 2H, ArH), 7.50 (t, J = 7.8 Hz, 2H, ArH), 7.88
(d, J = 7.8 Hz, 2H, ArH), 8.04 (s, 1H, Pyrimidine-H), 8.17 (s, 2H,
ArH), 8.16 (s, 1H, NH), 9.39 (s, 1H, NH), 12.08 (s, 1H, NH); IR
(KBr) υ: 3226 (NH), 2961 (ArH), 1645 (C = N), 1580, 1475, 1452
(Ar) cm-1. Anal. calcd for C18H12ClF3N6: C 53.41, H 2.99, N
20.85; found C, 53.23; H, 3.09; N, 20.55.
methylene]-malononitrile 2.
1 (1.34 g, 20 mmol), DBU
(2 mmol), and anhydrous 1,4-dioxane (20 mL) were added to
a 50-mL three-necked flask when the mixture was heated to
90ꢀC; the solution of 3-(trifluoromethyl)aniline (2.94 g,
20 mmol) in anhydrous 1,4-dioxane (5 mL) were added
dropwise slowly. After the addition of chemicals was
finished, the mixtures were allowed to be stirred under reflux
for 12 h until the reaction was complete (monitored by TLC).
The workup involved stripping of the solvent followed by
addition of water (50 mL) and extraction of the product
mixture into chloroform (25 mL*3), after phase separation,
drying over anhydrous magnesium sulfate, filtration, and
evaporation, the solid was filtered and recrystallized by
anhydrous methanol to give the target compound 2 as
colorless crystals in 65% yield. mp 157~158ꢀC; 1H NMR
(CDCl3, 600 MHz) d: 2.32 (s, 3H, CH3), 7.47 (s, 1H, ArH),
7.54 (s, 1H, ArH), 7.58(d, J = 6.8 Hz, 2H, ArH), 8.26 (s, 1H,
NH). Anal. calcd for C12H9F3N3S: C 50.88, H 2.85, N 14.83;
found C, 50.72; H, 2.99; N, 14.50.
5b.
(R = 3-CF3C6H4): white solid, yield: 85%, mp
201~203ꢀC; 1H NMR (DMSO-d6, 600 MHz) d: 7.13
(d, J = 7.2 Hz, 2H, ArH), 7.45 (t, J = 8.1 Hz, 2H, ArH), 7.75
(d, J= 7.8 Hz, 2H, ArH), 8.17 (s, 1H, Pyrimidine-H), 8.36 (s, 2H,
ArH), 8.96 (s, 1H, NH), 9.12 (s, 1H, NH), 12.56 (s, 1H, NH); IR
(KBr) υ: 3231 (NH), 2958 (ArH), 1668 (C = N), 1572, 1486, 1448
(Ar) cm-1. Anal. calcd for C19H12F6N6: C 52.06, H 2.76, N 19.17;
found C, 51.93; H, 2.99; N, 19.02.
5c. (R = Bn): colorless solid, yield: 95%, mp 216~218 C; 1H
NMR (DMSO-d6, 600 MHz) d: 4.54 (s, 2H, CH2), 7.10
(d, J = 7.8 Hz, 1H, ArH), 7.29 (d, J = 7.8 Hz, 1H, ArH),
7.36 (t, J = 7.8 Hz, 4H, ArH), 7.42 (t, J = 7.8 Hz, 1H, ArH),
7.70 (d, J = 7.8 Hz, 1H, ArH), 7.99 (s, 1H, ArH), 8.26
(s, 1H, Pyrimidine-H), 8.58 (s, 1H, NH), 8.98 (s, 1H, NH),
12.21 (s, 1H, NH); IR (KBr) υ: 3245 (NH), 2974 (ArH),
1648 (C = N), 1569, 1472, 1456 (Ar) cm-1. Anal. calcd for
C19H15F3N6: C 59.37, H 3.93, N 21.87; found C, 59.48; H,
3.84; N, 21.63.
Synthesis of 5-amino-3-(3-trifluoromethylanilino)-4-cyano-
1H-pyrazole 3.
2 (5.66 g, 20 mmol) and anhydrous methanol
(20mL) were added to a 50-mL three-necked flask, 85%
hydrazine hydrate (1.0g, 20 mmol) in anhydrous methanol (5mL)
were added dropwise slowly at room temperature. After the
addition of chemicals was finished, the mixtures were allowed to
be stirred under reflux for 1 h until the reaction was complete
5d. (R = C6H5): yellow solid, yield: 94%, mp 224~226ꢀC; 1H
NMR (DMSO-d6, 600MHz) d: 6.82 (t, J = 6.9 Hz, 2H, ArH), 7.28
(d, J = 7.2 Hz, 1H, ArH), 7.32 (t, J = 7.5 Hz, 1H, ArH), 7.55
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2014
5-Alkyl(aryl)-3-[(3-trifluoromethyl)anilino]-4,5-dihydro-1H-pyrazolo[4,3-d]pyrimidin-4-imines
659
(t, J = 7.8 Hz, 1H, ArH), 7.89 (d, J = 7.8 Hz, 1H, ArH), 8.04
(d, J = 7.2Hz, 1H, ArH), 8.14 (s, 1H, Pyrimidine-H), 8.37 (s, 1H,
ArH), 9.14 (s, 1H, ArH), 9.24 (s, 1H, NH), 9.82 (s, 1H, NH),
12.06 (s, 1H, NH); IR (KBr) υ: 3238 (NH), 2985 (ArH),
1651 (C= N), 1562, 1478, 1458 (Ar) cm-1. Anal. calcd for
C18H13F3N6: C 58.38, H 3.54, N 22.69; found C, 58.10; H, 3.79;
N, 22.73.
5e. (R = 4-CH3OC6H4): white solid, yield: 83%, mp
231~233ꢀC; 1H NMR (DMSO-d6, 600 MHz) d: 3.76 (s, 3 H,
CH3O), 6.96 (d, J = 8.4 Hz, 2H, ArH), 7.13 (d, J = 7.2 Hz, 1 H,
ArH), 7.18 (d,J = 7.8 Hz, 1 H, ArH), 7.44 (t, J = 7.8 Hz, 2 H,
ArH), 7.89 (s, 2H, ArH), 8.04 (s, 1H, Pyrimidine-H), 10.14
(s, 1H, NH), 10.61 (s, 1H, NH), 12.44 (s, 1H, NH); IR (KBr) υ:
3242 (NH), 2981 (ArH), 1647 (C = N), 1561, 1473, 1462 (Ar)
cm-1; EI-MS(70 eV) m/z (%): 400 (M+, 100), 379 (6), 238 (7),
134 (17), 108 (18). Anal. calcd for C19H15F3N6O: C 57.00, H
3.78, N 20.99; found C, 57.25; H, 3.87; N, 21.06.
8.20 (s, 1H, NH), 8.88 (s, 1H, NH), 12.79 (s, 1H, NH); IR
(KBr) υ: 3227 (NH), 2984 (ArH), 1650 (C = N), 1549, 1465,
1453 (Ar) cm-1. Anal. calcd for C15H13F3N6: C 53.89, H 3.92,
N 25.14; found C, 53.61; H, 4.04; N, 25.27.
5k.
(R = CH2CH2OH): white solid, yield: 87%, mp
227~228ꢀC; 1H NMR (DMSO-d6, 600 MHz) d: 3.69 (s, 2H,
CH2), 4.07 (s, 2H, CH2), 5.08 (s, 1H, OH), 7.19 (d, J = 7.8 Hz,
1H, ArH), 7.50 (t, J = 7.8 Hz, 1H, ArH), 7.76 (d, J = 7.8 Hz, 1H,
ArH), 7.91 (s, 1H, ArH), 8.01 (s, 1H, Pyrimidine-H), 8.06
(s, 1H, NH), 8.90 (s, 1H, NH), 12.71 (s, 1H, NH); IR (KBr) υ:
3385 (OH), 3221 (NH), 2959 (ArH), 1636 (C = N), 1581, 1499,
1475 (Ar) cm-1; EI-MS(70 eV) m/z (%): 338 (M+, 93), 294
(100), 250 (10), 145 (17), 44 (31). Anal. calcd for
C14H13F3N6O: C 49.71, H 3.87, N 24.84; found C, 49.92; H,
3.74; N, 24.60.
5l. (R = CH(CH3)CH2OH): white solid, yield: 81%, mp
208~209ꢀC; 1H NMR (DMSO-d6, 600 MHz) d: 1.07
(d, J = 7.2 Hz, 3H, CH3), 3.61 (d, J = 7.2 Hz, 2H, CH2), 3.95–3.98
(m, 1H, CH), 5.18 (s, 1H, OH), 7.15 (d, J = 7.2 Hz, 1H, ArH),
7.46 (t, J = 7.2 Hz, 1H, ArH), 7.70 (d, J = 7.2 Hz, 1H, ArH), 7.86
(s, 1H, ArH), 8.03 (s, 1H, Pyrimidine-H), 8.12 (s, 1H, NH), 8.83
(s, 1H, NH), 12.72 (s, 1H, NH); IR (KBr) υ: 3387 (OH), 3224
(NH), 2971 (ArH), 1633 (C = N), 1575, 1481, 1477 (Ar) cm-1.
Anal. calcd for C15H15F3N6O: C 51.14, H 4.29, N 23.85; found
C, 51.03; H, 4.10; N, 23.67.
5f. (R = C2H5): yellow solid, yield: 90%, mp 224~226ꢀC; 1H
NMR (DMSO-d6, 600 MHz) d: 1.23 (t, J = 7.8 Hz, CH3), 3.30
(q, J = 7.8 Hz, 2H, CH2), 7.14 (d, J = 7.2 Hz, 1H, ArH), 7.42
(t, J = 7.2 Hz, 1H, ArH), 7.45 (d, J = 7.8 Hz, 1H, ArH), 7.70
(s, 1H, ArH), 8.01 (s, 1H, Pyrimidine-H), 8.20 (s, 1H, NH),
8.80 (s, 1H, NH), 12.78 (s, 1H, NH); IR (KBr) υ: 3248 (NH),
2988 (ArH), 1652 (C = N), 1560, 1471, 1468 (Ar) cm-1. Anal.
calcd for C14H13F3N6: C 52.17, H 4.07, N 26.08; found C,
52.31; H, 3.90; N, 25.87.
5m. (R = i-Pr): white solid, yield: 89%, mp 196~198ꢀC;
1H NMR (DMSO-d6, 600 MHz) d: 1.19 (d, J = 6.6 Hz,
6H, 2CH3), 4.07–4.11 (m, 1H, CH), 7.11 (d, J = 7.8 Hz,
1H, ArH), 7.43 (t, J = 7.8 Hz, 1H, ArH), 7.72 (d, J = 7.8 Hz, 1H,
ArH), 8.02 (s, 1H, ArH), 8.06 (s, 1H, Pyrimidine-H), 8.10 (s, 1H,
NH), 9.00 (s, 1H, NH), 12.19 (s, 1H, NH); IR (KBr) υ: 3220
(NH), 2963 (ArH), 1635 (C = N), 1576, 1472, 1452 (Ar) cm-1.
Anal. calcd for C15H15F3N6: C 53.57, H 4.50, N 24.99; found C,
53.71; H, 4.34; N, 25.11.
5g. (R = Bu): white solid, yield: 95%, mp 214~216 ꢀC; 1H
NMR (DMSO-d6, 600 MHz) d: 0.89 (t, J = 7.2 Hz, 3H, CH3),
1.33–1.37 (m, 2H, CH2), 1.46–1.55 (m, 2H, CH2), 3.27
(t, J = 7.2 Hz, 2H, CH2), 7.11 (d, J = 8.1 Hz, 1H, ArH), 7.42
(t, J= 7.2 Hz, 1H, ArH), 7.70 (d, J= 7.8 Hz, 1H, ArH), 7.88 (s, 1H,
NH), 8.00 (s, 1H, ArH), 8.12 (s, 1H, Pyrimidine-H), 9.00
(s, 1H, NH), 12.10 (s, 1H, NH); IR (KBr) υ: 3231 (NH), 2982
(ArH), 1653 (C = N), 1565, 1473, 1466 (Ar) cm-1. Anal. calcd
for C16H17F3N6: C 54.85, H 4.89, N 23.99; found C, 54.59; H,
4.70; N, 24.05.
Herbicidal activity testing.
The herbicidal activity
measurement method was adapted according to a literature
method [13].
1
5h. (R = i-Bu): yellow solid, yield: 93%, mp 213~215ꢀC; H
NMR (DMSO-d6, 600 MHz) d: 0.88 (d, J = 7.2 Hz, 6H,
2CH3), 1.85–1.89 (m, 1H, CH), 2.99 (d, J = 7.2 Hz, 2H,
CH2), 3.37 (s, 1H, NH), 7.10 (d, J = 7.8 Hz, 1H, ArH), 7.42
(t, J = 7.8 Hz, 1H, ArH), 7.70 (d, J = 7.8 Hz, 1H, ArH), 8.00
(s, 1H, ArH), 8.15 (s, 1H, Pyrimidine-H), 8.28 (s, 1H, NH),
8.96 (s, 1H, NH), 12.16 (s, 1H, NH); IR (KBr) υ: 3235
(NH), 2980 (ArH), 1658 (C = N), 1561, 1471, 1469 (Ar)
cm-1; EI-MS(70 eV) m/z (%): 350 (M+, 100), 307 (5), 238
(7), 294 (96), 267 (28), 252 (12), 145 (17), 57 (22). Anal.
calcd for C16H17F3N6: C 54.85, H 4.89, N 23.99; found C,
54.94; H, 4.98; N, 23.75.
Acknowledgments. This work was supported by the Natural
Science Foundation of China (No. 20872046) and the Natural
Science Foundation of Hubei Province (No. 2008CDB086).
REFERENCES AND NOTES
[1] Sandmann, G.; Böger, P. In Herbicide Activity: Toxicology,
Biochemistry, and Molecular Biology; Roe, R. M., Burton, J. D., Kuhr,
R. J., Eds.; IOS Press: Amsterdam, 1997; pp 1–10.
[2] Sandmann, G. In Herbicidal Classes in Development: Mode of
Action, Targets, Genetic Engineering, Chemistry; Böger, P., Wakabayashi,
K., Hirai, K., Eds.; Springer: Berlin, 2002; pp 43–55.
[3] Mitchell, G. In Synthesis and Chemistry of Agrochemicals IV,
Baker, D. A., Fenyes, J. G., Moberg, W. K., Cross, B., Eds.; ACS
Symposium Series, American Chemical Society: Washington, DC,
1995; Vol. 584, pp 161–170.
[4] Sandmann, G.; Kowalczyk-Schroder S.; Taylor, H. M. Pestic
Biochem Physiol 1992, 42(1), 1.
[5] Sandmann, G.; Kunert, K. J.; Böger, P. Pestic Biochem
Physiol 1981, 15, 28.
[6] Cramp, M. C.; Gilmour, J.; Hatton, L. R. Pestic Sci 1987, 18(1), 15.
[7] Xia, Y.; Samuel, C.; Michael, C.; Hsingan, T.; Henry, V.;
Renee, C.; John, C.; Ahmad, F.; Robert, W.; Zhang, H. J Med Chem
1997, 40(26), 4372.
5i. (R = CH2CH2): white solid, yield: 83%, mp 196~198ꢀC;
1H NMR (DMSO-d6, 600 MHz) d: 2.80 (s, 2H, CH2), 3.96
(s, 2H, CH2), 7.14 (t, J = 7.8 Hz, 2H, ArH), 7.42–7.47 (m, 2H,
ArH), 7.70 (d, J = 7.2 Hz, 1H, ArH), 7.79 (d, J = 7.8 Hz, 1H,
ArH), 7.93 (s, 1H, ArH), 8.01 (s, 1H, ArH), 8.06 (s, 2 H, NH),
8.19 (s, 2H, Pyrimidine-H), 8.82 (s, 2H, NH), 12.05 (s, 2H,
NH); IR (KBr) υ: 3237 (NH), 2981 (ArH), 1672 (C = N), 1564,
1466, 1450 (Ar) cm-1. Anal. calcd for C26H20F6N12: C 50.82, H
3.28, N 27.35; found C, 50.94; H, 3.47; N, 27.13.
5j. (R = allyl): yellow solid, yield: 92%, mp 215~217ꢀC; 1H
NMR (DMSO-d6, 600 MHz) d: 4.61 (d, J = 7.8 Hz, 2H, CH2),
5.18 (d, J = 7.8 Hz, 2H, =CH2), 6.0–6.04 (m, 1H, =CH), 7.16
(d, J = 7.8 Hz, 1H, ArH), 7.47 (t, J = 7.2 Hz, 1H, ArH), 7.72
(d, J = 7.8 Hz, 1H, ArH), 7.98 (s, 2H, ArH + Pyrimidine-H),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

660
H.-B. Li and D.-Q. Shi
Vol 51
[8] Taliani, S.; La Motta, C.; Mugnaini, L.; Simorini, F.; Salerno,
[10] Ugarkar B. G.; Cottam, H. B.; McKernan, P. A.; Robins, R.
K.; Revankar, G. R.; J Med Chem 1984, 27(8), 1026.
S.; Marini, A. M.; Da Settimo, F.; Cosconati, S.; Cosimelli, B.; Greco, G.;
Vittorio, L.; Marinelli, L.; Novellino, E.; Ciampi, O.; Daniele, S.;
Trincavelli, M. L.; Martini, C. J Med Chem 2010, 53(10), 3954.
[9] Traxler, P.; Bold, G.; Frei, J.; Lang, M.; Lydon, N.; Mett, H.;
Buchdunger, E.; Meyer, T.; Mueller, M.; Furet, P. J Med Chem 1997,
40(22), 3601.
[11] Liu, T. L.; Xie, J. H.; Yang, Z. H. Chin J Org Chem 2000, 20, 900.
[12] Bell, A. S.; Sandwich, K.; Terrett, N. K. EP 0463756, 1991.
[13] Tang, W.; Shi, D. Q. J Heterocycl Chem 2010, 47, 162.
[14] Zhao, W. G.; Wang, S. H.; Wang, W. Y.; Li, Z. M. Huaxue
Shiji 2000, 22, 376.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet