Facile synthesis and biological evaluation of novel fluorine-containing N-nitro-N′-substituted phenylurea

Article abstract of DOI:10.1007/s11164-011-0308-9

Twenty-two novel N-nitro-N′-substituted phenyl-N-(2,6-dibromo-4- fluorophenyl)urea derivatives were designed and synthesized via a simple and convenient BTC 'one-pot' procedure using DMAP as the catalyst. The structures of all newly synthesized compounds were confirmed by IR, ¹H NMR, and elemental analysis, and a part has been identified by ¹³C NMR. The preliminary bioassay indicates that the target compounds possesses moderate herbicidal activity against Sorghum sudanense. However, some of the title compounds presented high plant growth regulating activity against rape.

Full text of DOI:10.1007/s11164-011-0308-9

Res Chem Intermed (2011) 37:1029–1039
DOI 10.1007/s11164-011-0308-9
Facile synthesis and biological evaluation of novel
fluorine-containing N-nitro-N0-substituted phenylurea
•
Yunchun Wang Zhongyuan Bai Zengjun Wei
•
•
•
Shengzhen Xu Xuegang Li Jianhong Li
•
•
•
Xiufang Cao Changshui Chen
Received: 17 March 2011 / Accepted: 29 March 2011 / Published online: 23 April 2011
Ó Springer Science+Business Media B.V. 2011
Abstract Twenty-two novel N-nitro-N0-substituted phenyl-N-(2,6-dibromo-4-
fluorophenyl)urea derivatives were designed and synthesized via a simple and
convenient BTC ‘one-pot’ procedure using DMAP as the catalyst. The structures of
1
all newly synthesized compounds were confirmed by IR, H NMR, and elemental
analysis, and a part has been identified by 13C NMR. The preliminary bioassay
indicates that the target compounds possesses moderate herbicidal activity against
Sorghum sudanense. However, some of the title compounds presented high plant
growth regulating activity against rape.
Keywords N-nitrourea ꢀ Synthesis ꢀ Biological activity
Introduction
Urea functionality is an important structural feature present in many bioactive
molecules, many of which exhibit herbicidal and antimicrobial activity [1], plant
and insect growth regulators [2], and as antagonists of natural receptors [3, 4].
Several ureid derivatives have also proved to be anti-tumor agents [5], and to inhibit
HIV protease and glycine transporter GlyT-2 [6]. However, most urea derivatives
were synthesized and studied for their herbicidal activity. It has been reported that
N-nitro-substituted anilines have a broad range of biological effects, including
herbicidal properties [7, 8], antifungal effects [9], and plant growth regulating
Y. Wang ꢀ Z. Bai ꢀ Z. Wei ꢀ S. Xu ꢀ X. Li ꢀ X. Cao (&) ꢀ C. Chen (&)
College of Science, Huazhong Agricultural University, Wuhan, China
e-mail: caoxiufang@mail.hzau.edu.cn
C. Chen
e-mail: chenchang@mail.hzau.edu.cn
J. Li
Department of Plant Protection, Huazhong Agricultural University, Wuhan, China
123

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Y. Wang et al.
activities [10]. Additionally, fluorine is a very unique element with the highest
electro negativity [11], smallest size next to hydrogen [12], high thermal stability
and lipophilicity [13], which endows various desirable pharmacodynamic attributes.
Thus, organofluorine compounds have been an interesting topic in the fields of
medicinal and agricultural chemistry for many years [14]. In the light of these
points, we attempt to synthesize a series of fluorine-containing N-nitro-substituted
anilines derivatives incorporating NH–CO–NH bridge units and explore novel broad
potential biological activities.
Our group were actively engaged in the research of the synthesis of N-nitrourea
derivatives [15–17] for a long time. The preliminary bioassay indicated that these
compounds displayed moderate herbicidal and plant growth regulating activities.
As a part of our extensive research, we designed and synthesized a series of
new N-nitro-N0-substituted phenyl-N-(2,6-dibromo-4-fluorophenyl)urea derivatives
(Scheme 1). The preliminary in vitro bioassay indicated that some title compounds
displayed moderate herbicidal activity and favorable plant growth regulating
activity. Compared with former N-nitro-N0-substituted phenyl-N-(2,4,6-trichlor-
ophenyl)urea derivatives, the fluorine-containing N-nitrourea derivatives present
better herbicidal activity against Sorghum sudanense.
Results and discussion
Synthesis of fluorine-containing N-nitro-N0-substituted phenylurea derivatives
4a–v
The target compounds N-nitro-N0-substituted phenyl-N-(2,6-dibromo-4-fluoro-
phenyl)urea derivatives 4a–v were conveniently synthesized according to
Scheme 1.
During the synthesis, a series of parallel experiments show that the key factors for
the formation of compound 2 is the acidity of nitric acid and for 4 is the steric effect
and negativity of substituents of various anilines. The optimal procedure indicates
Br
SO3H
NH2
O
iii
i
H
N
ii
F
F
NH2
F
NH2
F
F
Br
1
Br
Br
Br
Br
Br
Br
R
NO2
NH
NO2
N
NO2
vi
iv
v
H
N
NH2
F
F
Cl
F
N
O
O
Br
Br
1
3
4a-v
2
Scheme 1 General synthetic route for fluorine-containing N-nitro-N0-substituted phenylurea derivatives
4a–v. Reagents and conditions: i CH3COOH, Ac2O, 50 °C, 3 h. ii H2SO4, 170–180 °C, 2 h. iii H2O, Br2,
2 h, 25 °C. iv 90% HNO3, CH3COOH, 10–20 °C, 0.5–1 h; then Ac2O, 20–25 °C, 1–1.5 h. v BTC,
triethylamine, toluene, 0–5 °C, 1 h; then 50 °C, 2–3 h. vi Substituted amines, DMAP, triethylamine,
toluene, 50 °C; and then 50–80 °C, 4–7 h
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Fluorine-containing N-nitro-N0-substituted phenylurea
1031
Table 1 Respective different reaction conditions and physical data of compounds 4a–v
Compound
R
Time (h)
Temp. (°C)
Yield (%)
M.P. (°C)
4a
4b
4c
4d
4e
4f
4-Cl
5
5
4
5
5
5
5
5
5
5
6
5
5
5
5
5
7
6
6
7
7
6
50
50
50
50
50
50
50
50
60
70
80
50
50
50
50
50
60
60
60
60
70
60
78.3
65.6
80.2
72.3
76.3
78.8
68.3
80.2
61.2
58.7
58.3
69.6
65.9
56.3
68.4
53.2
54.3
50.2
62.8
56.7
48.7
53.6
223–224
212–213
210–212
221–223
248–250
214–215
232–234
218–220
209–210
216–214
226–227
200–201
208–210
250–252
234–236
264–265
218–220
238–240
235–237
207–209
208–210
265–267
3-Cl
H
2-Cl
2-CH3O
2-CH3
4g
4h
4i
3-CH3
4-CH3
4-Br
4j
3-Br
4k
4l
4-F
4-C2H5O
3,4-di-CH3O
2-CH3-3-Cl
2,4-di-CH3
2,6-di-CH3
3-CH3O
3,4-di-CH3
4-CH3O
2,3-di-CH3
2,5-di-CH3
–(CH)4–
4m
4n
4o
4p
4q
4r
4s
4t
4u
4v
that the crystal compounds 2 can only be successfully obtained by adding 90%
concentrated nitric acid. If the concentrate of nitric acid is more than or less than
90%, no crystals were obtained. During the preparation for compounds 4, the
substituents on para-position are propitious to increase yields than the compounds
bearing ortho-position substituents (Table 1). Meanwhile, if electron-donating
substituents are present on the aniline, the corresponding urea derivatives can be
obtained easily, but if electron-withdrawing substituents are present on the ring, the
reaction becomes difficult or the crystal compounds cannot be obtained, such as the
case for the nitro-substituted aniline, where there was no crystal compound obtained.
Biological activity evaluation
The herbicidal activities of the title compound 4a–v against Sorghum sudanense
have been investigated at the dosages 10, 25, 50, 100, and 200 mg/L compared with
distilled water and commercially available herbicide Diuron according to the
method described in the Experimental section. The IC50 values against Sorghum
sudanense of compounds 4a–v are listed in Table 2. In order to discuss
the structure–activity relationships, we also list the IC50 values against
Sorghum sudanense of N-nitro-N0-substituted phenyl-N-(2,4,6-trichlorophenyl)urea
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Y. Wang et al.
Table 2 Determination of IC50 values against Sorghum sudanense of compounds 4a–v and 5a–v
Br
Cl
R
R
NO2
N
NO2
N
H
N
H
N
F
Cl
O
O
Br
Cl
4a-v
5a-v
Compound
R
Active gradea
IC50 (mg/L)
Compound IC50 (mg/L)
of hypocotylsb
of formation-promoting
against rape
hypocotyl
Root
Hypocotyl
4a
4b
4c
4d
4e
4f
4-Cl
A
A
B
A
C
D
C
C
A
A
A
C
C
D
D
D
B
C
C
B
D
D
–
40.46c 297.38
5a
5b
5c
5d
5e
5f
306.24
267.90
333.45
382.02
191.36
119.33
189.57
203.94
332.11
208.99
163.91
264.06
292.58
574.84
522.97
306.97
–
3-Cl
84.58 201.76
189.27 147.23
97.49 212.06
176.62 151.42
H
2-Cl
2-CH3O
2-CH3
3-CH3
4-CH3
4-Br
132.58
96.95
4g
4h
4i
174.05 149.79
104.22 169.62
5g
5h
5i
145.40
175.76 145.79
128.30 98.77
143.71 241.46
130.36 96.55
98.02
4j
3-Br
5j
4k
4l
4-F
5k
5l
4-C2H5O
3,4-di-CH3O
2-CH3-3-Cl
2,4-di-CH3
2,6-di-CH3
3-CH3O
4m
4n
4o
4p
4q
4r
4s
5m
5n
5o
5p
5q
5r
5s
118.16 166.38
150.17 161.36
99.77 124.22
190.96 273.82
128.80 198.25
137.70 239.13
147.42 229.83
122.43 191.79
117.00 192.38
3,4-di-CH3
4-CH3O
237.52
–
4t
2,3-di-CH3
2,5-di-CH3
–(CH)4–
5t
–
4u
4v
Diuron
a
5u
5v
370.86
–
–
41.31
66.33
Active grade: A [ 70%, B [ 50%, C [ 30%, D \ 30% at the concentration of 10 mg/L
The IC50 values were obtained from the Master’s degree dissertation by Shen [17]
The best herbicidal activity
b
c
derivatives, named 5a–v, which are obtained under the same conditions [17]. As
shown in Table 2, compound 4a exhibited the highest herbicidal activity against
root, which is close to the commercial herbicide Diuron. Fluorine-introducing urea 4
always displayed higher herbicidal activity against hypocotyl than (2,4,6-trichlor-
ophenyl)urea derivatives 5.
The plant growth regulatory activity of title compounds against rape was
evaluated at the concentration of 10 mg/L, and the results are shown in Table 2.
From Table 2, we find that the compounds 4a, 4b, 4d, 4i, 4j, and 4k exhibited
123

Fluorine-containing N-nitro-N0-substituted phenylurea
1033
higher plant growth regulating activity than that of other compounds. It was
suggested that electron-withdrawing substituent halogens may cause the increase of
their plant growth regulatory activity.
Conclusions
The title compounds 4 were designed and synthesized by a simple and convenient
BTC ‘one-pot’ procedure using DMAP as the catalyst. Some of these compounds
had significant herbicidal activity against the roots of Sudanense. The introduction
of fluorine to benzene was useful for the improvement of herbicidal activity against
the hypocotyls of Sudanense. Especially, compound 4a displayed high herbicidal
activity and excellent plant growth regulating activity, and it can be developed as a
lead compound for further study.
Experimental
Instrumentation and chemicals
All reagents were commercially available and all solvents and liquid reagents were
dried by standard methods and distilled before use. The reactions were monitored by
thin layer chromatography (TLC) on Merck pre-coated silica GF254 plates
visualized with UV light. Melting points (uncorrected) were determined on an
XRC-1 apparatus (Sichuan University Scientific Instruments Factory, Chengdu,
China). IR spectra were recorded on FT-IR in KBr. 1H NMR and 13C NMR spectra
were collected on a Bruker DPX at 400 or DPX600 spectrometer at room
temperature in DMSO-d6 using tetramethylsilane (TMS) as the internal standard.
Chemical shifts are reported in ppm units with the use of the d scale.
General synthetic procedure for 2,6-dibromo-4-fluoroaniline 1
The key fluorine-containing intermediate 2,6-dibromo-4-fluoroaniline 1 was
obtained according to the method described in Scheme 1. 4-fluoroaniline was
treated with acetic anhydride in the presence of acetic acid at 50 °C for about 3 h to
yield N-(4-fluorophenyl)acetamide, which was further transformed to 2-amino-5-
fluorobenzenesulfonic acid using concentrated sulfuric acid at 170 to 180 °C for 2 h
[18]. Then, the 2-amino-5-fluorobenzenesulfonic acid was bromized with bromine
water to yield 2,6-dibromo-4-fluoroaniline 1.
General procedure for the preparation of fluorine-containing N-nitro-N0-
substituted phenylurea derivatives 4a–v
To a cooled solution of 2,6-dibromo-4-fluoroaniline 1 in glacial acetic acid,
dropwise 90% nitric acid was added, and then the nitrate salt precipitates out. After
30 min, acetic anhydride is added dropwise with stirring and the temperature
allowed to reach 18 to 25 °C. The reaction mixture darkens and becomes
123

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Y. Wang et al.
homogeneous, at which point the mixture is poured into ice-water. The resulting
precipitate is filtered, washed with water, and dissolved in aqueous 10% sodium
carbonate, followed by decolorization with activated carbon. The filtrate was
acidified with ice-cold 2 M hydrochloric acid to precipitate the 2,6-dibromo-4-
fluorophenylnitramine 2.
One-pot synthesis of compounds 3 and 4a–v: to a solution of BTC (bis(trichlo-
romethyl) (3.3 mmol) in 15 mL dry toluene at -5 to 0 °C with stirring, a solution of
compound 2 (10 mmol) and a catalytic amount of triethylamine (2 mL) in 50 mL
dry toluene was added dropwise. The reaction mixture was then removed from the
cooling bath and was heated at room temperature for 3 h to yield intermediate 3
without isolates. After quenching the unreacted phosgene with dry nitrogen,
substituted aniline in 20 mL of dry toluene with a catalytic amount of DMAP (4-
dimethylamino pyridine, 1 mmol) was added dropwise to the unseparated solution
containing compound 3, churned at 50–80 °C for 4–8 h (the respective different
reaction conditions are shown in Table 2), and then cooled to room temperature.
The desired compounds 4a–v were precipitated, filtered, and washed with toluene,
excess water, and acetone. Crude products were further purified by recrystallization
(DMF/acetone).
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(4-chlorophenyl)urea (4a)
1
White crystals. IR (KBr, cm-1): m 3268 (NH), 3084 (ArH), 1636 (CO); H NMR
(600 MHz, DMSO-d6): dH 9.09 (s, 1H, NH), 7.76 (d, 2H, J = 7.8 Hz, ArH), 7.48
(d, 2H, J = 8.4 Hz, ArH), 7.30 (d, 2H, J = 9 Hz, ArH). Anal. Calcd. for
C13H7Br2ClFN3O3: C, 33.40; H, 1.51; N, 8.99. Found: C, 33.12; H, 1.48; N, 9.03.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(3-chlorophenyl)urea (4b)
1
Light yellow crystals. IR (KBr, cm-1): m 3271 (NH), 3083 (ArH), 1646 (CO); H
NMR (600 MHz, DMSO-d6): dH 9.17 (s, 1H, NH), 7.75(d, 2H, J = 7.8 Hz, ArH),
7.67 (s, 1H, ArH), 7.25 (d, 2H, J = 6.6 Hz, ArH), 6.97 (d, 1H, J = 6.6 Hz, ArH).
Anal. Calcd. for C13H7Br2ClFN3O3: C, 33.40; H, 1.51; N, 8.99. Found: C, 33.42; H,
1.48; N, 9.05.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-phenylurea (4c)
1
Light yellow crystals. IR (KBr, cm-1): m 3271 (NH), 3078 (ArH), 1641 (CO); H
NMR (600 MHz, DMSO-d6): dH 8.93 (s, 1H, NH), 7.76 (d, 2H, J = 7.8 Hz, ArH),
7.44 (d, 2H, J = 7.8 Hz, ArH), 7.27 (t, 2H, J = 14.4 Hz, ArH), 6.95 (t, 1H,
J = 15.0 Hz, ArH). Anal. Calcd. for C13H8Br2FN3O3: C, 36.06; H, 1.86; N, 9.70.
Found: C, 36.01; H, 1.78; N, 9.63.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(2-chlorophenyl)urea (4d)
1
White crystals. IR (KBr, cm-1): m 3256 (NH), 3076 (ArH), 1653 (CO); H NMR
(600 MHz, DMSO-d6): dH 8.97 (s, 1H, NH), 8.14 (d, 1H, J = 7.8 Hz, ArH), 7.77
123

Fluorine-containing N-nitro-N0-substituted phenylurea
1035
(d, 2H, J = 7.8 Hz, ArH), 7.47 (m, 1H, ArH), 7.29 (t, 1H, J = 15.0 Hz, ArH), 7.04
(m, 1H, ArH). Anal. Calcd. for C13H7Br2ClFN3O3: C, 33.40; H, 1.51; N, 8.99.
Found: C, 33.32; H, 1.52; N, 9.08.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(2-methoxyphenyl)urea (4e)
1
White crystals. IR (KBr, cm-1): m 3253 (NH), 3081 (ArH), 1654 (CO); H NMR
(600 MHz, DMSO-d6): dH 8.43 (s, 1H, NH), 8.09 (d, 1H, J = 7.8 Hz, ArH), 7.77
(d, 2H, J = 7.8 Hz, ArH), 7.02 (d, 1H, J = 8.4 Hz, ArH), 6.94 (t, 1H, J = 13.8 Hz
ArH), 6.87(t, 1H, J = 15.0 Hz, ArH), 3.89 (s, 3H, OCH3). 13C NMR (125 MHz,
DMSO-d6); d 160.4, 158.7 (CF), 152.2, 147.3, 132.8, 128.7, 125.0, 124.9, 121.7,
120.5, 119.5, 119.3, 117.8, 110.6, 55.7. Anal. Calcd. for C14H10Br2FN3O4: C, 36.31;
H, 2.18; N, 9.07. Found: C, 36.23; H, 2.28; N, 8.98.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(2-methylphenyl)urea (4f)
1
Light yellow crystals. IR (KBr, cm-1): m 3272 (NH), 3083(ArH), 1642(CO); H
NMR (600 MHz, DMSO-d6): dH 8.47 (s, 1H, NH), 8.12 (s, 1H, ArH), 7.76 (d, 2H,
J = 7.8 Hz, ArH), 7.18 (d, 1H, J = 7.2 Hz, ArH), 7.13 (t, 1H, J = 15.6 Hz, ArH),
6.96 (t, 1H, J = 14.4 Hz, ArH), 2.08 (s, 3H, CH3). Anal. Calcd. for
C14H10Br2FN3O3: C, 37.61; H, 2.25; N, 9.40. Found: C, 37.63; H, 2.28; N, 9.43.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(3-methylphenyl)urea (4g)
1
Light yellow crystals. IR (KBr, cm-1): m 3273 (NH), 3080 (ArH), 1645 (CO); H
NMR (600 MHz, DMSO-d6): dH 8.81 (s, 1H, NH), 7.74 (d, 2H, J = 7.8 Hz, ArH),
7.27 (s, 1H, ArH), 7.19 (d, 1H, J = 8.4 Hz, ArH), 7.12 (t, 1H, J = 15.6 Hz, ArH),
6.75 (d, 1H, J = 7.2 Hz, ArH), 2.22 (3H, s, CH3). Anal. Calcd. for
C14H10Br2FN3O3: C, 37.61; H, 2.25; N, 9.40. Found: C, 37.53; H, 2.18; N, 9.33.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(4-methylphenyl)urea (4h)
1
Light yellow crystals. IR (KBr, cm-1): m 3272 (NH), 3079 (ArH), 1642 (CO); H
NMR (600 MHz, DMSO-d6): dH 9.29 (s, 1H, NH), 7.74(d, 2H, J = 7.8 Hz, ArH),
7.35 (d, 2H, J = 9 Hz, ArH), 7.05 (d, 2H, J = 8.4 Hz, ArH), 2.22 (s, 3H, CH3).
Anal. Calcd. for C14H10Br2FN3O3: C, 37.61; H, 2.25; N, 9.40. Found: C, 37.62; H,
2.18; N, 9.41.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(4-bromophenyl)urea (4i)
1
Yellow crystals. IR (KBr, cm-1): m 3263 (NH), 3085 (ArH), 1635 (COa); H NMR
(600 MHz, DMSO-d6): dH 9.20 (s, 1H, NH), 7.77 (d, 2H, J = 7.8 Hz, ArH), 7.45 (t,
4H, J = 19.2 Hz, ArH). Anal. Calcd. for C13H7Br3FN3O3: C, 30.50; H, 1.38; N,
8.21. Found: C, 30.54; H, 1.28; N, 8.24.
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Y. Wang et al.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(3-bromophenyl)urea (4j)
1
Yellow crystals. IR (KBr, cm-1): m 3267 (NH), 3080 (ArH), 1638 (CO); H NMR
(600 MHz, DMSO-d6): dH 9.18 (s, 1H, NH), 7.85 (s, 1H, ArH), 7.77 (d, 2H,
J = 7.8 Hz, ArH), 7.34 (d, 1H, J = 7.8 Hz, ArH), 7.23 (t, 1H, J = 16.2 Hz, ArH),
7.14 (d, 1H, J = 7.8 Hz, ArH). Anal. Calcd. for C13H7Br3FN3O3: C, 30.50; H, 1.38;
N, 8.21. Found: C, 30.46; H, 1.31; N, 8.21.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(4-fluorophenyl)urea (4k)
1
White crystals. IR (KBr, cm-1): m 3272 (NH), 3083 (ArH), 1640 (CO); H NMR
(600 MHz, DMSO-d6): dH 9.03 (s, 1H, NH), 7.76 (d, 2H, J = 7.8 Hz, ArH), 7.47
(q, 2H, J = 10.2 Hz, ArH), 7.11 (t, 2H, J = 17.4 Hz, ArH). Anal. Calcd. for
C13H7Br2F2N3O3: C, 34.62; H, 1.56; N, 9.32. Found: C, 34.54; H, 1.58; N, 9.24.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(4-ethoxyphenyl)urea (4l)
1
White crystals. IR (KBr, cm-1): m 3264 (NH), 3074 (ArH), 1630 (CO); H NMR
(600 MHz, DMSO-d6): dH 8.76 (s, 1H, NH), 7.75 (d, 2H, J = 8.4 Hz, ArH), 7.34
(d, 2H, J = 8.4 Hz, ArH), 6.84 (d, 2H, J = 9 Hz, ArH), 3.97 (q, 2H, J = 13.8 Hz,
CH2), 1.31 (t, 3H, J = 13.8 Hz, CH3). Anal. Calcd. for C15H12Br2FN3O4: C, 37.76;
H, 2.54; N, 8.81. Found: C, 37.83; H, 2.58; N, 8.78.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(3,4-dimethoxyphenyl)urea (4m)
1
White crystals. IR (KBr, cm-1): m 3260 (NH), 3075 (ArH), 1630 (CO); H NMR
(600 MHz, DMSO-d6): dH 9.76 (s, 1H, NH), 7.71 (d, 2H, J = 8.4 Hz, ArH), 7.03 (s,
1H, ArH), 6.94 (d, 1H, J = 7.2 Hz, ArH), 6.82 (d, 1H, J = 8.4 Hz, ArH), 3.69 (s,
3H, OCH3). Anal. Calcd. for C15H12Br2FN3O5: C, 36.54; H, 2.45; N, 8.52. Found:
C, 36.53; H, 2.50; N, 8.58.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(2-methyl-3-chlorophenyl)urea (4n)
1
White crystals. IR (KBr, cm-1): m 3258 (NH), 3085 (ArH), 1635 (CO); H NMR
(600 MHz, DMSO-d6): dH 8.48 (s, 1H, NH), 7.76 (d, 2H, J = 7.8 Hz, ArH), 7.64 (s,
1H, ArH), 7.17 (t, 2H, J = 15.0 Hz, ArH), 2.08 (s, 3H, CH3). Anal. Calcd. for
C14H9Br2ClFN3O3: C, 34.92; H, 1.88; N, 8.73. Found: C, 34.93; H, 1.85; N, 8.78.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(2,4-dimethylphenyl)urea (4o)
1
White crystals. IR (KBr, cm-1): m 3273 (NH), 3079 (ArH), 1645 (CO); H NMR
(600 MHz, DMSO-d6): dH 8.05 (s, 1H, NH), 7.75 (d, 2H, J = 7.8 Hz, ArH), 7.53 (s,
1H, ArH), 6.99 (s, 1H, ArH), 6.93 (d, 1H, J = 8.4 Hz, ArH), 2.22 (s, 6H, 2 9 CH3).
Calcd. for C15H12Br2FN3O3: C, 36.54; H, 2.45; N, 8.52. Found: C, 36.53; H, 2.50;
N, 8.58.
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Fluorine-containing N-nitro-N0-substituted phenylurea
1037
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(2,6-dimethylphenyl)urea (4p)
1
White crystals. IR (KBr, cm-1): m 3257 (NH), 3080 (ArH), 1633 (CO); H NMR
(600 MHz, DMSO-d6): dH 8.22 (s, 1H, NH), 7.73 (d, 2H, J = 7.8 Hz, ArH), 7.04 (s,
3H, ArH), 2.24 (s, 6H, 2 9 CH3). Calcd. for C15H12Br2FN3O3: C, 36.54; H, 2.45; N,
8.52. Found: C, 36.43; H, 2.52; N, 8.48.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(3-methoxyphenyl)urea (4q)
1
Light yellow crystals. IR (KBr, cm-1): m 3266 (NH), 3076 (ArH), 1643 (CO); H
NMR (600 MHz, DMSO-d6): dH 8.95 (s, 1H, NH), 7.76 (d, 2H, J = 7.2 Hz, ArH),
7.17 (t, 2H, J = 20.4 Hz, ArH), 6.96 (d, 1H, J = 8.4 Hz, ArH), 6.54 (d, 1H,
J = 8.4 Hz, ArH), 3.71(s, 3H, OCH3). Anal. Calcd. for C14H10Br2FN3O4: C, 36.31;
H, 2.18; N, 9.07. Found: C, 36.26; H, 2.29; N, 9.08.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(3,4-dimethylphenyl)urea (4r)
1
White crystals. IR (KBr, cm-1): m 3272 (NH), 3080 (ArH), 1648 (CO); H NMR
(600 MHz, DMSO-d6): dH 7.77 (d, 2H, J = 7.8 Hz, ArH), 7.23 (s, 1H, ArH), 7.16
(d, 1H, J = 7.2 Hz, ArH), 7.00 (d, 1H, J = 8.4 Hz, ArH), 2.16 (s, 6H, 2 9 CH3).
Calcd. for C15H12Br2FN3O3: C, 36.54; H, 2.45; N, 8.52. Found: C, 36.48; H, 2.46;
N, 8.49.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(4-methoxyphenyl)urea (4s)
1
Light yellow crystals. IR (KBr, cm-1): m 3265 (NH), 3076 (ArH), 1638 (CO); H
NMR (600 MHz, DMSO-d6): dH 8.80 (s, 1H, NH), 7.75 (d, 2H, J = 7.2 Hz, ArH),
7.36 (t, 2H, J = 6.6 Hz and J = 2.4 Hz, ArH), 6.85 (t, 2H, J = 9.0 Hz, ArH), 3.70
(s, 3H, OCH3). Anal. Calcd. for C14H10Br2FN3O4: C, 36.31; H, 2.18; N, 9.07.
Found: C, 36.32; H, 2.21; N, 8.99.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(2,3-dimethylphenyl)urea (4t)
1
White crystals. IR (KBr, cm-1): m 3273 (NH), 3077 (ArH), 1648 (CO); H NMR
(600 MHz, DMSO-d6): dH 8.15 (s, 1H, NH), 7.75 (d, 2H, J = 8.4 Hz, ArH), 7.43 (s,
1H, ArH), 7.02 (t, 1H, J = 15.6 Hz, ArH), 6.91 (d, 1H, J = 7.2 Hz, ArH), 2.25 (s,
3H, CH3), 2.15 (s, 3H, CH3). Calcd. for C15H12Br2FN3O3: C, 36.54; H, 2.45; N,
8.52. Found: C, 36.47; H, 2.48; N, 8.51.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(2,5-dimethylphenyl)urea (4u)
1
White crystals. IR (KBr, cm-1): m 3276 (NH), 3081(ArH), 1646 (CO); H NMR
(600 MHz, DMSO-d6): dH 8.48 (s, 1H, NH), 7.76 (d, 2H, J = 7.8 Hz, ArH), 7.56 (s,
1H, ArH), 7.05 (d, 1H, J = 6 Hz, ArH), 6.77 (d, 1H, J = 7.8 Hz, ArH), 2.22 (s, 3H,
2 9 CH3). Calcd. for C15H12Br2FN3O3: C, 36.54; H, 2.45; N, 8.52. Found: C,
36.53; H, 2.50; N, 8.58.
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Y. Wang et al.
N-nitro-N-(2,6-dibromo-4-fluorophenyl)-N0-(1-napthyl)urea (4v)
1
Pink crystals. IR (KBr, cm-1): m 3267 (NH), 3084 (ArH), 1641 (CO); H NMR
(600 MHz, DMSO-d6): dH 9.00 (s, 1H, NH), 8.18 (d, 1H, J = 7.8 Hz, napthylH),
7.94 (d, 2H, J = 7.8 Hz, napthylH), 7.77 (d, 2H, J = 1.2 Hz, ArH), 7.64 (d, 1H,
J = 7.2 Hz, napthylH), 7.61 (d, 1H, J = 7.2 Hz, napthylH), 7.56 (t, 1H,
J = 15.0 Hz, napthylH), 7.47 (t, 1H, J = 15.0 Hz, napthylH). Calcd. for
C17H12Br2FN3O3: C, 42.27; H, 2.09; N, 8.70. Found: C, 42.21; H, 2.12; N, 8.72.
Herbicidal activity testing
Herbicidal testing of the newly synthesized compounds 4 was carried out in a
greenhouse, at a temperature of 25 1 °C, relative humidity (RH) 60 5%, light
intensity 10 Klux, and photoperiod 8 h/day. Twenty seeds of rape were chosen for
testing. Seedlings were grown in 9-cm-diameter test plates containing two pieces of
filter paper and 9 mL of solution of the tested compound (10, 25, 50, 100, and
200 mg/L, respectively). Distilled water and N-3,4-dichloro-phenyl N0,N0-dimeth-
ylurea (Diuron), a commercially available herbicide on the market, were used as the
controls. The herbicidal activity was assessed as the inhibition rate in comparison
with the distilled water. For the entire bioassay test, each treatment was repeated
twice. The lengths of roots and hypocotyl are measured and the means are
calculated, and then the DPS2000 data processing system was utilized using
standard statistical software to perform the regression analysis in order to obtain the
IC50 values. The herbicidal activity is summarized in Table 2.
Plant growth regulating activity testing
A solution of title compounds in a small amount of dimethyl sulfoxide (DMSO) was
diluted with distilled water containing 0.1% Tween 80 to the concentration of
10 mg/L. Twenty seeds of rape are placed into a 9-cm-diameter plate containing
two pieces of filter paper and 9 mL of solution of the tested compound. The plate is
placed in a greenhouse and allowed to germinate for 96 h at a temperature of
25 1 °C. The mixture of the same amount of water, DMSO, and Tween 80 was
used as the control. Weeds treated with water were the blank test. Each treatment
was repeated twice and the lengths of the hypocotyl of the seedlings in each plate
were measured. The hypocotyl formation-promoting activity was calculated by the
method of (test - control)/blank (Table 1).
Acknowledgments We gratefully acknowledge the support of this work by ‘‘the Fundamental Research
Funds for the Central Universities’’ (2009BQ027, 2010JC001, 2008XKJC005).
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