Microwave-assisted synthesis of benzothiazoleurea derivatives

Article abstract of DOI:10.3184/030823410X12652244368051

A simple and efficient method has been developed for the synthesis of 1-substituted-3-(4-chlorobenzo[d]thiazol-2-yl) ureas (5), from substituted aromatic or aliphatic amino compounds and phenyl 4-chlorobenzo[d]thiazol-2-yl carbamate 4 using microwave irradiation without phosgene in good yields. The title products were characterised by ¹H NMR, ESI-MS, and elemental analysis.

Full text of DOI:10.3184/030823410X12652244368051

JOURNAL OF CHEMICAL RESEARCH 2010
RESEARCH PAPER 75
FEBRUARY, 75–79
Microwave-assisted synthesis of benzothiazoleurea derivatives
Wenbin Chena*, Kejian Lia, Yong Wangb and Zhen Xia
aState Key Laboratory of Elemento-organic Chemistry,Tianjin Key Laboratory of Pesticide Science, Institute of Elemento-organic Chemistry,
Nankai University, Tianjin 300071, P. R. China
bTianjin Institute of Plant Protection, Tianjin Academy of Agricultural Sciences, Tianjin 300192, P. R. China
A simple and efficient method has been developed for the synthesis of 1-substituted-3-(4-chlorobenzo[d]thiazol-2-yl)
ureas (5), from substituted aromatic or aliphatic amino compounds and phenyl 4-chlorobenzo[d]thiazol-2-yl
carbamate 4 using microwave irradiation without phosgene in good yields. The title products were characterised by
1H NMR, ESI-MS, and elemental analysis.
Keywords: benzothiazole urea; microwave irradiation; synthesis; biological activity, phenyl 4-chlorobenzo[d]thiazol-2-yl
carbamate
Heterocyclic compounds play a key role in the research and
development of new drugs because of their special chemical
structures and special physical properties. They are important
in medicine and for agriculture. Benzothiazole is an important
heterocycle and has a wide range of applications in the
pesticide, medicinal and other fields. Its aromaticity makes it
relatively stable, although as a heterocycle it has reactive sites
which allow for functionalisation. Benzothiazole compounds
are also important raw materials in the production of fluores-
cent whitening agents, fluorescent dye such as Thioflavin1 and
pharmaceutical drugs, such as Riluzole which blocks TTX
sensitive sodium channels.2 Benzothiazole compounds can
also be used as inhibitors of p56lck (Lck) in the T-cell prolif-
eration3 and inhibitors of HIV-1 protease with improved
potency and antiviral activities.4
Benzothiazole ureas have also been previously reported
to be local anaesthetics, potential hypoglycaemic agents and
antibacterials.5 In recent years benzothiazole-type compounds
have attracted considerable attention in anticancer research.6–12
Modified benzothiazole derivatives having additional func-
tional groups may have enhanced the biological activity.
Microwave-assisted organic chemistry (MAOC) has become
a valuable method in chemistry research during the past 20
years,13–18 and been widely accepted. 19–22 The development of
commercial microwave systems specifically designed for syn-
thesis makes this technique more convenient and accesible.
It gives improved opportunities for reproducibility, rapid syn-
thesis, rapid reaction optimisation and the potential discovery
of new chemistry.23–25 The beneficial effects of microwave
irradiation have become more important, especially when
ordinary reactions require forcing conditions or prolonged
reaction times.26,27
Although there are many feasible routes for the synthesis of
heterocyclic asymmetric urea derivatives, but these methods
are almost limited to addition of substituted amines to hetero-
cyclic isocyanates from phosgene. To develop multifunctional
libraries of 1, 3-disubstituted asymmetric urea derivatives and
optimise the structure of urea derivatives to find a new lead
compound, we here report a facile method without phosgene to
synthesise the novel asymmetric urea derivative, benzothiazole
heterocycle ureas, from substituted amino compounds and
phenyl 4-chlorobenzo[d]thiazol-2-yl carbamate using MAOC
conditions. Preliminary tests of their biological activities were
then carried out.
Results and discussion
We have used microwave irradiation to prepare the title com-
pounds and our results show that most reactions can be fin-
ished within 30 min in good yields. Products can be isolated by
filtering or recrystallisation and rarely is silica gel column
chromatography necessary. The reaction temperature was set
up at 120–180 °C, and the time was 15–25 min. The synthetic
route of the title compounds 5 is outlined in Scheme 1.
The compound 3, which was obtained from 2-chloroaniline
in two steps according to literature28 with some modification,
was treated with diphenyl carbonate and NaH in anhydrous
THF to give phenyl-4-chlorobenzo[d]thiazol-2-ylcarbamate 4
in acceptable yield. The title compounds 5 were produced by
aminolysis of compound 4 by various amines under micro-
wave irradiation. Meanwhile, compound 5a, 5l and 5w were
Scheme 1
* Correspondent. E-mail: wbchen@nankai.edu.cn

76 JOURNAL OF CHEMICAL RESEARCH 2010
Scheme 2
selected to be prepared by conventional heating conditions and
microwave irradiation. The results show that the reactants must
be refluxed in THF or toluene for 24 h to give acceptable yields
of 80%, 75% and 83%, respectively. So in these reactions,
microwave irradiation can accelerate reaction rate and reduce
the reaction time.
To evaluate the biological usefulness of the title compounds,
we are testing the insecticidal, herbicidal, fungicidal and plant
growth regulation activities. The results show that some title
compounds have good plant growth regulation and fungicidal
activities. Detailed studies are in progress.
In conclusion, we report a rapid, mild and efficient pro-
cedure under microwave conditions for the synthesis of 1-
substituted-3-(4-chlorobenzo[d]thiazol-2-yl) ureas from sub-
stituted aromatic or aliphatic amino compounds and phenyl
4-chlorobenzo[d]thiazol-2-yl carbamate 4 in good yields,
avoiding the use of phosgene. Preliminary results suggest that
the title compounds possess good fungicidal and plant growth
regulation activities.
In the above reaction, when R is substituted phenyl, and the
mole ratio of amine to intermediate 4 is 1.5–3, at a temperature
higher than 120 °C, the title compound was not obtained and
the symmetric urea substituted by the aniline was isolated. For
example, when 2-methylaniline was reacted with intermediate
4, the symmetric urea 6 was obtained, the structure of which
1
1
was determined by H NMR and ESI-MS. H NMR [DMSO,
400M Hz] δ = 8.21 (s, 2H, 2×NH), 7.78–7.76 (dd, J = 6.2 Hz,
1.8 Hz, 2H), 7.15–7.08 (dt, J = 4.8 Hz, 7.7 Hz, 4H), 6.92–6.89
(m, 2H), 2.23 (s, 6H, 2×CH ); ESI-MS (M+): Calcd C15H16N2O
240.3; found 241.3 (100%, 3M+1).
Experimental
Microwave irradiation was conducted using an Initiator
8
(Biotage)reactor. Melting points were determined using an X-4 digital
microscope melting point apparatus (Beijing Taike Co. Ltd.) and were
uncorrected. NMR spectra were recorded on a Varian Mercury Plus
400 NMR or Bruker Avance-300 NMR instrument in CDCl3 or
(CD )2SO. Chemical shifts (δ ) are reported in parts per million (ppm),
relat3ive to TMS as internal stHandard. Elemental analyses were carried
out on an MF-3 automatic analyser instrument.Mass measurements
were performed on a Polaris-Q GC-MS instrument from Finnigan
using negative ion electrospray (values for 35Cl and 79Br quoted) Flash-
column chromatography was performed using commercial grades of
silica gel 200~300 mesh. Analytical thin layer chromatography (TLC)
was performed on precoated silica gel 60 F254 plates, and spot visu-
alization was accomplished by UV light (254 nm) or phosphomolyb-
dic acid solution. Solvents were obtained from commercial sources
and purified according to the literature30 if necessary.
Eventually we found that when reaction temperature was
set at 120 °C, the ratio of 2-methylaniline to 4 was 1:1 and
irradiation was for 25 min, the desired product in 50% yield.
The structures of all the title compounds were confirmed by
1
elemental analysis, H NMR, and ESI-MS. The structure of
compound 5a has also been confirmed by X-ray diffraction.29
The molecular structure shows that the N3–C9 bond dis-
tance indicates a typical single bond, but the N2–C7 (1.365Å)
bond is much shorter than the N3–C9 (1.453Å) bond and
shows something of the character of a C–N double bond.
This is presumably due to the overlap of the non-bonding
orbital of the imino N2 atom with the π orbital of the thiazole
ring. The water molecules link with the urea derivative mole-
cules via O—H----O and N—H---O hydrogen bonding, which
helps to stabilise the crystal structure.
Preparation of 2-amino-4-chlorobenzothiazole 328
In a 100 mL four-necked flask equipped with a thermometer, mechan-
ical stirrer and condenser, were placed 2-chlorobenzenamine (7.65 g,
0.06 mmol, 1.0 equiv) and water (6 mL). To the mixture, was added
dropwise 5.64 g 98% concentrated sulfuric acid with the temperature
at about 50 °C. After addition, ammonium thiocyanate (4.7 g, 0.06
mmol, 1.0 equiv) was added partially, and the mixture was stirred at
45–50 °C for 2 h. When the solid had disappeared completely, the
mixture was heated to 70–80 °C for 5 h. Then 1 mL of water was
added and the mixture was heated for a further 8 h. After cooling the
mixture to room temperature, 20 mL of water was added and the solid
was filtered, washed with water and dried to obtain the light yellow
powder 2, 9.85 g, yield 78%.
The solid 2 (8.5 g, 0.046 mmol) was added to sulfur chloride
(50 mL) and heated to reflux for 3h. After cooling to room tempera-
ture, the mixture was filtered and washed with dichloromethane.
The solid was dissolved again in boiled water, and the pH was adjusted
to 9.0 with ammonia to precipítate a light yellow solid. This was
filtered off and dried to give the desired product 3, 6.7 g, yield 78%,
m.p. 201 °C (lit28, 201–202 °C).
Fig. 1 The molecular structure of compound 5a.
Preparation of phenyl 4-chlorobenzothiazole -2-yl carbamate 431
To dry THF (100 mL), was added NaH (3.6 g, 0.150 mol, 3 equiv)
cooling with an ice-water bath and stirring for 30 min. Then 2-amino-
4-chlorobenzo[d]thiazole (9.25 g, 0.05 mmol, 1equiv) in 100 mL dry
THF was added dropwise to the above mixture. After stirring for 1h,
diphenyl carbonate (21.4 g, 0.1 mmol, 2 equiv) was added and the
mixture was stirred overnight. The solvent was removed under reduced
pressure and the residue was diluted with ethyl acetate (150 mL),
washed with brine (50 mL × 3), and dried over Na2SO4. The solvent
was evaporated and the residue was separated by flash silica gel
1
Fig. 2 The unit cell of compound 5a.
column chromatography to give a white solid 7.3 g, yield 48%. H

JOURNAL OF CHEMICAL RESEARCH 2010 77
NMR [CDCl , 400 MHz]: δ = 10.86 (brs, 1H, NH), 7.70 (d, 1H, J =
7.9 Hz), 7.463(d, 1H, J = 7.9 Hz), 7.40 (t, 2H, J = 7.9Hz), 7.28–7.20
(m, 4H).
1H), δ7.27 (t, J = 7.8 Hz, 1H), 7.35 (s, 1H), 7.48 (d, J = 8.0 Hz, 1H),
7.92 (d, J = 8.0, 1H), 8.21 (d, J = 4.0 Hz, 1H, NH), 9.87 (s, 1H, NH).
ESI-MS: (M-1)− m/z(%) = 317(100). Elemental Anal. Calcd for
C H ClN OS(318.78): C, 52.75; H, 3.48; N, 17.58. Found: C, 52.62;
H1,43.1410; N,4 17.60%.
Preparation of title compounds; typical procedure:
A mixture of phenyl 4-chlorobenzo[d]thiazol-2-yl carbamate 4 (1
equiv) and the aliphatic or aromatic amine (1~1.5 equiv) in THF was
placed in a microwave synthetic reactor and treated at a certain tem-
perature, absorption level (usually high) and time. When the solution
was cooled, the precipitate from the reactant was filtered off and
washed with a mixture of hexane and ethyl acetate. The filtrate was
concentrated and recrystallised from ethyl acetate or purified by flash
silica gel column chromatography (hexane and ethyl acetate mixtures
as eluent), to yield another portion of product.
1-(4-chlorobenzo[d]thiazol-2-yl)-3-(5-bromopyridin-2-yl)urea
(C13H8BrClN3OS) (5f): White solid, yield 86%, m.p. 288–289 °C, 1H
NMR[DMSO, 400M Hz]: δ = 7.26–7.32 (m, 1H), 7.40 (t, J = 4 Hz,
1H), 7.76 (d, J = 8.4, 1H), 7.94–7.98 (m, 1H), 8.04 (t, J = 7.8 Hz, 1H),
8.43–8.49 (m, 1H), 9.74 (s, 1H, NH), 11.80 (s, 1H, NH). ESI-MS:
(M-1)− m/z(%) = 381(100). ElementalAnal. Calcd for C13H8BrClN4OS
(383.65): C, 40.70; H, 2.10; N, 14.60. Found: C, 40.51; H, 2.16; N,
14.47%.
1-(4-chlorobenzo[d]thiazol-2-yl)-3-(6-methylpyridin-2-yl)urea
1
1-butyl-3-(4-chlorobenzo[d]thiazol-2-yl) urea (C12H14ClN3OS)
(C14H11ClN4OS) (5g): White solid, yield 82%, m.p. 260–262 °C, H
1
(5a): White solid, yield 86%, m.p. 188–189 °C, H NMR [CDCl3,
NMR[DMSO, 400M Hz]: δ = 2.44 (s, 3H, CH3), 6.97 (d, J = 7.6 Hz,
1H), 7.23–7.26 (m, J = 4.0 Hz, 1H), 7.50 (d, J = 8 Hz, 2H), 7.71 (t,
J = 7.8 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 9.71 (s, 1H, NH). ESI-MS:
(M-1)− m/z(%) = 317(100). Elemental Anal. Calcd for C14H ClN OS
(318.78): C, 52.75; H, 3.48; N, 17.58. Found: C, 52.96;11H, 34.45;
N, 17.53%.
400M Hz]: δ = 0.91 (t, J = 7.2 Hz, 3H, CH3), 1.36–1.43 (m, 2H, CH2),
1.63–1.68 (m, 2H, CH2), 3.34 (d, J = 6.0 Hz, 2H, CH2), 7.13 (t, J = 8.0
Hz, 1H), 7.36 (d, J = 7.6 Hz, 1H), 7.58 (d, J = 7.6 Hz, 1H), 10.52 (s,
1H, NH). ESI-MS: (M-1)− m/z(%) = 282(100). Elemental Anal. Calcd
for C H ClN OS (283.78): C, 50.79; H, 4.97; N, 14.81. Found: C,
50.521;2H1,44.713; N, 14.80%.
1-(4-chlorobenzo[d]thiazol-2-yl)-3-(5-chloropyridin-2-yl)urea
1
1-(4-chlorobenzo[d]thiazol-2-yl)-3-(naphthalen-1-yl)urea
(C13H8Cl2N4OS) (5h): White solid, yield 88%, m.p. 275–276 °C, H
1
(C18H12ClN3OS) (5b): White solid, yield 85%, m.p. 242–245 °C, H
NMR[DMSO, 400M Hz] δ = 7.24 (t, J = 7.3, 1H), 7.48 (t, J = 6.6 Hz,
1H), 7.79 (d, J = 4.0 Hz, 1H), 7.90–7.94 (m, J = 3.4 Hz, 2H), 8.40
(s, 1H), 9.74 (s, 1H, NH), 11.80 (s, 1H, NH). ESI-MS: (M-1)−
m/z(%) = 337(100). ElementalAnal. Calcd for C13H8Cl2N4OS (339.2):
C, 46.03; H, 2.38; N, 16.52. Found: C, 46.0; H, 2.40; N, 16.30%.
1-(4-chlorobenzo[d]thiazol-2-yl)-3-(5-methylpyridin-2-yl)urea
NMR[DMSO, 400M Hz]: δ = 7.22 (t, J = 15.6 Hz, 1H), 7.63–7.47 (m,
4H), 7.73 (d, J = 8.4 Hz, 1H), 8.10–7.89 (m, 4H), 9.24 (s, 1H), 11.57
(s, 1H, NH). ESI-MS: (M-1)− m/z(%) = 352(100). Elemental Anal.
Calcd for C18H ClN OS (351.83): C, 61.10; H, 3.42; N, 11.88. Found:
C, 61.07; H, 3.1429; N3, 11.70%.
1
1-(4-chlorobenzo[d]thiazol-2-yl)-3-isopropylurea (C11H12ClN3OS)
(C14H ClN4OS) (5i): White solid, yield 82%, m.p. 270–271 °C, H
NMR1[1DMSO, 400M Hz]: δ = 2.23 (s, 3H, CH3), 7.24 (t, J = 7.8 Hz,
1H), 7.49 (d, J = 8.0 Hz, 2H), 7.65 (d, J = 8.4 Hz, 1H), 7.90 (d, J = 7.6
Hz, 1H), 8.20 (s, 1H), 9.76 (s, 1H, NH), 12.30 (s, 1H, NH). ESI-MS:
(M-1)− m/z(%) = 317 (100). Elemental Anal. Calcd for C14H11ClN4OS
(318.78): C, 52.75; H, 3.48; N, 17.58; Found: C, 52.52; H, 3.48; N,
17.70%.
1
(5c): White solid, yield 90%, m.p. 178–180 °C, H NMR [CDCl ,
400M Hz]: δ = 1.24 (d, J = 6.4 Hz, 6H), 4.00–4.05 (m, 1H), 7.15 (3t,
J = 8.0 Hz, 1H), 7.39 (d, J = 7.6 Hz, 1H), 7.60 (d, J = 7.6 Hz, 1H),
10.51 (s, 1H, NH). ESI-MS: (M-1)− m/z(%) = 268(100). Elemental
Anal. Calcd for C11H12ClN3OS (269.75): C, 48.98; H, 4.48; N, 15.58.
Found: C, 48.70; H, 4.58; N, 15.40%.
1-(4-chlorobenzo[d]thiazol-2-yl)-3-propylurea
(C11H12ClN4OS)
1-(4-chlorobenzo[d]thiazol-2-yl)-3-(4-methylpyrimidin-2-yl)urea
1
1
(5d): White solid, yield 87%, m.p. 200–202 °C, H NMR [DMSO,
400M Hz]: δ = 0.84 (t, J = 7.2 Hz, 3H), 1.38–1.51 (m, 2H), 3.06–3.12
(m, 2H), 6.59 (s, 1H), 7.16 (t, J = 8 Hz, 1H), 7.41 (d, J = 8.0 Hz, 1H),
7.83 (d, J = 8 Hz, 1H), δ = 11.17 (s, 1H, NH). ESI-MS: (M-1)−
m/z(%) = 268(100). Elemental Anal. Calcd for C11H ClN OS
(269.75): C, 48.98; H, 4.48; N, 15.58. Found: C, 48.71;12H, 43.27;
N, 15.39%.
(C13H ClN5OS) (5j): White solid, yield 35%, m.p. 252–254 °C, H
NMR1[0DMSO, 400M Hz]: δ = 2.45 (s, 1H), 6.96 (d, J = 7.6 Hz, 1H),
7.27 (t, J = 7.8 Hz, 1H), 7.50 (t, J = 7.0 Hz, 1H), 7.73 (t, J = 7.8 Hz,
1H), 7.93 (d, J = 8.1 Hz, 1H), 10.90 (s, 1H, NH), 13.1 (s, 1H, NH).
ESI-MS: (M-2)− m/z(%) = 317(100).
1-(4-chlorobenzo[d]thiazol-2-yl)-3-(pyridin-3-yl)urea (C13H9ClN4
OS) (5k): White solid, yield 81%, m.p. 250–251 °C, 1H NMR[DMSO,
400M Hz]: δ = 7.17–7.22 (m, J = 4.1 Hz, 1H), 7.40 (t, J = 4.1 Hz,
1H), 7.50 (d, J = 7.6 Hz, 1H), 7.91–8.09 (m, J = 10 Hz, 2H), 8.30
(s, 1H), 8.60 (s, 1H), 9.20 (s, 1H, NH), 11.50 (s, 1H, NH). ESI-MS:
1-(4-chlorobenzo[d]thiazol-2-yl)-3-(4-methylpyridin-2-yl)urea
1
(C14H ClN OS) (5e): White solid, yield 84%, m.p. 273–275 °C, H
NMR1[1DM3SO, 400M Hz]: δ = 2.3 (s, 3H, CH3), 6.96 (d, J = 4.8 Hz,
Table 1 The preparation conditions of the title compounds 5
Compound
R
Temperature/°C
Time/min
Yield/%
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
5r
n-Butyl
150
160
150
150
180
180
160
180
160
180
180
120
120
120
120
120
120
120
120
120
120
120
150
150
30
25
25
25
15
15
25
15
25
15
15
20
25
20
10
20
20
20
20
20
25
25
20
20
86
85
90
87
84
86
82
88
82
35
81
79
35
89
85
86
83
73
82
89
86
83
86
86
α-Naphthalenyl
i-Propyl
n-Propyl
4-Methylpyridin-2-yl
5-Bromopyridin-2-yl
6-Methylpyridin-2-yl
5- Chloropyridin- 2-yl
5-Methylpyridin-2-yl
4-Methylpyrimidin- 2-yl
Pyridin-3-yl
Phenyl
Benzyl
4-Methylphenyl
2-Methylphenyl
4-Chlorophenyl
2-Chlorophenyl
3-Chlorophenyl
4-Bromophenyl
4-Nitrophenyl
2-Bromophenyl
Piperidin-1-yl
Pyridin-2-yl
5s
5t
5u
5v
5w
5x
Pyrimidin-2-yl

78 JOURNAL OF CHEMICAL RESEARCH 2010
(M-1)−m/z(%) = 303(100). Elemental Anal. Calcd for C13H9ClN OS
(304.75): C, 51.23; H, 2.98; N, 18.38. Found: C, 51.08; H, 34.11;
N, 18.53%.
m/z(%) = 380(100). Elemental Anal. Calcd for C14H9BrClN OS
(382.66): C, 43.94; H, 2.37; N, 10.98. Found: C, 44.33; H, 23.04;
N, 10.88%.
1-(4-chlorobenzo[d]thiazol-2-yl)-3-phenylurea
(C14H10ClN3OS)
N-(4-chlorobenzo[d]thiazol-2-yl)piperidine-1-carboxamide (C13
H ClN3OS) (5v): White solid, yield 83%, m.p. 148–150 °C, 1H
N1M4 R[CDCl3, 300M Hz]: δ = 1.49 (s, 6H), 3.40 (d, J = 6.4 Hz, 4H),
7.08 (t, J = 10.6 Hz, 1H), 7.30 (d, J = 10.4 Hz, 1H), 7.58 (d, J = 10.8
Hz, 1H), 10.08 (s, 1H, NH). ESI-MS: (M-1)− m/z(%) = 294(100).
Elemental Anal. Calcd for C13H14ClN3OS(295.79): C, 52.79; H, 4.77;
N, 14.21. Found: C, 52.60; H, 4.54; N, 14.02%.
(5l): White solid, yield 79%, m.p. 285–286 °C, 1H NMR[DMSO,
300M Hz]: δ = 7.07 (t, J = 9.8 Hz, 1H), 7.24 (t, J = 10.4 Hz, 1H), 7.34
(t, J = 10.4 Hz, 2H), 7.42–7.60 (m, J = 4.0 Hz, 3H), 7.91 (d, J = 10.4
Hz, 1H), 9.01 (s, 1H, NH), 11.28 (s, 1H, NH). ESI-MS: (M-1)−
m/z(%) = 302(100). ElementalAnal. CalcdforC14H10ClN3OS(303.77):
C, 55.36; H, 3.32; N, 13.83; Found: C, 55.49; H, 3.10; N, 13.63%.
1-benzyl-3-(4-chlorobenzo[d]thiazol-2-yl)urea
(C15H12ClN3OS)
1-(4-chlorobenzo[d]thiazol-2-yl)-3-(pyridin-2-yl)urea (C13H9ClN4
OS) (5w): White solid, yield 86%, m.p. 278–280 °C, 1H NMR[DMSO,
300M Hz]: δ = 7.13 (t, J = 8.2 Hz, 1H), 7.27 (t, J = 10.4 Hz, 1H), 7.51
(d, J = 10.0 Hz, 1H), 7.60 (d, J = 10.8 Hz, 1H), 7.82–7.87 (m, 1H),
7.93 (d, J = 10.0 Hz, 1H), 8.37 (d, J = 4.4 Hz, 1H), 9.89 (s, 1H, NH),
12.36 (s, 1H, NH). ESI-MS: (M-1)− m/z(%) = 303(100). Elemental
Anal. Calcd for C13H9ClN OS (304.75): C, 51.23; H, 2.98; N, 18.38.
Found: C, 51.07; H, 2.87; 4N, 18.20%.
1
(5m):White solid, yield 35%, m.p. 199–200 °C, H NMR[DMSO,
400M Hz]: δ = 4.35 (d, J = 5.2 Hz, 2H, CH2), 7.09 (s, 1H), 7.17
(t, J = 7.8 Hz, 1H), 7.23 (t, J = 5.6 Hz, 1H), 7.34–7.28 (m, 4H), 7.42
(d, J = 11.6 Hz, 1H), 7.83 (d, J = 7.6 Hz, 1H), 11.36 (s, 1H, NH).
ESI-MS: (M-1)− m/z(%) = 316(100).
1-(4-chlorobenzo[d]thiazol-2-yl)-3-p-tolylurea
(C15H12ClN3OS)
1
(5n): White solid, yield 89%, m.p. 289–292 °C, H NMR[DMSO,
300M Hz]: δ = 2.27 (s 3H, CH3), 7.15 (d, J = 11.2 Hz, 2H), 7.24 (t,
J = 10.4 Hz, 1H), 7.40 (d, J = 10.8 Hz, 2H), 7.48 (d, J = 10.4 Hz, 1H),
7.91 (d, J = 10.0 Hz, 1H), 8.90 (s, 1H, NH), 11.24 (s, 1H, NH).
ESI-MS: (M-1)− m/z(%) = 316(100). Elemental Anal. Calcd for
C H ClN OS (317.79): C, 56.69; H, 3.81; N, 13.22. Found: C, 56.50;
H1,53.1628; N,3 13.05%.
1-(4-chlorobenzo[d]thiazol-2-yl)-3-(pyrimidin-2-yl)urea
(C H8
ClN5OS) (5x): White solid, yield 86%, m.p. 285–287 °C,121H
NMR[DMSO, 300M Hz]: δ = 7.26–7.32 (m, 2H), 7.52 (d, J = 10.4
Hz, 1H), 7.97 (d, J = 10.0 Hz, 1H), 8.80 (d, J = 6.4 Hz, 2H), 11.00 (s,
1H, NH), 12.93 (s, 1H, NH). ESI-MS: (M-1)− m/z(%) = 304(100).
Elemental Anal. Calcd for C12H8ClN5OS (305.74): C, 47.14; H, 2.64;
N, 22.91. Found: C, 47.07; H, 2.40; N, 22.78%.
1-(4-chlorobenzo[d]thiazol-2-yl)-3-o-tolylurea
(C15H12ClN3OS)
1
(5o): White solid, yield 85%, m.p. 268–270 °C, H NMR[DMSO,
300M Hz]: δ = 2.27 (s, 3H, CH3), 7.04 (t, J = 9.6 Hz, 1H), 7.20–7.28
(m, 3H), 7.50 (d, J = 10.4 Hz, 1H),7.85 (d, J = 10.4 Hz, 1H), 7.92 (d,
J = 6.4 Hz, 1H), 8.40 (s, 1H, NH), 11.61 (s, 1H, NH) ESI-MS: (M-1)−
m/z(%) = 316(100). ElementalAnal. CalcdforC15H12ClN3OS(317.79):
C, 56.69; H, 3.81; N, 13.22. Found: C, 56.82; H, 3.80; N, 13.20%.
1-(4-chlorobenzo[d]thiazol-2-yl)-3-(4-chlorophenyl)urea
The authors are grateful to the National Natural Science
Foundation of China (No. 20702027) and Natural Science
Foundation of Tianjin (No. 07JCYBJC00100) for financial
support.
1
Received 1 October 2009; accepted 12 January 2010
Paper 090815 doi: 10.3184/030823410X12652244368051
Published online: 26 February 2010
(C14H9Cl2N3OS) (5p): White solid, yield 86%, m.p. 278–280 °C, H
NMR[DMSO, 300M Hz]: δ = 7.25 (t, J = 10.6 Hz, 1H), 7.40 (d,
J = 11.6 Hz, 2H), 7.48–7.56 (m, J = 10.3 Hz, 3H), 7.92 (d, J = 9.6 Hz,
1H), 9.16 (s, 1H), 11.40 (s, 1H, NH). ESI-MS: (M-1)− m/z(%) =
336(100). Elemental Anal. Calcd for C H Cl2N OS (338.21): C,
49.72; H, 2.68; N, 12.42. Found: C, 49.71;14H,92.58;3N, 12.33%.
1-(4-chlorobenzo[d]thiazol-2-yl)-3-(2-chlorophenyl)urea(C14H9Cl2
N3OS) (5q): White solid, yield 83%, m.p. 282–285 °C, 1H NMR
[DMSO, 300M Hz]: δ = 7.14 (t, J = 10.2 Hz, 1H), 7.26 (t, J = 10.6
Hz, 1H), 7.37 (t, J = 9.0 Hz, 1H), 7.51 (t, J = 10.4 Hz, 2H), 7.93
(d, J = 10.4 Hz, 1H), 8.16 (d, J = 9.2 Hz, 1H), 8.78 (s, 1H, NH), 11.94
(s, 1H, NH). ESI-MS: (M-1)− m/z(%) = 336(100). Elemental Anal.
Calcd for C14H Cl2N OS.(338.21): C, 49.72; H, 2.68; N, 12.42. Found:
C, 49.71; H, 2.958; N3, 12.33%.
1-(4-chlorobenzo[d]thiazol-2-yl)-3-(3-chlorophenyl)urea(C14H9Cl2
N3OS)(5r):Whitesolid,yield73%,m.p.282–285 °C,1HNMR[DMSO,
300M Hz]: δ = 7.12–7.15 (m, 1H), 7.26 (t, J = 10.6 Hz, 1H), 7.37
(d, J = 6.8 Hz, 2H), 7.50 (d, J = 10.0 Hz, 1H), 7.71 (s, 1H), 7.93
(d, J = 10.4 Hz, 1H), 9.20 (s, 1H, NH), 11.45 (s, 1H, NH). ESI-MS:
(M-1)− m/z(%) = 336(100). Elemental Anal. Calcd for C14H Cl2N OS
(338.21): C, 49.72; H, 2.68; N, 12.42. Found: C, 49.59;9H, 23.57;
N, 12.26%.
1-(4-bromophenyl)-3-(4-chlorobenzo[d]thiazol-2-yl)urea (C14H9-
BrClN3OS) (5s): Yellow solid, yield 82%, m.p. 282–285 °C, 1H
NMR[DMSO, 300M Hz]: δ = 7.24 (t, J = 10.6 Hz, 1H), 7.47–7.54 (m,
5H), 7.91 (d, J = 10.4 Hz, 1H), 9.15 (s, 1H, NH),11.40 (s, 1H, NH).
ESI-MS: (M-1)− m/z(%) = 380(100). Elemental Anal. Calcd for C14H9-
BrClN3OS (382.66): C, 43.94; H, 2.37; N, 10.98.Found: C, 43.87; H,
2.21; N, 10.78.
1-(4-chlorobenzo[d]thiazol-2-yl)-3-(4-nitrophenyl)urea(C14H9ClN4
O3S) (5t):Yellow solid, yield 89%, m.p. 270–272 °C, 1H NMR[DMSO,
300M Hz]: δ = 7.27 (t, J = 10.6 Hz, 1H), 7.51 (d, J = 11.4 Hz, 1H),
7.77 (d, J = 12.0 Hz, 2H), 7.94 (d, J = 10.4 Hz, 1H), 8.24 (d, J = 12
Hz, 2H), 9.69 (s, 1H, NH), δ11.60 (s, 1H, NH). ESI-MS: (M-1)−
m/z(%) = 347(100). Elemental Anal. Calcd for C14H ClN4O S
(348.76): C, 48.21; H, 2.60; N, 16.06. Found: C, 47.86;9H, 2.636;
N, 16.01.
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