Synthesis and herbicidal activity of amide derivatives containing thiazole moiety

Article abstract of DOI:10.14233/ajchem.2013.13366

Twelve novel amide derivatives containing thiazole moiety were synthesized via a coupling reaction of [4-(substituted phenyl)thiazol-2- yl] acetonitrile and aryl isocyanates catalyzed by organic bases. Their structures were characterized by 1H NMR, FTIR, MS and elemental analysis. The preliminary bioassay indicated that these compounds exhibited moderate herbicidal activities against Echinochloa crusgalli and Amaranthus ascedense.

Full text of DOI:10.14233/ajchem.2013.13366

Asian Journal of Chemistry; Vol. 25, No. 4 (2013), 2149-2152
http://dx.doi.org/10.14233/ajchem.2013.13366
Synthesis and Herbicidal Activity of Amide Derivatives Containing Thiazole Moiety
1,*
1
2
JIAN-QUAN WENG , XING-HAI LIU and GUO-TONG TONG
1College of Chemical Engineering and Materials Science, Zhejiang University of Technology, Hangzhou 310014, Zhejiang Province, P.R. China
2Department of Chemical Engineering, Hangzhou Vocational and Technical College, Hangzhou 310018, Zhejiang Province, P.R. China
*Corresponding author: Tel: +86 571 88320220; E-mail: jqweng@zjut.edu.cn
(Received: 30 December 2011;
Accepted: 17 October 2012)
AJC-12300
Twelve novel amide derivatives containing thiazole moiety were synthesized via a coupling reaction of [4-(substituted phenyl)thiazol-2-
yl] acetonitrile and aryl isocyanates catalyzed by organic bases. Their structures were characterized by 1H NMR, FTIR, MS and elemental
analysis. The preliminary bioassay indicated that these compounds exhibited moderate herbicidal activities against Echinochloa crusgalli
and Amaranthus ascedense.
Key Words: Synthesis, Amide derivative, Thiazole, Herbicidal activity.
2-Bromo-1-(4-fluorophenyl)ethanone (1a)15, [4-(4-fluoro-
INTRODUCTION
phenyl)thiazol-2-yl]acetonitrile (3a)15, 2-bromo-1-(2,6-difluoro-
phenyl)ethanone (1b)16, 2-cyanothioacetamide (2)16 and [4-
(2,6-difluorophenyl)thiazol-2-yl] acetonitrile (3b)16 were
prepared according to literature procedures. Melting points
Nitrogen and sulfur linked heterocyclic compounds have
recently attracted considerable attention owing to their promi-
nent biological activity1-4. As one of the potent heterocyclic
compounds, thiazole derivatives played an important role in
were conducted on a X-4 melting-point apparatus and are
the field of novel agrochemicals because of their wide biolo-
gical activity, such as insecticidal5, fungicidal6, antiviral7,
herbicidal8 and plant-growth-regulating9 activities. Meanwhile,
it is reported that amides possess a diverse range of bioactivities
in agrochemical field, for example insecticidal10, fungicidal11,
herbicidal12 and acaricidal13 activity.
1
uncorrected. The H NMR spectra were recorded on Bruker
ADVANCE III instrument (500MHz) using TMS as an internal
standard and DMSO-d6 as solvents. FTIR spectra were recorded
on a NICOLET 6700 instrument. Mass spectra (ESI-MS) were
recorded on a Therm LCQ TM Deca XP plus instrument.
Elemental analyses were performed on a Vario EL elemental
analyzer.
It is reported that the isocyanates displayed high activities.
Carbamate derivatives can be easily prepared from isocyanates
readily react with an proton in certain compounds, such as
hydrogen of acids, alcohols and amines14. However, the reaction
of isocyanates with hydrogen of methylene group have seldom
been reported.
General procedure for the synthesis of aryl isocyanates
(4): To a solution of bis(trichloromethyl)carbonate (1.5 g, 5
mmol) in toluene (20 mL) with constant stirring at 0 ºC was
added dropwise substituted aniline (15 mmol) in toluene (10
mL). The reaction mixture was continued to be stirred at 0-5
ºC for 1 h and then heated to reflux until the solution turned
clear. The solution was then refluxed for another 1 h. After
cooling, the mixture was then evaporated in vacuo to obtain
corresponding aryl isocyanates (4) without further purification.
General procedure for the synthesis of the title amide
derivatives (5a-l): [4-(Substituted phenyl)thiazol-2-yl]
acetonitrile (10 mmol) and 4-dimethylamiopyridine (DMAP)
(1 mmol) was dissolved in 1,4-dioxane (40 mL) and aryl
isocyanate (12 mmol) was added dropwise to the mixture, then
the final mixture was refluxed for 12 h. The precipitate formed
was filtered and recrystallized from ethanol to give the amide
derivatives containing thiazole moeity (5a-l).
In view of these facts and also as a part of our work on the
development of bioactive heterocyclic compounds, twelve
novel amide derivatives containing thiazole moiety (5a-l) were
synthesized via a coupling reaction of [4-(substituted phenyl)
thiazol-2-yl] acetonitrile and aryl isocyanates catalyzed by
organic bases. Their structures were characterized by 1H NMR,
FTIR, MS and elemental analysis and their herbicidal activities
were also evaluated.
EXPERIMENTAL
All the solvents and other chemicals were used as received
from different commercial sources without further purification.

2150 Weng et al.
Asian J. Chem.
N-Phenyl-2-cyano-2-(4-(4-fluorophenyl)thiazol-2-
7.15-7.63 (m, 8H, ArH), 7.39 (s, 1H, SCH), 11.62 (s, 1H,
CHCN); IR (KBr, νmax, cm-1): 3305 (N-H), 2165 (CN), 1712
(C=O), 1634, 1452 (Ar); MS (ESI) m/z: 406 ([M + H]+);
elemental analysis (%), calcd. for C19H11N3OSF4: C, 56.30; H,
2.74; N, 10.37; found: C, 56.47; H, 2.79; N, 10.50.
yl)acetamide (5a): White solid, yield 82.2 %. m.p. 189-191
ºC; 1H NMR (DMSO-d6) δ: 4.04 (s, 1H, NH), 7.01-7.54 (m,
9H, ArH), 7.17 (s, 1H, SCH), 11.57 (s, 1H, CHCN); IR (KBr,
νmax, cm-1): 3318 (N-H), 2179 (CN), 1712 (C=O), 1639, 1453
(Ar); MS (ESI) m/z: 338 ([M + H]+). Elemental analysis (%),
calcd. for C18H12N3OSF: C, 64.08; H, 3.59; N, 12.46; found:
C, 64.17; H, 3.47; N, 12.54.
N-Phenyl-2-cyano-2-(4-(2,6-difluorophenyl)thiazol-2-
yl)acetamide (5i): White solid, yield 83.9 %, m.p. 193-195 ºC;
1H NMR (DMSO-d6) δ: 4.03 (s, 1H, NH), 7.05-7.54 (m, 8H,
N-m-Tolyl-2-cyano-2-(4-(4-fluorophenyl)thiazol-2-
yl)acetamide (5b): White solid, yield 76.5 %, m.p. 213-215
ArH), 7.15 (s, 1H, SCH), 11.57 (s, 1H, CHCN); IR (KBr, νmax,
cm-1): 3308 (N-H), 2176 (CN), 1711 (C=O), 1646, 1452 (Ar);
MS (ESI) m/z: 356 ([M + H]+); elemental analysis (%), calcd.
for C18H11N3OSF2: C, 60.84; H, 3.12; N, 11.82; found: C, 60.86;
H, 3.10; N, 11.84.
1
ºC; H NMR (DMSO-d6) δ: 2.33 (s, 3H, CH3), 4.02 (s, 1H,
NH), 7.11-7.36 (m, 8H, ArH), 7.37 (s, 1H, SCH), 11.63 (s,
1H, CHCN); IR (KBr, νmax, cm-1): 3302 (N-H), 2176 (CN),
1708 (C=O), 1637, 1450 (Ar); MS (ESI) m/z: 352 ([M + H]+);
Elemental analysis (%), calcd. for C19H14N3OSF: C, 64.94; H,
4.02; N, 11.96; found: C, 64.87; H, 3.92; N, 12.05.
N-o-Tolyl-2-cyano-2-(4-(2,6-difluorophenyl)thiazol-2-
yl)acetamide (5j): White solid, yield 78.6 %, m.p. 203-205 ºC;
1H NMR (DMSO-d6) δ: 2.35 (s, 3H, CH3), 4.02 (s, 1H, NH),
6.97-7.40 (m, 7H, ArH), 7.35 (s, 1H, SCH), 11.52 (s, 1H,
CHCN); IR (KBr, νmax, cm-1): 3306 (N-H), 2173 (CN), 1715
(C=O), 1640, 1450 (Ar); MS (ESI) m/z: 340.0 ([M + H]+);
elemental analysis (%), calcd. for C19H13N3OSF2: C, 61.78; H,
3.55; N, 11.38; found: C, 61.89; H, 3.42; N, 11.54.
N-p-Tolyl-2-cyano-2-(4-(4-fluorophenyl)thiazol-2-
yl)acetamide (5c): White solid, yield 79.0 %, m.p. 193-195
1
ºC; H NMR (DMSO-d6) δ: 2.31 (s, 3H, CH3), 4.03 (s, 1H,
NH), 7.09-7.32 (m, 8H, ArH), 7.33 (s, 1H, SCH), 11.59 (s,
1H, CHCN); IR (KBr, νmax, cm-1): 3307 (N-H), 2172 (CN),
1702 (C=O), 1637, 1452 (Ar); MS (ESI) m/z: 352 ([M + H]+);
Elemental analysis (%), calcd. for C19H14N3OSF: C, 64.94; H,
4.02; N, 11.96; found: C, 65.03; H, 3.87; N, 12.10.
N-(4-Chlorophenyl)-2-cyano-2-(4-(2,6-difluorophenyl)-
thiazol-2-yl)acetamide (5k): White solid, yield 84.0 %, m.p.
198-200 ºC; 1H NMR (DMSO-d6) δ: 4.00 (s, 1H, NH), 7.08-
7.52 (m, 7H, ArH), 7.38 (s, 1H, SCH), 11.59 (s, 1H, CHCN);
IR (KBr, νmax, cm-1): 3308 (N-H), 2179 (CN), 1709 (C=O),
1636, 1450 (Ar); MS (ESI) m/z: 390 ([M + H]+); elemental
analysis (%), calcd. for C18H10N3OSClF2: C, 55.46; H, 2.59;
N, 10.78; found: C, 55.79; H, 2.56; N, 10.54.
N-(2-Chlorophenyl)-2-cyano-2-(4-(4-fluorophenyl)-
thiazol-2-yl)acetamide (5d): White solid, yield 83.0 %, m.p.
189-191 ºC; 1H NMR (DMSO-d6) δ: 4.00 (s, 1H, NH), 7.04-
7.52 (m, 8H, ArH), 7.34 (s, 1H, SCH), 11.70 (s, 1H, CHCN);
IR (KBr, νmax, cm-1): 3305 (N-H), 2183 (CN), 1704 (C=O),
1640, 1452 (Ar); MS (ESI) m/z: 372 ([M + H]+); elemental
analysis (%), calcd. for C18H11N3OSClF: C, 58.15; H, 2.98; N,
11.30; found: C, 58.27; H, 3.08; N, 11.47.
N-(4-(Trifluoromethyl)phenyl)-2-cyano-2-(4-(2,6-
difluorophenyl)thiazol-2-yl)acetamide (5l): White solid,
yield 85.8 %, m.p. 194-196 ºC; 1H NMR (DMSO-d6) δ: 4.01
(s, 1H, NH), 7.13-7.62 (m, 7H,ArH), 7.41 (s, 1H, SCH), 11.66
(s, 1H, CHCN); IR (KBr, νmax, cm-1): 3312 (N-H), 2181 (CN),
1720 (C=O), 1640, 1452 (Ar); MS (ESI) m/z: 424 ([M + H]+);
elemental analysis (%), calcd. for C19H10N3OSF5: C, 53.90; H,
2.39; N, 9.93; found: C, 54.07; H, 2.36; N, 10.11.
N-(3-Chlorophenyl)-2-cyano-2-(4-(4-fluorophenyl)-
thiazol-2-yl)acetamide (5e): White solid, yield 80.7 %, m.p.
193-195 ºC; 1H NMR (DMSO-d6) δ: 4.01 (s, 1H, NH), 7.12-
7.63 (m, 8H, ArH), 7.37 (s, 1H, SCH), 11.62 (s, 1H, CHCN);
IR (KBr, νmax, cm-1): 3312 (N-H), 2162 (CN), 1710 (C=O),
1640, 1450 (Ar); MS (ESI) m/z: 372 ([M + H]+); elemental
analysis (%), calcd. for C18H11N3OSClF: C, 58.15; H, 2.98; N,
11.30; found: C, 58.22; H, 2.83; N, 11.50.
Bioassay of herbicidal activities: The solutions of the
title compounds 5 (100 mg/L) were prepared by dissolving
them in N,N-dimethylformamide with the addition of a little
Tween-80 and proper water. There were three replicates for
each treatment. The mixture of the same amount of N,N-
dimethylformamide, Tween-80 and water was used as the
control (CK). Herbicidal testing of the title compounds 5 was
carried out in a plant growth room. Temperature (24 1) ºC,
RH 60 5 %, light intensity 10 Klux, photoperiod 8 h/day.
Twenty seeds of each one of weed species including Echinochloa
crusgalli and Amaranthus ascedense were chosen for testing.
Seedlings were grown in the test plate of 9 cm diameter conta-
ining two pieces of filter paper and 9 mL solution of the tested
compound (100 mg/L). The herbicidal activity was assessed
as the inhibition rate in comparison with the control. The herbi-
cidal rating score based on visual observation. Range from 0-
100 %, 0 % means no effect, 100 % means complete killing.
N-(4-Chlorophenyl)-2-cyano-2-(4-(4-fluorophenyl)-
thiazol-2-yl)acetamide (5f): White solid, yield 83.5 %, m.p.
198-200 ºC; 1H NMR (DMSO-d6) δ: 4.00 (s, 1H, NH), 7.04-
7.50 (m, 8H, ArH), 7.36 (s, 1H, SCH), 11.55 (s, 1H, CHCN);
IR (KBr, νmax, cm-1): 3310 (N-H), 2179 (CN), 1715 (C=O),
1638, 1450 (Ar); MS (ESI) m/z: 372 ([M + H]+); elemental
analysis (%), calcd. for C18H11N3OSClF: C, 58.15; H, 2.98; N,
11.30; found: C, 58.31; H, 3.13; N, 11.43.
N-(3-(Trifluoromethyl)phenyl)-2-cyano-2-(4-(4-fluoro-
phenyl)thiazol-2-yl)acetamide (5g): White solid, yield 85.2
%, m.p. 189-192 ºC; 1H NMR (DMSO-d6) δ: 4.02 (s, 1H, NH),
7.13-7.65 (m, 8H, ArH), 7.40 (s, 1H, SCH), 11.63 (s, 1H,
CHCN); IR (KBr, νmax, cm-1): 3306 (N-H), 2163 (CN), 1708
(C=O), 1632, 1450 (Ar); MS (ESI) m/z: 406 ([M + H]+);
elemental analysis (%), calcd. for C19H11N3OSF4: C, 56.30; H,
2.74; N, 10.37; found: C, 56.51; H, 2.66; N, 10.53.
RESULTS AND DISCUSSION
N-(4-(Trifluoromethyl)phenyl)-2-cyano-2-(4-(4-fluoro-
phenyl)thiazol-2-yl)acetamide (5h): White solid, yield 81.6
%, m.p. 187-189 ºC; 1H NMR (DMSO-d6) δ: 4.00 (s, 1H, NH),
Twelve novel amide derivatives containing thiazole
moiety (5) were synthesized from a coupling reaction of

Vol. 25, No. 4 (2013)
Synthesis and Herbicidal Activity of Amide Derivatives Containing Thiazole Moiety 2151
[4-(substituted phenyl)thiazol-2-yl]acetonitrile (3) and aryl
isocyanates (4) catalyzed by organic bases according to the
route as shown in Scheme-I and the yields were not optimized.
It is found that [4-(4-fluorophenyl)thiazol-2-yl]acetonitrile
(3a) can react with phenyl isocyanate in presence of the
4-dimethylamiopyridine (DMAP) to give the condensed
product 5a in high yield in the described reaction conditions
(Scheme-II, Table-1, entry 4). The use of other organic bases,
such as 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU), triethyl-
amine (Et3N), diethylamine (Et2NH), pyridine (Py) and the
condensing reagent 1,3-dicyclohexylcarbodiimide (DCC) gave
only low or moderate yields of 5a (Table-1, entry 1-3,5,6). No
reactions occurred without the base catalysts. Thus, the
reactions of 3 with other aryl isocyanates were occurred at
refluxing temperature in the presence of DMAP, leading to
the desired compounds (5b-5l) in 76.5-85.8 % yields. It is
notably that these compouds were synthesized from a coupling
reaction of aryl isocyanates with hydrogen of methylene(CH2),
which have seldom been reported. All the compounds were
11.52-11.70 ppm as a singlet due to the influence of both
electron-withdrawing groups cyano (-CN) and carbonyl
(-C=O), which indicated the conversion of -C=C-OH group.
Herbicidal activities: The herbicidal activity of all
compounds 5 against Echinochloa crus-galli (barnyard grass)
and Amaranthus ascedense (amaranthus lividus) has been
investigated at the dosage of 100 mg/L using known procedure17
compared with the control (CK). The results of herbicidal
activity testing are listed in Table-2. The results of bioassay
showed that all compounds exhibited moderate herbicidal
activity against Echinochloa crusgalli and Amaranthus
ascedense at the concentration of 100 mg/L and some of them
exhibited moderate herbicidal activity against the root of
Echinochloa crus-galli. For example, compounds 5d, 5f, 5g,
5h and 5l showed > 70 % inhibitory rate to root of Echinochloa
crus-galli. It is worthy to note that the compounds bearing an
electron-withdrawing group at the benzene ring (e.g., 5d, 5e,
5f, 5g, 5h) displayed higher herbicidal activity against the root
of Echinochloa crusgalli than those compounds bearing an
electron-donating group (e.g., 5b, 5c).
1
identified and characterized by H NMR, FTIR, MS and
elemental analysis.
TABLE-2
HERBICIDAL ACTIVITIES OF TITLE
COMPOUNDS 5a-l AT 100 mg/L
TABLE-1
ORGANIC BASES CATALYZED REACTIONS
OF COMPOUND 3a WITH PhNCO
Relative inhibition (%)
Entry
Organic base
DBU
Isolated yield (%)
Compounds
Echinochloa crusgalli
Amaranthus ascedense
1
2
3
4
5
6
5.6
Root
Stalk
Root
Stalk
Et3N
64.5
43.8
82.2
69.0
32.2
5a
5b
5c
5d
5e
5f
5g
5h
5i
57.8
54.4
52.4
73.2
69.8
73.5
78.0
77.4
60.8
56.7
60.8
78.2
0.0
43.6
51.8
43.6
47.3
39.5
50.0
36.2
52.6
53.4
33.9
39.5
47.7
0.0
55.3
52.6
49.5
58.2
54.9
56.7
68.5
61.8
58.6
53.2
56.3
69.2
0.0
45.0
41.2
29.5
33.3
32.0
37.5
40.1
52.0
46.9
51.7
42.7
48.5
0.0
Et2NH
DMAP
Py
DCC
In the infrared spectrum (FT-IR) of compound 5, N-H
stretching absorption signal appears at 3318-3302 cm-1 and
the characteristic stretching vibration signals of ν(C=O)
appears at 1720-1702 cm-1. In the 1H NMR spectrum of 5, the
-NH proton signals were observed at about 4.00 ppm as a singlet
and the -CH (linked cyano) proton signals were observed at
5j
5k
5l
CK
CN
S
O
R1
S
R1
NCO (4)
N
O
S
CH2Br
R2
CNCH2CNH2 (2)
R1
NH
R2
N
CH2CN
Base
5
3
1
5a, R1=4-F, R2=H; 5b, R1=4-F, R2=3-CH3; 5c, R1=4-F, R2=4-CH3; 5d, R1=4-F, R2=2-Cl;
5e, R1=4-F, R2=3-Cl; 5f, R1=4-F, R2=4-Cl; 5g, R1=4-F, R2=3-CF3; 5h, R1=4-F, R2=4-CF3;
5i, R1=2,6-2F, R2=H; 5j, R1=2,6-2F, R2=2-CH3; 5k, R1=2,6-F, R2=4-Cl; 5l, R1=2,6-2F, R2=4-CF3;
Scheme-I: Synthetic route for compounds 5a-I
CN
S
N
O
S
Base catalyst (10 mol%)
1,4-dioxane, reflux
F
NCO
+
NH
N
F
CH2CN
3a
5a
Scheme-II: Reactions of compound 3a with PhNCO catalyzed by organic bases

2152 Weng et al.
Asian J. Chem.
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ACKNOWLEDGEMENTS
This work was funded by National Natural Science
Foundation of China (No. 30900959) and the Key Laboratory of
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