Synthesis of 1-Acyl-3-isopropenylbenzimidazolone derivatives and their activity against botrytis cinerea

Article abstract of DOI:10.1021/jf903855y

A series of 1-acyl-3-isopropenylbenzimidazolone derivatives were synthesized, and their structures were characterized by ¹H and ¹³C NMR and elemental analysis. Their fungicidal activities against Botrytis cinerea were also evaluated

Full text of DOI:10.1021/jf903855y

2668 J. Agric. Food Chem. 2010, 58, 2668–2672
DOI:10.1021/jf903855y
Synthesis of 1-Acyl-3-isopropenylbenzimidazolone
Derivatives and Their Activity against Botrytis cinerea†
§
,
S
HENG-KUN
L
I
,§ ZHI-QIN
J
W
I
,§ J
I
-WEN
Z
HANG,§ ZHENG-YAN
,§,#
G
UO
AND
EN-JUN
W *
U
§Institute of Pesticide Science, Northwest Agricultural and Forestry University, Yangling,
Shaanxi 712100, China, and #State Key Laboratory of Elemento-organic Chemistry, Nankai University,
Tianjin 300071, China
A series of 1-acyl-3-isopropenylbenzimidazolone derivatives were synthesized, and their structures
were characterized by 1H and 13C NMR and elemental analysis. Their fungicidal activities against
Botrytis cinerea were also evaluated by spore germination assay. The acrylic acid, methacrylic acid,
4-chlorophenyl acetic acid, and 2-chlorobenzoic acid derivatives exhibited strong fungicidal activity.
This implied that benzimidazolones might be potential fungicide leading compounds.
KEYWORDS: Benzimidazolone derivatives; synthesis; fungicidal activities
INTRODUCTION
Scheme 1
Gray mold, which is caused by Botrytis cinerea, is one of the
most common diseases on vegetable and fruit crops (1). Its
development is dependent upon favorable climatic conditions,
and it has been a serious threat in greenhouses when humidity
is high and temperature is moderate. Protecting crops against
B. cinerea requires multiple applications of fungicides, during the
whole period from bud burst until ripening. However, with the
extensive use of synthetic fungicides, B. cinerea has developed
resistance to many commercialized products (2, 3).
Benzimidazolone derivatives have been found to exhibit anti-
HIV (4), antitrichinellosis (5), antinociceptive (6), antitumor ac-
tivities (7), and other pharmacological activities (8-11), whereas
only a few of them exhibit antimicrobial activities. For example,
the benzimidazolone derivative bearing a sugar residue on the
aromatic nitrogen effectively inhibits the growth of bacteria such
as Bacillus cereus, Streptomyces chartreusis, and Escherichia
coli (12). However, to the best of our knowledge, there has been
no report on the fungicidal activity of benzimidazolones against
plant pathogens.
bioactivities of isopropenylbenzimidazolone derivatives were still
not thoroughly investigated.
In this paper, we prepared a series of isopropenylbenzimida-
zolone derivatives; herein the alkyl carbonyl or aromatic carbonyl
was introduced to the nitrogen atom by amide bond (Scheme 1,
compounds II-1-II-26). Their fungicidal activities against
B. cinerea were evaluated by the method of spore germination,
and several compounds exhibited strong inhibition. Here we
report the exciting results. The structure-activity relationship
of these benzimidazolone derivatives is also discussed.
1-Isopropenylbenzimidazolone (Scheme 1, compound I),
which could be prepared by the condensation of o-phenylenedia-
mine with acetoacetic ester (13), is often used as the intermediate
to synthesize other benzimidazolones (7, 14, 15). In most cases,
isopropenyl, playing the role of amine protecting group, was
removed or substituted by other groups in the succeeding
procedures. In other cases, substituents were introduced to the
other nitrogen atom of 1-isopropenylbenzimidazolone. In a
recent paper, five sulfonamide derivatives of isopropenylbenzi-
midazolone were synthesized and their cytotoxicities against
several strains of cancer cell evaluated (7). In general, the
MATERIALS AND METHODS
Instruments. The melting points of the products were determined on
an X-4 apparatus (Beijing Tech Instrument Co., Beijing, China) and are
uncorrected. 1H and 13C NMR spectra were taken on a Bruker Avance 600
MHz (600 MHz for 1H and 150 MHz for 13C, respectively) spectrometer in
CDCl3 solution with TMS as an internal standard. Elemental analyses
were carried out on an Elementar Vairo EL analyzer.
Synthetic Procedures. Isopropenyl benzimidazolone (I) (Zhengzhou
Sigma Chemical Co., Henan, China), bis(trichloromethyl)carbonate (GL
Biochem Co., Shanghai, China), carboxylic acids, dichloromethane, and
triethylamine were commercial reagents (Sinopharm Chemical Reagent
Co., Shanghai, China). Target compounds (II-1-II-n) were synthesized by
the acylations of I with corresponding carboxylic acid or acyl chloride (7)
(Scheme 1; Table 1).
†Part of the ECUST-Qian Pesticide Cluster.
*Address correspondence to this author at the Institute of Pesticide
Science, Northwest Agricultural and Forestry University, No. 3
Taicheng Road, Yangling, Shaanxi 712100, China (telephone þ86-
29-87093987; fax þ86-29-87093987; e-mail wenjun_wu@263.net).
Method A. General Synthetic Procedures for II-1- II-19. With nitrogen
protection, to a solution of I (0.174 g, 1 mmol) in dichloromethane (10 mL)
pubs.acs.org/JAFC
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Article
J. Agric. Food Chem., Vol. 58, No. 5, 2010 2669
Table 1. Title Compounds and Inhibition of Spore Germination against B. cinerea
were added triethylamine (0.3 mL, 2.1 mmol) and carboxylic acid
(1 mmol). After the mixture had been stirred for 5 min in an ice-water
bath, bis(trichloromethyl) carbonate (BTC, 40 mg, 1 mmol) in dichlor-
omethane (2 mL) was added, and the mixture was stirred overnight at
room temperature. Saturated NaHCO3 solution (20 mL) was added to the
mixture, and the mixture was extracted by dichloromethane (3 ꢀ 15 mL).
The organic extracts were combined, washed with water and saturated
NaCl solution in that order, dried over Na2SO4, and finally concentrated
under vacuum. The concentrated mixture was subjected to a silica gel
column, and eluted by the mixture of petroleum ether and ethyl acetate
(5:1, v/v) to give target compounds.
Na2SO4, and finally concentrated under vacuum. After purification with a
silica gel column as described above, target compounds were obtained.
1-Acetyl-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one (II-1).
Yield, 60.1%; mp, 102-104 °C; 1H NMR (CDCl3), δ 2.20 (s, 3H, CH3 of
isopropenyl), 2.77 (s, 3H, CH3 of acetyl), 5.26 (s, 1H, CdCH2), 5.47 (s,
1H, CdCH2), 7.06 (d, J = 8.0 Hz, 1H, Ph), 7.14-7.27 (m, 2H, Ph), 8.22 (d,
J = 8.0 Hz, 1H, Ph); 13C NMR (CDCl3), δ 19.8 (CH3 of isopropenyl), 25.8
(CH3 of acetyl), 105.6, 115.1, 115.9, 122.9, 124.6, 126.4, 129.3, 137.0, 150.8
(CO), 170.6 (CO of acetyl). Anal. Calcd for C12H12N2O2: C, 66.65; H, 5.59;
N, 12.96. Found: C, 66.82; H, 5.65; N, 12.82.
1-(Prop-1-en-2-yl)-3-propionyl-1H-benzo[d]imidazol-2(3H)-one (II-2).
Yield, 65.8%; mp, 126-128 °C; 1H NMR (CDCl3), δ 1.26 (t, J = 7.5 Hz,
3H, CH3 of propionyl), 2.19 (s, 3H, CH3 of isopropenyl), 3.19 (q, J= 7.5 Hz,
2H, CH2 of propionyl), 5.25 (s, 1H, CdCH2), 5.47 (s, 1H, CdCH2), 7.06 (d,
J = 8.0 Hz, 1H, Ph), 7.14-7.27 (m, 2H, Ph), 8.24 (d, J = 8.0 Hz, 1H, Ph);
13C NMR (CDCl3), δ 8.2 (CH3 of propionyl), 19.8 (CH3 of isopropenyl),
31.0 (CH2 of propionyl), 108.6, 115.4, 115.9, 122.9, 124.4, 126.6, 129.4, 137.1,
150.7 (CO), 174.6 (CO of propionyl). Anal. Calcd for C13H14N2O2: C, 67.81;
H, 6.13; N, 12.17. Found: C, 67.96; H, 6.19; N, 12.09.
Method B. General Synthetic Procedures for II-20-II-26. With nitrogen
protection, to a solution of I (0.174 g, 1 mmol) in dichloromethane (10 mL)
was added triethylamine (0.3 mL, 2.1 mmol). Carboxylic chloride (1 mmol) in
dichloromethane (2 mL) was added in an ice-water bath, and the mixture was
stirred for 5 h at room temperature. After the solvent had been evaporated,
saturated NH4Cl solution (10 mL) was added, and the mixture was extracted
by dichloromethane (3 ꢀ 15 mL). The organic extracts were combined,
washed with water and saturated NaCl solution in that order, dried over

2670 J. Agric. Food Chem., Vol. 58, No. 5, 2010
Li et al.
1-Butyryl-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one (II-3). Yield,
90.0%; mp, 104-106 °C; 1H NMR (CDCl3), δ 1.05 (t, J = 7.5 Hz, 3H,
CH3 of butyryl), 1.81 (m, 2H, CH2 of butyryl), 2.19 (s, 3H, CH3 of
isopropenyl), 3.15 (t, J = 7.5 Hz, 2H, CH2 of butyryl), 5.25 (s, 1H,
CdCH2), 5.47 (s, 1H, CdCH2), 7.06 (d, J = 8.0 Hz, 1H, Ph), 7.16-7.27
(m, 2H, Ph), 8.24 (d, J = 8.0 Hz, 1H, Ph); 13C NMR (CDCl3), δ 13.7 (CH3
of butyryl), 17.6 (CH2 of butyryl), 19.8 (CH3 of isopropenyl), 39.3 (CH2 of
butyryl), 108.6, 115.4, 115.9, 122.9, 124.4, 126.6, 129.4, 137.1, 150.7 (CO),
173.7 (CO of butyryl). Anal. Calcd for C14H16N2O2: C, 68.83; H, 6.60; N,
11.47. Found: C, 68.92; H, 6.65; N, 11.37.
2-phenylacetyl), 108.6, 115.7, 116.0, 123.0, 124.7, 126.5, 127.1, 128.5,
129.4, 129.9, 133.5, 136.9, 150.4 (CO), 171.7 (CO of 2-phenylacetyl). Anal.
Calcd for C18H16N2O2: C, 73.95; H, 5.52; N, 9.58. Found: C, 74.12; H,
5.60; N, 9.46.
1-(2-(4-Chlorophenyl)acetyl)-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-
2(3H)-one (II-10). Yield, 73.6%; mp, 90-92 °C; 1H NMR (CDCl3), δ 2.20
(s, 3H, CH3), 4.51 (s, 2H, CH2 of (4-chlorophenyl)acetyl), 5.27 (s, 1H,
CdCH2), 5.49 (s, 1H, CdCH2), 7.06 (d, J = 8.0 Hz, 1H, Ph), 7.12-7.38
(m, 6H, Ph), 8.20 (d, J = 8.0 Hz, 1H, Ph); 13C NMR (CDCl3), δ 19.8,
42.8 (CH2 of (4-chlorophenyl)acetyl), 108.7, 115.7, 116.0, 123.1, 124.8,
126.5, 128.7, 129.5, 131.3, 132.0, 133.1, 136.9, 150.6 (CO), 171.2 (CO of
(4-chlorophenyl)acetyl). Anal. Calcd for C18H15N2O2Cl: C, 66.16; H, 4.63;
N, 8.57. Found: C, 66.38; H, 4.69; N, 8.45.
1-Pentanoyl-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one (II-4).
Yield, 88.4%; mp, 114-116 °C; 1H NMR (CDCl3), δ 0.97 (t, J = 7.8 Hz,
3H, CH3 of pentanoyl), 1.42-1.46 (m, 2H, CH2 of pentanoyl), 1.76 (m,
2H, CH2 of pentanoyl), 2.19 (s, 3H, CH3), 3.11 (t, J = 7.4 Hz, 2H, CH2 of
pentanoyl), 5.26 (s, 1H, CdCH2), 5.47 (s, 1H, CdCH2), 7.06 (d, J = 8.0
Hz, 1H, Ph), 7.14-7.27 (m, 2H, Ph), 8.24 (d, J = 8.0 Hz, 1H, Ph); 13C
NMR (CDCl3), δ 13.9 (CH3 of pentanoyl), 19.8, 22.3(CH2 of pentanoyl),
26.2(CH2 of pentanoyl), 37.2 (CH2 of pentanoyl), 108.6, 115.4, 115.9,
122.9, 124.4, 126.6, 129.4, 137.0, 150.7 (CO), 174.0 (CO of pentanoyl).
Anal. Calcd for C15H18N2O2: C, 69.74; H, 7.02; N, 10.84. Found: C, 69.95;
H, 7.24; N, 10.65.
1-(2-(Naphthalen-2-yl)acetyl)-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-
2(3H)-one (II-11). Yield, 72.5%; mp, 128-130 °C; 1H NMR (CDCl3), δ
2.25 (s, 3H, CH3), 4.99 (s, 2H, CH2 of 2-(naphthalen-2-yl)acetyl), 5.32 (s,
1H, CdCH2), 5.51 (s, 1H, CdCH2), 7.08-7.14 (m, 2H, Ph), 7.20-7.25 (m,
1H, Ph), 7.46-7.53 (m, 4H, Ph), 7.83-7.94 (m, 4H, Ph), 8.16 (d, J = 8.0
Hz, 1H, Ph); 13C NMR (CDCl3), δ 19.9, 41.4 (CH2 of 2-(naphthalen-2-
yl)acetyl), 108.7. 115.7, 116.1, 123.0, 123.9, 124.7, 125.4, 125.7, 126.3,
126.6, 128.2, 128.3, 128.8, 129.5, 130.3, 132.4, 133.8, 137.0, 150.9 (CO),
171.4 (CO of 2-(naphthalen-2-yl)acetyl). Anal. Calcd for C22H18N2O2: C,
77.17; H, 5.30; N, 8.18. Found: C, 77.35; H, 5.39; N, 8.09.
1-Hexanoyl-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one (II-5).
Yield, 90.1%; mp, 42-44 °C; 1H NMR (CDCl3), δ 0.92 (t, J = 7.8 Hz, 3H,
CH3 of hexanoyl), 1.36-1.43 (m, 4H, 2 ꢀ CH2 of hexanoyl), 1.78 (t, J =
7.8 Hz, 2H, CH2 of hexanoyl), 2.19 (s, 3H, CH3), 3.16(t, J = 7.8 Hz, 2H,
CH2 of hexanoyl), 5.27 (s, 1H, C=CH2), 5.47 (s, 1H, C=CH2), 7.06 (d, J =
8.0 Hz, 1H, Ph), 7.14-7.23 (m, 2H, Ph), 8.24 (d, J = 8.0 Hz, 1H, Ph);
13C NMR (CDCl3), δ 13.9 (CH3 of hexanoyl), 19.8, 22.5 (CH2 of
hexanoyl), 23.8 (CH2 of hexanoyl), 31.3 (CH2 of hexanoyl), 37.4 (CH2
of hexanoyl), 108.6, 115.4, 115.9, 122.9, 124.4, 126.6, 129.4, 137.1, 150.7
(CO), 173.9 (CO of hexanoyl). Anal. Calcd for C16H20N2O2: C, 70.56; H,
7.40; N, 10.29. Found: C, 70.68; H, 7.52; N, 10.15.
1-(3-Phenylpropanoyl)-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one
1
(II-12). Yield, 51.2%; mp, 78-80 °C; H NMR (CDCl3), δ 2.18 (s, 3H,
CH3), 3.11 (t, J = 7.0 Hz, 2H, CH2 of 2-phenylacetyl), 3.50 (t, J = 7.0 Hz,
2H, CH2 of 2-phenylacetyl), 5.24 (s, 1H, CdCH2), 5.46 (s, 1H, CdCH2),
7.05 (d, J = 8.0 Hz, 1H, Ph), 7.14-7.27 (m, 7H, Ph), 8.24 (d, J = 8.0 Hz,
1H, Ph); 13C NMR (CDCl3), δ 19.8, 30.1 (CH2 of 2-phenylacetyl), 39.0
(CH2 of 2-phenylacetyl), 108.6, 115.4, 115.9, 122.9, 124.6, 126.1, 126.5,
128.4, 128.6, 129.4, 137.0, 140.6, 150.4 (CO), 172.9 (CO of 2-phenylacetyl).
Anal. Calcd for C19H18N2O2: C, 74.49; H, 5.92; N, 9.14. Found: C, 74.65;
H, 6.03; N, 8.95.
1-Isobutyryl-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one (II-6).
Yield, 89.7%; mp, 88-90 °C; 1H NMR (CDCl3), δ 1.26 (d, J = 7.4 Hz,
3H, CH3 of isobutyryl), 1.30 (d, J = 7.4 Hz, 3H, CH3 of isobutyryl), 2.22
(s, 3H, CH3 of isopropenyl), 4.02-4.06(m, 1H, CH of isobutyryl), 5.26 (s,
1H, CdCH2), 5.47 (s, 1H, CdCH2), 7.06 (d, J = 8.0 Hz, 1H, Ph),
7.14-7.27 (m, 2H, Ph), 8.23 (d, J = 8.0 Hz, 1H, Ph); 13C NMR (CDCl3), δ
18.9 (2 ꢀ CH3 of isobutyryl), 19.8 (CH3 of isopropenyl), 34.3 (CH of
isobutyryl), 108.6, 115.4, 116.1, 122.9, 124.4, 126.9, 129.5, 137.1, 150.4
(CO), 178.3 (CO of isobutyryl). Anal. Calcd for C14H16N2O2: C, 68.83; H,
6.60; N, 11.47. Found: C, 68.95; H, 6.65; N, 11.35.
1-(2-Phenylbutanoyl)-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-
one (II-13). Yield, 65.1%; mp, 48-50 °C; 1H NMR (CDCl3), δ 0.92 (t, J =
7.8 Hz, 3H, CH3 of 2-phenylbutanoyl), 1.91, 2.26 (m, 2H, CH2 of
2-phenylbutanoyl), 2.14 (s, 3H, CH3), 5.20 (s, 1H, CdCH2), 5.44 (s, 1H,
CdCH2), 5.26 (m, 1H, CH of 2-phenylbutanoyl), 6.99 (d, J = 7.0 Hz, 1H,
Ph), 7.10-7.33 (m, 5H, Ph), 7.48 (d, J = 7.0, 2H, Ph), 8.25 (d, J = 8.0, 1H,
Ph); 13C NMR (CDCl3), δ 12.1 (CH3 of 2-phenylbutanoyl), 19.7, 27.4
(CH2 of 2-phenylbutanoyl), 52.0 (CH of 2-phenylbutanoyl), 108.4, 115.6,
116.0, 122.8, 124.5, 126.8, 127.1, 128.4, 128.8, 129.3, 136.9, 138.5, 150.3
(CO), 174.5 (CO of 2-phenylbutanoyl). Anal. Calcd for C20H20N2O2: C,
74.98; H, 6.29; N, 8.74. Found: C, 75.16; H, 6.38; N, 8.46.
1-(2-Ethylbutanoyl)-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one
(II-7). Yield, 91.0%; mp, 118-120 °C; 1H NMR (CDCl3), δ 0.97 (t, J =
7.0 Hz, 6H, 2 ꢀ CH3 of 2-ethylbutanoyl), 1.66 (m, 4H, 2 ꢀ CH2 of 2-
ethylbutanoyl), 2.20 (s, 3H, CH3), 2.30-2.32 (m, 1H, CH of 2-
ethylbutanoyl), 5.27 (s, 1H, CdCH2), 5.48 (s, 1H, CdCH2), 7.06 (d,
J = 8.0 Hz, 1H, Ph), 7.16-7.26 (m, 2H, Ph), 8.26 (d, J = 8.0 Hz, 1H, Ph);
13C NMR (CDCl3), δ 11.6 (2 ꢀ CH3 of 2-ethylbutanoyl), 19.7, 24.3 (2 ꢀ
CH2 of 2-ethylbutanoyl), 47.4 (CH of 2-ethylbutanoyl), 105.8, 114.9,
114.7, 122.6, 124.2, 126.0, 129.3, 137.1, 151.0 (CO), 170.4 (CO of 2-
ethylbutanoyl). Anal. Calcd for C16H20N2O2: C, 70.56; H, 7.40; N, 10.29.
Found: C, 70.72; H, 7.48; N, 10.15.
1-(2-(4-Methoxyphenyl)acetyl)-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-
2(3H)-one (II-14). Yield, 80.1%; mp, 118-120 °C; 1H NMR (CDCl3), δ
2.20 (s, 3H, CH3), 3.80 (s, 3H, CH3 of 2-(4-methoxyphenyl)acetyl), 4.48 (s,
2H, CH2 of 2-(4-methoxyphenyl)acetyl), 5.26 (s, 1H, CdCH2), 5.48 (s, 1H,
CdCH2), 6.89 (d, J = 7.8 Hz, 2H, Ph), 7.05 (d, J = 8.0 Hz, 1H, Ph),
7.14-7.22 (m, 2H, Ph), 7.30 (d, J = 7.8 Hz, 2H, Ph), 8.21 (d, J = 8.0 Hz,
1H, Ph); 13C NMR (CDCl3), δ 19.8, 42.6 (CH2 of 2-(4-methoxyphenyl)-
acetyl), 55.2 (CH3 of 2-(4-methoxyphenyl)acetyl), 108.6, 113.9, 115.6,
116.0, 122.9, 124.6, 125.6, 126.7, 129.5, 130.9, 137.0, 150.7 (CO), 158.7,
172.1 (CONH). Anal. Calcd for C19H18N2O3: C, 70.79; H, 5.63; N, 8.69.
Found: C, 70.93; H, 5.72; N, 8.50.
1-(4-Methylpentanoyl)-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one
(II-8). Yield, 81.1%; mp, 70-72 °C; 1H NMR (CDCl3), δ 0.96 (d, J = 7.6
Hz, 6H, 2 ꢀ CH3 of 4-methylpentanoyl), 1.66-1.69 (m, 2H, CH2 of
4-methylpentanoyl), 1.66-1.69 (m, 1H, CH of 4-methylpentanoyl), 2.20
(s, 3H, CH3), 3.18 (t, J = 7.6, 2H, CH2 of 4-methylpentanoyl), 5.26 (s, 1H,
CdCH2), 5.47 (s, 1H, CdCH2), 7.06 (d, J = 8.0 Hz, 1H, Ph), 7.16-7.26
(m, 2H, Ph), 8.23(d, J = 8.0 Hz, 1H, Ph); 13C NMR (CDCl3), δ 19.8, 22.4
(2 ꢀ CH3 of 4-methylpentanoyl), 27.7 (CH2 of 4-methylpentanoyl), 32.9
(CH of 4-methylpentanoyl), 35.5 (CH2 of 4-methylpentanoyl), 108.6,
115.5, 115.9, 122.9, 124.4, 126.6, 129.4, 137.1, 150.7 (CO), 174.2 (CO of
4-methylpentanoyl). Anal. Calcd for C16H20N2O2: C, 70.56; H, 7.40; N,
10.29. Found: C, 70.75; H, 7.49; N, 10.12.
1-(2-Phenoxyacetyl)-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-
one (II-15). Yield, 46.4%; mp, 118-120 °C; 1H NMR (CDCl3), δ 2.22 (s,
3H, CH3), 5.29 (s, 1H, CdCH2), 5.50 (s, 1H, CdCH2), 5.43 (s, 2H, CH2 of
2-phenoxyacetyl), 6.99-7.03 (m, 4H, Ph), 7.17-7.32 (m, 4H, Ph), 8.25
(d, J = 7.8 Hz, 1H, Ph); 13C NMR (CDCl3), δ 19.8, 68.3 (CH2 of
2-phenoxyacetyl), 108.9, 114.8, 115.6, 115.8, 121.6, 123.3, 125.1, 125.9,
129.5, 130.0, 136.8, 150.6 (CO), 157.9, 168.6 (CO of 2-phenoxyacetyl).
Anal. Calcd for C18H16N2O3: C, 70.12; H, 5.23; N, 9.09. Found: C, 70.34;
H, 5.30; N, 8.89.
1-(2-(4-Chlorophenoxy)acetyl)-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-
2(3H)-one (II-16). Yield, 77.5%; mp, 136-138 °C; 1H NMR (CDCl3), δ
2.22 (s, 3H, CH3), 5.29 (s, 1H, C=CH2), 5.50 (s, 1H, CdCH2), 5.40 (s, 2H,
CH2 of 2-(4-chlorophenoxy)acetyl), 6.93-6.96 (m, 2H, Ph), 7.09 (d, J =
8.0 Hz, 1H, Ph), 7.19-7.27 (m, 4H, Ph), 8.23 (d, J = 8.0 Hz, 1H, Ph); 13C
NMR (CDCl3), δ 19.8, 68.5 (CH2 of 2-(4-chlorophenoxy)acetyl), 109.0,
1-(2-Phenylacetyl)-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one
(II-9). Yield, 59.2%; mp, 124-126 °C; 1H NMR (CDCl3), δ 2.20 (s, 3H,
CH3), 4.54 (s, 2H, CH2 of 2-phenylacetyl), 5.27 (s, 1H, CdCH2), 5.49 (s,
1H, CdCH2), 7.06 (d, J = 8.0 Hz, 1H, Ph), 7.12-7.38 (m, 7H, Ph), 8.21
(d, J = 8.0 Hz, 1H, Ph); 13C NMR (CDCl3), δ 19.8, 43.5 (CH2 of

Article
J. Agric. Food Chem., Vol. 58, No. 5, 2010 2671
115.8, 116.1, 123.4, 124.6, 125.2, 125.6, 126.6, 129.4, 130.0, 136.7, 150.5
(CO), 156.4, 168.2 (CO of 2-(4-chlorophenoxy)acetyl). Anal. Calcd for
C18H15ClN2O3: C, 63.07; H, 4.41; N, 8.17. Found: C, 63.22; H, 4.49; N,
8.00.
150.3 (CO), 167.9 (CO of 4-chlorobenzoyl). Anal. Calcd for
C17H13N2O2Cl: C, 65.29; H, 4.19; N, 8.96. Found: C, 65.45; H, 4.25; N,
8.75.
1-(2-Chlorobenzoyl)-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one
(II-24). Yield, 96.4%; mp, 82-86 °C; 1H NMR (CDCl3), δ 2.12(s, 3H,
CH3), 5.23 (s, 1H, CdCH2), 5.39 (s, 1H, CdCH2), 7.09 (d, J = 7.8 Hz, 1H,
Ph), 7.21-7.47 (m, 6H, Ph), 8.27 (d, J = 7.8 Hz, 1H, Ph); 13C NMR
(CDCl3), δ 19.6, 108.9, 115.0, 115.5, 123.1, 124.8, 126.1, 126.7, 128.1,
129.2, 129.9, 130.7, 131.5, 135.1, 136.8, 149.6 (CO), 166.3 (CO of 2-
chlorobenzoyl). Anal. Calcd for C17H13N2O2Cl: C, 65.29; H, 4.19; N, 8.96.
Found: C, 65.40; H, 4.29; N, 8.78.
1-(4-(1H-Indol-3-yl)butanoyl)-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-
2(3H)-one (II-17). Yield, 65.4%; mp, 176-178 °C; 1H NMR (CDCl3), δ
2.18 (s, 3H, CH3), 2.22 (m, 2H, CH2 of 4-(indol-3-yl)butanoyl), 2.92 (m,
2H, CH2 of 4-(indol-3-yl)butanoyl), 3.27 (m, 2H, CH2 of 4-(indol-3-
yl)butanoyl), 5.24 (s, 1H, CdCH2), 5.46 (s, 1H, CdCH2), 7.03-7.22 (m,
5H, Ph or heterocycle), 7.25 (s, 1H, heterocycle), 7.33 (d, J = 7.5 Hz, 1H,
Ph), 7.65 (d, J = 7.5 Hz, 1H, Ph), 7.99 (s, 1H, NH), 8.23 (d, J = 8.0 Hz,
1H, Ph); 13C NMR (CDCl3), δ 19.8, 24.4 (CH2 of 4-(indol-3-yl)butanoyl),
24.5 (CH2 of 4-(indol-3-yl)butanoyl), 37.2 (CH2 of 4-(indol-3-
yl)butanoyl), 108.5, 111.0, 115.5, 115.7, 115.9, 118.9, 119.1, 121.5, 121.8,
122.8, 124.4, 126.6, 127.4, 129.4, 136.3, 137.0, 150.1 (CO), 173.4 (CO of
4-(indol-3-yl)butanoyl). Anal. Calcd for C22H21N3O2: C, 73.52; H, 5.89;
N, 11.69. Found: C, 73.69; H, 5.98; N, 11.52.
1-(Furan-2-carbonyl)-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one
(II-25). Yield, 64.2%; mp, 104-106 °C; 1H NMR (CDCl3), δ 2.19 (s, 3H,
CH3), 5.29 (s, 1H, CdCH2), 5.46 (s, 1H, CdCH2), 6.61 (dd, J = 3.6, 1.2
Hz, 1H, CH of furan-2-carbonyl), 7.09 (d, J = 7.8 Hz, 1H, Ph), 7.16-7.26
(m, 2H, Ph), 7.54 (d, J = 3.6 Hz, 1H, CH of furan-2-carbonyl), 7.70 (d,
J = 1.2 Hz, 1H, CH of furan-2-carbonyl), 7.84 (d, J = 7.8, 1H, Ph); 13C
NMR (CDCl3), δ 19.8, 109.0, 112.3 (CH of furan-2-carbonyl), 114.3,
115.1, 121.6 (CH of furan-2-carbonyl), 122.7, 124.3, 126.9, 129.8, 137.2,
146.1 (CH of furan-2-carbonyl), 147.4 (C of furan-2-carbonyl), 149.9
(CO), 157.0 (CO of furan-2-carbonyl). Anal. Calcd for C15H12N2O3: C,
67.16; H, 4.51; N, 10.44. Found: C, 67.42; H, 4.62; N, 10.26.
1-Acryloyl-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one (II-18).
Yield, 77.1%; mp, 108-110 °C; 1H NMR (CDCl3), δ 2.20 (s, 3H, CH3 of
isopropenyl), 5.27 (s, 1H, CdCH2), 5.48 (s, 1H, CdCH2), 5.99 (d, J = 16.2
Hz, 1H, CH2 of acryloyl), 6.68 (d, J = 12.8 Hz, 1H, CH2 of acryloyl), 7.06
(d, J = 8.0 Hz, 1H, Ph), 7.15-7.27 (m, 2H, Ph), 7.74 (dd, J = 16.2, 12.8
Hz, 1H, CH of acryloyl), 8.23 (d, J = 8.0 Hz, 1H, Ph); 13C NMR (CDCl3),
δ 19.8, 108.7, 115.5, 116.5, 123.0, 124.7, 126.6, 129.1 (CH2 of acryloyl),
129.7, 132.1 (CH of acryloyl), 137.0, 150.7 (CO), 165.3 (CO of acryloyl).
Anal. Calcd for C13H12N2O2: C, 68.41; H, 5.30; N, 12.27. Found: C, 68.60;
H, 5.36; N, 12.15.
1-Isonicotinoyl-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one (II-26).
Yield, 81.0%; mp, 132-134 °C; 1H NMR (CDCl3), δ 2.15 (s, 3H, CH3),
5.26 (s, 1H, CdCH2), 5.44 (s, 1H, CdCH2), 7.12 (d, J = 8.4 Hz, 1H, Ph),
7.22-7.30 (m, 2H, Ph), 7.55 (d, J = 7.8, 2H, Ph), 8.10 (d, J = 8.4 Hz, 1H,
Ph), 8.79 (d, J = 7.8, 2H, Ph); 13C NMR (CDCl3), δ 19.7, 109.2, 115.3,
115.4, 121.9, 123.2, 125.2, 126.3, 130.0, 136.8, 141.5, 150.0 (CO), 167.2 (CO
of isonicotinoyl). Anal. Calcd for C16H13N3O2: C, 68.81; H, 4.69; N, 15.05.
Found: C, 69.03; H, 4.75; N, 14.86.
Microorganism and Preparation of Spore Suspension. The tested
fungal pathogen, B. cinerea, was provided by the Institute of Plant Disease,
Northwest A&F University. The strain was retrieved from the storage tube
and cultured for 2 weeks at 20 °C on potato dextrose agar (PDA, Difco).
Plates were then flooded with sterile distilled water, and conidia were
scraped with a glass stick. Mycelial debris was removed by filtration
through double-layer cheesecloth, and the spores were harvested and
suspended in sterile distilled water containing 0.1% (v/v) Tween 20. Spores
were counted using a hemocytometer and adjusted to 1.0 ꢀ 106 spores/
mL (16).
Spore Germination Assay. The tested samples (10 mg) dissolved in
methanol (0.1 mL) were diluted with sterile distilled water to prepare 10
mL stock solution, which was further diluted to prepare test solutions in
which the final concentration of methanol was <1% (v/v). A series of
concentrations of tested samples and one control (1% methanol with
sterile distilled water) were separately tested for spore germination of B.
cinerea. The samples were inoculated with spore suspension of B. cinerea
containing 1.0 ꢀ 106 spores/mL. Aliquots of 10 μL of prepared spore
suspension were placed on separate glass slides in triplicate. Slides
containing the spores were incubated in a moisture chamber at 25 °C
for 6 h. Each slide was then observed under the microscope for spore
germination. The spore-generated germ tubes were enumerated, and
percentage of spore germination was calculated. Pyrimethanil was pre-
ferred as the positive control.
1-Methacryloyl-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one (II-19).
Yield, 45.2%; mp, 124-126 °C; 1H NMR (CDCl3), δ 2.17 (s, 3H, CH3 of
methacryloyl), 2.21 (s, 3H, CH3), 5.25 (s, 1H, CdCH2), 5.44 (s, 1H,
CdCH2), 5.41, 5.61 (s, 2H, CH2 of methacryloyl), 7.08 (d, J = 8.0 Hz, 1H,
Ph), 7.14-7.26 (m, 2H, Ph), 7.98 (d, J = 8.0 Hz, 1H, Ph); 13C NMR
(CDCl3), δ 19.7, 20.1 (CH3 of methacryloyl), 108.9, 110.0 (CH2 of
methacryloyl), 114.8, 114.9, 122.8, 124.4, 126.6, 129.6, 137.5, 140.5 (C of
methacryloyl), 154.8 (CO), 170.3 (CO of methacryloyl). Anal. Calcd for
C14H14N2O2: C, 69.41; H, 5.82; N, 11.56. Found: C, 69.72; H, 5.95; N,
11.26.
1-Benzoyl-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one (II-20).
Yield, 86.3%; mp, 118-120 °C; 1H NMR (CDCl3), δ 2.16 (s, 3H, CH3),
5.26 (s, 1H, CdCH2), 5.42 (s, 1H, CdCH2), 7.12 (d, J = 8.4 Hz, 1H, Ph),
7.18-7.26 (m, 2H, Ph), 7.49 (t, J = 7.4, 2H, Ph), 7.60 (t, J = 7.4 Hz, 1H,
Ph), 7.80 (d, J = 7.4 Hz, 2H, Ph), 7.97 (d, J = 8.4, 1H, Ph); 13C NMR
(CDCl3), δ 19.7, 109.0, 114.7, 114.9, 122.8, 124.5, 127.0. 128.0, 129.3,
129.9, 132.8, 133.6, 137.1, 150.2 (CO), 168.5 (CO of benzoyl). Anal. Calcd
for C17H14N2O2: C, 73.37; H, 5.07; N, 10.07. Found: C, 73.56; H, 5.18; N,
9.86.
1-(4-Nitrobenzoyl)-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one
(II-21). Yield, 46.1%; mp, 142-144 °C; 1H NMR (CDCl3), δ2.14 (s, 3H,
CH3), 5.26 (s, 1H, CdCH2), 5.44 (s, 1H, CdCH2), 7.14 (d, J = 7.8 Hz, 1H,
Ph), 7.23-7.30 (m, 2H, Ph), 7.88 (d, J = 9.0 Hz, 2H, Ph), 8.10 (d, J = 7.8
Hz, 1H, Ph), 8.20 (d, J = 9.0 Hz, 2H, Ph); 13C NMR (CDCl3), δ 19.7,
109.3, 115.2, 115.3, 123.2, 123.3, 125.3, 126.3, 129.7, 130.0, 136.8, 139.7,
149.6, 150.0 (CO), 167.1 (CO of 4-nitrobenzoy). Anal. Calcd for
C17H13N3O4: C, 63.16; H, 4.05; N, 13.00. Found: C, 63.42; H, 4.15; N,
12.80.
Statistical Analysis. The experimental data of the fungicidal activities
were analyzed using SPSS 13.0 for Windows.
1-(2-Nitrobenzoyl)-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one
(II-22). Yield, 90.1%; mp, 146-148 °C; 1H NMR (CDCl3), δ 2.07 (s, 3H,
CH3), 5.21 (s, 1H, CdCH2), 5.39 (s, 1H, CdCH2), 7.06 (d, J = 8.0 Hz, 1H,
Ph), 7.24-7.31 (m, 2H, Ph), 7.52 (d, J = 8.2 Hz, 1H, Ph), 7.66 (t, J = 8.2,
1H, Ph), 7.80 (t, J = 8.2, 1H, Ph), 8.25 (d, J = 8.0 Hz, 1H, Ph), 8.37 (d, J =
8.2, 1H, Ph); 13C NMR (CDCl3), δ 19.6, 109.0, 115.5, 115.7, 123.3, 124.1,
125.2, 126.1, 127.8, 129.8, 130.4, 132.3, 134.6, 136.6, 145.0, 150.0 (CO),
165.6 (CO of 2-nitrobenzoyl). Anal. Calcd for C17H13N3O4: C, 63.16; H,
4.05; N, 13.00. Found: C, 63.32; H, 4.18; N, 12.75.
RESULTS AND DISCUSSION
Synthesis. N-Acyl derivatives of isopropenyl benzimidazolone
could be readily synthesized by the acylation of I with corre-
sponding carboxylic acid or acyl chloride in good yields. II-1 had
been reported to be synthesized using the same procedure (13),
and it could also be prepared from 4-methyl-2,3-dihydro-1H-1,5-
benzodiazepin-2-one by acetylation inpyridine (17). In a program
of screening antitumor compounds, II-20 was once obtained by
reaction of benzoyl chloride with I (7), but the fungicidal activity
of these two compounds was not mentioned in the references.
The title compounds, including II-1 and II-20, were character-
ized with 1H NMR, 13C NMR, and elemental analysis.
1-(4-Chlorobenzoyl)-3-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one
(II-23). Yield, 65.0%; mp, 138-140 °C; 1H NMR (CDCl3), δ 2.16 (s, 3H,
CH3), 5.26 (s, 1H, CdCH2), 5.43 (s, 1H, CdCH2), 7.12 (d, J = 7.8 Hz, 1H,
Ph), 7.19-7.26 (m, 2H, Ph), 7.45 (d, J = 8.0, 2H, Ph), 7.74(d, J = 8.0 Hz,
2H, Ph), 7.96 (d, J = 7.8 Hz, 1H, Ph); 13C NMR (CDCl3), δ 19.7, 109.1,
114.8, 115.0, 122.9, 124.7, 126.8, 128.9, 129.9, 130.8, 131.9, 137.1, 139.1,

2672 J. Agric. Food Chem., Vol. 58, No. 5, 2010
Li et al.
Fungicidal Acitivity. The fungicidal activities of the title com-
pounds against B. cinerea were evaluated by spore germination
assay, and the results are listed in Table 1. The fungicidal activity
was strongly influenced by the acyl group on the nitrogen atom.
Among the saturated aliphatic acid derivatives (II-1-II-5), the
activities became higher with extension of the carbon chain.
When a side chain was introduced to the main carbon chain, a
methyl or an ethyl at the R-position (II-6 and II-7) helped with
their activities, because their activities were much higher than
those of II-2 and II-3. However, compound II-8, with a methyl
group at the γ-position of pentanoyl, gave a little lower activity
than corresponding compound II-4. Similarly, II-17, with a bulky
indole ring at the γ-position of butanoyl, also exhibited lower
activity.
The introduction of a hydrophobic benzene ring to the alkyl
chain increased the fungicidal activities to a large extent. Phenyl-
ethylcarbonyl derivative II-12 and benzylcarbonyl derivatives
(II-9, II-10, and II-13) showed much higher activities than
corresponding alkyl derivatives II-1-II-3. Among them, 4-clor-
obenzylcarbonyl compound II-10 exhibited uncommon activity,
with a median inhibitory concentration (IC50) value of 17.27 μg/
mL. Phenoxyacetyl compound II-15 and 4-chlorophenoxyacetyl
compound II-16 also gave moderate activities with II-16 higher
than II-15, which also indicates that a chloro atom at the para-
position of the benzene ring could increase the activity. Com-
pound II-11, bearing a bulky phenanthryl, gave very low activity.
Compared to most of the alkyl acyl derivatives and control
compound pyrimethanil, acrylamide compounds II-18 and II-19
showed higher activities, as their median inhibitory concentration
(IC50) values were only 32.42 and 63.45 μg/mL, respectively. This
implied that R,β-unsaturated carbonyl might play an important
role in their fungicidal activity.
Substituted benzoyl (II-20, II-21, II-23, and II-24) and other
aromatic carbonyl derivatives (II-25 and II-26) of isopropenyl
benzimidazolone also exhibited stronger inhibiting activity than
alkyl acyl derivatives and pyrimethanil. The type and position of
the substituted group introduced to the benzene ring could
obviously affect the bioactivity. When chloro was introduced to
the ortho- or para-position of benzoyl, their activities were
much higher than corresponding nitro derivatives. Of all the
compounds, II-24 exhibited the highest inhibiting activity, with
IC50 = 17.17 μg/mL.
In conclusion, 1-acyl-3-isopropenylbenzimidazolone deriva-
tives were prepared and their fungicidal activities against
B. cinerea evaluated. Although some derivatives of acrylamide,
phenylacetamide, and benzamides exhibited good fungicidal ac-
tivity, there is no obvious structure-activity relationship tendency
in general. Indeed, the experiment mentioned above is only a
preliminary investigation, and there are more works to be carried
out. Nevertheless, because the core skeleton of benzimidazolone
possesses great potential in structure modification, it deserves
further investigation. The progress will be reported in the future.
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Received for review July 31, 2009. Revised manuscript received January
13, 2010. Accepted January 15, 2010. This work was funded by grants
from the National Key Project for Basic Research (No.
2010CB126100), the National Natural Science Foundation of China
(No. 20672087 and 30971935), and the Province Key Technologies
R&D Program of Shaanxi, China (2009K02-04).
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