Synthesis and structure-activity relationships of substituted cinnamic acids and amide analogues: A new class of herbicides

Article abstract of DOI:10.1021/jf8034385

In the present investigation, substituted cinnamic acids (3-hydroxy, 4-hydroxy, 2-nitro, 3-nitro, 4-nitro, 3-chloro, and 4-methoxy) and their amide analogues with four different types of substituted anilines have been synthesized. The synthesized compounds have been screened for their germination inhibition activity on radish (Raphanus sativus L. var. Japanese White) seeds at 50, 100, and 200 ppm concentrations, and the activity was compared with standard herbicide, metribuzin formulation (sencor). Significant activity was exhibited by all of the compounds. It was observed that with the increase in concentration of the test solution, the activity also increased. All of the compounds showed more than 70% inhibition at 100 ppm concentration except 4-hydroxy cinnamanilide. The compound, 2-chloro (4′-hydroxy) cinnamanilide was the best among the tested compounds, and it was found to be at par with the standard, metribuzin at all concentrations. Thus, it can be concluded that substituted cinnamic acids and their amide analogues may be developed as potential herbicides.

Full text of DOI:10.1021/jf8034385

J. Agric. Food Chem. 2009, 57, 3261–3265 3261
Synthesis and Structure-Activity Relationships of
Substituted Cinnamic Acids and Amide Analogues:
A New Class of Herbicides
SHIPRA VISHNOI,* VIKASH AGRAWAL, AND VIRENDRA K. KASANA
Department of Chemistry, G.B.PUA & T., Pantanagar-263 145, Uttarakhand, India
In the present investigation, substituted cinnamic acids (3-hydroxy, 4-hydroxy, 2-nitro, 3-nitro, 4-nitro,
3-chloro, and 4-methoxy) and their amide analogues with four different types of substituted anilines
have been synthesized. The synthesized compounds have been screened for their germination
inhibition activity on radish (Raphanus sativus L. var. Japanese White) seeds at 50, 100, and 200
ppm concentrations, and the activity was compared with standard herbicide, metribuzin formulation
(sencor). Significant activity was exhibited by all of the compounds. It was observed that with the
increase in concentration of the test solution, the activity also increased. All of the compounds showed
more than 70% inhibition at 100 ppm concentration except 4-hydroxy cinnamanilide. The compound,
2-chloro (4′-hydroxy) cinnamanilide was the best among the tested compounds, and it was found to
be at par with the standard, metribuzin at all concentrations. Thus, it can be concluded that substituted
cinnamic acids and their amide analogues may be developed as potential herbicides.
KEYWORDS: Substituted cinnamic acids; cinnamic acid amide analogues; radish (Raphanus sativus L.);
metribuzin; germination inhibition activity
INTRODUCTION
The biocides developed from allelochemicals have important
advantages with respect to traditional herbicides, fungicides, or
insecticides since they have novel modes of action, high
biodegradability, and low environmental impact (8). The three
main groups of allelochemicals that have been identified in
wheat are phenolic acids (9, 10), hydroxamic acids (11-14),
and short chain fatty acids (15, 16). Phenolic acids and
hydroxamic acids are produced by living wheat plants and either
exuded by the plants or released following the degradation of
plant material, whereas short chain fatty acids are secondary
products produced by anaerobic fermentation of polysaccharides.
Substituted cinnamic acids are widely distributed in the plant
kingdom and are found in coffee beans, olives, propolis, fruits,
and vegetables. They are found usually as simple derivatives
including amide, esters, sugar esters, and glycosides (1).
Hydroxycinnamic acid esters are widely distributed in the plant
kingdom and are reported as cellular antioxidants, anti-inflam-
matory agents, or inhibitors of enzymes involved in cell
proliferation, and some biological activities (2–4).
Weeds compete with crops for sunshine, water, nutrients, and
space and thus influence the growth of crops and undermine
both crop quality and yield. Since the discovery of the herbicide
2,4-dichlorophenoxyacetic acid (2,4-D) by Zimerman and
Hithcock, the agrochemical industry has successfully developed
a wide range of herbicides with various chemical structures and
modes of actions (5). But the main problem associated with
the use of herbicides is the occurrence of herbicide resistant
weeds. According to one estimate, worldwide at least 315 weed
biotypes, 183 weed species including 110 dicots and 73
monocots have been reported to have acquired resistance to
important herbicides (6). Therefore, it is necessary to develop
efficient herbicides with novel structures and modes of actions
to overcome the resistance of weeds. During the past three
decades, efforts have been focused on discovering new alle-
lochemicals with potential application in weed management (7).
The two hydroxamic acids found most abundantly in wheat,
2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) and
2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA), have been stud-
ied extensively ranging from their isolation to synthetic
analogues (17-21), whereas phenolic acids have been studied
either for their joint allelochemical effects with hydroxamic acids
(22) or for joint action of their mixtures. Studies show
contrasting results. Reigosa et al. (23) reported additive effects
of phenolic acids, whereas Inderjit et al. (24) have found mostly
antagonistic interactions between phenolic acids. In contrast,
Einhellig et al. (25-27) have reported synergistic effects with
a mixture of phenolic acids. This discrepancy in results may be
due to the use of different statistical methods or allelochemicals
actually exhibiting variable activity.
The mode of action of wheat alleochemicals is not fully
understood. Einhellig (28) and Blum et al. (29) have suggested
that phenolic acids depolarized the cell membrane, affecting
membrane ATPase activity and ion flux.
* To whom correspondence should be addressed. Tel: +91-
9410117808. Fax: +91-5944-233637. E-mail: vishnoi_shipra@
rediffmail.com.
10.1021/jf8034385 CCC: $40.75  2009 American Chemical Society
Published on Web 04/15/2009

3262 J. Agric. Food Chem., Vol. 57, No. 8, 2009
Scheme 1. Synthesis of Substituted Cinnamic Acids
Vishnoi et al.
Scheme 2. Synthesis of Amides of Substituted Cinnamic Acids
A literature survey shows that phenolics, specificially having
the cinnamic acid moiety, have not been studied extensively
by synthesizing their analogues and determining the activity.
To the best of our knowledge, we are the first to report the
herbicidal activity in cinnamic acid derivatives. Therefore, the
objectives of the present study were to synthesize some
substituted cinnamic acids and their amide analogues to
determine their activity. This work is in continuation of our
program to search potential and novel compounds with promis-
ing herbicidal activity.
Table 1. Mean Percent Seed Germination Inhibition Values of Substituted
Cinnamic Acids
mean percent inhibition values
name of the compounds
50 ppm
100 ppm
200 ppm
CD at 5%
metribuzin (standard)
3-hydroxy cinnamic acid
4-hydroxy cinnamic acid
2-nitro cinnamic acid
3-nitro cinnamic acid
4-nitro cinnamic acid
3-chloro cinnamic acid
4-methoxy cinnamic acid
CD at 5%
80.00
56.66
53.33
70.00
70.33
70.00
53.33
56.66
10.59
93.33
86.66
73.33
86.66
80.00
93.33
76.66
66.66
9.34
100.00
100.00
100.00
100.00
100.00
96.66
93.33
93.33
4.99
13.30
9.40
9.40
6.65
6.65
6.65
11.51
11.51
EXPERIMENTAL PROCEDURES
General. Melting points were determined on a Bu¨chi B-540
apparatus and are uncorrected. UV spectra were taken on a Genesys
1
10 UV-vis spectrophotometer, H NMR spectra were recorded on a
Bruker Avance 400 NMR spectrophotometer, and IR spectra were
recorded on a Bruker IR spectrophotometer. The chemicals used in
the present study, 3-hydroxy benzaldehyde, 4-hydroxy benzaldehyde,
2-nitro benzaldehyde, 3-nitrobenzaldehyde, 4-nitro benzaldehyde,
3-chlorobenzaldehyde, 4-methoxy benzaldehyde, malonic acid, piperi-
dine, aniline, 2-chloro aniline, 4-nitro aniline, and 4-methyl aniline,
were purchased from M/S Sigma-Aldrich Chemical Co. (USA), and
pyridine, triethylamine, and phosphorus oxychloride were purchased
from M/S Merck India Chemicals Company. Metribuzin (Sencor 70
WP) was obtained from M/S Bayer AG, Germany. All of the chemicals
were of AR grade. The radish (R. satiVus L. var. Japanese White) seeds
were obtained from Vegetable Research Centre, G. B. Pant University
of Agriculture and Technology, Pantnagar, India.
Preparation of Substituted Cinnamic Acids. The substituted
cinnamic acids were synthesized using Doebner-Knoevenagel modi-
fication (30). Cinnamic acids were prepared by mixing substituted
benzaldehydes (60 mM), malonic acid (100 mM), pyridine (20 mL),
and piperidine (0.8 mL) together and stirring on a magnetic stirrer for
4 days (Scheme 1). The reaction progress was monitored over silica
gel TLC plates. The reaction mixture was then poured in excess of
diluted HCI. Precipitates obtained were filtered, washed with cold water
repeatedly, and dried. The yields were between 70-98% (Chart 1,
Supporting Information).
Preparation of Substituted Cinnamic Acid Amide Analogues. All
of the amides were synthesized using the method described by
Greenstein and Winitz (31). To a solution of acid (1.0 mM) in
chloroform containing triethylamine (0.1 mL) and amino compound
(1.2 mM) was added dropwise POC13 (2.0 mM) at 0 °C with constant
stirring. Triethylamine (0.2 mM) was then added in one portion. The
reaction mixture was stirred for another 30 min at low temperature
and then poured into crushed ice; the organic phase separates out. The
aqueous phase was extracted with dichloromethane, and combined
layers were washed successively with diluted HC1, aqueous NaHCO3,
water and dried over anhydrous CaCl2 (Scheme 2). Evaporation of
solvent gave residues of varying colors, which were recrystallized from
ethanol/chloroform (80:20). The yields were between 48-92% (Charts
2-5, Supporting Information).
prepared by serial dilution of stock solution of 500 ppm of the
compounds in ethanol. The test solutions of standard metribuzin (sencor)
were also prepared by serial dilution in distilled water. Each compound
was dissolved in a minimum amount of ethanol, which was suspended
in distilled water with Tween-20 (3 mL/l). Seeds of radish (R. satiVus
L.) prior to sowing in Petri dishes (9 cm diameter) were surface
sterilized with distilled water followed by 95% ethanol for 15 s and
finally with distilled water. Ten seeds were taken in each Petri dish.
Double layered filter paper was placed in the Petri dishes on which 7
mL of each test solution was poured. A mixture of distilled water/
ethyl alcohol/Tween-20 (97: 2.5: 0.5) was taken as the control. All
treatments were replicated three times with CRD fashion. The radish
seeds were allowed to germinate at 25 ( 2 °C in an incubator with
12 h of photoperiod. The seed germination process was observed after
five days of incubation and seeds were considered to be germinated
when the protrusion of radical was evident (32). After 120 h, the number
of seeds germinated in each Petri dish was counted, and percent seed
germination inhibition values were calculated.
Statistical Analysis. The percent seed germination inhibition values
were determined and subjected to analysis of variance (ANOVA).
Critical differences (CDs) were calculated at p e 0.05.
RESULTS AND DISCUSSION
Synthesis. Spectral analysis of two cinnamic acid intermedi-
ates (3-chloro and 4-methoxy cinnamic acid) and one of the
amides (3-chloro cinnamanilide) was carried out. The structure
of substituted cinnamic acids and their amides are displayed in
Figures 1 and 2 in Supporting Information.
Seed Germinatin Inhibition Activity. Percent seed germina-
tion inhibition values of compounds at different concentrations
are given in Tables 1 and 2. Perusal of Table 1 clearly indicates
that there is significant increase in mean percent inhibition values
with increasing concentrations. Activities of 2-nitro cinnamic
acid, 3-nitro cinnamic acid, and 4-nitro cinnamic acid are at
par with the standard at all concentrations, whereas 4-hydroxy
cinnamic acid was found at par with the standard only at 200
ppm.
Bioassay. A bioassay based on seed germination was used to study
seed germination inhibition activity of the synthesized compounds. Test
solutions of concentration 50 ppm, 100 ppm, and 200 ppm were

Substituted Cinnamic Acids and Amide Analogues
J. Agric. Food Chem., Vol. 57, No. 8, 2009 3263
Table 2. Mean Percent Seed Germination Inhibition Values of Substituted
Cinnamanilides
Table 4. Mean Percent Seed Germination Inhibition Values of Substituted
4-Nitro Cinnamanilides
mean percent inhibition values
mean percent inhibition values
name of the compounds
50 ppm
100 ppm
200 ppm
CD at 5%
name of the compounds
50 ppm 100 ppm 200 ppm CD at 5%
metribuzin (standard)
3-hydroxy cinnamanilide
4-hydroxy cinnamanilide
2-nitro cinnamanilide
3-nitro cinnamanilide
4-nitro cinnamanilide
3-chloro cinnamanilide
4-methoxy cinnamanilide
CD at 5%
80.00
53.33
50.00
73.33
70.00
83.33
70.00
53.33
9.34
93.33
86.66
63.33
86.66
73.33
90.00
93.33
76.66
11.17
100.00
100.00
96.66
100.00
100.00
100.00
100.00
93.33
13.30
9.40
14.87
9.40
6.65
6.65
6.65
11.51
metribuzin (standard)
80.00
80.00
86.66
73.33
73.33
60.00
76.66
93.33
83.33
96.66
86.66
96.66
66.66
83.33
96.66
11.71
100.00
96.66
100.00
96.66
100.00
93.33
96.66
100.00
7.06
13.30
9.40
9.40
11.51
9.40
9.40
4-nitro-(3′-hydroxy) cinnamanilide
4-nitro-(4′-hydroxy) cinnamanilide
4-nitro-(2′-nitro) cinnamanilide
4-nitro-(3′-nitro) cinnamanilide
4-nitro-(4′-nitro) cinnamanilide
4-nitro-(3′-chloro) cinnamanilide
16.29
9.40
4-nitro-(4′-methoxy) cinnamanilide 76.66
CD at 5% 9.99
4.99
Table 3. Mean Percent Seed Germination Inhibition Values of Substituted
2-Chloro Cinnamanilides
Table 5. Mean Percent Seed Germination Inhibition Values of Substituted
4-Methyl Cinnamanilides
mean percent inhibition values
mean percent inhibition values
name of the compounds
metribuzin (standard)
2-chloro-(3′-hydroxy) cinnamanilide 56.66
2-chloro-(4′-hydroxy) cinnamanilide 86.66
2-chloro-(2′-nitro) cinnamanilide
2-chloro-(3′-nitro) cinnamanilide
2-chloro-(4′-nitro) cinnamanilide
2-chloro-(3′-chloro) cinnamanilide
2-chloro-(4′-methoxy) cinnamanilide 76.66
CD at 5% 12.23
50 ppm 100 ppm 200 ppm CD at 5%
name of the compounds
metribuzin (standard)
4-methyl-(3′-hydroxy) cinnamanilide 80.00
4-methyl-(4′-hydroxy) cinnamanilide 70.00
4-methyl-(2′-nitro) cinnamanilide
4-methyl-(3′-nitro) cinnamanilide
4-methyl-(4′-nitro) cinnamanilide
4-methyl-(3′-chloro) cinnamanilide
4-methyl-(4′-methoxy) cinnamanilide 70.00
CD at 5% 10.59
50 ppm 100 ppm 200 ppm CD at 5%
80.00
93.33
80.00
96.66
93.33
93.33
86.66
53.33
83.33
9.34
100.00
93.33
100.00
100.00
100.00
100.00
76.66
96.66
6.11
13.30
9.40
9.40
80.00
93.33
86.66
86.66
80.00
86.66
90.00
83.33
93.33
8.65
100.00
100.00
100.00
93.33
96.66
100.00
93.33
100.00
6.11
13.30
13.30
6.65
86.66
83.33
80.00
33.33
9.40
9.40
13.30
11.51
11.51
63.33
73.33
83.33
70.00
9.40
11.51
6.65
9.40
6.65
Electron withdrawing groups on the benzene ring of acids
tend to increase the activity as is evident from the higher values
exhibited by 2-nitro cinnamic acid, 3-nitro cinnamic acid, and
4-nitro cinnamic acid, whereas electron donating groups (-OH
and -OCH3) on the benzene ring decrease the activity. This trend
is more prominent at lower concentrations, i.e., 50 ppm. At
higher concentration, there is no correlation between the
presence of electron withdrawing/electron donating groups and
activity.
In Table 2, seed germination inhibition values of amide
derivatives prepared by aniline and substituted cinnamic acids
are given. The seed germination inhibition values are found to
increase significantly with increasing concentrations, except for
3-nitro cinnamanilide for which activity at 50 ppm and 100 ppm
is at par. At 50 ppm concentration, 2-nitro cinnamanilide and
4-nitro cinnamanilide exhibit activity at par with standard
metribuzin. At 50 ppm concentration, higher values of activity
are observed in the case of amide derivatives having -NO2 and
-Cl group substituents at the benzene ring of the acid moiety,
and lower values are observed for amide derivatives containing
substituents -OH and -OCH3 on the benzene ring of the acid
moiety.
In Table 3, the data of seed germination inhibition activity
of amide derivatives of substituted cinnamic acids with o-chloro
aniline are presented. The seed germination inhibition values
of all of the compounds increase significantly with increase in
concentration. The activities of 2-chloro-(4′-hydroxy) cinna-
manilide, 2-chloro-(2′-nitro) cinnamanilide, 2-chloro-(3′-nitro)
cinnamanilide, 2-chloro-(4′-nitro) cinnamanilide, and 2-chloro-
(4′-methoxy) cinnamanilide are at par with that of standard
metribuzin at all concentrations. Here, the effect of the presence
of the electron withdrawing group (-NO2 and -Cl) and electron
donating groups (-OH and -OCH3) on the benzene ring of the
acid moiety cannot be correlated with the activity. Here, the
effect of electron withdrawing group -Cl on the benzene ring
of the amine moiety seems to have an overriding electronic
effect that decides the activity.
The seed germination inhibition activity data of amide
derivatives of substituted cinnamic acids with p-nitro aniline
is displayed in Table 4. At 50 ppm concentration, 4-nitro-
(3′-hydroxy) cinnamanilide, 4-nitro-(4′-hydroxy) cinnama-
nilide, 4-nitro-(3′-chloro) cinnamanilide, and 4-nitro-(4′-
methoxy) cinnamanilide exhibit seed germination inhibition
activity at par with the standard. The 4-nitro-(2′-nitro)
cinnamanilide, 4-nitro-(3′-nitro) cinnamanilide, and 4-nitro-
(4′-nitro) cinnamanilide are showing less activity due to the
presence of the -NO2 group on the benzene ring of the amine
moiety. We have already discussed that the presence of
different substituents on the benzene ring of the amine moiety
increases the activity, but in this class of amides, the trend
is reversed. The reversal in trend may be due to the presence
of the -NO2 group at fourth position in the benzene ring of
the amine moiety. It seems that the presence of the electron
withdrawing group on the benzene ring of the amine moiety
is the overriding factor in deciding the electronic effect that
is responsible for the activity.
In Table 5, seed germination inhibition values of substituted
cinnamic acids with p-methyl aniline are recorded. Perusal of
the table reveals that at 50 ppm concentration only 4-methyl-
(3′-hydroxy) cinnamanilide, 4-methyl-(3′-nitro)cinnamanilide,
and 4-methyl-(4′-nitro) cinnamanilide are at par with the
standard. There is no definite trend observed in activity.
Higher values are attributed to the presence of electron
withdrawing groups, and lower values due to presence of
electron donating groups. It is clear from these results that
activity is considerably affected by electronic effects. At
higher (100 and 200 ppm) concentration, these electronic
effects do not give a clear trend of activity. This may be due
to the fact that most of the compounds of these two bear
limiting activity; therefore, differentiation in activity cannot
be established on the basis of electronic effects. But this does

3264 J. Agric. Food Chem., Vol. 57, No. 8, 2009
Vishnoi et al.
not mean that the electronic effect is not playing its role in
deciding the activity.
2-Chloro-(3′-chloro) Cinnamanilide. M.P. 119 °C; yield
68.6%. λmax (nm)/DCM, 274. IR υmax (cm-1, KBr): 3287, 2987.7,
1758, 1660.6, 1589, 1536, 1439.7. 1H NMR (400 MHz, CDCl3):
δ (ppm) 6.6 (1H, d, J ) 16 Hz, -CHdCH-), 7.7 (1H, d, J ) 16
Hz, -CHdCH-), 6.19 (1H, s br, -NH).
Comparison of activity of the compounds with the standard
clearly indicates that all of the compounds except 4-methoxy
cinnamanilide are at par with the standard metribuzin at 200
ppm concentration, while at 100 ppm concentration, 3-hydroxy
cinnamanilide, 2-nitro cinnamanilide, 4-nitro cinnamanilide, and
3-chloro cinnamanilide are at par with the standard, and at 50
ppm, only 2-nitro cinnamanilide and 4-nitro cinnamanilide are
at par with the standard herbicide.
ACKNOWLEDGMENT
We acknowledge the assistance of the staff at NMR Structural
Biology Facility at the Wadsworth Center.
Omokawa et al. (33) have tried to establish the structure-
herbicidal activity relationship of R-phenylsulfonyl propanamide.
Effect of substituents at the aromatic moiety of the compounds
was studied in which the compounds substituted with the alkyl
group (electron donating group) were found to remarkably
increase the activity. In pyrazole-4-carboxamide derivatives,
Ohno et al. (34) have correlated the effect of substituents on
the benzene moiety of the compound with herbicidal activity.
Some substituents (alkyl and halogens) have been found to
increase activity, but a clear trend was not observed.
Supporting Information Available: Synthesis of substituted
cinnamic acids, substituted cinnamic acids with aniline, sub-
stituted cinnamic acids with o-chloro aniline, substituted cin-
namic acids with p-nitro aniline, substituted cinnamic acids with
p-methyl aniline, and structures of substituted cinnamic acids,
substituted cinnamanilides, substituted 2-chloro cinnamanilides,
substituted 4-nitro cinnamanilides, and substituted 4-methyl
cinnamanilides. This material is available free of charge via the
Internet at http://pubs.acs.org.
Kawamura et al. (35) investigated that in 2,4-diarylpyrim-
idines, substituents in two phenyl rings are very important for
activity. For one phenyl ring at the pyrimidine 4-position, a meta
substituent enhanced herbicidal activity, while ortho or para
substituents gave a reduction or complete loss of activity.
All of the tested compounds have been found to exhibit
promising seed germination inhibition activity. The compound
2-chloro (4′-hydroxy) cinnamanilide was found to have excellent
activity, which is at par with the standard, metribuzin. The
compounds, 2-chloro (3′-nitro) cinnamanilide, 2-chloro (2′-nitro)
cinnamanilide, and 4- nitro cinnamanilide, have also been shown
promising herbicidal activity. Therefore, we can conclude that
substituted cinnamic acids and their amide analogues can be
developed as a new class of herbicides.
LITERATURE CITED
(1) Kavitha, J.; Vanisree, M.; Subbaraju, G. V. Synthesis of O-
geranylconiferyl alcohol, a metabolite of Fagara rhetza. Indian
J. Chem. 2000, 40, 522–523.
(2) Chan, R. I.; San, R. H.; Stich, H. F. Mechanisim of inhibition of
N-methyl-N′-nitro-N-nitrosoguanidine-induced mutagenesis by
phenolic compounds. Cancer Lett. 1986, 31 (1), 27–34.
(3) Chen, H.; Muramato, K.; Yamauchi, F.; Nokihara, K. Antioxidant
activity of designed peptides based on the antioxidative peptides
isolated from digests of a soybean protein. J. Agric. Food Chem.
1996, 44 (9), 2619–2623.
(4) Laranjinha, J.; Vierira, O.; Almeida, L.; Madeira, V. Inhibition
of metmyoglobin/H2O2-dependent low density lipoprotein lipid
peroxidation by naturally occurring phenolic acids. Biochem.
Pharmacol. 1996, 51 (4), 395–402.
(5) Bo¨ger, P.; Wakabayashi, K.; Hirai, K. Herbicide Class. In
DeVelopment, Mode of Action, Targets, Genetic Engineering,
Chemistry; Springer-Verlag: Berlin, Germany, 2002; pp 364.
(6) Heap, I. International Survey of Herbicide Resistant Weeds. http://
www.weedscience.org (accessed Nov 29, 2007).
(7) Macias, F. A. In Allelopathy: Organism, Processes and Applica-
tions; Dakshini, K. M. M., Einhellig, F. A., Eds.; ACS Symposium
Series 582; American Chemical Society: Washington, DC, 1995.
(8) Rice, E. L. Biological Control of Weeds and Plant Diseases,
University of Oklahoma Press: Norman, U.K., 1995.
(9) Blum, U.; Wentworh, T. R.; Klein, K.; Worsham, A. D.; King,
L. D.; Gerig, T. M.; Lyu, S. W. Phenolic acid content of soils
from wheat-no till, wheat-conventional till and fallow-conventional
till soybean cropping systems. J. Chem. Ecol. 1991, 17, 1045–
1068.
(10) Wu, H.; Haig, T.; Pratley, J.; Lemerle, D.; An, M. Allelochemicals
in wheat (Triticum aestiVum L.): Variation in phenolic acids in
short tissues. J. Chem. Ecol. 2001, 27, 125–135.
(11) Wu, H.; Haig, T.; Pratley, J.; Lemerle, D.; An, M. Distribution
and exudation of allelochemicals in wheat Triticum aesti-
VumJ. Chem. Ecol. 2000, 26, 2141-2154.
Analytical and Spectral Characterization Data. 3-Chloro
Cinnamic Acid. M.P. 191 °C; yield 95.2%. λmax (nm)/DCM,
274. IR υmax (cm-1, KBr): 3075.4, 2881.7, 1696.9, 1638, 1596,
1
1476.4, 1303.7, 980.8, 749.8. H NMR (400 MHz, CDCl3): δ
(ppm) 6.43 (1H, d, J ) 16 Hz, -CHdCH-), 7.64 (1H, d, J ) 16
Hz, -CHdCH-), 7.94 (1H, s, H-2), 7.35 (m, benzene ring).
4-Methoxy Cinnamic Acid. M.P. 174 °C; yield 78.4%. λmax
(nm)/DCM, 304. IR υmax (cm-1, KBr): 3400-3300, 3110-3075,
1
2937, 1686.9, 1622.8, 1596, 1476.5, 1414.6, 1315.4. H NMR
(400 MHz, CDCl3): δ (ppm) 6.28 (1H, d, J ) 16 Hz, -CHdCH-),
7.57 (1H, d, J ) 16 Hz, -CHdCH-), 3.81 (3H, s), 7.48 (2H,
Ar, d, J ) 13 Hz, H-3, H-5), 6.90 (2H, Ar, d, J ) 14.5 Hz,
H-2, H-6).
3-Chloro Cinnamanilide. M.P. 110 °C; yield 81.2%. λmax
(nm)/DCM, 283. IR υmax (cm-1, KBr): 3289.6, 3125.4, 3058.6,
1657.4, 1627, 1565, 1472, 1441.2. 1H NMR (400 MHz, CDCl3):
δ (ppm) 6.45 (1H, d, J ) 16 Hz, -CHdCH-), 7.64 (1H, d, J )
16 Hz, -CHdCH-), 7.97 (1H, s br, -NH), 7.6 (m, benzene
ring).
4-Nitro-(3′-chloro) Cinnamanilide. M.P. 168 °C; yield 87.8%.
λmax (nm)/DCM, 265. IR υmax (cm-1, KBr): 3356.6, 2984.7,
1
(12) Niemeyer, H. Hydroxamic acids (4-hydroxy-1, 4-benzoxazin-3-
ones) defence. Chemicals in Gramineae. Phytochemistry 1988,
27, 3349–3358.
(13) Copaja, S. V.; Nicol, D.; Wratten, S. D. Accumulation of
hydroxamic acids during wheat germination. Phytochemistry 1999,
50, 17–24.
(14) Wu, H.; Haig, T.; Pratley, J.; Lemerle, D.; An, M. Allelochemicals
in wheat (Triticum aestiVum L.): production and exudation of 2,4-
dihydroxy-7-methoxy-1, 4-benzoxazin-3-one. J. Chem. Ecol. 2001,
27, 1691–1700.
1696.4, 16321.7, 1475.7, 1401, 1304. H NMR (400 MHz,
CDCl3): δ (ppm) 6.45 (1H, d, J ) 16 Hz, -CHdCH-), 7.68
(1H, d, J ) 16 Hz, -CHdCH-), 5.52 (1H, s br, -NH), 6-8 (m,
benzene ring).
4-Methyl-(3′-chloro) Cinnamanilde. M.P. 194 °C; yield
89.4%. λmax (nm)/DCM, 253. IR υmax (cm-1, KBr): 3236, 2938.7,
1664, 1550, 1402, 1343. 1H NMR (400 MHz, CDCl3): δ (ppm)
6.75 (1H, d, J ) 16 Hz, -CHdCH-), 7.64 (1H, d, J ) 16 Hz,
-CHdCH-), 6.30 (3H, s, -CH3).

Substituted Cinnamic Acids and Amide Analogues
J. Agric. Food Chem., Vol. 57, No. 8, 2009 3265
(15) Lynch, J. M. Production and phytotoxicity of acetic acid in
anaerobic soils containing plant residues. Soil Biol. Biochem. 1978,
56, 503–510.
(26) Ramussen, J. A.; Einhellig, F. A. Inhibitory effects of combination
of three phenolic acids on grain sorghum germination. Plant Sci.
Lett. 1979, 14, 69–74.
(16) Tang, C. S.; Waiss, A. C. Short Chain fatty acids as growth
inhibitors in decomposing wheat straw. J. Chem. Ecol. 1978, 4,
225–232.
(27) Einhellig, F. A.; Schon, M. K.; Rasmussen, J. A. Synergistic
effects of four cinnamic acid compounds on grain sorghum. J.
Plant Growth Regul. 1982, 1, 251–258.
(17) Regina, G. B.; Karl, H. Differential exudation of two benzoxazi-
noids: One of the determining factors for seedling allelopathy of
triticeae species. J. Agric. Food Chem. 2005, 53, 250–261.
(18) Macias, F. A.; Marin, D.; Alberto, O. P.; Castellano, D.; Simonet,
A. M.; Jose, M. G. M. Structure-activity relationship (SAR) studies
of Benzoxazinones, their degradation products and analogues.
Phytotoxicity on problematic weeds AVena fatua L. and Lolium
rigidum Gaud. J. Agric. Food Chem. 2006, 54, 1040–1048.
(19) Hansen, L. M. Effect of 6-methoxy benzoxazolin-2-one (MBOA)
on the reproduction rate of the grain aphid (Sitobion aVenae F.).
J. Agric. Food Chem. 2006, 54, 1031–1035.
(28) Einhellig, F. A. Mechanism of Action of Allelochemicals in
Allelopathy. In Allelopathy. Organism, Processes and Applica-
tions; Dakshini, K. M. M., Einhiellig, F. A., Eds.; American
Chemical Society: Washington, DC, 1995; pp 96-116.
(29) Blum, U.; Shafer, S.; Lehman, M. Evidence for inhibitory
interaction involving phenolic acids in field soil: concepts vs
experimental model. Crit. ReV. Plant Sci. 1999, 18, 673–693.
(30) Furniss, B. S.; Hannaford, H. J.; Smith, P. W. G.; Tatchell, A. R.
In Vogel’s Text Book of Practical Organic Chemistry, Vth ed.;
ELBS; Bath Press Ltd.: U.K., 1989; pp 1040.
(20) Macias, F. A.; Marin, D.; Bastidas, A. O.; Chinchilla, D.; Simonet,
A. M.; Jose, M. G. M. Isolation and synthesis of allelochemicals
from Gramineae: Benzoxazinones and related compounds. J.
Agric. Food Chem. 2006, 54, 991–1000.
(21) Villagrasa, M.; Guillamon, M.; Labandeira, A.; Taberner, A.;
Eljarrat, E.; Barcelo, D. Benzoxazinoid allelochemicals in wheat:
Distribution among foliage, roots and seeds. J. Agric. Food Chem.
2006, 54, 1009–1015.
(22) Jia, C.; Kudsk, P.; Mathiassen, S. K. Joint action of benzoxazinone
derivatives and phenolic acids. J. Agric. Food Chem. 2006, 54,
1049–1057.
(23) Reigosa, M. J.; Sonto, X. C.; Gonzales, L. Effect of phenolic
compounds on the germination of six weed species. Plant Growth
Regul. 1999, 28, 83–88.
(24) Inderjit; Streibig, J. C.; Olofrdotter, M. Joint action of phenolic
acid mixtures and its significance in allelopathy research. Physiol.
Plant 2002, 114, 422–428.
(25) Einhellig, F. A.; Rasmussen, J. A. Synergistic inhibitory effects
of vanillic and p-hydroxy benzoic acids on radish and grain
sorghum. J. Chem. Ecol. 1978, 4, 425–436.
(31) Greenstein, J. P.; Winitz, M. In Chemistry of the Aminoacid; John
Wiley: New York, 1961; Vol. II, pp 1009.
(32) Bewley, D.; Black, M. Seeds: Physiology of DeVelopment and
Germination; Plenum Press: New York, 1985.
(33) Omokawa, H.; Ichizen, N.; Tabogami, S.; Takamatsu, T. Structure-
herbicidal activity relationship of R-phenylsulfonyl propanamide.
Agric. Biol. Chem. 1985, 49, 3551–3555.
(34) Ohno, R.; Watanabe, A.; Matsukawa, T.; Ueda, T.; Sakurai, H.;
Hori, M.; Hirai, K. Synthesis and herbicidal activity of new
pyrazole-4-carboxamide derivatives. J. Pestic. Sci. 2004, 29, 15–
26.
(35) Kawamura, S.; Sato, J.; Hamada, T.; Sakai, M.; Sanemitsu, Y.
Synthesis and herbicidal activity of some 2,4-diarylpyrimidines.
J. Agric. Food Chem. 1993, 41, 288–291.
Received for review November 3, 2008. Revised manuscript received
January 11, 2009. Accepted January 14, 2009.
JF8034385