G Model
CCLET-3742; No. of Pages 4
2
J.-Q. Huo et al. / Chinese Chemical Letters xxx (2016) xxx–xxx
3. Results and discussion
3.1. Synthesis
Heterocyclic compounds are important lead sources for drug
and pesticide development and the methods for their construction
are well reported [21–23]. Our former research discovered one
compound, containing furan and pyrazole ring, which could be
studied as an herbicide lead. This study focused on optimization of
this lead and a series of novel N-(3-furan-2-yl-1-phenyl-1H-
pyrazol-5-yl) amides derivatives from 3-(furan-2-yl)-1 -phenyl-H-
pyrazol-5-amine (3) was synthesized. We first tried to prepare 3-
(furan-2-yl)-1-phenyl-H-pyrazol-5-amine (3) using EtOH as the
solvent, and the cycling reaction of 2-furoylacetonitrile with
phenylhydrazine was progressed at the reflux temperature. By-
product was formed and the yield of the desired product was low.
However, after optimization of the reaction conditions, the yield
was increased from 54.01% to 90.09% [24]. 2-Furoylacetonitrile
was allowed to react with phenylhydrazine at 130 8C for 1 h, and
the desired 3-(furan-2-yl)-1-phenyl-H-pyrazol-5-amine (3) was
successfully generated with over 90% yield.
During the synthesis of the target compounds (6), intermediate
3 did not react completely, and the retention factor values of the
target compounds and intermediate 3 were very close. It was
difficult to separate and purify the target compounds using column
chromatography. After washing with HCl, the alkalic intermediate
was easily moved, and the purification efficiency of the target
compounds by chromatography was significantly improved. The
chemical structures of the target compounds were confirmed by
spectroscopic data, and these data are given in Supporting
Fig. 1. The structure of herbicide lead compound 12007063.
standard. The high resolution mass spectra were recorded on an
Agilent 6520-QTOF LC/MS having ESI source in positive mode.
Synthesis of the title compounds was conducted as shown in
Scheme 1. Methyl furan-2-carboxylate (compound 1) was
prepared according to literature [16]. Intermediate 2 was prepared
3
via the reaction of methyl furan-2-carboxylate with CH CN and
NaH in toluene by refluxing for 24 h [17]. The cyclization of
compound 2 with phenylhydrazine gave intermediate 3. Com-
pounds 5a–5t were obtained by the reaction of 4a–4t with SOCl
and a catalytic amount of DMF by refluxing. Compounds 6a–6t
were synthesized by way of a condensation reaction using Et N as
the base in CH Cl . The structures of all newly synthesized
2
3
2
2
1
13
compounds were characterized by melting points, H NMR,
NMR and HRMS.
C
2
.2. Biological assay
The herbicide activity of the target compounds was evaluated
through foliar treatment [18]. The symptoms were monitored at
8 h post-treatment and compared with the control group. The
4
grading standard [19] for the inhibition effect is shown in Table 1.
The target plants tested for herbicide efficacy were Digitaria
sanguinalis L., Echinochloa crusgalli L., Amaranthus retroflexus L.,
Portulaca oleracea L. and Arabidopsis thaliana.
The fungicide activity of the target compounds was tested using
the fungi growth inhibition method [20]. Representative fungi
used in this study included Alternaria solani (AS), Botrytis cinerea
information. Here, the spectroscopic data of 6t were given as a
1
representative. 6t: H NMR (400 MHz, CDCl
3
):
d
8.82 (s, 1H, NH),
7.49 (d, 3H, J = 7.2 Hz, Ph-H), 7.43 (dd, 3H, J = 15.7, 7.6 Hz, Ar-H),
7.09 (s, 1H, Pyrazole-H), 6.90 (d, 1H, J = 7.3 Hz, Ph-H), 6.79 (d, 1H,
J = 8.1 Hz, Ph-H), 6.77 (d, 1H, J = 3.5 Hz, Furan -H), 6.67 (d, 1H,
J = 8.0 Hz, Ph-H), 6.51 (d, 1H, J = 1.7 Hz, Furan-H), 4.73 (s, 2H, –
1
3
OCH
CDCl
2
–), 3.04 (s, 2H, CH
2
), 1.43 (s, 6H, 2Â CH
3
). C NMR (101 MHz,
(BC), Cercospora arachidicola(CA), Gibberella zeae (GZ), Phy-
3
): 165.77, 148.34, 147.67, 144.48, 142.22, 141.68, 137.51,
d
tophthora infestans (Mont) de Bary (PI), Physalospora piricola (PP),
Pellicularia sasakii (PS), Sclerotinia sclerotiorum (SS), and Rhizoctonia
cerealis (RC).
135.56, 129.80, 129.47, 128.38, 124.57, 120.73, 119.90, 114.59,
111.31, 106.75, 95.44, 88.16, 69.20, 43.07, 28.18. HRMS(ESI)
+
[M+H] calcd. for C25
H
23
N
3
O
4
: 430.1767, found: 430.1760.
o
(i) CH
3
CN (3.0 equiv.), NaH (3.0 equiv.), Toluene, reflux for 24 h; (ii) Phenylhydrazine (1.0 equiv.), 130 C for 1 h, yield 90.09%;
(iii) SOCl
2
(5.0 equiv.), DMF (a catalytic amount ), reflux for 5 h; (iv) Et
3
N (1.2 equiv.), CH
2
Cl, room temperature overnight.
Scheme 1. Synthesis of the target compounds.