Synthesis and Herbicidal Activity of 5-Heterocycloxy-3-methyl-1-substituted-1H-pyrazoles

With the objective of finding valuable herbicidal candidates, a series of new 5-heterocycloxy-3-methyl-1-substituted-1H-pyrazoles were synthesized and their herbicidal activities were evaluated. The bioassay results showed that some compounds exhibited excellent herbicidal activities at the concentration of 100 mg/L, and compound 5-chloro-2-((3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)oxy)pyrimidine showed bleaching activity to green weeds. In greenhouse conditions, this compound also showed excellent post-emergence herbicidal effect against Digitaria sanguinalis L. at the dosage of 750 g a. i. ha−1.

Molecules 2015, 20, page-page 2 above was represented in Figure 1. The pyrazolylpyrimidine derivatives have been reported to show inhibition of chlorophyll and carotenoid biosynthesis in our previous work [30,31]. In view of the above mentioned facts and in continuation of our interest in the synthesis of pyrazole heterocycles, the synthesis and herbicidal activities of these novel pyrazole derivatives are described in this paper.

Synthesis
The synthetic route of a series of pyrazole derivatives were shown in Scheme 1. The chemical structures of fourteen target compounds were listed in Table 1. The structures of these compounds were confirmed by 1 H-NMR (see Supplementary Materials), 13 C-NMR (see Supplementary Materials), MS, Elemental analysis, and FT-IR. The compound 5b was synthesized according to the method of preparing 3,5-dimethyl-1-(2,2,2-trifluoroethyl)-1-H-pyrazole reported in the literature [29].

Synthesis
The synthetic route of a series of pyrazole derivatives were shown in Scheme 1. The chemical structures of fourteen target compounds were listed in Table 1. The structures of these compounds were confirmed by 1 H-NMR (see Supplementary Materials), 13 C-NMR (see Supplementary Materials), MS, Elemental analysis, and FT-IR. The compound 5b was synthesized according to the method of preparing 3,5-dimethyl-1-(2,2,2-trifluoroethyl)-1-H-pyrazole reported in the literature [29].
Molecules 2015, 20, page-page 2 above was represented in Figure 1. The pyrazolylpyrimidine derivatives have been reported to show inhibition of chlorophyll and carotenoid biosynthesis in our previous work [30,31]. In view of the above mentioned facts and in continuation of our interest in the synthesis of pyrazole heterocycles, the synthesis and herbicidal activities of these novel pyrazole derivatives are described in this paper.

Synthesis
The synthetic route of a series of pyrazole derivatives were shown in Scheme 1. The chemical structures of fourteen target compounds were listed in Table 1. The structures of these compounds were confirmed by 1 H-NMR (see Supplementary Materials), 13 C-NMR (see Supplementary Materials), MS, Elemental analysis, and FT-IR. The compound 5b was synthesized according to the method of preparing 3,5-dimethyl-1-(2,2,2-trifluoroethyl)-1-H-pyrazole reported in the literature [29].

Growth Inhibition of Weed Roots and Shoots
The herbicidal activities of the target compounds were determined with Brassica campestris L.  Table 2. All compounds showed inhibitory effect on the roots growth of B. campestris, A. retroflexus, P. oleracea, and D. sanguinalis and the shoots growth of P. alopecuroides and E. crus-galli. Compounds 6d and 7d showed excellent inhibition effect against all tested dicotyledonous and monocotyledonous plants at 100 mg/L. Compound 6d exhibited excellent bleaching activities to B. campestris, P. alopecuroides, E. crus-galli, and D. sanguinalis, and even bleached D. sanguinalis at the concentration of 10 mg/L. Among these target compounds, only compound 6d showed best bleaching activity. It was possible that pyrimidine group played a key role in bleaching phytotoxicity. Comparing the compounds 6d and 7d, the presence of bromine at the 4-position on the pyrazole ring had a negative effect on bleaching activity.
It could be seen from Table 2, compounds 6a-6d showed better herbicidal effect than compounds 6e-6i. The derivatives with 2,2,2-trifluoroethyl at the 1-position on pyrazole showed better inhibition effect than that of compounds substituted with the phenyl group, indicating the 2,2,2-trifluoroethyl group on the pyrazole ring played an important role in inhibition. Compounds 6d and 6h had better inhibition activities than compounds 6a-6c and 6e-6g, indicating that the bulkiness of fused heterocyclic substitute at pyrazole ring might be attributable to the decreased of herbicidal activity. Comparing the activities of compounds 6 and compounds 7, the electron-withdrawing bromine group at C-4 had no beneficial effect on activity.

Growth Inhibition of Weed Roots and Shoots
The herbicidal activities of the target compounds were determined with Brassica campestris L.  Table 2. All compounds showed inhibitory effect on the roots growth of B. campestris, A. retroflexus, P. oleracea, and D. sanguinalis and the shoots growth of P. alopecuroides and E. crus-galli. Compounds 6d and 7d showed excellent inhibition effect against all tested dicotyledonous and monocotyledonous plants at 100 mg/L. Compound 6d exhibited excellent bleaching activities to B. campestris, P. alopecuroides, E. crus-galli, and D. sanguinalis, and even bleached D. sanguinalis at the concentration of 10 mg/L. Among these target compounds, only compound 6d showed best bleaching activity. It was possible that pyrimidine group played a key role in bleaching phytotoxicity. Comparing the compounds 6d and 7d, the presence of bromine at the 4-position on the pyrazole ring had a negative effect on bleaching activity.
It could be seen from Table 2, compounds 6a-6d showed better herbicidal effect than compounds 6e-6i. The derivatives with 2,2,2-trifluoroethyl at the 1-position on pyrazole showed better inhibition effect than that of compounds substituted with the phenyl group, indicating the 2,2,2-trifluoroethyl group on the pyrazole ring played an important role in inhibition. Compounds 6d and 6h had better inhibition activities than compounds 6a-6c and 6e-6g, indicating that the bulkiness of fused heterocyclic substitute at pyrazole ring might be attributable to the decreased of herbicidal activity. Comparing the activities of compounds 6 and compounds 7, the electron-withdrawing bromine group at C-4 had no beneficial effect on activity.

Growth Inhibition of Weed Roots and Shoots
The herbicidal activities of the target compounds were determined with Brassica campestris L.  Table 2. All compounds showed inhibitory effect on the roots growth of B. campestris, A. retroflexus, P. oleracea, and D. sanguinalis and the shoots growth of P. alopecuroides and E. crus-galli. Compounds 6d and 7d showed excellent inhibition effect against all tested dicotyledonous and monocotyledonous plants at 100 mg/L. Compound 6d exhibited excellent bleaching activities to B. campestris, P. alopecuroides, E. crus-galli, and D. sanguinalis, and even bleached D. sanguinalis at the concentration of 10 mg/L. Among these target compounds, only compound 6d showed best bleaching activity. It was possible that pyrimidine group played a key role in bleaching phytotoxicity. Comparing the compounds 6d and 7d, the presence of bromine at the 4-position on the pyrazole ring had a negative effect on bleaching activity.
It could be seen from Table 2, compounds 6a-6d showed better herbicidal effect than compounds 6e-6i. The derivatives with 2,2,2-trifluoroethyl at the 1-position on pyrazole showed better inhibition effect than that of compounds substituted with the phenyl group, indicating the 2,2,2-trifluoroethyl group on the pyrazole ring played an important role in inhibition. Compounds 6d and 6h had better inhibition activities than compounds 6a-6c and 6e-6g, indicating that the bulkiness of fused heterocyclic substitute at pyrazole ring might be attributable to the decreased of herbicidal activity. Comparing the activities of compounds 6 and compounds 7, the electron-withdrawing bromine group at C-4 had no beneficial effect on activity.

Growth Inhibition of Weed Roots and Shoots
The herbicidal activities of the target compounds were determined with Brassica campestris L.  Table 2. All compounds showed inhibitory effect on the roots growth of B. campestris, A. retroflexus, P. oleracea, and D. sanguinalis and the shoots growth of P. alopecuroides and E. crus-galli. Compounds 6d and 7d showed excellent inhibition effect against all tested dicotyledonous and monocotyledonous plants at 100 mg/L. Compound 6d exhibited excellent bleaching activities to B. campestris, P. alopecuroides, E. crus-galli, and D. sanguinalis, and even bleached D. sanguinalis at the concentration of 10 mg/L. Among these target compounds, only compound 6d showed best bleaching activity. It was possible that pyrimidine group played a key role in bleaching phytotoxicity. Comparing the compounds 6d and 7d, the presence of bromine at the 4-position on the pyrazole ring had a negative effect on bleaching activity.
It could be seen from Table 2, compounds 6a-6d showed better herbicidal effect than compounds 6e-6i. The derivatives with 2,2,2-trifluoroethyl at the 1-position on pyrazole showed better inhibition effect than that of compounds substituted with the phenyl group, indicating the 2,2,2-trifluoroethyl group on the pyrazole ring played an important role in inhibition. Compounds 6d and 6h had better inhibition activities than compounds 6a-6c and 6e-6g, indicating that the bulkiness of fused heterocyclic substitute at pyrazole ring might be attributable to the decreased of herbicidal activity. Comparing the activities of compounds 6 and compounds 7, the electron-withdrawing bromine group at C-4 had no beneficial effect on activity. 6c Molecules 2015, 20, page-page 3

Growth Inhibition of Weed Roots and Shoots
The herbicidal activities of the target compounds were determined with Brassica campestris L.  Table 2. All compounds showed inhibitory effect on the roots growth of B. campestris, A. retroflexus, P. oleracea, and D. sanguinalis and the shoots growth of P. alopecuroides and E. crus-galli. Compounds 6d and 7d showed excellent inhibition effect against all tested dicotyledonous and monocotyledonous plants at 100 mg/L. Compound 6d exhibited excellent bleaching activities to B. campestris, P. alopecuroides, E. crus-galli, and D. sanguinalis, and even bleached D. sanguinalis at the concentration of 10 mg/L. Among these target compounds, only compound 6d showed best bleaching activity. It was possible that pyrimidine group played a key role in bleaching phytotoxicity. Comparing the compounds 6d and 7d, the presence of bromine at the 4-position on the pyrazole ring had a negative effect on bleaching activity.
It could be seen from Table 2, compounds 6a-6d showed better herbicidal effect than compounds 6e-6i. The derivatives with 2,2,2-trifluoroethyl at the 1-position on pyrazole showed better inhibition effect than that of compounds substituted with the phenyl group, indicating the 2,2,2-trifluoroethyl group on the pyrazole ring played an important role in inhibition. Compounds 6d and 6h had better inhibition activities than compounds 6a-6c and 6e-6g, indicating that the bulkiness of fused heterocyclic substitute at pyrazole ring might be attributable to the decreased of herbicidal activity. Comparing the activities of compounds 6 and compounds 7, the electron-withdrawing bromine group at C-4 had no beneficial effect on activity.

Growth Inhibition of Weed Roots and Shoots
The herbicidal activities of the target compounds were determined with Brassica campestris L.  Table 2. All compounds showed inhibitory effect on the roots growth of B. campestris, A. retroflexus, P. oleracea, and D. sanguinalis and the shoots growth of P. alopecuroides and E. crus-galli. Compounds 6d and 7d showed excellent inhibition effect against all tested dicotyledonous and monocotyledonous plants at 100 mg/L. Compound 6d exhibited excellent bleaching activities to B. campestris, P. alopecuroides, E. crus-galli, and D. sanguinalis, and even bleached D. sanguinalis at the concentration of 10 mg/L. Among these target compounds, only compound 6d showed best bleaching activity. It was possible that pyrimidine group played a key role in bleaching phytotoxicity. Comparing the compounds 6d and 7d, the presence of bromine at the 4-position on the pyrazole ring had a negative effect on bleaching activity.
It could be seen from Table 2, compounds 6a-6d showed better herbicidal effect than compounds 6e-6i. The derivatives with 2,2,2-trifluoroethyl at the 1-position on pyrazole showed better inhibition effect than that of compounds substituted with the phenyl group, indicating the 2,2,2-trifluoroethyl group on the pyrazole ring played an important role in inhibition. Compounds 6d and 6h had better inhibition activities than compounds 6a-6c and 6e-6g, indicating that the bulkiness of fused heterocyclic substitute at pyrazole ring might be attributable to the decreased of herbicidal activity. Comparing the activities of compounds 6 and compounds 7, the electron-withdrawing bromine group at C-4 had no beneficial effect on activity.

Growth Inhibition of Weed Roots and Shoots
The herbicidal activities of the target compounds were determined with Brassica campestris L.  Table 2. All compounds showed inhibitory effect on the roots growth of B. campestris, A. retroflexus, P. oleracea, and D. sanguinalis and the shoots growth of P. alopecuroides and E. crus-galli. Compounds 6d and 7d showed excellent inhibition effect against all tested dicotyledonous and monocotyledonous plants at 100 mg/L. Compound 6d exhibited excellent bleaching activities to B. campestris, P. alopecuroides, E. crus-galli, and D. sanguinalis, and even bleached D. sanguinalis at the concentration of 10 mg/L. Among these target compounds, only compound 6d showed best bleaching activity. It was possible that pyrimidine group played a key role in bleaching phytotoxicity. Comparing the compounds 6d and 7d, the presence of bromine at the 4-position on the pyrazole ring had a negative effect on bleaching activity.
It could be seen from Table 2, compounds 6a-6d showed better herbicidal effect than compounds 6e-6i. The derivatives with 2,2,2-trifluoroethyl at the 1-position on pyrazole showed better inhibition effect than that of compounds substituted with the phenyl group, indicating the 2,2,2-trifluoroethyl group on the pyrazole ring played an important role in inhibition. Compounds 6d and 6h had better inhibition activities than compounds 6a-6c and 6e-6g, indicating that the bulkiness of fused heterocyclic substitute at pyrazole ring might be attributable to the decreased of herbicidal activity. Comparing the activities of compounds 6 and compounds 7, the electron-withdrawing bromine group at C-4 had no beneficial effect on activity.

Growth Inhibition of Weed Roots and Shoots
The herbicidal activities of the target compounds were determined with Brassica campestris L.  Table 2. All compounds showed inhibitory effect on the roots growth of B. campestris, A. retroflexus, P. oleracea, and D. sanguinalis and the shoots growth of P. alopecuroides and E. crus-galli. Compounds 6d and 7d showed excellent inhibition effect against all tested dicotyledonous and monocotyledonous plants at 100 mg/L. Compound 6d exhibited excellent bleaching activities to B. campestris, P. alopecuroides, E. crus-galli, and D. sanguinalis, and even bleached D. sanguinalis at the concentration of 10 mg/L. Among these target compounds, only compound 6d showed best bleaching activity. It was possible that pyrimidine group played a key role in bleaching phytotoxicity. Comparing the compounds 6d and 7d, the presence of bromine at the 4-position on the pyrazole ring had a negative effect on bleaching activity.
It could be seen from Table 2, compounds 6a-6d showed better herbicidal effect than compounds 6e-6i. The derivatives with 2,2,2-trifluoroethyl at the 1-position on pyrazole showed better inhibition effect than that of compounds substituted with the phenyl group, indicating the 2,2,2-trifluoroethyl group on the pyrazole ring played an important role in inhibition. Compounds 6d and 6h had better inhibition activities than compounds 6a-6c and 6e-6g, indicating that the bulkiness of fused heterocyclic substitute at pyrazole ring might be attributable to the decreased of herbicidal activity. Comparing the activities of compounds 6 and compounds 7, the electron-withdrawing bromine group at C-4 had no beneficial effect on activity.

Growth Inhibition of Weed Roots and Shoots
The herbicidal activities of the target compounds were determined with Brassica campestris L.  Table 2. All compounds showed inhibitory effect on the roots growth of B. campestris, A. retroflexus, P. oleracea, and D. sanguinalis and the shoots growth of P. alopecuroides and E. crus-galli. Compounds 6d and 7d showed excellent inhibition effect against all tested dicotyledonous and monocotyledonous plants at 100 mg/L. Compound 6d exhibited excellent bleaching activities to B. campestris, P. alopecuroides, E. crus-galli, and D. sanguinalis, and even bleached D. sanguinalis at the concentration of 10 mg/L. Among these target compounds, only compound 6d showed best bleaching activity. It was possible that pyrimidine group played a key role in bleaching phytotoxicity. Comparing the compounds 6d and 7d, the presence of bromine at the 4-position on the pyrazole ring had a negative effect on bleaching activity.
It could be seen from Table 2, compounds 6a-6d showed better herbicidal effect than compounds 6e-6i. The derivatives with 2,2,2-trifluoroethyl at the 1-position on pyrazole showed better inhibition effect than that of compounds substituted with the phenyl group, indicating the 2,2,2-trifluoroethyl group on the pyrazole ring played an important role in inhibition. Compounds 6d and 6h had better inhibition activities than compounds 6a-6c and 6e-6g, indicating that the bulkiness of fused heterocyclic substitute at pyrazole ring might be attributable to the decreased of herbicidal activity. Comparing the activities of compounds 6 and compounds 7, the electron-withdrawing bromine group at C-4 had no beneficial effect on activity.

Growth Inhibition of Weed Roots and Shoots
The herbicidal activities of the target compounds were determined with Brassica campestris L.  Table 2. All compounds showed inhibitory effect on the roots growth of B. campestris, A. retroflexus, P. oleracea, and D. sanguinalis and the shoots growth of P. alopecuroides and E. crus-galli. Compounds 6d and 7d showed excellent inhibition effect against all tested dicotyledonous and monocotyledonous plants at 100 mg/L. Compound 6d exhibited excellent bleaching activities to B. campestris, P. alopecuroides, E. crus-galli, and D. sanguinalis, and even bleached D. sanguinalis at the concentration of 10 mg/L. Among these target compounds, only compound 6d showed best bleaching activity. It was possible that pyrimidine group played a key role in bleaching phytotoxicity. Comparing the compounds 6d and 7d, the presence of bromine at the 4-position on the pyrazole ring had a negative effect on bleaching activity.
It could be seen from Table 2, compounds 6a-6d showed better herbicidal effect than compounds 6e-6i. The derivatives with 2,2,2-trifluoroethyl at the 1-position on pyrazole showed better inhibition effect than that of compounds substituted with the phenyl group, indicating the 2,2,2-trifluoroethyl group on the pyrazole ring played an important role in inhibition. Compounds 6d and 6h had better inhibition activities than compounds 6a-6c and 6e-6g, indicating that the bulkiness of fused heterocyclic substitute at pyrazole ring might be attributable to the decreased of herbicidal activity. Comparing the activities of compounds 6 and compounds 7, the electron-withdrawing bromine group at C-4 had no beneficial effect on activity.

Growth Inhibition of Weed Roots and Shoots
The herbicidal activities of the target compounds were determined with Brassica campestris L.  Table 2. All compounds showed inhibitory effect on the roots growth of B. campestris, A. retroflexus, P. oleracea, and D. sanguinalis and the shoots growth of P. alopecuroides and E. crus-galli. Compounds 6d and 7d showed excellent inhibition effect against all tested dicotyledonous and monocotyledonous plants at 100 mg/L. Compound 6d exhibited excellent bleaching activities to B. campestris, P. alopecuroides, E. crus-galli, and D. sanguinalis, and even bleached D. sanguinalis at the concentration of 10 mg/L. Among these target compounds, only compound 6d showed best bleaching activity. It was possible that pyrimidine group played a key role in bleaching phytotoxicity. Comparing the compounds 6d and 7d, the presence of bromine at the 4-position on the pyrazole ring had a negative effect on bleaching activity.
It could be seen from Table 2, compounds 6a-6d showed better herbicidal effect than compounds 6e-6i. The derivatives with 2,2,2-trifluoroethyl at the 1-position on pyrazole showed better inhibition effect than that of compounds substituted with the phenyl group, indicating the 2,2,2-trifluoroethyl group on the pyrazole ring played an important role in inhibition. Compounds 6d and 6h had better inhibition activities than compounds 6a-6c and 6e-6g, indicating that the bulkiness of fused heterocyclic substitute at pyrazole ring might be attributable to the decreased of herbicidal activity. Comparing the activities of compounds 6 and compounds 7, the electron-withdrawing bromine group at C-4 had no beneficial effect on activity.

Growth Inhibition of Weed Roots and Shoots
The herbicidal activities of the target compounds were determined with Brassica campestris L.  Table 2. All compounds showed inhibitory effect on the roots growth of B. campestris, A. retroflexus, P. oleracea, and D. sanguinalis and the shoots growth of P. alopecuroides and E. crus-galli. Compounds 6d and 7d showed excellent inhibition effect against all tested dicotyledonous and monocotyledonous plants at 100 mg/L. Compound 6d exhibited excellent bleaching activities to B. campestris, P. alopecuroides, E. crus-galli, and D. sanguinalis, and even bleached D. sanguinalis at the concentration of 10 mg/L. Among these target compounds, only compound 6d showed best bleaching activity. It was possible that pyrimidine group played a key role in bleaching phytotoxicity. Comparing the compounds 6d and 7d, the presence of bromine at the 4-position on the pyrazole ring had a negative effect on bleaching activity.
It could be seen from Table 2, compounds 6a-6d showed better herbicidal effect than compounds 6e-6i. The derivatives with 2,2,2-trifluoroethyl at the 1-position on pyrazole showed better inhibition effect than that of compounds substituted with the phenyl group, indicating the 2,2,2-trifluoroethyl group on the pyrazole ring played an important role in inhibition. Compounds 6d and 6h had better inhibition activities than compounds 6a-6c and 6e-6g, indicating that the bulkiness of fused heterocyclic substitute at pyrazole ring might be attributable to the decreased of herbicidal activity. Comparing the activities of compounds 6 and compounds 7, the electron-withdrawing bromine group at C-4 had no beneficial effect on activity.

Growth Inhibition of Weed Roots and Shoots
The herbicidal activities of the target compounds were determined with Brassica campestris L.  Table 2. All compounds showed inhibitory effect on the roots growth of B. campestris, A. retroflexus, P. oleracea, and D. sanguinalis and the shoots growth of P. alopecuroides and E. crus-galli. Compounds 6d and 7d showed excellent inhibition effect against all tested dicotyledonous and monocotyledonous plants at 100 mg/L. Compound 6d exhibited excellent bleaching activities to B. campestris, P. alopecuroides, E. crus-galli, and D. sanguinalis, and even bleached D. sanguinalis at the concentration of 10 mg/L. Among these target compounds, only compound 6d showed best bleaching activity. It was possible that pyrimidine group played a key role in bleaching phytotoxicity. Comparing the compounds 6d and 7d, the presence of bromine at the 4-position on the pyrazole ring had a negative effect on bleaching activity.
It could be seen from Table 2, compounds 6a-6d showed better herbicidal effect than compounds 6e-6i. The derivatives with 2,2,2-trifluoroethyl at the 1-position on pyrazole showed better inhibition effect than that of compounds substituted with the phenyl group, indicating the 2,2,2-trifluoroethyl group on the pyrazole ring played an important role in inhibition. Compounds 6d and 6h had better inhibition activities than compounds 6a-6c and 6e-6g, indicating that the bulkiness of fused heterocyclic substitute at pyrazole ring might be attributable to the decreased of herbicidal activity. Comparing the activities of compounds 6 and compounds 7, the electron-withdrawing bromine group at C-4 had no beneficial effect on activity.

Growth Inhibition of Weed Roots and Shoots
The herbicidal activities of the target compounds were determined with Brassica campestris L.  Table 2. All compounds showed inhibitory effect on the roots growth of B. campestris, A. retroflexus, P. oleracea, and D. sanguinalis and the shoots growth of P. alopecuroides and E. crus-galli. Compounds 6d and 7d showed excellent inhibition effect against all tested dicotyledonous and monocotyledonous plants at 100 mg/L. Compound 6d exhibited excellent bleaching activities to B. campestris, P. alopecuroides, E. crus-galli, and D. sanguinalis, and even bleached D. sanguinalis at the concentration of 10 mg/L. Among these target compounds, only compound 6d showed best bleaching activity. It was possible that pyrimidine group played a key role in bleaching phytotoxicity. Comparing the compounds 6d and 7d, the presence of bromine at the 4-position on the pyrazole ring had a negative effect on bleaching activity.
It could be seen from Table 2, compounds 6a-6d showed better herbicidal effect than compounds 6e-6i. The derivatives with 2,2,2-trifluoroethyl at the 1-position on pyrazole showed better inhibition effect than that of compounds substituted with the phenyl group, indicating the 2,2,2-trifluoroethyl group on the pyrazole ring played an important role in inhibition. Compounds 6d and 6h had better inhibition activities than compounds 6a-6c and 6e-6g, indicating that the bulkiness of fused heterocyclic substitute at pyrazole ring might be attributable to the decreased of herbicidal activity. Comparing the activities of compounds 6 and compounds 7, the electron-withdrawing bromine group at C-4 had no beneficial effect on activity.

Growth Inhibition of Weed Roots and Shoots
The herbicidal activities of the target compounds were determined with Brassica campestris L.  Table 2. All compounds showed inhibitory effect on the roots growth of B. campestris, A. retroflexus, P. oleracea, and D. sanguinalis and the shoots growth of P. alopecuroides and E. crus-galli. Compounds 6d and 7d showed excellent inhibition effect against all tested dicotyledonous and monocotyledonous plants at 100 mg/L. Compound 6d exhibited excellent bleaching activities to B. campestris, P. alopecuroides, E. crus-galli, and D. sanguinalis, and even bleached D. sanguinalis at the concentration of 10 mg/L. Among these target compounds, only compound 6d showed best bleaching activity. It was possible that pyrimidine group played a key role in bleaching phytotoxicity. Comparing the compounds 6d and 7d, the presence of bromine at the 4-position on the pyrazole ring had a negative effect on bleaching activity.
It could be seen from Table 2, compounds 6a-6d showed better herbicidal effect than compounds 6e-6i. The derivatives with 2,2,2-trifluoroethyl at the 1-position on pyrazole showed better inhibition effect than that of compounds substituted with the phenyl group, indicating the 2,2,2-trifluoroethyl group on the pyrazole ring played an important role in inhibition. Compounds 6d and 6h had better inhibition activities than compounds 6a-6c and 6e-6g, indicating that the bulkiness of fused heterocyclic substitute at pyrazole ring might be attributable to the decreased of herbicidal activity. Comparing the activities of compounds 6 and compounds 7, the electron-withdrawing bromine group at C-4 had no beneficial effect on activity.

Screening in Greenhouse Conditions
Seven target compounds 6a-6d, 7a, 7b, 7d with higher inhibitory effects on the growth of tested plants in preliminary herbicidal bioassays were further screened in greenhouse conditions. From the biological assay results in Table 3, each compound showed herbicidal activities in postemergence treatment at the dosage of 750 g a. i. ha´1, especially monocotyledonous weed D. sanguinalis was most sensitive to compound 6d. It was also found that when the 5-position of the pyrazole was modified by a pyrimidine group, compound 6d had better inhibitory effect on D. sanguinalis than other target compounds, the inhibition rate of the fresh weights reaching 82%. The bioassay results indicated that the substituted group at the 5-position of the pyrazole ring played an important role for herbicidal activity. The 4-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]-6-(prop-2-yn-1-yloxy)pyrimidine reported in our previous work [30] was very close to compound 6d, structurally, but it showed less herbicidal activity than compound 6d in greenhouse conditions, the difference between these two structures lay in that the pyrimidine was substituted at the 1-position of the pyrazole ring [30] and at the 5-position of the pyrazole ring in this paper, we might conclude that the substituted position on the pyrazole ring also played an important role for herbicidal activity.

Inhibitory Effect of the Compound 6d on Chlorophyll of Weed
In order to evaluate the bleaching activities of compound 6d, the changes in chlorophyll contents of treated seedlings were tested. The IC 50 value of compound 6d and positive control (diflufenican) were shown in Table 4. Compound 6d inhibited the synthesis of chlorophyll, and showed the same inhibition activity as commercial standard diflufenican against B. campestris. Gramineous weed P. alopecuroides, E. crus-galli, and D. sanguinalis were slightly sensitive to diflufenican than compound 6d and compound 6d deserved further studies on structure optimization and biological efficacy as the bleaching herbicidal inhibitor.

Analysis and Instruments
Elemental analyses (C, H, N) were performed with a Vario EL III elemental analyzer (Elementar Analysensysteme Gmbh, Hanau, Germany) at the Institute of Chemistry, Chinese Academy of Sciences. Infrared spectra were taken on a Nicolet IR 200 FT-IR instrument (Thermo Scientific, Waltham, MA, USA). 1 H-NMR spectra and 13 C-NMR were obtained at 400 MHz using a Bruker AVANCE III 400 spectrometer (Bruker Corp., Billerica, MA, USA) in CDCl 3 solution with TMS as an internal standard. Mass spectra (MS) were recorded in a Agilent 6110 spectrometer (Agilent, Santa Clara, CA, USA). Melting points were measured on a SGW X-4 melting point apparatus (Shanghai Precision Scientific Instrument Co., Ltd., Shanghai, China) and are uncorrected. All reagents and solvents were obtained from commercial suppliers.

Synthesis of Compounds 6a-6i
Compound 5a (1.5 mmol) and powdered potassium carbonate (2.25 mmol) were added into dimethylsulfoxide (20 mL). 2, 6-Dichlorobenzoxazole (1.5 mmol) was added to the solution and the mixture was stirred at room temperature for 3 h. The mixture was diluted with water (20 mL) and extracted with diethyl ether (30 mLˆ2). The extract was washed with water and saturated brine, dried over anhydrous sodium sulfate, the filtrate was concentrated in vacuo. The residue was further purified by silica gel column chromatography (ethyl acetate/petroleum ether: 1/10 as the eluent) to give compound 6a as a white solid. Compounds 6b-i were synthesized using the same procedures.

Inhibitory Effect of the Target Compounds on the Growth of Weed Roots and Shoots
Solutions of 1 g/L and 10 g/L of the tested compounds in DMF were prepared. Agar powder (5 g) was put into boiling distilled water (1 L) until it dissolved, and then cooled down to 40-50˝C. The solution (0.2 mL) containing testing compound and melting agar (19.8 mL) was mixed, and this mixture was added to a 120 mL cup with 4.5 cm diameter. The agar plate without test compound was used as an untreated control. The 15 seeds of B. campestris, A. retroflexus, P. oleracea, P. alopecuroides, E. crus-galli, and D. sanguinalis were put on the surface of the agar plate. These cups were covered with glass lids, and the cultivation conditions were kept at 25˘1˝C, 50%-55% relative humidity, and 12 h in the light and 12 h in the dark alternating for seven days. The experiments were conducted in three replicates. Seven days later, the roots lengths of B. campestris, A. retroflexus, P. oleracea, and D. sanguinalis and the shoots lengths of P. alopecuroides, and E. crus-galli were measured. The growth inhibitory rate related to untreated control was determined.

Treatment in Greenhouse Conditions
Twenty seeds of test plants were planted (0.6 cm depth) in plastic boxes (9 cm diameter) containing sandy soil. The plastic boxes were placed at 22-25˝C in a greenhouse. The experiments were conducted in three replicates. The seedlings (one leaf and one stem) of the dicotyledonous weed and the seedlings (two leaf and one stem) of the monocotyledonous weed were sprayed with the test compounds at the concentration of 750 g a. i. ha´1. The emulsions of tested compounds were prepared by dissolving them in DMF with the addition proper water contained 0.1% Triton X-100. The fresh weights were determined 15 days later, and the percentage inhibition relative to the water-sprayed controls was calculated.

Inhibitory Effect of the Compound 6d on Chlorophyll of Weeds
To evaluate the bleaching activity of compound 6d, the changes in chlorophyll contents of treated seedlings were evaluated by Arnon's method [34] as modified by Lichtenthaler [35]. Bleached seedlings of B. campestris, P. alopecuroides, E. crus-galli, and D. sanguinalis with different concentrations were obtained by the method described above. Chlorophyll a and b were extracted from 50 mg of leaf tissue per treatment in 8 mL of 80% acetone in water for 24 h. The absorbance was measured at 663 nm and 646 nm, respectively. The contents of chlorophyll a and b in leaf tissue were finally calculated by the following formula: for chlorophyll a, Ca = 12.21A 663´2 .81A 646 ; for chlorophyll b, C b = 20.13A 646´5 .03A 663 . The concentration causing 50% inhibition (IC 50 ) of in vitro activity for the selected compounds were obtained by analyzing inhibition curves of the activity values (%) versus the logarithm of inhibitory concentration. Diflufenican was selected as the positive control. At least five doses in the inhibitory range were considered, and three replicates were performed under the same conditions.

Conclusions
In conclusion, the design, synthesis, and structure-activity relationships of a series of pyrazoyl derivatives have been described. Some compounds displayed an efficient bleaching effect and herbicidal activities against monocotyledonous and dicotyledonous weeds. The herbicidal tests showed that when the 5-position of the pyrazole ring was substituted by heterocycle, the corresponding compounds presented herbicidal activities, especially compound 6d possessed good herbicidal activity against D. sanguinalis at the dosage of 750 g a. i. ha´1.