Herbicidal Activity of IC

Eel white eclipta Amr common amaranth Xan Siberian cocklebur Car hairy bittercress For purslane Med clover Ech barnyard grass Dig crab grass 

0-Dialkyl (-(substituted phenoxyacetoxy)alkylphosphonates lA-IF including 103 compounds as potential PDHc inhibitors were conveniently synthesized by the condensation of 1-hydroxyalkylphosphonates M2 and substituted phenoxyacetyl chlorides M5 in the presence of base under mild reaction conditions. 

IC-22 showed much higher herbicidal activity than that of those repoted plant PDHc inhibitors, acylphosphinates and acylphosphonates[l, 27]. Those compounds exhibited 80-100 % inhibition against weeds at 2.8 kg/ha but at this rate they had shown unacceptable phytotoxicity to the crops. Compared with acylphosphinates and acylphosphonates, IC-22 exhibited promising herbicidal activity and selectivity for development as a selective post-emergence herbicide which may be used for broadleaf weed control in monocot crop fields. 

Through the optimization of lead strucmres lA, (9,(9-dimethyl l-(2,4-dichloro-phenoxyacetoxy)ethylphosphonate (IC-22) was found to be a potential herbicide [22], with an effective inhibition against plant PDHc El (see Chap. 7). 

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In this chapter, we describe the synthesis, herbicidal activity and structure-activity relationship (SAR) of alkylphosphonates lA-IK. Herbicidal activity of IC-22 and IG-21 will be discussed in detail. 

The herbicidal activity of IC-IF including lA and IB were evaluated at different rates in the greenhouse. Substituted phenoxyacetic acid as an structure unit of auxin-type herbicide was contained in the stracture of lA-IF, therefore an auxin-type herbicide 2,4-D was used as a positive control for the test in the greenhouse. Considering 2,4-D against broadleaved weeds for post-emergence at a recommended rate of 0.2-2.0 kg ai/ha, a preliminary bioassay was first carried out at... 

Thirty-four of IC were prepared to test their herbicidal activity. Further optimization was focused on the substituents (Scheme 2.13). The herbicidal activity of IC is listed in Tables 2.19 and 2.20. 

Table 2.32 Herbicidal activity of IC-22 for post-emergence application ...

Table 7.7 Inhibitory potency against PDHc and herbicidal activity of IC-22, IG-21, IIB-2, and...

Phenyl hydrazidoyl chlorides, la and lb, had been studied extensively by Upjohn Company as insecticides (S) and herbicides (fi), but, at the time nothing had been reported about the biological activity of Ic. 

According to the results of SAR for IB series, structure IB was further optimized to produce four series of novel 0,0-dimethyl 1-(substituted phenoxyacetoxy)al-kylphosphonates IC-IF (Scheme 1.24). In this IC-IF series. Me group as R, R and H as R" were kept in structure lo, further modification of substituents R and Yn was carried out to validate our speculation that such modification would increase the herbicidal activity. When Me as R and R different substituents R and Y were introduced into parent structure lo to produce IC-IF series including 63 compounds. Pre-emergence and post-emergence herbicidal activity of compounds IC-IF were systematically evaluated at different rates in the greenhouse. 

Bioisosterism is an important aspect in designing bioactive compounds. For example, phosphinate unit is often used to replace the phosphonate unit to obtain a more active compound. Bailie et al. s SAR analyses showed that the replacement of methoxyl in acylphosphonate (1-1) by methyl to produce acylphosphinate (1-2), would significantly improve the inhibitory potency and herbicidal activity. Therefore, we were interested in examining herbicidal activity of the alkylphosphinates. On the basis of (9,(9-dimethyl 1-(substituted phenoxyacetoxy)alkylphosphonates IC, several novel series of (9-methyl [1-(substituted phenoxyacetoxy)alkyl]meth-ylphosphinates lllA-lllG including 54 compounds were designed and synthesized (Scheme 1.29). 

Table 2.20 Structure and post-emergence herbicidal activity of 0,0-dimethyl 1-(substituted phenoxyacetoxy)alkylphosphonates IC ...

Herbicidal Activity of 0,0-Dimethyl l-(Substituted Phenoxyacetoxy)Alkylphosphonates IC... 

The bioassays of IC showed that herbicidal activity could be greatly affected by different substituents Y on the phenoxy-benzene ring. However, the difference in the moiety including H, Me, Et, n-Pr and n-Bu seems to have no significant change on herbicidal activity at 1.5 kg ai/ha. On the basis of structure IC, the stmcture of R was changed to CCI3 to form a series of ID (Scheme 2.14), further modification was only focused on substituents Y . Fourteen of ID were prepared and their herbicidal activity was tested. The herbicidal activity of ID is listed in Tables 2.21 and 2.22. 

In order to confirm the pre-emergence herbicidal activity of 1-(substituted phenoxyacetoxy)alkylphosphonates, seven compounds were chosen for further herbicide activity assay at a lower rate for pre-emergence herbicidal activity. As shown in Table 2.27, they displayed very poor herbicidal activity against tested plants for pre-emergence application except IA-4 and IC-2 with 48-53 % inhibitory potency against dicotyledonous plants at 450 g ai/ha. All tested compounds had no pre-emergence herbicidal activity against tested plants at 150 or 75 g ai/ha, irrespective of difference in structure. 

Table 4.14 Herbicidal activity of phosphinates IIIC and phosphonates IC, IE, and IF ... 

SAR analysis showed that substitutent 4-F as Yj, on the phenoxy-benzene ring was much beneficial to the post-emergence herbicidal activity of alkylphosphinates HIE. However substitutent 4-F as Yj, was not beneficial to the post-emergence herbicidal activity of alkylphosphonates IC. For both alkylphosphinates HIE and alkylphosphonates IC, the introduction of 2-F or 2,4-F2 as Yj, could result in a sharp decrease in post-emergence herbicidal activity. 

As seen from Table 5.15, IVC-I6 and IVC-18 only had 80-90 % inhibition against leaf mustard, but weaker herbicidal effect against common amaranth and white eclipta at 37.5 g ai/ha. Other compounds IVC-I5 and IVC-I9 showed much weaker herbicidal effect against tested broad-leaved weeds at 37.5 g ai/ha. The herbicidal activity of cyclic phosphonates IVC-I5, IVC-I6, IVC-18, and IVC-I9 were not comparable to clacyfos (IC-22, HW02). 

The characteristics and differences of enantiomers of these alkylphosphonates lA and IC will be examined on the basis of the study of herbicidal activity, crop safety, toxicity and environmental safety. At this stage, several optically active alkylphosphonates in the lA and IC series were tested for their enantiomeric selectivity in herbicidal activity and acute aquatic toxicity. In this section, the synthesis and herbicidal activity of optically active alkylphosphonates lA and IC are introduced. The differences of enantiomers of these alkylphosphonates lA and IC together with their racemates are discussed. 

In order to investigate enantiomeric selectivity of chiral alkylphosphonates in the lA and IC series, the herbicidal activity of several optically active alkylphosphonates as typical compounds were evaluated by a preliminary bioassay. 

Ji2 was the most significant contributor to herbicidal activity, explaining over 70% of the biological variance. Including ic and L improved the equation to over 90%. No significant correlations were found between herbicidal activity and any of the electronic parameters (a, F). 

SAR analyses indicated that herbicidal activity could be increased greatly by optimizing r R, R, R" and Yn in phosphonate lo. 0,C>-dimethyl l-(2,4-dichlorophenoxyacetoxy)ethylphosphonate IC-22 (HW02, clacyfos) was found to be the most effective compound among lA—IF series against broadleaf in postemergence application at the rate of 18.75—450 g ai/ha (see Chap. 2). IC-22 also showed much higher and practical herbicidal activity than that of acylphosphinates or acylphosphonates 1. 

All substituted alkylphosphonates lA-IJ and IVC-IVE studied or reported previously were only based on their racemic forms. Considering the importance of chirality for herbicidal active, the synthesis and the biological activities of their optical counterparts would be very important. The methods of asymmetric synthesis of both chiral 1-hydroxyphosphonates and cyclic 1-hydroxy phosphonates, and several optically active 1 -(substituted phenoxyacetoxy)alkylphosphonates were hence set up. So far, several series of optically active 1-(substituted phenoxyacetoxy) alkylphosphonates including lA, IC, IE, IF series were prepared (Scheme 1.34) and their biological activities were evaluated. Their asymmetric synthesis, enantiomeric selectivity in herbicidal activity, acute aquatic toxicity, and SAR discussion are summarized in Chap. 6. 

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