Bifenazate

Bifenazate is the only member of this class. It is an acaricide with contact activity for controlling a variety of phytophagous mites on all types of ornamental plants. Its oral LD50 in rats is >5000 mg/kg. 

Serendipity in the traditional screening approaches is, up to now, one of the main resources for discovering acaricides with novel biochemical and physiological targets [2]. Based on the discovery that fungicidal phenylhydrazide compounds had some acaricidal activity, a synthesis program was initiated in Crompton Co. Research in 1990. From among several hundred carbazate derivatives synthesized and evaluated for acaricidal activity the methoxy-biphenyl-substituted carbazate (bifenazate. Fig. 30.2.1, Table 30.2.1) was selected for development [3]. 

In the USA, bifenazate was first approved and registered as a reduced-risk acari-cide for the ornamental market (1999) and soon thereafter for crops such as apples, pears, peaches, plums, grapes, cotton, strawberries and hops. Bifenazate is now under worldwide development for the selective control of spider mites acting against eggs, larvae, nymphs and mites under the trade names Floramite , Acramite , and Mitekohne . 

In Europe, bifenazate received a unanimous positive vote by the EU legislative meeting for Annex I inclusion under Council Directive 91/414/EEC in 2005 [4]. Preliminary results from studies on the mode of action of bifenazate in insects indicate that, at high concentrations, bifenazate acts on the postsynaptic GABA receptor in the insect nervous system. This mode of action has not yet been con-... 

The discovery, synthesis, structure-activity relationship and biology of this new class of carbazate acaricides and bifenazate is described in this chapter. 

Bifenazate belongs to the carbazate class, a new type of acaricide chemistry defined by the general formula shown in Fig. 30.2.2 (Table 30.2.2) [5-7]. 

After the discovery that ortho-biphenyl substituted hydrazide compounds [5] had acaricidal activity in the pesticide discovery screen (Table 30.2.3) several hundred - structurally diverse - biphenyl-substituted carbazate analogs were synthesized, and, in an optimization process using a bioassay with the two spotted spider mite (Tetranychus urticae Koch), isopropyl-2-(4-methoxy[l,l -biphenyl]-3-yl) hydrazine carboxylate (bifenazate) [3, 8] was identified as the most advantageous compound. 

Compound 1 was made from 4-hydroxy biphenyl, which was also an intermediate for an alternate synthesis of bifenazate and the hydroxy-analogs [11]. 

Table 30.2.4 LC50S of bifenazate against different development stages of T. urticae.

Bifenazate shows a broad activity spectrum on phytophagous mites such as Tetra-nychus spp. Eutetranychus spp., Oligonychus spp. and Panonychus spp. Compared with propargite the compound is 30-100-fold more active against adults, nymphs and larvae, e.g., of Tetranychus urticae (in cowpeas) [3] (Table 30.2.4). 

The activity of bifenazate remains nearly constant over the temperature range 15-35 °C, allowing its use under a wide range of conditions. 

The favorable ecobiological profile of bifenazate is remarkable [4, 13-15]. The compound does not affect beneficial insects, neither pollinating insects nor beneficial predatory mites nor wasps (Table 30.2.5). 

Table 30.2.5 Ecobiological properties of bifenazate against beneficial insects.

Neuroactive Miticides - Bifenazate 1109 Table 30.2.6 Registration status of bifenazate (status 2004). 

Bifenazate is characterized as a compound with very low toxicity to beneficial arthropods at recommended application rates. Especially in uses under IPM situations and in combination with predatory mites the compound is very advantageous. 

These ecobiological and also the toxicological properties, the rapid soil dissipation, the decreased application frequency and improved efficacy compared with existing compounds of bifenazate, together with the first introduction for use in ornamentals, led to the introduction of Floramite in the United States under the reduced risk status (Table 30.2.6) [3, 17, 18]. 

With its carbazate chemistry, bifenazate, a structurally new mitidde with favorable biological properties, has been identified and brought to the crop protection market. 

I wish to thank the many Chemtura employees who had contributed to the success of bifenazate. 

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