Changes in the Activity and Selectivity of Herbicides by Selective Fluorine Substitution, Taking Bentranil and Classic® Analogues as Examples

Abstract

The introduction of fluorine atoms into 2-phenyl-4H-3,1-benzoxazin-4-one (bentranil) led to sweeping changes in its herbicidal properties in some cases, and 5-fluoro-2-phenyl-4H-3,1-benzoxazin-4-one ('fluorobentranil') was found to be the most active compound. It can be prepared from 2-amino-6-fluoro-benzoic acid or by direct halogen exchange of 5-chloro-2-phenyl-4H-3,1-benzoxazin-4-one. The latter reaction was investigated on a pilot scale, including a high-temperature (350 °C) potassium fluoride halogen exchange without solvent. When sulfolane was used as a solvent, a side reaction at 220 °C – partial decomposition to a diphenylether – could be prevented by addition of a small amount of a radical scavenger. Other intermediates with a pseudohalogen substitution were obtained by side-chain chlorination of suitable methylsulfanyl benzoic acid precursors and halogen exchange. 'Fluorobentranil' shows good broad-leaf activity and selectivity on rice, cereals and maize. In a second case study, the fluoro-substituted anthranilic acids mentioned above were also found to be appropriate for synthesizing herbicidal sulfonylurea (SU) compounds via Meerwein reaction of their aniline function. Methyl 2-[({[(4chloro-6-methoxy-2-pyrimidinyl)-amino]carbonyl}amino)sulfonyl]-6-fluorobenzoate is an example of a SU that is compatible with maize, whereas the unsubstituted Classic® analogue is not selective.