Isoxaflutole: the background to its discovery and the basis of its herbicidal properties

This paper reviews the discovery of isoxaflutole (IFT), focusing on the che mical and physico-chemical properties which contribute to the herbicidal be haviour of this new herbicide. IFT (5-cyclopropyl-1,2-isoxazol-4-yl alpha a lpha alpha -trifluoro-2-mesyl-p-tolyl ketone) is a novel herbicide for pre- emergence control of a wide range of important broadleaf and grass weeds in corn and sugarcane. The first benzoyl isoxazole lead was synthesised in 1989 and IFT in 1990, a nd the herbicidal potential of the latter was identified in 1991. The decis ion to develop the molecule was taken after two years of field testing in N orth America. The biochemical target of IFT is 4-hydroxyphenylpyruvate diox ygenase (HPPD), inhibition of which leads to a characteristic bleaching of susceptible species. The inhibitor of HPPD is the diketonitrile derivative of IFT formed from opening of the isoxazole ring. The diketonitrile (DKN) i s formed rapidly in plants following root and shoot uptake. The DKN is both xylem and phloem mobile leading to high systemicity. IFT also undergoes co nversion to the DKN in the soil. The soil half-life of IFT ranges from 12h to 3 days under laboratory conditions and is dependent on several factors s uch as soil type, pH and moisture. The log P of IFT is 2.19 and the water s olubility is 6.2 mg litre(-1), whereas the corresponding values for the DKN are 0.4 and 326mg litre(-1), respectively. These properties restrict the m obility of IET, which is retained at the soil surface where it can be taken up by surface-germinating weed seeds. The DKN, which has a laboratory soil half-life of 20-30 days, is more mobile and is taken up by the roots. In a ddition to influencing the soil behaviour of IFT and DKN, the greater lipop hilicity of IET leads to greater uptake by seed, shoot and root tissues. In both plants and soil, the DKN is converted to the herbicidally inactive be nzoic acid. This degradation is more rapid in maize than in susceptible wee d species and this contributes to the mechanism of selectivity, together wi th the greater sowing depth of the crop. (C) 2001 Society of Chemical Indus try.