Industrial Syntheses of Active Compounds

The initial laboratory-scale syntheses of kresoxim-methyl started from o-bro-motoluene, which was first brominated in the side-chain with NBS. Substitution with o-cresol leads to the benzyl phenyl ether. The carbon skeleton of the final product resulted from a Grignard reaction with methyl 1-imidazolyloxalate. Reaction with methoxyamine gave a mixture of ( )- and (Z)-isomers, which can be isomerised, either with the aid of acids or photochemically. Fortunately, the biologically active isomer is also the thermodynamically more stable one. [57, 58] 

For large-scale production, this synthesis is not suitable on account of the cost involved in the side-chain bromination and the Grignard reaction. In addition, the yields are unsatisfactory. 

Starting material for the industrial synthesis is phthalide, which may be obtained by hydrogenation of phthalic anhydride. Reaction with o-cresol leads to the corresponding carboxyUc acid, which is converted via its acid chloride into the acyl cyanide. A Pinner reaction and treatment with methoxyamine finally give kresoxim-methyl. [59] 

Azoxystrobin is built up in an elegant and convergent synthesis from three building blocks 3-(methoxymethylene)-benzo-2(3ff)-furanone, 4,6-dichloropyrim-idine and 2-hydroxybenzonitrile. [61,62] 

The strobUurin class of fungicides is derived from a secondary metabolite 

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