Flazasulfuron

Flazasulfuron is a sulfonylurea herbicide used for controlling the unwanted growth of grass, broad-leaved weeds and sedges. The mode of action of flazasulfuron is through the inhibition of the enzyme acetolactate synthase (ALS), which results in the inhibition of amino acid synthesis, cell division and ultimately plant growth. Flazasulfuron can be used on both pre-emergent weeds and post-emergent weeds. Growth ceases within hours of the application of the compound. Symptoms include leaf discolouration, desiccation, necrosis and ultimately plant death within 20 – 25 days of application. It is a white, water-soluble solid.

Synthesis
The synthesis of flazasulfuron begins with the one pot chlorination and chlorine/fluorine exchange of 3-picoline (1). This reaction is performed in the gas phase in a purpose built reactor where the desired product (2) is one of the components of the crude product mixture. Treatment of (2) with sodium hydrosulfide gives (3) by nucleophillic aromatic substitution. Acidic oxidation with chlorine produces the sulfonylchloride which is filtered off and added directly to chilled concentrated ammonia solution to produce 3-trifluoromethylpyridin-2-yl sulfonamide (4). Treatment with diphenylcarbonate (5) and sodium hydride gives the carbamate (6). Finally, flazasulfuron is obtained by the reaction of (6) with 4,6-dimethoxy-1-aminopyrimidine in dioxane.

An alternative strategy is to use (4) as nucleophile with the O-phenylcarbamate of 4,6-dimethoxy-1-aminopyrimidine (7) as electrophile in the presence of DBN.