Chlorsulfuron synthesis

Extensive use of two more recendy developed classes of herbicides will further dramatically reduce the amount of appHed to control weeds. The sulfonylurea herbicides are extremely active compounds first discovered in the mid-1970s at DuPont they have been discussed extensively (78). Sulfonjiurea herbicides have experienced a rapid and widespread success since thek commercial introduction in 1982 with chlorsulfuron (Table 5). The sulfonylureas are appHed at rates of 2—75 g/ha. The chemistry of the sulfonylurea molecule permits the synthesis of a very large number of useful analogues, consequentiy many new herbicides are anticipated for crop production. As of this writing (1996), over 350 patents have been issued to about 27 agricultural companies covering tens of millions of stmctures known or expected to be herbicidaHy active. 

This procedure is satisfactory for the synthesis of a variety of aryl sulfonamides. The heterocyclic intermediate used in the synthesis of chlorsulfuron is prepared according to K. R. Hoffmann and F. C. Schaeffer (Ref. 5) as shown in Figure 5. 

Lolium biotypes exist which have resistance to the sulfonylurea herbicides chlorsulfuron and metsulfuron methyl (4). The biotype used in the studies presented here is resistant to both these sulfonylurea herbicides. Sulfonylurea herbicides inhibit the chloroplastic enzyme acetolactate synthase (ALS), also known as acetohydroxyacid synthase (AHAS) (16). Inhibition of this enzyme results in disruption of the synthesis of the branched-chain amino acids valine and isoleucine (161. The imidazolinone herbicides also inhibit ALS Q2). In some species auxins can protect against chlorsulfuron inhibition (S. Frear, USDA North Dakota, personal communication) the mechanistic basis for this protection is not known. We have measured the ALS activity in the resistant and susceptible Lolium and have also checked for any induction of ALS activity following treatment with the sulfonylurea herbicide chlorsulfuron. 

In 1982, DuPont introduced the sulfonylurea herbicides which are effective at remarkably low dose rates an important example is chlorsulfuron 22 used for selective control of broad-leaved weeds in cereals at rates of 10-40 gha this herbicide can be prepared from chlorobenzene 21 (Scheme 5) (see also Chapter 6, ref 33), The first stage of the synthesis, namely the reaction of chlorobenzene with chlorosulfonic acid yields a mixture of the o- and / -sulfonyl chlorides, which may be separated by fractional distillation, since the o-isomer has the lower bp (Chapter 6, ref 33). 

ALS inhibitors Inhibition of ALS (branched chain amino acid synthesis) Chlorsulfuron 88 57 145... 

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