Flazasulfuron

Flazasulfuron
Names
	Preferred IUPAC name N-[(4,6-Dimethoxypyrimidin-2-yl)carbamoyl]-3-(trifluoromethyl)pyridine-2-sulfonamide
	Other names Katana, Shibagen
Identifiers
CAS Number	104040-78-0 ;
3D model (JSmol)	Interactive image;
ChemSpider	84440;
ECHA InfoCard	100.123.655
PubChem CID	93539;
UNII	3SB13WWV30 ;
CompTox Dashboard (EPA)	DTXSID3034610 ;
	InChI InChI=1S/C13H12F3N5O5S/c1-25-8-6-9(26-2)19-11(18-8)20-12(22)21-27(23,24)10-7(13(14,15)16)4-3-5-17-10/h3-6H,1-2H3,(H2,18,19,20,21,22) Key: HWATZEJQIXKWQS-UHFFFAOYSA-N; InChI=1/C13H12F3N5O5S/c1-25-8-6-9(26-2)19-11(18-8)20-12(22)21-27(23,24)10-7(13(14,15)16)4-3-5-17-10/h3-6H,1-2H3,(H2,18,19,20,21,22) Key: HWATZEJQIXKWQS-UHFFFAOYAQ;
	SMILES COc1cc(nc(n1)NC(=O)NS(=O)(=O)c2c(cccn2)C(F)(F)F)OC;
Properties
Chemical formula	C13H12F3N5O5S
Molar mass	407.3
Appearance	white solid
Melting point	166-170
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

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.^[1]

Synthesis

The synthesis of flazasulfuron begins with the one pot chlorination and chlorine/fluorine exchange of 3-picoline^[2] (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.^[3] 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).^[4] 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.

References

^ Appleby, Arnold P.; Müller, Franz; Carpy, Serge (2001). "Weed Control". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a28_165. ISBN 978-3-527-30673-2.
^ Unger, Thomas A. (1996). "Flazasulfuron". Pesticide Synthesis Handbook. pp. 180–182. doi:10.1016/B978-081551401-5.50148-9. ISBN 978-0-8155-1401-5.
^ Tsukamoto, Masamitsu; Nakamura, Tadashi; Kimura, Hirohiko; Nakayama, Hitoshi (20 May 2021). "Synthesis and application of trifluoromethylpyridines as a key structural motif in active agrochemical and pharmaceutical ingredients". Journal of Pesticide Science. 46 (2): 125–142. doi:10.1584/jpestics.D21-012. PMC 8175224. PMID 34135675.
^ EP 0184385B1, Fumio Kimura et al., "N-[(4,6-Dimethoxypyrimidin-2-YL)Aminocarbonyl]-3-trifluoromethylpyridine-2-sulfonamide or salts thereof, herbicidal composition containing the same, and processs for the production of the compound", published 1986

[1] Appleby, Arnold P.; Müller, Franz; Carpy, Serge (2001). "Weed Control". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a28_165. ISBN 978-3-527-30673-2.

[2] Unger, Thomas A. (1996). "Flazasulfuron". Pesticide Synthesis Handbook. pp. 180–182. doi:10.1016/B978-081551401-5.50148-9. ISBN 978-0-8155-1401-5.

[3] Tsukamoto, Masamitsu; Nakamura, Tadashi; Kimura, Hirohiko; Nakayama, Hitoshi (20 May 2021). "Synthesis and application of trifluoromethylpyridines as a key structural motif in active agrochemical and pharmaceutical ingredients". Journal of Pesticide Science. 46 (2): 125–142. doi:10.1584/jpestics.D21-012. PMC 8175224. PMID 34135675.

[4] EP 0184385B1, Fumio Kimura et al., "N-[(4,6-Dimethoxypyrimidin-2-YL)Aminocarbonyl]-3-trifluoromethylpyridine-2-sulfonamide or salts thereof, herbicidal composition containing the same, and processs for the production of the compound", published 1986

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