- Rapid Multigram-Scale End-to-End Continuous-Flow Synthesis of Sulfonylurea Antidiabetes Drugs: Gliclazide, Chlorpropamide, and Tolbutamide
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A multigram-scale robust, efficient, and safe end-to-end continuous-flow process for the diabetes sulfonylurea drugs gliclazide, chlorpropamide, and tolbutamide is reported. The drugs were prepared by the treatment of an amine with a haloformate affording carbamate, which was subsequently treated with a sulfonamide to afford sulfonylurea. Gliclazide was obtained in 87% yield within 2.5 minutes total residence time with 26 g/h throughput; 0.2 kg of the drug was produced in 8 hours of running the system continuously. Chlorpropamide and tolbutamide were both obtained in 94% yield within 1 minute residence time with 184-188 g/h throughput; 1.4-1.5 kg of the drugs was produced in 8 hours of running the system continuously. N-Substituted carbamates were used as safe alternatives to the hazardous isocyanates in constructing the sulfonyl urea moiety.
- Sagandira, Cloudius R.,Watts, Paul
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supporting information
(2021/12/02)
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- A facile synthesis of sulfonylureas: Via water assisted preparation of carbamates
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A novel and simple approach to the synthesis of sulfonylureas has been reported. It involved the reaction of various amines with diphenyl carbonate to yield the corresponding carbamates, which subsequently reacted with different sulphonamides to produce different sulfonylureas in excellent yields. The first reaction of diphenyl carbonate with amines was carried out in aqueous:organic (H2O:THF, 90:10) medium at room temperature to produce carbamates that paved a straightforward route to sulfonylureas after reaction with sulfonamides. The above process avoided traditional multistep protocols and the use of hazardous, irritant, toxic and moisture sensitive reagents such as phosgene, isocyanates and/or chloroformates.
- Tanwar, Dinesh Kumar,Ratan, Anjali,Gill, Manjinder Singh
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p. 4992 - 4999
(2017/07/11)
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- Mechanosynthesis of pharmaceutically relevant sulfonyl-(thio)ureas
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We demonstrate the first application of mechanochemistry to conduct the synthesis of sulfonyl-(thio)ureas, including known anti-diabetic drugs tolbutamide, chlorpropamide and glibenclamide, in good to excellent isolated yields by either stoichiometric base-assisted or copper-catalysed coupling of sulfonamides and iso(thio)cyanates. the Partner Organisations 2014.
- Tan, Davin,?trukil, Vjekoslav,Mottillo, Cristina,Fri??i?, Tomislav
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supporting information
p. 5248 - 5250
(2014/05/06)
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- Synthesis of sulfonylurea derivatives used as oral antidiabetics by the selenium-assisted carbonylation using carbon monoxide with sulfur
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Sulfonylurea derivatives including useful antidiabetics (Tolbutamide, Chlorpropamide) were synthesized in good yields from benzene-sulfonamides with thiocarbamates in the presence of DBU. Thiocarbamates were prepared by the selenium-assisted carbonylation
- Mizuno, Takumi,Kino, Takanobu,Ito, Takatoshi,Miyata, Toshiyuki
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p. 3081 - 3089
(2007/10/03)
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- Lewis Acid Catalysed Preparation of some Carbamates and Sulphonylureas. Application to the Determination of Enantiomeric Purity of Chiral Alcohols
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Lewis acids such as boron trifluoride-diethyl ether and aluminium chloride catalyze the reaction of alcohols and sulphonamides with isocyanates, affording carbamates and sulphonylureas, respectively, in acceptable yield.Applied to the formation of diastereoisomeric carbamates from chiral alcohols using Pirkle's reagents, , this technique provides a convenient method for determination of enantiomeric purity.
- Irie, Hiroshi,Nishimura, Masataka,Yoshida, Morihiro,Ibuka, Toshiro
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p. 1209 - 1210
(2007/10/02)
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- Preparation of sulfonylureas
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Sulfonylureas are prepared by reacting a hydroxyethyl carbamate with an alkali metal salt of a substituted benzene sulfonamide, the alkali metal being selected from the group comprising sodium, potassium and lithium.
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