Sulfonyl chlorides reaction with amides

Diuretic activity can be retained in the face of replacement of one of the sulfonamide groups by a carboxylic acid or amide. Reaction of the dichlorobenzoic acid, 174, with chlorsulfonic acid gives the sulfonyl chloride, 175 this is then converted to the amide (176). Reaction of that compound with furfuryl ine leads to nucleophilic aromatic displacement of the highly activated chlorine at the 2 position. There is thus obtained the very potent diuretic furosemide (177). ... 

Finally, attachment of a rather complex side chain to the para position of the benzene ring on the sulfonamide leads to the very potent, long-acting oral antidiabetic agent, glyburide (215). Preparation of this compound starts with the chlorosul-fonation of the acetamide of 3-phenethylamine (209). The resulting sulfonyl chloride (210) is then converted to the sulfonamide (211) and deacylated (212). Reaction with the salicylic acid derivative, 213, in the presence of carbodiimide affords the amide, 214. Condensation of that with cyclohexylisocyanate affords glyburide (215). ... 

Sulfonyl chlorides as well as esters and amides of sulfonic acids can be hydrolyzed to the corresponding acids. Sulfonyl chlorides can by hydrolyzed with water or with an alcohol in the absence of acid or base. Basic catalysis is also used, though of course the salt is the product obtained. Esters are readily hydrolyzed, many with water or dilute alkali. This is the same reaction as 10-4, and usually involves R —0 cleavage, except when R is aryl. However, in some cases retention of configuration... 

The combinatorial reactions chosen for the novel amines were amide bond formation and sulfonamide formation. The novel carboxylic acids were derivatized to simple amides. For the amine reactions, we chose two simple carboxylic acids (propionic acid and benzoic acid) and two simple sulfonyl chlorides (methyl-sulfonyl chloride and benzenesulfonyl chloride) as the capping groups. Propyl amine and benzylamine were chosen as the capping groups to react with the novel carboxylic acids. Because only one reactant will be variable, these combinatorial libraries were essentially 1 x N libraries, where the one reactant was a simple reactant and the N component is the novel amines or acids. 

We have seen that amines react with acyl chlorides to give amides. A very similar reaction occurs with sulfonyl chlorides to give sulfonamides. An... 

Figure 10 Schematic representation of the most common reactions for labeling an amine (a) reaction with isothiocyanate to give a thiourea (b) reaction with a Succinimidil ester to give an amide (c) reaction with a sulfonyl chloride to give a sulfonamide (d) reaction with an aldehyde to give an imine (Schiff s base) and (e) reaction with a carbodiimide-activated carboxylic acid to give an amide.

Activation with sulfonic acid chlorides is more general, rendering amides with the possible participation of symmetric anhydrides after disproportionation. This method has also found use in the synthesis of modem 3-lactam antibiotics. However, in peptide chemistry this activation method leads to unwanted side reactions, like formation of nitriles in the cases of glutamine and asparagine, and racemization. In a convenient one-pot procedure, the carboxylic acids are activated by sulfonyl chlorides under solid-liquid phase transfer conditions using solid potassium carbonate as base and a lipophilic ammonium salt as catalyst. ... 

Sulfonyl halides (e.g. benzenesulfonyl chloride) form adducts (11) with acid amides in an equilibrium reaction. From these adducts or via adducts of this type 0-sulfonated lactim ethers, isonitriles, adenine, nitriles, amidines, amidinium salts and formic acid esters were prepared. The adducts from DMF and chlorosulfonamides (12) can be used to prepare amidines or amidrazones. A/-Chlorosulfonylcarboxylic acid amides yield nitriles on treatment with DMF or other tertiary amides, presumably via an acid amide sulfonyl chloride complex (13 equation 3). ... 

Some of these transformations were accompanied by additional reactions, e.g. formylation of the aromatic or heteroaromatic - nucleus or CH-acidic methyl groups further dehydration of amides to nitriles was observed. Adducts from amides and PCI3, sulfonyl halides or SO2CI2/SCXZI2 from which amidines can be obtained by reaction with amine derivatives (compare Section 2.7.2.5 and refs. 5 and 14) have not found wide application for this purpose. An interesting reaction is the preparation of the amidine (294 equation 158) from 7V-pentafluorophenylformamide. By thermal decomposition of the adducts from secondary amides and 7V,iV-dialkylcarbamoyl chlorides amidinium salts were synthesized from which the amidines (295 equation 159) were set free by treatment with bases. " ... 

The amino group of 4-amino-3-pyrazolin-5-ones reacts normally. Acylation occurs readily with a wide variety of acylating agents. Amides are formed by reaction with acid chlorides,50,533,984,1414,1473 acids618,984,1471 and esters in the presence of phosphorus pentoxide.1471 Thioformamides have been prepared by reaction with dithioformic acid and its salts.472,556,1374 Sulfonyl chlorides react to form sulfonamides.98,489,984,1249,1504 Chlorophosphates react with 4-amino-3-pyrazolin-5-ones to form phosphoramide derivatives.509,1498... 

Preparation of 45 [44] The amides and sulfonamides were synthesized by treating N-benzyhnethylamine 44 (0.302 g, 2.5 mmol) with an acid chloride or sulfonyl chloride (3.5 mmol) in DMF (2 mL) containing triethylamine (5 mmol). The reaction mixture was stirred for 4 h and then quenched with potassium sarcosinate (0.127 g, 1 mmol) and water (6 mL). The product 45 was isolated by filtration in the case of sohds, and extracted into ethyl acetate (10 mL) in the case of oils. In the latter case, evaporation of the solvent from the organic extract gave fhe product. 

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