Reaction with sulfonamide salts

Anions of secondary-sulfonamides, especially N-substituted tosylamidate ions, have emerged as premier partners for C-N bond forming reactions with alkynyliodonium salts. To a much lesser extent secondary-carboxamidate ions have also been used for this purpose. For example, the sequential treatment of -substituted tosylamides with n-butyllithium and phenyl(trimethylsi-lylethynyl)iodonium triflate (26) affords the corresponding N-trimethylsi-lylethynyl-p-toluenesulfonamides, which can be desilylated with tetrabutylam-monium fluoride in wet THF (Scheme 51) [ 151 ]. It is noteworthy that the presence of such groups as n-Bu and CH2 = CH(CH2)2- in the tosylamidate ions did... 

Allylic alkylations. Highly regioselective alkylation of both hard and soft nucleophiles (phenolates, sulfonamides, and phenylsulfonylacetic esters, respectively) is also possible with the Rh catalyst modified by the added (MeOl P, The countercation seems to play an important role in the displacement with alkali phenolates to afford branched allylic ethers thus, reaction with Li salts shows the highest regioselectivity but the product yields are low. The best compromise is to use Na phenolates. 

Nitrate and nitrite The nitrate and nitrite content of cheeses that have been treated with these salts can be determined by reduction with cadmium followed by reaction with sulfonamide and N-l,nap-hthylethylenediamine hydrochloride. This produces a colored compound that can be quantified spectro-photometrically. 

Although Beringer s arylations of aniline and piperidine resulted in poor yields, reactions with sulfonamides dehvered the N-arylated products in 50% yield under basic conditions [87]. McEwen found that arylation of sodium azide was facile at 80 °C in dioxane/water, delivering arylazides in excellent yields [88]. The chemoselective arylation of azides has been demonstrated with an luisymmetric polyfluorinated salt [90], and a computational study supports the ligand coupling pathway [32, 33]. 

Feldman reported a route to dihydropyrroles, pyrroles, and indoles via the reaction of sulfonamide anions with alkynyliodonium triflates <96JOC5440>. Thus, upon nucleophilic addition of the anion of 91 to the p-carbon of the alkynyliodonium salt, the alkylidene carbene 92 is generated which can the undergo C-H insertion to the desired product 93. 

The classic syntheses of the antibacterial sulfonamides involve reaction of the appropriate arylamine with an acid addition salt of p-amino-benzenesulfonyl chloride, or p-nitrobenzenesulfonyl chloride followed by reduction. Chemical interest largely resides in preparation of the corresponding arylamines. For the synthesis of sulfacytine (134), N-ethyl uracil (131) was converted to its thioamide (132) by reaction with phosphorous pentasulfide. The newly introduced sulfur is then displaced with ammonia in methanol to give 133. Standard reactions complete... 

With sulfonamide-derived chloramine salts bearing smaller organic substituents on the sulfur, for example, methanesulfonamide-derived chloramine salt 111 (chloramine-M) as the oxidant, better results are obtained. This reagent can be prepared separately and added to the reaction mixture as the stable anhydrous... 

The Curtius rearrangement provides a route to carbamates of a-amino sulfonamides (Scheme 25). 108 Reaction of the ethyl ester of an a-bromo acid 52 with Na2S03 yielded the sodium salt of the corresponding sulfonic acid 53. Treatment of 53 with PQ5 afforded the sulfonyl chloride 54 which on reaction with an amine gave the sulfonamide 55. The latter... 

The NH groups of sulfonamide functions are also readily alkylated. The 1,2,6-thiadiazine dioxide (74) gives the 2-methyl derivative on treatment with iodomethane in acetone in the presence of potassium carbonate <65CI(L)182). The 1,3,2,4,6-dithiatriazine (75) forms a silver salt (64MI22800), and reaction of the salt with iodomethane gives the expected TV-methyl compound. 

Sulfonamides may be directly synthesized from sulfonic acid salts by treatment with triphenylphosphine ditriflate followed by an amine <2004JA1024>. This procedure, that avoids the generation of sulfonic acids, converts sulfonic acid salt 129 to sulfonamide 130 in 81% yield (Equation 92). Problems associated with the removal of triphenylphosphine oxide by-products can be alleviated by performing the reaction with polystyrene-supported phosphine. 

Monohalogenothiazoles, 567 nucleophilic substitution reactions, 322 with amines. 567 with ArSH, 567 with benzamide, 567 with OH", 567 with OR", 567 relative reactivities, 568 with SR", 567 with sulfinic acid salts, 567 with sulfonamide, 567 reactions, with alkyl halides, 574 with n-butyllithium, 573 with Gtignard reagents, 573 reeduction of, with nickel, 573 with zinc, 573... 

The monosubstituted sulfonamide from a primary amine has an acidic hydrogen attached to nitrogen. Reaction with potassium hydroxide converts this amide into a soluble salt which, if the amine contained fewer than eight carbons is at least partly soluble. Acidification of this solution regenerates the insoluble amide. 

A colorimetric method for microdetermination of sulfonamides based on diazotization of the drug with sodium nitrite and hydrochloric acid has been reported (59). The diazonium salt is then coupled with 8-hydroxyquinoline in alkaline medium and the absorbance of the developed color measured at its maximum wavelength. A similar method involves diazotization and coupling of the sulfonamide with indole in alkaline solution to form an intense yellow azo dye which exhibits maximum absorption at 449 nm. Beer s law is obeyed over the concentration range 1-32 /ig/ml with a relative standard deviation of less than 2% (60). The reaction of sulfonamides with chloramine-T in sulfuric acid gives a yellow product which is suitable for the determination of sulfonamides in different formulations. It has an accuracy similar to that of the Bratton and Marshall method (61). 

Dutt-Wormall reaction. Preparation of dia-zoaminosulfinates by reaction of diazonium salts with aryl- or alkylsulfonamides followed by alkaline hydrolysis to the corresponding sulfinic acid of the sulfonamide and the azide. 

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... 

Chlorosulfonation of 2-ethoxybenzoic acid was found to be very regioselective a mole of thionyl chloride needs to be added to ensure the intermediate sulfonic acid is converted to the sulfonyl chloride (see Scheme 16.3). The sulfonyl chloride was converted to sulfonamide 9 by reaction with A-methylpiperazine. Initially triethylamine was used as a base, and compound 9 could only be isolated as its hydrochloride-triethylamine double salt, which was very insoluble and difficult to use in subsequent steps. A key breakthrough was obtained when it was discovered that sulfonamide 9 also could be isolated as its highly crystalline zwitterion. 

Deamination of primary amines. The conversion of primary amines into N-sulfonamides under Schotten-Baumann conditions is the basis for the classical Hinsberg test. Baumgarten et aO have found that N-sulfonamides can be converted into N,N-disulfonimides, usually in high yield, by conversion into the sodium salt (NaH) and subsequent reaction with a sulfonyl chloride in DMF as solvent ... 

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