Sulfonyl chlorides hydrolysis

N -Heterocyclic Sulfanilamides. The parent sulfanilamide is manufactured by the reaction of A/-acetylsulfanilyl chloride with excess concentrated aqueous ammonia, and hydrolysis of the product. Most heterocycHc amines are less reactive, and the condensation with the sulfonyl chloride is usually done in anhydrous media in the presence of an acid-binding agent. Use of anhydrous conditions avoids hydrolytic destmction of the sulfonyl chloride. The solvent and acid-binding functions are commonly filled by pyridine, or by mixtures of pyridine and acetone. Tertiary amines, such as triethylamine, may be substituted for pyridine. The majority of A/ -heterocycHc sulfanilamides are made by simple condensation with A/-acetylsulfanilyl chloride and hydrolysis. 

Sulfonamides, as a class, are simple to manufacture once the isolation conditions for the moderately stable sulfonyl chloride have been estabUshed. Basically all processes iavolve the addition of the sulfonyl chloride paste to excess ammonia or amine ia aqueous solution. The product can usually be filtered off ia a reasonably pure form with only the hydrolysis product remaining ia the Hquor. 

Early recommendations for cross-linking CSM involved the use of divalent metal oxides to form metal sulfonate cross-links (24). The mechanism involves the hydrolysis of the sulfonyl chloride group with a carboxyHc acid, ie, stearic acid, which produces water at curing temperatures. 

Pyrazolesulfonic acids, like (493), have high melting points (Table 24) and probably exist as the zwitterions (497). They are very stable to hydrolysis and only afford pyrazolones at high temperatures. The replacement of the SO3H group by bromine has also been reported (B-76MI40402). Pyrazole-3-, -4- and -5-sulfonic acids react with phosphorus pentachloride to form sulfonyl chlorides. 

Pyrimidine-4-sulfonic acid, 2,6-dimethyl-reactions, 3, 97 Pyrimidinesulfonic acids acidic pif 3, 60 reactions, 3, 96 synthesis, 3, 138 Pyrimidine-2-sulfonic acids acidic pK, 3, 60 reactions, 3, 97 Pyrimidine-4-sulfonic acids hydrolysis, 3, 97 Pyrimidine-2-sulfonyl chloride synthesis, 3, 138... 

Sulfonamides (R2NSO2R ) are prepared from an amine and sulfonyl chloride in the presence of pyridine or aqueous base. The sulfonamide is one of the most stable nitrogen protective groups. Arylsulfonamides are stable to alkaline hydrolysis, and to catalytic reduction they are cleaved by Na/NH3, Na/butanol, sodium naphthalenide, or sodium anthracenide, and by refluxing in acid (48% HBr/cat. phenol). Sulfonamides of less basic amines such as pyrroles and indoles are much easier to cleave than are those of the more basic alkyl amines. In fact, sulfonamides of the less basic amines (pyrroles, indoles, and imidazoles) can be cleaved by basic hydrolysis, which is almost impossible for the alkyl amines. Because of the inherent differences between the aromatic — NH group and simple aliphatic amines, the protection of these compounds (pyrroles, indoles, and imidazoles) will be described in a separate section. One appealing proj>erty of sulfonamides is that the derivatives are more crystalline than amides or carbamates. 

The aromatic sulfonyl chlorides which have no a-hydrogen and thus cannot form sulfenes give acylic sulfones. Thus 1-piperidinopropene on reaction with benzene sulfonyl chloride (9J) gave 2-benzenesulfonyl-l-piperidinopropene (153). Similarly the enamine (28) reacts with p-toluene-sulfonyl chloride to give the 2-p-toluenesulfonylcyclohexanone (154) on hydrolysis (/OS). 

The drugs are available by one of two fairly straightforward routes. Chlorosulfonation of acetanilide gives the corresponding sulfonyl chloride (88) reaction with the appropriate amine gives the intermediate, 89. Hydrolysis in either acid or base leads to the sulfanilamide (90). 

This sequence is equally applicable to keto esters. Thus, condensation of guanidine with ethyl acetoacetate gives the pyrimidone, 134. Elaboration as above gives the pyrimidine, IJ5 acylation with the sulfonyl chloride (88) followed by hydrolysis yields sulfamerazine (107). Reaction of guanidine with beta dicarbonyl compounds gives the pyrimidine directly. Condensation of the base with acetonyl acetone affords the starting amine for sulfadimidine (108). ... 

Since the ring nitrogen at 3 is now comparable in reactivity to the amine at 4, acylation with one equivalent of 88 gives a mixture of products. The desired product, sulfaisodimidine (109), can be obtained by acylation with an excess of the sulfonyl chloride (140) followed by alkaline hydrolysis. The rate of saponification of the sulfonamide group attached to the ring nitrogen is sufficiently greater to cause it to be lost selectively. 

The corresponding AfA -sulfonyldiimidazole, prepared from sulfonyl chloride and imidazole, is of surprisingly low reactivity in every respect. It forms stable crystals of m.p. 141 °C which can be sublimed in vacuum and recrystallized from ethanol without alcoholysis. Even in dilute aqueous hydrochloric acid hydrolysis occurs only very slowly. 

Both sulfonyl chloride and isothiocyanate will hydrolyze in aqueous conditions therefore, the solutions should be made freshly for each labeling reaction. Absolute ethanol or dimethyl formamide (best grade available, stored in the presence of molecular sieve to remove water) should be used to dissolve the reagent. The hydrolysis reaction is more pronounced in dilute protein solution and can be minimized by using a more concentrated protein solution. Caution DMSO should not be used with sulfonyl chlorides, because it reacts with them. 

The kinetics of hydrolysis of the sulfone of 3,7-dibenzothiophendi-sulfonyl chloride have been investigated in a 70% dioxane-water mixture. Hydrolysis rates were measured both conductometrically and titrimetrically. 

Cycloaddition of ynamines with sulfenes (generated from sulfonyl chlorides) to give thiete sulfones 132 and 133 has been reported by Truce et (Eq. 21). Acid hydrolysis yields the corresponding enols (134). Other compounds that have been prepared in this manner are 135 and 136. Sulfene... 

This procedure has an advantage over direct sulfonation in that sulfonyl chlorides usually are soluble in organic solvents and may be easily separated from the reaction mixture. Also, the sulfonyl chloride is a more useful intermediate than the sulfonic acid, but can be converted to the acid by hydrolysis if desired ... 

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