Sulfonic acids from sulfonamides

Sulfonic acids from the simplest members of the benzene series can be purified by distillation in a high vacuum,122 but purification is usually undertaken through the sulfonyl chlorides or sulfonamides. 

Chloromethanesulfonyl chloride reacts with 2-aminopyridine to give 2-(chloromethylsulfonamido)pyridine. AT-2-Pyridylalkanesulfonamides are formed from 2-ammopyridine and an alkane sulfonic acid these sulfonamides are amphoteric. ... 

General Reaction Chemistry of Sulfonic Acids. Sulfonic acids may be used to produce sulfonic acid esters, which are derived from epoxides, olefins, alkynes, aHenes, and ketenes, as shown in Figure 1 (10). Sulfonic acids may be converted to sulfonamides via reaction with an amine in the presence of phosphoms oxychloride [10025-87-3] POCl (H)- Because sulfonic acids are generally not converted directiy to sulfonamides, the reaction most likely involves a sulfonyl chloride intermediate. Phosphoms pentachlotide [10026-13-8] and phosphoms pentabromide [7789-69-7] can be used to convert sulfonic acids to the corresponding sulfonyl haUdes (12,13). The conversion may also be accompHshed by continuous electrolysis of thiols or disulfides in the presence of aqueous HCl [7647-01-0] (14) or by direct sulfonation with chlorosulfuric acid. Sulfonyl fluorides are typically prepared by direct sulfonation with fluorosulfutic acid [7789-21-17, or by reaction of the sulfonic acid or sulfonate with fluorosulfutic acid. Halogenation of sulfonic acids, which avoids production of a sulfonyl haUde, can be achieved under oxidative halogenation conditions (15). 

Five replicate recoveries of flucarbazone-sodium, sulfonic acid, sulfonamide and NODT from soil fortified at 0.001 mgkg averaged 97, 90, 100 and 87%, respectively. Therefore, the LOQ is 0.001 mg kg for each analyte. 

The imidazolides required for these reactions can be prepared from sulfonyl chlor-ides[1] or sulfonic anhydrides[2] and imidazole, or by treatment of the corresponding sulfonic acid with CDI,[1] ImSOIm,[3] or ImS02Im[3] (see Section 10.1.1). However, for the synthesis of sulfonamides it is more convenient to employ a one-pot reaction starting from the free sulfonic acid, CDI or ImSOIm, and the appropriate amine [1]... 

Sulfonic acids, R(Ar)S03H, form derivatives similar to those of carboxylic acids (see Table 16-3). These are sulfonyl chlorides, sulfonates (esters), and sulfonamides. The transsulfonylation reactions are similar to the transacylation reactions, except that the ester and amide cannot be made directly from the acid. See Problem 13.17 for preparation of sulfonyl chlorides and esters and Problem 13.18 for use of sulfonate esters as substrates in S l and S,42 reactions. 

Alternatively, sulfonamides can also be prepared by oxidation of sulfinamides with periodate (Entry 3, Table 8.8) or with MCPBA [125]. Polystyrene-bound sulfonyl chlorides, which can be prepared from polystyrene-bound sulfonic acids by treatment with PCI5, SOCI2 [126-129], CISO3H [130], or SO2CI2/PPI13 [131], react smoothly with amines to yield the corresponding sulfonamides (Entry 4, Table 8.8). Support-bound carbamates of primary aliphatic or aromatic amines can be N-sulfonylated in the presence of strong bases, and can therefore be used as backbone amide linkers for sulfonamides (Entries 5 and 6, Table 8.8). 

Aromatic amides, sometimes referred to as aryiamides, exhibit the same relationship. Note the relationship of benzoic acid Cg H5 COOH with benzamide Q H5 CONH2. Thiamides are derived from amides in which there is substitution of the O atom by a sulfur atom. Thus, acetamide NHa- CO- CH3, becomes thiacetamide NH2- CS- CH3 or acetanilide C6 H5- NH- CO- CH3 becomes thiacetanilide C6 H5- NH- CS- CH3. Sulfonamides arc derived from the sulfonic acids. Thus, bcnzcnc-sulfonic acid Cg H5 SO2- OH becomes benzene-sulfonamide Cg Hs- SOv NH2. See also Sulfonamide Drugs. 

The water-soluble reactive phthalocyanine dyes (see Section 2.8) yield brilliant turquoise and green shades not available from any other dye category. The most important reactive phthalocyanine dyes contain copper or nickel as their central atom they are substituted with sulfonic acid groups and also with reactive groups joined via sulfonamide bridges. An example is C.I. Reactive Blue 15, 74459 [12225-39-7] (23) ... 

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. 

A primary or secondary amine attacks a sulfonyl chloride and displaces chloride ion to give an amide. Amides of sulfonic acids are called sulfonamides. This reaction is similar to the formation of a sulfonate ester from a sulfonyl chloride (such as tosyl chloride) and an alcohol (Section 11-5). 

The molecule contains a sulfonamide and a benzene ring as well as the part that interests us most—a bicydic aromatic heterocyclic system of a pyrazole fused to a pyrimidine. We shall discuss in detail how Pfizer made this part of the molecule and just sketch in the rest. The sulfonamide can be made from the sulfonic acid that can be added to the benzene ring by electrophilic aromatic sulfonation (Chapter 22). 

Sulfonamides can be directly synthesized from sulfonic acid salts by treatment with triphenylphosphine ditriflate followed by an amine <2004JA1024>. 

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