Sulfonic acids and sulfonyl chlorides

Procure building blocks Purchase or synthesize amines, acids, acid chlorides, sulfonic acids, and sulfonyl chlorides... 

Sulfonic acids and sulfonyl chlorides can also be prepared from sulfinic acids by oxidation with sodium permanganate (equation 590) [556] and chlorine in water (equation 591) [656], respectively. 

Chen, J Preparation of Alkane Sulfonic Acids and Sulfonyl Chlorides by Oxidation of Alkanethiols and Dialkyl Disulfides. U.S. Patent 6,124,497,, Sep 26, 2000. 

The mam derivatives of the sulfonic acids are obtained by converting them to the corresponding sulfonyl chlorides Hence sulfonic acids and sulfonyl chlorides are often identified through the same derivatives... 

Esters are prepared from carboxylic acids by the reaction between an acid chloride and an alcohol or between a carboxylic acid and an alcohol under acidic conditions. Both sulfonic acids and sulfonyl chlorides react with alcohols to form sulfonate esters. When butanesulfonyl chloride (177) reacts with propanol, usually in the presence of a base such as triethylamine, propyl butanesulfonate (180) is formed. A wide range of sulfonyl esters can be formed this way from an alcohol and a sulfonic acid. 

Sulfonic acid groups (SO3H) are both bulky and electron-withdrawing consequently once one sulfonic acid group has been introduced into the aromatic nucleus, the resultant arylsulfonic acid will be more resistant towards further sulfonation. The latter will require more drastic conditions and the product will contain the two sulfonic acid groups in the 1,3-position with respect to each other. With reactive substrates, e.g. aromatic hydrocarbons, halides or ethers, mono-chlorosulfonation is often best achieved at low temperature in ftie presence of chloroform, dichloromethane or 1,2-dichloroethane to moderate the reaction and avoid disulfonation. Suter and Weston S described the experimental procedures for the sulfonation of aromatic hydrocarbons, halides and ethers and many early references and details of the synthesis of sulfonic acids and sulfonyl chlorides are included in Suter s comprehensive text." ... 

Introducing the Tau residue into a peptide according to the first approach demands protection of the amino group, usually in the form of a Z-derivative and turning the sulfonic acid into sulfonyl chloride. Synthesis of (j-su Ifonamidopeptides via an iterative process, both in solution and in the solid phase, has been described.11201 Chiral methylene sulfinamide peptides can be synthesized both in solution and in the solid phase using the sulfonyl chlorides derived from enantiomerically pure 2-substituted taurines under mild coupling conditions (DMAP catalysis and excess methyl trimethylsilyl dimethylketene acetal as a proton trap).11261... 

Sulfide groups attached to other carbon functionalities, e. g. the cyano and amidine groups in 16 and 17, respectively, are oxidized to the sulfonic acid or sulfonyl chloride with cleavage of the S — C bond.J02-303... 

The SO2 and SO groups of sulfur compounds produce sbong infrared bands in the 1400-1000 cm range. The expected S=0 stretching bands for sulfoxides, sulfones, sulfonic acids, sulfonamides, sulfonyl chlorides and sulfonates are given in Table 4.11. The other bonds involving sulfur, such as S-H, S-S and C-S, produce weaker infrared bands. Compounds, such as sulfides and mercaptans. 

In Figure 11.2, a sulfonate ester is the leaving group, and reaction with a nucleophile breaks the weaker C-0 bond to generate a sulfonate anion (26). This anion is resonance stabilized and quite stable, which means it is relatively unreactive as a nucleophile. The combination of a weak C-0 bond and the stability and poor reactivity of the sulfonate anion makes sulfonate esters good leaving groups. The most common sulfonate esters (see Chapter 20, Section 20.11) are those derived from methanesulfonic acid, benzenesulfonic acid, or 4-methylbenzenesulfonic acid. Formation of sulfonate esters from sulfonic acids or sulfonyl chlorides will be discussed in Section 11.7.3 and in Chapter 20,... 

Thus far, the chapter has been devoted to the chemistry of carboxylic acid derivatives. Another important class of organic acids is the sulfonic acids (see 175 X = OH). In principle, sulfonic acids should give the same t3rpes of derivatives as the carboxylic acids acid chlorides, esters, and amides. This section will explore some of these common sulfonic acid derivatives sulfonyl chlorides (175 ... 

Subsequent conversion of a sulfonic acid to a sulfonyl chloride has been demonstrated with the use of hazardous phosphorous pentachloride/ phosphorous oxychloride and heating (170-180 °C), or with dimethyl-formamide and thionyl chloride, the product of which has the potential to form by-products with the DMF. Though more mild methods have been developed for the conversion of sulfonic acids to sulfonyl chlorides, such as cyanuric chloride under neutral conditions, these methods still require the preparation of the sulfonic acid. ... 

Sulfonylation. Under Friedel-Crafts reaction conditions, sulfonyl haUdes and sulfonic acid anhydrides sulfonylate aromatics (139), a reaction that can be considered the analogue of the related acylation with acyl haUdes and anhydrides. The products are sulfones. Sulfonyl chlorides are the most frequently used reagents, although the bromides and fluorides also react ... 

The iso)tazole ring is rather resistant to sulfonation. However, on prolonged heating with chlorosulfonic acid, 5-methyl-, 3-methyl- and 3,5-diraethyl-isoxazoles are converted into a mixture of the sulfonic acid and the corresponding sulfonyl chloride. The sulfonic acid group enters the 4-position even when other positions are available for substitution. The sulfonation of the parent isoxazole occurs only under more drastic conditions (20% oleum) than that of alkyl isoxazoles isoxazole-4-sulfonic acid is obtained in 17% yield. In the case of 5-phenylisoxazole (64), only the phenyl nucleus is sulfonated to yield a mixture of m-and p-arenesulfonic acid chlorides (65) and (66) in a 2 1 ratio (63AHC(2)365). 

Diaryl sulfones can be formed by treatment of aromatic compounds with aryl sulfonyl chlorides and a Friedel-Crafts catalyst. This reaction is analogous to Friedel-Crafts acylation with carboxylic acid halides (11-14). In a better procedure, the aromatic compound is treated with an aryl sulfonic acid and P2O5 in polypho-sphoric acid. Still another method uses an arylsulfonic trifluoromethanesulfonic anhydride (ArS020S02CF3) (generated in situ from ArS02Br and CF3S03Ag) without a catalyst. ... 

As with the carboxyhc acid group, the reactivity of these sulfonic acid derivatives may be predicted from the properties of the leaving group, and sulfonyl chlorides are the most reactive (see... 

In the case of sulfonylation (Scheme 10) [56] and sulfinylation reactions [34], Bi salts proved again to be efficient catalysts. In contrast to the arylsulfonylation, which is under partial control of triflic acid, depending on the substrates, a complete synergistic effect between triflic acid and Bi chloride has been found in the alkanesulfonylation of arenes. In this case, the formation of mixed triflic/alkane-sulfonic anhydrides leads to the active electrophilic species. The formation of the latter exclusively requires the transient formation of a Bi chlorobistriflate species that acts as an intermediate shuttle for triflic acid, leading to the formation of the mixed anhydride precited (Scheme 11). Our experiments have shown that triflic... 

Mannitol hexanitrate is obtained by nitration of mannitol with mixed nitric and sulfuric acids. Similarly, nitration of sorbitol using mixed acid produces the hexanitrate when the reaction is conducted at 0—3°C and at —10 to —75°C, the main product is sorbitol pentanitrate (117). Xylitol, ribitol, and L-arabinitol are converted to the pentanitrates by fuming nitric acid and acetic anhydride (118). Phosphate esters of sugar alcohols are obtained by the action of phosphorus oxychloride (119) and by alcoholysis of organic phosphates (120). The 1,6-dibenzene sulfonate of D-mannitol is obtained by the action of benzene sulfonyl chloride in pyridine at 0°C (121). To obtain 1,6-dimethanesulfonyl-D-mannitol free from anhydrides and other by-products, after similar sulfonation with methane sulfonyl chloride and pyridine the remaining hydroxyl groups are acetylated with acetic anhydride and the insoluble acetyl derivative is separated, followed by deacetylation with hydrogen chloride in methanol (122). Alkyl sulfate esters of polyhydric alcohols result from the action of sulfur trioxide—trialkyl phosphates as in the reaction of sorbitol at 34—40°C with sulfur trioxide—triethyl phosphate to form sorbitol hexa(ethylsulfate) (123). 

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 ... 

Sulfonic acids and carboxylic acids can be converted into their acid chlorides by treatment with phosphorus pentachloride or phosphorus oxychloride. Thionyl chloride, SOCl is effective for the synthesis of acyl chlorides, and sulfonyl chlorides can be prepared directly from the aromatic compound by reaction with an excess of chlorosulfonic acid. The acid chlorides are efficient Friedel-Crafts acylating agents, yielding sul-... 

Sulfinic acids and sulfoxides are not particularly common, being readily oxidized to the sulfonic acids and sulfones, respectively. Sulfonic acids have high melting points and probably exist as zwitterions. They are amphoteric, but mainly display the characteristics of weak acids. The sulfonic acid group activates an adjacent halogen to nucleophilic displacement, and may itself be displaced, e.g. reaction of alkylamines with benzimidazole-2-sulfonic acid. Imidazolesulfonic acids resist esterification and acid chloride formation, and are only hydrolyzed by concentrated hydrochloric acid at 170 °C the 2-isomers are more resistant than the 4- or 5-isomers. Aqueous alkali converts the free acids into hydroxy derivatives. Sulfonyl chlorides are accessible via the thiols (Section 4.07.3.6.1) which react with ammonia to form sulfonamides, or are reduced by tin(II) chloride to thiols (77JHC889). 

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