Sulfones reaction with amine

The group of Caddick has described the synthesis of functionalized sulfonamides by microwave-assisted displacement of pentafluorophenyl (PFP) sulfonate esters with amines (Scheme 6.159) [306]. Their ease of handling due to their higher crystallinity, along with their long shelf-life and their ability to react under aqueous reaction conditions, makes these an attractive alternative to sulfonyl chlorides. The microwave-assisted reaction of alkyl PFP esters with amines is a facile process which proceeds cleanly and in good yields with a number of different amines, including primary, secondary, and sterically hindered amines, and anilines. Optimum condi-... 

The conjugate addition of heteronucleophiles to activated alkenes has been used very often in organic synthesis to prepare compounds with heteroatoms [3 to various activating functional groups, e.g. ketones, esters, nitriles, sulfones, sulfoxides and nitro groups. As in the Michael reaction, a catalytic amount of a weak base is usually used in these reactions (with amines as nucleophiles, no additional base is added). 

On reaction with amines R NHR, only the AE (reaction sequence A) with C—O bond scission will lead to amination product 37 and sulfonic acid 38, whereas the competing attack on the sulfonyl group (reaction sequence B) with S—O bond scission will lead to 2-(l//)-pyridinone (27) and a sulfonamide 39, thus decreasing the yield of the desired amination product (cf. 209 210 in Section IV,E). This B-type of scission is also... 

The 4-hydroxythiophenol solid support or phenol-sulfide linker 5u [238] can be used for anchoring carboxylic acids in the presence of carbo-diimides to give an acid-stable ester linkage that can be activated toward nucleophilic attack by amines by oxidation to the sulfone. However, although the acid stability has been confirmed, it has been reported that prior oxidation of the anchor is unnecessary for release of amides by reaction with amines by either an intermolecular [239] or intramolecular pathway [240]. 

Sulfonyl chlorides are highly reactive derivatives of sulfonic acid and possess similar properties and reactivity to acid chlorides of carbo Q lates. The reaction with nucleophiles such as amines requires alkaline conditions (pH 9-10) and proceeds through the formation of an unstable pentavalent transition state (Scheme 1.10). Hydrolysis is a major competing reaction in water therefore the reaction with amines proceeds with better yield when done in organic solvents. Sulfonyl chlorides have played an important role in bioconjugation chemistry, since sulfonic acids can be easily converted into sulfonyl chlorides using thionyl chloride or phosphorus pentachloride in non-aqueous conditions. ... 

In SPOS, the choice of the linker that serves to attach the library scaffold to the polymer support is critical. As a result, a variety of elegant linking methods have been developed that enable the introduction of additional diversity into the products during the cleavage reactions. The sulfone linker is an example of a safety-catch linker that can be cleaved from resins by using nucleophilic substitution reactions with amines. 

To explore the diversity of this methodology, various amines (R R N diversity elements) were used to liberate the 1,3,4-oxadiazoles 11 and 1,3,4-thiadiazoles 12 from the functionalized sulfone-containing resin. Cleavage reactions with amines generally afforded the desired products in high yields (22 examples, 72-30% yields. Table 10.10). 

Resorcinol Derivatives. Aminophenols (qv) are important intermediates for the syntheses of dyes or active molecules for agrochemistry and pharmacy. Syntheses have been described involving resorcinol reacting with amines (91). For these reactions, a number of catalysts have been used / -toluene sulfonic acid (92), zinc chloride (93), zeoHtes and clays (94), and oxides supported on siUca (95). In particular, catalysts performing the condensation of ammonia with resorcinol have been described gadolinium oxide on siUca (96), nickel, or zinc phosphates (97), and iron phosphate (98). 

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). 

SuIfona.tlon, Sulfonation is a common reaction with dialkyl sulfates, either by slow decomposition on heating with the release of SO or by attack at the sulfur end of the O—S bond (63). Reaction products are usually the dimethyl ether, methanol, sulfonic acid, and methyl sulfonates, corresponding to both routes. Reactive aromatics are commonly those with higher reactivity to electrophilic substitution at temperatures > 100° C. Tn phenylamine, diphenylmethylamine, anisole, and diphenyl ether exhibit ring sulfonation at 150—160°C, 140°C, 155—160°C, and 180—190°C, respectively, but diphenyl ketone and benzyl methyl ether do not react up to 190°C. Diphenyl amine methylates and then sulfonates. Catalysis of sulfonation of anthraquinone by dimethyl sulfate occurs with thaHium(III) oxide or mercury(II) oxide at 170°C. Alkyl interchange also gives sulfation. 

Aminoisoxazoles can be determined photometrically by reaction with sodium 1,2-naph-thoquinone-4-sulfonate and selective extraction of the resulting dye into CCI4 for absorbance measurements. This class of compound can be determined in the presence of sulfonamides, sulfanilamides, hydroxylamines and other select amines (74MI41610). 

Sulfonates react with a variety of nucleophiles. Synthesis of M A -bis(trifluoro-methyl)aminotnfluoromethanesulfonate and its reactions with nucleophiles were investigated [33] (equation 31) (Table 13). Nucleophilic attack occurs at either nitrogen or sulfur amines give complex mixtures [33]. Polyfluoroalkyl fluorosul-fates react with amines, alcohols, or alkoxides to yield polyfluoroalkyl sulfamates and dialkyl sulfates, respectively [34] (equation 32) (Table 13). In these reactions. 

The reaction with methanesulfonyl chloride in the presence of a proton abstracter like triethyl amine gave not the enamine, but a cyclic amino-sulfone (64). 

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