Sulfone intermediate

Amide-Based Sulfonic Acids. The most important amide-based sulfonic acids are the alkenylarnidoalkanesulfoiiic acids. These materials have been extensively described ia the Hterature. A variety of examples are given ia Table 5. Acrylarnidoalkanesulfoiiic acids are typically prepared usiag technology originally disclosed by Lubrizol Corporation ia 1970 (80). The chemistry iavolves an initial reaction of an olefin, which contains at least one aHyhc proton, with an acyl hydrogen sulfate source, to produce a sulfonated intermediate. This intermediate subsequendy reacts with water, acrylonitrile, and sulfuric acid. 

Studies to clarify the earlier poor conversion of 10 into IOS have also been published by Yoshimura et al. [22,23]. These authors have made extensive use of NMR to characterize the main components of the sulfonated intermediates of internal olefins. By keeping the neutralization temperature below 35°C, internal olefins were converted to sulfonates with the same yield as that of a-olefins. 

Giblin, G.M.P., Jones, C.D., Simpkins, N.S. (1997) A Concise Stereoselective Synthesis of Epi-batidine Employing Conjugate Addition to an Alkenyl Sulfone Intermediate as the Key Step. Syniett, 589-590. 

DNA and RNA may be modified with hydrazide-reactive probes by reacting their cytosine residues with bisulfite to form reactive sulfone intermediates. These derivatives undergo transamination to couple hydrazide- or amine-containing probes (Draper and Gold, 1980) (Chapter 27, Section 2.1). 

The direct sulfonadon of alkylaminotriphenylmethane dyes gives mixtures of substituted products. Although dyes containing anilino or benzylamino groups give more selective substitution, a sulfonated intermediate such as 3[(lV-ethy]-A-pheny]-amino)methy]]benzenesu]fonic acid (ethylbenzylanilinesulfonic acid) is the preferred starting material. 

Sulfonation. The direct sulfonation of alkylaminotriphenylmethane dyes gives mixtures of substituted products. Although dyes containing anilino or benzylamino groups give more selective substitution, a sulfonated intermediate such as 3[(N-ethyl-N-phenylamino)methyl]benzenesulfonic acid (ethylbenzylanilinesulfonic acid) is the preferred starting material. However, Patent Blue V [354649-0], Cl Acid Blue 3, was made from 3-hydroxybenzaldehyde and two moles of diethyl aniline, followed by sulfonation of the leuco base and oxidation to the dye. FD C Green 2 [5141 -20-8/,... 

To a 0°C solution of penicillanic acid (0.046 mol) in 32 ml water and 48 ml acetonitrile was slowly added KMn04 (0.061 mol) and 6 ml concentrated H2SO4 dissolved in 120 ml water. At the end of the addition 50% aqueous sodium bisulfite was added until a clear solution resulted and anhydrous ammonia passed into the solution until a pH of 3 was reached. Thereafter the sulfone intermediate precipitated and was collected in 78% yield. H- and C-NMR and IR data supplied. 

This traceless linker allows fhe synthesis of a number of different heterocycles starting from fhe solid-phase-bound sulfone intermediate 139, which can be built up in a few steps from fhe sulfinate 138. The potential of fhis traceless linker is outlined in Scheme 66 [161, 162]. 

In its original form,94 the Julia reaction consisted of the formation of a carbon-carbon double bond through the coupling of a sulfonyl-stabilized anion and a carbonyl compound to generate a P-hydroxy sulfone, followed by a reductive elimination to afford the alkene (Eq. 47). A subsequent study of its scope and stereochemistry led to improved reaction conditions, which are now widely used.206 Alternative methods to synthesize the P-hydroxy sulfone intermediates, such as the addition of sulfonyl carbanions to esters with subsequent reduction of the ketone to the P-hydroxy sulfone, are also known (Eq. 121).207... 

By far, the most widely used method is the alkylation of an a-sulfonyl carbanion followed by reductive removal of the sulfonyl group. Different electrophiles such as alkyl halides, sulfonates, sulfinates, acetates, oxiranes, and electron-deficient multiple bonds are employed for the formation of the new C-C bond. Palladium-catalyzed it-allylic alkylation with a-sulfonyl carbanions is also a commonly used method. After the C-C bond formation, the conditions for the final desulfonylation reaction with the appropriate reagent will depend on the structure of the sulfone intermediate. 

Synthesis of (+)-Eurylene. The reaction of a-sulfonyl anions with carboxylic acid derivatives is used as the key step in the construction of various natural products. The resulting (3-oxo sulfone intermediate is then further elaborated and/or desulfonylated to afford the desired product. A variety of carboxylic acid derivatives has been used, esters being most often employed, as depicted in Eq. 149 for the synthesis of the triterpene polyether (+)-eurylene.149... 

Scheme 18.14 Trapping the volatile imine with sodium bisulfite to make the stable sulfone intermediate.

Diels-Alder reaction, catalyzes the cycloaddition between terachlorothiophene dioxide and iV-ethylmaleimide. This reaction occurs via a bridged sulfone intermediate forming tetrachlorophthalimide through sulfone elimination and spontaneously oxidative aromatization (Fig. 3B). This catalyst displays an effective molarity (EM=kca/ku cat) of 1000 M, which is extremely efficient for a bimolecular reaction catalyzed by an antibody. The hapten used to elicit this antibody is a derivative of endo hexachloronor-bomene. which is a shape mimic of the transition state. Because it has less structural similarity to the aromatic product, product inhibition in the lE9-catalyzed reaction is avoided. 

The same strategy of using sulfone intermediate 30 was applied by Fluryn, Wipf, and coworkers (15MI1225) in the synthesis of the ATPases associated with diverse cellular activities ATPase p97 inhibitor 35, which contains a 2-aryl-5-SF5-indole fragment as one of the molecule... 

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