Subject sulfoxides

During the synthesis of peptides that contain 4-methoxybenzyl-protected cysteine residues, sulfoxide formation may occur. These sulfoxides, when treated with HF/ anisole, form thiophenyl ethers that cannot be deprotected therefore, the peptides should be subjected to a reduction step prior to deprotection. ... 

This chapter is an attempt to present a balanced treatment of the subject, concentrating on recent developments in the area and emphasizing the chemistry of small-ring sulfones and sulfoxides as a particular distinct category within the chemistry of the sulfone and sulfoxide functional groups. 

Viewed from the standpoint of molecular orbital theory, as it has developed during the last decade or so3, the above simple pictures of the sulfur bonding in a dialkyl sulfide are somewhat naive but they serve to introduce the subject and act as a basis for discussing the bonding in sulfoxides and sulfones. It will be convenient to use the second of the two pictures as the basis for further discussion, i.e. that involving the use of 3sp3 hybridized orbitals on sulfur. 

Corey and Chaykovsky had discovered that dimethyl sulfoxide is converted to methyl-sulfinyl carbanion upon treatment with sodium hydride114 and that this conjugate base of DMSO reacts with various electrophiles115. This finding has opened up various reactions with a-sulfmyl carbanions derived from sulfoxides, since the sulfinyl function can be removed either by thermolysis or by subjecting the compound to reductive desulfurization. Thus a-sulfmyl carbanions have become versatile synthetically useful reagents. 

In the reaction of 88 with /(-phenethyl bromide, l-phenethyl-3-phenylpropyl methyl sulfoxide and bis-3-phenylpropyl sulfoxide, besides 3-phenylpropyl methyl sulfoxide are obtained118. Sulfoxides, bearing a /1-hydrogen to the sulfmyl function, give olefins upon thermolysis. Utilizing this reaction, Trost and Bridges120 alkylated benzyl phenyl sulfoxide, 3,4-methylenedioxybenzyl phenyl sulfoxide, phenylthiomethyl phenyl sulfoxide, phenylsulfinylmethyl phenyl sulfoxide and cyanomethyl phenyl sulfoxide with alkyl, allyl and benzyl halides and subjected these sulfoxides to thermolysis, obtaining olefins in one-pot processes. 

Owing to the reversible nature of the allylic sulfenate/allylic sulfoxide interconversion, the stereochemical outcome of both processes is treated below in an integrated manner. However, before beginning the discussion of this subject it is important to point out that although the allylic sulfoxide-sulfenate rearrangement is reversible, and although the sulfenate ester is usually in low equilibrium concentration with the isomeric sulfoxide, desulfurization of the sulfenate by thiophilic interception using various nucleophiles, such as thiophenoxide or secondary amines, removes it from equilibrium, and provides a useful route to allylic alcohols (equation 11). 

Novi and coworkers124 have shown that the reaction of 2,3-bis(phenylsulfonyl)-l,4-dimethylbenzene with sodium benzenethiolate in dimethyl sulfoxide yields a mixture of substitution, cyclization and reduction products when subjected at room temperature to photostimulation by a sunlamp. These authors proposed a double chain mechanism (Scheme 17) to explain the observed products. This mechanism is supported by a set of carefully designed experiments125. The addition of PhSH, a good hydrogen atom donor, increases the percent of reduction products. When the substitution process can effectively compete with the two other processes, the increase in the relative yield of substitution (e.g., with five molar equivalents of benzenethiolate) parallels the decrease in those of both cyclization and reduction products. This suggests a common intermediate leading to the three different products. This intermediate could either be the radical anion formed by electron transfer to 2,3-bis(phenylsulfonyl)-l,4-dimethylbenzene or the a radical formed... 

Phenol, the simplest and industrially more important phenolic compound, is a multifunctional monomer when considered as a substrate for oxidative polymerizations, and hence conventional polymerization catalysts afford insoluble macromolecular products with non-controlled structure. Phenol was subjected to oxidative polymerization using HRP or soybean peroxidase (SBP) as catalyst in an aqueous-dioxane mixture, yielding a polymer consisting of phenylene and oxyphenylene units (Scheme 19). The polymer showed low solubility it was partly soluble in DMF and dimethyl sulfoxide (DMSO) and insoluble in other common organic solvents. 

Rearrangements involving sulfoxides have played an important role in the development of the chemistry of sulfoxides. It is therefore not surprising that all major literature surveys on sulfoxides " , or their sulfenate precursors , also include a discussion of this subject. However, while excellent and detailed coverage exists for certain rearrangements of general mechanistic and synthetic interest, such as, for example, the Pummerer " or the related penicillin sulfoxide-cephalosporin " rearrangement, the treatment of all... 

Three excellent reviews cover this subject through the early 1980s . The second review summarizes through 1981 the methods used for determining the enantiomeric purity and the absolute configuration of sulfoxides, and the third review summarizes this area through 1983. ... 

Ketosulfoxides are subject to chelation control when reduced by DiBAlH in the presence of ZnCl2.141 This allows the use of chirality of the sulfoxide group to control the stereochemistry at the ketone carbonyl. 

The desulfurization process reported by the authors was a hybrid process, with a biooxidation step followed by a FCC step. The desulfurization apparently occurs in the second step. Thus, the process seems of no value, since it does not remove sulfur prior to the FCC step, but only oxidizes it to sulfoxides, sulfones, or sulfonic acids. The benefit of such an approach is not clearly outlined. The benefit of sulfur conversion can be realized only after its removal, and not via a partial oxidation. Most of the hydrotreatment is carried out prior to the FCC units, partially due to the detrimental effect that sulfur compounds exert on the cracking catalyst. It is widely accepted that the presence of sulfur, during the regeneration stage of the FCC units, causes catalyst deactivation associated with zeolite decay. In general terms, the subject matter of this document has apparent drawbacks. 

Arylazo-4-(3-ethoxycarbonylureido)furoxans 62, which were synthesized by the reactions of 4-amino-3-arylazo-furoxans with ethoxycarbonyl isocyanate, were subjected to cascade rearrangements under the action of potassium r/-butoxidc in dimethylformamide or by heating in dimethyl sulfoxide to form 4-amino-2-aryl-5-nitro-2//-l,2,3-triazoles 63 (Scheme 13) <2001MC230, 2003RCB1829>. 

Tomas et al. [281] have calculated the tautomeric equilibrium of 1,2,3-benzotriazole in the gas phase and compared their results to experimental data [282] derived from ultraviolet spectroscopy. Experiment suggests that 35 is about 4 kcal/mol more stable than 34 this result is consistent with calculations [281] at the MP2/6-31G level, which predict 35 to be 2.5 kcal/mol more stable than 34. The same level of theory predicts 33 to be 5.0 kcal/mol more stable than 32 in the parent triazole system. Although experimental data are available indicating 35 to be the dominant tautomer in CDCf and d6-dimethyl sulfoxide solutions [279, 283], this equilibrium does not appear to have been the subject of any modeling, continuum or otherwise. It may prove to be somewhat challenging, however. Tomas et al. point out that correlation effects favor 35 by about 5 kcal/mol at the MP2 level AMI, PM3, and HF calculations with moderate basis sets all predict... 

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