Alkyl Benzyl Sulfides Research Articles

Investigation of steric and electronic effects in the copper-catalysed asymmetric oxidation of sulfides

Steric and electronic effects in the copper-catalysed asymmetric oxidation of aryl benzyl, aryl alkyl and alkyl benzyl sulfides have been investigated. The presence of an aryl group directly attached to the sulfur is essential to afford sulfoxides with high enantioselectivities, with up to 97% ee for 2-naphthyl benzyl sulfoxide, the highest enantioselectivity achieved to date for copper-catalysed asymmetric sulfoxidation. In contrast, the benzyl substituent can be replaced by sterically comparable groups with no effect on enantioselectivity. Copper-mediated oxidation of substituted aryl benzyl sulfides display modest steric and electronic effects resulting in comparable or lower enantioselectivities to those obtained with the unsubstituted benzyl phenyl sulfide.

Oxidation of sulfides to sulfones with hydrogen peroxide in the presence of acetic acid and Amberlyst 15

The oxidation of thioanisole to its sulfone with hydrogen peroxide (H2O2) in the presence of acetic acid and Amberlyst 15 was investigated and found to be a simple and effective method. Oxidation experiments in the absence of acetic acid or Amberlyst 15 confirmed the essentiality of these components for the complete oxidation of thioanisole to its sulfone with H2O2. In the two-step oxidation process of sulfide, in the oxidation of sulfide to sulfoxide, H2O2 plays a major role, whereas in the oxidation of sulfoxide to sulfone, peracetic acid formed with H2O2 in the presence of acetic acid and Amberlyst 15 plays a major role. Sulfone formation increased with an increase in H2O2, temperature and Amberlyst 15 and decreased with acetic acid. However, with a very low amount of acetic acid, sulfone formation decreased due to water in H2O2 and released in the reaction. Reutilization of Amberlyst 15 for six cycles resulted in a 6.8 % decrease in sulfone yield and 3.4 % decrease in oxygenation. Dialkyl, dibenzyl, diphenyl, alkylaryl, arylbenzyl, alkylbenzyl sulfides are completely oxidized with this oxidation system to their corresponding sulfones. The reactivity of sulfides is in the order dialkyl > dibenzyl > diphenyl sulfides, which is in line with their order of nucleophilicity.

Dioxygenase-catalysed mono-, di- and tri-oxygenation of dialkyl sulfides and thioacetals: chemoenzymatic synthesis of enantiopure cis-diol sulfoxides

Toluene dioxygenase (TDO)-catalysed monooxygenation of methylsulfanylmethyl phenyl sulfide 1 and methylsulfanylmethyl 2-pyridyl sulfide 4, using whole cells of Pseudomonas putida UV4, occurred exclusively at the alkyl aryl sulfur centre to yield the alkyl aryl sulfoxides 2 and 5 respectively. These sulfoxides, accompanied by the dialkyl sulfoxides 3 and 6, were also obtained from naphthalene dioxygenase (NDO)-catalysed sulfoxidation of thioacetals 1 and 4 using intact cells of P. putida NCIMB 8859. Enzymatic oxidation of methyl benzyl sulfide 7, 2-phenyl-1,3-dithiane 19, and 2-phenyl-1,3-dithiolane 23, using TDO, gave the corresponding dialkyl sulfoxides 8, 20 and 24 as minor bioproducts. TDO-catalysed dioxygenation of the alkyl benzyl sulfides 7, 15 and 17 and the thioacetals 19 and 23, with P. putida UV4, yielded the corresponding enantiopure cis-dihydrodiols 9, 16, 18, 21 and 25 as major metabolites and cis-dihydrodiol sulfoxides 14, 22 and 26 as minor metabolites, resulting from a tandem trioxygenation of substrates 7, 19 and 23 respectively. Chemical oxidation, of the enantiopure cis-dihydrodiol sulfides 9, 16, 18 and 21 with dimethyldioxirane (DMD), gave separable mixtures of the corresponding pairs of cis-dihydrodiol sulfoxide diastereoisomers 14 and 27, 28 and 29, 30 and 31, 22 and 32. While dialkyl sulfoxide bioproducts 3, 6, 20 and 24 were of variable enantiopurity (27–≥98% ee), alkyl aryl monosulfoxides 2 and 5, cis-dihydrodiols 9, 16, 18, 21 and 25 and cis-dihydrodiol sulfoxide bioproducts 14, 22 and 26 were all single enantiomers (≥98% ee). The absolute configurations of the products, obtained from enzyme-catalysed (TDO and NDO) and chemical (DMD) oxidation methods, were determined by stereochemical correlation, circular dichroism, and X-ray crystallographic methods.

Mechanism of the Solution-Phase Reaction of Alkyl Sulfides with Atomic Hydrogen. Reduction via a 9-S-3 Radical Intermediate.

The low selectivity of benzyl alkyl sulfide fragmentation subsequent to its reaction with atomic hydrogen is indicative of a reaction that proceeds via an early transition state. The competitive reduction of a series of substituted-benzyl alkyl sulfides was insensitive to the substituent on the aromatic ring (rho = -0.13, r = 0.99). The relative rates of fragmentation of a series of the substituted-benzyl alkyl sulfides gave a V-shaped Hammett plot. Both electron-donating and electron-withdrawing groups destabilized the transition state (rho = +0.99, r = 0.999; rho = -0.82, r = 0.992). Since the relative rates of disappearance of the alkyl benzyl sulfides are not substituent dependent, but the relative rates of fragmentation are, a 9-S-3 intermediate is preferred as the structure leading to products.

Mechanism of Sulfur Inversion in Sulfide Complexes of Gold(I) and Gold(III)

Abstract Kinetic parameters for the sulfur inversion in various gold chloride complexes of alkyl benzyl sulfides were measured by the dynamic NMR method in order to obtain conclusive evidence for the inversion mechanism. A feature of kinetic data is that entropies of activation are nearly zero both in the gold(III) and gold(I) complexes, this suggesting that the sulfur inversion takes place via pyramidal inversion mechanism without breakage of the Au–S coordination bonds but not the dissociative mechanism. The negligible solvent effect on the inversion rates in the gold(III) and gold(I) complexes supports this mechanism as well. The barrier to sulfur inversion is higher by 2.9 kcal mol−1 in the gold(III) complexes than in the corresponding gold(I) complexes. The formal gold(II) complex exists as 1 : 1 mixture of gold(I) and gold(III) complexes in solution, each of them showing the dynamic behavior independently. The effect of oxidation state of the central gold atom on the sulfur inversion is discussed on the basis of MO calculation.

Microbial oxidation of benzyl sulfides and bibenzyl by Mortierella isabellina and Helminthosporium species

The biotransformation of 1,2-diphenylethane by the fungus Mortierella isabellina ATCC 42613, and that of a series of alkyl benzyl sulfides by the fungi M. isabellina and Helminthosporium species NRRL 4671 have been studied. Mortierella hydroxylates 1,2-diphenylethane in low yield, giving (S)-1,2-diphenylethanol with an enantiomeric purity of 33%. Bioconversions of deuterium-labelled and racemic 1,2-diphenylethanol by M. isabellina demonstrate that this organism performs reversible oxidation/reduction of the alcohol. Biotransformations of n-alkyl benzyl sulfides by H. species give predominantly the (S) enantiomer of sulfoxide, with no sulfone formation, but M. isabellina, although showing a general preference for the oxidation of alkyl benzyl sulfides to (R) sulfoxides, also generates sulfones from n-alkyl benzyl sulfides in a time-dependent manner that suggests a stereoselective removal of (R) sulfoxide. The latter microorganism can be used, however, for the production of (R)-benzyl methyl and benzyl isopropyl sulfoxides, and gives (S)-benzyl tert-butyl sulfoxide in low yield. Key words: biotransformation, enzymes, sulfoxides.

Cooxidation reaction in the singlet oxygenation of cyclic and benzylic sulfides: S-hydroperoxysulfonium ylide intermediate as a new epoxidizing species

The reaction of singlet oxygen with a series of 3-benzoyl-4-(methoxycarbonyl) thiazolidine derivatives and alkyl benzyl sulfides in methylene chloride in the presence of olefins has been investigated. The reaction of singlet oxygen with the sulfides caused cooxidation of olefins to the corresponding epoxides in substantial yields. The epoxidation of olefins by the active oxidizing species generated in photosensitized oxygenation of the sulfides is provided, suggesting that the new epoxidizing species is probably the S-hydroperoxysulfonium ylide intermediate derived from a persulfoxide intermediate by intramolecular α-proton abstraction

Formation of C–S Bond by the Elimination of Perfluorocarboxylic Acid

Abstract Thiirane was readily generated from 2-mercaptoethyl trifluoroacetate or pentafluoropropionate by the intramolecular elimination of the perfluorocarboxylic acid with triethylamine. Alkyl benzyl sulfides were also prepared from benzyl trifluoroacetate or pentafluoropropionate and alkanethiols by the intermolecular elimination of the perfluorocarboxylic acid