Benzyl Methyl Sulfoxide Research Articles

Methanesulfinylation of Benzyl Halides with Dimethyl Sulfoxide.

A phenyltrimethylammonium tribromide-mediated nucleophilic substitution/oxygen transformation reaction of benzyl halides with DMSO has been developed. In this transition-metal-free reaction, DMSO acts as not only a solvent but also a "S(O)Me" source, thus providing a convenient method for the efficient and direct synthesis of various benzyl methyl sulfoxides.

Chiral non-racemic sulfoxides by asymmetric alkylation of alkanesulfenates in the presence of a chiral ammonium phase-transfer catalyst derived from Cinchona alkaloid

Based on a previous study involving arenesulfenates, the enantioselective S-alkylation of benzyl and alkyl sulfenates R1SO− with alkyl halides, mediated by a cinchonidinium phase-transfer catalyst, was evaluated as a conceptually different synthetic approach to chiral sulfoxides. Direct application of our standard organocatalytic protocol, with methyl iodide as the electrophile, was rather disappointing mainly as a result of a sluggish release of the sulfur nucleophiles. However, slight modifications of the reaction conditions allowed the isolation of (R)-benzyl methyl sulfoxide in a 60% yield and a 38% ee, whereas (R)-cyclohexyl methyl sulfoxide was produced in a 34% yield and a 47% ee.

Pyramidal inversion mechanism of simple chiral and achiral sulfoxides: A theoretical study

The pyramidal inversion mechanism of simple sulfoxides was studied, employing ab initio and DFT methods. The convergence of the geometrical and energetic parameters of H2SO and DMSO with respect to the Hamiltonian and basis set was analyzed in order to determine a computational level suitable for methyl phenyl sulfoxide (3), methyl 4-cyanophenyl sulfoxide (4), diphenyl sulfoxide (5), 4,4'-dicyanodiphenyl sulfoxide (6), benzyl methyl sulfoxide (7) and benzyl phenyl sulfoxide (8). The DFT B3LYP/6-311G(d,p) level was chosen for further calculations of larger sulfoxides. The barriers DeltaE calculated for the pyramidal inversion mechanism of sulfoxides 3-8 are in the range of 38.7-47.1 kcal/mol. These values are in good agreement with the experimental barriers for racemization via the pyramidal inversion mechanism. A resonance effect of a phenyl ring selectively stabilizes the transition state conformations, decreasing the energy barrier for pyramidal inversion by about 3 kcal/mol, compared to a similar molecule without a phenyl substituent. Introducing electron withdrawing groups (cyano) at the para positions of the phenyl ring(s) causes a further decrease of the energy barrier.

Molecular recognition of l-leucyl- l-alanine: enantioselective inclusion of alkyl methyl sulfoxides

A simple aliphatic dipeptide, l-leucyl- l-alanine (Leu-Ala), includes several alkyl methyl sulfoxides enantioselectively to form inclusion crystals. From single-crystal X-ray analyses of three inclusion compounds of dimethyl sulfoxide (DMSO), isobutyl methyl sulfoxide, and benzyl methyl sulfoxide, it was elucidated that Leu-Ala molecules self-assemble to form layer structures and the sulfoxides are included via hydrogen bonding in a cavity between these layers. The inclusion cavity has methyl group and isobutyl group at its each side, and the guest sulfoxide is placed in such a manner that its methyl group faces toward the methyl of the Leu-Ala cavity. When the alkyl group of the sulfoxide is comparably large, it is located in the residual space of the cavity to attain effective crystal packing. Thus, the sulfoxides having a comparably large group such as isobutyl, butyl, and benzyl are included with a high ( R)-enantioselectivity in Leu-Ala crystals.

Synthesis and spectroscopic behavior of highly luminescent Eu3+–dibenzoylmethanate (DBM) complexes with sulfoxide ligands

In this paper the synthesis, characterization and photoluminescent behavior of the [RE(DBM)3L2] complexes (RE=Gd and Eu) with a variety of sulfoxide ligands; L=benzyl sulfoxide (DBSO), methyl sulfoxide (DMSO), phenyl sulfoxide (DPSO) and p-tolyl sulfoxide (PTSO) have been investigated in solid state. The emission spectra of the Eu(3+)-beta-diketonate complexes show characteristics narrow bands arising from the 5D0-->7F(J) (J=0-4) transitions, which are split according to the selection rule for C(n), C(nv) or C(s) site symmetries. The experimental Judd-Ofelt intensity parameters (Omega2 and Omega4), radiative (A(rad)) and non-radiative (A(nrad)) decay rates, and R02 for the europium complexes have been determined and compared. The highest value of Omega2 (61.9x10(-20)cm2) was obtained to the complex with PTSO ligand, indicating that Eu3+ ion is in the highly polarizable chemical environment. The higher values of the experimental quantum yield (q) and emission quantum efficiency of the emitter 5D0 level (eta) for the Eu-complexes with DMSO, DBSO and PTSO sulfoxides suggest that these complexes are promising Light Conversion Molecular Devices (LCMDs). The lower value of quantum yield (q=1%), for the hydrated complex [Eu(DBM)3H2O], indicates that the luminescence quenching occurs via multiphonon relaxation by coupling with the OH-oscillators from water molecule coordinated to rare earth ion. The pure red emission of the Eu-complexes has been confirmed by (x, y) color coordinates.

Enantioselective inclusion of ( R)-phenylglycyl-( R)-phenylglycine with benzyl methyl sulfoxides

A crystalline dipeptide, ( R)-phenylglycyl-( R)-phenylglycine ( RR- 1 ), recognized p-halobenzyl methyl sulfoxides with high R-enantioselectivity (86–99% ee) to form inclusion compounds. The single-crystal X-ray analyses showed that RR- 1 molecules are arranged in parallel and zigzags via hydrogen bonding to construct a pleated sheet. The guest molecules that form hydrogen bond with +NH 3 of RR- 1 are accommodated in the channel cavity between the layers. In contrast to the inclusion crystals of parent benzyl methyl sulfoxide, in which a rectangular cavity is formed, the cavity including p-halobenzyl methyl sulfoxides becomes rhomboidal. We also examine the guest exchange in these inclusion compounds and it was found that the guest exchanges occur when the host structure changes.

Chemical activation of cytochrome c proteins via crown ether complexation: cold-active synzymes for enantiomer-selective sulfoxide oxidation in methanol.

Supramolecular complexation with 18-crown-6 significantly converted catalytically inactive cytochrome c (biological form) to catalytically active synzyme (artificial form). Although a family of cytochrome c proteins does not work as enzymes in nature, crown ether complexation modified their heme coordination structures and functionally activated them to promote the asymmetric oxidation of racemic sulfoxides at low temperature. Horse heart, pigeon breast, and yeast cytochrome c proteins were demonstrated to form supramolecular complexes with 18-crown-6 in methanol, which effectively oxidized (S)-isomers of naphthyl methyl sulfoxide, methyl tolyl sulfoxide, isopropyl phenyl sulfoxide, benzyl methyl sulfoxide, and 4-methylsulfenyl acetophenone at -40 degrees C. Because horse heart and pigeon breast cytochromes c exhibited more efficient and higher enantiomer-selective activities than yeast cytochrome c, a proper combination of cytochrome c and crown ether offers a new class of cold-active synzymes promoting nonbiological asymmetric oxidation.

Enantioselective inclusion of methyl phenyl sulfoxides and benzyl methyl sulfoxides by (R)-phenylglycyl-(R)-phenylglycine and the crystal structures of the inclusion cavities

Crystalline (R)-phenylglycyl-(R)-phenylglycine [(R,R)-1] includes methyl phenyl sulfoxides (2 and 3) and benzyl methyl sulfoxides (4) with high enantioselectivity. The dipeptide exhibited different stereoselectivity depending on four structural isomers of methyl tolyl sulfoxide (C(8)H(10)OS): R for methyl 2-tolyl sulfoxide, S for methyl 3-tolyl sulfoxide, and racemic for methyl 4-tolyl sulfoxide. A structural isomer, benzyl methyl sulfoxide, was included in racemic form. Chlorophenyl methyl sulfoxides 3 (C(7)H(7)ClOS) with a similar volume showed the same enantioselectivity for their recognition. By single-crystal X-ray analyses of these inclusion compounds, it was elucidated that (R,R)-1 molecules self-assembled to form layer structures and included the sulfoxides between these layers and that the origin of the enantioselectivity based on chiral cavities was induced by conformation of the C-terminal phenyl group of the dipeptide. The relative position between the ammonio proton and the C-terminal phenyl group in one molecule of the dipeptide determined the stereochemistry of the methyl sulfinyl groups to be recognized. Various positional isomers of methyl xylyl sulfoxide having the formula of C(9)H(12)OS were subjected to the enantioselective inclusion by (R,R)-1 crystals and these results are also discussed.

Biotransformation of organic sulfides: Part. 10. Formation of chiral ortho- and meta-substituted benzyl methyl sulfoxides by biotransformation using Helminthosporium species NRRL 4671

Benzyl methyl sulfides substituted with methyl, chloro, cyano, bromo, methoxy, nitro and amino groups in the ortho or meta positions of the aromatic ring have been converted to ( S) sulfoxides by biotransformation using the fungal biocatalyst Helminthosporium species NRRL 4671. The enantiomeric excesses for meta-substituted examples were high in those cases where the substituent was of a polar nature, and comparable to those observed for the corresponding para-substituted substrates. With one exception ( o-amino), the ortho-substituted examples gave sulfoxides of lower enantiomeric purity. The role of a suitably located polar substituent on an aryl ring of the substrate in ensuring a high enantiomeric excess in sulfoxidation by Helminthosporium species has been confirmed by the biotransformations of 4-(methylthiomethyl)benzyl alcohol and 2-(4-nitrophenyl) ethyl methyl sulfide, which give sulfoxides of much higher optical purity than those obtained from the corresponding unsubstituted substrates.

Cis-(R,S)-Bis(benzyl methyl sulfoxide)dichloroplatinum(II)

The coordination around the Pt atom in the title compound [PtCl2(C8H10OS)2] is pyramidally distorted from cis square-planar; two chloride ions form Pt-Cl bonds of 2.310 (3) and 2.307 (3) Å and two benzyl methyl sulfoxide groups form Pt-S bonds of 2.241 (2) and 2.233 (2) Å.

ChemInform Abstract: Optical Resolution of Methyl Phenyl and Benzyl Methyl Sulfoxides and Alkyl Phenylsulfinates by Complexation with Chiral Host Compounds Derived from Tartaric Acid.

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Biotransformation of organic sulfides. Part 6. Formation of chiral para-substituted benzyl methyl sulfoxides by Helminthosporium species NRRL 4671

The fungus Helminthosporium species NRRL 4671 has been used for the biotransformation of a series of para -substituted benzyl sulfides with substituent groups consiting of trifluoromethyl, halo, hydroxy, methoxy, acetoxy, nitro, cyano, amino, acetamido, acyl and carboxylic acid units. In all cases, sulfoxide formation occurred in good yield and with predominant ( S ) chirality at the sulfur position. A minor amount of sulfone product was also obtained from the halo- and methoxy-substituted substrates. Graphic

Biological Sciences and Analytical Chemistry. Application of micellar electrokinetic chromatography for monitoring the kinetic resolution of sulfoxides by dimethyl sulfoxide reductase.

Recently, micellar electrokinetic chromatography (MEKC) has been successfully applied to the separation of electrically neutral compounds. In this study, we applied this method in order to determine simultaneously organic sulfoxide and sulfide; benzyl methyl sulfoxide (BMSO) and benzyl methyl sulfide (BMS), respectively. Dimethyl sulfoxide (DMSO) reductase from Rhodobacter sphaeroides f. sp. denitrificans deoxygenates (S)-BMSO preferably. The MEKC method gave reliable estimates of BMSO concentration without any pretreatment, therefore, the (R)-isomer could be recovered with high enantiomeric excess by stopping the reaction at the conversion rate of 50%. Using this detection method, (R)-BMSO was recovered with good chemical and optical yields. The simple and rapid measurement by MEKC was proved to be suitable for the kinetic resolution of racemic sulfoxide by the enzymatic reaction.

Optical resolution of methyl phenyl and benzyl methyl sulfoxides and alkyl phenylsulfinates by complexation with chiral host compounds derived from tartaric acid

The title sulfoxides and sulfinates are resolved by complexation with chiral host compounds derived from tartaric acid.

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.

Reactions of cis-[Pt(sulfoxide)2Cl2] with silver salts and synthesis of hydroxo-bridged platinum(II) complexes with sulfoxides

Platinum(II) compounds of the type cis-[Pt(L)2X2] where L = tetramethylenesulfoxide (TMSO), ethylmethylsulfoxide (EMSO), di-n-propylsulfoxide (DPSO), benzylmethylsulfoxide (BMSO), and dibenzylsulfoxide (DBSO) and X = Cl− and I− have been synthesized. The reactions of these compounds with a silver salt were studied in aqueous solution. Monomers of the type cis-[Pt(L)2(ClO4)2] (L = TMSO, EMSO, and DBSO), cis-[Pt(EMSO)2(SO4)] and hydroxy-bridged oligomers were isolated. Dimers, cis-[Pt(L)2(OH)]2(NO3)2 (L = TMSO, DPSO), and cis-[Pt(EMSO)2(OH)]2SO4 and possibly a trimer (cis-[Pt(EMSO)2(OH)]3)2(SO4)3 were characterized. The compounds were studied by infrared spectroscopy and by 1H nmr.

Towards a complete account of diastereotopic hydrogen isotope exchange of carbon acids. III. Base-catalyzed exchange of sulfoxides. Evidence for exchange by inversion

The rate constants for deuteroxide and hydroxide catalyzed H → D and D → H exchange of benzodihydrothiophene oxide (1a) and several of its deuterated analogs 1b, 1c, and 1d at 30.00 ± 0.05 °C are reported along with the rate constants for D → H exchange of deuterated benzyl methyl sulfoxides 2b and 2c. Application of the steady-state assumption to schemes involving equilibrating pyramidal anions yield equations which are used to fit experimentally determined (kf/ks)H → D and (kf/ks)D → H ratios. The analysis supports our view that exchange of the diastereotopic protons (deuterons) occurs by inversion. The inversion component contributes significantly to exchange of the "slow" proton (deuteron) of a diastereotopic pair and this accounts for the observation that (kf/ks)D → H < (kf/ks)H → D. This study establishes an upper limit of 6 kcal for the barrier to inversion of the carbanions derivable from 1 and 2, if pyramidal anions are formed.

Intermolecular Pummerer Rearrangement Reactions of Alkyl Phenyl and Dialkyl Sulfoxides with Acetic Anhydride

Abstract The Pummerer reactions of alkyl phenyl sulfoxides, PhS(O)R (R: methyl and isobutyl), and benzyl methyl sulfoxide with acetic anhydride were found to proceed through the intermolecular acetoxyl migration, based on the 18O-tracer experiments with 18O-labeled sulfoxides and unlabeled acetic anhydride.

Stereochemical aspects of the Pummerer reaction. Diastereotopic selectivity in the deprotonation of oxysulfonium cations

The diastereomeric RS/SR- and RR/SS-benzyl-α-d methyl sulfoxides have been subjected to the Pummerer reaction with acetic anhydride and with trifluoroacetic anhydride. The ethoxysulfonium fluoroborate derivatives of these sulfoxides have been subjected to the Pfitzner–Moffatt reaction with sodium hydride in tetrahydrofuran. The deuterium contents of the starting materials and of the Pfitzner–Moffatt product have been determined by mass spectrometry. The deuterium contents of the α-acyloxybenzyl methyl sulfoxides formed in the Pummerer reaction have been determined by 1Hmr spectroscopy. The resulting data permit the calculation of the diastereotopic selectivities and isotope effects associated with the deprotonation of oxysulfonium cations. The selectivities are found to be lower by a factor of about 10 than those observed in the formation of the benzyl-α-d methyl sulfoxides by hydrogen–deuterium exchange of benzyl methyl sulfoxide. Nevertheless, the existence of selectivity in the Pummerer reactions rules out a sulfurane and a dication as sole product-determining intermediates. The factors contributing to this low selectivity are discussed.

Stereochemical aspects of the Pummerer reaction. Regioselectivity as a criterion for the differentiation of ylide and E2 pathways in the product-determining step of the reactions of benzyl methyl halo- and oxysulfonium cations

The conversion of [Formula: see text] (X = Cl, OCH3, OCOCH3, OCOCHCl2, OCOCF3) to a regioisomeric mixture of p-Y-C6H4CHXSCH3 and p-Y-C6H4CH2SCH2X has been studied as a function of X, Y, and deuteration in the benzyl and methyl positions. The conclusion is reached that, when X is acyloxy, the transformation of the sulfonium cation to an α-thiocarbonium ion and thence to the products proceeds via an E2 pathway. Trifluoroacetic anhydride is a much more reactive reagent than acetic anhydride for Pummerer reactions of benzyl methyl sulfoxides. However, with other sulfoxides, this reagent is not as effective as acetic anhydride. Acetyl trifluoroacetate is not effective as a Pummerer reagent.