S. Oae

Mechanism of elimination reactions : The E2 reactions of substituted α-phenylethyl bromides

Abstract The rates of the base-catalysed elimination of a series of substituted α-phenylethyl bromides have been determined in t-BuOK-t-BuOH, t-BuOK-t-BuOH-DMSO and EtONa-EtOH systems. The Hammett ϱ values obtained were, although small and not in linear correlation with σ values, positive in all cases. β-Methyl group retarded the rate in t-BuOK-t-BuOH and in t-BuOK-t-BuOH-DMSO, but enhanced it in EtONa-EtOH. β-Hydrogen kinetic isotope effects were 5·0, 3·5 and 3·4, respectively. The nature of transition states is discussed in the light of these observations.

Reduction of semipolar sulphur linkages with carbodithioic acids and addition of carbodithioic acids to olefins

Abstract Carbodithioic acids react with trivalent sulphur compounds bearing semipolar linkages (sulphoxides, sulphonium ylides and sulphilimines), to give the corresponding sulphides and add to olefins to afford dithioesters. The orientation of olefin addition is controlled by the olefin nature. Michael type addition takes place with olefins bearing an electron-withdrawing group α to the double bond while Markownikoff addition occurs with olefins bearing an electron-donating group. With vinyl and allyl sulphoxides, both addition and reduction took place simultaneously, and new dithioesters were obtained.

Model pathways for enzymatic oxidate demethylation—I : The mechanism of the reaction of dimethyl sulphoxide with acetic anhydride

Abstract The reaction of sulphoxides with at least one methyl or methylene group with carboxylic acid anhydride, called the Pummerer reaction, gives α-acyloxy derivatives of the corresponding sulphide. The mechanism of this reaction was studied by oxygen-18 tracer technique. The reaction between dimethyl sulphoxide and acetic anhydride appears to proceed through an intermolecular rearrangement by nucleophilic attack of acetate anion on methylene carbon atom of the intermediate II. The implications of this reaction and the enzymatic oxidative demethylation are considered in connection with a previous investigation with t-amine N-oxides.

3d-orbital resonance in divalent sulphides—IV: Acidity of hydrogen atom adjacent to mercapto groups☆☆☆

Abstract The rates of base-catalysed hydrogen-isotope exchange reactions of various sulphides and their corresponding oxygen analogues have been measured in order to compare the relative acidifying effects of mercapto and alkoxy groups toward α-hydrogen atoms. Practically no exchange reaction was abserved in the oxygen compounds, whereas, with the sulphur compounds, the reaction readily takes place, the rate being increased several powers of ten by the substitution of one additional mercapto group. Furthermore, dramatic rate increase was observed when an open chain compound, orthothioformate was cyclized to the corresponding bicyclic compound. These observations are interpreted in terms of the 3d orbital resonance of the sulphur atom.Abstract The rates of base-catalysed hydrogen-isotope exchange reactions of various sulphides and their corresponding oxygen analogues have been measured in order to compare the relative acidifying effects of mercapto and alkoxy groups toward α-hydrogen atoms. Practically no exchange reaction was abserved in the oxygen compounds, whereas, with the sulphur compounds, the reaction readily takes place, the rate being increased several powers of ten by the substitution of one additional mercapto group. Furthermore, dramatic rate increase was observed when an open chain compound, orthothioformate was cyclized to the corresponding bicyclic compound. These observations are interpreted in terms of the 3d orbital resonance of the sulphur atom.

3d-orbital resonace in divalent sulphides—V activity of α-hydrogen atom of cyclic mercaptals☆☆☆

Abstract Previously,1 it was found that the base-catalysed hydrogen exchange reactions of sulphides is effected 3d orbital resonance involving uncharged sulphur groups. This investigation now extended to several syclic mercaptals, reveals that ring size and conformation affect the exchange rates substantially. Unsubstituted cyclic mercaptals are more reactive than the open chain compounds, the relative rates of open chain, five- and six-membered ring compounds bein 39.9, 516 and 214 respectively. Alkyl substituents reduce the rates substantially in both open chain and cyclic mercaptals; the relative rates of ethyl subtituted compounds being 1·00 for acyclic, 19·1 for five-, 1·55 for six- and 5·37 for seven-membered cyclic compounds. This rate reduction is greater by a factor of about 4—5 for six-membered cyclic compounds 214/1·55 = 138) than for the other compounds. These results are interpreted in terms of comformational changes, solvation and the 3d orbital resonance of sulphur atoms.

The mechanisms of the reactions of p-toluenesulfonyl chloride with isoquinoline- and pyridine n-oxides☆

Abstract The mechanisms of the reactions of isoquinoline- and pyridine N-oxides have been studied using oxygen-18 as a tracer. p-Toluenesulfonyl chloride labeled with 18O was reacted with isoquinoline N-oxide, yielding 4-tosyloxyisoquinoline, a portion of which was further hydrolyzed yielding 4-hydroxyisoquinoline. The analytical results suggest that the main path of this reaction proceeds via “intimate ion pair” as depicted by VI. In the reaction of pyridine N-oxide with p-toluenesulfonyl chloride, 18O tracer study suggests that a similar rearrangement via “intimate ion pair” as VI takes place with the formation of 3-tosyloxypyridine.

A novel cyclization reaction of o-carboxyphenyl and o-carbamoylphenyl sulfoxides : Formation of benzoxathiane, dihydrobenzothiazine and benzoisothiazoline derivatives

Abstract When o -carboxyphenyl or o -carbamoylphenyl sulfoxide was heated with a large excess of acetic anhydride at 100–130° for 1–3 h, 6-membered heterocyclic compounds, i.e. , 3,1 - benzoxathian-4 - one and 2,3 - dihydro - 1,3 - benzothiazin - 4 - one, and a 5-membered heterocyclic compound, i.e. , 1,2-benzoisothiazolin-3-one were obtained in good yield. Cyclization would take place by the initial intramolecular nucleophilic attack of either the sulfinyl O atom at ortho -carbonyl carbon or the N atom of the amide group at ortho -sulfinyl S atom to give a 5-membered cyclic acyloxysulfonium salt or aminosulfonium salt, which undergoes an intramolecular Pummerer rearrangement to afford the heterocyclic compounds.

Model pathways for enzymatic oxidative demethylation—II : Polonovski reaction of N,N-dimethylaniline N-oxide, pummerer reactions of dimethyl, n-butyl methyl and methionine sulphoxide with acetylating agents and their implications in enzymatic demethylation

Abstract The reaction of N,N-dimethylaniline N-oxide with acetylphenylphosphate proceeds under a mild condition giving o -acetoxy-N,N-dimethylaniline. Similarly, acetylphenylphosphate is also effective in causing the Pummerer reaction of dimethyl sulphoxide giving the corresponding acetoxymethyl sulphide. The reaction of methionine sulphoxide with acetic anhydride gives α- acetoxy derivative of methionine. The resulting ester hydrolyses in the hydrochloric acid into homocysteine,formaldehyde and acetic acid. This demethylation reaction is discussed as a possible model pathway for the enzymatic oxidative demethylation of methionine to homocysteine.

The decomposition of diacyl peroxides—I : The thermal decomposition of primary and secondary diacyl peroxide

Abstract The mechanism of ester formation in the thermal decomposition of a few primary and secondary diacyl peroxides has been investigated by the analysis of both the 18O-distributions and the stereochemical configurations of the resulting esters, using 18O-labelled and/or optically active diacyl peroxides. The decomposition of primary diacyl peroxides is mainly homolytic. Acetyl peroxide, the lowest member of the primary diacyl peroxide series, was found to decompose only homolytically. The decomposition of δ-phenylvaleryl peroxide, a higher primary homologue, was mainly by homolytic cleavage of the OO bond, however 30% of the ester formed was a product of heterolysis involving carboxy inversion. Ester formation from secondary diacyl peroxides, such as β-phenylisobutyryl and α-methylbutyryl peroxides, was found to proceed mainly through the heterolytic carboxy-inversion process. Carboxy-inversion is discussed in the light of other similar rearrangements.The mechanism of ester formation in the thermal decomposition of a few primary and secondary diacyl peroxides has been investigated by the analysis of both the 18O-distributions and the stereochemical configurations of the resulting esters, using 18O-labelled and/or optically active diacyl peroxides. The decomposition of primary diacyl peroxides is mainly homolytic. Acetyl peroxide, the lowest member of the primary diacyl peroxide series, was found to decompose only homolytically. The decomposition of δ-phenylvaleryl peroxide, a higher primary homologue, was mainly by homolytic cleavage of the OO bond, however 30% of the ester formed was a product of heterolysis involving carboxy inversion. Ester formation from secondary diacyl peroxides, such as β-phenylisobutyryl and α-methylbutyryl peroxides, was found to proceed mainly through the heterolytic carboxy-inversion process. Carboxy-inversion is discussed in the light of other similar rearrangements.

Steric effects in the reaction of alkyl-phenyl and dialkyl-sulphides with chloramine-T

Abstract The rate of the reaction of dialkyl- and alkyl-phenyl-sulphides with TsNHCl increases with the increasing +I effect of the S-substituents, while the steric effect is only of minor importance. Rate constants of the reaction of dialkyl sulphides can be correlated with the Taft equation (ϱ * = −1.96, δ = 0.285). The effect of ring size of cyclic sulphides on the reaction is discussed. The change of the rate constants with varying S-alkyl substituents is in agreement with a sterically unhindered electrophilic addition of Cl + on bivalent sulphur, leading to chlorosulphonium ion. Sulphimides and sulphoxides are formed from the chlorosulphonium intermediates in the subsequent S N -type reactions with different steric control.