515-46-8Relevant articles and documents
Nucleophilic Substitution at Sulphonyl Sulphur. Part 2. Hydrolysis and Alcoholysis of Aromatic Sulphonyl Chlorides
Ballistreri, Francesco P.,Cantone, ALfio,Maccarone, Emanuele,Tomaselli, Gaetano A.,Tripolone, Mario
, p. 438 - 441 (1981)
Kinetics of hydrolysis, methanolysis and ethanolysis of furan-2 and -3-, thiophen-2- and -3-, and benzene-sulphonyl chlorides have been measured.Fair correlations with Taft ?* values for heterocycles are found; more satisfactory trends are observed by applying the two-parameter (polar and steric) Taft-Pavelich equation, particularly for the hydrolysis reaction including data for aliphatic sulphonyl chlorides.In this case the negative δ value, which is related to the steric parameter, is consistent with steric acceleration due to relief of strain in the transition state.Alcoholysis rates of substituted thiophen-2-sulphonyl chlorides (5-CH3, 5-Cl, 4-NO2, and 5-NO2) have been also measured in order to compare the substituent effects with those already observed for hydrolysis.The data are in accord with previous findings, that an SN2 type mechanism takes place which is shifted toward an SN1 process (looser transition state) or an SAN process (tighter transition state) in the hydrolysis and alcoholysis reactions, respectively.
Processes for the Preparation of SGLT-2 Inhibitors, Intermediates Thereof
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Paragraph 0157, (2019/01/04)
The present invention relates to novel, improved processes for the preparation of sodium glucose co-transporter 2 (SGLT-2) inhibitors and novel intermediates thereof. More particularly, the present invention relates to a novel, improved process for the preparation of gliflozin compounds such as empagliflozin and dapagliflozin, intermediates thereof. The product obtained from the processes of present invention may be amorphous or crystalline, or in the form of amorphous/crystalline solid dispersions/solutions with pharmaceutically acceptable polymers and preparation process thereof. Also, the products obtained from the present invention may be used for the preparation of medicaments for the prevention and/or treatment of diseases and conditions associated with SGLT-2 inhibition.
A kinetic study on nucleophilic displacement reactions of aryl benzenesulfonates with potassium ethoxide: Role of K+ ion and reaction mechanism deduced from analyses of LFERs and activation parameters
Um, Ik-Hwan,Kang, Ji-Sun,Shin, Young-Hee,Buncel, Erwin
supporting information, p. 490 - 497 (2013/03/13)
Pseudofirst-order rate constants (kobsd) have been measured spectrophotometrically for the nucleophilic substitution reactions of 2,4-dinitrophenyl X-substituted benzenesulfonates 4a-f and Y-substituted phenyl benzenesulfonates 5a-k with EtOK in anhydrous ethanol. Dissection of k obsd into kEtO- and kEtOK (i.e., the second-order rate constants for the reactions with the dissociated EtO - and ion-paired EtOK, respectively) shows that the ion-paired EtOK is more reactive than the dissociated EtO-, indicating that K + ion catalyzes the reaction. The catalytic effect exerted by K + ion (e.g., the kEtOK/kEtO- ratio) decreases linearly as the substituent X in the benzenesulfonyl moiety changes from an electron-donating group (EDG) to an electron-withdrawing group (EWG), but it is independent of the electronic nature of the substituent Y in the leaving group. The reactions have been concluded to proceed through a concerted mechanism from analyses of the kinetic data through linear free energy relationships (e.g., the Bronsted-type, Hammett, and Yukawa-Tsuno plots). K+ ion catalyzes the reactions by increasing the electrophilicity of the reaction center through a cyclic transition state (TS) rather than by increasing the nucleofugality of the leaving group. Activation parameters (e.g., ΔH? and ΔS?) determined from the reactions performed at five different temperatures further support the proposed mechanism and TS structures.
5-ALA ester formulations and use thereof
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, (2012/01/02)
The present invention is directed to particles comprising 5-ALA esters salts, formulation thereof, related methods of preparation and methods of use thereof. In particular, the invention relates to particles comprising 5-ALA esters salts, formulation thereof useful in the treatment of a cancer and/or the diagnosis of a cancer cell such as in photodynamic therapy or photodynamic diagnosis.
The SN3-SN2 spectrum. Rate constants and product selectivities for solvolyses of benzenesulfonyl chlorides in aqueous alcohols
Bentley, T. William,Jones, Robert O,Kang, Dae Ho,Koo, Sun
scheme or table, p. 799 - 806 (2010/06/16)
Rate constants for a wide range of binary aqueous mixtures and product selectivities (S) in ethanol - Water (EW) and methanol-water (MW) mixtures, are reported at 25 °C for solvolyses of benzenesulfonyl chloride and the 4-chloro - Derivative. S is defined as follows using molar concentrations: S =([ester product]/[acid product]) × ([water solvent]/[alcohol solvent]). Additional selectivity data are reported for solvolyses of 4-Z-substituted sulfonyl chlorides (Z - OMe, Me, H, Cl and NO2) in 2, 2, 2-trifluoroethanol-water. To explain these results and previously published data on kinetic solvent isotope effects (KSIEs) and on other solvolyses of 4-nitro and 4-methoxybenzenesulfonyl chloride, a mechanistic spectrum involving a change from third order to second order is proposed. The molecularity of these reactions is discussed, along with new term 'SN3-SN2 spectrum' and its connection with the better established term 'S N2-SN1 spectrum'. Copyright
Process for preparation of oxyglutaric acid ester derivatives
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, (2008/06/13)
A process for preparing an oxyglutaric acid ester derivative of the formula: STR1 in which each of R1 and R2 is C1-5 alkoxy, C1-7 aralkyloxy, C7-9 halogenated aralkyloxy or phenyl, R4 is a hydroxyl-protecting group, and R5 is C1-10 alkyl which may have a substituent, comprises the steps of reacting a methyl phosphonate derivative or methyl phosphine oxide derivative with an oxyglutaric acid mono-ester to give a reaction product which comprises an oxyglutaric acid derivative having a phosphorus-containing group and a pentenedioic acid mono-ester (by-product), removing the pendenedioic acid mono-ester from the reaction product to isolate the oxyglutaric acid derivative, and converting the isolated oxyglutaric acid derivative into the oxyglutaric acid ester derivative. A process for obtaining an optically active oxyglutaric acid ester derivative is also disclosed.
Intermediacy of o-sulfonylium arenide ylides in the reactions of arenesulfonyl derivatives with strong bases: Insight into the puzzling rearrangement of N-arylarenesulfonamides into 2-aminodiaryl sulfones
Eisch, John J.,Qian, Yun,Chiu, Chingchen S.
, p. 1392 - 1398 (2007/10/03)
Benzenesulfonyl derivatives, PhSO2E, such as benzenesulfonyl fluoride, phenyl benzenesulfonate, and N-methyl-N-phenylbenzenesulfonamide, have been found to undergo ortho-lithiation with lithium 2,2,6,6-tetramethylpiperidide (LTMP) in THF at -78 °C. The resulting lithio derivatives undergo 1,3-elimination of LiE to form the transient o-sulfonylium benzenide. The latter ylide, which may be stabilized by its carbenoid character and its complexation with LiE, can be trapped by benzophenone acting as a 1,3-dipolarophile to form the adduct, 3,3-diphenyl-1,2-benzoxathiole 1,1-dioxide. The alternative formation of the latter cyclic sulfonate by reaction of the initially formed o-lithio derivative with benzophenone and by subsequent cyclization was shown not to occur. If not trapped with benzophenone, such an ylide decomposes partly into SO2 and benzyne and then undergoes self-condensation to yield poly(phenylene-o,o′-biphenylene sulfones). o-Sulfonylium benzenide also can be captured by lithium alkoxides, either present adventitously or intentionally added, to generate the corresponding alkyl benzenesulfonate. However, such alkoxides, unaided by LTMP, are themselves unable to extract an ortho-proton from benzenesulfonyl fluoride or from N-methyl-N-phenylbenzenesulfonamide to yield the corresponding o-lithio derivative. With benzenesulfonyl fluoride the lithium alkoxide can also form the sulfonate ester by direct substitution at the sulfonyl group. The Closson-Hellwinkel rearrangement of N-methyl-N-phenylbenzenesulfonamide into o-(methylamino)diphenyl sulfone by RLi or LTMP is reinterpreted as proceeding by way of the 2-lithio- or 2,6-dilithiobenzenesulfonyl derivative which eliminates lithium N-methylanilide to form the o-sulfonylium benzenide or its 6-lithio derivative. Attack of the latter ylide, acting as an electrophile, upon the ortho-position of the presumably complexed LiNMePh then consummates the rearrangement.
Photooxidation of Sulfenic Acid Derivatives. 5. The Reaction of Singlet Oxygen with Ethyl Phenyl Sulfenate
Clennan, Edward L.,Chen, Ming-Fang
, p. 6444 - 6447 (2007/10/03)
The reaction of ethyl phenylsulfenate ester with singlet oxygen was investigated.The total rate of disappearance of singlet oxygen induced by the sulfenate ester, kT, was measured by monitoring the quenching of the emission of singlet oxygen at 1270 nm.This result coupled with a measurement of the rate of product formation reveals that ethyl phenylsulfenate ester does not physically quench singlet oxygen.Quantitative trapping studies with Ph2S and Ph2SO suggest that only one intermediate is kinetically required on the reaction surface.This is in dramatic contrast to sulfides and sulfenamides which require two intermediates.The implications of these results are discussed.
Metal ion catalysis in nucleophilic displacement reactions at carbon, phosphorus, and sulfur centers. III. Catalysis vs. inhibition by metal ions in the reaction of p-nitrophenyl benzenesulfonate with ethoxide
Pregel, Marko J.,Dunn, Edward J.,Buncel, Erwin
, p. 1846 - 1858 (2007/10/02)
The rate of the nucleophilic displacement reaction of p-nitrophenyl benzenesulfonate (1) with alkali metal ethoxides in ethanol at 25 deg C has been studied by spectrophotometric techniques.For lithium ethoxide, sodium ethoxide, potassium ethoxide, and cesium ethoxide, the observed rate constants increase in the order LiOEt NaOEt CsOEt KOEt.The effect of added crown ether and cryptand complexing agents was also investigated.Addition of complexing agent to the reaction of KOEt results in the rate decreasing to a minimum value corresponding to the reaction of free ethoxide.Conversely, addition of complexing agent ot the reaction of LiOEt results in the rate increasing to a maximum value that is identical to the minimum value seen in the reaction of KOEt in the presence of excess complexing agent.In complementary experiments, alkali metal ions were added in the form of unreactive salts.Addition of a K+ salt to the reaction of KOEt increases the reaction rate, while addition of a Li+ salt to the reaction of LiOEt decreases the rate.The involvment of metal ions in the reaction of 1 is proposed to occur via reactive alkali metal - ethoxide ion pairs.The kinetic data are analyzed in terms of an ion pairing treatment that allows the calculation of second-order rate constants for free ethoxide and metal-ethoxide ion pairs. the kinetic data are analyzed in terms of an ion pairing treatment that allows the calculation of second-order rate constants for free ethoxide and metal-ethoxide ion pairs; the rate constants increase in the order LIOEt EtO- NaOEt CsOEt KOEt.Thus, Li+ is an inhibitor of the reaction of ethoxide with 1, while the other metals ions studied are all catalysts.Equilibrium constants for the association of the various metal ions with the transition state are calculated using a thermodynamic cycle, and are compared to association of the various metal ions with the transition state are calculated using a thermodynamic cycle, and are compared to association constants in the ground state.Consistent with the observed kinetic results, Li+ is found to stabilize the ground state more than the transition state, while Na+, K+, and Cs+ all stabilize the transition state more than the ground state. the trend in the magnitude of the transition state stabilization is interpreted in terms of interactions of the transition state with bare or solvated metal ions.It is concluded that the transition state for the reaction of 1 with ethoxide forms solvent separated ion pairs with alkali metal ions.Analogous data were available for the reaction of p-nitrophenyldiphenylphosphinate (2) with ethoxides, where Li+, Na+, K+, and Cs+ all function as catalysts, and the results are analyzed as above.In contrast to the sulfonate system, it is proposed that the phosphinate transition state forms contact ion pairs with alkali metal ions.The difference is attributed to a greater localization of negative ...
Sulphur-based Directed Benzylic Metallations: Lithiations of Alkylarenesulphonates
Alo, Babajide I.,Familoni, Oluwole B.,Marsais, Francis,Queguiner, Guy
, p. 1611 - 1614 (2007/10/02)
Benzylic anions (6) are obtained by regio-specific lithiations of ethyl 2-methylbenzenesulphonates.Evidence for the presence of the ethyl 2-lithiomethylbenzenesulphonates was obtained by efficient quenching studies with a range of electrophiles.Lithiations of the 2,4-dimethyl compound (9) gave the 2-lithiomethyl anion only, indicative of a predominant co-ordination mechanism in the lithiations.
