Effect of nucleophile basicity on intramolecular nucleophilic aminolysis reactions of carbonate diesters

Fife, Thomas H.; Hutchins, J. E. C.

doi:10.1021/ja00404a036

Cited by 27 publications

(15 citation statements)

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“…As for carboxylate esters [45], carbonate ester hydrolysis is expected to proceed through a tetrahedral intermediate by a stepwise mechanism [46]. The rate limiting step being the formation of the tetrahedral intermediate by addition of the hydroxide ion [46,47]. Scheme 1.…”

Section: Reactivity Of Carbonate Estersmentioning

confidence: 99%

“…Intramolecular catalysis of carbonate ester hydrolysis by the carboxylate anion may also be the cause of the high lability of the salicylic acid carbonate esters studied by Dittert et al at pH 7.4 as compared to pH 12 [50]. Other examples of intramolecular catalysis involved in carbonate ester hydrolysis can be found [47,62]. Further investigations are required to distinguish whether the increased rate of hydrolysis is due to intramolecular nucleophilic catalysis or general base catalysis involving the carboxylic acid group.…”

Section: Reactivity Of Carbonate Estersmentioning

confidence: 99%

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Bioreversible Derivatives of Phenol. 2. Reactivity of Carbonate Esters with Fatty Acid-like Structures Towards Hydrolysis in Aqueous Solutions

Østergaard

Larsen

2007

Molecules

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A series of model phenol carbonate ester prodrugs encompassing derivatives with fatty acid-like structures were synthesized and their stability as a function of pH (range 0.4 -12.5) at 37 o C in aqueous buffer solutions investigated. The hydrolysis rates in aqueous solutions differed widely, depending on the selected pro-moieties (alkyl and aryl substituents). The observed reactivity differences could be rationalized by the inductive and steric properties of the substituent groups when taking into account that the mechanism of hydrolysis may change when the type of pro-moiety is altered, e.g. n-alkyl vs. t-butyl. Hydrolysis of the phenolic carbonate ester 2-(phenoxycarbonyloxy)-acetic acid was increased due to intramolecular catalysis, as compared to the derivatives synthesized from ω-hydroxy carboxylic acids with longer alkyl chains. The carbonate esters appear to be less reactive towards specific acid and base catalyzed hydrolysis than phenyl acetate. The results underline that it is unrealistic to expect that phenolic carbonate ester prodrugs can be utilized in ready to use aqueous formulations. The stability of the carbonate ester derivatives with fatty acid-like structures, expected to interact with the plasma protein human serum albumin, proved sufficient for further in vitro and in vivo evaluation of the potential of utilizing HSA binding in combination with the prodrug approach for optimization of drug pharmacokinetics. Molecules 2007, 12 2397

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Section: Reactivity Of Carbonate Estersmentioning

confidence: 99%

Section: Reactivity Of Carbonate Estersmentioning

confidence: 99%

Bioreversible Derivatives of Phenol. 2. Reactivity of Carbonate Esters with Fatty Acid-like Structures Towards Hydrolysis in Aqueous Solutions

Østergaard

Larsen

2007

Molecules

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“…The kinetics and mechanisms of the aminolysis of diaryl carbonates are well documented. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] Some of these reactions have been described as stepwise, through a zwitterionic tetrahedral intermediate (T ± ), [3][4][5][6][7][8][9][10][11] whereas others have been found to be concerted, i.e. with no T ± intermediate in a single step.…”

Section: Introductionmentioning

confidence: 99%

Kinetics and mechanism of the aminolysis of bis(4‐nitrophenyl) carbonate and O‐(4‐nitropheny) S‐(4‐nitrophenyl) thio and dithiocarbonate

Castro

Aliaga

Gazitúa

et al. 2013

J of Physical Organic Chem

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The kinetics of the reactions of secondary alicyclic amines with bis(4‐nitrophenyl) carbonate (1), S‐(4‐nitrophenyl) O‐(4‐nitrophenyl) thiocarbonate (2) and S‐(4‐nitrophenyl) O‐(4‐nitrophenyl) dithiocarbonate (3) were studied at 25.0 °C. The reactions of 1 were studied in water and those of 2 and 3 in 44 wt% ethanol–water. These reactions are concerted. The HPLC analyses of the reactions of 2 and 3 with morpholine show that both 4‐nitrophenoxide and 4‐nitrobenzenethiolate ions are the nucleofuges. Copyright © 2013 John Wiley & Sons, Ltd.

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“…The kinetics and mechanisms of the aminolysis of diaryl carbonates are well documented 1–16. Some of these reactions have been described as stepwise, through a zwitterionic tetrahedral intermediate (T ± ) 3–11, whereas others have been found to be concerted, i.e., with no T ± intermediate in a single step 12–16.…”

Section: Introductionmentioning

confidence: 99%

Concerted aminolysis of diaryl carbonates: Kinetic sensitivity on the basicity of the nucleophile, nonleaving group, and nucleofuge

Castro

Cubillos

Iglesias

et al. 2012

Int J of Chemical Kinetics

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The kinetics of the reactions of 4-methylphenyl, phenyl, and 4-chlorophenyl 2,4,6-trinitrophenyl carbonates (1, 2, and 3, respectively) with a series of anilines and secondary alicyclic (SA) amines has been carried out spectrophotometrically in 44 wt% ethanol-water, at 25.0 • C, ionic strength 0.2 M. The Brønsted plots (statistically corrected) for the reactions of carbonates 1-3 with anilines and SA amines were linear with slopes (β N ) in the range of 0.69-0.78 and 0.45-0.48, respectively, attributed to a concerted mechanism. The negative values found for the sensitivity of log k N to the basicity of the nonleaving (β nlg ) and leaving (β lg ) groups are discussed. Anilines are more reactive than isobasic SA amines, probably because of the greater steric hindrance offered by the latter. C 2012 Wiley Periodicals, Inc. Int J Chem Kinet

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Effect of nucleophile basicity on intramolecular nucleophilic aminolysis reactions of carbonate diesters

Cited by 27 publications

References 0 publications

Bioreversible Derivatives of Phenol. 2. Reactivity of Carbonate Esters with Fatty Acid-like Structures Towards Hydrolysis in Aqueous Solutions

Bioreversible Derivatives of Phenol. 2. Reactivity of Carbonate Esters with Fatty Acid-like Structures Towards Hydrolysis in Aqueous Solutions

Kinetics and mechanism of the aminolysis of bis(4‐nitrophenyl) carbonate and O‐(4‐nitropheny) S‐(4‐nitrophenyl) thio and dithiocarbonate

Concerted aminolysis of diaryl carbonates: Kinetic sensitivity on the basicity of the nucleophile, nonleaving group, and nucleofuge

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