Intramolecular General Acid Catalysis Research Articles

Efficient intramolecular general acid catalysis of the hydrolysis of a dialkyl acetal

The hydrolysis of benzaldehyde acetal 3, catalysed by the neighbouring carboxy group, is some 105 times faster than that of a comparable system 6, which does not form a strong intramolecular hydrogen bond in the transition state for the reaction.

Neighboring Carboxyl Group Participation in the Hydrolysis of Acetals. Hydrolysis of o-Carboxybenzaldehyde cis- and trans-1,2-Cyclohexanediyl Acetals

The plot of log kobsd vs pH for the hydrolysis of o-carboxybenzaldehyde trans-1,2-cyclohexanediyl acetal at 50 °C in H2O has four unit changes of slope in the pH range 2−9. The plot is here described by proceeding from low pH to high pH. The observed hydronium ion- and water-catalyzed reactions at pH < 6 have rate constants that are similar, but not identical, to those for hydrolysis of the acylal 3-[(trans-2-hydroxycyclohexyl)oxy]phthalide, which was isolated from the reaction at pH 3, and synthesized independently. The pH−log rate constant profile for hydrolysis of the acetal bends downward near pH 6 to give a slope of −1.0. Oxocarbonium ion hydrolysis is then a water reaction. At pH 7 the mechanism of the reaction changes to attack of OH- on the oxocarbonium ion intermediate. A change in rate-determining step takes place at pH 8 to hydronium ion-catalyzed ring opening of the anionic species of the acetal, or the kinetically equivalent intramolecular general acid catalysis in ring opening of the neutral...

Kinetics and mechanism of general acid-catalysed thiolytic cleavage of 9-anilinoacridine

The rates of the reactions of 2-mercaptoethanol (2-ME) with 9-anilinoacridine (9-ANA) have been studied in the buffer solutions of 2-ME, hydroxylamine, phosphate and morpholine. Both ionised and non-ionised forms of 2-ME and free hydroxylamine show nucleophilic reactivity toward protonated 9-ANA. The rate constants for general acid-catalysed thiolytic cleavage of protonated 9-ANA reveal a Brønsted plot of slope (α) of 0.93 which indicates that probably the rate-determining step involves proton transfer in a thermodynamically unfavourable direction. A stepwise mechanism for thiolysis has been suggested. General acid catalysis could be detected for thiolysis of non-protonated 9-ANA only in the buffer solutions of phosphate and morpholine. General acid catalysis seems to be unimportant when the nucleophile is non-ionised 2-ME which is attributed to the probable occurrence of intramolecular general acid catalysis.

Differential Reactivity of Two Types of N-Glycolylneuraminic Acid Dimers toward Enzymatic and Nonenzymatic Hydrolysis of Their Interketosidic Linkages

The kinetics of acid- and sialidase-catalyzed hydrolysis of the interketosidic linkages of two different disialic acids, Neu5Gcα2→5-OglycolylNeu5Gc and Neu5Gcα2→8Neu5Gc, were studied. The former sequence was recently identified in the polysialic acid chains of a sialic acid-rich glycoprotein isolated from the egg jelly coat of two different species of sea urchins, and the latter was previously found in the cortical alveolar-derived polysialoglycoprotein from rainbow trout eggs. At pH values < 3.8, the rate of hydrolysis of Neu5Gcα2→5-OglycolylNeu5Gc was greater than that of Neu5Gcα2→8Neu5Gc. Paradoxically, however, Neu5Gcα2→5-OglycolylNeu5Gc was more stable than Neu5Gcα2→8Neu5Gc at pH values > 3.8. These findings indicate a greater contribution of intramolecular general acid catalysis to the lability of the α2→5-ketosidic linkage. Neu5Gcα2→5-OglycolylNeu5Gc was a poor substrate for Arthrobacter ureafaciens, Clostridium perfringens, and Vibrio cholerae sialidases, in contrast to Neu5Gcα2→8Neu5Gc. Neu5Gcα2→5-OglycolylNeu5Gc was essentially resistant to hydrolysis by A. ureafaciens sialidase.

Highly efficient intramolecular general acid catalysis of enol ether hydrolysis, with rapid proton transfer to carbon

The hydrolysis of E and Z enol ether groups in the 8-position of 1-dimethylaminonaphthalene is catalysed by the neighbouring dimethylammonium group with remarkable efficiency. Similar compounds lacking a neighbouring general acid have been studied in strong acid, but the half-lives of 4Z and 4E below pH 3 are of the order of 10 s at 39 °C and external acid catalysis cannot be detected. The effective molarity is estimated as >60 000 M, the highest known for proton-transfer catalysis. This is ascribed to effective hydrogen-bond stabilisation of the in-flight proton. So efficient is proton transfer to carbon that the rate-determining step is probably not proton transfer to carbon but opening of the intramolecular hydrogen bond of the oxocarbocation intermediate 7. The tight intramolecular H-bonding responsible for the high efficiency of catalysis prevents significant H/D exchange with solvent D2O.

Most efficient intramolecular general acid catalysis of acetal hydrolysis by the carboxy group

The hydrolysis of 4-methoxymethoxybenzisoxazole-3-carboxylic acid (halflife 31 s at 39 °C) is the fastest measured for a methoxymethyl acetal: catalysis by the neighbouring CO2H group is facilitated by a strong intramolecular hydrogen bond.

Efficient intramolecular general acid catalysis of enol ether hydrolysis. Hydrogen-bonding stabilisation of the transition state for proton transfer to carbon

The intrinsically low efficiency of intramolecular general acid–base catalysis is enhanced when the proton transfer generates a strong intramolecular hydrogen bond. This principle is shown to apply to proton transfer to carbon: the carboxy groups of methyl vinyl ethers 3E and 3Z derived from 2-carboxyphenylacetaldehyde act as general acids to catalyse the hydrolysis of the neighbouring enol ether groups with effective molarities (EM) of about 300 and 2000 M, respectively. The solvent deuterium isotope effects confirm that the usual mechanism for enol ether hydrolysis is operative. In this system the oxocarbocation intermediate is trapped by the neighbouring carboxylate group to give the acylal 6, rather than the formal product of hydrolysis.

Amino acid catalytic effect on the transamination reaction between pyridoxal 5′-phosphate and L-serine

Abstract The kinetic study of Schiff base formation between pyridoxal 5′-phosphate (PLP) and L-serine and its subsequent transamination to yield pyridoxamine 5′-phosphate (PMP) and ketoacidate ion has been carried out over a wide pH range by fluorescence and UV—Vis measurements. The kinetic constants of Schiff base formation are compared with constants of other PLP—amino acid systems, showing the existence of an intramolecular general acid catalysis of PLP and general basic catalysis of the amino acid. The rate-determining step of the schiff base transamination is the isomerization of this compound to ketoimine, since the rate constants for disappearance of Schiff base coincide with the rate constants for PMP formation. This process is catalyzed by the OH−/H2O system and the monoprotonated amino acid.

Evidence for intramolecular electrostatic catalysis as a possible mechanism in the hydrolysis of vinyl ethers in aqueous solution

The hydrolysis of the vinyl ether functional group in 2-methoxybicyclo [2.2.2] oct-2-ene-1-carboxylic acid has been found to be catalyzed by intramolecular electrostatic catalysis by the carboxylate ion of the substrate. The rate constant ratios of the charged and the neutral form of the substrate are 32.3 and 31.2 for catalysis by hydronium ion and acetic acid, respectively. This is in contrast to ratios that have been found for vinyl ethers hydrolyzed by intramolecular general-acid catalysis, where large rate ratios for catalysis by hydronium ion but small rate ratios, normally a factor 2, when catalyzed by acetic acid are observed. The solvent isotope effect, 3.4±0.5, is close to what has been predicted for electrostatic catalysis in the hydrolysis of prostacyclin

Efficient intramolecular general acid catalysis of vinyl ether hydrolysis by the neighbouring carboxylic acid group

Intramolecular catalysis by the CO2H group of the hydrolysis of E-1-methoxy-2-(2-carboxyphenyl)ethylene 5, shows an effective molarity of almost 300 M, the highest measured for intramolecular proton transfer to carbon.

Kinetics of decomposition of O-acyl derivatives of salicylamide and related compounds

Salicylamide hemisuccinate ethyl ester, salicylamide hemiglutarate methyl ester, O-acetyl- N-methylsalicylamide, and O-acetyl- N, N-diethylsalicylamide were synthesized, and the kinetics and mechanisms of their decompositions in aqueous buffers at various pH values were studied. The results support a mechanism in which the predominant feature is a transacylation reaction involving intramolecular attack of the amide anion on the carbonyl carbon of the neighboring ester group. In the case of O-acetyl- N-methyl salicylamide and O-acetyl- N, N-diethylsalicylamide, where the ionization of the amide group is blocked, the predominant reaction was found to be hydrolysis of the ester groups rather than O-to- N-acyl transfer. The reaction rates for the glutarate hemiester were found to be faster than those for the corresponding ethyl ester at pH values around 7.0. These results confirm a previously proposed mechanism in which a second intramolecular general acid catalysis involving the free carboxyl group on the hemiester moiety accelerates the transacylation rate.

Effects of anionic micelles on the intramolecular general-base-catalysed hydrazinolysis and hydrolysis of phenyl salicylate. Evidence for a porous cluster micelle

The hydrazinolysis of phenyl salicylate has been studied in the presence and absence of micelles of sodium dodecyl sulphate (SDS) at 30 °C. The nucleophilic reaction of hydrazine with ionized phenyl salicylate (PS–) involves intramolecular general-base catalysis while the probable intramolecular general-acid catalysis could not be detected in the reaction of non-ionized phenyl salicylate (PSH) with hydrazine. Kinetic data for both hydrolysis and hydrazinolysis of phenyl salicylate are explained in terms of the pseudophase model of micelles. The rate constants for hydrolysis and hydrazinolysis of PS– in micellar pseudophase are either insignificant or significantly smaller compared with the corresponding rate constants in aqueous pseudophase. This is attributed largely to considerably low water activity in the specific micellar environment where micellar bound PS– molecules exist. The micellar bound reactants (PSH and PS–) and products (non-ionized and ionized phenol and N-hydrazinylsalicylamide) appear to exist in the micellar environments of different water activity. The rate constants, Kobs′ increase ca. fivefold with increased [NaOH] from 0.001 to 0.040 mol dm–3 at 0.2 mol dm–3 SDS and 0.08 mol dm–3 NH2NH2. This is attributed to an increase in [PS–] with increase in [NaOH]. These observations favour the porous cluster micellar structure. The values of Kobs remain unchanged with increased concentration of 1,4-diazabicyclo[2.2.2]octane from 0.06 to 0.60 mol dm–3 at 0.3 mol dm–3 SDS, 0.05 mol dm–3 NaOH, and 37 °C. This shows that the presence of SDS micelles does not change the reaction mechanism of aqueous pseudophase hydrolysis and aminolysis of PS–.

Intramolecular general base catalysis and the rate-determining step in the nucleophilic cleavage of ionized phenyl salicylate with primary and secondary amines

The nucleophilic second-order rate constants for the reactions of ionized phenyl salicylate (PS–) with primary and secondary amines have revealed Bronsted plots of slopes βnuc1= 0.52 ± 0.06 and βnuc2= 0.27 ± 0.05, respectively. The suggested stepwise reaction mechanism involves the intramolecular proton transfer from cationic nitrogen to the anionic phenolic oxygen to form the monoanionic tetrahedral addition intermediate as the rate-determining step. The low value of βnuc2 is attributed to the extensive of proton transfer in the late transition state while the large value of βnuc1 is ascribed to the proton transfer in the early transition state of the rate-determining step. However, these low and high values of βnuc2 and βnuc1 respectively, are also compatible with the occurrence of respective early and late transition states in the rate-determining step involving concerted intramolecular general base-catalysed nucleophilic attack at the carbonyl carbon of PS–. Significantly large positive deviations from Bronsted plots have been observed for the reactivities of α-nucleophiles toward PS–. Monoprotonated ethane-1,2-diamine is ca. 20-fold more reactive than would be expected from its basicity, and this is attributed to the occurrence of the intramolecular general acid catalysis. The reactions of PS– with hydroxylamine and N-methylhydroxylamine involve ca.70% aminolysis and ⩽30% transesterification while those with tris-(2-hydroxyethyl)amine involve 100% transesterification. The extremely low reactivity of ammonia compared with that of primary amines of similar basicity indicates that it does not belong to a series of homologous primary amines in its nucleophilic reactivity toward PS–.

Concerning the weakness of intramolecular general acid catalysis in the hydrolysis of vinyl ethers. o‐carboxy‐α‐methoxy‐β,β‐dimethylstyrene

AbstractThe rate of hydrolysis of the aromatic vinyl ether o‐carboxy‐α‐methoxy‐β,β‐dimethylstyrene was found to be accelerated 25‐fold by ionization of its carboxylic acid group, but the effective molarity which may be calculated if all of this rate acceleration is ascribed to intramolecular general acid catalysis is only EM = 1 · 1 m. This is similar to the small effective molarities found before for intramolecular catalysis by carboxylic acid groups of aliphatic vinyl ethers, which shows that, unlike the situation in other intramolecular reactions, e.g. ketone enolization, the extra rigidity of aromatic over aliphatic systems does not improve the efficiency of intramolecular catalysis in vinyl ether hydrolysis.It is suggested that this behaviour is the result of reduced conjugation between the vinyl ether group and the aromatic ring in the transition state of the vinyl ether hydrolysis reaction, which retards the rate and offsets any improvement effected by increased rigidity of the aromatic system.

Kinetic evidence for intramolecular general-acid catalysis in the hydrolysis of a prostacyclin model

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTKinetic evidence for intramolecular general-acid catalysis in the hydrolysis of a prostacyclin modelNils Aake Bergman, Marie Jansson, Yvonne Chiang, and A. Jerry KresgeCite this: J. Org. Chem. 1988, 53, 11, 2544–2547Publication Date (Print):May 1, 1988Publication History Published online1 May 2002Published inissue 1 May 1988https://doi.org/10.1021/jo00246a026RIGHTS & PERMISSIONSArticle Views54Altmetric-Citations4LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (429 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Aminoketone enolisation: influence of increasing chain length on intramolecular catalysis

Kinetic results are reported on the rates of ionisation of piperidino- and morpholino-phenones of varying chain length [PhCO(CH2)n [graphic omitted]H2], X = CH2 or O; n= 2–5] in buffer and dilute hydroxide solution, as measured by their rates of halogenation. For both series of aminoketones two important factors are responsible for a high reactivity relative to acetophenone: the positive charge on the protonated (and N-methylated) derivatives, which has a strong influence in the α-(n= 1) and β-(n= 2) position, and intramolecular general base catalysis by the neutral amino group, which has a maximum effect for the δ-(n= 4) derivative. Results for the more acidic protonated morpholinoketones are almost identical to those of corresponding piperidinoketones and show no evidence of intramolecular general acid catalysis. The reduced basicity of the morpholino group is reflected in lower rate constants for the intramolecular general base-catalysed reaction.

Stability of prostacyclin analogues: an unusual lack of reactivity in acid-catalyzed alkene hydration.

Prostacyclin analogue 5 undergoes specific acid-catalyzed hydration (kH+ = 1.9 x 10(-7)M-1 sec-1 at 25 degrees C) and a pH-independent oxidation reaction (k0 = 1.2 x 10(-10) sec-1 at 25 degrees C) above pH approximately 5. The hydration reaction for 5 is much slower than for other structurally similar exocyclic alkenes, even though the rate-determining step is proton transfer. This slowness of reaction and an analysis of the pH-rate profile show that 5 does not exhibit significant intramolecular general acid catalysis, as does prostacyclin.

Prostacyclin: evidence that intramolecular general-acid catalysis by its carboxylic acid group is responsible for the extra hydrolytic lability

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProstacyclin: evidence that intramolecular general-acid catalysis by its carboxylic acid group is responsible for the extra hydrolytic labilityY. Chiang, M. J. Cho, B. A. Euser, and A. Jerry. KresgeCite this: J. Am. Chem. Soc. 1986, 108, 14, 4192–4196Publication Date (Print):July 1, 1986Publication History Published online1 May 2002Published inissue 1 July 1986https://doi.org/10.1021/ja00274a057RIGHTS & PERMISSIONSArticle Views91Altmetric-Citations26LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (679 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Kinetics and mechanism of the cyclisation of 2′,6′-dihydroxy-4,4′-dimethoxy-chalcone; influence of the 6′-hydroxy group on the rate of cyclisation under neutral conditions

The Ph–rate profile for the cyclisation of the title compound has been established under aqueous conditions and is accounted for in terms of contributions from uncatalysed cyclisation of neutral, monoanionic, and dianionic chalcone species, together with an acid-catalysed cyclisation. At high pH the reaction does not go to completion and a kinetic term representing hydroxide promotion of the reverse ring-opening reaction of the flavanone anion intervenes. Rate coefficients for all contributing reactions and dissociation constants for the chalcone and its monoanion are established. The chalcone monoanion cyclises about 440 times faster than the neutral chalcone and about 3 times faster than the dianion. The known ease of cyclisation under neutral conditions of 2′,6′-dihydroxychalcones as compared with other 2′-hydroxychalcones is considered to be associated with two contributing factors: (i) a much larger first dissociation constant of the chalcone which results in a higher proportion of the chalcone being present as the reactive monoanion at neutral pH; (ii) specially high reactivity of the chalcone monoanion associated with intramolecular general acid catalysis by the 6′-OH group. The latter is implicated through the observation of a large kinetic isotopeeffect for monoanion cyclisation, which is 5.7 times slower in D2O than in H2O. This isotope effect also establishes for the monoanion that the s-cis→ s-trans conformational isomerisation of the monoanion must be a pre-equilibrium rather than the rate-determining stage in the cyclisation.

Kinetics and mechanism of tertiary amine-catalysed aqueous cleavage of maleimide

The reaction rates of the aqueous cleavage of maleimide in the presence of buffer solutions of trimethylamine, 1,4-diazabicyclo[2.2.2]octane, triethylamine, and triethanolamine have been studied at 30 °C. Both the ionized (S) and non-ionized (SH) forms of maleimide are reactive towards the free base component of buffer solutions of trimethylamine and 1,4-diazabicyclo[2.2.2]octane. These amines have exhibited general acid-catalysed and uncatalysed nucleophilic attack at carbonyl carbon of both SH and S–. Triethylamine has been found to be essentially unreactive towards SH and S– while triethanolamine has revealed significant nucleophilic reactivity towards SH and S–. The observed nucleophilic reactivity of triethanolamine and absence of such reactivity in the case of triethylamine have led to the proposal that the nucleophilic site in triethanolamine is the internally hydrogen-bonded hydroxy group rather than the free amine group. The absence of intermolecular general acid catalysis in the reactions of SH and S– with triethanolamine is attributed to both the steric effect as well as probable intramolecular general acid catalysis. A pre-association stepwise mechanism is proposed for the reactions of tertiary amines with S–while a stepwise mechanism has been favoured for the reactions of amines with SH.