On the disappearance of the gem-dimethyl effect: the base-catalysed cyclization of ethyl hydantoates †

Atay, Ergun; Blagoeva, Iva B.; Kirby, Anthony J.; Pojarlieff, Ivan G.

doi:10.1039/a802884b

Cited by 12 publications

(5 citation statements)

References 21 publications

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“…The rate profiles are closely similar at higher pHs also, when the reaction is calculated in terms of the free acid (see below). The negative slope between pH 4-6 marks the ionization of the COOH group in a region of watercatalyzed reaction of the free acid, reaction (2).…”

Section: Kinetics and Mechanisms Ph-rate Profiles For The Cyclization...mentioning

confidence: 99%

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A normal gem-dimethyl effect in the base-catalyzed cyclization of ω-( p-nitrophenyl)hydantoic acids: evidence for hindered proton transfer in the permethylated esters †

Blagoeva

Kirby²,

Kochiyashki

et al. 2000

J. Chem. Soc., Perkin Trans. 2

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The cyclization of hydantoic acids 2-UA and 3-UA -kinetics, solvent kinetic isotope effects (SKIE) and buffer catalysis -were studied in an attempt to explain the disappearance of the gem-dimethyl effect (GDME) in the specific base-catalyzed cyclization of hydantoic esters. pH-Rate profiles for both acids (after correction for ionization and for reversibility at high pH) show two regions of unit slope corresponding to different mechanisms. For 2-UA at high pH and 3-UA at lower pH the mechanism is considered to involve rate-determining attack by the ureido anion on the neutral carboxy group, consistent with the observed inverse SKIE. The normal GDME of 15 provides strong evidence that anomalies observed with the esters do indeed result from steric hindrance to proton transfer. The change to rate determining departure of OH Ϫ with 2-UA is caused at low pH by acid catalysis of the reversion of the tetrahedral intermediate (T Ϫ ) to reactants, while with 3-UA at high pH this takes place through T 2Ϫ . The GDME favours attack on the carboxylate anion but makes ring opening more difficult, thus decreasing acid inhibition. The observed β = 0.44 for general base catalysis of the cyclization of 2-UA is consistent with concerted deprotonation and attack of the ureido group. With 3-UA two simultaneous general base-catalyzed reactions take place: slow deprotonation of the ureido group (β = 1.0) and attack of the ureide anion on the carboxy anion aided by the buffer conjugate acid. The estimated GDME is 2800 for the equilibrium between acid anion and hydantoin, ‡ but only 45 and 15 for catalysis by H 3 O ϩ and OH Ϫ , respectively: both reactions are presumed to go through early transition states.

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Section: Kinetics and Mechanisms Ph-rate Profiles For The Cyclization...mentioning

confidence: 99%

“…This was allowed for as described in ref. 2. The glycine buffers used covered a pH range of 2.2 to 3.5.…”

Section: General Base Catalysismentioning

confidence: 99%

A normal gem-dimethyl effect in the base-catalyzed cyclization of ω-( p-nitrophenyl)hydantoic acids: evidence for hindered proton transfer in the permethylated esters †

Blagoeva

Kirby²,

Kochiyashki

et al. 2000

J. Chem. Soc., Perkin Trans. 2

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“…Other methods are preferred for this purpose [27,28,30]. At the same time, the formation of hydantoins as byproducts of glycolurils synthesis from ureas and 40% solution of glyoxal or 4,5-dihydroxyimidazolidin-2-ones at pH 1 has been observed by us earlier [5].…”

Section: Saturation Of T-bumentioning

confidence: 97%

Synthesis of first representatives of 3,3′-bi(6,8-dialkyl-2,4-dioxa-6,8-diazabicyclo[3.3.0]octan-7-ones)

Sigachev

Кравченко

Газиева

et al. 2006

Journal of Heterocyclic Chemistry

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The first representatives of 3,3′‐bi(2,4‐dioxa‐6,8‐diazabicyclo[3.3.0]octan‐7‐ones) have been synthesized by a reaction of glyoxal as form of 2,2′‐bi(4,5‐dihydroxy‐1,3‐dioxalane) with N,N′‐dialkylureas. Their structures have been supported by X‐ray analysis. 1,3‐Dialkylimidazolidine‐2,4‐diones (hydantoins) have been isolated as by‐products and their formation mechanism has been experimentally confirmed.

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“…With the more acidic glycine and formate buffers pH increased upon dilution and the changes in pH and % free base were calculated as described previously. 3 The kinetic behaviour of the substrates in buffers was examined as follows. The rates determined at a certain buffer ratio were plotted against total buffer concentration.…”

Section: General Base Catalysismentioning

confidence: 99%

Kinetics and mechanism of the cyclization of ω-(p-nitrophenyl)-hydantoic acid amides: steric hindrance to proton transfer causes a 104-fold change in rateElectronic supplementary information (ESI) available: Observed first-order rate coefficients, constants for solvent and buffer catalysis for the cyclization reactions. See http://www.rsc.org/suppdata/ob/b2/b211040g/

Angelova

Kirby²,

Koedjikov

et al. 2003

Org. Biomol. Chem.

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The pH-rate profiles for the cyclization of primary 2,3-dimethyl and 2,2,3-trimethyl-hydantoinamides (2-UAm and 3-UAm respectively) differ strikingly from those for the cyclizations of the corresponding N-methylated amides 2-MUAm and 3-MUAm; which are dominated by the water reaction, spanning some 6 pH units. For the cyclization of UAm the plateau extends over no more than two pH units. The difference is due to the slower base-catalyzed cyclization of the N-methylamides. The solvent kinetic isotope effect for this hydroxide-catalyzed reaction is close to 1.2, consistent with a slow protonation by water of the amino-group of the negatively charged tetrahedral intermediate. General base catalysis was observed with bases of pKBH up to 8. The Brønsted beta are compatible with a hydrogen bonding mechanism for the GBC. In the gem-dimethyl compounds 3 the leaving group is flanked by substituents on both sides. The N-methyl group in 3-MUAm hinders frontal access of the proton, causing a 14000 fold decrease in rate. This is only 3800 fold in the compound with one methyl group at position 2.

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On the disappearance of the gem-dimethyl effect: the base-catalysed cyclization of ethyl hydantoates †

Cited by 12 publications

References 21 publications

A normal gem-dimethyl effect in the base-catalyzed cyclization of ω-( p-nitrophenyl)hydantoic acids: evidence for hindered proton transfer in the permethylated esters †

A normal gem-dimethyl effect in the base-catalyzed cyclization of ω-( p-nitrophenyl)hydantoic acids: evidence for hindered proton transfer in the permethylated esters †

Synthesis of first representatives of 3,3′-bi(6,8-dialkyl-2,4-dioxa-6,8-diazabicyclo[3.3.0]octan-7-ones)

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