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• 100-28-7 4-Nitrophenyl isocyanate 

Relevant academic research and scientific papers

The gem-dimethyl effect on reactivities in cyclizations through tetrahedral intermediates. Cyclization of methyl-substituted methyl amides of 5-(p-nitrophenyl)hydantoic acids

The cyclization of the title hydantoinamides, UA, to 3-(4-nitrophenyl)hydantoins, Hyd, is general-base catalysed. Reversible hydrolysis of the product hydantoin from the 2,3-dimethylhydantoinamide, 2-UA, above pH = 7 is a complicating feature. The rate profiles for cyclization comprise one acid-catalysed, two neutral and two hydroxide-catalysed regions in the pH-region 0-10. Solvent kinetic isotope effects indicate rate-determining expulsion of the methylamino group in the acid-catalysed reaction. These also agree with general-base catalysis at low pH being concerted with nucleophillic attack of the ureido group. At high pH the tetrahedral intermediate is in equilibrium with the reactants and the rate is limited by proton transfers producing T±. The accelerations upon methyl substitution vary strongly with the various processes observed and may be explained in terms of a general gem-dimethyl effect increasing along the reaction coordinate from reagent through cyclic tetrahedral intermediate to final ring product. As the effects for the breakdown of the intermediate are opposite in the forward and reverse directions, this changes the partitioning ratio and in turn could change the rate-determining step.

Multiple changes rate-determining, step the acid base catalyzed cyclizations of ethyl N-(p-nitrophenyl)hydantoates caused by methyl substitution

The slopes of the pH-rate profiles for the cyclization of 2-methyl- and 2,3-dimethyl hydantoates 1-NPU and 2-NPU between pH 1 and 7 change from 1 to 0 and then back to 1. A reaction first order in H+ was observed with the latter compound. The 2

Hydrolysis of 4-imino-imidazolidin-2-ones in acid and the mechanism of cyclization of hydantoic acid amides

The hydrolysis of iminohydantoins generates the same tetrahedral intermediate T as that obtained in the cyclization of hydantoic acid amides to hydantoins. The ratio of the products of imine hydrolysis under kinetic control is determined by the relative height of the barriers of the breakdown of T to amide or to hydantoin. Thus the partitioning of products unequivocally proves which is the rate determining step in the cyclization reaction - formation or breakdown of T. UV and 1H NMR monitoring of the acid catalyzed hydrolysis of four 5-substituted 4-imino-1-methyl-3-(4-nitrophenyl)imidazolidin- 2-ones 1 found hydantoins 3 as the only products. The kinetics of hydrolysis of imines were measured in 0.001-1 M HCl. Contrary to the remaining imines, 1,5-dimethyl-4-imino-3-(4-nitrophenyl)imidazolidin-2-one 1b is readily oxidized as stock solution in THF containing peroxides to 1,5-dimethyl-5-hydroxy-4-imino- 3-(4-nitrophenyl)imidazolidin-2-one 1d. In all cases, hydrolysis was found to be zero order with respect to [H+]. As imines are fully protonated under the acidity studied, this is evidence of a transition state of a single positive charge. Comparison of imine hydrolysis rates with previous data on rates of cyclization of the corresponding amides of hydantoic acids allowed conditions (acid concentration, substitution pattern - gem-dimethyl effect) to be found that guaranteed kinetic control of the products obtained. Thus it was unequivocally proven that formation of the tetrahedral intermediate is rate determining in the cyclization of hydantoic acid amides. The small steric effects upon methyl substitution at 5-C and a solvent kinetic isotope effect kH/kD of 1.72 favour a mechanism for imine hydrolysis whereby the rate is limited by water attack on the protonated imine concerted with proton transfer from attacking water to a second water molecule. The Royal Society of Chemistry.

Kinetics and mechanism of the cyclization of ω-(p-nitrophenyl)-hydantoic acid amides: Steric hindrance to proton transfer causes a 104-fold change in rate

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 Bronsted β 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.

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

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- with 2-UA is caused at low pH by acid catalysis of the reversion of the tetrahedral intermediate (T-) to reactants, while with 3-UA at high pH this takes place through T2-. 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 simultaneously 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 H3O+ and OH-, respectively: both reactions are presumed to go through early transition states.