Fátima Norberto

Oxidation of the methyl groups of N,N-dimethylbenzamides by a cytochrome P450 mono-oxygenase model system

Abstract Oxidation of N,N -dimethylbenzamides to the corresponding N -formyl- N -methylbenzamides using tetraphenylporphyrinato-iron(III)-Bu t OOH is independent of the substituent in the aryl ring of the benzamide group and subject to a kinetic deuterium isotope effect of 5.6. These results are consistent with a mechanism involving direct hydrogen atom abstraction from the substrate.

Kinetics and mechanism of nitrosation of clonidine: a bridge between nitrosation of amines and ureas

Nitrosation of clonidine has been studied kinetically both in acid medium (with nitrous acid) and in basic medium (with 2,2-dichloroethyl nitrite). The reactive form in acid medium was found to be the protonated clonidine (pKa 8.18). The absence of catalysis by halides or thiocyanate, the existence of general base catalysis, and the measured solvent isotope effect all indicate that the reaction mechanism is different from that for the N-nitrosation of amines. Specifically, kinetic results indicate that the attack of the nitrosating agent on the substrate is not the rate determining step of the process, and suggest a mechanism that shows parallels with that found for ureas. However, in slightly basic medium, the reaction of clonidine with the alkyl nitrite occurs through the free base form of clonidine, as shown by the influence of acidity upon the reaction rate. In this case, the kinetic behaviour is similar to that exhibited by amines.

Mechanism of hydrolysis of substituted N-thiazolylcarbamate esters in OH- solutions

Substituted secondary N-thiazolylcarbamate esters and some tertiary N-methyl, N-thiazolyl carbamate esters have been synthesised and the mechanism of the OH- catalysed hydrolyses investigated. These proved to be E1cB and BAc2 respectively, and this behaviour was compared with that of other carbamates.

Synthesis and reactivity of phenyl-N-methyl-N- thiobenzoylcarbamate in basic media

Phenyl-N-methyl-N-thiobenzoylcarbamate was prepared from the reaction of thiobenzamide anion with phenylchloroformate in DMF and kinetic data obtained for the basic hydrolysis, have been interpreted in terms of a BAc2 mechanism involving general bases catalysis.

Kinetics and mechanism of acid hydrolysis of 1-methyl-1-nitroso-3-p-tolylsulfonylguanidine and 1-methyl-1-nitroso-3-benzoylguanidine

Kinetics of acid hydrolysis of 1-methyl-1-nitroso-3-p-tolylsulfonylguanidine 2 and of two 1-methyl-1-nitroso-3-benzoylguanidines (4-unsubstituted and 4-chloro) 5 and 6 have been studied. For the acid hydrolysis of 1-methyl-1-nitroso-3-p-tolylsulfonylguanidine 2, the absence of catalysis by thiocyanate ion, and the value of the kinetic solvent isotope effect indicate that either a rate determining proton transfer followed by fast denitrosation or a concerted pathway is involved in the mechanism. In the case of the acid hydrolysis of 1-methyl-1-nitroso-3-benzoylguanidines 5 and 6 it was observed that the protonated form decomposes via two parallel pathways. One involves a slow nucleophilic attack concerted with an intramolecular proton transfer, and the other a slow concerted denitrosation, where a second proton transfer and NO+ expulsion are simultaneous.

Nitrosation of N-Methyl-4-tolylsulfonylguanidine†

Kinetic studies for the nitrosation of N-methyl-4-tolylsulfonylguanidine identify a mechanism involving rapid nitrosation of the N-methyl nitrogen atom followed by slow, general-base-catalysed proton transfer.

N-nitroso compounds. Part 1. Structure and decomposition of N-nitroso-2-arylimidazolines in aqueous acidic media

Kinetic measurements for the acid-catalysed decomposition of N-nitroso-2-arylimidazolines are reported. Reactions are first-order in both [substrate] and [H+]. Two products are formed; an oxazoline, which is the product of hydrolysis of the amidine moiety, and the parent imidazoline formed by denitrosation of the substrate. These products arise from two competing pathways both of which are acid catalysed. The solvent isotope effects for the denitrosation, kNOD+/kNOH+, and amidine hydrolysis, kAD+/kAH+, are 3.1 and 3.5, respectively. The denitrosation pathway, but not amidine hydrolysis, is catalysed by nucleophilic anions, and a value of 1.7 for the Swain–Scott constant, s, is obtained. In the absence of nucleophilic anions, amidine hydrolysis is preferred over denitrosation, kAH+ being twice as large as kNOH+ at 25 °C. Substitutents in the 2-aryl ring affect the rate of decomposition giving Hammett ρ values of 0.7 for denitrosation and 1.0 for amidine hydrolysis, which reflect the proximity of the reacting centres to the substituents. Values of the activation parameters are ΔHNO‡ 74 kJ mol–1, ΔHA‡ 74 kJ mol–1, ΔSNO‡–48 J K–1 mol–1 and ΔSA‡–43 J K–1 mol–1. The data are interpreted in terms of a fast equilibrium protonation of the substrate, followed by competitive attack at the protonated substrate, either of water or nucleophilic anions at the nitroso nitrogen atom, or of water at the amidine carbon atom. Protonation is required to activate the substrate, the substrate being recovered from neutral or alkaline solutions unchanged. The mechanism is discussed with reference to the analogous reactions of N-nitrosoamines and N-nitrosoamides.

Alkaline hydrolysis of tertiary N-(2-pyridyl)carbamates. Contradictory evidence between nucleophilic and general base catalysis

Abstract The mechanism of the alkaline hydrolysis of phenyl N-methyl-N-(2-pyridyl)carbamate was investigated in order to evaluate the type of catalysis involved. The kinetic solvent isotope effect, the α-effect for the hydrolysis in peroxymonocarbonate ion, the Brønsted plot, and the isolation of the product resulting from trapping the unsaturated intermediate with piperidine, confirmed that the alkaline hydrolysis of phenyl N-methyl-N-(2-pyridyl)carbamate proceeds through a BAC2 mechanism with nucleophilic catalysis rather than a general base catalysis as initially thought.

Hydrolysis of benzothiazolylcarbamates in basic media

Secondary benzothiazolylcarbamates hydrolyse in basic media by an E1cB mechanism, while the corresponding tertiary carbamate hydrolyse by a general base BAc2 mechanism

Hydrolysis of aryl N-methyl-N-arylsulfonylcarbamates

Tertiary sulfonylcarbamates 1 were prepared by reaction of a sulfonamide anion with aryl chloroformates. These previously unreported compounds hydrolyse in aqueous media to the parent sulfonamide and phenol. The pH–rate profile shows both spontaneous and base-catalysed processes. The reaction is also catalysed by buffers. Kinetic data for the hydrolysis of these compounds by HO− are best interpreted in terms of a mechanism involving rate-limiting formation of a tetrahedral intermediate from nucleophilic attack of hydroxide ion at the carbamate carbonyl carbon atom. For the 4-nitrophenylsulfonyl compound 1h decomposition of the tetrahedral intermediate appears to be rate-limiting with the sulfonamide anion, rather than the phenoxide, functioning as the leaving group. The buffer-catalysed process is consistent with general base-catalysed attack of water at the carbamate carbonyl carbon atom.