X.L. Armesto

Oxidation of aliphatic amines by aqueous chlorine

Abstract The oxidation of aliphatic amines by aqueous chlorine has been studied. The kinetic behaviour is similar for primary, secondary and tertiary aliphatic amines, the elementary step being the transfer of chlorine from the hypochlorous acid molecule to the nitrogen of the free amino group. Chlorination of aliphatic primary and secondary amines involves some water molecules in the transition state. Inductive effects are also discussed.

Aqueous chemistry of N-halo-compounds

Halogens in aqueous solution are still used world-wide as disinfectants. During the process of halogenation, the substances present in water undergo several chemical processes, yielding relatively unstable intermediate species; their life-times in the medium depend on their structure and on the physico-chemical conditions. Several low molecular weight hydrocarbons are formed during water halogenation, some of them potent mutagens and/or carcinogens. Halogenation also takes place in vivo involving the system myeloperoxidase/H2O2/halide, which increases the relevance of such reactions and opens new research fields.

First Steps in the Oxidation of Sulfur-Containing Amino Acids by Hypohalogenation: Very Fast Generation of Intermediate Sulfenyl Halides and Halosulfonium Cations

Abstract Sulfur-containing amino acids show an extraordinary binding towards HOCl/ClO−. During the process, the Cl is transferred from the O to the S of the amino acid. Met reacts with HOCl one order of magnitude faster than the non-S containing amino acids (k (Met+HOCl) =8.7·10 8 mol −1 dm 3 s −1 ). Instead, Cys reacts as its thiolate (RS−), two orders-of-magnitude faster (k ( RS − + HOCl ) =1.2·10 9 mol −1 dm 3 s −1 ). Cys reacts also with ClO− (k ( RS − + ClO − ) =1.9·10 5 mol −1 dm 3 s −1 ). Such processes take place much more readily than the corresponding N-halogenation of the non-sulfur containing amino acids. To our knowledge, these are the first kinetic measurements of the rate of formation of sulfenyl halides and halosulfonium cations in aqueous solution. Sulfenyl chlorides and chlorosulfonium ions derived from amino acids are elusive, and sulfide-type amino acids (Met) eventually yield sulfoxides (MetO), while thiol-type amino acids (Cys) lead to disulfides (Cys^Cys) and sulfonic acids (Cya). The fate of sulfur-containing amino acids upon oxidation with HOCl/ClO− seems to be related to their mutagen-inactivation ability.

α-amino acids chlorination in aqueous media

The reaction of chlorination of α-amino acids for 6 < pH < 11 has been studied. The reaction is an aliphatic electrophilic substitution, the rate determining step being the transfer of the chlorine atom between the HOCl oxygen and the nitrogen of the α-amino acid free amino group.

Acid-base equilibria and decomposition of secondary (N-Cl)-α-amino acids.

Abstract The decomposition of (N-Cl)-Sarcosine, (N-Cl),(N-Me)-Alanine, (N-Cl)-Proline, (N-CI),(N-Me)-Valine, and (N-Cl)-2-piperidine carboxylic acid (Pipecolic acid) was studied under acid conditions. The results suggest the participation of the four possible species of the (N-Cl)-α-amino acid. A reaction mechanism is proposed which allows us to estimate the rate constant for the decomposition of each species, as well as the yet unknown macroscopic, microscopic and tautomeric equilibrum constants. The relation between the different rate and equilibrium constants is also analyzed.

Evidence for an intramolecular elimination mechanism in the aqueous decomposition of (N-Cl)-alcoholamines

Abstract (N-Cl)-alcoholamines decompose in aqueous medium through two main reaction paths: an intramolecular elimination and a fragmentation. Both mechanisms take place following a pre-equilibrium deprotonation of the β-hydroxyl group of the (N-Cl)-compound. Evidences for both pathways are given and a very high effective molarity (EM=0.2·10 6 M) is reported for the intramolecular process.

Decomposition of N-chloro-α-amino acids in alkaline medium

The decomposition of the N-Cl and N-Br derivatives of L-glycine and L-sarcosine in alkaline medium shows a first-order dependence, with respect to the N-halo-α-amino acid and to the concentration of hydroxide ions. From the leaving group effect and the primary deuterium kinetic isotope effect, and in the framework of the principle of non-perfect synchronization, the conclusion can be drawn that the decomposition of the N-halo-α-amino acids in alkaline medium can be satisfactorily described through an (AxhDHDN) mechanism with a carbanion and reactant-like transition state.

Understanding the mechanism of base-assisted decomposition of (N-halo),N-alkylalcoholamines.

The base-assisted decomposition of (N-X),N-methylethanolamine (X = Cl, Br) takes place mainly through two concurrent processes: a fragmentation and an intramolecular elimination. The global process follows second order kinetics, first order relative to both (N-X),N-methylethanolamine and base. Interaction of the base with the ionizable hydroxylic hydrogen triggers the reaction. The intramolecular elimination pathway leads to formaldehyde and 2-aminoethanol as reaction products via base-assisted proton transfer from the methyl to the partially unprotonated hydroxylic oxygen, with loss of halide. Meanwhile, the fragmentation pathway leads to methylamine and two equivalents of formaldehyde via bimolecular base-promoted concerted breakage of the molecule into formaldehyde, halide ion and N-methylmethanimine. Kinetic evidences allow a crude estimation of the concertedness and characterization of the transition structure for both processes, which are slightly asynchronous, the proton transfer to the base taking place ahead of the rest of the molecular events. The degree of asynchroneity increases as the bases become weaker. Electronic structure calculations, at the B3LYP/6-31++G** level, on the fragmentation pathway support the proposed mechanism.

EVIDENCE FOR THE INTERMEDIACY OF N-(2-IMINO, 1-OXO-PROPYL)-GLYCINE IN THE BASE-CATALYZED DECOMPOSITION OF N-HALO-DIPEPTIDES

Abstract N-(2-imino, 1-oxo-propyl)-glycine are readily formed as intermediates in the base-catalyzed decomposition of (N-X)-Ala-Gly. These compounds suffer a subsequent hydrolysis to the corresponding N-(1,2-dioxo-propyl)-glycine.