Proton transfer secondary reactions

Several MALDl ionization-relevant papers have appeared in a special issue of the European Journal of Mass Spectrometry (volume 12,2006) Proton transfer reactions in the plume were the object of experimental work by the Kinsel group and calculations by Beran and co-workers. Hoteling et al. considered electron transfer secondary reactions, which are also of relevance for the fullerenes studied with solvent-firee methods by Drewello s group. Finally, cluster ionization and desolavtion processes were investigated by Tabet and CO-workers " Also appearing in 2006 was a mechanisms review by Knochenmuss in The Analyst ... 

Since matrix is nearly always a key reactant in the plume, it is particularly important to understand matrix ions and their reactivity. Matrix can be involved in proton, electron, and cation transfer secondary reactions. As a result, matrix ions associated with all these reactions can often be observed in the mass spectra. Thermodynamic data for several matrices and their various clusters, fragments, and ionic forms have been accumulating. Experiment and theory are today generally in quite good agreement, see Table 5.1. 

Depending on the mechanism, primary ions may be matrix or analyte, or both. Primary ions are created in a dense environment, perhaps even clusters and particles, but must reach a low-density regime to become available for mass analysis. During the expansion, primary ions react with neutrals to make the secondary ions observed in the mass spectrum. These secondary reactions are the key to understanding many MALDI phenomena and are the final theme to be discussed here. There are three types of charge transfer secondary reactions known in MALDI proton, electron, and cation transfer. The characteristics of each will be discussed below, but aU lead to qualitatively similar effects in MALDI mass spectra. 

Figure 5.8. Positive-mode MALDI spectra versus matrix-analyte mole ratio (DCTB matrix) for an equimolar five-component mixture. A, M-T data ionization potential (IP), 6.04 eV (CAS number 124729-98-2) B, TTB IP, 6.28 eV (76185-65-4) C, NPB IP, 6.45eV (123847-85-8) D, rubrene IP, 6.50eV (104751-29-9) E, D2NA IP, 7.06 eV (122648-99-1). The molar mixing ratios of matrix to analyte arc indicated for each spectrum. TTiese analytes are observed exclusively as radical cations, and they exhibit matrix and analyte suppression effects analogous to those known from proton or cation transfer secondary reactions. Low ionization potential (IP) analytes suppress high IP analytes and matrix. (Adapted from Ref. 32.)...

When applied to the synthesis of ethers the reaction is effective only with primary alcohols Elimination to form alkenes predominates with secondary and tertiary alcohols Diethyl ether is prepared on an industrial scale by heating ethanol with sulfuric acid at 140°C At higher temperatures elimination predominates and ethylene is the major product A mechanism for the formation of diethyl ether is outlined m Figure 15 3 The individual steps of this mechanism are analogous to those seen earlier Nucleophilic attack on a protonated alcohol was encountered m the reaction of primary alcohols with hydrogen halides (Section 4 12) and the nucleophilic properties of alcohols were dis cussed m the context of solvolysis reactions (Section 8 7) Both the first and the last steps are proton transfer reactions between oxygens... 

The ratio ARH/ARj (monoalkylation/dialkylation) should depend principally on the electrophilic capability of RX. Thus it has been shown that in the case of t-butyl halides (due to the chemical and electrochemical stability of t-butyl free radical) the yield of mono alkylation is often good. Naturally, aryl sulphones may also be employed in the role of RX-type compounds. Indeed, the t-butylation of pyrene can be performed when reduced cathodically in the presence of CgHjSOjBu-t. Other alkylation reactions are also possible with sulphones possessing an ArS02 moiety bound to a tertiary carbon. In contrast, coupling reactions via redox catalysis do not occur in a good yield with primary and secondary sulphones. This is probably due to the disappearance of the mediator anion radical due to proton transfer from the acidic sulphone. 

The reaction-center proteins for Photosystems I and II are labeled I and II, respectively. Key Z, the watersplitting enzyme which contains Mn P680 and Qu the primary donor and acceptor species in the reaction-center protein of Photosystem II Qi and Qt, probably plastoquinone molecules PQ, 6-8 plastoquinone molecules that mediate electron and proton transfer across the membrane from outside to inside Fe-S (an iron-sulfur protein), cytochrome f, and PC (plastocyanin), electron carrier proteins between Photosystems II and I P700 and Au the primary donor and acceptor species of the Photosystem I reaction-center protein At, Fe-S a and FeSB, membrane-bound secondary acceptors which are probably Fe-S centers Fd, soluble ferredoxin Fe-S protein and fp, is the flavoprotein that functions as the enzyme that carries out the reduction of NADP+ to NADPH. 

The crucial step in self-alkylation is decomposition of the butoxy group into a free Brpnsted acid site and isobutylene (proton transfer from the Fbutyl cation to the zeolite). Isobutylene will react with another t-butyl cation to form an isooctyl cation. At the same time, a feed alkene repeats the initiation step to form a secondary alkyl cation, which after accepting a hydride gives the Fbutyl cation and an -alkane. The overall reaction with a linear alkene CnH2n as the feed is summarized in reaction (10) ... 

Primary amines react readily with nitrosating agents (Scheme 3.1) to provide deamination products. The intermediates, primary nitrosamines (RNHNO), are not stable therefore after a series of rapid reactions, they give rise to the diazonium ion (RN2+), and then decompose to the final products. The reactions of secondary amines can stop at the nitrosamine stage, since no a-hydrogen atoms are available for the necessary proton transfer reactions, which lead to diazonium ion formation. 

This method is based on the polarimetric measurement of the optical activity induced by the KIE in a reaction mixture containing an isotopic quasiracemate, i.e. an approximately 50/50 mixture of the (+)-H and (-)-D substrate or vice versa, as one of the reactants. Variants of the method were independently reported by Bergson et al. (1977), Nadvi and Robinson (1978) and Tencer and Stein (1978). Later the method was successfully applied, particularly by Matsson and co-workers (Matsson, 1985 Hussenius etal., 1989 Hussenius and Matsson, 1990) to determine both primary and secondary KIEs in proton transfer reactions, and by Sinnott and co-workers (Bennet et al., 1985 Ashwell et al., 1992 Zhang et al., 1994) to determine both primary and secondary as well as heavy-atom KIEs for reactions of carbohydrate derivatives. 

Since morpholine and piperidine are stereochemically similar but exhibit different pKa values, the difference between their rates in the reactions of the fluoro-substrates in acetonitrile could be also due to a change in mechanism, whereby proton transfer from the intermediate 1 in equation 1 becomes rate-limiting when the reagent is morpholine. The change from an uncatalysed to a base-catalysed reaction with decrease in basicity of the nucleophile is well known in ANS for both primary and secondary amines1 200. 

Ab initio MO calculations were carried out on the hydrolysis of CH3CI, with explicit consideration of up to 13 water solvent molecules. The treatments were at the HF/3-21G,HF/6-31G,HF/6-31 G orMP2/6-31 G levels. Forn > 3 three important stationary points were detected in the course of the reaction. Calculations for n = 13 at the HF/6-31 G level reproduced the experimental activation enthalpy and the secondary deuterium KIE. The proton transfer from the attacking water to the water cluster occurs after the transition state, in which O-C is 1.975 A and C-Cl is 2.500 A. 

Class (3) reactions include proton-transfer reactions of solvent holes in cyclohexane and methylcyclohexane [71,74,75]. The corresponding rate constants are 10-30% of the fastest class (1) reactions. Class (4) reactions include proton-transfer reactions in trans-decalin and cis-trans decalin mixtures [77]. Proton transfer from the decalin hole to aliphatic alcohol results in the formation of a C-centered decalyl radical. The proton affinity of this radical is comparable to that of a single alcohol molecule. However, it is less than the proton affinity of an alcohol dimer. Consequently, a complex of the radical cation and alcohol monomer is relatively stable toward proton transfer when such a complex encounters a second alcohol molecule, the radical cation rapidly deprotonates. Metastable complexes with natural lifetimes between 24 nsec (2-propanol) and 90 nsec (tert-butanol) were observed in liquid cis- and tra 5-decalins at 25°C [77]. The rate of the complexation is one-half of that for class (1) reactions the overall decay rate is limited by slow proton transfer in the 1 1 complex. The rate constant of unimolecular decay is (5-10) x 10 sec for primary alcohols, bimolecular decay via proton transfer to the alcohol dimer prevails. Only for secondary and ternary alcohols is the equilibrium reached sufficiently slowly that it can be observed at 25 °C on a time scale of > 10 nsec. There is a striking similarity between the formation of alcohol complexes with the solvent holes (in decalins) and solvent anions (in sc CO2). 

These species, for oxygen-containing compounds, have a large stability (in excess of 20 kcal mol - ) and require a very loose association. This stability allows for partial proton transfer to the alcohol, even when the ester has a larger proton affinity than the alcohol. The scheme is also consistent with the picture that reactions will take place only at centres prone to form a carbenium ion, namely secondary or tertiary carbon centres. 

The thiophene ring is opened and sulfur extruded as hydrogen sulfide when 3,4-dinitrothiophene is reacted with piperidine. The product contains two nitroenamine units coupled to each other (Scheme 140). Other secondary amines react similarly (69CC549). Secondary aliphatic amines also react with 2-nitrothiophene to form the nitrodienamines (426) in 50-80% yield. It is believed that the reaction involves addition of the amine at position 5, followed by proton transfer and ring opening to give the thiol which, in the presence of air, oxidatively dimerizes to (426) (Scheme 141). In one case the thiol has been trapped as the silver salt and methylated (74JCS(P1)2357). 

The gas-phase heats of formation obtained from pulsed ion cyclotron resonance (ICR) spectroscopy showed that the tertiary 1-cyclopropyl-1-methylethyl cation (20) is more stable than the 1-phenyl-1-methylethyl cation by 0.8 kcalmol 1, while the secondary 1-cyclo-propylethyl cation (18) is less stable than the 1 -phenylethyl cation by 4.8 kcal moT125. Thus a substantial reversal of the stabilization of the phenyl over cyclopropyl groups is observed. The results were also rationalized by STO-3G calculations for the isodesmic reaction involving proton transfer (equation 71). 

The order of acidity of various liquid alcohols generally is water > primary > secondary > tertiary ROH. By this we mean that the equilibrium position for the proton-transfer reaction (Equation 15-1) lies more on the side of ROH and OHe as R is changed from primary to secondary to tertiary therefore, tert-butyl alcohol is considered less acidic than ethanol ... 

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