Free Carbonium Ions Research Articles

5] Trifluoroacetic acid cleavage and deprotection of resin-bound peptides following synthesis by Fmoc chemistry

The successful assembly of a peptide sequence represents only half the challenge of solid-phase peptide synthesis (SPPS). The side-chain protecting groups and linkers designed for fluorenylmethyloxycarbonyl (Fmoc) protocols are labile to trifluoroacetic acid (TFA). The procedure described is suitable for the various linkers cleaved by TFA, whether producing C-terminal acids or amides. Commercially available and suggested linker-resins for generating peptide acids are 4-alkoxybenzyl alcohol, 4-hydroxymethylphenoxyacetic acid (HMPA/PAB), and 2 chlorotrityl chloride. Under certain circumstances, TFA can cleave both at the linker-peptide bond and at the attachment point of the linker to the resin. Consequently, two events may occur. The free carbonium ion of the linker may alkylate Trp, with the resulting peptide exhibiting a more hydrophobic high-performance liquid chromatography (HPLC) elution behavior and a higher mass than the desired peptide. In addition, the cleavage yield may be noticeably reduced due to a reaction between a Trp or Cys residue and the linker ion while still attached to the resin. In a study of the correlation between the proximity of Trp to Arg in a sequence and extent of modification of Trp, it was found that this side reaction is greatest when Trp and Arg are separated by one residue.

Quantum molecular study of sulfur mustard

The sulfur mustard, HD, a chemical warfare agent, has been studied by ab initio quantum molecular computations (HF/6-31G* and 6-31G) on its various forms (neutral, ethylene sulfonium, and free carbonium ions). The geometries of these molecules have been completely optimized and the minimal energy conformations determined with their associated charge distributions. We discuss these results on electrostatic properties with respect to the mechanism of DNA alkylation by HD and compare them with our previous study of the nitrogen mustard mechlorethamine.

Photolysis of diphenylmethyl diphenylacetate in the presence and absence of cupric ion: the fate of the diphenylmethyl radical

Abstract The photolysis of diphenylmethyl diphenylacetate, a relatively clean source of the diphenylmethyl radical, has been studied in acetonitrile, methanol and mixtures of the two solvents with and without added cupric ion. Photolysis of the ester only in either solvent results in the production of CO2 and tetraphenylethane as the main products, with a quantum yield of 0.15 ± 0.02 for the decomposition of the ester. The addition of millimolar amounts of copper(II) to the photolysis mixture changes the product distribution dramatically. Free radical products are suppressed and the major products can be attributed to reactions of an oxidized diphenylmethyl species. In the presence of methanol, good yields of methyl diphenylmethyl ether are obtained. Rate constants and activation energies for the reactions involved are reported. Flash photolysis experiments confirm the production of diphenyl-methyl radiclas from the ester. In the absence of copper(II) their major fate is recombination to the ethane. The recombination involves a semi-benzene intermediate. In the presence of copper(II) the transient absorption due to diphenylmethyl is suppressed and a transient attributed to an organo- copper intermediate is observed. No absorption due to a free carbonium ion was detected.

Kinetics of nucleophilic attack on coordinated organic moieties. XVIII. Nucleophilicity of anions towards the tricarbonyl-(η-benzene) manganese (I) cation.

Kinetic results for the addition of OH − to [Mn(CO) 3(η-C 6H 6)] + (I) in water (eq. 1, X  OH) obey the expression k obs  k OH[OH −], and give a k OH value of 290 mol −1 dm 3 s −1 at 20.0°C and ionic strength of 0.25 mol dm −3. The analogous reaction of NaCN with I in water fits the two-term expression k obs = k OH[OH −] + k CN[CN −], and leads to a k CN value of 0.8 mol −1 dm 3 s −1 at 20.0°C and ionic strength of 0.25 mol dm −3. Interestingly, the related reaction (eq. 1, X  N 3) is too rapid to follow by stopped-flow spectrophotometry, indicating the overall rate trend N 3 − » OH − » CN −. This unusual nucleophilicity order, unexpected on the basis of both basicity and polarizability, is similar to that previously observed for anion addition to free carbonium ions.

A new method for fluorination of sterols

Diethylaminosulfurtrifluoride (DAST) is a good fluorinating reagent for sterols. The fluorinating reactions proceed through SN 2 mechanism, while reactions through free carbonium ion are responsible for rearrangements and eliminations.

Mechanism of catalysis for the hydration of substituted styrene oxides by hepatic epoxide hydrase

The effect of aryl substituents on the rate at which epoxide hydrase catalyzes the addition of water to styrene and cis-stilbene oxides has been examined. Plots of log V m for each substrate versus the Hammett σ constants for the substituent suggest that a nucleophilic attack occurs and that a free carbonium ion form of the substrate is not involved at the rate-determining step in the mechanism. For the stilbene oxides, high selectivity for attack by water at the carbon atom with [S] absolute stereochemistry was observed.

Aromatic substitutions by [3H3]methyl decay ions. A comparative study of the gas- and liquid-phase attack on benzene and toluene

A nuclear technique based on the spontaneous decay of tritiated precursors that allows the generation of free carbonium ions of exactly the same nature in different environments, has been exploited in a comparative study of aromatic alkylation by CT3+ ions, both in the gas phase at various pressures and in the liquid phase. The differences between the reactivity pattern of the methyl cation in the two environments can be essentially reduced to the much greater efficiency of collisional stabilization in the condensed phase, allowing a larger fraction of the excited arenium ions, from the highly exoenergetic (ΔH° < 335 kJ mol–1) attack of the CT3+ ions on benzene and toluene, to survive dissociation and/or isomerization. The mechanism of the major competitive processes promoted by CT3+ attack on arenes, i.e. methylation, tritiodemethylation, and methyldemethylation are discussed, and the substrate and positional selectivity of the CT3+ ions from the decay of CT4 is compared with that of more conventional alkylating reagents.

The acid-catalysed hydrolysis of tetramethyloxiran: a re-investigation

The acid-catalysed hydrolysis of tetramethyloxiran yields 2,3-dimethylbutane-2,3-diol (ca. 98%) and 3,3-dimethylbutan-2-one (<1%). This result differs markedly from that previously reported and widely quoted as evidence for a free carbonium ion. It must now be concluded that reaction involves bimolecular attack by water on the protonated epoxide.

Neutral Salt Effects on Cationic Polymerization of N-Vinylcarbazole Initiated by Protonic Acids

Cationic polymerization of N-vinylcarbazole(VCZ) initiated by perchloric acid or trichloroacetic acid(TCA) in three different solvents(nitrobenzene(NB), ethylene dichloride(EDC), and benzene(Bz)) was studied at 30°C in the presence and absence of neutral electrolytes(tetra-n-butylammonium perchlorate(TBP) and tetraethylammonium perchlorate(TEP)). The kinetic quantity determined was the chain-transfer constant to methanol. Since chain-transfer constant is affected by the nature of kinetic chain carrier, the study of neutral salt effects on chain-transfer constants provides useful information on whether the cationic chain carrier is free or ion-paired. Measurements for six combinations of three solvents and two initiators either in the presence of TBP or in its absence afforded the following pieces of information.(1) The presence of TBP enhanced the chain-transfer constant in polar media. However, no neutral salt effects were observed in benzene, indicating that the growing carbonium ion in benzene is tightly ion-paired and the addition of TBP cannot affect the ionic association.(2) In EDC, the chain-transfer constants of methanol are very much enhanced by the addition of neutral electrolyte. The results were interpreted assuming that the rate of propagation decreases in the presence of TBP whereas the rate of chain-transfer reaction is relatively unaffected. A study of the deuterium isotope effect using methanol-d supports this view.(3) In NB, the propagating species in the absence of TBP seem to be free carbonium ions since the kind of initiator does not influence the chain-transfer constant. In this system, the growing cation would be strongly solvated and stabilized.(4) Dependence of the rate of polymerization on neutral salts was also investigated. The rate of polymerization is, however, a complex function of various rate constants and conclussion is difficult.Chain-transfer constants are very sensitive to the nature of propagating species and their determinations as functions of neutral electrolyte concentration would provide a useful procedure to study the ionic equilibria of the carbonium ion and ion pairs.

Competitive reactions of nucleophiles—III : The azide probe

The azide competition factors ( k N 3 ,−/ k SOH) of cyclopentyl mesylate ( 1), 1-methylcyclopentyl chloride ( 2), cyclohexyl brosylate ( 3), benzhydryl chloride ( 4), benzhydryl bromide ( 5), 3β-cholestanyl brosylate ( 6), 3α-cholestanyl brosylate ( 7), 2-methyl-2-adamantyl chloride ( 8), 1-adamantyl bromide ( 9) and 2-adamantyl tosylate ( 10) were determined. Tertiary substrates ( 2, 8, 9) invariably gave lower k N 3 −/ k SOH values than secondary ones ( 1, 3, 4, 5, 7); opposite from what is expected on the basis of the stabilities of the respective free carbanium ions. This was explained by the attack of the nucleophile on ion pair(s) rather than on free carbonium ions. The magnitude of the competition factor seems to yield useful mechanistic information only in two extreme cases, i.e. direct displacement (S N2) and free stable carbonium ions (tertiary aromatic substrates-dissociative S N1 mechanism). In all other cases, especially with secondary substrates, the mechanistic evaluation of the k N 3 −/ k SOH values is ambiguous and in our opinion of doubtful value.

Fundamental studies on cationic polymerizations: Molecular weights and molecular weight distributions of polyisobutylenes produced by γ‐irradiation (free ions) and chemical catalysis (ion pairs)

AbstractThe molecular weights (M̄n, M̄v, and M̄w) and molecular weight distributions of polyisobutylenes synthesized by γ‐irradiation in the range 29 to −78°C have been determined. The plots of log M̄n, log M̄v, and log M̄w versus 1/T are linear and parallel (EM̄ = −6.36 ± 0.5), and M̄w/M̄n ≈ 3.0 ± 0.5 over this temperature range. The viscosity‐average molecular weights of polyisobutylenes obtained by γ‐irradiation were compared with those of polymers prepared by BF3, EtAlCl2, and AlCl3. It is found that, at the same polymerization temperature, the M̄v of radiation‐induced polyisobutylenes, which propagate by free carbonium ions, is significantly higher than those synthesized by the Lewis acids, which probably propagate via ion pairs. The implications of these findings are discussed, and it is concluded that the counterion in the proximity of the growing cation impedes propagation to a greater extent than it does the competing process of chain transfer to monomer.

Free carbonium ions in the anodic oxidations of alkanecarboxylates, alkaneboronates, and alkyl halides

Free carbonium ions in the anodic oxidations of alkanecarboxylates, alkaneboronates, and alkyl halides

Competitive reactions of nucleophiles : Solvolyses of cyclopropylcarbinyl and cyclobutyl methanesulfonates in the presence of NaBH 4

Cyclopropylcarbinyl (I) and cyclobutyl (II) mesylates were solvolysed in aqueous diglyme with or without added NaBH 4 under a variety of conditions. The reaction products were isolated and analyzed by VPC. A mixture containing cyclopropylcarbinyl, cyclobutyl and minor quantities of homoallyl products, was obtained in all cases. The proportion of the unsaturated compound was greater in hydrocarbon than in carbinol products, the composition of the mixture depending upon reaction conditions and the starting mesylate. Thus, solvolysis of both I and II yielded cyclopropylcarbinol and cyclobutanol in a ratio of nearly 1:1, while in the hydrocarbon products methylcyclopropane predominated over cyclobutane by a factor of 3 in the reactions of I and by a factor of 2 in the reactions of II. It was shown that a direct displacement reaction of the BH 4 ion on the primary mesylate I is not competitive with the solvolysis and cannot therefore be responsible for the above results. It was found that a better yield in hydrocarbons was obtained with I and II than with (1-methylcyclopropyl)carbinyl (III) and 1-methylcyclobutyl (IV) mesylates. The unexpected fact that the BH 4 − ion competes more efficiently with water for intermediates formed in solvolyses of I and II than for those of III and IV was confirmed by determination of competition factors of N 3 − ion vs water. In all cases, intermediates formed from I and II showed more discrimination in their reactions with reagents differing in nucleophylicity than did those formed from III and IV. The results indicate that the attack of the nucleophile occurs mostly on the ion pair formed in the rate determining step. The latter reaction is apparently subject to reactivity relationships typical for a direct displacement reaction and not characteristic for free carbonium ions. These facts should be borne in mind when conclusions concerning the structure of carbonium ions are drawn from the composition and structure of solvolysis products. It is concluded that the ion pairs trapped by NaBH 4 have different structures, depending upon the starting isomeric mesylate. It is shown that the formation of an equilibrating mixture of classical ions or ion pairs as intermediates in these reactions cannot account for experimental results.

Propagation reactions in the copolymerization of styrene and p-chlorostyrene by perchloric acid

The kinetics of the homopolymerization of p-chlorostyrene by perchloric acid in ethylene dichloride have been found to be similar to those of styrene but with a lower value of the propagation rate constant at 25°: k p = 290 l. mol −1 min −1. The copolymer compositions in copolymerization with styrene yield values of the reactivity ratios r 1( styrene)=2·0±0·, r 2=0·43±0·05 very similar to values found with Friedel-Crafts catalysts. Combination of these results with the value of the homopropagation rate constant for styrene, k 11 = 1050, under the same conditions yields values for the cross-propagation constants k 12=525 l. mol p1 min -1 and k 12=670 l. mol p-1 min -1 The propagating species derived from styrene is therefore more reactive than that from p-chlorostyrene, i.e. the opposite effect to that expected if the propagating species were a free carbonium ion. A complex mechanism for the propagation reaction is indicated.

Studies on the Mechanism of Olefin-Alcohol Interconversion. The Effect of Acidity on the O18 Exchange and Dehydration Rates of t-Alcohols

Evidence from the acidity and temperature dependence of the rates of O18 exchange and dehydration of t-alcohols was obtained; this evidence indicates that these two reactions proceed by common initial steps but involve different rate-determining steps. The results appear to eliminate a mechanism in which a carbonium ion isomerizes to a pi -complex in the rate-determining step of the alcohololefin interconversion. Present results are found to be consistent with mechanisms which involve (in the formation of olefin from alcohol) either a rate-determining reaction of a free carbonium ion with water or the isomerization of an encumbered carbcnium ion intermediate, R⁺... OH², to a pi -complex. The encumbered carbonium ion classification is proposed for intermediates which possess substantial carbonium ion character and involve leaving or entering groups of either neutral or various charge types. The mechanism involving the encumbered carbonium ion intermediate is favored. (auth)