Allylic Carbocation Research Articles

A Schmidt route to 1-azabicyclo[x.y.0]alkanes: a comparison of carbocation stabilizing groups

Abstract The intramolecular Schmidt reactions of tertiary alkyl, tertiary benzylic, tertiary propargylic, and tertiary allylic carbocations with tethered azides are reported. Using product analysis and deuterium labeling studies, the role of cation rearrangement prior to Schmidt reaction is reported.

ChemInform Abstract: Novel Synthetic Method for N-Allylcarbamates from Allyl Ethers Using Chlorosulfonyl Isocyanate.

Abstract Various allyl ethers were converted into the corresponding N-allylcarbamates using chlorosulfonyl isocyanate (CSI) via the stable allylic carbocation rather than β-lactam through [2+2] cycloaddition. The reaction of cinnamyl methyl ether with CSI afforded only methyl N-cinnamylcarbamate at 0°C, but at 20°C, it produced a mixture of methyl N-cinnamylcarbamate and methyl N-(1-phenylprop-2-enyl)carbamate in a 2.7:1 ratio.

Novel synthetic method for N-allylcarbamates from allyl ethers using chlorosulfonyl isocyanate

Various allyl ethers were converted into the corresponding N-allylcarbamates using chlorosulfonyl isocyanate (CSI) via the stable allylic carbocation rather than β-lactam through [2+2] cycloaddition. The reaction of cinnamyl methyl ether with CSI afforded only methyl N-cinnamylcarbamate at 0°C, but at 20°C, it produced a mixture of methyl N-cinnamylcarbamate and methyl N-(1-phenylprop-2-enyl)carbamate in a 2.7:1 ratio.

FTIR and UV−Vis Spectroscopic Study of Interaction of 1-Butene on H−Ferrierite Zeolite

The interaction of 1-butene with zeolite H−ferrierite has been studied at increasing temperatures (between 300 and 670 K) by using IR and UV−vis spectroscopies, with the aim to isolate in situ the species precursors to isobutene and high-temperature coke. The bimolecular mechanism of conversion of butene to isobutene on the fresh catalyst has been confirmed, since low branched C8 chains are observed. At 300 K, the main products of the interaction are the butene isomers 2-cis- and 2-trans-butene. At temperatures between 300 and 393 K, the presence of monoenic allylic carbocations is observed, and at temperatures between 473 and 573 K, neutral and carbocationic polyenes are present. At temperatures ≥ 623 K, the polyenyl unsaturated chains cyclize to form mono- and polycyclic aromatics. These experimental features are explained on the basis of mechanisms in which the protonated intermediates (formed by protonation of butene) can produce, by further reaction with butene molecules, mainly two kinds of products: (i) polyenyl allyl carbocations (by a butene hydride abstraction) and (ii) octane carbocations (by dimerization), which then evolve (by cracking) to isobutene.

Rearrangement of epoxides in non-aldol aldol process: Allylic vs. Tertiary and secondary carbocationic centers

It has been shown that allylic carbocations are formed in preference to tertiary or secondary carbocations in the rearrangement of substituted epoxides. However protection of the alkene as a bromo ether allows for the desired rearrangement and production of intermediates for the synthesis of the cytotoxic tedanolides.

Propene adsorption and reaction on zeolites and pillared clays

Comparative IR and UV-Vis spectroscopic studies of propene adsorption and reaction on H-mordenite, dealuminated H-mordenite, dealuminated mazzite, montmorillonite and Al13-pillared montmorillonite have been carried out. On all systems propene is first transformed into polymeric species (CnH2n+1+). On HMOR (both as such and dealuminated), allylic carbocations are successively produced by loss of H2, the monoenic species (CnH2n−1+) being formed at room temperature and the dienic (CnH2n−3+) and trienic (CnH2n−5+) species at higher temperatures. These species are not observed on the other systems, although they are presumably formed as unstable intermediates. In fact, on all the zeolites studied here two cyclic penta-atomic and hexa-atomic allylic carbocations have been observed for the first time. On all systems, the final products of reaction are polyaromatic species which, on the basis of their reaction with NH3 still exhibit unsaturated carbocation behaviour. The activity of the various samples depends on their pore dimensions and on the nature of acidic sites involved: the larger the available pore space, the more branched is the polymer and the more difficult it is to observe allylic carbocations. Evidence is provided for a Bronsted-induced mechanism.

The acid-catalysed rearrangements of 4,5-bis(2-thienylhydroxymethyl)-1,3-dithiole-2-thione

Under strongly acidic conditions, the title compound 1 readily participates in several possible rearrangement pathways, affording a product distribution which is relative to the choice of solvent and acid catalyst. Thus, using chloroform or acetone as the solvents and HBr or HClO4 as the catalysts, compounds 2–4 have been isolated and fully characterised; in addition, compound 5 was identified in the reaction mixture and characterised by 1H NMR spectroscopy. The reaction kinetics of the transformations have been studied by 1H NMR spectroscopy, using deuterated chloroform or acetone as the NMR solvents. A key intermediate in the reaction mechanisms is the allylic carbocation 6, which rearranges to give the fused system 3; in the presence of bromide anions, the carbocation forms an ion-pair intermediate 7, leading to the formation of compounds 2, 4 and/or 5, depending on the solvent.

Biogenesis and biological function of marine algal oxylipins.

The biogenetic source of most marine algal oxylipins, which are many and of diverse structure, can logically be unified through a common lipoxygenase-derived hydroperoxide to epoxy allylic carbocation transformation. The biological role of oxylipins in algae remains an enigma, although numerous ideas have been put forth. Herein, we hypothesize and provide some evidence for an osmoregulatory role for these metabolites.

Epoxy allylic carbocations as conceptual intermediates in the biogenesis of diverse marine oxylipins.

Marine organisms, especially marine algae, are extremely rich in a diversity of novel oxylipin structures. Many of these oxylipins contain functionalities and rings of a type and location unknown in mammalian systems. In this perspective reviewing marine oxylipins, a proposal is formulated for the central intermediacy of an epoxy allylic carbocation in the biogenesis of these diverse structures. This proposal is strengthened by the relatively large number of examples which are consistent with this type of mechanistic transformation.

Conformational studies and electronic structures of tamoxifen and toremifene and their allylic carbocations proposed as reactive intermediates leading to DNA adduct formation.

Toremifene, a compound which differs from tamoxifen by the substitution of a chlorine atom for a hydrogen atom in the ethyl group, is significantly less potent than tamoxifen in causing DNA adduct formation in rats. To examine the relationship of the DNA adduct-forming ability of these compounds with their physicochemical properties such as stable conformation and chemical reactivity, we carried out molecular mechanics, molecular dynamics, and quantum mechanics calculations for the two compounds. For tamoxifen, six stable conformers were identified by conformational search with CFF91 force field. Molecular dynamics simulations showed that these were often interconverted within 1.0 ns. On the other hand, although the conformation of stable conformers and dynamical behavior of toremifene were almost the same as those of tamoxifen, a few conformations were slightly different from those of tamoxifen owing to the effect of the chlorine atom at chloroethyl group. In addition, the stability of the allylic carbocation, which had been proposed as the reactive intermediate leading to DNA adduct formation, was calculated with both semiempirical and density functional methods. Results showed that the carbocation intermediate of toremifene was less stable than that of tamoxifen by 4-5 kcal/mol, suggesting that toremifene was less frequently activated to the intermediate than tamoxifen. Furthermore, the carbocation intermediates of two other tamoxifen derivatives, 4-iodotamoxifen and droxifene, which show no DNA adduct-forming ability, were also less stable compared with that of tamoxifen. These calculated results suggest a close relation between the stability of the proposed carbocation intermediate and DNA adduct-forming ability.

Ethene adsorption and reaction on some zeolites and pillared clays

In the acidic solids used in this study, ethene undergoes a cationic polymerisation started by proton transfer. The larger the dimensions of the micropores, the higher is the degree of branching of the polymeric cationic species obtained. Such saturated polymeric cationic species evolve upon thermal treatment by loss of hydrogen to allylic carbocations (linear mono-, di- and trienic species as well as penta-cyclo and hexacyclo monoenic species), which are precursors to aromatics. All species have been characterised both in the infrared (IR) and ultraviolet (UV) regions. The overall chemistry is very close to that of propene on the same systems, though ethene appears less reactive.

3 + 2] and [3 + 3] Cycloadditions of Azides with Allylic Carbocations

Azides undergo unprecedented low-temperature [3+2] or [3+3] cyclo- additions with allylic carbocations, producing triazolines or dihydrotriazines

Characterization of a Model for Consecutive First-Order Reactions: Redox Chemistry of Bile Acids

Bile acids and other sterols when introduced into 70-80% sulfuric acid yield chromophores showing absorption bands between 300 and 315 nm and between 370 and 385 nm. These absorption bands have been attributed to allylic (between 300 and 315 nm) and dienylic (between 370 and 385 nm) carbocations formed in a sequence of reactions involving oxidation-reduction equilibria (hydride transfer), accompanied by acid-base reactions. Kinetics of such reactions may be modeled using Eq. (1): [formula] where A corresponds to the starting material, B to an allylic carbocation, and C to a dienylic species. Reactions which follow Eq. (1) show distinctive features in plots of concentration of A, B, and C as a function of time. For example, a plot of logarithm of A vs time may be strictly linear, or may be nonlinear, consisting of two linear segments. Furthermore, a plot of B vs time may or may not show the presence of maximum and in a plot of C vs time a point of inflection and period of induction may or may not be distinguishable. We have derived quantitative definitions for each of these features and denoted them as characteristic features. The degree to which a characteristic feature determines the shape of the overall concentration-time plot depends on the relative values of the individual rate constants (k1, k−1, k2, and k−2. In this paper a procedure was developed which uses arrays of contour plots based on rate constants as coordinates that show for what range of rate constant values each of the characteristic features is distinguishable in the particular concentration vs time plot. In addition, the contour plot approach is utilized in the determination of rate constant values for reaction of 0.0001 M chenodeoxycholic acid in 78.9 and 74.3% sulfuric acid/water solution at 60°C. The following results were obtained:[formula]

Amidinium cation as a mimic of allylic carbocation: synthesis and squalene synthetase inhibitory activity of an amidinium analog of a carbocation intermediate.

Amidinium cation as a mimic of allylic carbocation: synthesis and squalene synthetase inhibitory activity of an amidinium analog of a carbocation intermediate.

Spectrophotometric Determination of Bile Acids; An Evaluation

Bile acids can be determinated by measuring absorbance in the ranges between 290 and 310 nm or between 370 and 390 nm of species which are formed when bile acids react in 77.8 wt.% sulfuric acid at 70 °C for 30 min. The absorption bands at about 300 nm correspond to a formation of allylic carbocations, those at about 380 nm to dienylic carbocations. The absorbance was found to be linear function of concentration between 1 and 5 . 10-5 mol l-1. Measurements of absorbance were compared for 11 bile acids. The method can be used for analysis of dilute solutions of these acids, e.g. in estimating their solubility.

Revision of the stereochemistry in trichodiol, trichotriol and related compounds, and concerning their role in the biosynthesis of trichothecene mycotoxins

Trichodiol and trichotriol are shown to have 9β-hydroxyls (trichothecene numbering), not 9α-hydroxyls as quoted in the literature. The C-9 configurations in other related trichodiene derivatives also need reassignment. Compounds with a 9β-hydroxyl are readily converted into a mixture of 9β- and 9α-hydroxy isomers on treatment with acid, typically in a ratio of about 4: 1. An allylic carbocation intermediate is postulated, and the same carbocation can be generated from 11-hydroxy analogues such as isotrichodiol. Cyclization to trichothecenes occurs in the presence of a 2-hydroxyl. The natural occurrence of both 9β- and 9α-isomers of trichodiol (in Trichothecium roseum) and of trichotriol (in Fusarium culmorum) suggests these result from acid-catalysed isomerization of isotrichodiol and isotrichotriol, respectively, via the appropriate carbocations. Accordingly, trichodiol and trichotriol are probably artefacts rather than biosynthetic intermediates on the pathway to trichothecenes. This is borne out by the results of competitive feeding experiments which indicate that the incorporation of isotrichodiol into trichothecenes is not influenced by trichodiol, and only marginally by trichotriol. Isotrichotriol did repress incorporations, so the pathway to trichothecenes is now proposed to proceed via isotrichodiol and isotrichotriol, not via trichodiol and trichotriol. Pre-sambucoin, a further product from acid-catalysed cyclization of isotrichodiol, is an efficient precursor of sambucoin in Fusarium culmorum. Isotrichotriol and the new metabolise 8α-hydroxyisotrichodiol were isolated from xanthotoxin-inhibited cultures of F. culmorum.

ADDITIONS OF NUCLEOPHILES TO VINYL PHOSPHONIUM SALTS. A USEFUL WAY TO OBTAIN NEW SYNTHONS

Abstract The vinylphosphonium salts 2. obtained from allenyl compounds 1. are phosphorus synthetic equivalents of γ functionalized allylic carbocations. Nucleophilic addition reactions give polyfunctional phosphonium salts, useful starting materials for further investigations. As a function of the basicity of the nucleophile, the addition reaction is in competition with elimination of the phosphorus group in 2, leading to reformation of the allenic starting material 1.

Reactions of 2-Deoxy-4, 5-O-Isopropylidene-D-Erythro- and D-Threo-Pent-1-Enose Derivatives

ABSTRACT The reactivity of the title compounds has been studied toward different nucleophiles and electrophiles. Unlike other ketene dithioacetals, compounds 3-5 did not add nucleophiles to the double bond. Instead, in the presence of Lewis acids they underwent substitution reaction at position 3. If the nucleophile was not strong enough, formation of 6 and 7 were observed. With 2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranose (18), a 3:1 mixture of 11 and 12 was formed from 4. These observations may be interpreted in terms of easy formation of the allylic carbocation I which gives diastereomers with nucleophiles. However, this allylic ether-like behaviour was ruled out by the fact that compounds 9 and 10 did not undergo [2,3] sigmatropic rearrangement with lithium diisopropylamide. With N-bromosuccinimide compound 3 gave the 2-bromo derivative 8. Compounds 3 and 8 resisted common mercury salt assisted demercaptalization procedures.

Reactions of selenium stabilized allylic carbocations with 1-(trimethylsilyloxy)cyclohexene

In favorable cases the title reactions occur efficently and with high regioselectivity; they allow interesting functionalization of a simple carbonyl compound through allylic selenoxide syn-elimination and/or [3,2] sigmatropic rearrangement.

Electroanalytical and optical methods in the study of analytically important reactions

The use of polarography and spectrophotometry in the study of analytically important reactions is demonstrated on two examples: determination of arginine based on reaction with 1,2-dicarbonyl compounds, and determination of bile acids in strongly acidic media. Guanidine and arginine react at 25 °C with biacetyl in three reaction steps of considerably different rates, none of them involving the formation of a heterocycle. Only the decrease of biacetyl concentration can be followed by polarography, but neither this method nor spectrophotometry enabled following of intermediates or products. Therefore attention has been paid to the reaction of the guanidino grouping with 9,10-phenanthrenequinone (I), which behaves like an orthoquinone rather than a 1,2-diketone. Compound I reacts with two hydroxide ions and forms a stable geminal diol dianion. Reaction of I with a third hydroxide ion results in a trianion which undergoes a benzilic acid rearrangement. The nature of the species reacting with the guanidino grouping is being studied. Bile acids can be determined based on absorption at 310 and 380 nm in 70–80% H 2SO 4. The chromophores are allylic and dienylic carbocations formed in a reaction of a carbocation and olefin. The latter results from dissociation of the carbocation. In the study of the dependence of kinetics of this reaction on acidity, the problem of reaction of ethanol (used as co-solvent) with sulfuric acid was encountered. Equilibrium constants for the reaction of ethanol and methanol with sulfuric acid were measured. From their dependence on acidity it follows that ROH reacts with HSO 4 − to yield ROH +SO 3 −. For ROH 2 + ⇌ ROH + H + approximate values of K ROH = 5 × 10 3 liters mol −1 for ethanol and 1.8 × 10 4 liters mol −1 for methanol were found.