Free Carbocations Research Articles

Simple and Practical Conversion of Benzoic Acids to Phenols at Room Temperature.

Phenols are important organic molecules because they have found widespread applications in many fields. Herein, an efficient and practical approach to prepare phenols from benzoic acids via simple organic reagents at room temperature is reported. This approach is compatible with various functional groups and heterocycles and can be easily scaled up. To demonstrate its synthetic utility, bioactive molecules and unsymmetrical hexaarylbenzenes have been prepared by leveraging this transformation as strategic steps. Mechanistic investigations suggest that the key migration step involves a free carbocation instead of a radical intermediate. Considering the abundance of benzoic acids and the utility of phenols, it is anticipated that this method will find broad applications in organic synthesis.

Anthony Ledwith CBE. 14 August 1933—5 January 2015

Tony Ledwith's early work at University of Liverpool is best known for the identification, characterization and use of free carbocations; in particular, demonstrating their advantages in allowing very high rates of vinyl addition and ring opening polymerizations. During a long career in academia and industry, his research predominantly focused on cationic and cation-radical mechanisms, but ranged across many aspects of polymerization mechanisms, properties and the applications of polymeric materials. His interests were always very wide, for example in surface characterization and modification. In his industrial career, his company was one of the very early adopters of scanning probe microscopies. He was an energetic enthusiast and became heavily involved in science politics, to the considerable benefit of the UK community, particularly chemists and polymer chemists.

Gold(III) Chloride‐Catalyzed Diastereoselective Alkylation Reactions with Chiral Benzylic Acetates

AbstractGold(III) chloride was shown to be an efficient catalyst for the diastereoselective CC bond formation of various chiral para‐methoxybenzylic acetates and different nucleophiles. All electrophilic acetates carried next to the reacting center a stereogenic carbon center bound to a functional group (FG), a methyl substituent and a proton. Selectivities were good (dr>80/20) in favor of the anti‐product for FG=COOMe, NO2, CN and in favor of the syn‐product for FG=SO2Et, PO(OEt)2. The reactions proceed most likely via a free carbocation, in which a face differentation is facilitated by a preferred conformation. Several arene nucleophiles were shown to be compatible with the catalysis conditions providing the corresponding substitution products in high yields (13 examples, 62–98%). Moreover, other nucleophiles (allyltrimethylsilane, trimethylsilyl cyanide, 2,2‐dimethyl‐3‐(trimethylsilyloxy)butane, p‐toluenesulfonamide, and acetylacetone) reacted with a representative chiral electrophile in a high yielding and diastereoselective fashion.

Dynamics for the Reactions of Ion Pair Intermediates of Solvolysis

AbstractFor Abstract see ChemInform Abstract in Full Text.

A Topological Study of the Transition States of the Hydrogen Exchange and Dehydrogenation Reactions of Ethane on a Zeolite Cluster

The transition states of the hydrogen exchange and dehydrogenation reactions of ethane on a zeolite acid site are calculated using the density functional theory and analyzed with the atoms-in-molecules method. The transition state for the hydrogen exchange reaction is characterized by a slightly ionic interaction between a distorted H-ethonium structure, C2H7+, and a negatively charged zeolite cluster. No free carbocation is found. The dehydrogenation reaction, on the other hand, shows a transition state with three well-defined fragments, namely, an ethyl cation, C2H5+, a negatively charged zeolite cluster, and a H2 pseudomolecule, in which the H−H bond is somewhat larger than the equilibrium value in H2. The interaction between those fragments can be described as a closed-shell one, typical of rather ionic systems.

Radical Clock Substrates, Their C−H Hydroxylation Mechanism by Cytochrome P450, and Other Reactivity Patterns: What Does Theory Reveal about the Clocks' Behavior?

There is an ongoing and tantalizing controversy regarding the mechanism of a key process in nature, C-H hydroxylation, by the enzyme cytochrome P450 (Auclaire, K.; Hu, Z.; Little, D. M.; Ortiz de Montellano, P. R.; Groves, J. T. J. Am. Chem. Soc. 2002, 124, 6020-6027. Newcomb, M.; Aebisher, D.; Shen, R.; Esala, R.; Chandrasena, P.; Hollenberg, P. F.; Coon, M. J. J. Am. Chem. Soc. 2003, 125, 6064-6065). To definitely resolve this controversy, theory must first address the actual systems that have been used by experiment, and that generated the controversy. This is done in the present paper, which constitutes the first extensive theoretical study of such two experimental systems, trans-2-phenylmethyl-cyclopropane (1) and trans-2-phenyl-iso-propylcyclopropane (4). The theoretical study of these substrates reveals that the only low energy pathway for C-H hydroxylation is the two-state rebound mechanism described originally for methane hydroxylation (Ogliaro, F.; Harris, N.; Cohen, S.; Filatov, M.; de Visser, S. P.; Shaik, S. J. Am. Chem. Soc. 2000, 122, 8977-8989). The paper shows that the scenario of a two-state rebound mechanism accommodates much of the experimental data. The computational results provide a good match to experimental results concerning the very different extents of rearrangement for 1 (20-30%) vs 4 (virtually none), lead to product isotope effect for the reaction of 1, in the direction of the experimental result, and predict as well the observed metabolic switching from methyl to phenyl hydroxylation, which occurs upon deuteration of the methyl group. Furthermore, the study reveals that an intimate ion pair species involving an alkyl carbocation derived from 4 gives no rearranged products, again in accord with experiment. This coherent match between theory and experiment cannot be merely accidental; it comes close to being aproof that the actual mechanism of C-H hydroxylation involves the two-state reactivity revealed by theory. Analysis of the rearrangement modes of the carbocations derived from 1 and 4 excludes the participation of free carbocations during the hydroxylation of these substrates. Finally, the mechanistic significance of product isotope effect (different isotope effects for the rearranged and unrearranged alcohol products) is analyzed. It is shown to be a sensitive probe of two-state reactivity; the size of the intrinsic product isotope effect and its direction reveal the structural differences of the hydrogen abstraction transition states in the low-spin vs high-spin reaction manifolds.

ChemInform Abstract: A Study of Essentially Free Carbocations Derived via Diazonium and Oxo Diazonium Ions in the Liquid Phase.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A Study of Essentially Free Carbocations Derived via Diazonium and Oxo Diazonium Ions in the Liquid Phase

Nitrogen- and nitrous oxide-separated ion pairs containing 4-substituted benzyl cations and carboxylate or tosylate anions were prepared by thermolysis of N-nitroso- and N-nitroamides, acidification of phenyldiazomethane, and nitrosation of N-benzyl-O-benzoylhydroxylamine. The cations were generated in benzene/toluene and benzene/anisole mixtures and were found to partition between the counterion and the solvent and between the aromatic cosolvent and benzene. A familial relationship among the methods was observed. As the cation became more reactive, the yield of solvent-derived products (SDPs) rose and the ratio of rate constants for its reaction with toluene versus benzene, kT/kB, fell. The yield of SDP also rose as the temperature was decreased and as N2 was replaced by N2O; however, kT/kB remained unchanged. Inert diluents had no effect on kT/kB but decreased hydrocarbon yield by 40% on 2-fold dilution. In the presence of reactive diluents that are converted into secondary alkylating agents, both the %...

Inadequacies of the SN1 Mechanism

Although it has been recognized for half a century that alkyl carbocations are extremely reactive and can exist only in the vacuum of the mass spectrometer or in nonnucleophilic solvents like the superacids, textbooks of organic chemistry still present them as well-defined intermediates in solvolytic displacement reactions. A planar free carbocation intermediate is used as a simple model to explain racemization in solvolysis; but the problem is that racemization is never complete, the enantiomer in excess having the inverted configuration. Also, the unimolecularity has never been demonstrated, but is an assumption only.Racemization is commonly observed for reactions that are reversible, as in the hydrolysis of an alkyl chloride. It is also necessary that either the substrate, the product, or both can undergo a degenerate reaction. This is equivalent to saying that both the attacking nucleophile and the leaving nucleofuge can play both roles. Such exchanges were demonstrated by isotopic labeling 40 years a...

The Direct Alkylation of π-Rich, Acid-Sensitive Heterocyclic Compounds via Essentially Free Carbocations1

Alkylation of pi-rich heteroaromatics such as pyrroles and furans by the standard Friedel-Crafts approach is impractical because the acid catalysts employed (Brønsted or Lewis) induce polyalkylation, ring opening, and polymerization. The present study describes the facile benzylation of pi-excessive heteroaromatics using the nitrosoamide approach, which generates nitrogen-separated carbocation-counterion ion-pairs as the alkylating agent with no catalyst being required. N-Nitrosoamides are favorable sources of carbocations because of the following variables: mildness of the conditions required to generate cations, high reactivity of the unsolvated carbocations formed, solubility of the precursors in a wide range of solvents, homogeneity of the reactions, wide range of decomposition temperatures possible, straightforward chemistry, and excellent product balance. The majority of the cations that are generated in pyrrole (80%) are intercepted by the solvent, and only 20% are intercepted by the counterion; this result provides support for the intermediacy of nitrogen-separated ion-pairs in deamination. A nucleophilicity scale is presented for reactions of selected nucleophiles with essentially free carbocations.

Studies on Mercury(II)-Mediated Opening of Bi- and Tercyclopropane Arrays

The first examples of the mercury(II)-mediated ring opening of bicyclopropane and tercyclopropane arrays have been investigated. The presence of an adjacent cyclopropyl group dramatically increased the rate of the mercury-mediated opening of the first cyclopropane in a cyclopropane array. In contrast to the mercury-mediated ring opening of monocyclopropanes which usually undergo a concerted ring-opening mechanism, electrophilic openings of cyclopropane arrays occurred through a stabilized, free carbocation. Excellent regio- and stereoselectivities were observed in the mercury-mediated intramolecular openings of the second cyclopropanes in the cyclopropane arrays, giving rise to the formation of enantiomerically pure, highly substituted tetrahydrofurans.

The decomposition of aliphatic N-nitro amines in aqueous sulfuric acid. Bisulfate as a nucleophile

In aqueous sulfuric acid, aliphatic N-nitro amines decompose to N2O and alcohols. An excess acidity analysis of the observed rate constants for the reaction shows that free carbocations are not formed. The reaction is an acid-catalyzed SN2 displacement from the protonated aci-nitro tautomer, the nucleophile being a water molecule at acidities below 82–85% H2SO4, and a bisulfate ion at higher acidities. Bisulfate is the poorer nucleophile by a factor of about 1000. Twelve compounds were studied, of which results obtained for nine at several different temperatures enabled calculation of activation parameters for both nucleophiles. The reaction appears to be mainly enthalpy controlled. The intercept standard-state rate constants are well correlated by the σ* values for the alkyl groups; the slopes are negative, with a more negative value for the slower bisulfate reaction. Interestingly the m≠m* slopes also correlate with σ*, although the scatter is bad. Key words: N-nitro amines, excess acidity, bisulfate, nucleophiles, acid-catalyzed, kinetics.

In situ free radical and carbocation reactions between alkylbenzenes promoted by a bentonite clay

The reaction between n-alkylbenzenes and bromine catalyzed with a bentonitic clay in absence of light, afforded directly substituted phenyl methanes or α-halogenated alkylbenzenes. This one-pot general method, can be used for the preparation of benzylhalides, alkyl substituted or unsubstituted methylene bridge phenyl methanes.

炭素-炭素二重結合(特にエノン類)への分子フッ素の付加反応

Some recent topics concerning the addition of molecular fluorine to C=C bonds are discussed together with the mechanistic clarification of the syn-addition and the formation of the rearrangement products. The entire scheme for the addition reaction is the formation of a perpendicular π-complex at the initial stage, which leads to a tight ion pair as the transition state. The tight ion pair then either collapses directly to the syn-addition product, or affords indirectly the carbocation rearrangement product. It is postulated that the direct precursor of the rearrangement products is not a free carbocation but a loose ion pair which is formed from the tight ion pair.

Ion–molecule pairs as intermediates in solvolysis. Catalysis by the pyridine leaving group on the elimination reaction

AbstractSolvolysis of the 1‐(1‐methyl‐1‐phenylethyl)pyridinium cation (1‐P+) in 25% (v/v) acetonitrile in water at 60°C provides the alcohol 2‐hydroxy‐2‐phenylpropane (1‐OH) as the main product along with the alkene 2‐phenylpropene (3). The formation of the elimination product 3 is promoted by the leaving pyridine. Thus, eight times more 3 is obtained from 1‐P+ than from the protonated ether 1‐OMeH+. Hydron abstraction by the leaving pyridine is only two times less efficient than with AcO− as leaving group. The results indicate that the ion–molecule pair 1+ –P has a significant lifetime. The elimination product is formed mainly from the ion–molecule pair. The free carbocation yields almost exclusively the substitution product.

Experiments Directed Towards the Synthesis of Anthracyclinones. XVIII. Novel Dioxepins From the Boron-Trifluoride Catalyzed Cyclization of Methallyl Anthraquinone Acetals

Boron trifluoride mediated cyclizations of ortho-methallyl-substituted homochiral anthraquinone acetals yield novel dioxepins, which are probably formed via free carbocation intermediates.

Number and structure of solvolysis intermediates. Part 1. A comparison of nucleophilic reactions on in situ generated carbocations with solvolysis reactions for 2,2-dimethyl-1-(p-methoxyphenyl)propyl cation

2,2-Dimethyl-1-(p-methoxyphenyl)propyl cation has been generated by treatment of the corresponding chloride with AgSbF6 in SO2–CH2Cl2(20% CD2Cl2) at –98 °C and its 13C NMR spectrum observed. The reactions of the generated carbocation with methanol or phenol give products with a rearranged carbon atom skeleton and non-rearranged products with complete racemization, as expected for a typical carbocation reaction, whereas the solvolysis of the corresponding p-nitrobenzoate in phenol affords exclusively the non-rearranged products with partial retention of configuration. Such distinctions between generated carbocation reactions and the solvolysis reactions indicate that no dissociated (free) carbocation intermediate intervenes even in this solvolysis system, i.e., it is one of a few systems which have been hitherto confirmed to proceed via multiple intermediate stages.

Free radical pathways in the nitrous acid deamination of α-aminonitriles

Free radicals and carbocations are generated competitively in nitrous acid deamination reactions of α-aminonitriles; in the absence of addedd scavengers the radicals are trapped by NO2 and by NO.

A kinetic study of nucleophilic addition to the alkene in dicarbonyl(alkene)(arene)manganese cations

Nucleophilic addition of tertiary phosphines to (arene)Mn(CO) 2(alkene) + cations occurs at the alkene ligand to give σ-alkyl type products. A kinetic and thermodynamic study of this reaction shows that the transition state is an early one. The relative nucleophilic reactivities are the same as those found for addition to coordinated cyclic π-hydrocarbons and free carbocations.

On the reaction of alcohols with halocarbenes. Are carbocations intermediates?

There is no evidence for hydride shift in the reaction of alcohols 1 and 2 with dichlorocarbene. Accordingly, the intermediate cannot be a free carbocation. It is suggested that the products are formed through a combination of S Ni and direct displacement reactions in which tight ion pairs are involved.