Theoretical insight on the treatment of ß-hexachlorocyclohexane waste through alkaline dehydrochlorination.

The occurrence of 4.8-7.2 million tons of hexachlorocyclohexane (HCH) isomers stocked in dumpsites around the world constitutes a huge environmental and economical challenge because of their toxicity and persistence. Alkaline treatment of an HCH mixture in a dehydrochlorination reaction is hampered by the low reactivity of the ß-HCH isomer (HCl elimination unavoidably occurring through syn H-C-C-Cl arrangements). More intriguingly, the preferential formation of 1,2,4-trichlorobenzene in the ß-HCH dehydrochlorination reaction (despite the larger thermodynamical stability of the 1,3,5-isomer) has remained unexplained up to now, though several kinetic studies had been reported. In this paper, we firstly show a detailed Density Functional study on all paths for the hydroxide anion-induced elimination of ß-HCH through a three-stage reaction mechanism (involving two types of reaction intermediates). We have now demonstrated that the first reaction intermediate can follow several alternative paths, the preferred route involving abstraction of the most acidic allylic hydrogen which leads to a second reaction intermediate yielding only 1,2,4-trichlorobenzene as the final reaction product. Our theoretical results allow explaining the available experimental data on the ß-HCH dehydrochlorination reaction (rate-determining step, regioselectivity, instability of some reaction intermediates).

Copper-catalyzed cyclopropanation reaction of but-2-ene.

The mechanism of the copper(I)-catalyzed cyclopropanation reaction for methyl diazoacetate with both (Z)- and (E)-but-2-ene stereoisomers has been studied using the 6-311++G(d,p) basis set by means of M06-2X and O3LYP functionals. According to both methods, the rate-limiting step is the formation of a copper-carbene intermediate, formed by association between methyl diazoacetate and bis(acetonitrile)-copper(I) ion with the concomitant extrusion of dinitrogen. Cis/trans diastereoselectivity for the cyclopropanation reaction of a 1,2-disubstituted alkene ((Z)-but-2-ene) has been theoretically studied for the first time through the proper location of transition states on the potential-energy surface with the O3LYP method, since no transition structures could be found with the M06-2X functional due to the extreme flatness of the potential-energy surface. The calculated stereoselectivities involving two acetonitrile ligands or one dichloromethane molecule show qualitative agreement with experimental data. This study allows attributing the origin of the selectivity to steric interactions between the ligands of the catalyst system and the olefin substituents. The comparison between the corresponding activation barriers for the direct insertion step shows a higher reactivity for the Z stereoisomer of but-2-ene, consistently with the larger reactant destabilization through steric interactions.

A DFT study on the mechanism of the sulfonic acid + alcohol esterification reaction.

Four alternative mechanisms for the benzenesulfonic acid + methanol esterification reaction have been studied at the B3LYP/aug-cc-pVTZ level. The participation of a pentacoordinate sulfur intermediate (in either neutral or protonated form) can be disregarded according to energy considerations. Instead, results show a low activation barrier for the SN1 pathway (through a sulfonylium cation intermediate) and a moderate barrier for the SN2 path (involving protonated methanol as an alkylating reagent).

Theoretical study on the BF3-catalyzed Meinwald rearrangement reaction.

The mechanisms of the BF3-catalyzed Meinwald rearrangement reactions of five epoxides in dichloromethane solution have been studied at the M062X/6-311++G(2df,2pd) level. Accordingly, the Lewis acid-epoxide complex can react through several alternative pathways, though three phases (ring opening, C-C bond rotation, and hydrogen or alkyl group migration) are required in any path. In some cases, a concerted pathway (involving all three successive phases) is found. Otherwise, the reaction takes place through a reaction mechanism involving a zwitterion or a BF3 addition compound (formed by fluoride transfer from the BF3 moiety to the incipient carbocationic center generated by C-O bond rupture) or both as reaction intermediate(s). The BF2-bound fluorohydrin yields the reaction product through a concerted process involving fluoride transfer from the C-F bond to the OBF2 group and hydrogen or alkyl group migration, as first demonstrated in this work. Effects of a number of features (solvent effects, concurrent hydrogen/alkyl group migration, carbocation substitution, benzylic conjugation) are also discussed.

Stereochemical outcome of copper-catalyzed C-H insertion reactions. An experimental and theoretical study.

The combination of chiral preparative HPLC separation, VCD measurements, and theoretical calculations allows the unambiguous determination of the absolute configuration of the conformationally flexible products of copper-catalyzed carbene insertion reactions. DFT calculations were used to predict the stereochemical outcome of the copper-bis(oxazoline)-catalyzed C-H insertion reaction between methyl diazophenylacetate and tetrahydrofuran and also to predict the absolute configuration of the major stereoisomers derived from the same reaction with different cyclic ethers. These predictions were verified experimentally through NMR and VCD spectroscopy and allowed rationalization of the stereochemical outcome of these reactions without further derivatization of the products, which can be prblematic under certain conditions as described herein.

Theoretical insights into enantioselective catalysis: the mechanism of the Kharasch-Sosnovsky reaction.

The mechanism of the Kharasch-Sosnovsky reaction has been investigated using B3 LYP/6-31G* calculations on a chiral reaction model [cyclohexene+tert-butyl perbenzoate-->cyclohex-2-enyl benzoate+tert-butyl alcohol, catalyzed by a chiral bisoxazoline-copper(I) complex]. Although two previous reaction mechanisms have been considered, the results are consistent with a new mechanistic pathway. This path involves ligand exchange between the catalyst-cyclohexene complex with tert-butyl perbenzoate to give a catalyst-perester complex, which undergoes an (either one- or two-step) oxidative addition reaction to yield a copper(III) complex. The limiting step of the Kharasch-Sosnovsky reaction consists of an intramolecular step involving the abstraction of an allylic hydrogen from cyclohexene [which is pi-bound to the copper(III) complex]. The resulting allyl-copper(III) complex (subsequent to the loss of tert-butanol) can undergo a haptotropic rearrangement by means of an eta1-allyl/eta3-allyl equilibrium, leading to scrambling between vinylic and allylic positions when an isotopically labeled substrate is used. The allyl-copper(III) ion undergoes a stereospecific reductive elimination involving the pi-bond migration to yield a reaction product-catalyst complex, which can regenerate the alkene-copper(I) complex by ligand exchange. The proposed reaction mechanism is consistent with all known experimental results (including enantioselectivity data).

Conformational preferences of methacrolein in Diels-Alder and 1,3-dipolar cycloaddition reactions.

A B3LYP/6-31G* study has been carried out for the reactions of methacrolein with cyclopentadiene, parent nitrone, 1-pyrroline-1-oxide, and (Z)-C,N-diphenylnitrone, in which the coordination of a Lewis acid (borane) and the solvent polarity (dichloromethane) have been taken into account. Calculated activation parameters, regioselectivities (for 1,3-dipolar cycloaddition reactions), and endo/exo stereoselectivities show good agreement with available experimental data. Gas-phase calculations show a varied behavior of the s-cis/s-trans TS stability for noncatalyzed reactions (from the systematic s-cis preference for the cyclopentadiene reaction to the systematic s-trans predilection encountered in the diphenylnitrone cycloaddition). BH3 coordination leads to a preferential stabilization of s-trans TSs in the reactions of cyclopentadiene (exo approach) and diphenylnitrone but a larger stabilization of s-cis structures in the processes involving the parent nitrone or 1-pyrroline-1-oxide. Additionally, a rather systematic preferential stabilization of s-trans structures is induced by solvent polarity in most reactions. As a consequence, an s-trans preference is predicted in solution for both thermal and catalyzed types of reactions in most approaches. Such a conclusion is consistent with some experimental results suggesting a preference for a particular conformation of the methacrolein-Lewis acid complexes.

Solvent effects on the 9-hydroxymethylanthracene + N-ethylmaleimide Diels-Alder reaction. A theoretical study.

[structure: see text] The origin of the high reaction rates of the 9-hydroxymethylanthracene + N-ethylmaleimide Diels-Alder reaction in fluorous solvents and supercritical carbon dioxide is analyzed through a combination of regression analyses and theoretical calculations. Both approaches allow the solvent effects on the activation barrier (a decrease by solvophobic interactions, an increase by dipolarity-polarizability) to be attributed to the existence of a hydrogen bond between the two reactants in the transition state, refuting a previous hypothesis based on strong solvophobic interactions.

Theoretical insights into the role of a counterion in copper-catalyzed enantioselective cyclopropanation reactions.

The effect of a coordinating counteranion on the mechanism of Cu(I)-catalyzed cyclopropanation has been investigated extensively for a medium-sized reaction model by means of theoretical calculations at the B3LYP/6-31G(d) level. The main mechanistic features are similar to those found for the cationic (without a counteranion) mechanism, the rate-limiting step being nitrogen extrusion from a catalyst-diazoester complex to generate a copper-carbene intermediate. The cyclopropanation step takes place through a direct carbene insertion of the metal-carbene species to yield a catalyst-product complex, which can finally regenerate the starting complex. However, the presence of the counteranion has a noticeable influence on the calculated geometries of all the intermediates and transition structures. Furthermore, the existence of a preequilibrium with a dimeric form of the catalyst, together with a higher activation barrier in the insertion step, explains the lower yield of cyclopropane products observed experimentally in the presence of chloride counterion. The stereochemical predictions of a more realistic model (made by considering a chiral bis(oxazoline)-copper(i) catalyst) have been rationalized in terms of the lack of significant steric repulsions, and the model shows good agreement with the low enantioselectivities observed experimentally for these kinds of catalytic systems.