Chameleonic reactivity of vicinal diazonium salt of acetylenyl-9,10-anthraquinones: synthetic application toward two heterocyclic targets.

The nature of products in the diazotization of 1-amino-2-acetylenyl-9,10-anthraquinones strongly depends on the nature of substituents at both the alkyne and at the anthraquinone core. Donor substitution (NHAr, OH) at the fourth position stabilizes the diazonium salt at C1, decelerating electrophilic cyclization at the arylethynyl substituent at C2. This effect allows the replacement of the diazonium with azide group and subsequent closure into isoxazole ring with preservation of the alkyne. In contrast, electrophilic 5-exo-dig cyclizations to condensed pyrazoles is observed for the combination of donor substituents at the aryl alkyne moiety and an OAc substituent at C4. The latter process provides a new synthetic route to 3-ethynyl-[1,9-cd]isoxazol-6-ones that are difficult to access otherwise. DFT calculations suggest that donor substituents have only a minor effect on alkyne and diazonium polarization in the reactant but provide specific transition state stabilization by stabilizing the incipient vinyl cation. This analysis provides the first computational data on electrophilic 5-exo-dig cyclization in its parent form and the nucleophile-promoted version. This cyclization is a relatively fast but endothermic process that is rendered thermodynamically feasible by the enol-keto tautomerization with concomitant aromatization in the five-membered heteroaromatic ring. Computations suggest that the importance of nucleophilic assistance in the transition state for a relatively weak nucleophile such as water is minor because the energy gain due to the Lewis base coordination to the carbocationic center is more than compensated for by the unfavorable entropic term for the bimolecular proces.

Energy distribution and redistribution and chemical reactivity. The generalized delta overlap-density method for ground state and electron transfer reactions: a new quantitative counterpart of electron-pushing.

A new approach to prediction of organic reactions and understanding of the electron flow involved in the reaction mechanisms is presented. The method developed permits comparison of electronic structures of species different in multiplicity, charge, and geometry based on use of spin- and charge-independent entities-"overlap corrected density matrices". The method utilizes the basis orbitals of one molecule A (e.g. reactant) in the computation of a second molecule, B, derived from the first by an approach to product. This then provides two Overlap-Density Matrices with a common set of basis (e.g. hybrid) orbitals. Subtraction of Overlap-Density Matrix B from Matrix A affords the Delta Overlap-Density Matrix. Each element of the Delta Overlap-Density matrix gives the change in electron population of a bond or of a single hybrid orbital. Molecule B may differ from A by the addition or loss of an electron, by stretching of a bond, by electronic excitation, or by some other perturbation. The Delta Overlap-Density matrices afford a detailed description of the reaction process and provide predictions of overall reactions including such subtleties as regiochemistry.