A mechanistic insight into the effect of piperidine as an organocatalyst on the [3 + 2] cycloaddition reaction of benzalacetone with phenyl azide from a computational study.

Several transition structures (TSs) for catalyst-free [3 + 2] cycloaddition and two plausible mechanistic pathways for the organocatalyzed [3 + 2] cycloaddition (32CA) between benzalacetone and phenyl azide were located by quantum chemistry methods. Calculations were carried out with B3LYP, MPWB1K and M06-2X functionals using 6-31G(d) and 6-311G(d,p) basis sets in gas and solvent phases. The calculated activation barriers imply that the lowest barrier pathway is the catalyzed process producing 3-regioisomers through the iminium intermediate and not through the dienamine route. Electronic displacements along the reaction path have been examined using a topological analysis of the electron-localization function (ELF). ELF topological analyses along the intrinsic reaction coordinates (IRC) of both catalyzed and uncatalyzed 32CA reactions indicated that while the first C1-N1 single bond is formed as a dative bond, the formation of the second C2-N3 bond takes place via a C-to-N coupling between the interacting centers of the reagents. Moreover, the ELF analyses imply that the reaction mechanism is a two-stage one-step process in the presence of a piperidine organocatalyst, while bond formation in an uncatalyzed process is almost synchronous.

Investigation into the regiochemistry of some isoxazoles derived from 1,3-dipolar cycloaddition of 4-nitrobenzonitrile oxide with some dipolarophiles: a combined theoretical and experimental studies.

Reaction of 4-nitrobenzonitrile oxide (2) which was generated in situ with acrylo nitrile (3), methyl methacrylate (4) and allyl bromide (5) as dipolarphile afforded the new 7a, 8a and 9a compounds respectively. Reactivity and regiochemistry of these reactions were investigated using activation energy calculations and density functional theory (DFT)-based reactivity indexes. The theoretical 13C NMR chemical shifts of the cycloadducts which were obtained by GIAO method were comparable with the observed values.

3-Ethyl-sulfanyl-5-methyl-1-phenyl-7-(pyrrolidin-1-yl)-1H-pyrimido[4,5-e][1,3,4]thia-diazine.

In the crystal structure of the title compound, C(18)H(21)N(5)S(2), the thia-diazine six-membered ring and pyrrolidine five-membered ring display boat and envelope conformations, respectively. The crystal structure contains weak C-H⋯N and C-H⋯S hydrogen bonding.

Design and synthesis of pyrimido[4,5-b][1,4]benzothiazine derivatives, as potent 15-lipoxygenase inhibitors.

A group of 2-substituted pyrimido[4,5-b][1,4]benzothiazines were designed, synthesized, and evaluated as potential inhibitors of 15-lipoxygenase (15-LO). Compounds 4d and 4e showed the best IC50 of 15-LO inhibition (IC50=18 and 34 microM, respectively). All compounds were docked into 15-LO. As a result the sulfur atom was oriented toward the iron atom of the active site of 15-LO. We suggest the interaction of the iron atom is essential for the activity of the inhibitors.