Synthesis and reactions of “biginelli-compounds”. Part I

Various reactions of 2-oxo(or thioxo)-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid derivatives (Biginelli-compounds) were investigated. The site of methylation and acylation on 6-methyl-4-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester 1a and its 2-oxo derivative 9a was studied. The synthesis of pyrimido[2,3-b]thiazines and thiazolo[3,2-a]pyrimidines was accomplished by condensation of 1a with 1,3-and 1,2-dielectrophiles. A Dimroth-like rearrangement yielding 6H-1,3-thiazines can be observed when 1a was treated with dimethylformamide and phosphorus oxychloride. The formation of indeno[1,2-d]pyrimidines can be achieved by intramolecular Friedl-Crafts acylation of 9a and 13 , respectively. Finally a route for the preparation of 4,6-disubstituted-pyrimidine-5-carbonitriles is presented, starting with Biginelli-compound 25 .     

Computational design of S‐nitrosothiol “click” reactions

To address a long‐standing problem of finding efficient reactions for chemical labeling of protein‐based S‐nitrosothiols (RSNOs), we computationally explored hitherto unknown (3+2) cycloaddition RSNO reactions with alkynes and alkenes. Nonactivated RSNO cycloaddition reactions have high activation enthalpy (>20 kcal/mol at the CBS‐QB3 level) and compete with alternative S—N bond insertion pathway. However, the (3+2) cycloaddition reaction barriers can be dramatically lowered by coordination of a Lewis acid to the N atom of the —SNO group. To exploit this effect, we propose to use reagents with Lewis acid and a strain‐activated carbon–carbon multiple bond linked by a rigid scaffold, which can react with RSNOs with small activation enthalpies (～5 kcal/mol) and high reaction exothermicities (～40 kcal/mol). The proposed efficient RSNO cycloaddition reactions can be used for future development of practical RSNO labeling reactions. © 2013 Wiley Periodicals, Inc.     

“Superpermeability” and “pumping” of atomic hydrogen through palladium membranes

Permeation of atomic as well as molecular hydrogen through palladium membranes has been investigated experimentally in the temperature range from room temperature to 200 °C and at a higher incident flux of hydrogen atoms on palladium surface than in previous studies. The results demonstrate that phenomena of ‘superpermeability’ and ‘pumping’ of atomic gases through metal membranes are of a common nature. A theoretical model based on chemical thermodynamics and diffusion theory adequately describes the quantitative relationships observed in experiments. It was found that permeability of atomic hydrogen depends strongly on the magnitude of surface incident flux and membrane temperature.     

Origin of the “endo rule” in Diels–Alder reactions

Detailed density functional theory calculations definitively rationalize the preference for the endo cycloadduct (also known as endo rule) in text‐book thermal Diels–Alder reactions involving maleic anhydride and cyclopentadiene or butadiene. This selectivity is mainly caused by an unfavorable steric arrangement in the transition‐state region of the exo pathway which translates into a more destabilizing activation strain. In contrast with the widely accepted, orbital‐interaction‐based explanation for the endo rule, it is found that neither the orbital interactions nor the total interaction between the deformed reactants contributes to the endo selectivity. © 2013 Wiley Periodicals, Inc.