Isonitriles from the Baylis-Hillman adducts of acrylates: viable precursor to tetrazolo-fused diazepinones via post-Ugi cyclization

Stereocontrolled synthesis of substituted isonitriles from the Baylis-Hillman adducts of acrylates has been developed. Ugi reaction of these isonitriles with TMSN₃, aliphatic amines, and aldehydes or ketone affords 1-substituted tetrazoles which have been demonstrated to be suitable substrates for producing tetrazolo-fused diazepinones.     

A 2-D tetrazole-based Zn(II) coordination polymer: crystal structure,dielectric constant,and luminescence

A tetrazole-based Zn(II) coordination polymer, [Zn(TMPT)₂] _n (1) (TMPT?=?5-(4-((1H-1,2,4-triazol-1-yl)methyl)phenyl)-2H-tetrazole), was synthesized by in situ reaction of 4-((1H-1,2,4-triazol-1-yl)methyl)benzonitrile, Zn(NO₃)_2?·?6H₂O, and NaN₃ under hydrothermal conditions and structurally characterized by single-crystal X-ray diffraction. Complex 1 contains π–π stacking interactions between tetrazole rings and phenyl rings of the 2-D ordered layered structural framework, which contribute to the dielectric response. In addition, 1 was demonstrated to display strong blue fluorescence emissions in the solid state at room temperature.     

The tetrazole–azide tautomerism of some nitrotetrazolo [1,5-a]pyridines studied by NMR, IR spectroscopy and molecular orbital calculations

The 6-nitro- and 8-nitro- groups in the tetrazolo[1,5-a]pyridine molecule exhibit completely different influences on the tetrazole–azide equilibrium. Introduction of the methyl-, nitro-, azido groups or a bromine atom in positions 5, 6, 7 or 8 of the nitrotetrazolopyridine produce changes in the equilibrium constants. Based on the IR spectra taken in the solid state, the tetrazole structure was assigned for almost all the compounds studied. Only one of them, 2,6-diazido-3-nitropyridine, exists in the diazido-form in the solid. The ¹H, ¹³C, ¹⁵N, and ¹⁷O NMR spectral parameters (coupling constants, chemical shifts) as well as ab initio molecular orbital calculations were used to describe the tetrazole–azide tautomerism in solutions. The differences in the NMR parameters between the neutral compound (6,8-dinitrotetrazolo[1,5-a]pyridine) and its σ-adducts are also included as data for distinguishing between both molecules.     

Theoretical studies on tautomerism of tetrazole derivatives by polarisable continuum method (PCM)

Computational calculations at B3LYP/6-31++G(d,p) level were employed in the study of the predominant tautomeric forms of 1-H and 2-H tetrazole derivatives (5-NO₂, 5-CF₃, 5-F, 5-H, 5-NH₂, 5-OH, 5-CH₃) in the gas phase and solution using PCM model. For electron withdrawing derivatives in the gas phase and solution 2-H forms are more stable and dominant form. For electron releasing groups in the gas phase and solution with low dielectric constants the 2-H form is more stable but in solvents with high dielectric constants 1-H isomer is dominant form. In addition variation of dipole moments and charges on atoms in the solvents are studied.     

Organometallic Lewis Acids LX. Pentacarbonylrhenium Complexes [(OC)5Re‐L]+BF4– with N‐Donor‐Ligands L = Tetrazole,Dimetylaminopyridine (DMAP), Triphenyliminophosphoranes and with Triphenylphosphine Oxide

By reaction of (OC)₅ReFBF₃ with tetrazole, 5‐methyltetrazole, p‐dimethylaminopyridine, several triphenyliminophosphoranes, and with triphenylphosphine oxide cationic complexes [(OC)₅Re‐L]⁺BF4^– were prepared.     

Synthesis,Crystal Structures,and Luminescent Properties of a Series of Coordination Compounds bearing Quinoline‐2‐tetrazolato Ligands

Four new coordination compounds, [Cd(L¹)₂]_n ( 1 ), [Mn(L¹)₂]_n ( 2 ), [Zn(L¹)(NA)] ( 3 ), and [Pb(L¹)₂(H₂O)] ( 4 ) were obtained on the basis of the in‐situ ligand reactions of quinoline‐2‐carbonitrile (QCN) and NaN₃ under solvothermal conditions. 1 and 2 are 1D isostructural chains, where the central metal atoms are six‐coordinate by six nitrogen atoms in a distorted octahedron. The cycloaddition reaction of QCN and NaN₃ in the presence of hydrated ZnCl₂ occur with the aid of the ancillary ligand nicotinic acid (NA), where NA not only provides an acidic environment but also serves as an ancillary ligand. The extended structure of 3 is a 1D ladder‐like polymer. Compound 4 is a mononuclear Pb²⁺ compound. All the compounds were structurally characterized by X‐ray crystallography and their luminescent properties were investigated in detail.     

Liver‐Targeted Small‐Molecule Inhibitors of Proprotein Convertase Subtilisin/Kexin Type 9 Synthesis

Targeting of the human ribosome is an unprecedented therapeutic modality with a genome‐wide selectivity challenge. A liver‐targeted drug candidate is described that inhibits ribosomal synthesis of PCSK9, a lipid regulator considered undruggable by small molecules. Key to the concept was the identification of pharmacologically active zwitterions designed to be retained in the liver. Oral delivery of the poorly permeable zwitterions was achieved by prodrugs susceptible to cleavage by carboxylesterase 1. The synthesis of select tetrazole prodrugs was crucial. A cell‐free in vitro translation assay containing human cell lysate and purified target mRNA fused to a reporter was used to identify active zwitterions. In vivo PCSK9 lowering by oral dosing of the candidate prodrug and quantification of the drug fraction delivered to the liver utilizing an oral positron emission tomography ¹⁸F‐isotopologue validated our liver‐targeting approach.     

Density Function Theory Study on Effects of Different Energetic Substituent Groups and Bridge Groups on Performance of Carbon-Linked Ditetrazole 2N-Oxides

Based on the parent tetrazole 2N-oxide, six series of novel carbon-linked ditetrazole 2N-oxides with different energetic substituent groups (-NH₂, -N₃, -NO₂, NF₂, -NHNO₂) and energetic bridge groups (-CH₂-, -CH₂-CH₂-, -NH-, -N=N-, -NH-NH-) were designed. The overall performance and the effects of different energetic substituent groups and energetic bridge groups on the performance were investigated by density functional theory and electrostatic potential methods. The results showed that most of designed compounds have oxygen balance around zero, high heats of formation, high density, high energy, and acceptable sensitivity, indicating that tetrazole N-oxide is a useful parent energetic compound employed for obtaining high energy compounds, even only combined with some very common energetic substituent groups and bridge groups. Comprehensively considering the effects on energy and sensitivity, the -NO₂, -NF₂, -NH-and -NH-NH-are appropriate substituent groups for combining tetrozale N-oxide to design new energetic compounds, while -NH₂, -N₃, -CH₂-CH₂-, and -N=N-are inappropriate.     

Construction of Three Coordination Compounds Formed by in‐situ Ligand Reaction of 1‐Cyanobenzoimidazole

Solvothermal reactions of 1‐cyanobenzoimidazole, NaN₃, and hydrated M^IICl₂ (M = Mn, Zn, Cu) in a mixture of EtOH/H₂O in the presence of NH₄Cl afforded a mononuclear complex [Mn(L¹)₂(H₂O)₄] ( 1 ), a 3D polymer [Zn(L¹)(OH)]_n ( 2 ), and a linear polymer {[Cu(Bim)]}_n ( 3 ), respectively, where the ligand L¹ is formed in‐situ from [3+2] dipolar cycloaddition of N₃^– with nitrile and the ligand Bim is in‐situ formed from C–N bond cleavage of 1‐cyanobenzoimidazole. (L¹ = 5‐benzoimidazoyltetrazolate, Bim = benzoimidazole). All the compounds were characterized by IR spectroscopy, elemental analysis, and thermo‐gravimetric analysis (TGA), and their structures were determined by X‐ray crystallography. The solid state luminescent properties of 2 and 3 were also investigated at room temperature.