Aminoazoles in the three-component synthesis of 7-substituted 6-ethoxycarbonyl-5-methyl-4,7-dihydroazolo[1,5-a]pyrimidines

The three-component synthesis of 7-substituted 6-ethoxycarbonyl-5-methyl-4,7-dihydroazolo[1,5-a]pyrimidines was carried out for the first time by the reactions of aminoazoles (3-aminopyrazole, 3-amino-1,2,4-triazole, or 5-aminotetrazole) with acetoacetic ester and aliphatic, aromatic, or heteroaromatic aldehyde.     

Molecular and crystal structure of 5,7-diphenyl-7-methyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine

The molecular and crystal structures of 5,7-diphenyl-7-methyi-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine have been studied by X-ray structural methods. The crystal is monoclinic,a=16.112(3),b=13.489(3),c=14.480(3)Å, =101.62(2)°,Z=8, space groupC2/c,R=0.071. The presence of short intermolecular contacts indicates considerable steric strain in the molecule. The dihydropyrimidine ring exists in an unevenly planar boat conformation. Increasing the steric strain of the dihydrocycle leads to a twisted conformation.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1912–1914, November, 1993.     

Conformational mobility of the six-membered ring in 5-oxo-1,3-cyclohexadiene and its derivatives

Molecular mechanics and MNDO calculations showed that the six-membered ring in the molecule of 5-oxo-1,3-cyclohexadiene possesses high conformational mobility. The transition from a planar equilibrium conformation to a distorted sofa conformation in which the C(sp²)-C(=O)-C(sp³)-C(sp²) torsion angle is equal to ±30° increases the energy of the molecule by less than 1 kcal mol^–1. The influence of steric (R = Me, Et, Prⁱ, Bu^t) and electronic (R = NH₂, NO₂) effects of substituents R on the equilibrium conformation and mobility of the carbocycle has been analyzed. Both types of substituents at unsaturated C atoms do not change the equlibrium conformation or flexibility of the six-membered ring. Substituents at saturated C atoms cause the transition of the carbocycle to the distorted sofa conformation and significantly restrict its mobility. The electronic structures of 5-oxo-1,3-cyclohexadiene and its amino and nitro derivatives have been analyzed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 849–854, May, 1995.     

The effect of substituents on the conformational mobility of the heterocycle in 1,4-dihydropyrimidine and its derivatives

The equilibrium geometry of 1,4-dihydropyrimidine, 4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine, and their alkyl (Me, Et, Prⁱ, Bu^t) and phenyl derivatives has been calculated by molecular mechanics method. The equilibrium conformation of unsubstituted molecules is planar, but it is easily transformed to the boat conformation with a small change in the conformational energy. The effect of substituents on the geometry and conformational mobility of the dihydropyrimidine ring has been studied.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1394–1397, August, 1994.     

Nitroazines. 15. Contraction of the pyrimidine ring in 6-nitroazolo[1,5-a]pyrimidines

It is shown that contraction of the pyrimidine ring occurs when 6-nitro-7-oxo-4,7-dihydroazolo[1,5-a]pyrimidines are heated with hydrazine hydrate. Complexes of 4-nitropyrazole with 5-aminoazoles, the structures of which were proved by x-ray diffraction analysis, are formed in a similar reaction of nitrosubstituted azolopyrimidines that do not contain an oxo function.See [1] for Communication 14.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 665–668, May, 1991.     

SnAr Reactions of 2,4-Diazidopyrido[3,2-d]pyrimidine and Azide-Tetrazole Equilibrium Studies of the Obtained 5-Substituted Tetrazolo[1,5-a]pyrido[2,3-e]pyrimidines

A straightforward method for the synthesis of 5-substituted tetrazolo[1,5-a]pyrido[2,3-e]pyrimidines from 2,4-diazidopyrido[3,2-d]pyrimidine in SnAr reactions with N-, O-, and S- nucleophiles has been developed. The various N- and S-substituted products were obtained with yields from 47% to 98%, but the substitution with O-nucleophiles gave lower yields (20–32%). Furthermore, the fused tetrazolo[1,5-a]pyrimidine derivatives can be regarded as 2-azidopyrimidines and functionalized in copper(I)-catalyzed azide-alkyne dipolar cycloaddition (CuAAC) and Staudinger reactions due to the presence of a sufficient concentration of the reactive azide tautomer in solution. In total, seven products were fully characterized by their single crystal X-ray studies, while five of them were representatives of the tetrazolo[1,5-a]pyrido[2,3-e]pyrimidine heterocyclic system. Equilibrium constants and thermodynamic values were determined using variable temperature ¹H NMR and are in agreement of favoring the tetrazole tautomeric form (ΔG₂₉₈ = −3.33 to −7.52 (kJ/mol), ΔH = −19.92 to −48.02 (kJ/mol) and ΔS = −43.74 to −143.27 (J/mol·K)). The key starting material 2,4-diazidopyrido[3,2-d]pyrimidine presents a high degree of tautomerization in different solvents.     

Nucleophilic ring-opening of the azole and azine moieties in 6-nitro-1,2,4-triazolo[1,5-a]pyrimidin-7-ones

The effects of the nature of the nucleophile and the structure of 6-nitrotriazolo[1,5-a]pyrimidinones on the direction of the ring opening were investigated. The triazole ring is opened under the action of strong bases, such as alkoxides or alkalis, to form 2-cyanoaminopyrimidinones and then 2-aminopyrimidinones. The results of the reactions with N-nucleophiles depend on the accessibility of position 5 of the heterocycle. Thus, sterically hindered secondary amines react with 5-methyltriazolopyrimidinones to give 2-guanidinopyrimidinones and then 2-aminopyrimidinones. In the absence of a substituent at position 5, the azine ring is opened to form 4-alkyl-3-amino-1,2,4-triazoles and 3-amino-2-nitroacrylamides. Under the action of primary amines, only the pyrimidine fragment is cleaved.     

Oxidative Aromatization of 4,7-Dihydro-6-nitroazolo[1,5-a]pyrimidines: Synthetic Possibilities and Limitations,Mechanism of Destruction,and the Theoretical and Experimental Substantiation

The reaction tolerance of the multicomponent process between 3-aminoazoles, 1-morpholino-2-nitroalkenes, and aldehydes was studied. The main patterns of this reaction have been established. Conditions for the oxidation of 4,7-dihydro-6-nitroazolo[1,5-a]pyrimidines were selected. Previous claims that the 4,7-dihydro-6-nitroazolo[1,5-a]pyrimidines could not be aromatised have now been refuted. Compounds with an electron-donor substituent at position seven undergo decomposition during oxidation. The phenomenon was explained based on experimental data, electro-chemical experiment, and quantum-chemical calculation. The mechanism of oxidative degradation has been proposed.     

1,2,4-Triazoles. XXV. The effect of pyridine substitution on the isomerization of s-Triazolo[4,3-a] pyridines into s-Triazolo[1,5-a] pyridines

The isomerization of s-triazolo[4,3-a]pyridines into s-triazolo[1,5-a]pyridines is greatly facilitated by electron withdrawing nitro substituents in the pyridine ring and retarded by electron donating amino groups.     

Benzannulation of 5-methyl-7-phenyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine with chalcones and their synthetic equivalents as a method for the synthesis of tetrazolo[5,1-b]quinazolines

Derivatives of tetrahydrotetrazolo[5,1-b]quinazolines were synthesized by the reactions of 5-methyl-7-phenyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine with α,β-unsaturated carbonyl compounds and their synthetic equivalents in methanol in the presence of sodium methoxide. The spontaneous or specifically target oxidation of these derivatives gives rise to aromatic tetrazoloquinazolines. The reaction pathways and mechanisms were discussed. The structures of the resulting compounds were confirmed by IR and ¹H NMR spectroscopy, mass spectrometry, and elemental analysis. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1971–1976, September, 2008.     

Studies on 4,7-di-substitution effects of one ligand in [Ru(phen)3]2+ with DFT method

Studies on the complex [Ru(phen)3]2+ (phen = 1,10-phenanthroline) and its derivatives with 4,7-di-substitution on one ligand(phen) were carried out using the DFT method at the B3LYP/LanL2DZ level of theory. The trends in the substituent effects caused by the electron-pushing group (OH) and the electron-withdrawing group (F), on the electronic structures and the related properties, for example, the energies and the components of some frontier molecular orbitals, the spectroscopy properties, and the net charge populations of some main atoms of the complexes, etc., have been investigated. The computational results show that the substituents have some interesting effects on the electronic structures and the related properties of the complexes. First, according to the analysis of components of LUMO of the complexes, the electron-withdrawing group (F) can activate the main ligand (the substituted ligand, i.e., 2R-phen) and passivate the coligands, on the contrary, the electron-pushing group (OH) can activate the coligands and passivate the main ligand in the first electronic excited states of complexes. Second, both the electron-pushing group (OH) and the electron-withdrawing group (F) can cause a red shift in the electronic ground bands. Third, the characteristics of the atomic net charge populations on the main ligand can also be analyzed in detail by means of a schematic map expressed by several series of arrowheads based on the law of polarity alternation and the idea of polarity interference. The most negative charges are populated on N1, the next most net negative charges are populated on C3 among the skeleton atoms for the three complexes, etc. The computational results can be better used to explain some experimental phenomena and trends.     

Immobilized sulfonic acid functionalized ionic liquid on magnetic cellulose as a novel catalyst for the synthesis of triazolo[4,3-a]pyrimidines

The Brønsted acidic ionic liquid 1-(propyl-3-sulfonate) vinyl imidazolium hydrogen sulfate [IL] was supported on modified magnetic cellulose. The physical structure, composition, and functional groups of the novel supported ionic liquid catalyst were characterized via XRD, FT-IR, EDS, SEM, VSM, TGA, TEM, and BET techniques. Owing to the combination of nano-support features and flexible imidazolium linkers, it acted as a “quasi-homogeneous” catalyst to catalyze the preparation of triazolo[4,3-a]pyrimidine derivatives by a one-pot three-component reaction of active methylene compounds (ethyl cyanoacetate or malononitrile), aminotriazole and aryl aldehydes. The catalyst shows good catalytic activity for the synthesis of triazolo pyrimidines after six times of recycling.     

The "hockey sticks" effect revisited: the conformational and electronic properties of 3,7-dithia-1,5-diazabicyclo[3.3.1]nonane from the QTAIM perspective

The conformational effects in bicyclo[3.3.1]nonanes, while thoroughly studied, have not yet received the full theoretical explanation. R. F. W. Bader's quantum theory of atoms in molecules presents unique opportunities for studying the stereoelectronic interactions (SEI) and weak intramolecular bonding leading to these effects. Here, we report the study of 3,7-dithia-1,5-diazabicyclo[3.3.1]nonane by means of the topological analysis of the calculated (MP2(full)/6-311++G**) and experimental (X-ray derived) charge density to reveal the origins of the so-called "hockey sticks" effect observed in similar compounds. A new explanation of the relative stability of bicyclo[3.3.1]nonane conformers based on the analysis of the QTAIM atomic energies is given. The H···H and S···S interactions in bicyclo[3.3.1]nonane and its dithia derivatives are shown to be significant factors contributing to the differences in the relative stability of the conformers.     

Theoretical study on phosphorescence efficiency and color tuning from orange to blue-green of Ir(III) complexes based on substituted 2-phenylimidazo[1,2-a]pyridine ligand

The geometrical structures, phosphorescence quantum yields, and electroluminescence (EL) efficiency of six iridium(III) complexes containing 2-phenylimidazo[1,2-a]pyridine ligand are investigated by density functional theory (DFT), which show a wide color tuning of photoluminescence from orange (λ(em) = 550 nm) to blue-green (λ(em) = 490 nm). The calculated results shed some light on the reasons of the remarkably manipulated excited-state and EL properties through substitution effect. The Mulliken charge calculation reveals that attached -CF(3) groups on phenyl and imidazo[1,2-a]pyridine (impy) moieties (4) can make both of them as electron-deficient region, which will lead to the contraction of the whole coordination sphere and strengthen the metal-ligand interaction. While attaching two -CF(3) groups on phenyl ring can make it more electron-deficient, which will induce electron transferring from acac and impy fragment to phenyl ring, and also result in the contracted structure. The largest metal-to-ligand charge transfer ((3)MLCT) character and the smaller S(1)-T(1) energy gap (ΔE(S(1)-T(1))) value increase the emission quantum yields of 4 and 6 than other complexes. For EL efficiency, because of the similar highest occupied molecular orbital (HOMO) levels of 4 and 6 to that of holes injection material poly(N-vinylcarbazole) (PVK) and the larger dipole moments, majority hole will be accumulated on the HOMO of 4 and 6. Combination with the lower lowest unoccupied molecular orbital energy levels compared with PVK, the recombination zones of 4 and 6 can be well confined within emitting material layer (EML) and lead to the higher EL efficiency.     

Selective (15)N-labeling and analysis of (13)C-(15)N J couplings as an effective tool for studying the structure and azide-tetrazole equilibrium in a series of tetrazolo[1,5-b][1,2,4]triazines and tetrazolo[1,5-a]pyrimidines

Two general methods for the selective incorporation of an (15)N-label in the azole ring of tetrazolo[1,5-b][1,2,4]triazines and tetrazolo[1,5-a]pyrimidines were developed. The first approach included treatment of azinylhydrazides with (15)N-labeled nitrous acid, and the second approach was based on fusion of the azine ring to [2-(15)N]-5-aminotetrazole. The synthesized compounds were studied by (1)H, (13)C, and (15)N NMR spectroscopy in both DMSO and TFA solution, in which the azide-tetrazole equilibrium is shifted to tetrazole and azide forms, respectively. Incorporation of the (15)N-label led to the appearance of (13)C-(15)N J coupling constants (J(CN)), which can be measured easily using either 1D (13)C spectra with selective (15)N decoupling or with amplitude modulated 1D (13)C spin-echo experiments with selective inversion of the (15)N nuclei. The observed J(CN) patterns permit unambiguous determination of the type of fusion between the azole and azine rings in tetrazolo[1,5-b][1,2,4]triazine derivatives. Joint analysis of J(CN) patterns and (15)N chemical shifts was found to be the most efficient way to study the azido-tetrazole equilibrium.     

Influence of laterally attached alkyl groups on the conformational behaviour of a basic calix[4]arene: combined NMR,molecular mechanics and X-ray study

Three new calixarenes 3–5 featuring an alkyl residue of different chain lengths attached to one of the central ring methylene groups of the basic calix[4]arene 1 have been prepared. A systematic study that includes also the lower homologous compound 2 showing the effect of the alkyl substitution on the conformational behaviour of the calixarene framework in comparison with the unsubstituted parent compound 1 is reported. The application of special 2D NMR techniques, 2D-EXSY and ROESY methods at various temperatures establishes that calixarenes 2–5 adopt the partial cone conformation of lower symmetry and far less the symmetric cone and 1,2-alternate conformations. In solution, they undergo a fast interconversion with relatively low activation energies of about 15 kcal/mol at room temperature. The conformer distribution is well reproduced by molecular mechanistic calculations (MMFF94), indicating the present conformers to assume the lowest steric energies. A single-crystal X-ray structure of the lateral ethyl derivative 2 corroborates these results, showing the molecule in a sterically favourable partial cone conformation.     

MNDO calculations on borazine derivatives. The substitution of one [HNBH] fragment for one [HCCH] fragment in benzene to form the azaborines and the nature of the cyclotrimer of the 1,2-isomer

The three azaborine isomers with the formula C₄H₆BN, 1,2-, 1,4-, and 1,3-azaborine ( I , II , and III ), have been examined using MNDO (m odified n eglect of d iatomic o verlap) calculations. The most stable azaborine was I (heat of formation -8.147 kcal/mol), followed by II (+11.60 kcal/mol) and III (+16.64 kcal/mol). Qualitatively, although the π- and π*-orbitals calculated for the azaborines exhibited an ordering similar to that in benzene and borazine, the HOMO/LUMO energy differences (9.27, 9.68, and 8.44 eV, respectively) were smaller than was the difference calculated for borazine (12.81 eV), but of the same magnitude as the difference for benzene (9.76 eV). With the exception of borazine, each molecule had a π-orbital for the HOMO and a π*-orbital for the LUMO ; borazine's LUMO was a π*-orbital. The calculated shapes and atomic contributions for the π-and π*-orbitals of the azaborines were best described as “hybrids” of the π- and π*-orbitals of benzene and borazine. As was observed for the π- and π*-orbitals of borazine, the azaborines exhibited increased orbital density at the nitrogen atom in the π-bonding orbitals and at boron in the π-antibonding orbitals, as would be predicted from electronegativity considerations. Although I and II exhibited significant double- and single-bond localization, all of the ring bonds in III were delocalized. The delocalization in III was not uniform but, rather, resembled two inequivalent fused allyl systems. The cyclotrimer ( IV ) of 1,2-azaborine (heat of formation -44.07 kcal/mol), based purely on thermodynamic considerations, was predicted to form spontaneously from three monomer molecules with the concurrent loss of three molecules of dihydrogen. The cyclotrimers that could theoretically be produced from 1,2-azaborine without the loss of dihydrogen ( IVc and IVt ) were each calculated to be less stable (heats of formation +24.45, and +33.29 kcal/mol, respectively) than was the experimentally observed IV . The carbon molecules triphenylene ( TP ) and cis- and trans-4a,4b,8a,8b,12a,12b- hexahydrotriphenylene ( TPc and TPt ) (heats of formation +76.79, +101.6, and +103.1 kcal/mol, respectively) were each calculated to be less stable than were the azaborine cyclotrimer analogs, as was observed in comparisons of benzene with the azaborines and borazine.     

Effect of the trifluoroacetyl group on the direction of the recyclization of the pyrazine ring in 6-trifluoroacetylpyrrolo[1,2-a]pyrazinium salts

A cyclotransformation of 6-trifluoroacetylpyrrolo[1,2-a]pyrazinium salts involving the trifluoroacetyl group carbon atom was discovered and investigated. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1714–1719, November, 2007.     

Mechanism of methane activation by electrophiles generated in the AlBr5 system: An MNDO/PM3 study of the potential energy surface of the [AlBr5+CH4] system

Fragments of the potential energy surfaces (PES) of the AlBr₅ (I) and [AlBr₅+CH₄] (II) systems were studied by the MNDO/PM3 method. Five local minima corresponding to Br₂·AlBr₃ donor-acceptor complexes were found on the PES of system I. Two of these complexes have a pronounced ionic character. In system II, among the products of barrierless addition of Br₂·AlBr₃ complexes to CH₄, the methane molecule is activated only in two complexes. These are products of the attack of the most electrophilic AlBr₅ complexes on a H atom of the methane molecule. The potential barriers to conversion of these products into complexes with structures formally corresponding to the products of the attack of electrophiles on a C−H bond (the Olah scheme) or the C atom of methane molecule (the Schreiner scheme) were calculated. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 802–808, May, 2000.