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The derivatives of 1,2,4- triazole have attracted great attention among medicinal chemists due to their wide range of biological activity, good pharmacodynamic and pharmacokinetic profiles, and low toxicity, that necessitates the development of various synthesis methods and a comprehensive study of their reaction mechanisms. A detailed investigation of possible pathways for formation of new spiro-condensed [1,2,4]triazolo[1,5-c]quinazolines, that combine two structural domains with different biological properties, was performed by computational study at the SMD/B3lyp/6-31+G(d) theory level. The mechanism of interaction between [2-(3-hetaryl-1,2,4-triazol-5-yl)phenyl]amine and cyclohexanone in methanol involves three main processes: formation of carbinolamine by addition of an amine to double bond C=O, elimination of a water molecule, and intramolecular cyclization leading to formation of spiro compounds. Results show increase in reactivity of reactants during acid-catalyzed reaction compared to uncatalyzed one. The nature of the heterocyclic substituent on the triazole ring has little effect on the reaction energy, while the mechanism is unchanged. [ABSTRACT FROM AUTHOR]

Mechanisms for formation and hydrolysis of biologically active 2-substituted [1,2,4]triazolo[1,5-c]quinazolines were modeled at the SMD/B3LYP/6–31 + G(d) theory level. Obtained results revealed that internal heterocyclization of hetarylcarboxylic acid (3H-quinazolin-4-ylidene)-hydrazides involves a proton transfer from nitrogen atom of quinazoline system to oxygen atom of carbonyl group, cyclization with formation of [1,2,4]triazolo[4,3-c]quinazoline system, elimination of molecule of water. Dimroth rearrangement using the ANRORC mechanism of 2-hetaryl[1,2,4]triazolo[4,3-c]quinazolines leads to 2-hetaryl[1,2,4]triazolo[1,5-c]quinazolines. The rearrangement is catalyzed by molecule of water and consists of an addition of molecule of water to quinazoline cycle that facilitates its sequential opening, rotation of 1,2,4-triazole, cycle closure and elimination of molecule of water. Acid-catalyzed hydrolysis of 2-hetaryl[1,2,4]triazolo[1,5-c]quinazolines involves protonation of nitrogen atom of quinazoline cycle, an addition of molecule of water to protonated [1,2,4]triazolo[1,5-c]quinazoline system, opening of quinazoline cycle, an addition of second molecule of water, elimination of formic acid, and deprotonation. Substituents influence insignificantly on activation barriers for formation and hydrolysis of 2-hetaryl[1,2,4]triazolo[1,5-c]quinazolines. [ABSTRACT FROM AUTHOR]

1,2,4-Triazole is a popular scaffold in drug design. According to chemical nature, the triazole ring tends to prototropic tautomerism. Tautomeric phenomena are important for studying the chemical reactivity and interaction of drugs based on triazole with biomolecules in the human body. Theoretical modeling was used to assign structures of newly synthesized 2-(3-hetaryl-1,2,4-triazol-5-yl)anilines. The procedure included quantum-chemical SMD/M06-2X/6–311++G(d,p) calculation of the relative stability for possible tautomers, simulation of UV/vis spectra for the most stable forms, and comparison of the resulting curves with the experimental spectral data taking into account the Boltzmann weighting. The influence of the substituents in triazole ring on tautomeric equilibrium was elucidated. NBO charge distribution, dipole moment, molecular electrostatic potential, and HOMO/LUMO gap for the most stable tautomers were analyzed. [ABSTRACT FROM AUTHOR]

The algorithm for generating and estimating the probability of possible reaction pathways for multichannel bimolecular interactions was used to predict the reaction products in the reagent ratio of 1:1 and 1:2. Here, we have considered the possible reaction pathways of the reaction of amine (1S,2S,4S)-bicyclo[2.2.1]hept-5-en-2-ylmethanamine (1) with epoxides 2-((cyclohexyloxy)methyl)oxirane (2), 2-(phenoxymethyl)oxirane (3), N-(oxiran-2-ylmethyl)-N-phenylbenzenesulfonamide (8) in order to explain experimental observed data, which indicate differences in the reactivity of glycidyl ethers and glycidylsulfonamide with framework amines. Based on the proposed algorithm (Borysenko et al. 2021), we have investigated the reaction in the reagent ratio of 1:1 and 1:2. Calculated values of activation barriers indicate a low probability of formation of interaction products of amine (1) with epoxide (8) with a (1:2) reagent ratio due to steric hindrances in the reaction center. [ABSTRACT FROM AUTHOR]

The DNAN (2,4-dinitroanisole), NTO (3-nitro-1,2,4-triazol-5-one), and NQ (nitroguanidine) are important insensitive energetic materials used in military applications. They may find their way to the environment during manufacturing, transportation, storage, training, and disposal. A detailed investigation of possible mechanisms for self-degradation of radical anions formed by addition of solvated electron to DNAN, NTO, and NQ species was performed by computational study using the PCM(Pauling)/M06-2X/6-311++G(d,p) approach. Obtained results suggest that only NQ radical anion is able for self-degradation by elimination of nitrite anion. Formation of urea radical on the earlier stage of the NQ radical anion degradation was also predicted. [ABSTRACT FROM AUTHOR]

Algorithm for generation and assessment of probability of possible reaction pathways for multiple-channel bimolecular interactions is presented. The proposed algorithm comprises a combination of few steps. They include conformational search for reaction intermediate using the molecular mechanics (MMX) approach, based on the obtained conformation construction of structures of transition states and pre-reaction complexes, and calculation activation energies to further determine the probable reaction pathways. The proposed algorithm could be adopted for investigation of chemical and biochemical reactions of different types. Here, we have considered the reaction of bicyclo[2.2.1]hept-5-en-endo-2-ylmethylamine (1) with glycidyl ether (2) in a neutral environment that proceeds through SN2-like mechanism forming bipolar ion (3) which is a good starting point for identification of the reaction channels. Conformational properties of intermediate (3) have been investigated using stochastic conformational search. From the 95 localized conformations within 10 kcal/mol of global minimum that have been obtained, 63 unique transition state conformations were generated and optimized by using the PM7 and M062X/6-31G(d) methods for accurate estimation of overall rate constant of reaction. The most energetically favorable pathways have been investigated at the M062X/6-31G(d) level of theory taking into account the influence of solvent. [ABSTRACT FROM AUTHOR]

It is well known that nitroguanidine (NQ) undergoes photodegradation when exposed to UV-radiation. However, the mechanism of NQ photolysis is not fully understood. Earlier investigations have shown that nitrocompounds undergo to their triplet state population through crossing of electronic singlet and triplet excited state potential energy surfaces due to the nitrogroup rotation and nonplanarity under electronic excitation. Therefore, it is expected that under electronic excitation, the presence of nitrogroup in NQ would also lead to the population of electronic lowest energy triplet state. To shed a light on the degradation of NQ in alkaline solution under electronic excitation, we performed a detailed investigation of a possible degradation mechanism at the IEFPCM/B3LYP/6-311++G(d,p) level in the electronic lowest energy triplet state. We found that degradation ability of NQ in the electronic triplet state would be significantly larger than in the electronic ground singlet state. It was revealed that the photodecomposition of nitroguanidine might occur through several pathways involving N–N and C–N bond ruptures, nitrite elimination, and hydroxide ion attachment. Nitrogen of nitrogroup would be released in the form of nitrite and nitrogen (I) oxide. Computationally predicted intermediates and products of nitroguanidine photolysis such as nitrite, hydroxyguanidine, cyanamide, and urea correspond to experimentally observed species. [ABSTRACT FROM AUTHOR]

Novel derivatives of 2-(1H-(bi)pyrazol-3-yl)phenols and 2-(1,4(5)-(benzo)diazepin-4-yl)phenols were obtained in the reaction of (4-amino-2H-chromen-2-ylidene)malondialdehyde and 4H-chromen-4-imines with 1,2-, 1,3-, and 1,4-dinucleophiles proceeding as a cascade reaction initiated by the Michael reaction. [ABSTRACT FROM AUTHOR]

The initial steps of copper electrocrystallization process from aqueous solutions have been studied at DFT level of theory. It has been shown that Cu(HO) unit is the final product of Cu-ions electroreduction. From this particle clusters Cu·aq are formed and grow. Aggregation of copper atoms to the Cu·aq clusters consists of two steps. The first step includes condensation of Cu(HO) units to hydrated clusters Cu(HO) (n = 2-6). At the second step bonding of Cu(HO) particles is accompanied by dehydration of clusters yielding Cu(HO) structures (n > m). Cluster Cu·aq has been singled out as key structure based on calculated values of energies and Cu-Cu bond distances of Cu·aq clusters. This cluster is of D symmetry which is typical for copper microcrystals formed from aqueous solutions in electrocrystallization processes on foreign surface. This key particle could be considered as a critical nucleus. Number of copper atoms therein matches average dimension of critical nucleus. [ABSTRACT FROM AUTHOR]

5-Endo-trig cyclizations are generally considered to be kinetically unfavourable, as described by Baldwin's rules. Consequently, observation of this mode of reaction under kinetic control is rare. This is usually ascribed to challenges in achieving appropriate approach trajectories for orbital overlap in the transition state. Here, we describe a highly enantio- and diastereoselective route to complex indanes bearing all-carbon quaternary stereogenic centres via a 5-endo-trig cyclization catalysed by a chiral ammonium salt. Through computation, the preference for the formally disfavoured 5-endo-trig Michael reaction over the formally favoured 5-exo-trig Dieckmann reaction is shown to result from thermodynamic contributions to the innate selectivity of the nucleophilic group, which outweigh the importance of the approach trajectory as embodied by Baldwin's rules. Our experimental and theoretical findings demonstrate that geometric and stereoelectronic constraints may not be decisive in the observed outcome of irreversible ring-closing reactions. [ABSTRACT FROM AUTHOR]

Many chemical phenomena occur in solution. Different solvents can change the optical activity of chiral molecules. The optical rotation angles of solutes of 75 amino acids in dimethylformamide, water and methanol were analyzed using the quantitative structure-activity relationships approach. For an accurate description of chirality, we used specific quantum chemical descriptors, which reflect the properties of a chiral center, and continuous symmetry measures. The set of specific quantum chemical descriptors for atoms located near the chiral center, such as Mulliken charges, the sum of Mulliken charges on an atom (with the hydrogen charges summed up with the adjacent non-hydrogen atoms), and nuclear magnetic resoncance tensors was applied. To represent solvent effects, we used mixture-like structural simplex descriptors and quantum chemical descriptors obtained for structures optimized for specified solvent using PBE1PBE/6-31G** level of theory with the polarizable continuum model. Multiple linear regression, M5P, and locally weighted learning techniques were used to achieve accurate predictions. The specific quantum chemical descriptors proposed here demonstrated high specificity in the majority of the developed models and established direct quantitative structure-property relationships. [ABSTRACT FROM AUTHOR]

A correction to the article "Catalytic Enantioselective Synthesis of Indanes by a Cation-Directed 5-Endo-Trig Cyclization," by researcher Craig P. Johnston and colleagues is presented.