Nitrogen-rich Heterocyclic Compounds Research Articles

Deprotonation-assisted electrochemical synthesis of copper nitrotriazole with excellent ignition performance

Electrochemical synthesis serves as a green and efficient method with great application potential. However, it has not been extensively applied in the synthesis of energetic materials. Nitrogen-rich heterocyclic compounds, as a new generation of energetic materials, enjoy advantages such as eco-friendliness, high energy output, and excellent safety performance. This study reports the electrochemical cathodic synthesis of copper nitrotriazole [Cu(NTz)2] using copper chloride and 3-nitro-1,2,4-triazole as a reaction substrate and triethylamine as a deprotonation agent. The obtained Cu(NTz)2 comprises uniform spherical particles of nano lamellae. As the dosage of triethylamine increased from 50 μL to 150 μL, Cu(NTz)2 gradually grew into compact solid spherical particles, significantly increasing the energy output. Notably, the heat release increased from 711 J g−1 to 1301 J g−1, accompanied by a significant positive elevation of ignition performance and peak combustion pressure in the process of confined combustion. This greatly boosted the energetic performance of Cu(NTz)2. Moreover, Cu(NTz)2 demonstrates insensitivity to electrostatic discharge (E50＞225 mJ) and friction (FS＞360 N), suggesting excellent safety performance. Owing to its outstanding energetic and safety performance, Cu(NTz)2 boasts great potential for application as pyrotechnic compositions, including military gas-producing and incendiary agents. Moreover, it has been corroborated that Cu(NTz)2 can be applied as a micro ignitor.

Crystal Structure and Noncovalent Interactions of Heterocyclic Energetic Molecules.

Nitrogen-rich heterocyclic compounds are important heterocyclic substances with extensive future applications for energetic materials due to their outstanding density and excellent physicochemical properties. However, the weak intermolecular interactions of these compounds are not clear, which severely limits their widespread application. Three nitrogen-rich heterocyclic compounds were chosen to detect their molecular geometry, stacking mode and intermolecular interactions by crystal structure, Hirshfeld surface, RDG and ESP. The results show that all atoms in each molecule are coplanar and that the stacking mode of the three crystals is a planar layer style. A large amount of inter- and intramolecular interaction exists in the three crystals. All principal types of intermolecular contacts in the three crystals are N···H interactions and they account for 40.9%, 38.9% and 32.9%, respectively. Hydrogen bonding, vdW interactions and steric effects in Crystal c are stronger than in Crystals a and b. The negative ESPs all concentrate on the nitrogen atoms in the three molecules. This work is expected to benefit the crystal engineering of heterocyclic energetic materials.

Self-assembly of iodine-containing oxidants with nitrogen-rich heterocyclic compounds for novel energetic biocidal agents

Iodine-rich energetic compounds are a special class of functional biocidal materials. Balancing the inherent competing needs for both high-iodine contents and high-energies in these materials remains a challenge. In this work, four novel iodine-rich energetic compounds were designed and synthesized through the crystal engineering-driven self-assembly of nitrogen-rich heterocyclic compounds and iodine-containing oxidants such as HIO3 and H5IO6. The structures and performance of these iodine-rich energetic compounds were investigated. Among them, compound 3 possessed a relatively high iodine content (46.32%) while maintaining an excellent detonation performance (detonation velocity: 7445 m s−1, and detonation pressure: 41.2 GPa, respectively). This work demonstrates the effectiveness of crystal engineering-driven self-assembly for the development of potential iodine-rich energetic biocidal agents.

Crystal Engineering-Driven Self-Assembly of Iodine-Containing Oxidants with Nitrogen-Rich Heterocyclic Compounds for Novel Energetic Biocidal Agents

Crystal Engineering-Driven Self-Assembly of Iodine-Containing Oxidants with Nitrogen-Rich Heterocyclic Compounds for Novel Energetic Biocidal Agents

Self-Assembly of Nitrogen-Rich Heterocyclic Compounds with Oxidants for the Development of High-Energy Materials.

The development of energetic materials with high energy and low sensitivity has attracted immense interests due to their widespread applications in aerospace technology and national defense. In this work, a promising self-assembly strategy was developed to prepare three high-energy materials (1-3) through the introduction of oxidant molecules into the crystal voids of the parent materials. The structures of these new materials were comprehensively examined by infrared spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and single-crystal X-ray diffraction. In these materials, three unique layer structures with hcb, sql, and interrupted sql topologies were observed, which were formed by the fused-ring-based energetic components. Windows with hexagonal, square, and rectangular structures were observed within these layer structures, which were occupied by H2O2, NO3-, and ClO4-, respectively. Oxidant molecules interacted with parent molecules via hydrogen bonds to form crystal structures of these materials. Moreover, the energetic property of these materials was estimated by computing methods. The calculation results revealed that these self-assembly materials exhibit excellent energetic properties. The highest energetic performance was observed for compound 3. The detonation velocity, detonation pressure, and specific impulse values were up to 9339 m·s-1, 42.5 GPa, and 308 s, respectively, which were greater than those of HMX. Furthermore, these materials exhibited good sensitivity, which was closely related to their unique crystal structures. The high performance of these materials indicated that the self-assembly strategy should be a promising method for the development of novel energetic materials.

Synthesis and cytotoxic activity evaluation of some new 1, 3, 4-oxadiazole, 1, 3, 4-thiadiazole and 1, 2, 4- triazole derivatives attached to phthalimide.

Background and purpose:In the last few decades, nitrogen-rich heterocyclic compounds such as 1, 3, 4-thiadiazoles, 1, 2, 4-triazoles and 1, 3, 4-oxadiazoles have received considerable attention because of their notable biological properties, especially cytotoxic effects. The small molecules of mentioned azole derivatives revealed very intensive antitumor activity. In addition, phthalimide-thiadiazole and naphthalimide-triazole hybrid derivatives have shown remarkable cytotoxic effects. According to these observations, some of the hybrid derivatives containing the phthalimide-five-membered azoles were prepared in three steps in this research.Experimental approach:The thiol group of azoles was treated with ethyl chloroacetate which was followed by a reaction with hydrazine hydrate to provide acid hydrazide derivatives. Subsequently, the corresponding acid hydrazides were utilized to prepare the final derivatives through the reaction with phthalic anhydride. Cytotoxic activity of final compounds was evaluated against MCF-7 and HeLa cell lines using MTT assay.Findings/Results:Compound 3d containing two phthalimide moieties in its structure showed a significant improvement in cytotoxic activity with an IC50 value of 29 μM against HeLa cell line. Compounds 3a-3c showed less cytotoxic effects against both cell lines.Conclusion and implications:The combination of the thiadiazole nucleus with two phthalimide structures increased the cytotoxic activity against the HeLa cell line. This increase in cytotoxic activity is probably due to its being more lipophilic characteristic and interaction of this derivative with the biological targets of two directions.

Phthalazinone Scaffold: Emerging Tool in the Development of Target Based Novel Anticancer Agents.

Phthalazinones are important nitrogen-rich heterocyclic compounds which have been a topic of considerable medicinal interest because of their diversified pharmacological activities. This versatile scaffold forms a common structural feature for many bioactive compounds, which leads to the design and development of novel anticancer drugs with fruitful results. The current review article discusses the progressive development of novel phthalazinone analogues that are targets for various receptors such as PARP, EGFR, VEGFR-2, Aurora kinase, Proteasome, Hedgehog pathway, DNA topoisomerase and P-glycoprotein. It describes mechanistic insights into the anticancer properties of phthalazinone derivatives and also highlights various simple and economical techniques for the synthesis of phthalazinones.

3,4-Bis(3-tetrazolylfuroxan-4-yl)furoxan: A Linear C-C Bonded Pentaheterocyclic Energetic Material with High Heat of Formation and Superior Performance.

The design and preparation of new nitrogen-rich heterocyclic compounds are of considerable significance for the development of high-performing energetic materials. By combining nitrogen-rich tetrazole and oxygen-rich furoxan, a linear C–C bonded pentaheterocyclic energetic compound, 3,4-bis(3-tetrazolylfuroxan-4-yl) furoxan (BTTFO), was synthesized using a facile and straightforward method. Comprehensive X-ray analysis reveals the key role of hydrogen bonds, π–π interactions, and short contacts in the formation of dense packing of BTTFO and explains why a long chain-shaped molecule has a high density. This multicyclic structure incorporating three furoxan and two tetrazole moieties results in an exceptionally high heat of formation (1290.8 kJ mol–1) and favorable calculated detonation performances (vD, 8621 m s–1, P, 31.5 GPa). The interesting structure and fascinating properties demonstrated the feasibility of a linear multicyclic approach as a high-energy-density skeleton. Additionally, the thermodynamic parameters, electrostatic potential (ESP), and frontier molecular orbitals were also studied to get a better understanding of structure–property correlations.

New nitrogen-rich heterocyclic compounds to build 3D energetic metal complexes

By introducing hydroxymethyl into nitrogen-rich heterocyclic compounds, we designed and synthesized a new ligand. The three dimensional (3D) energetic metal complexes sodium and potassium salts of new ligand were investigated for heat-resistant energetic materials.

Aminonitro Groups Surrounding a Fused Pyrazolotriazine Ring: A Superior Thermally Stable and Insensitive Energetic Material

Nitrogen-rich heterocyclic compounds offer promising potential backbones for constructing various high energy density compounds. Selective diazotization of 3,5-diamino-4-nitropyrazole (1) with tert...

Rhodium(iii)-catalyzed diverse [4 + 1] annulation of arenes with 1,3-enynes via sp3/sp2 C-H activation and 1,4-rhodium migration.

Nitrogen-rich heterocyclic compounds have a profound impact on human health. Despite the numerous synthetic methods, diversified, step-economic, and general synthesis of heterocycles remains limited. C-H bond functionalization catalyzed by rhodium(iii) cyclopentadienyls has proven to be a powerful strategy in the synthesis of diversified heterocycles. Herein we describe rhodium(iii)-catalyzed sp2 and sp3 C-H activation-oxidative annulations between aromatic substrates and 1,3-enynes, where alkenyl-to-allyl 1,4-rhodium(iii) migration enabled the generation of electrophilic rhodium(iii) π-allyls via remote C-H functionalization. Subsequent nucleophilic trapping of these species by various sp2-hybridized N-nucleophiles delivered three classes (external salts, inner salts, and neutral azacycles) of five-membered azacycles bearing a tetrasubstituted saturated carbon center, as a result of [4 + 1] annulation with the alkyne being a one-carbon synthon. All the reactions proceeded under relatively mild conditions with broad substrate scope, high efficiency, and excellent regioselectivity. The synthetic applications of this protocol have also been demonstrated, and experimental studies have been performed to support the proposed mechanism.

Microwave synthesis, crystal structure, antioxidant, and antimicrobial study of new 6-heptyl-5,6-dihydrobenzo[4,5]imidazo[1,2-c]quinazoline compound

BackgroundAlthough the development of antibiotic and antioxidant manufacturing, the problem of bacterial resistance and food and/or cosmetics oxidation still needs more efforts to design new derivatives which can help to minimize these troubles. Benzimidazo[1,2-c]quinazolines are nitrogen-rich heterocyclic compounds that possess many pharmaceutical properties such as antimicrobial, anticonvulsant, immunoenhancer, and anticancer.ResultsA comparative study between two methods, (microwave-assisted and conventional heating approaches), was performed to synthesise a new quinazoline derivative from 2-(2-aminophenyl)-1H-benzimidazole and octanal to produce 6-heptyl-5,6-dihydrobenzo[4,5]imidazo[1,2-c]quinazoline (OCT). The compound was characterised using FTIR, 1H and 13C NMR, DIMS, as well as X-ray crystallography. The most significant peak in the 13C NMR spectrum is C-7 at 65.5 ppm which confirms the cyclisation process. Crystal structure analysis revealed that the molecule grows in the monoclinic crystal system P21/n space group and stabilised by an intermolecular hydrogen bond between the N1–H1A…N3 atoms. The crystal packing analysis showed that the molecule adopts zig-zag one dimensional chains. Fluorescence study of OCT revealed that it produces blue light when expose to UV-light and its’ quantum yield equal to 26%. Antioxidant activity, which included DPPH· and ABTS·+ assays was also performed and statistical analysis was achieved via a paired T-test using Minitab 16 software with P < 0.05. Also, the antimicrobial assay against two Gram-positive, two Gram-negative, and one fungus was screened for these derivatives.ConclusionsUsing microwave to synthesise OCT have drastically reduced reaction time, and increased yield. OCT show good antioxidant activity in one of the tests and moderate antimicrobial activity.

Synthesis and cytotoxic evaluation of novel quinazolinone derivatives as potential anticancer agents.

Nitrogen-rich heterocyclic compounds represent a unique class of chemicals with especial properties and have been modified to design novel pharmaceutically active compounds. In this study, a series of novel quinazolinone derivatives with substituted quinoxalindione were synthesized in two parts. In the first part, 6-(4-amino-3-methylphenoxy)quinoxaline-2,3(1H,4H)-dione was prepared from para-amino -m-crozol in 5 steps. In the next part, 2-alkyl-4H-benzo[d][1,3]oxazin-4-one derivatives were obtained from antranilic acid. Then reaction of 6-(4-amino-3-methylphenoxy)quinoxaline-2,3(1H,4H)-dione with 2-alkyl-4H-benzo[d][1,3]oxazin-4-one derivatives resulted in the production of final componds. The structures of synthesized compounds were confirmed by IR and 1H-NMR. Cytotoxic activity of the compounds were evaluated at 0.1, 1, 10, 50 and 100 μM concentrations against MCF-7 and HeLa cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Almost all new compounds showed cytotoxic activity in both cell lines. Among tested compounds, 11g displayed the highest cytotoxic activity against both cell lines.

Pyridazinone: an attractive lead for anti-inflammatory and analgesic drug discovery.

In spite of the availability of a large number of anti-inflammatory and analgesic agents, fighting pain and inflammation remains a common problem. The current review article discusses the need of novel therapeutic targets for risk-free anti-inflammatory and analgesic therapy and summarizes some new agents in various stages of drug discovery pipeline. Pyridazin-3(2H)-ones are nitrogen-rich heterocyclic compounds of considerable medicinal interest due to their diverse biological activities. The current review article focuses on progressive development of this attractive scaffold for the design and synthesis of new pyridazinone-based anti-inflammatory and analgesic agents. Mechanistic insights into the anti-inflammatory and analgesic properties of pyridazinone derivatives and various synthetic techniques used for their synthesis are also described.

Theoretical study of ionization and one‐electron oxidation potentials of N‐heterocyclic compounds

A number of density functionals was utilized to predict gas-phase adiabatic ionization potentials (IPs) for nitrogen-rich heterocyclic compounds. Various solvation models were applied to the calculation of difference in free energies of solvation of oxidized and reduced forms of heterocyclic compounds in acetonitrile (AN) for correct reproduction of their standard oxidation potentials. We developed generally applicable protocols that could successfully predict the gas-phase adiabatic ionization potentials of nitrogen-rich heterocyclic compounds and their standard oxidation potentials in AN. This approach is supported by a MPW1K/6-31+G(d) level of theory which uses SMD(UA0) approximation for estimation of solvation energy of neutral molecules and PCM(UA0) model for ionized ones. The mean absolute derivation (MAD) and root mean square error (RMSE) of the current theoretical models for IP are equal to 0.22 V and 0.26, respectively, and for oxidation potentials MAD = 0.13 V and RMSE = 0.17.

Practical and innate carbon–hydrogen functionalization of heterocycles

Nitrogen-rich heterocyclic compounds have had a profound impact on human health, as these chemical motifs are found in a large number of drugs used to combat a broad range of diseases and pathophysiological conditions. Advances in transition metal-mediated cross-coupling have simplified the synthesis of such molecules; however, the development of practical and selective C–H functionalization methods that do not rely upon prefunctionalized starting materials is an underdeveloped area.1–9 Paradoxically, the innate properties of heterocycles that make them so desirable for biological applications render them challenging substrates for direct chemical functionalization, such as limited solubility, functional group incompatibilities, and reagent/catalyst deactivation. Herein we report that zinc sulfinate salts9 can be used to transfer alkyl radicals to heterocycles, allowing for a mild, direct and operationally simple formation of medicinally relevant C–C bonds while reacting in an orthogonal fashion to other innate C–H functionalization methods (Minisci, borono-Minisci, electrophilic aromatic substitution, transition metal-mediated C–H insertion, C–H deprotonation).2–7,9 A toolkit of these reagents was prepared and reacted across a wide range of heterocycles (natural products, drugs, building blocks) without recourse to protecting group chemistry, and can even be employed in a tandem fashion in a single pot in the presence of water and air.

ChemInform Abstract: The Synthesis of Novel Nitrogen-Rich Heterocyclic Compounds.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.