Nitrogen-rich Heterocycles Research Articles

Tuning the optical properties of BODIPY dyes by N-rich heterocycle conjugation using a combined synthesis and computational approach

We report a systematic tuning of optical properties of BODIPY dyes by conjugation of nitrogen-rich heterocycles, and underlying nitrogen influence by TDDFT calculations.

Synthesis, X-ray characterization, Hirshfeld surface analysis and DFT calculations on tetrazolyl-phenol derivatives: H-bonds vs C–H…π/π…π interactions

Tetrazoles are nitrogen rich heterocycles with a broad spectrum of medicinal properties and potential for use as drugs. A significant number of FDA approved drugs incorporate the tetrazole moiety indicating the versatile pharmaceutical potential associated with this heteroaromatic skeleton. Owing to the higher number of nitrogen atoms and σ-lone pairs, tetrazoles offer the opportunity to control structural topology through non-covalent interactions. In this perspective, the present research is focused on the investigation of various non-covalent interactions in a series of tetrazole derivatives (5a–c) incorporating a linear aliphatic chain (eight to fifteen carbon atoms) at N-2 and with a phenol moiety at the only carbon atom of the tetrazole ring. The detailed X-ray crystallographic investigations revealed the formation of various supramolecular architectures employing non-covalent interactions of a diverse nature. Further insights into these intermolecular interactions were obtained using Hirshfeld surface analysis and DFT calculations focusing on the H-bonds, C–H…π and π–π interactions in the structures. These contacts have been characterized by combining the quantum theory of “atoms-in-molecules” (QTAIM) with the non-covalent interaction index (NCIplot).

Computational studies on nitro derivatives of BN indole as high energetic material.

Nitrogen-rich heterocycles and their nitro derivatives are one of the important classes of energetic materials. In the present study, the computational methods have been applied to determine the thermodynamic and detonation properties of nitro derivatives of BN indole molecule. Structure optimization and electronic energy of the designed molecules are determined using the density functional theory. The gas-phase heat of formation of the species concerned is determined by the atomization method. Wave function analysis-surface analysis suite (WFA-SAS) has been applied to determine the condensed phase heat of formation and crystal density of designed molecules. Bond dissociation energy (BDE) is determined to identify the trigger bond. The energy gap between highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) has been calculated to predict the stability of the molecule. Impact sensitivity and detonation properties of designed species are calculated. The calculated parameters show that among all the designed molecules, the molecule A6 (1,2,3,5,6,7-Hexanitrobnindole) has the properties to be considered as a high density energetic molecule.

Energetic materials based on poly furazan and furoxan structures

Furazan and furoxan represent fascinating explosophoric units with intriguing structures and unique properties. Compared with other nitrogen-rich heterocycles, most poly furazan and furoxan-based heterocycles demonstrate superior energetic performances due to the higher enthalpy of formation and density levels. A large variety of advanced energetic materials have been achieved based on the combination of furazan and furoxan moieties with different kinds of linkers and this review provides an overview of the development of energetic poly furazan and furoxan structures during the past decades, with their physical properties and detonation characteristics summarized and compared with traditional energetic materials. Various synthetic strategies towards these compact energetic structures are highlighted by covering the most important cyclization methods for construction of the hetercyclic scaffolds and the following modifications such as nitrations and oxidations. Given the synthetic availabilities and outstanding properties, energetic materials based on poly furazan and furoxan structures are undoubtedly listed as a promising candidate for the development of new-generation explosives, propellants and pyrotechnics.

Facile Synthesis and Accelerated Combustion Effect of Micro-/Nanostructured Amorphous and Crystalline Metal Coordination Compounds Based on N,N-Bis[1H-tetrazol-5-yl]amine

Energetic coordination compounds (ECCs) based on nitrogen-rich heterocycles has continued to attract considerable attention owing to their great potential in military and civilian fields. Besides the components, micro-/nanostructures and solid states also play a significant role in tuning the performance of energetic coordination compounds. Herein, Na(Hbta)(H2 bta)(H2O)3 (1) was synthesized through the optimized hydrothermal reaction of sodium dicyanamide and sodium azide in the presence of acetic acid. Its structure was further confirmed by single-crystal X-ray diffraction analysis. Then, five micro-/nanostructured metal-Hbta complexes were prepared via mild metathesis reaction and then freeze-drying technology. These as-prepared materials exhibit different solid states and show insensitivity to external mechanical stimuli (impact sensitivity, >40 J; friction sensitivity, >360 N). Additionally, they possessed outstanding performance in accelerating ammonium perchlorate (AP) thermal decomposition by decre...

Theoretical studies on a new series of 1,2,3,4-tetrazine 1,3-dioxide annulation with an imidazole ring or oxazole ring.

To continue our previous work, the structure and some properties of a new series of 1,2,3,4-tetrazine 1,3-dioxides annulated with an imidazole ring or oxazole ring were studied in this paper. Four imidazolo-v-tetrazine 1,3-dioxides (ITDOs) I1-I4 and eight oxazolo-v-tetrazine 1,3-dioxides (OTDOs) O1-O8 were designed. We employed the density functional theory (DFT) in B3LYP/6-311++G(d,p) to study their geometrical structures and the homodesmotic reaction method to calculate the enthalpies of formation. Detonation properties and stabilities were also studied. Generally speaking, ITDOs and OTDOs have more preferable stabilities than TTDOs or pyrazolo-TDOs. I3, I4, O1, and O2 were found to be comparable to the energy level of RDX; O5 and O6 are even as powerful as HMX. The stabilities analysis in this paper can also prove that the five-membered ring deformation and the steric hindrance change caused by the different substituents will affect the stabilities of the structures of 1,2,3,4-tetrazine 1,3-dioxides annulated with a five-membered nitrogen-rich heterocycle. Other factors, such as the position of the electron-withdrawing substituents or the position of coordinated oxygen atom, are worthwhile to investigate in future work.

Unclogging electron-transporting channels via self-assembly for improving light harvesting and stability of dye-sensitized solar cells

Two nitrogen-rich heterocycle donor dyes, NP-2 and NP-3, have been strategically designed and synthesized to construct functionalized self-assembly layers. Through the formation of N⋯H hydrogen bonds between these nitrogen-rich heterocycle donors and 4-tert-butylbenzoic acid (PTBBA), the electron leak points (imine group (N)) may be plugged, thus blocking excited-state electron lateral transferring between the adsorbed dyes and electron leaking from electron-transporting channel into the electrolyte. Furthermore, the huge 3-dimensional sizes of such supramolecule sensitizers can not only suppress dye aggregation, but enhance the photoresponse capacity in visible region. Therefore, the devices based on NP-2@PTBBA and NP-3@PTBBA, which obtained by the cocktail sensitization procedures, can be improved by increasing the open-circuit photovoltage (Voc) without any loss of the short-circuit photocurrent density (Jsc) owing to the synergy effect between self-assembly and co-sensitization. Although the device based on NP-3/PTBBA via the stepwise sensitization procedure delivers lower efficiency, it can remain at 103.14% of the initial efficiency as a result of parallel increase in Jsc and Voc values. Overall, the design principles provide a clear road map of supramolecular dye-sensitized solar cells (SDSSCs) and demonstrate the potential of 1,3,5-triazine-based dyes in solar cells research.

3-(5-Amino-1,2,4-triazole)-1,2,4-oxadiazole: A new biheterocyclic scaffold for the synthesis of energetic materials

Nitrogen-rich heterocycles are increasingly used in energetic chemistry with the aim to achieve superior performance of the new energetic materials. Combining such building blocks into biheterocycles increases energy output while at the same time retains low sensitivity. Herein, we report the synthesis and characterization of a compound containing a 5-amino-1,2,4-triazole moiety connected with a 1,2,4-oxadiazole ring. The trichloromethyl group attached to the oxadiazole ring offers an attractive point for further transformations into potentially energetic compounds.

C-H Arylation in the Formation of a Complex Pyrrolopyridine, the Commercial Synthesis of the Potent JAK2 Inhibitor, BMS-911543.

The development of an improved short and efficient commercial synthesis of the JAK2 inhibitor, a complex pyrrolopyridine, BMS-911543, is described. During the discovery and development of this synthesis, a Pd-catalyzed C-H functionalization was invented which enabled the rapid union of the key pyrrole and imidazole fragments. The synthesis of this complex, nitrogen-rich heterocycle was accomplished in only six steps (longest linear sequence) from readily available materials.

Synthesis, single crystal analysis, biological and docking evaluation of tetrazole derivatives

Tetrazoles are conjugated nitrogen-rich heterocycles considered as bio-isosteres of carboxylic acids. Tetrazoles owing to their conjugated structures serve as biologically relevant potent scaffolds. The present research paper reports the successful synthesis and single crystal analysis of three different tetrazole derivatives (2, 4, 6). The synthesized tetrazole derivatives were evaluated for their possible cytotoxicity LD50 (52.89, 49.33, 17.28 μg/ml) and antileishmanial activities IC50 (0.166, 10, 5.0 μg/ml). Moreover, molecular docking studies were performed to determine the possible interaction sites of the tetrazole derivatives (2, 4, 6) with TryR, an enzyme involved in the redox metabolism of the Leishmania parasite. Docking computations demonstrates that the tetrazole derivatives (2, 4, 6) established prominent binding interactions with the key residues of the TryR and possess the potential to effectively inhibit the catalytic activities of the enzyme. The results suggested that the synthesized tetrazole derivative (2, 4, 6) can be possible hit candidates which can be tested further against amastigote stage of parasite and then in an animal model of leishmaniasis.

Nitrogen-Rich Copper(II) Bromate Complexes: an Exotic Class of Primary Explosives †.

Because of the ongoing very challenging search for potential replacements of the currently used toxic lead-based primary explosives, new synthetic strategies have to be developed. In particular, the smart concept of energetic coordination compounds (ECC) has proven to hold great potential to solve this difficult and complex problem. The herein-described approach combines the exotic and neglected class of copper(II) bromate ECC with different environmentally friendly nitrogen-rich heterocycles, which exhibit the energetic properties of powerful primary explosives. The concept is the simple adjustment of the energetic properties of the complexes through alteration of the corresponding azoles. Six new copper(II) bromate complexes with reasonable sensitivities are featured in this study, which were synthesized in a practical and straightforward fashion, assured through easy access to copper(II) bromate obtained by metathesis reaction. Obtained compounds were comprehensively characterized through various analytical methods such as low-temperature X-ray diffraction, IR spectroscopy, and elemental analysis. Their sensitivities toward impact and friction were assessed through BAM standard techniques, together with their sensitivity against electrostatic discharge. Evaluation of the energetic properties of the newly synthesized compounds included examination of the respective thermal stabilities by differential thermal analysis. Furthermore, the complexes were tested regarding their behavior toward laser irradiation. Additionally, to receive insight into a possible correlation between the laser-investigated compounds' optical absorption and their ability to ignite by exposure to laser irradiation, UV-vis-near-IR spectra were recorded.

Nitrogen Rich Heterocycles as a Privileged Fragment in Lead Discovery

Nitrogen Rich Heterocycles as a Privileged Fragment in Lead Discovery

15N-Labelling and structure determination of adamantylated azolo-azines in solution.

Determining the accurate chemical structures of synthesized compounds is essential for biomedical studies and computer-assisted drug design. The unequivocal determination of N-adamantylation or N-arylation site(s) in nitrogen-rich heterocycles, characterized by a low density of hydrogen atoms, using NMR methods at natural isotopic abundance is difficult. In these compounds, the heterocyclic moiety is covalently attached to the carbon atom of the substituent group that has no bound hydrogen atoms, and the connection between the two moieties of the compound cannot always be established via conventional 1H-1H and 1H-13C NMR correlation experiments (COSY and HMBC, respectively) or nuclear Overhauser effect spectroscopy (NOESY or ROESY). The selective incorporation of 15N-labelled atoms in different positions of the heterocyclic core allowed for the use of 1H-15N (JHN) and 13C-15N (JCN) coupling constants for the structure determinations of N-alkylated nitrogen-containing heterocycles in solution. This method was tested on the N-adamantylated products in a series of azolo-1,2,4-triazines and 1,2,4-triazolo[1,5-a]pyrimidine. The syntheses of adamantylated azolo-azines were based on the interactions of azolo-azines and 1-adamatanol in TFA solution. For azolo-1,2,4-triazinones, the formation of mixtures of N-adamantyl derivatives was observed. The JHN and JCN values were measured using amplitude-modulated 1D 1H spin-echo experiments with the selective inversion of the 15N nuclei and line-shape analysis in the 1D 13С spectra acquired with selective 15N decoupling, respectively. Additional spin–spin interactions were detected in the 15N-HMBC spectra. NMR data and DFT (density functional theory) calculations permitted to suggest a possible mechanism of isomerization for the adamantylated products of the azolo-1,2,4-triazines. The combined analysis of the JHN and JCN couplings in 15N-labelled compounds provides an efficient method for the structure determination of N-alkylated azolo-azines even in the case of isomer formation. The isomerization of adamantylated tetrazolo[1,5-b][1,2,4]triazin-7-ones in acidic conditions occurs through the formation of the adamantyl cation.

Pyrolysis of Energetic Ionic Salts Based on Nitrogen-rich Heterocycles

Energetic ionic salts based on nitrogen-rich heterocycles are expected to usher in a new era in the fields of propellants, explosives, and pyrotechnics owing to their excellent combustion characteristics, green nature, and the ability to tailor them based on requirements. The review focuses on an important aspect of these compounds, other than the synthesis procedure and physico-chemical characterisation, that is frequently overlooked, i.e. the decomposition pathways and the associated chemical kinetic parameters, which are essential to elucidate and simulate their combustion characteristics. The reaction mechanisms of four major families of energetic ionic salts, explored by various experimental and numerical techniques, are reported in detail.

Energetic 4,4'-Oxybis[3,3'-(1-hydroxytetrazolyl)]furazan and Its Salts.

Energetic compounds that incorporate multiple nitrogen-rich heterocycles are of great interest for high-density energetic materials. A facile synthetic strategy to combine an oxy bridge and furazan groups, as well as tetrazole-ols, into a molecule (5) was found. Some energetic salts based on 5 were prepared by neutralization. All of the compounds were fully characterized. Additionally, the structure of 7 has been elucidated by single-crystal XRD analysis. Physicochemical and energetic properties were also studied; these show that these newly designed energetic salts exhibit good thermal stabilities. Hydroxylammonium salt (6) has a detonation performance and sensitivities comparable with those of 1,3,5-trinitroperhydro-1,3,5-triazine (RDX).

Some nitrogen-rich heterocycles derivatives as potential explosives and propellants: A theoretical study

Four types of nitrogen-rich heterocycles substituted with -NO2, -NHNO2 and -C(NO2)3 explosophoric groups were explored as potential explosives and propellants materials. The calculated crystal density (?0)and the condensed phase heat of formation (?H?0f)for each of the twelve structures investigated shows that all these derivatives possess high (1.834-1.980 g cm-3)(?H?0f) and (605-2130 kJ kg-1) values. Interesting properties such as detonation velocity (D), pressure (P) and specific impulse (Isp) were calculated using the Kamlet-Jacobs method and ISPBKW thermochemical code. Detonation velocity and pressure in excess of 8.44 km s-1 and 32.87 GPa was obtained in all cases. Furthermore, trinitromethyl substituted derivatives shows performance exceeding that of HMX with an estimated D = 9.32-9.72 km s-1 and P = 40.61-43.82 GPa. Some -NO2 and -NHNO2 substituted derivatives were shown to be impact insensitive while retaining good detonation performance and thus are regarded as potential replacement for current RDX -based explosives. Finally, the calculated specific impulse (Isp between 248 and 270 s) of all investigated derivatives indicate that these energetic materials can be considered as possible ingredient in future rocket propellant compositions.

Dancing with Energetic Nitrogen Atoms: Versatile N-Functionalization Strategies for N-Heterocyclic Frameworks in High Energy Density Materials.

Nitrogen-rich heterocycles represent a unique class of energetic frameworks featuring high heats of formation and high nitrogen content, which have generated considerable research interest in the field of high energy density materials (HEDMs). Although traditional C-functionalization methodology of aromatic hydrocarbons has been fully established, studies on N-functionalization strategies of nitrogen-containing heterocycles still have great potential to be exploited by virtue of forming diverse N-X bonds (X = C, N, O, B, halogen, etc.), which are capable of regulating energy performance and the stability of the resulting energetic compounds. In this sense, versatile N-functionalization of N-heterocyclic frameworks offers a flexible strategy to meet the requirements of developing new-generation HEDMs. In this Account, the role of strategic N-functionalization in designing new energetic frameworks, including the formation of N-C, N-N, N-O, N-B and N-halogen bonds, is emphasized. In the family of N-functionalized HEDMs, energetic derivatives, by virtue of forming N-C bonds, are the most widely used type due to the good nucleophilic capacity of most heterocyclic backbones. Although introduction of carbon tends to decrease energetic performance, significant improvement in material sensitivity makes this strategy attractive for safety concerns. More importantly, most "explosophores" can be readily introduced into the N-C linkage, thus providing a promising route to various HEDMs. Formation of additional N-N bonds typically gives rise to higher heats of formation, implying the potential enhancement in detonation performance. In many cases, the increased hydrogen bonding interactions within N-N functionalized heterocycles also improve thermal stability accordingly. Introduction of a single N,N'-azo bridge into several azole moieties leads to an extended nitrogen chain, demonstrating a new strategy for designing high-nitrogen compounds. The strategy of N-O functionalization has become an increasingly efficient tool for exploring new HEDMs with both high energy and low sensitivity. As a highly dense building block, introduction of oxygen not only improves density significantly but also gives rise to a better oxygen balance. Furthermore, the N-O functionalized strategy is highly suitable for a broad variety of N-heterocycles including five-membered azoles and six-membered azines. Newly explored N-halogen and N-B functionalization strategies have endowed the resulting HEDMs with some new energetic characteristics. Typical examples include the N-halogenated fused triazole and FOX-7 as potential hypergolic oxidizers with very short ignition delay times. In addition, some exploratory studies of N-B functionalized heterocycles have expanded energetic applications as hypergolic ionic liquids, green pyrotechnic colorants, and high-oxygen carriers. Overall, flexible N-functionalization methodologies involving different N-X bond formation have not only provided an efficient approach to diverse energetic ingredients but also expanded the application scope of energetic materials. Discussion and perspectives of N-functionalized protocols are given to summarize possible structure-property correlations, thus providing efficient guidelines for future design of new HEDMs.

Pyridazine N-Oxides as Precursors of Metallocarbenes: Rhodium-Catalyzed Transannulation with Pyrroles.

Pyridazine N-oxides are used for the first time as precursors of metallocarbenes. These nitrogen-rich heterocycles led to the discovery of a novel acceptor and donor-acceptor enalcarbenoids. The synthetic utility of these metallocarbenes was demonstrated in the rhodium-catalyzed denitrogenative transannulation of pyridazine N-oxides with pyrroles to the valuable alkyl, 7-aryl, and 7-styryl indoles. The transannulation strategy was applied to the synthesis of a potent anticancer agent.

Coordination Polymers with High Energy Density: An Emerging Class of Explosives

Coordination polymers (CPs) have recently emerged as a promising class of high energy materials useful for the synthesis of tailored energetic materials. CPs have shown potential to improve energetic performance relative to conventional organic energetic materials with regard to density, oxygen balance, sensitivity, and heat of detonation. Thus far, a variety of energetic linkers have been applied, and success has been achieved across a number of structure classes including nitrogen-rich heterocycles and azides. Here, the current progress in the field of energetic CPs, both from the standpoint of structure and properties, is reviewed, and a perspective on current challenges and promising future directions for the field are delineated. Inasmuch as structure/function relationships have been elucidated for CPs with particular applications in mind, these are discussed as well as shortcomings in experimental work required to firmly establish predictive principles within the realm of energetic materials.

Group 4 complexes supported by nitrogen-rich heterocycles bearing chalcogen donor atoms

Equimolar and excess ratio reactions of ligands [H{4,5-(P(E)Ph2)2tz}] [tz=1,2,3-triazole; E=S (1), Se (2)] with Ti(NR2)4 (R=Me, Et) yielded the disubstituted complexes [Ti(NR2)2{κ2-N,E-(4,5-(P(E)Ph2)2tz}2] [E=S, R=Me (3), Et (4); E=Se, R=Me (5), Et (6)], while the reactions of 1 and 2 with Ti(NEt2)2Cl2 gave the monosubstituted complexes [Ti(NEt2)Cl2{κ2-N,E-(4,5-(P(E)Ph2)2tz}] [E=S (7), Se (8)]. The reaction of M(NR2)4 (M=Zr, Hf, R=Me, Et) with 1 and 2 failed. However, the zirconium and hafnium disubstituted complexes, [M(NR2)2{κ2-N,E-(4,5-(P(E)Ph2)2tz}2] [M=Zr, E=S, R=Me (11), Et (12); M=Hf, E=S, R=Me (13), Et (14); M=Zr, E=Se, R=Et (15); M=Hf, E=Se, R=Et (16)] were obtained from the silylated derivatives [SiMe3{κ1-N-(4,5-(P(E)Ph2)2tz}] [E=S(9), Se(10)] and the corresponding metal amides M(NR2)4. In addition, the facile hydrolysis of 5, 7 and 8 with trace amounts of water led to the isolation of compounds 17–19, which contain Ti–O–Ti frameworks.