Seven-membered Heterocyclic Ring Research Articles

Synthesis of benzimidazole-fused 1,4-benzoxazepines and benzosultams spiro-connected to a 2-oxindole core via a tandem epoxide-opening/SNAr approach.

While hundreds of literature reports describe the preparation of spirooxindole-based five- and six-membered heterocycles, the construction of seven-membered heterocyclic rings spiro-connected to a 2-oxindole core has so far been less developed. Herein, we disclose a base-mediated (4 + 3) annulation of spiro-epoxyoxindoles and 2-(2-fluoroaryl)-1H-benzoimidazoles or 2-fluoro-N-arylbenzenesulfonamides toward the synthesis of two new classes of spirooxindole-based polycyclic systems. Mechanistically, this conceptually simple and high atom-economical reaction proceeds via an SN2-like intermolecular epoxide ring-opening, accompanied by a concomitant intramolecular SNAr reaction. From a synthetic aspect, the notable features of the process are its full regioselectivity, operational simplicity using readily available substrates under transition-metal-free conditions, high yields, and broad substrate scope.

Synthesis, Characterization, and Evaluation of Antioxidant and Physical Properties of New Bifunctional Aromatic Monomers Containing Imine and Heterocyclic Rings in The Main Chain.

New various monomers with di amine functional groups have been synthesized, containing di azomethine or di seven-membered heterocyclic rings in the backbone. A condensation reaction of benzidine with 4-amino benzaldehyde with some drops of glacial acetic acid in ethanol absolute prepared bi-functional amino groups monomer with azomethine core P1(4-[(1E)-[4[4-(E)-(4-aminophenyl)methylidene]amino]phenyl}phenylimino methyl aniline). The next step was the Cycloaddition reaction of P1 with succinic, malic, and phthalic anhydrides used to obtain aromatic heterocyclic monomers with oxazepane and oxazepine rings containing lactone and lactam groups. All the synthesized monomers were characterized spectrally with many techniques (FT.IR,1 H1.NMR, C13-NMR) that were used to investigate the functional groups in the structure of monomers. Monitoring the progress and completion of the reaction was performed using thin-layer chromatography (TLC). Physical characterizations, including detecting the melting point, purity, colour, retardation factor, molecular formula, and molecular weight, the polarized optical microscope (POM) used for Image-based microscopic interpretation of prepared compounds. All the prepared monomers are considered effective antioxidant agents as they give free radicals scavenging over 60%, reaching 80 %; this activity makes them useful in large numbers of industries as they can scavenge the free radicals that the industrial product may be exposed, which increases its shelf life and enhance its effectiveness.

Dimeric Benzodiazepines as Peptide Mimetics to Overcome p53-Dependent Drug Resistance of Tumors.

Benzodiazepines that consist of one α- and one β-amino acid residues linked together in a seven-membered heterocyclic ring could be treated as small, rigid, cyclic dipeptides capable of exhibiting a wide range of biological activities. During our research on novel analogues of anthramycin, a tricyclic antibiotic benzodiazepine, we developed the synthesis of two benzodiazepine dimers, obtained through the cyclization of appropriate linear tripeptides. The synthesized compounds were tested on a panel of seven cancer and normal cell lines. The developed molecules exhibited promising cytotoxic activity against the lung cancer cell lines A549 and NCI-H1299 and the epidermoid carcinoma cell line A-431. Moreover, they showed significant selectivity compared to the reference cell lines (BJ-human normal skin fibroblasts and MRC-5-human normal lung cell line). When tested on two isogenic cell lines, HCT116 and HCT116p53-/- (colon cancer), contrary to cisplatin being used as a positive control, the obtained compounds showed a cytotoxic effect independent of the p53 protein status. For the above reasons, the obtained compounds can be considered a new group of promising anticancer agents, useful in the fight against p53-dependent drug resistance in cancers. They can also be treated as convenient, leading structures suitable for further optimization and searching for more active and selective molecules.

The skeleton of 5,7-fused bicyclic imidazole-diazepine for heat-resistant energetic materials

In light of the low yields and complex reaction routes of some well-known 5,5-fused and 5,6-fused bicyclic compounds, a series of 5,7-fused bicyclic imidazole-diazepine compounds were developed with high yields by only two efficient steps. Significantly, the seven-membered heterocyclic ring has a stable energetic skeleton with multiple modifiable sites. However, the 5,7-fused bicyclic energetic compounds were rarely reported in the area of energetic materials. Three neutral compounds 1, 2 and 4 were synthesized in this work. To improve the detonation performances of the 5,7-fused neutral compounds, corresponding perchlorate 1a and 2a were further developed. The physicochemical and energetic performances of all newly developed compounds were experimentally determined. All newly prepared energetic compounds exhibit high decomposition temperatures (Td: 243.8–336 °C) and low mechanical sensitivities (IS: >15 J, FS: >280 N). Among them, the velocities performances of 1a (Dv = 7651 m/s) and 4 (Dv = 7600 m/s) are comparable to that of typical heat-resistant energetic material HNS (Dv = 7612 m/s). Meanwhile, the high decomposition temperature and low mechanical sensitivities (Td = 336 °C; IS = 32 J; FS > 353 N) of 4 are superior to that of HNS (Td = 318 °C; IS = 5 J; FS = 250 N). Hence, the 5,7-fused bicyclic compounds with high thermostability, low sensitivities and adjustable detonation performance have a clear tendency to open up a new space for the development of heat-resistant energetic materials.

Biheterocyclic Coumarins: A Simple Yet Versatile Resource for Futuristic Design and Applications in Bio-molecular and Material Chemistry

Abstract: Coumarin derivatives occur widely in nature and are a part of both traditional and modern advancements in synthesis and application. To date, thousands of coumarin derivatives have been synthesized in lab or isolated from plant and marine life. These are essentially 2- pyrone core fused with a benzene ring and belong to the family of aromatic oxygen heterocycles. Coumarin in conjugation with various other heterocyclic systems has provided a robust framework for tuning the properties associated with the parent structure. The frequency of reports has increased for these biheterocyclic systems from the mid twentieth century. Biheterocyclic coumarins have also attracted the attention of many organic and pharmaceutical chemists as these systems serve as useful synthetic intermediates in the synthesis of analogs of existing drugs. Their application in the design of effective organocatalysts and chemosensors has further extended their versatility. Coumarin biheterocyclic core is utilized in the rational design and tuning of complex molecular entities in molecular recognition, analytical and material chemistry. This review highlights the advancements in the synthesis and applications of coumarin-linked nitrogen, oxygen, and sulfur heterocycles. It also provides an account of five-, six-, and seven-membered heterocyclic rings linked to coumarin core. Critical physicochemical properties coupled with their application will make this review useful for synthetic chemists and drug discovery labs. A comprehensive spectrum of literature in this review will facilitate further development of biheterocycles along with their promising applications in the future.

A Modular Approach to Dibenzo-fused ϵ-Lactams: Palladium-Catalyzed Bridging-C-H Activation.

Tricyclic ring systems possessing a dibenzo structure joined to a seven-membered heterocyclic ring frequently show important biological activities. However, a modular approach to these molecules based on efficient intermolecular reaction of readily available chemicals is lacking. Herein, an unprecedented palladium-catalyzed formal [4+3] annulation for modular construction of these tricyclic systems is described. This reaction features easily accessible reactants (o-haloarylaldehydes and N-tosylhydrazones), broad substrate scope, and excellent functional group compatibility. The synthetic potential is demonstrated by the easy scale-up reactions, late-stage modification of complex molecules, and collective synthesis of bioactive molecules and approved drugs.

Synthesis, Identification and Biological Activity of New Heterocyclic Compounds from Reaction of New Schiff-Bases with Phathalic Anhydride

Series of new Schiff bases and their derivatives (Oxazepine) have been synthesized during two steps. The first step synthesis of imines derivatives (1-10) by the condensation reaction of 1, 7-diaminohepatane and 1,8-diaminooctane with different substituted aromatic aldehydes by using glacial acetic acid as catalyst. The second step includes reaction of the prepared Schiff bases derivatives with phathalic anhydride in dry benzene to obtain seven-membered heterocyclic ring derivatives (11-15). The biological activities of some prepared compounds were also studied against different kinds of bacteria. The new derivatives were confirmed by suing a range of experimental techniques including 1HNMR, 13C NMR, IR and Mass spectra.

Intramolecular Aminoazidation of Unactivated Terminal Alkenes by Palladium-Catalyzed Reactions with Hydrogen Peroxide as the Oxidant.

The palladium-catalyzed aminoazidation of aminoalkenes yielding azidomethyl-substituted nitrogen-containing heterocycles was developed. The procedure requires oxidative conditions and occurs at room temperature in the presence of hydrogen peroxide and NaN3 as the azide source. These conditions provide selective exo-cyclization/azidation of the carbon-carbon double bond, furnishing a versatile approach toward five-, six-, and seven-membered heterocyclic rings.

Получение 1-метил-5-фенил-7-хлор-1,3-дигидро- 2Н-[1,4]-бензодиазепина-2-она

At present, benzodiazepine derivatives being used widely, they continue to occupy a leading position among the drugs of the anxiolytic group. Most anxiolytics of the benzodiazepine structure are derivatives of 1,4-benzodiazepine. The basis of the chemical benzodiazepine structure consists of a benzene ring connected to a seven-membered heterocyclic ring containing two nitrogen atoms (diazepine) at positions 1 and 4. All the benzodiazepine derivatives used in the clinic also have a second benzene ring attached to carbon. The presence of a halogen or a nitro group is essential to display its activity. Diazepam (1-methyl-5-phenyl-7-chloro-1,3-dihydro-2H- [1,4] benzodiazepin-2-one) is in the list of necessary and important medicinal products. The urgent issue is the development of a new method to synthesize 1-methyl-5-phenyl-7-chloro-1,3-dihydro-2H-[1,4]-benzodiazepines-2-one that would allow producing the drug in the required quantities and for mass consumption. The search for possible effective ways of synthesizing 1-methyl-5-phenyl-7-chlorine-1,3-dihydro-2H-[1,4]-benzodiazepines-2-one for manufacturing application is of great scientific and practical interest. The purpose of our work is to search for a rational method to synthesize the target product, experimental study of the chemical processes to develop the most optimal methods to produce the product. The technology to produce 1-methyl-5-phenyl-7-chlor-1,3-dihydro-2H-[1,4]-benzodiazepine-2-one on an industrial scale was developed. The synthesis of 2-benzoyl-2',4-dichloro-N-methylacetanilide by condensation of 2-methylamine-5-chlorobenzophenone with chloracetyl chloride in carbon tetrachloride without further treatment of the reaction mass with water and sodium carbonate was developed. The highest yield of 1-methyl-5-phenyl-7-chlorine-1,3-dihydro-2H-[1,4]-benzodiazepines-2-one was shown to be obtained if the cyclization reaction is carried out in isopropyl alcohol. The reaction mixture composition in interaction of 2-benzoyl- 2',4 -dichloro-N-methylacetanilide with urotropin plays the defining role in the formation of the target product.

Synthesis and Identification of Heterocyclic Compounds (Oxazepine, Tetrazole) Derived from Benzidine as Photostabilizing for Poly vinyl chloride

This research describes preparation of new four compounds (A2-A5) having 1,3-oxazepine and Tetrazole rings. The first step involves reaction of benzidine (A1) with aromatic aldehyde (cinnamaldehyde) in ethanol as a solvent in the presence of acid as catalyst to yield the Schiff base (A2), Schiff base (A2) was condensed with maleic anhydride and phthalic anhydride in dry benzene to give a seven-membered heterocyclic ring derivative (A3, A4), In addition, we synthesis novel tetrazole derivative (A5) from the reaction of Schiff base (A2) with sodium azide in tetrahydrofuran. The structure of synthesized compounds were identified by spectral methods [FTIR, ¹H-NMR, and ¹³C-NMR] and measurement physical properties. The photo stabilization of poly (vinyl chloride) films by compounds (A1-A5) was studied. The Photostabilization activities of these compounds were determined by monitoring the carbonyl and hydroxyl indexes values with irradiation time. The changes in viscosity average molecular weight of PVC with irradiation time were studied by using tetrahydrofuran as a solvent. The influence of concentrations additives (range 0.1-0.5wt) on the rate of photodegradation and Photostabilization course was studied. Therefore, we found that was an increase Photostabilization rates with increasing concentrations of additives. In addition, Studying the effect of film thickness and the results showed that an increase in film thickness would reduce the rate of photolysis. The results indicated that Photostabilisation proportion of plastic in the presence of additives follow the trend: (PVC blank) > PVC+A1> PVC+A2 > PVC+A5> PVC+A4> PVC+A3. According to the results obtained, it proposed mechanisms depending on the structure of the additive.

Hydride transfer initiated ring expansion of pyrrolidines toward highly functionalized tetrahydro-1-benzazepines.

A novel hydride transfer initiated ring expansion of 4-pyrrolidinyl isatins to synthesize tetrahydro-1-benzazepines has been developed. This methodology represents an atom- and step-economical protocol to assemble seven-membered polycyclic amines from pyrrolidine derivatives in one step.

Synthesis, Characterization, Biological Activity Studies of Schiff Bases and 1,3-Oxazipene Derived from 1,1 -Bis (4-aminophenyl) -4-Phenyl Cyclohexane

A series of new Schiff bases and 1, 3-Oxazepine derivatives have been synthesised from condensation compound (1,1 -bis (4-aminophenyl) -4-phenyl cyclohexane [C1] with different aromatic aldehydes in the presence of catalytic glacial acetic acid to produce the Schiff bases [2-4]. These Schiff bases were reacted with maleic anhydride and phthalic anhydride in dry benzene to give seven-membered heterocyclic ring derivatives [5-10]. The structure formula of these compounds were confirmed by using FT-IR, (1H and 13C) NMR spectroscopy. The synthesized compounds were screened for their anti‐bacterial activity using ampicillin as a standard drug.

Novel oxazepinedione-derived symmetric dimers: synthesis and mesophase characterisation of seven-membered heterocyclic compounds

ABSTRACTThe synthesis and characterisation of three sets of symmetric dimeric compounds composed of seven-membered oxazepinedione heterocyclic rings were carried out. All the dimers possess the tetradecyl- (n = 14) alkyl side chain attached to the nitrogen atom of the oxazepinedione core. The oxazepinedione core in turn was connected with varied connecting spacers (n = 4, 6, 8, 10 and 12). The dimers were spectroscopically characterised by FT-IR, 1H-NMR, 13C-NMR and elemental analysis techniques. The compounds were investigated for liquid crystalline properties using differential scanning calorimetry and polarising optical microscopy with heating assembly. The precursor imines 2a–e itself started exhibiting liquid crystalline SmA/tilted hexatic mesophase. Further fusion of 2a–e with maleic anhydride, succinic anhydride and phthalic anhydride gave the novel oxazepinedione-derived symmetric dimers 3a–e, 4a–e and 5a–e respectively. The dimers 3a–e and 4a–e did not exhibit any liquid crystal (LC) properties. However, the phthalic anhydride-fused oxazepinediones 5a–e show monotropic nematic liquid crystalline phase. The results indicate that the formation of mesophase is dependent on the type of fused oxazepinedione ring.

Mixed Boron(III) and Phosphorous(V) Complexes of meso-Triaryl 25-Oxasmaragdyrins.

Two unprecedented mixed B(III) /P(V) complexes of meso-triaryl 25-oxasmaragdyrins were synthesized in appreciable yields under mild reaction conditions. These unusual 25-oxasmaragdyrin complexes containing one or two seven-membered heterocyclic rings comprised of five different atoms (B, C, N, O, and P) were prepared by reacting B(OH)(Ph)-smaragdyrin and B(OH)2 -smaragdyrin complexes, respectively, with POCl3 in toluene at reflux temperature. The products were characterized by HRMS and 1D- and 2D-NMR spectroscopy. X-ray crystallography of one of the mixed B(III) /P(V) smaragdyrin complexes indicated that the macrocycle is significantly distorted and contains a stable seven-membered heterocyclic ring within the macrocycle. The bands in the absorption and emission spectra were bathochromically shifted with reduced quantum yields and singlet-state lifetimes relative to the free base, meso-triaryl 25-oxasmaragdyrin. The mixed B(III) /P(V) complexes were difficult to oxidize but easier to reduce than the free base. The DFT-optimized structure of the 25-oxasmaragdyrin complex with two seven-membered heterocycles indicated that it was a bicyclic spiro compound with two half-chair-like conformers. This was in contrast to the chair-like conformation of the complex with a single seven-membered heterocyclic ring. Moreover, incorporation of a second phosphate group in the former case stabilized the bonding geometry and resulted in higher stability, which was reflected in the bathochromic shift of the absorption spectra, more-positive oxidation potential, and less-negative reduction potential.

ChemInform Abstract: A Facile, One Pot Method for the Synthesis of 4‐Acyl‐1,2‐dihydro‐3‐benzazepines, Based on the Ring Expansion of Natural and Synthetic 3,4‐Dihydroisoquinoline Pseudo Bases.

Abstract A new, one-pot approach to 4-acyl-1,2-dihydro-3-benzazepines has been proposed proceeding via a six- to seven-membered heterocyclic ring expansion under the action of α-haloketones.

A facile, one pot method for the synthesis of 4-acyl-1,2-dihydro-3-benzazepines, based on the ring expansion of natural and synthetic 3,4-dihydroisoquinoline pseudo bases

A new, one-pot approach to 4-acyl-1,2-dihydro-3-benzazepines has been proposed proceeding via a six- to seven-membered heterocyclic ring expansion under the action of α-haloketones.

Crystal structure of 6,9-dimethyl-7H-[1,2,4]triazolo[4,3-b][1,2,4]triazepin-8(9H)-one 0.40-hydrate.

In the mol­ecule of the title compound, C7H9N5O·0.40H2O, the seven-membered heterocyclic ring exhibits a boat conformation, whereas the five-membered triazole ring is almost planar (r.m.s. deviation = 0.005 Å). In the crystal, centrosymmetric dimers are linked by pairs of C—H⋯O hydrogen bonds into dimers, which are further connected via O—H⋯N and C—H⋯N hydrogen bonds, forming a three-dimensional network. The structure contains a partially occupied water mol­ecule lying on a twofold axis with an occupancy factor of 0.4.

Hexafluoroantimonic Acid Catalysis: Formal [3+2+2] Cycloaddition of Aziridines with Two Alkynes

A practical method for the synthesis of azepine derivatives, a typical seven-membered heterocyclic ring system, was developed and involves the use of hexafluoroantimonic acid to catalyze a formal [3+2+2] cycloaddition of aziridines with two alkynes. This method was applicable to two of the same or different terminal alkynes for the [3+2+2] cycloaddition with unactivated aziridines, and furnished the corresponding azepine derivatives in good yields with good levels of chemo- and regioselectivity. The mechanism was also discussed according to the results of the in situ HRMS and (1)H NMR analysis.

Methods for the synthesis of xanthine-derived polycyclic fused systems

Abstract Xanthines are a widely known group of alkaloids, commonly used as bronchodilators and psycho and cardiac stimulants. Most of their actions are principally connected with either antagonism of adenosine receptors or phosphodiesterase inhibition; nevertheless, other profiles of their biological activity – antiviral, antitumor or anticancer – are also known. Here, we present a review of the main synthetic methods to obtain xanthine-derived heterocyclic fused systems. The five-, six- or seven-membered heterocyclic ring is attached to the purine-2,6-dione core with one or two bridgehead (ring junction) nitrogen atoms. The biological activity profile of the individual heterocyclic systems is mentioned.

Synthesis and Anti-Bacterial Study of Novel Compounds with Bis ( Four- , five- , and Seven-Membered ) Heterocyclic Rings

Synthesis and Anti-Bacterial Study of Novel Compounds with Bis ( Four- , five- , and Seven-Membered ) Heterocyclic Rings