Synthesis Of Novel Benzo Research Articles

Synthesis of novel benzo[d] imidazole bearing α-aminophosphonate and their antimicrobial evaluation

The antimicrobial activity of seven α-aminophosphonate derivatives was evaluated. These new compounds were synthesized via a one-pot reaction of the Kabachnik-Fields between 2-((1H-benzo[d]imidazol-2-yl)thio)acetohydrazide, aldehyde derivatives, and diethyl phosphite in the presence of magnesium triflate as a catalyst. The novel compounds are identified by analytical and spectroscopic techniques. The use of magnesium triflate as a catalyst revealed short reaction time (1 h), in 10 mol%.The activity of the new compounds was against the Gram-positive bacteria Bacillus cereus, and Staphylococcus aureus, as well as the Gram-negative bacteria Salmonella typhimurium, Escherichia coli, Pseudomonas aeruginose, and the fungus Candida albicans. The results indicated that most of the new compounds have moderate to high potency as antibacterial and antifungal agents. And the theoretical study confirmed that the compounds excel in binding with a more stable binding energy than the antibiotic penicillin, and this was confirmed by laboratory results. In the case of Escherichia coli ATCC® 25922™, only 5a and 5e displayed significant inhibitory activities equal to or greater than the reference drug. Most of the new compounds (5c–5 g) revealed high potency against Salmonella typhimurium ATCC® 14028™. The highest value is for 5d which has the high inhibitory activity against Cadida albicans.

A green and eco-efficient protocol for the synthesis of benzo-[7]-annulene-1,3-dicarbonitriles by using simple mortar pestle grinding

The synthesis of novel benzo-[7]-annulene-1,3-dicarbonitrile analogues has been accomplished using an environmentally friendly and green protocol. This mortar and pestle grinding method that is both ethically responsible and commercially practical. By producing the necessary benzo-[7]-annulene-1,3-dicarbonitrile analogues with good results (89%–97%) in a short reaction time (≤30 min), this approach successfully indicates that even aldehydes with severe steric hindrance play an active part in the process. The faster work-up processes, the reduction of operating difficulties, and the increased yields are notable among its advantages over earlier systems. This strategy uses a mortar and pestle grinding method, which is well known for following guidelines that are both economically sensible and environmentally friendly. It is important to note that this novel approach offers a considerable advancement over earlier approaches that were characterized by drawn-out work-up procedures, operational complexity, and low yields.

Application of the aza‐Wittig reaction for efficient synthesis of diversely substituted benzo[f]Chromeno[2,3‐d]pyrimidine and benzo[f]chromeno[2,3‐d][1,2,4]triazolopyrimidine derivatives

AbstractAn efficient synthesis of novel benzo[f]Chromeno[2,3‐d]pyrimidine and unknown benzo[f]chromeno[2,3‐d][1,2,4]triazolopyrimidine derivatives is described utilizing ethyl‐2‐amino‐4‐phenyl‐4H‐benzo[f]chromene‐3‐carboxylate as precursor via aza‐Wittig reaction. The process proved to be simple, high‐yielding, and efficient.

Synthesis of two nitrogen-containing polyaromatic compounds through gold catalysis/DBU-promoted cyclizations.

This work reports an efficient synthesis of novel benzo[7,8]indolizino[2,3,4,5-ija]quinazoline derivatives between 2-(2-ethynylaryl)acetonitriles 1 and anthranils 2. The synthetic approach involves the initial formation of 7-formylindole intermediates that can be implemented by DBU to activate a novel indole-nitrile-aldehyde cyclization.

Multicomponent domino protocol for the one-pot synthesis of novel benzo[a]phenazin-5-ol derivatives

Multicomponent domino protocol for the one-pot synthesis of novel benzo[a]phenazin-5-ol derivatives

Synthesis of novel benzo[6,7]cyclohepta[1,2-b]thieno[3,2-e]pyridines and their bis-analogues linked to different spacers: Approach to a new ring system

The synthesis of benzosuberone-fused heterocyclic derivatives is an increasingly intriguing subject. The current study reports the synthesis of the new ring system benzo[6,7]cyclohepta[1,2-b]thieno[3,2-e]pyridine. At first, new 2-thioxo-2,5,6,7-tetrahydro-1H-benzo[6,7]cyclohepta[1,2-b]pyridine-3-carbonitriles were prepared and taken as versatile precursors for the present study. Afterward, a succession of α-bromoketones were combined with the newly generated synthons in ethanol that also included two equivalents of sodium ethoxide. After 2–3 h of heating at reflux, a novel series of benzo[6,7]cyclohepta[1,2-b]thieno[3,2-e]pyridines was obtained in 86–93% yields. Using a similar protocol, a novel series of benzosuberone-fused bis(thieno[3,2-e]pyridines) linked to different spacers was obtained. Therefore, two pyridine-2(1H)-thiones equivalents were reacted with one equivalent of the respective bis(α-bromoketones) in ethanol containing four equivalents of sodium ethoxide. The reaction mixture was refluxed for 4–6 h to produce the corresponding bis(benzo[6,7]cyclohepta[1,2-b]thieno[3,2-e]pyridines) in 67–76% yields. Both spectral data and elemental analyses were used to elucidate the structure of new products.

Synthesis of Novel Benzo[b][1,6]naphthyridine Derivatives and Investigation of Their Potential as Scaffolds of MAO Inhibitors.

In this work, 2-alkyl-10-chloro-1,2,3,4-tetrahydrobenzo[b][1,6]naphthyridines were obtained and their reactivity was studied. Novel derivatives of the tricyclic scaffold, including 1-phenylethynyl (5), 1-indol-3-yl (8), and azocino[4,5-b]quinoline (10) derivatives, were synthesized and characterized herein for the first time. Among the newly synthesized derivatives, 5c-h proved to be MAO B inhibitors with potency in the low micromolar range. In particular, the 1-(2-(4-fluorophenyl)ethynyl) analog 5g achieved an IC50 of 1.35 μM, a value close to that of the well-known MAO B inhibitor pargyline.

One-pot synthesis of new benzo[4,5]imidazo[2,1-b]pyrimido[4,5-d][1,3] thiazine-2,4(3H)-dione and benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one derivatives as new anti-cancer components

An efficient and one-pot process has been developed for the synthesis of novel benzo[4,5]imidazo[2,1-b]pyrimido[4,5-d][1,3]thiazine-2,4(3H)-diones and benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-ones from CH acids, aldehydes and 2-mercaptobenzimidazole using hexyltriphenylphosphonium bromide ionic liquid (HTPB) as a green promoter and solvent at ambient temperature. The reaction afforded products in high yields and short reaction times, bypassing the conventional harsh reaction conditions and without the need for using volatile solvents. In addition, we evaluated the anti-cancer activity of these compounds on different cancer cells, including A431, PC3, and Panc1 and HDF (human dermal fibroblast) normal cells. Notably, we found that these synthesized compounds have prominent anti-cancer effects on skin, prostate, and pancreatic cancers.

Synthesis and antimicrobial activity of novel benzo[4', 5']-imidazo[1',2':1,2]pyrrolo[3,4-b]isoxazolo[4,5-e]pyridines

Synthesis of novel benzo [4',5'] imidazo [1',2':1,2] pyrrolo [3,4- b ] isoxazolo [4,5- e ] pyridines 8 has been achieved by reaction of 1-(prop-2-yn-1-yl)-1 H -benzo [ d ] imidazo-2-carbaldehydes 5 with 5-amino -3-methylisoxazole 6 in presence of InCl 3 in CH 3 CN media, followed by reaction of imine 7 with BF 3 .Et 2 O in DCE at 80°C. The newly synthesized title compounds 8 have been evaluated for their in vitro antimicrobial activity. Compounds 8 exhibit potent antimicrobial activity compared to that of standard drugs.

Microwave-assisted synthesis of benzo[b]phosphole oxide derivatives by oxidative addition of acetylenes and secondary phosphine oxides or alkyl phenyl-H-phosphinates

A new and practical microwave (MW)-assisted method was developed for the fast and efficient oxidative addition of secondary phosphine oxides or alkyl phenyl-H-phosphinates and acetylenes. The reaction was optimized in respect of the oxidative agent, the reaction time, the temperature and the molar ratio of the starting materials. The protocol developed enabled the synthesis of novel benzo[b]phosphole oxide derivatives under mild conditions for a short reaction time. By the use of special reagents, such as alkyl phenyl-H-phosphinates or ethyl phenylpropiolate, reactive groups (phosphinic acid ester and carboxylic ester) could be integrated into the benzophosphole skeleton, which may be further functionalized towards various synthetic directions, therefore, fine-tuning the optical properties of the target molecules. The crystal structure of a benzo[b]phosphole oxide derivative was investigated by X-Ray diffraction, which gave structural information about the compound and its molecular interactions in the crystal.

An Efficient, Green, Microwave-assisted Synthesis of Benzo[a]furo[2, 3-c]phenazine Derivatives with TiO2-SO3H as Cost-effective and Recyclable Catalyst under Solventfree Conditions.

A rapid, efficient, and environmentally benign procedure for the synthesis of novel furo [2,3-c]phenazine derivatives has been developed via reactions of 2-hydroxynaphthalene-1,4-dione, arylglyoxals, and indole in the presence of TiO2-SO3H-catalyst (TSAC) as a recyclable heterogeneous catalyst under solventfree conditions using microwave irradiation. This study describes a successful approach for the synthesis of 2-(4-bromophenyl)-1-(1H-indol-3- yl) benzo[a]furo[2,3-c] phenazine in the presence of TiO2-SO3H-catalyst using microwave irradiation. In this paper, we report an efficient and convenient method for the synthesis of phenazine derivatives from benzo[a]phenazin-5-ol, arylglyoxal derivatives, and indoles in the presence of TiO2-SO3H-catalyst under microwave irradiation. All reagents and solvents were purchased from Merck and Aldrich and used without further purification. 1H NMR spectra (DMSO) were recorded on the Gemini-500 MHz spectrophotometer with TMS as an internal standard. To investigate the reaction conditions for the synthesis of 2-(4-bromophenyl)-1-(1Hindol- 3-yl) benzo[a]furo [2, 3-c] phenazine derivatives, we performed a reaction between 2-hydroxynaphthalene- 1,4-dione (1 mmol) and aromatic 1,2-diamines (1 mmol) as a model. We demonstrated a green and straightforward procedure for the efficient synthesis of novel benzo[ a]furo[2, 3-c] phenazine derivatives in high yields via a one-pot, four-component domino protocol by using TiO2-SO3H as a mild, effective, non-toxic, and inexpensive solid acid catalyst without the addition of an organic co-solvent.

Synthesis of novel benzo[4,5]imidazo[1,2-a]pyrimido- [4,5-d]pyrimidine derivatives as potent antimicrobial agents

Synthesis of novel benzo[4,5]imidazo[1,2-a]pyrimido[4,5-d] pyrimidines 5/6 has been achieved by reaction of 2-amino-4-aryl-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carbonitriles 4 with formaldehyde/urea. The key intermediate 4, is obtained by reaction of 2-aminobenzaldehyde 1 with aromatic aldehyde and malononitrile by a three-component one-pot process. The newly synthesized title compounds 5/6 have been evaluated for their in vitro antimicrobial activity. Compounds 5 and 6 exhibit potent antimicrobial activity compared to that of standard drugs.

DABCO-catalyzed Five-component Domino Protocol for the Synthesis of Novel Benzo[a]pyrazolo[4’,3’:5,6]pyrano[2,3-c]phenazines in PEG-400 as an Efficient Green Reaction Medium

Currently green chemistry techniques are attracting wide attention due to their environmental, health, and economic benefits. These green techniques include the use of polyethylene glycol (PEG-400)...

One-pot, multi-component synthesis of ethyl (E)-1-(3-ethoxy-3-oxoprop-1-en-1-yl)-2-aryl-2,5-dihydro-1H-benzo[b][1,4]diazepine-3-carboxylate derivatives

A new methodology for the synthesis of novel benzo[b][1,4]diazepine derivatives via a one-pot, multi-component reaction of benzaldehyde, o-phenylenediamine, and ethyl propiolate has been developed. Readily available starting materials, operationally simple, metal-free reaction conditions, simplicity of product isolation and good yields are key advantages of this methodology. The structure of the benzo[b][1,4]diazepines were confirmed by NMR, HRMS and XRD.

Amine‐carbon disulfide promoted synthesis of novel benzo[e][1,3]thiazepin‐5(1H)‐one derivatives

AbstractIn this paper, a simple method is introduced for the synthesis of novel 4‐substituted‐3‐thioxo‐3,4‐dihydrobenzo[e][1,3]thiazepin‐5(1H)‐one derivatives. The synthesis is based on a two‐step reaction of 2‐methylbenzoic acid, an amine, and carbon disulfide. In the first step, 2‐methylbenzoic acid reacts with sulfuric acid in ethanol, followed by the reaction with N‐bromosuccinimide to produce ethyl 2‐(bromomethyl)benzoate. Amine and carbon disulfide react in a separate flask in basic medium to give carbamodithioate salt. Carbamodithioate and ethyl 2‐(bromomethyl)benzoate react together in dimethylformamide to produce the desired 4‐substituted‐3‐thioxo‐3,4‐dihydrobenzo[e][1,3]thiazepin‐5(1H)‐one derivatives. The method is simple and fast and is applicable to a wide variety of substrates and gives the desired products in high isolated yields.

NiFe2O4@SiO2@glucose amine nanoparticle catalyzed reaction of azo-linked thiosalicylic acid with CO2: Access to azo-linked benzo[d]oxathiine-2,4-diones

The first, clean, environmentally benign and effective synthesis of novel benzo[d]oxathiine-2,4-dione derivatives via reaction of synthetized azo-linked thiosalicylic acid with carbon dioxide promoted by amino glucose‐functionalized silica‐coated NiFe2O4 nanoparticles in aqueous media without using any other harmful organic solvents or reagents was reported. The catalyst could easily be separated from the reaction mixture by using an external magnetic field and it was reusable. High purity of the desired products, eco‐friendliness, aqueous media, short reaction time and easy workup procedure can be mentioned as the other advantages of this method. All of synthesized compounds were characterized by IR, NMR and elemental analyses.

Microwave-assisted Multi-component Domino Reaction for the Green Synthesis of Novel Benzo[a]pyrano[3',4':5,6]pyrano[2,3-c]phenazines Using H3PW12O40 as Efficient, Cost-effective and Recyclable Catalyst

In recent years, green chemistry techniques have attracted considerable attention in the chemical industry and academic research laboratories due to environmental, health, and economic benefits.1–5...

H3PW12O40@nano‐ZnO: An efficient, recyclable, and eco‐friendly catalyst for the green synthesis of novel benzo[a]pyrimido[5′,4′:5,6]pyrano[2,3‐c]phenazines via sequential multicomponent reactions under microwave irradiation

A simple, efficient, single‐pot synthesis of novel heteroaryl‐substituted benzo[a]pyrimido[5′,4′:5,6]pyrano[2,3‐c]phenazines has been developed via initial Knoevenagel, subsequent Michael, and final heterocyclization reactions of 2‐hydroxynaphthalene‐1,4‐dione, o‐phenylenediamine, aromatic aldehydes, and barbituric acid in the presence of H3PW12O40@nano‐ZnO as a recyclable heterogeneous catalyst in EtOH under microwave irradiation (MWI). This sequential green process with several advantages, such as operational simplicity, high yield, low cost, easy handling, eco‐friendliness and reusability of the catalyst, absence of any tedious work‐up or purification, and avoidance of hazardous or toxic reagents/catalysts/solvents, opens an effective and convenient way to pyrano‐functionalized benzophenazine systems, which are promising compounds for different biomedical applications.

Nano-Fe3O4-Promoted Five-Component Domino Reactions for the Green Synthesis of Novel Benzo[a]phthalazino[2′,3′:1,2]pyrazolo[3,4-c]phenazines in PEG-400 as an Efficient Eco-Friendly Reaction Medium

ABSTRACTNovel benzo[a]phthalazino[2′,3′:1,2]pyrazolo[3,4-c]phenazines containing both biologically active benzophenazine and pyrazolophthalazine templates are synthesized using a single-pot, five-component reaction involving 2-hydroxynaphthalene-1,4-dione, aromatic 1,2-diamines, hydrazine hydrate, phthalic anhydride, and benzaldehydes catalyzed by magnetic iron(III) oxide nanoparticles (Fe3O4 MNPs) in polyethylene glycol (PEG-400) as an inexpensive, non-toxic, and effective medium at 70°C. In this domino protocol, seven bonds (C−C, 4C−N, 2C=N) and three new rings are efficiently formed and this new green process provides the salient features such as the following: operational simplicity, high yields, low cost, reusability of Fe3O4 MNPs and PEG-400, absence of any tedious workup or purification, and avoidance of hazardous or toxic reagents/catalysts/solvents.

Organocatalytic approach toward the green one-pot synthesis of novel benzo[f]chromenes and 12H-benzo[5,6]chromeno[2,3-b]pyridines

An efficient tandem reaction approach is described to prepare novel benzo[f]chromenes from 2,3-dihydroxynaphthalene, malononitrile and aldehydes using 10 mol% guanidine hydrochloride as the catalyst under solvent-free conditions. The method was also extended to the preparation of novel 12H-benzo[5,6]chromeno[2,3-b]pyridines from 2-aminoprop-1-ene-1,1,3-tricarbonitrile instead of malononitrile under the same reaction conditions. The described one-pot three-component reaction is characterized by short reaction times, high-product yield, mild reaction conditions, simple workup procedure, and simple purification.