Current Organic Synthesis - Volume 21, Issue 7, 2024

Among the many reports published on strategies applicable to synthesizing pyrazolines and its analogs, The 1,3-dipolar cycloaddition offers a remarkably wide range of utility. Many 1,3-dipolar cycloaddition reactions used for the synthesis of pyrazolines provide better selectivity, eco-friendly, and less expensive chemical processes. In the presented study, we have reviewed various recently adopted strategies for the synthesis of pyrazoline, which followed the 1,3-dipolar cycloaddition reactions mechanism and classified them based on starting materials such as nitrile imines, diazo compounds, different zwitter ions, chalcones, and isoprene units. The manuscript also focused on the synthesis of pyrazolines starting from Seyferth−Gilbert reagents (SGR) and Psilostachyin (PSH) reagents. We hope this work will help those engaged or have plans to research pyrazoline or its analogs, as synthetic protocols based on starting material are rarely available for pyrazolines. Thus, this article holds a valuable complement to the development of newer pyrazoline and its derivatives.

Medical researchers have paid close attention to the green synthesis of oxazine and thiazine derivatives since they provided a lead molecule for the creation of numerous possible bioactive compounds. This review provides more information on green synthesis, which will be very helpful to researchers in creating the most effective, affordable, and clinically significant thiazine and oxazine derivatives that are anticipated to have strong pharmacological effects. This has resulted in the identification of several substances with a wide range of intriguing biological functions. This article's goal is to examine the numerous green chemical processes used to create oxazine and thiazine derivatives and their biological activity. We anticipate that researchers interested in oxazine and thiazine chemicals will find this material to be useful. We anticipate that medicinal chemists looking for new active medicinal components for drug discovery and advance progress will find this review of considerable interest.

The chemistry of heterocyclic compounds has been a topic of research interest. Some five-membered heterocyclic compounds have been the subject of extensive research due to their different types of pharmacological effects. The five-membered nitrogen-containing heterocyclic compounds pyrazole, pyrazoline, and pyrazolone derivatives have a lot of interest in the fields of medical and agricultural chemistry due to their diverse spectrum of therapeutic activities. Various substituted pyrazole, pyrazoline, and pyrazolone compounds exhibited diverse pharmacological effects like Anti-microbial, anti-inflammatory, anti-tubercular, anti-fungal, anti-malarial, anti-diabetic, diuretic, anti-depressant, anticonvulsant, antioxidant, anti-leishmanial, antidiabetic, and antiviral, etc. In recent decades, the synthesis of numerous pyrazole, pyrazoline, and pyrazolone derivatives by different synthetic methods as well as research into their chemical and biological behavior have become more important. This review focuses on synthetic methods of the pyrazole, pyrazoline, and pyrazolone derivatives, which have significant biological properties and a variety of applications.

Allenamides are special allenes, and the unique reactivity, selectivity (both stereoselective and regionally selective) and stability of allenamides have been widely studied. In this review, the development of the free radical transformation of allenamides over the last few years will be summarized. This review discusses in detail in three parts: intermolecular radical addition to C- X (X = N, S, O, Se) bonds, metal salt mediated cyclization of allenamides, and photocatalytic cyclization of allenamides. In addition, reasonable details of the mechanisms are provided for the vast majority of these transformations.

Background: Pyrazolines and azo-pyrazolines are influential groups of heterocyclic compounds with two nitrogen atoms inside the five-membered ring. They play an important role in a wide range of biological processes, such as antifungal, antioxidant, antimalarial and other antimicrobial activities. Objective: The main objective of this study is to synthesize some new heterocyclic compounds with antioxidant and antimicrobial activity Methods: One-pot three components and traditional synthesis of new azo-pyrazoline compounds were achieved in this work. The preparation process has been started by diazotizing 4-(6-methylbenzothiazol-2-yl) benzamine and its coupling reaction with 4-hydroxy acetophenone producing azo-acetophenone, followed by benzylation with benzyl chloride to form the starting material, azo-benzyloxy acetophenone. A series of substituted benzaldehydes were reacted with the latter compound via one pot and classical methods, forming new chalcones containing azo linkages and benzyloxy moieties, which were then converted into new target azo-pyrazoline derivatives. Results: The structures of the synthesized compounds were confirmed by spectroscopic techniques using FT-IR, ¹H-NMR, ¹³C-NMR, and ¹³C- DEPT- 135 spectra. Finally, the synthesized compounds were screened for their antioxidant and antimicrobial activities against Staphylococcus aureus and Escherichia coli. Conclusion: Overall, the one-pot three-component synthesis of pyrazoline compounds generally provides advantages in terms of efficiency, simplicity, and time-consumption compared to classical synthesis methods. Hence, the study advocates the one-pot method because it eliminates the tedious process of making chalcones, which takes time, materials, and unnecessary effort. Therefore, this is the most convenient and effective approach to green chemistry.

Introduction: Benzothiazolamine-based bisthiourea precursors were prepared in good yields. These bisthiourea derivatives were cyclized into symmetrical Bis Methyl 2-[3-(benzothiazol- 2-yl)-2-terephthaloyl-bis-4-oxo-thiazolidin-5-ylidene]acetates, by their condensation with (DMAD) dimethyl but-2-meditate in the presence of dry methanol. Materials and Methods: All these compounds were evaluated for their biological applications. Antioxidant activities were performed by adopting a DPPH radical assay, and an in vitro enzyme inhibition assay was performed to investigate their enzyme inhibitory potential against butyrylcholinesterase (BChE) and acetylcholinesterase (AChE). Results: Molecular modeling and QSAR studies were performed to monitor the binding propensity of imidathiazolidinone derivatives with enzymes and DNA. Also, electronic and steric descriptors were calculated to determine the effect of structure on the activity of imidathiazolidinone derivatives. Conclusion: The characterization of all the synthesized compounds was done by their physical data, FT-IR, NMR and elemental analysis.

Aims: In order to study on structure-activity relationships of benzofurans. Background: Benzofuran is a kind of natural compound widely existing in nature with pharmacological effects. The development of new anticancer benzofuran derivatives has attracted more and more attention. Methods: We have introduced an active quinazoline unit into piperazine-substituted benzofuran, prepared a series of quinazoline-benzofuran compounds, and evaluated cytotoxic activity against a panel of human tumor cell lines by MTT assay. Results: 48 novel quinazoline-substituted benzofuran derivatives have been prepared, and in vitro, cytotoxic activity against five human tumor cell lines was evaluated. The results indicated that some quinazoline-benzofuran conjugates showed selective inhibitory activity against tumor cell lines. Conclusion: We have found that compound 14x displayed excellent cytotoxic activity, which could be considered a potential anticancer agent.

Background: Oxidation is a valuable tool in preparative organic chemistry. Oxoammonium salts and nitroxides have proven valuable as reagents and catalysts in this endeavor. Objective: The objective of this study is to scale up the oxidative amidation, ester formation, and nitrile formation using nitroxide as an organocatalyst. Methods: Oxidative functionalization reactions were scaled from the 1 mmol to the 1 mole level. Sodium persulfate was used as the primary oxidant, and a nitroxide was employed as a catalyst. The products of the reactions were isolated in analytically pure form by extraction with no need for column chromatography. Results: The oxidative amidation and esterification of aldehydes can be scaled up from 1 mmol to 1 mole effectively, with comparable product yields being obtained at each increment. This work shows that conditions developed on a small scale can be transferred to a larger scale without reoptimization. The oxidative functionalization of aldehydes to prepare nitriles is not amenable to direct scale-up due to the concomitant formation of significant quantities of the corresponding carboxylic acid, thereby compromising the product yield. Conclusion: Two of the three oxidative transformations studied here can be scaled up successfully from the 1 mmol to the 1 mole level.

Background: Pyrazolopyridines are interesting fused heterocyclic pharmacophores that combine pyrazole and pyridine; two privileged nuclei extensively studied and with a wide range of applications. They can be obtained by a broad variety of synthetic methods among which multicomponent reactions have gained importance, especially from 5-aminopyrazoles and dielectrophilic reagents. However, the search for new approaches more in tune with sustainable chemistry and the use of unconventional heating in three-component synthesis are open and highly relevant study fields. Methods: A novel, practical and efficient three-component synthesis of cycloalkane-fused pyrazolo[ 4,3-e]pyridines was developed through a tandem reaction of 5-aminopyrazoles, cyclic ketones and electron-rich olefins, using microwave induction in perfluorinated solvent and iodine as catalyst. Results: The microwave-induced three-component approach applied in this work promoted the construction of 10 new pyrazolopyridines with high speed and excellent control of regioselectivity, favoring the linear product with good yields; where the versatility of electron-rich olefins in iodine-catalyzed cascade heterocyclizations, granted the additional benefit of easy isolation and the possibility to reuse the fluorous phase. Conclusion: Although pyrazolopyridines have been synthetically explored because of their structural and biological properties, most of the reported synthetic methods use common or even toxic organic solvents and conventional heating or multi-step processes. In contrast, this study applied a multicomponent methodology in a single step by microwave induction and with the versatility provided in this case by the use of perfluorinated solvent, which allowed easy isolation of the final product and recovery of the fluorous phase.

As a novel and environmentally friendly Brönsted acid, imidazole hydrochloride was used to promote the synthesis of 2,3-disubstituted-4(3H)-quinazolinone from o-aminobenzoic acid and DMF derivatives. The essence of this reaction is a multicomponent reaction, which constructs multiple chemical bonds between different components through the transamidation of imidazole hydrochloride. This protocol showed a wide range of functional group tolerance, and a series of quinazolinones were synthesized in low to moderate yields without metal catalysts, oxidants or other additives.