Letters in Organic Chemistry - Volume 19, Issue 1, 2022

An unprecedented copper-catalyzed reaction of acetylene analogs with dialkyl azo dicarboxylate and benzazole analogs via a cross-coupling sequence was reported. A library of triazolobenzazole fused ring systems including [1,2,3] triazolo [3,4-b] [1,3] benzothiazole, [1,2,3] triazolo [3,4-b] [1,3] benzoxazole and [1,2,3] triazolo[3,4-b][1,3]benzimidazole structures were obtained in moderate to excellent yields under very mild reaction conditions. Structural confirmation of the final products became possible using different methods like spectroscopy and elemental analysis. The control experiments indicated C-H activation of acetylene by copper salts, followed by cycloaddition between a 2-(phenylethynyl)benzo[d]azol-3(2H)-yl anion and azo dicarboxylate as the key mechanistic feature. The broad substrate scope with simple and easily affordable starting materials, as well as mild reaction conditions are the noticeable attributes of this methodology, which provides facile access to the desired products.

An efficient methodology for the synthesis of 1,3-thiazolidin-4-ones using L-Proline as catalyst under aqueous conditions has been developed. The one-pot, multicomponent reaction of aromatic/ heterocyclic aldehyde, aromatic amine and thioglycolic acid at room temperature give 1,3- thiazolidin-4-ones in moderate to good yields. Further, the current approach is notably greener than traditional methods, with an E-factor of 3.1 and an eco scale score of 96. The developed protocol offers several features, such as being simple, environmentally benign, energy-efficient, economic, mild conditions, shorter reaction time.

Zn(OAc)2•2H2O-catalyzed one-pot multicomponent reaction of Betti bases using β- naphthol, aldehydes, and amines, under neat conditions in moderate to excellent yields (68- 96%) is reported in this study. This synthetic protocol offers several advantages, such as operational simplicity, shorter reaction period, high yields, and easy work-up procedures.

In this study, naturally occurring clay halloysite has been used to synthesize novel halloysite functionalized sulfonic acid in two steps, i.e. functionalization followed by oxidation, and its catalytic activity has been estimated for one-pot synthesis of Hantzsch 1,4-dihydropyridines under green solventfree conditions. Spectroscopic studies such as FTIR, TGA, elemental analysis and first-principles-based quantum chemical studies have been employed to characterize the catalyst. Recyclability without significant loss of catalytic activity has been observed for several runs.

An efficient method for the Sonogashira coupling reaction between aryl halides and terminal alkynes has been developed. The reaction was performed in ionic liquid 1-butyl-3- methylimidazolium tetrafluoroborate ([Bmim][BF4]) under microwave irradiation. High yields of products were obtained in a very short reaction time. Moreover, the medium and catalyst could be recovered and reused three times without considerable decrease in reaction yields.

A novel series of diimino dihydroquinazoline derivatives were synthesized from isocyanides and guanidine analogs in quantitative yields by applying an efficient, inexpensive, one-pot copper-catalyzed intramolecular C-H activation reaction under mild conditions. The structures were confirmed on the basis of IR, 1HNMR, 13C NMR, mass spectral and elemental analysis data. The protocol offers advantages like short reaction time, a simple workup process, high yields, and an environmentally benign methodology. Interestingly, better results (yield = 82%) were observed in terms of the yield obtained by using a mixture of CuI, Cs2CO3 and acetonitrile as the catalyst, base, and solvent, respectively. The data also suggested that compound 5i is produced with the highest yield (87%) from the corresponding diisopropyl carbon diimide, 4-nitroaniline and phenyl isocyanide. Finally, a mechanistic explanation for the reaction promoted by cuprous iodide (CuI) was proposed on the basis of previous investigations and our experimental observations.

The synthesis of axially chiral compounds has attracted a great deal of attention in recent years. Herein, an efficient and economical synthetic route has been developed for 2-(3- carbamoylpyridin-2-yl) nicotinamide pyridine salts, axially chiral compounds. The starting material 1,10-phenanthroline is readily available. In this study, 2-(3-carbamoylpyridin-2-yl) nicotinamide pyridine salts are obtained in moderate to good yields. This protocol includes simple operations and has easy scalability. In addition, the axial chirality of the products is also preliminary studied.

The catalytic display of supported heterogeneous catalysts is essentially reliant on their constitutive elements, including active species and supports. Accordingly, the scheme and development of active catalysts with synergistically enhanced outcomes between active sites and supports are of high importance. A simple NaBH4 reduction method was used to synthesize cylindrical amine-functionalized silica nanotubes supported Ru catalyst (ASNT@Ru catalyst), including amine functionality. The physicochemical properties of the material were analyzed by various analytical methods such as SEM-TEM analysis, N2 physisorption, ICP-OES, XPS, etc., and all the data were found in good agreement with each other. Amine-free SNT support using the calcination process was also synthesized to examine the effect of amine in ASNT support on the uniform Ru dispersion. Taking advantage of the fundamental physical and chemical properties of ASNT support and well-distributed Ru NPs, the ASNT@Ru catalyst was utilized for CO2 hydrogenation reaction, which gave excellent catalytic activity/ stability in terms of a good quantity of the formic. Catalysts recycling was recorded five times, and formic acid was obtained in good quantity.

An efficient synthetic route for the novel bis-imdizo[1,2-a]pyridine-3-yl)methane (2a-k) derivatives have been developed using acetic acid and two drops of trifluoroacetic acid at 40-45oC, resulting in 60-72% yields. An attempt to synthesize bis(Imidazo[1,2-a]pyridin-3-yl)methyl chloride derivatives by the reaction between two moles of imidazo[1,2-a]pyridine, one mole of chloroacetaldehyde in acetic acid, and two drops of trifluoroacetic acid was not successful, instead underwent dehydrohalogenation to yield vinyl derivatives (4a-d).

A novel, mild and efficient protocol to synthesize dibrominated propanamides has been developed. The presented methodology provides several merits, such as easy-to-handle and stable brominated substrate, catalyst-free, additive-free, and facile experimental operation. The study on the preliminary mechanism indicated that a free radical pathway might be involved in the presented reaction.

The novel synthetic route to the antipsychotic drug Cariprazine was developed and demonstrated on a commercial scale. The synthesis of Cariprazine is achieved from N-(4- oxocyclohexyl) acetamide by using various reactions such as Wittig-Horner reaction, reduction of alkene, hydrolysis of ester, deacylation, amidation, reduction of Weinreb amide to yield the corresponding aldehyde, and finally reductive amination of aldehyde in the presence of the corresponding amine to form Cariprazine. In this article, we report a novel intermediate 2-[trans-4- (3,3-Dimethylureido)cyclohexyl]-N-methoxy-N-methyl acetamide by avoiding potentially genotoxic substances/intermediates, tedious, drastic reaction conditions.

A Dansyl functionalized fluorescent probe (DFFP) has been intended, synthesized, and well-characterized (NMR, IR, Mass, SEM, SCXRD), capable of sensing trace amounts of water contaminant in hygroscopic deuterated solvents by changing colour under UV irradiation. A distinct bathochromic shift in emission spectra of probe DFFP and the visual colour change (Green to Yellow) under UV lamp are the key evidence of the presence of water contaminant. To prove the potentiality of the probe while detecting the remnant water, we did some experimental studies along with exhaustive theoretical evaluation. DFT (Energy optimization and other calculations) helped in better understanding the sensing mechanism and the mode of interactions among probe-water-solvent. Total electron density mapped over Electrostatic Potential Surface and calculation of ESP charges helped in locating more electron-dense regions in the ground state. The involvement of TD-DFT studies helped in finding the possible electronic transitions and corresponding absorption bands. Moreover, the probe is capable of sensing ethanolic water vapour in the gaseous phase. Due to high fluorescence and being nontoxic to cells, probe DFFP could be used as a potential cell imaging dye. It has been employed in a human cancer cell line (A549), and fluorescent confocal microscopic images were obtained.

Background: Schizophrenia is a severe mental disorder that affects around 1% of the population worldwide. The available antipsychotics alleviate the positive symptoms of the illness. However, their effect on the negative and cognitive symptoms is limited. The fruit powder of Terminalia bellerica has been found to possess antipsychotic activity, which might be useful in treating the symptoms of schizophrenia. Objective: The present study was performed to evaluate the affinity of the active constituents of Terminalia bellerica towards macromolecular drug targets involved in the pathophysiology of schizophrenia and, thereby, determine the structural features of the ligands involved in the interactions with the proposed targets. Methods: A molecular docking study was carried out on ten active constituents of Terminalia bellerica with four-drug targets involved in the aetiology of schizophrenia. These targets are dopamine, N-methyl- D-aspartate, Gamma-aminobutyric acid, and phosphodiesterase 10A receptors. The binding interactions between the target proteins and the ligands with the highest affinities were studied thoroughly. Results: β-sitosterol, ellagic acid, and quercetin displayed high binding affinity toward all the macromolecular drug targets. Results: β-sitosterol, ellagic acid, and quercetin displayed high binding affinity toward all the macromolecular drug targets. β-sitosterol possesses a high binding affinity for the dopamine receptor, while quercetin has high binding affinities for both dopamine and N-methyl-D-aspartate receptor. On the other hand, ellagic acid formed stronger binding interactions with Gamma-aminobutyric acid and phosphodiesterase 10A. Conclusion: Terminalia bellerica can serve as a new anti-psychotic drug from natural sources with more promising development.