Current Organic Synthesis - Volume 15, Issue 5, 2018

Background: Enantioselective reduction reactions play a key role to synthesize compounds of industrial importance. A number of metal and biocatalysts have been developed for their use in this reaction. Chiral ionic liquids (CILs) have been widely used as the reaction medium and the organocatalysts in enantioselective reduction reactions. Objective: This paper focuses on the systematic literature review about the use of chiral ionic liquids (CILs) in the enantioselective reduction reaction. The mechanistic aspects of these species are also taken into account. Conclusion: This review concludes that a number of chiral ionic liquids (CILs) have been successfully employed as the organocatalysts and the reaction medium in the enantioselective reduction reactions. The review also gives an insight into the role of these species in the reaction mechanism. For most of the reactions, chiral ionic liquids provide promising results in terms of yield and enantioselectivity. The recyclability of these chiral moieties from the reaction mixtures offers an additional benefit for the use of these species in asymmetric reactions.

Background: Our research group has a longstanding interest in the synthesis of novel functionalized heteroaromatic compounds, and the development of new methods for this purpose. During our ongoing investigations, we recently had an instance to check the reproducibility of some published results concerning the chemistry of arylhydrazonals, enamines and other functionally substituted carbonyl compounds. This work has led to the discovery of some new rearrangements, and the revision of the structures originally assigned to several molecules. Objective: This review surveys some correction of several erroneous reports that have appeared in the literature, and presents some interesting new rearrangements discovered in the course of investigating older reports. Results: The crystallographic studies revealed that the condensation of arylhydrazonals with active methylenenitriles yields arylazoniconates rather than pyridazenones as previously reported. Additionally, phenathylthiocyanate reacts with malononitrile to afford thiazoles rather than the previously reported condensation with the carbonyl group. In another example, the reaction of phenethylmalononitrile with hydrazine yields pyrazolopyridazenes rather than phenacylpyrazol-3,5-diamine. In yet another case, several interesting Dimrothtype rearrangements were observed when malononitrile was condensed with enaminones, contradicting earlier reports. Unexpectedly, these enaminones underwent self-trimerization to yield 1,3,5-trisubstituted benzenes under certain conditions. Enaminonitriles also undergo interesting and novel Dimroth rearrangements when reacted with cyclohexanedione or dehydroacetic acid derivatives. Conclusion: We have shown that the structures of several complex heterocyclic compounds that have been reported in the literature over the last 50 years were incorrectly assigned, possibly because the authors who originally reported them were using substandard or outdated analytical equipments.

Background: The synthesis of a variety of bisheterocyclic compounds has received a great attention not only as main chain polymers but also because many biologically active natural and synthetic products have molecular symmetry. In the synthesis of bisheterocyclic, researchers tried to extend the existing method by using a broad range of protocols to improve the various scope and limitations regarding their yield, purity and mostly on the various biological applications. Objective: The significance of this review lies in the fact that bisheterocycles reported here display diverse chemical, structural and biological properties which makes them potential candidates for the further investigations. Conclusion: This review article is associated with the study of the synthesis and varied applications of different bisheterocycles. These compounds have been built around the variety of intermediate chains such aliphatic, olefinic, alkynic and aromatic linkers. The presence of two heterocyclic moieties together in the same molecule either symmetrically or non-symmetrically has been found to influence the biological profiles of the resultant bis organic molecules. So, there is plenty of scope upon the development of the new bisheterocyclic in order to investigate the effect of the length and flexibility of the linkers upon their biological and other properties.

Background: Literature data on the synthesis and structure of oximes of nucleosides and related nitrogenous bases from pyrimidine and purine were reviewed. Synthesis of novel heterocyclic systems from nucleoside oximes related pyrimidine oximes was described. The biological activity of derivatives of nucleoside and nitrogenous base oximes was also reviewed. Objective: The review focuses on the recent progress in the area of nucleoside oxime synthesis, reactions and biological activity. Conclusion: In summary, literature data on the synthesis and structure of oximes of nucleosides and related nitrogenous bases derived from pyrimidine, which play an important role in the biological processes, were reviewed. Synthesis of novel heterocyclic systems from nucleoside oximes related pyrimidine oximes was described. The biological activity of derivatives of nucleoside and nucleotide oximes was also reviewed. The studied class of compounds show a wide range of imino-amino and imino-nitroso tautomerism, which was investigated in the presented literature by 1H, 13C and 15N NMR spectroscopy methods. Also, according to the authors point of view, due to imino-amino and/or imino-nitroso tautomerism the nucleoside oximes show interesting activity. Most of the compounds exhibit biological activity characteristic of not only oxime derivatives, but also activity of hydroxylamines or nitroso compounds.

Background: Amide bond formation reactions are the most important transformations in (bio)organic chemistry because of the widespread occurrence of amides in pharmaceuticals, natural products and biologically active compounds. The Beckmann rearrangement is a well-known method used for the preparation of secondary amides from ketoximes. But, most of the traditional protocols used for the Beckmann rearrangement create enormous amount of wastes. Thus, the atom economical synthesis of amides has got high priority among the chemists. However, under classical Beckmann conditions, aldoximes do not rearrange into the corresponding primary amides. Indeed, reactions of aldoximes lead to nitriles. In recent years, it has been demonstrated that the aldoxime rearrangements can be carried out efficiently and selectively with the help of metal catalysts. Objective: This review focuses on the recent progress in the amides synthesis via ketoxime and aldoxime rearrangements. Applications of the rearrangements in the synthesis of heterocycles and natural products are also covered in this review. Conclusion: In the first part of the review, relevant pathways of oxime rearrangements are discussed and it is shown that several catalytic systems have been developed for the atom-economical synthesis of N-substituted amides from ketoximes. But similar reactions with aldoximes are, however, more challenging. The advances reached in the aldoxime rearrangement are also covered in this review. It is revealed that a large variety of homogeneous and heterogeneous metal catalysts have been developed to affect aldoxime rearrangements.

Aim and Objective: The objective of our work was to study the peculiarities of transformations of fluorine-containing flavone-3-carboxylates with N-nucleophiles, including biogenic amines and amino acids. Materials and Methods: 6,7,8-Trifluoro and 5,6,7,8-tetrafluoroflavone-3-carboxylates were involved in interactions with a number of N-nucleophiles, such as pyrrolidine, morpholine, proline, arginine, gammaaminobutyric acid, beta-alanine, histamine, dopamine and amantadine under different reaction conditions. All synthesized compounds were characterized by NMR 1H, 19F (NMR 13C for some compounds) and IR spectroscopic data, and elemental analysis. Results: 3-(Ethoxycarbonyl)polyfluoroflavones react with morpholine, pyrrolidine and L-proline to form 7- monosubstituted flavone-3-carboxylates. For the reactions of tetrafluoroflavone with pyrrolidine and morpholine, the formation of 5,7-disubstituted products is also possible. Interaction with gamma-aminobutyric acid leads to the 4-{[3-ethoxy-2-(2-hydroxypolyfluorobenzoyl)-3-oxo-1-phenylprop-1-enyl]amino}butanoic acids as a result of the pyrone ring opening. In reactions with dopamine, histamine, L-arginine and β-alanine, polyfluoroflavone-3-carboxylates underwent a chromone-coumarin rearrangement. 3-(Ethoxycarbonyl)tetrafluoroflavone forms with amantadine the nucleophilic aromatic substitution product, while trifluoro-substituted analog gives the chromone-coumarin rearrangement product. Conclusion: This work showed possibilities of chemical modification of polyfluorinated flavones in the reactions with amines depending on the structure of the nucleophilic reagent. Synthesized compounds are of interest for biological testing.

Aim and Objective: In recent studies, chemistry of heterocyclic compounds, especially isoxazoles, has been widely considered by organic chemistry researchers because they have been found in many molecules, including naturally occurring bioactive compounds, pharmaceuticals, and agrichemicals. Isoxazol- 5(4H)-ones and their derivatives, on the other hand, have significant biological properties can be mentioned as examples of antibacterial, anti-inflammatory, antifungal, anticancer, analgesic, fungicidal, and insecticidal activities. Therefore, the development of ecofriendly methods, such as three-component processes, for the synthesis of isoxazol-5(4H)-ones is highly desirable. This work focus on the one-pot, three-component reaction (3-CR) of aldehydes, hydroxylamine hydrochloride, and three β-ketoester using catalytic amounts of sulfanilic acid (SA) aimed at the synthesis of isoxazol-5(4H)-ones. Another aim of this study is to use water as a green solvent for the above-mentioned 3-CR. Materials and Methods: Using SA as an efficient organocatalyst, the multicomponent cyclocondensation of aromatic/hetero-aromatic aldehydes, hydroxylamine hydrochloride, and ethyl acetoacetate/ethyl 4- chloroacetoacetate/ethyl benzoylacetate has been implemented. The reactions were carried out in water as a green solvent at room temperature. The corresponding heterocyclic products were separated by simple filtration and washing with water. Also, the solvent was removed from the filtrate by evaporation to recycle the catalyst. Results: It was found that SA act as the catalyst for the synthesis of 4-arylidene-3-substituted isoxazole-5(4H)- ones via three-component reaction of aromatic/hetero-aromatic aldehydes, hydroxylamine hydrochloride, and three β-dicarbonyl compounds (ethyl acetoacetate, ethyl 4-chloroacetoacetate, and ethyl benzoylacetate). Optimization of the catalyst quantity and solvent showed that the highest yield was achieved with 20 mol% of SA in aqueous media. 4-Arylidene-3-substituted isoxazole-5(4H)-ones have been successfully synthesized in the presence of SA catalyst. Conclusion: The SA catalyst could be recovered easily from the filtrate via evaporation of solvent and reused many times. The present synthetic method is a simple, green, clean, and environmentally friendliness alternative for synthesizing 4-arylidene-3-substituted isoxazole-5(4H)-ones. Reactions were performed without the use of heating, microwave and ultrasound irradiations.