Letters in Organic Chemistry - Volume 14, Issue 6, 2017

Background: Even though several review articles have been written outlining the various methods of synthesis and biological activities of benzofurans, there has been no report of a review which covers the period ranging from 2005-2017. The present review aims to throw some light on the latest research in the field of synthesis of this famous moiety and highlight its biological activities. Methods: We have carried out the literature survey of the articles published on this nucleus during the last decade and studied them precisely in order to identify the most efficient developments that have occurred in its methods of synthesis and biological activities. All the screened papers were arranged on the basis of the protocol involved in the synthesis. Results: Almost a hundred papers have been reviewed for writing this article. More than fifty percent illustrate the varied approaches that have been employed towards the synthesis of benzofuran and its derivatives. Due to the growing awareness towards sustainable development, methodologies based on green chemistry that involve the use of green solvents, nanoparticles etc. have also been developed and are highlighted in this review. This medicinally advantageous scaffold possesses diverse pharmaceutical activities like anti-inflammatory, anti-oxidant, anti-tumor, anti-HIV, anti-platelet, analgesic etc. We have herein tried to focus on some of the most relevant biomedical applications of this nucleus. Conclusion: Looking at a single decade of active research on benzofuran nucleus it can be concluded that several exciting developments have been made with respect to its synthesis which includes the emergence of use of nanoparticles, microwave and green solvents. Intensive progress has been seen in the biomedical applications of its derivatives as described in this review. This moiety forms the platform that can be engineered with varying structural configurations and numerous multifunctionalities for the synthesis of several new lead compounds which can pave the way for hither to unprecedented applications in pharmaceutics.

Background: Designing efficient methods for the synthesis of complex molecules with predefined functionalities is a challenging task in modern organic chemistry. In this context, multicomponent reactions (MCRs), by virtue of their applications, constitute a central academic and industrial investigation domain. Recently, MCRs involving vinylogous Michael addition have attracted increasing interest as one of the most useful key reactions for the synthesis of poly substituted benzene derivatives such as spiro[cyclohexanes-1,3'-indoline]-2';,3-diones, spiroacenaphthylene, benzo[α]cyclooctenes, etc. Therefore, development of an efficient method for a MCR which encompass vinylogous Michael addition as vital reaction is of current interest. Methods: We explored catalytic efficiency of DABCO in the multi-component reaction of cyclic ketone, aldehyde and two moles of malononitrile for the synthesis of functionalized condensed bicyclic compounds viz tetrahydroindenes, tetrahydronaphthalenes, hexahydrobenzo[7] annulenes and hexahydrobenzo[ 8]annulenes. Results: The reaction conditions were optimized by screening of catalyst and solvent. Employing optimized reaction conditions library of bicyclic compounds viz. tetrahydroindenes, tetrahydronaphthalenes, hexahydrobenzo[7]annulenes and hexahydrobenzo[8]annulenes were synthesized in short time duration. The synthesized products were characterized by 1H, 13C, IR and MS. Spectral data obtained was in good agreement with the structure of products. Conclusion: We disclosed DABCO catalyzed multi-component reaction of aldehyde, cyclic ketone and malononitrile furnished corresponding tetrahydronaphthalenes, tetrahydroindalenes, hexahydrobenzo[7] annulenes and hexahydrobenzo[8]annulenes, with a high level of complexity. Notably, this methodology provides a facile access to various multi-functional compounds. The operational simplicity and good yields, combined with step and atom-economic aspects, clean reactions yielded pure products, hence no requirement of tedious chromatographic purification makes this synthetic strategy highly attractive and promising approach from sustainable and practical chemistry.

Background: The compounds with three-dimensional and ionic structures have attracted considerable attentions because of their unique characteristics as a drug carrier and catalyst. Star-like poly ionic compounds are a new generation of three-dimensional structures which have both; the exclusive ionic features and three-dimensional structures. Recently, we reported the synthesis of diazonium salts from aniline derivatives using carboxyl and nitrite functionalized graphene quantum dots. Methods: Nitrite-functionalized star-like polyionic (NFSP) compound was synthesized as a new generation of three-dimensional nanocatalyst. Herein, the use of NFSP as an efficient reagent and nanocatalyst for the diazotization of aniline derivatives and subsequent synthesis of azo dyes via the reaction with active phenolates under solvent-free conditions was reported. Results: In order to demonstrate the positive impact of NFSP efficiency, the reaction times and yields of the products were compared with other methods and catalysts which have been reported previously. The brilliant performance of NFSP can be ascribed to multifunctional reagent and also trapping the ingredient within catalyst cavities. Conclusion: A highly effective and cost-effective method has been developed for the preparation of azo dyes. In reported method, new three-dimensional catalyst with highly ionic characteristic and multifunctional nitrosonium source is available. These special features reduced the required amount of catalyst, reaction time and also increased the efficiency of catalyst.

Background: Nowaday's reductive dechlorination is a powerful tool for the degradation of chlorinated aromatic compounds (CACs). Due to their accumulation in the food chains, they are released into water, soil and air from household or industrial facilities. Methods: The present methodology deals with one pot reductive dechlorination reaction at room temperature in the presence of novel cobalt(II)phthalocyanine as a catalyst. Results: A series of chlorinated aromatic compounds (CACs) were degraded into dechlorinated aromatic compounds (DACs); via one pot reductive dechlorination reaction at room temperature in the presence of novel cobalt(II)phthalocyanine as catalyst within (110-120). Conclusion: The CoPc catalyst has exhibited high activity and stability for the room temperature reductive dechloroniation of CACs. This reductive dechlorination strategy has excellent yield, more high recovery of catalyst, simple experimental working up as well as isolation procedures.

Background: Plectranthus cylindraceus, a bushy leafy herb, is commonly used in folk medicine in some countries such as Saudi Arabia for the treatment of sore throats, skin, digestive and respiratory diseases and for personal hygiene as deodorant and disinfectant. Its oil is reported to possess antimicrobial, nematicidal, and antioxidant activities. Previous phytochemical investigation of P. cylindraceus resulted in the isolation of sesquiterpenes and flavonoids as main constituents of the plant. The aim of present study is to isolate and identify new chemical constituents from the Saudi Arabian P. cylindraceus. Method: The crude MeOH extract was separated by vacuum liquid chromatography (VLC), using hexane, EtOAc, and MeOH. The EtOAc fraction was chromatographed on silica gel, sephadex LH-20, and RP18 columns, affording four compounds. The structure elucidation of these compounds was achieved with the aid of 1D and 2D NMR (1H-1H COSY, HSQC, and HMBC) as well as HR-MS and comparison with literature. Results: Four pure compounds were isolated and identified as: maaliol (1), plectranol A (2), penduletin (3), and chrysosplenol D (4) from MeOH extract of P. cylindraceus. Conclusion: A new sesquiterpene, namely plectranol A (2), along with three known compounds, was isolated from the aerial parts of Plectranthus cylindraceus.

Background: Carboxylic acid derivatives are well recognized as important class of reagents frequently used in the preparation of a variety of fine or special chemicals such as amides, esters, peptides, drugs, and dyes. Although several methods were developed for the preparation of these compounds, many of them present difficulties, including low yield, high reaction temperature, harsh reaction conditions, tedious work-up, and incompatibility with scale-up. Methods: The synthesis of carboxylic anhydrides is developed through the reaction of carboxylic acids with TsCl in the presence of K2CO3 and acetonitrile as a solvent under ultrasound irradiation and conventional conditions. In addition, one-pot synthesis of acyl azides was carried out in the presence of produced carboxylic anhydrides and the addition of sodium azide under identical condition. Results: A series of carboxylic anhydrides and acyl azides were synthesized using TsCl under ultrasound irradiation and conventional stirring with simple procedure, mild reaction conditions, high yields, and scale-up ability without any restriction. In most cases, the reaction under ultrasound irradiation was better in both yields and the reaction times compared to the conventional method. Conclusion: A convenient method has been developed for the preparation of carboxylic anhydrides and acyl azides under ultrasound irradiation and conventional stirring. The present method is practical and a highly effective alternative for previous reports. The major advantages of this method are: (i) simplicity of the procedure (ii) high yields and high purity of product (iii) scale-up capacity without considerable limitation in conventional system. Under ultrasound irradiation short reaction times as compared to conventional method are observed; yields are comparable to or better than conventional method.

Background: The Strecker reaction is a first reported multicomponent reaction for the preparation of a-aminonitriles. The a-aminonitriles are important intermediates for various aminoacids, 1,2-diazines, heterocycles and biologically active compounds like Saframycin A and Ecteinascidin 746. The preparation of a-aminonitriles by Strecker approach using MCR attracted many research groups owing atom economy to avoid multistep synthesis and to follow Green chemistry principles. Methods: A-aminonitriles have been synthesized using Strecker reaction by treatment of aldehydes, amines, with TMSCN in the presence of Cu(BF4)2.xH2O as a catalyst in one pot under neat conditions. Various aromatic and aliphatic aldehydes have been studied with different primary and secondary amines. Results: The reaction condition has been optimized by choosing a model reaction under various solvents and found good yields under neat conditions. Moreover, various catalytic amounts of Cu(BF4)2.xH2O has also been studied and found 3 mole% providing better yields. The reaction has been studied with different substrates of aldehydes and amines. Some of the products were characterized by comparison of their spectral data (1H NMR, 13C NMR, IR and MS) and physical properties with those of authentic samples reported in the literature. Conclusion: Afacile and efficient one-pot synthesis of a-amino nitriles at ambient temperature using copper(II)tetrafluoroborate as a novel catalyst under solvent-free conditions via Strecker reaction is reported. The process is simple and environmentally benign using the commercially available and inexpensive catalyst.

Background: The biological significance of glycoconjugates has stimulated much synthetic activity in oligosaccharide synthesis, the sulfate group in sulfated oligosaccharides has been shown to be constitutively involved in the interaction of ligands with selectins, establishing combinatorial methods for the synthesis of sulfated oligosaccharide library may be useful for screening of ligands of selectins. Results: Random sulfation of a partial benzyl protected Lewis A trisaccharide in pyridine provided a sulfated trisaccharide mixture. After hydrogenation with Pd/C and purification on Sephadex A-50 column, a monosulfated trisaccharide library was obtained as a mixture. The H-H COSY NMR spectrum of this mixture showed that this mixture contains all five possible monosulfated Lewis A trisaccharides with acceptable ratio. Conclusion: Random sulfation of a partial protected oligosaccharide was demonstrated as the most efficient method so far for the synthesis of monosulfated oligosaccharide library.

Background: The design of biologically-active compounds is a challenging viewpoint in medicinal chemistry, and pyrazoles play a crucial role as biologically-active molecules. Methods: Up to now, a few examples have been reported for the synthesis of pyrazoles catalyzed by heterogeneous catalysts. In this work, a new boehmite silylpropyl amine sulfamic (m-SABNPs) was applied as a catalyst for one-pot synthesis of pyrazole derivatives. Results: It was found that this heterogeneous sulfamic acid is a highly efficient catalyst for the syntheses of 5-amino-1,3-aryl-1H-pyrazole-4-carbonitriles and pyrazolopyranopyrimidines in good to excellent yields and can be recovered by a simple filtration of the reaction solution and reused for five consecutive runs without significant loss of catalytic activity. Moreover, its structure was characterized by FT-IR spectroscopy, TGA, XRD, TEM and SEM techniques. Conclusion: An efficient, and convenient method was proposed for the synthesis of pyrazole derivatives catalyzed by heterogeneous sulfamic acid in high-to-excellent yields. This method offers several advantages like milder reaction condition, shorter reaction time, cleaner reaction, and reusability of the catalyst.