Current Organic Synthesis - Volume 17, Issue 4, 2020

Phthalimide derivatives have been presenting several promising biological activities in the literature, such as anti-inflammatory, analgesic, antitumor, antimicrobial and anticonvulsant. The most well-known and studied phthalimide derivative (isoindoline-1,3-dione) is thalidomide: this compound initially presented important sedative effects, but it is now known that thalidomide has effectiveness against a wide variety of diseases, including inflammation and cancer. This review approaches some of the recent and efficient chemical synthesis pathways to obtain phthalimide analogues and also presents a summary of the main biological activities of these derivatives found in the literature. Therefore, this review describes the chemical and therapeutic aspects of phthalimide derivatives.

Background: The sulfonyl groups are general structural moieties present in agrochemicals, pharmaceuticals, and natural products. Recently, many efforts have been focused on developing efficient procedures for preparation of organic sulfones. Materials and Methods: Water, a proton source, is considered one of the most ideal and promising solvents in organic synthesis for its easy availability, low cost, nontoxic and nonflammable characteristics. From the green and sustainable point of view, more and more reactions are designed proceeding in water. Objective: The review focuses on recent advances of sulfonylation reactions proceeding in water. Sulfonylation reactions using sodium sulfinates, sulfonyl hydrazides, sulfinic acids, and sulfonyl chlorides as sulfonating agents were introduced in detail. Results and Discussion: In this review, sulfonylation reactions proceeding in water developed in recent four yields were presented. Sulfonylation reactions using water as solvent have attracted more and more attention because water is one of the most ideal and promising solvents in organic synthesis for its facile availability, low cost, nontoxic and nonflammable properties. Conclusion: Numerous sulfonating agents such as sodium sulfinates, sulfonyl hydrazides, sulfinic acid, sulfonyl chlorides and disulfides are efficient for sulfonylation reactions which proceed in water.

Background: Hydrazonoyl halides are convenient for the synthesis of arylazothiazoles. Materials and Methods: A series of novel arylazothiazoles were efficiently synthesized from the reaction of hydrazonoyl chlorides with 2-(adamantan-2-ylidene)hydrazinecarbothioamide or 2-(ferrocenyl-1-ylidene)hydrazinecarbo-- thioamide in dioxane used as an aprotic solvent because of its lower toxicity and higher boiling point (101 °C) and triethylamine at reflux. The reaction mechanistic pathway proceeded by the nucleophilic substitution reaction by the elimination of hydrogen chloride to give thiohydrazonates as intermediate, which in situ undergo intramolecular cyclization and loss of water molecule to afford the final product of novel arylazothiazoles. This method is simple with good yield and excellent purities. Results and Discussion: The synthetic schemes for the final products are proposed and discussed. The chemical structures of the final products were identified by different techniques, such as elemental analysis, Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), and mass spectrometry (MS). Conclusion: In this article, we prepared arylazothiazoles from the reaction of 2-(adamantan-2-ylidene)hydrazinecarbothioamide or 2-(ferrocenyl-1-ylidene)hydrazinecarbothioamide with hydrazonoyl halides.

Introduction: An instrumental strategy for α-iminonitrile derivatives preparation by Fe3O4@cellulose-OSO3H (MCSA) as an eco-friendly nanocatalyst and oxidative agent in aerobic condition, is presented. Materials and Methods: Through this method, a one-pot three-component condensation reaction of various aldehydes, primary amines and trimethylsilylcyanide (TMSCN) were applied to synthesize the desired products. It was performed in absolute ethanol and under a mild condition by using the presented nanocatalyst. High reaction yields were obtained through using the presented magnetic agent, as well. Moreover, the threecomponent reactions were executed using accessible and economical precursors. The convenient separation and recyclability of the used nanocatalyst were also precisely investigated. Results and Discussion: In this research, we identified novel α-iminonitrile derivatives using 1H NMR, 13C NMR, CHN, and FT-IR analyses, as well. In order to determine the well-known derivatives, we used FT-IR method as well as comparing their melting points with those of reported. Conclusion: In summary, an extremely efficient method was used for the environmentally-friendly synthesis of α-iminonitrile derivatives that are important bioactive substances. The catalytic oxidative coupling reaction afforded the products via a one-pot three-component condensation reaction of various aldehydes, primary amines and TMSCN with great reaction yields, in ethanol under mild conditions.

Background: Aripiprazole is a quinolinone derivative. It shows a high affinity for neurotransmitters dopamine and serotonin receptors, which can overcome the blood-brain barrier (BBB) to reach the central nervous system (CNS) to exert therapeutic effects. Its radioiodination may lead to high radiochemical yield and improved its affinity. Aripiprazole radioiodination is an aromatic electrophilic substitution. Objective: Herein, we investigate the favorable atom site of the aromatic electrophilic substitution of aripiprazole by calculating the Fukui indices of heavy atoms and ESP charges of the parent molecule. Methods: The calculations have been carried out at the B3LYP/LanL2DZ level of theory. The iodinated aripiprazole structure is confirmed by comparing the experimental and the predicted 1H NMR chemical shifts of the parent molecule and its iodinated forms. Results: Finally, the electronic properties of aripiprazole and its iodinated form were calculated at the same level of theory. Nucleophilic Fukui indices and ESP charges calculations confirm that C8 is the most favorable site of the electrophilic substitution. The calculated electronic properties (e.g, gap energy, electron affinity, and electronegativity) of aripiprazole and its iodinated form reveal the higher reactivity of iodinated aripiprazole compared with aripiprazole. Conclusion: This may explain the higher affinity of iodinated aripiprazole and the increase of its radiochemical yield.

Background: Imidazo[1,2-a]pyrimidinone, quinazolinone and amide derivatives have attracted a lot of interest because of their broad scope of biological and pharmacological activities. There are a lot of methods reported in the literature for their synthesis. Therefore, we became interested in developing a convenient synthetic method for the preparation of imidazoquinazolinone and amide derivatives. Objective: NiFe2O4@SiO2 @glucose amine were synthesized, characterized and have been used for the green, effective and mild multicomponent synthesis of quinazolinones, benzoimidazo[1,2-a]pyrimidinones and amides under solvent-free conditions in short reaction times and excellent yields. To expand of the scope of this avenue, multicomponent synthesis of mono and bis novel amides was tested for the first time. All of the products were characterized by mp, FT-IR, NMR and elemental analysis. Methods: Aldehyde (1mmol), 2-amino benzimidazole (1 mmol), dimedone (1mmol) or indane-1,3-dione (1 mmol) for the synthesis of quinazoline or imidazopyrimidinones and arene (1mmol), anhydride (1mmol), 2- aminobenzimidazole (1mmol) for the synthesis of amides in the nanocatalyst NiFe2O4@SiO2@glucose amine (0.15mol%: 0.05g) were stirred by a magnet for the required reaction time. After completion of the reaction, as indicated by TLC, the products were collected and recrystallized from ethanol if necessary. Results: We present a novel avenue for the synthesis of benzimidazo[1,2-a] pyrimidinones, quinazolinones and amides in the presence of NiFe2O4@SiO2@glucose amine under solvent-free conditions. Conclusion: In conclusion, we developed NiFe2O4@SiO2 @glucose amine-catalysed multicomponent synthesis of quinazolinones and imidazo[1,2-a]pyrimidinones using the reaction of benzaldehyde, dimedone or indane-dione and 2-aminobenzimidazole and multicomponent synthesis of amides using arenes, cyclic anhydrides and 2-aminobenzimidazole by a solvent-free technique. This method proves to be a robust and innovative approach for the synthesis of a biologically important structure. The operational simplicity, the excellent yields of products, ease of separation and recyclability of the magnetic catalyst, waste reduction and high selectivity are the main advantages of this method. Furthermore, this new avenue is cheap and environmentally benign.

Background: An eco-friendly, operationally simple and efficient reaction is shown between various 2,6-bis-(substituted-benzylidene)-cyclohexanones and differently substituted hydrazine in the presence of acetic acid. Methods: The reaction between various 2,6-bis-(substituted-benzylidene)-cyclohexanones and differently substituted hydrazine in the presence of acetic acid afforded 7-Benzylidene-substituted-phenyl-3,3a,4,5,6,7- hexahydro-2H-indazole in 74 to 92 % yield in short reaction time using the grindstone technique. Results and Discussion: The notable advantages of this method include mild synthetic conditions, weak acid catalysis, and non-hazardous solvent which make this method environmentally safer. Conclusion: In conclusion, we have developed an efficient, simple and eco-friendly method for the synthesis of 7-Benzylidene-substituted-phenyl-3,3a,4,5,6,7-hexahydro-2H-indazole by grinding technique. The notable benefits of this method are waste minimization, no organic solvent required, simple procedure, easy work-up, and clean reaction profile.