Current Organic Synthesis - Volume 17, Issue 6, 2020

Background: Flavonoid is a family of compounds present in the everyday consumption plants and fruits, contributing to a balanced diet and beneficial health effects. Being a scaffold for new drugs and presenting a wide range of applicability in the treatment of illnesses give them also an impact in medicine. Among the several types of flavonoids, flavone and isoflavone derivatives can be highlighted due to their prevalence in nature and biological activities already established. The standard synthetic route to obtain both halogenated flavones and isoflavones is through the use of already halogenated starting materials. Halogenation of the flavone and isoflavone core is less common because it is more complicated and involves some selectivity issues. Objective: Considering the importance of these flavonoids, we aim to present the main and more recent synthetic approaches towards their halogenation. Methods: The most prominent methodologies for the synthesis of halogenated flavones and isoflavones were reviewed. A careful survey of the reported data, using mainly the Scopus database and halogenation, flavones and isoflavones as keywords, was conducted. Results: Herein, a review is provided on the latest and more efficient halogenation protocols of flavones and isoflavones. Selective halogenation and the greener methodologies, including enzymatic and microbial halogenations, were reported. Nevertheless, some interesting protocols that allowed the synthesis of halogenated flavone and isoflavone derivatives in specific positions using halogenated reagents are also summarized. Conclusion: Halogenated flavones and isoflavones have risen as noticeable structures; however, most of the time, the synthetic procedures involve toxic reagents and harsh reaction conditions. Therefore, the development of new synthetic routes with low environmental impact is desirable.

The natural beauty and purity of our planet has been contaminated deeply due to human selfish activities such as pollution, improper waste management, and various industrial and commercial discharges of untreated toxic by-products into the lap of nature. The collective impact of these hazardous suspensions into the natural habitat is very deadly. Challenges due to human activity on the environment have become ubiquitous. The chemical industry has a major role in human evolution and, predictably, opened gates of increased risk of pollution if the production is not done sustainably. In these circumstances, the notion of Green Chemistry has been identified as the efficient medium of synthesis of chemicals and procedures to eradicate the toxic production of harmful substances. Principles of Green Chemistry guide the scientist in their hunt towards chemical synthesis which requires the use of solvents. These solvents contaminate our air, water, land and surrounding due to its toxic properties. Even though sufficient precautions are taken for proper disposal of these solvents but it is difficult to be recycled. In order to preserve our future and coming generation from the adverse impacts associated with solvents it is very important to find alternative of this which will be easy to use, reusable and also eco-friendly. Solvents are used daily in various industrial processes as reaction medium, as diluters, and in separation procedures. As reaction medium, the role of solvent is to bring catalysts and reactants together and to release heat thus affecting activity and selectivity. The proper selection of the solvent considering its biological, physical and chemical properties is very necessary for product separation, environmental, safety handling and economic factors. Green solvents are the boon in this context. They are not only environmentally benign but also cost effective. The biggest challenge faced by the chemists is adaptation of methods and selection of solvents during chemical synthesis which will give negligible waste product and will remain human and nature friendly. During designing compounds for a particular reaction it is difficult to give assurance regarding the toxicity and biodegradability of the method. Chemists are still far away from predicting the various chemical and biological effects of the compounds on the back of the envelope. To achieve that point is formidable task but it will definitely act as inspiration for the coming generation of chemists. The green solvents are undoubtedly a far better approach to eliminate the negative impacts and aftermath of any chemical synthesis on the environment. Our study in this review covers an overview of green solvents, their role in safer chemical synthesis with reference to some of the important green solvents and their detail summarization.

Background: Sulfonated carbon-based solid acids (CBSAs) have been reported as an efficient solid acid catalyst for many acid-catalyzed reactions. Furthermore, the use of carbon obtained from biomass waste has been explored and these materials showed a higher catalytic performance and higher stability compared to other solid acids. Objective: Novel biomass carbon-based solid acids nanoparticles with high catalytic activity in organic transformation, such as Grape pomace waste-SO3H Nanoparticles (GPW-SO3H NPs), were successfully synthesized. Materials and Methods: Grape pomace waste-SO3H Nanoparticles (GPW-SO3H NPs) were successfully synthesized. The grape pomace waste was dried in an oven at a temperature of 70°C and crushed to powder using an electric spice grinder. A mixture of powdered grape pomace waste (1 g) and concentrated sulfuric acid (>98%, 10 mL) was stirred at room temperature. Then, the resultant mixture was transferred into a 100 mL sealed Teflon-lined autoclave and kept at 180°C for 12 h. After cooling to room temperature, the resulting black solid was dried at 100°C in an oven under vacuum and the sulfonic acid-functionalized magnetic nanoparticles (Fe3O4@C-SO3H) were obtained. Results and Discussions: The catalytic activity of GPW-SO3H was assessed through an easy and rapid protocol developed for the one-pot synthesis of 14-aryl-14-H-dibenzo [a,j]xanthene, arylmethylene [bis(3- hydroxy-2-cyclohexene-1-one)], bis(indolyl)alkane and 2-amino-4-aryl-7-hydroxy-4H-chromene-3-carbonitrile derivatives in excellent yields. The advantages of this method include use of waste material for catalyst synthesis, high yields, mild reaction conditions, uncomplicated work-up procedures, neutral conditions, and recoverable catalyst. Conclusion: We have shown that biomass-derived solid acids, prepared from grape pomace waste, serve as a non-toxic, inexpensive and a promising eco-friendly and novel carbon-based solid acid nanocatalyst for organic transformations.

Background: The pyrano[2,3-c]pyrazole derivatives are important building blocks of many biologically active compounds owing to their diverse biological potential for example, anti-inflammatory, anticancer, anti-microbial and anti-oxidant properties. Objective: Keeping in mind the wide range of applications of pyrano[2,3-c]pyrazoles, herein we intended to develop a novel synthetic methodology for dihydropyranopyrazoles. We were also interested in determining the influence of amino acids and dipeptides as a catalyst on the synthesis of pyrano[2,3-c]pyrazole derivatives. Methods: To achieve our objectives, we used a one-pot multi-component reaction of ethyl 3-oxobutanoate, propanedinitrile, hydrazine monohydrate and several substituted benzaldehydes by using different catalysts and solvents to synthesize our desired products in the presence of various catalysts. Results and Discussion: We found that optimal conditions for the preparation of pyrano[2,3-c]pyrazoles were L-cysteine (0.5 mol) in the presence of water:ethanol (9:1) at 90 °C. Various 1,4-dihydropyrano[2,3- c]pyrazoles were afforded by using several substituted benzaldehydes in 66-97% yields. Conclusion: We described a green and environmentally benign method to synthesize pyrano[2,3-c]pyrazoles in a one-pot four component reaction of ethyl 3-oxobutanoate, propanedinitrile, hydrazine monohydrate and different substituted benzaldehyde in the presence of L-cysteine in aqueous ethanol (9:1) at 90 °C. Excellent yields of the products, simple work-up, easily available starting materials, use of green solvents, naturally occurring catalyst, non-toxicity, non-chromatographic purification and environmentally benign reaction conditions are some main advantages of this protocol.

Background: Thiazolidinoneones are important pharmaceutical compounds because of their biological activities. Several methods for the synthesis of 4-thiazolidinones are widely reported in the literature. The main synthetic routes to synthesize 1,3-thiazolidin-4-ones involve three components reaction between amine, a carbonyl compound and thioglycolic acid. Objective: s-Proline covalented silicapropyl modified magnetic nanoparticles (Fe3O4@SiO2-Pr @s-proline) were prepared. The antibacterial activity of synthesized nanoparticles against four bacterias was investigated that showed that 30 Mg/L of synthesized nanoparticles is a suitable concentration for bacterial inhibitory. Finally, the catalytic application of the synthesized s-Proline covalented silicapropyl modified magnetic nanoparticles for the synthesis of thiazolidinones and pyrazolyl thiazolidinones under stirring in aqueous media was evaluated. All of the synthesized organic compounds were characterized by mp, FT IR, 1H NMR, 13C NMR and elemental analysis. Materials and Methods: A combination of aldehyde (1.0 mmol), thioglycolic acid (1.0 mmol), various amines (1mmol) and 0.05 g Fe3O4@SiO2propyl@L-proline, were reacted at room temperature under stirring in 10 mL water. After completion of the reaction, as indicated by TLC (4:1 hexane: ethylacetate), the reaction mixture was filtered in the presence of an effective magnetic bar to separate the nanocatalyst. The nanocatalyst was washed with a mixture of hot EtOH: H2O two times. The crude products were collected and recrystallized from ethanol, if necessary. Results and Discussion: We present a novel avenue for the synthesis of thiazolidinones in the presence of Fe3O4@SiO2-Pr @s-proline under solvent-free conditions. Conclusion: In conclusion, we have synthesized Fe3O4@SiO2-Pr@s-proline nanoparticles. Their biological activity against 4 bacterias was investigated. It released that 30Mg/L is the suitable concentration of synthesized nanoparticle for bacterial inhibitory. The catalytic efficiency of the catalyst was checked in the multicomponent reaction of various aldehyde, thioglycolic acid and various amines under stirring. This nanoparticle is a new organic-inorganic hybrid nanoparticle. 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 catalytic method. Furthermore, this new avenue is inexpensive and environmentally benign.

Aims: Synthesis of pyrrolo[1,2-d][1,4]benzoxazines and pyrrolo[1,2-a]pyrazines using magnetic nanoparticles. Background: One-pot, three component reaction for the synthesis of pyrrolo[1,2-d][1,4]benzoxazines and pyrrolo[1,2-a]pyrazines is reported. For the synthesis of pyrrolo[1,2-d][1,4]benzoxazines use of 2- aminophenols, dialkylacetylenedicarboxylates and β -nitrostyrene derivatives and Pyrrolo[1,2-a]pyrazines synthesized from reaction of ethylenediamine, dialkylacetylenedicarboxylates and β-nitrostyrene derivatives is discussed. Materials and Methods: 2-aminophenol (0.5 mmol) and dimethylacetylenedicarboxylate (0.5 mmol) in water (3 ml) were stirred at room temperature for 10 min. Then, β-nitrostyrene (0.5 mmol) and Fe3O4@SiO2@LArginine- SA MNPs (0.07 g) were added and the mixture was refluxed for 5 h. After completion of the reaction, the mixture was cooled to room temperature and the catalyst was separated with external magnet and product extracted with dichloromethane. More purification of products was performed by column chromatography (nhexane/ ethyl acetate 4:1). Ethylenediamine (0.6 mmol) was added to dialkylacetylenedicarboxylate (0.6 mmol) in 3 ml water and was stirred for 10 min at room temperature. Later, β -nitrostyrene (0.5 mmol) and Fe3O4@SiO2@L-Arginine-SA MNPs (0.06 g) were added to mixture reaction and refluxed for 3 h. After completion, the mixture reaction was cooled to room temperature and the catalyst was separated by an external magnet. Then, the product was extracted with dichloromethane. For more purification column chromatography was used (n-hexane/ethylacetate 1:1). Results and Discussions: In this research, we have synthesized new derivatives of pyrrolo[1,2- d][1.4]benzoxazines and pyrrolo[1,2-a]pyrazines in green conditions consisting of use of water as a green solvent and magnetic nanoparticles. Conclusion: In this research, we have synthesized new derivatives of pyrrolo[1,2-d][1.4]benzoxazines and pyrrolo[1,2-a]pyrazines in green conditions consisting of use of water as a green solvent and magnetic nanoparticles which were easily separated from mixture with an external magnet and had the capability to be recovered and reused. Also, in this work, the yield was good and the time of reactions was low compared with prior research.

Introduction: Quinoxalines show diversified applications in the field of medicinal chemistry. Materials and Methods: Therefore, we have designed a highly efficient, environmentally benign and one-pot protocol for the synthesis of 2-phenylquinoxaline from the reaction of Acetophenone, N-bromosuccinimide and 1,2-phenylenediamine under ultrasound irradiation in glycerol-water. Results and Discussion: We observed that, although the reaction efficiently completed in all of these solvents, the use of glycerol-water with different ratios gives consistently higher yields (89–94%) and decreases reaction times. Conclusion: The main advantages of this protocol are that it is a green method, avoids the use of toxic catalysts and volatile organic medium and the product is obtained with excellent yield.

Background: The phthalocyanines a series of compounds involves four iso-indole units linked by aza nitrogen atoms bonded with metal atoms that are normally located in the center a phthalocyanines ring. Some of the central metal-phthalocyanines can be excited by ultraviolet light and emit a fluorescence in far-red region. Objective: To synthesize a derivative of phthalocyanines namely 4,4',4' '-tri-(dodecenyl succinic anhydride)- 4' ' '-(5-amino salicylic acid) zinc phthalocyanine with a zinc central metal. Materials and Methods: The reaction of 4- nitro Phthalonitrile and 4- amino Phthalonitrile with ZnCl2 in the presence of dimethyl amino ethanol afforded 4,4',4' '-triamino-4' ' '-nitro zinc phthalocyanine. This product reacted with 5-amino salicylic acid to yield tetra-(5-amino salicylic acid) zinc phthalocyanine. A dodecenyl succinic anhydride was added on the amine group of benzoic rings to afford 4,4',4' '-tri-(dodecenyl succinic anhydride)-4' ' '-(5-amino salicylic acid) zinc phthalocyanine(I), the target compound. Results and Discussion: Compound I is successfully synthesized with a yield of 72% from tetra-(5-amino salicylic acid) zinc phthalocyanine with dodecenyl succinic anhydride. Conclusion: The newly synthesized molecule of 4,4',4' '-tri-(dodecenyl succinic anhydride)-4' ' '-(5-amino salicylic acid) zinc phthalocyanine (I), tetra-(5-amino salicylic acid) zinc phthalocyanine(E) and 4,4',4' '- triamino-4' ' '-nitro zinc phthalocyanine (S). The reaction of 4- nitro Phthalonitrile and 4- amino and the structure of compound I is confirmed and its formation was proven.