Practical Cu-catalyzed amination of functionalized heteroaryl halides

The amination of a variety of highly functionalized heterocyclic bromides has been accomplished using a CuI/proline catalyst system. The current study significantly expanded the scope of the reaction by using examples relevant to drug discovery programs and has demonstrated reaction rate acceleration using microwave heating.     

Microwave-assisted solid-phase synthesis of 5-carboxamido-N-acetyltryptamine derivatives

[reaction: see text] The synthesis of the indole skeleton of new melatoninergic analogues was realized using solid-phase methodology in association with microwave irradiation. This combination speeds up the solid-phase drug discovery process in rigorously established conditions.     

Developments towards regioselective synthesis of 1,2-disubstituted benzimidazoles

1,2-Disubstituted benzimidazoles play an important role in several areas and particularly as drug discovery targets. Herein, several methods to assemble these structures are reviewed, from the classical approaches to the more recently developed metal-catalyzed intramolecular amination process, the cascade arylamination/condensation reaction and polymer-supported benzimidazole assembly under microwave conditions.     

Microwave synthesis of zeolites. 2. Effect of vessel size, precursor volume, and irradiation method

The enhancement of synthesis reactions under microwave heating is dependent on many complex factors. We investigated the importance of several reaction engineering parameters relevant to microwave synthesis. Of interest to this investigation were the reaction vessel size, volume of precursor reacted, microwave power delivery, and microwave cavity design. The syntheses of NaY zeolite and beta-zeolite were carried out under a number of varying conditions to determine the influence of these parameters on the nucleation rate, the crystallization rate, and the particle size and morphology. The rates of NaY and beta-zeolite nucleation and crystallization were more rapid in the multimode CEM MARS-5 oven compared to the more uniform field CEM Discover. The faster synthesis rate in the MARS-5 may be the result of the multimode microwave electric field distribution. Slower rates of NaY and beta-zeolite formation observed in the Discover and a circular waveguide may be the result of a more uniform microwave electric field distribution. Changes in reaction vessel size and precursor volume during the microwave synthesis of beta- and NaY zeolite were found to influence the rate of zeolite formation. These results indicate that reactor geometry needs to be considered in the design of systems used for microwave synthesis. Comparative synthesis reactions were carried out with conventional heating, and microwave heating was shown to be up to over an order of magnitude faster for most of these syntheses.     

Regioselective Synthesis of 3‐(Imidazol‐4‐yl) Indolin‐2‐Ones under Microwave Heating

A formal [3 + 2] cyclization reaction of 3‐(2‐oxo‐2‐arylethylidene)indolin‐2‐ones and amidines has been developed, regioselectively affording a series of new 3‐(imidazol‐4‐yl)indolin‐2‐ones in good to excellent yields. The reaction was easily conducted in ethylene glycol using Cs₂CO₃ as a base promoter under microwave irradiation. Flexible structural modification, and broad functional group compatibility as well as mild reaction conditions make this strategy a useful and attractive process of library generation for drug discovery.     

Three‐Component Synthesis of Spiro[indoline‐3,4′‐pyrazolo[3,4‐b]pyridines] under Microwave Irradiation

A domino three‐component strategy with high efficiency for the synthesis of spiro[indoline‐3,4′‐pyrazolo[3,4‐b ]pyridines] from easily available isatins, pyrazol‐5‐amines and β‐ketonitriles under microwave heating. During reaction process, HOAc plays dual roles as reaction media as well as a Brønsted acid‐promoter. Flexible structural modification, broad functional group compatibility and mild reaction conditions make this strategy a useful and attractive process of library generation for drug discovery.     

Design,synthesis and spectroscopic characterisation of a focused library based on the polyandrocarpamine natural product scaffold

A focused library based on the marine natural products polyandrocarpamines A ( 1 ) and B ( 2 ) has been designed and synthesised using parallel solution‐phase chemistry. In silico physicochemical property calculations were performed on synthetic candidates in order to optimise the library for drug discovery and chemical biology. A library of ten 2‐aminoimidazolone products ( 3–12 ) was prepared by coupling glycocyamidine and a variety of aldehydes using a one‐step stereoselective aldol condensation reaction under microwave conditions. All analogues were characterised by NMR, UV, IR and MS. The library was evaluated for cytotoxicity towards the prostate cancer cell lines, LNCaP, PC‐3 and 22Rv1. Copyright © 2013 John Wiley & Sons, Ltd.     

“讲一练二考三”理念在有机化学实验教学中的运用——以苯甲酸的制备为例

采用微波辐射及相转移催化剂改进了高锰酸钾氧化制备苯甲酸实验,系统研究了微波功率、反应温度、反应时间、反应物物质的量比、催化剂用量等因素对产率的影响,并同电热套加热方式进行了比较.结果表明,该反应的最佳条件为:微波辐射时间40 min,微波功率80 W,反应温度80℃,相转移催化剂氯化苄基三乙铵用量为甲苯的0.2当量,高锰酸钾与甲苯的物质的量比为4.5:1.与电热套加热方式相比,微波辐射法缩短了反应时间,并显著提高了反应效率.以苯甲酸制备实验为例介绍了“讲一练二考三”教学新理念及其在有机化学实验教学实践中的运用.     

Regioselectively Synthesis of Thiazolo[4,5‐a]acridines and Oxazolo[5,4‐a]thiazolo[5,4‐j]acridines via Multicomponent Domino Reactions

A regioselective three‐component reaction of aromatic aldehydes, 2‐hydroxy‐1,4‐naphthoquinone and benzo[d]thiazol‐5‐amine in HOAc under microwave irradiation has been developed. A series of new thiazolo‐fused benzo[h]acridines were synthesized with high chemical yields in this one‐pot reaction. The resulting thiazolo‐fused acridines were employed to further react with aldehydes and ammonium acetate to give polycyclic‐fused oxazolo[5,4‐a]thiazolo[5,4‐j]acridines. The present synthesis shows several advantages, such as operational simplicity, fast reaction rates, which makes it a useful and attractive process of library generation for drug discovery.     

微波干法催化芳香醛与绕丹宁及N-苯基绕丹宁的缩合反应

利用微波辐射和固体碱性载体试剂催化绕丹宁及N-苯基绕丹宁和芳香醛的缩合反应合成了14个绕丹宁衍生物并研究了影响反应的因素。     

Microwave-induced organic reaction enhancement (more) chemistry: Techniques for rapid,safe and inexpensive synthesis

Synthetic organic reactions have been conducted under microwave irradiation in open vessels in unaltered domestic microwave ovens. Reaction times vary from a few seconds for sub-milligram reactions to about 15 minutes for reactions carried out on a scale of hundreds of grams. Promising results have been obtained for several condensations, as well as the Bischler-Napieralski reaction, the Wolff-Kishner reduction, free radical dehalogenation reactions, and other standard synthetic operations. Rapid catalytic transfer hydrogenation using ammonium formate as the source of hydrogen has been conducted at about 100-130 °C under microwave irradiation. Meaningful, safe and inexpensive synthetic experiments for undergraduate and pre-college students have been developed and tested. The MORE chemistry techniques make it possible to use simple apparatus and very short reaction times. Commercial microwave ovens are now essential equipment in our research and teaching laboratories [1-3]. These ovens are relatively inexpensive, easy to move from one laboratory and set up in another, and safe to operate. Glass, plastics, and ceramics are essentially transparent to microwaves whereas many organic compounds are dipolar in nature and absorb microwave energy readily. We have found that untraditional experimental arrangements are possible for conducting a wide variety of organic reactions in open vessels inside domestic microwave ovens. Depending on the quantity of reactants, most reactions (on a scale of milligrams to several grams) can be completed in minutes instead of hours. One important element of our “Microwave-induced Organic Reaction Enhancement” (MORE) chemistry is the proper choice of a microwave energy transfer agent as the reaction medium.     

Use of a silicon carbide multi-well plate in conjunction with microwave heating for rapid ligand synthesis, formation of palladium complexes, and catalyst screening in a Suzuki coupling

The preparation of a library of bis-imidazolium salts and corresponding palladium complexes is reported. These complexes are screened as catalysts in the Suzuki reaction between 4-bromoanisole and phenylboronic acid. Each step is performed in parallel using a 24-position silicon carbide plate and microwave heating. The plate allows for use of standard glass vials as reaction vessels. The ease and speed of operation show the potential for microwave heating in conjunction with the silicon carbide plate as a tool for catalyst screening.     

A one-pot,two-step microwave-assisted synthesis of highly functionalized benzoxazoles using solid-supported reagents (SSRs)

A one-pot, two-step protocol for the microwave-assisted solid-phase synthesis of substituted benzoxazoles has been developed starting from different polymer-bound esters we previously designed as solid-supported reagents (SSRs) for the acylation of amines, alcohols and phenols. The combination of a parallel synthesizer and a microwave reactor allowed to quickly prepare a collection of substituted benzoxaxoles in high purity and satisfactory yields. This protocol is amenable for automation and could be used for the preparation of combinatorial libraries in drug discovery programs.     

Fast Microwave‐Mediated Bulk Polycondensation of d,l‐Lactic Acid

The polycondensation of D ,L ‐lactic acid upon microwave irradiation was studied. The results of polycondensation by means of microwave were compared to those obtained from conventional heating of lactic acid at 100°C, and it was found that the reaction proceeds with much higher rate upon microwave irradiation. The oligomer mixtures formed were investigated by means of matrix‐assisted laser desorption/ionization mass spectrometry (MALDI MS). The molecular mass of the poly(lactic acid) formed under microwave irradiation was found to increase with irradiation time, and the formation of cyclic oligomers after 20 min of reaction time was also revealed.     

An environmentally friendly,cost effective synthesis of quinoxalines: the influence of microwave reaction conditions

A convenient, environmentally friendly and novel synthesis of quinoxalines using silica gel as the catalyst is described. The choice of microwave conditions has been shown to have a substantial impact on the reaction outcome with closed-vessel microwave irradiation resulting in the formation of quinoxalines in high yields and short reaction times. Preliminary mechanistic investigations have indicated that a slight build-up in pressure has a major impact on the reaction outcome.     

4,7,10-三(叔丁氧碳酰甲基)-1,4,7,10-四氮杂环十二烷-1-乙酰肼的微波合成

以轮环藤宁为起始原料,依次与溴乙酸叔丁酯,溴乙酸乙酯和水合肼反应合成了一种核磁共振对比剂螯合前体--4,7,10-三(叔丁氧碳酰甲基)-1,4,7,10-四氮杂环十二烷-1-乙酰肼（4）,其结构经¹H NMR, ¹³C NMR, FT-IR和MS(ESI)表征。研究了溶剂、水合肼用量、微波功率和反应时间对4收率的影响。结果表明：乙醇为溶剂,水合肼10 eq.,于400 W微波反应10 min, 4（粉末固体）收率90%。     

Evolution of microwave irradiation and its application in green chemistry and biosciences

Microwave-assisted organic reactions have been applied as an effective technique in organic synthesis. Microwave irradiation often leads to shorter reaction times, increased yields, easier workup, matches with green chemistry protocols, and can enhance the region and stereo selectivity of reactions. In fact, the high usefulness of microwave-assisted synthesis encouraged us to increase the efficiency of several organic transformations and synthesis. High-speed microwave-assisted chemistry has attracted a considerable amount of attention in recent years and has been applied successfully in various fields of synthetic organic chemistry, proteins, peptides, drug discovery, and green chemistry. The various roles of microwave-assisted organic chemistry in green and sustainable chemistry are discussed, beginning with the strategies, technologies, and methods that were employed routinely at the time of the first reports of microwave applications. Microwave processing has several advantages over conventional sintering/heating, such as the reduction in cycle time, energy efficiency, eco-friendliness, and providing finer microstructures, leading to improved mechanical properties. Herein, we also describe the evolution of the microwave and some early applications of microwave assistance in the biomolecular sciences and treatment of solid malignant tumors.     

An Open Vessel,Pulse-Microwave Technique for Wet Ashing of Metal-Contaminated Animal Tissues

Abstract

Wet ashing of whole fish arid standard mammalian liver samples for metal determinations is effectively achieved through low power pulse microwave treatment using a domestic grade microwave oven. The reaction is carried out in an open Erlenmeyer flask while held within a much larger sealed container. The latter may be any inexpensive vessel that is microwave proof. The power setting is approximately 70 watts. The oven is programmed to deliver microwaves for 10 seconds every three minutes for a total of 19 minutes. Efficiency of recovery is generally within 10% of the known amounts. The pulse microwave protocol avoids the high temperatures and pressures that create the risk of explosions.     

Microwave Flow Chemistry as a Methodology in Organic Syntheses,Enzymatic Reactions,and Nanoparticle Syntheses

Several studies have used microwaves as a heat source for carrying out various types of reactions employing circulation reaction vessels. The microwave flow chemical synthesis methodology is most appropriate in the use of microwaves in chemical syntheses. It can attenuate the problem of microwave heating (non‐uniform heating and penetration depth) and maximize the benefits (rapid heating and first temperature adjustments). In this brief review, we examine and explain some of the relevant features of microwave heating with applicative examples of the usage of microwave flow chemistry equipment in carrying out organic syntheses, enzymatic reactions, and (not least) nanoparticle syntheses.     

星际分子微波波谱研究进展

介绍了星际分子研究的概况,对微波波谱作为研究星际分子的重要方法的特点、特殊方法和技术以及取得的进展进行了综述,特别对近年来的微波波谱星际分子研究进行了分类介绍,提出了目前研究的难点并展望了发展趋势.