摘要:

Green Chemistry Books Green Chemistry Theory and Practice P T Anastas and J C Warner Oxford University Press Oxford 1998 160 pp. ISBN 0-19-850234-6 Price £45 Green Chemistry Frontiers in Benign Chemical Synthesis and Processes P T Anastas and T C. Williamson Oxford University Press Oxford 1998 448 pp ISBN 0-19-850 170-6 Price £65 It is both fortuitous and appropriate that the first issue of this journal should be shortly preceded by the publication of two very interesting books by Paul Anastas founder and promoter of Green Chemistry. The two are very different. The first Green Chemistry Theory and Practice is a real book written by Anastas who is based at the US Environmental Protection Agency and John Warner recently appointed professor at the University of Massachusetts at Boston.By contrast the second Green Chemistry Frontiers in Benign Chemical Synthesis and Processes is a collection of single and multi-authored chapters edited by Anastas and his EPA colleague Tracy Williamson. The books are intended to be complementary and successfully avoid any but the most trivial overlap. Green Chemistry Theory and Practice is intended to be a student text and it tells a story. It begins by briefly summarizing some of the more shameful episodes of chemical manufacture Times Beach where dioxins in waste oil contaminated the road-side and forced the US federal government to buy up and demolish the whole town; the Love Canal (Niagara Falls) where a school and housing were imprudently built on a chemical waste dump; the Cuyahoga river which caught fire in 1969; and finally the tragedy at Bhopal where the unintended release of methyl isocyanate killed perhaps thousands of those living in shanties near the plant.The authors are careful to put these relatively rare incidents into context and to stress the more general problems of chemical emission and waste. Quite early on they introduce the ‘equation’ Risk = function [Hazard Exposure] and define Green Chemistry as ‘the utilization of a set of principles that reduces or eliminates the use or generation of hazardous substances in the design manufacture and application of chemical products’. This is a usefully succinct definition which I have used successfully with my own students.The main part of the book centers on the twelve principles of Green Chemistry which it is perhaps appropriate to quote here in our first issue. 1 It is better to prevent waste than to treat or clean up waste after it is formed. 2 Synthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product. 3 Wherever practicable synthetic methodologies should be designed to use and generate substances that possess little or no toxicity to human health and the environment. 4 Chemical products should be designed to preserve efficacy of function while reducing toxicity. 5 The use of auxiliary substances (e.g. solvents separation agents etc.) should be made unnecessary wherever possible and innocuous when used.6 Energy requirements should be recognized for their environmental and economic impacts and should be minimized. Synthetic methods should be conducted at ambient temperature and pressure. 7 A raw material or feedstock should be renewable rather than depleting wherever technically and economically practicable. 8 Unnecessary derivatization (blocking group,protection/ deprotection temporary modification of physical/chemical processes) should be avoided whenever possible. 9 Catalytic reagents (as selective as possible) are superior to stoichiometric reagents. 10 Chemical products should be designed so that at the end of their function they do not persist in the environment and break down into innocuous degradation products.11 Analytical methodologies need to be Photo B. Case C G BOOKS developed further to allow for realtime in-process monitoring and control prior to the formation of hazardous substances. 12 Substances and the form of a substance used in a chemical process should be chosen so as to minimize the potential for chemical accidents including releases explosions and fires. These principles are explained briefly and are then expanded into whole chapters (or large parts thereof). As the summary of a vision the book is brilliant. One can feel the enthusiasm of the authors throughout. As a student text it probably fails albeit gallantly.There are really too few chemical examples to justify its use as a course text. It would be very difficult to set an examination based on the book; one could hardly ask the students to memorize the ‘Twelve Principles’ like the Catechism. Nevertheless the book is potentially very valuable. I see it as a vehicle for initiating a fruitful dialogue between chemical producers and regulatory enforcers without the confrontation which often characterizes such interactions. Green Chemistry Frontiers in Benign Synthesis and Processes is quite different; it contains serious chemistry and is targeted on practicing chemists. It consists of 20 chapters by a total of 68 authors all but three of whom are US-based. It begins with an overview by Anastas and Williamson which is a broad précis of ‘Green Chemistry Theory and Practice’ without the Twelve Principles.The remaining chapters are grouped under six headings; Alternative feedstocks and Green Chemistry February 1999 G21 B O O K S C G reagents Catalysis Biocatalysis and bioprocessing Alternative solvents Uses of carbon dioxide and lastly Alternative synthesis and processing. Multi-authored books have problems and this one is no exception. The most serious is the disparity in the level of the chapters. Some chapters begin at a high level with no concessions to the nonspecialist reader as for example in the chapter on Palladium-catalyzed Allylic Alkylation by Barry Trost who also wrote the Foreword to the book.Others like the chapter on pollution prevention via molecular recognition by John Warner (co-author of Green Chemistry Theory and Practice) begin at a level which is almost too elementary and risks hiding the elegance of the chemistry. Undoubtedly each reader will pick out different chapters but I particularly enjoyed two co-incidentally the two with the most authors. The chapter on the design of green oxidants by Terry Collins and his 11 co-workers gives an excellent account of the long development of stable transition metal complexes for catalyzing oxidation by H2O2. It is one of the few chapters which attempt to explain why the chemistry worked and not merely how (it contains the only molecular orbital diagram in the book).The other chapter which I enjoyed was from Steve Buelow and his 10 co-authors summarizing their recent research in homogeneous catalysis in supercritical CO2. This chapter is particularly welcome because the group at Los Alamos has been quite slow in publishing their results presumably for reasons of intellectual property. Overall the book gives a useful snap-shot of the current state of Green Chemistry. Admittedly it is heavily biased towards the USA but after all Green Chemistry was born in Washington. The major Italian Green Chemistry Consortium is represented in the chapter by its founder Pietro Tundo and Maurizio Selva. As far as I can judge most authors have given due credit to non-US groups in their field but it is a pity that there are no contributions from UK or Japan both of which have active Green Chemistry Groups.More seriously there is only one chapter from industry the last one in the book. It is a lively account of environmental improvements in the commercial synthesis of progesterone by Bradley Hewitt of Pharmacia and Upjohn. The absence of industrial contributions is particularly sad in view of the excellent industrial examples which have been highlighted by the US Presidential Green Chemistry Challenge G22 Green Chemistry February 1999 initiated by Anastas and his colleagues four years ago. In summary these are excellent books but they are for libraries for regulators or serious practitioners of Green Chemistry. Nevertheless the message is clear.Green Chemistry is hard it is intellectually challenging but most of all it is fundamental to the future of chemical production. Martyn Poliakoff School of Chemistry The University of Nottingham Nottingham UK NG7 2RD (A member of the IUPAC Working Party on Synthetic Design for Green Chemistry) Organic Reactions in Aqueous Media Chao-Jun Li and Tak-Hang Chan John Wiley & Sons Inc. New York 1997 214 pp ISBN 0-471-16395-3 Price $59.95 Many approaches for minimising the environmental impact of a chemical process involve reducing the quantities of chemicals consumed in that process. This may be by replacing stoichiometric reagents with catalytic ones or running the reaction without any solvent at all.In many organic reactions the second option may not be possible as the solvent is involved in the reaction either directly or indirectly by stabilising transition states or acting as a heat transfer medium. On too may occasions sadly little consideration is given to the choice of solvent it is chosen because it worked in the last reaction or because it is readily available. Where a solvent must be used water is without doubt the most acceptable in terms of cost and environmental impact. However despite its large liquid range and extremely high specific heat capacity it is frequently overlooked as a solvent for organic reactions perhaps because of a misplaced belief that organic reactions must require an organic solvent.Written by leading researchers in the field Organic Reactions in Aqueous Media endeavours to show that this belief is far from true citing hundreds of examples of common more obscure reactions which can be performed in water aqueous salt solutions and mixed water-organic co-solvent systems. An illustrative example given in the book is the Barbier-Grignard reaction which is of great synthetic importance due to the formation of a carbon-carbon bond. Undergraduate practical classes teach students to perform this type of reaction under scrupulously anhydrous conditions using magnesium or zinc metal and the reaction is followed by an aqueous workup step. Recent research has however produced a startlingly different procedure which exploits the relatively low first ionisation energy of indium along with its resistance to boiling water and reluctance to form oxides.Using indium metal in place of magnesium allows Barbier- Grignard reactions to be performed in water and the reaction conditions are mild enough to allow the use of functional groups such as acetals and carboxylic acids which would not survive the conventional system. Covering numerous other examples there are chapters on nucleophilic additions and substitutions oxidations reductions and hydrogenations and metal catalysed organic reactions including Heck reactions and hydroformylations. There is also a short but vital chapter on industrial applications of some of these reaction systems.There is a strong overall bias towards synthetic organic chemistry ranging from small relatively simple molecules right up to natural products and multi-ring compounds with a greater emphasis on what can be done than why the reactions proceed. However the introduction to the book does discuss the factors which may influence reactivity in aqueous systems reactions and solubilities in supercritical water and the ‘hydrophobic effect’. The use of aqueous salt solutions is considered too the ability to alter the internal pressure of an aqueous solution by changing the concentration or nature of the solute may be exploited in reactions which are strongly influenced by pressure. For example the rate of the Diels–Alder reaction between cyclopentadiene and butenone in water is doubled on the addition of lithium chloride. This volume is an excellent and enlightening attempt to bring together current knowledge on the surprisingly wide range of organic reactions which may be performed in aqueous systems. Water as a solvent may not be the solution to every problem but it should certainly be high on the list of solvents to try. If a new edition of this book were to be published in ten years time I would be very surprised if the chapter on industrial applications had not grown enormously. SJT

ISSN:1463-9262    

DOI:10.1039/gc990g21

出版商:RSC    

年代:1999

数据来源: RSC

摘要:

Massachusetts Toxics Use Reduction Act TURA establishes six toxics By the end of the 1980s significant shifts had occurred in attitudes towards pollution. Particularly in the United States phrases such as pollution control were being replaced by pollution prevention or source reduction. In one US state this ethos was enshrined in law. Becky Allen examines the impact of the Massachusetts Toxics Use Reduction Act on chemical users in the state and whether it could have an effect on green chemistry. As Green Chemistry goes to press the latest data on the use of toxic chemicals and generation of toxic waste in Massachusetts during 1997 are being analysed by the Massachusetts Toxics Use Reduction Institute and the Department of Environmental Protection.The analysis – due for release in Spring 1999 – is significant because enshrined in the Toxics Use Reduction Act 1989 (TURA) is the target to cut toxic waste generation in the state by 50% by 1997. However between 1990 and 1996 Massachusetts firms had already reduced hazardous waste generation by 34% and cut their use of toxic chemicals by 24%. According to the Massachusetts Toxic Reduction Programme* ‘A central goal of TURA is to cut in half by 1997 the quantity or toxic and hazardous wastes generated by Massachusetts industries – using toxic use reduction techniques – while enhancing the capacity of Massachusetts businesses to grow and prosper.’ The Act itself defines toxics use reduction as ‘in-plant changes in production processes or raw materials that avoid or eliminate the use of toxic or hazardous substances or generation of hazardous by-products per unit of product so as to reduce risk to the health of workers consumers or the environment without shifting risks between workers consumers or parts of the environment.’ TURA only applies to certain industries in the state including mining and manufacturing to companies with over ten full-time employees and firms that manufacture process or use specified volumes of chemicals on various US Environmental Protection Agency lists.Where it does apply companies are required to file annual reports giving quantities of each listed chemical used or generated and to submit a toxics use reduction plan every two years.Fees are charged by the state for filing the forms and for help in preparing plans. A cost-benefit analysis between 1990 and 1997 estimates total savings to businesses under TURA of $14 million excluding any net benefit due to reduced occupational and environmental exposures. Costs totalling $76.6 million include compliance costs of $49.4 million as well as capital investment by Planning toxics use reduction use reduction techniques l chemical input substitution l product reformulation l production unit redesign or modification l production unit modernisation l improvement in operations and maintenance l closed-loop recycling The goal of TURA is to cut toxic and hazardous wastes generated by Massachusetts industries while enhancing the capacity of businesses to grow and prosper in a business involves a step-by-step process l setting goals and priorities l analysing the process l identifying TUR options l evaluating TUR options l implementing TUR changes l measuring progress F EAT U R E C G Green Chemistry February 1999 G23 F E AT U R E Textile printing is one area where companies are participating in TURA programmes GC businesses.Benefits largely accrued from savings in firms’ operating costs ($88.2 million). Among the 600 companies participating in the TURA programme is the Cranston Print Works Company of Webster MA. Cranston prints and finishes cotton and blended fabrics and the printing process involves acid treatment of dyes.Process changes included in-process acid recycling and carbon dioxide treatment of wastewater. Top five toxic chemicals used in Massachusetts (by volume) 1 Styrene monomer 2 Copper 3 Sodium hydroxide 4 Hydrochloric acid 5 Sulfuric acid Top five toxic chemicals generated as by-product in Massachusetts (by volume) 1 Sodium hydroxide 2 Toluene 3 Sulfuric acid 4 Methyl ethyl ketone 5 Ethyl acetate G24 Green Chemistry February 1999 The acid stream in-line recovery unit has reduced the company’s annual acetic acid use by over 130,000 kilos and the substitution of carbon dioxide for sulfuric acid to treat the alkaline wastewater has eliminated an annual use of sulfuric acid of around 1.2 million kilos.According to Cranston the capital expenditure on the acid recycling system was $235,000 and $93,000 on the carbon dioxide wastewater system. Annual savings include $84,000 previously spent on acetic acid and $200,000 in wastewater treatment costs. Despite its impact on chemical use and waste generation TURA has been a less important catalyst for green chemistry in Massachusetts (a state which does not have a large chemical manufacturing sector) than consumer pressure. Feedback from industry in Massachusetts supports the business theory that customer needs drive new products and innovation says Liz Harriman of the Massachusetts Toxics Use Reduction Institute. According to Harriman ‘I do not think that the chemical industry in Massachusetts has felt strongly motivated to go to green chemistry by TURA .. . However some progressive chemical companies and formulators of chemistries have made a lot of progress in going to safer formulations.’ Instead Harriman thinks that the impetus will come from further down the supply chain. ‘It makes sense that the users of toxic chemicals have nothing to lose and everything to gain by going to less hazardous cost-effective materials. On the other hand it is risky and expensive for chemical manufacturers to develop new materials when the existing ones are working and selling . . . We are counting on the users of those chemicals and formulations who are more motivated to use safer chemistries to convince their suppliers that “that's what the customer wants.” This is of course a much more convincing argument for the chemical company,’ she says. *Massachusetts is Cleaner & Safer Report on the Toxics Use Reduction Program Massachusetts Toxics Use Reduction Programme 1997. Evaluating Progress a Report on the Findings of the Massachusetts Toxics Use Reduction Program Evaluation Massachusetts Toxics Use Reduction Programme 1997.

ISSN:1463-9262    

DOI:10.1039/gc990g23

出版商:RSC    

年代:1999

数据来源: RSC

摘要:

Venice – the venue for the first Green Chemistry Summer School First Postgraduate Summer School on Green Chemistry Venice Italy August 29 – September 6 1998 The First Postgraduate Summer School on Green Chemistry was held in Venice Italy (August 29 – September 6 1998) at the new campus of Venice International University (VIU – http://www.unive.it/ –viu) on the island of San Servolo. Its aim was to teach young graduate and postgraduate chemists from different European countries how to approach pollution prevention from a chemical standpoint. It was the first of a series of three Summer Schools the second will be held from September 6 to 12 1999; and the third in the year 2000. The deadline to apply for this years’ School is 15 June (see http://www.unive.it/inca).Each Summer School is organized by the Italian National Interuniversity Consortium ‘Chemistry for the Environment’ (INCA). Its director Professor Pietro Tundo chair of Organic Chemistry of the Department of Environmental Sciences of Ca’ Foscari University in Venice is an active researcher in Green Chemistry. He was among the first European scientists to indicate Green Chemistry as a fundamental tool to approach pollutant source reduction for the chemical industry. Funding is provided through activity no. 4 of the ‘Training and Mobility of Researchers’ (TMR) program of the European Commission entitled ‘Euroconferences Summer Schools and Practical Training Courses’ (http://www.cordis.lu/tmr/home.html).It covers travel and lodging scholarships for European students who are accepted at the School while funds to cover instructors’ expenses come in part from INCA itself. To reduce costs and to accelerate and simplify application procedures all contacts are maintained through a web page (http://www.unive.it/inca) and the authors’ e-mail alvise@unive.it. C G E V E NT The intended participants are young researchers in chemistry (the age limit is 35) from the European Union either from academia or industry interested in understanding the issues of pollution prevention and to address them through the innovation of chemical processes and also in view of the need to anticipate the evolution of environmental regulations for the chemical industry.Instructors are selected based on their internationally recognized contribution to research and promotion of Green Chemistry. Lessons are at the level of state-of-the-art research contributions but also cover background material extensively. Existing clean chemical processes case histories and topics related to current research in Green Chemistry are explained in order to familiarize students with the strategies behind designing ‘greener’ synthetic routes. For the first year emphasis was given to the description of chemical technologies for new catalytic processes and to the use of alternative solvents and reagents; a total of 12 lessons were held. Policy issues which steer the development of Green Chemistry at the industrial academic and governmental levels were also widely discussed prompted by the interest shown by students.Forty-five students attended from thirteen different countries. A poster session gave them the opportunity to establish new contacts and to exchange information about their research in Green Chemistry. Posters of high scientific level were presented by most of the students attending; three were judged outstanding and were presented with a book award and a certificate by the instructors. Marcella Bonchio (in Professor Scorrano’s group at the University of Padova) was recognized for her work on ‘Ti(IV) and Zr(IV)/chiral trialkanolamine peroxo complexes a new class of catalytic enantio selective oxidants’; William Gray (in Professor Poliakoff’s group at the University of Nottingham UK) won with a poster on ‘Organic reactions in supercritical fluids’; and Annegret Stark (in Professor Seddon’s group at The Queen’s University of Belfast UK) for Green Chemistry February 1999 G25 E V E N T C G a poster on the ‘Manufacture of two important ionic liquids’.The following is a short summary of the lectures divided into the three focus areas of last year’s Summer School. Each session often evolved into an interactive discussion rather than a traditional lecture which followed the pattern laid out by the speaker. Catalytic processes The development of new catalytic systems proved to be one of the most commonly used approaches towards cleaner chemical processes.In fact seven of the twelve lectures had catalysis as the main focus. In particular solid catalysts were treated extensively since they have the advantage of being non-toxic easy to handle and recoverable; they can be made polyfunctional; and they may afford shape selectivity and minimize waste. Bernard Witholt (ETH – Zürich Switzerland) described the use of biocatalysis in the production of a variety of compounds both in aqueous media and in organic solvents. An overview of the advantages of enzyme catalysis was given i.e. stereo- and regio-specificity limited use of toxic reagents limited generation of harmful side products technical advantages not to mention the psychological advantage of being able to label the products as ‘biological’.Future trends to expand the scope of biocatalysis were finally outlined. Mieczyslaw Makosza (Polish Academy of Sciences Poland) was among the first scientist in the early 1960s to develop phase transfer catalysis and to explain the mechanism of the reaction at the interface. His lecture described a number of applications of this technique (e.g. in carbene chemistry) and it highlighted the environmental advantages of this technique over traditional processes and its applicability even at the industrial level. James Clark (University of York UK) showed the applications of heterogenised catalysts (e.g. zeolite and clay supported peracids fluorides hydroxides metals alkoxides etc.) for a variety of reactions.These catalysts have the advantage of being non-toxic easy to handle and recoverable and minimize waste. Michel Guisnet (Universite de Poitiers France) described zeolites their chemical characteristics and their applications as catalysts for reactions such as oxidations reductions alkylations and in the refining industry (e.g. for hydrocracking and isomerization). Other reactions which occur selectively in the presence of zeolites were also addressed. G26 Green Chemistry February 1999 Jose M. Lopez Nieto (Universidad Politecnica de Valencia Spain) talked about supported acid and superacid solid materials and their use as alternative catalysts for reactions of the petrochemical industry.In addition the alkylation reaction of isobutane catalyzed by solid acids was discussed. Ferruccio Trifirò (Università di Bologna Italy) compared the traditional processes for the production of methyl methacrylate and cyclohexanone oxime with alternative industrial processes of low environmental impact. The use of n-butane in place of benzene for the production of maleic anhidride was also covered. The second part of this lesson was devoted to heterogeneous oxidation catalysts for the production of fine chemicals en route to more sustainable chemical processes. Wolfgang Hölderich (RWTH Aachen Germany) focused on the characterization by spectroscopic methods of solid catalysts used for industrial ammoximation and isomerization reactions.Alternative solvents and reagents The use of new harmless inexpensive and recoverable solvent systems in place of traditional toxic organic solvents is another area of widespread interest. Joe DeSimone (University of North Carolina at Chapel Hill USA) was among the first to recognize the applicability of fluid CO2 as a solvent for extractions separations and chemical reactions. The development of perfluorinated surfactants for these purposes using CO2 as the non-polar solvent was described. The industrial application of such systems to the dry-cleaning industry in the US gave a clear indication of the industrial applicability of research in the field of Green Chemistry. Jan Engberts (University of Groningen The Netherlands) showed that Diels–Alder reactions are accelerated in water relative to organic solvents; an effect that can be explained by hydrophobic destabilization of the initial state and by the stabilization of the transition state.In some case water showed also a favorable effect on selectivity. Lewis-acid catalysis in water was also addressed showing that in some cases extremely efficient catalysis can be obtained. Kenneth Seddon (The Queen’s University of Belfast UK) gave a captivating lecture on the preparation and use of ionic liquids as clean solvents. Among the advantages of such solvent systems are their high polarity large liquid range low vapor pressure easy recovery and stability to water.Ionic liquids can be designed to optimize a reaction and are promising for two-phase catalysis. In addition a promising area for the development of cleaner processes is to replace harmful reagents with Green reagents. Pietro Tundo (Università Ca’ Foscari di Venezia Italy) developed a lecture on the use of dimethyl carbonate (DMC) as a green reagent. DMC is now produced by oxidative carbonylation of methanol rather than from phosgene. It was shown that it can be successfully employed in methoxycarbonylation reactions and methylation reactions in place of traditional toxic and dangerous reagents such as dimethyl sulfate and methyl iodide. Green Chemistry Research Policies A lecture was devoted to the factors that stimulated the birth of the concepts behind Green Chemistry.Joe Breen (The Green Chemistry Institute USA) and Paul Anastas (Environmental Protection Agency USA) described the approach taken in the U.S. to encourage industry and academia to pursue the development of cleaner chemical technologies. Many examples were given of successful greener processes which are currently being developed by industry and academia. The need for efficient dissemination of information on Green Chemistry at all levels of society industry government and academia was stressed. A round-table discussion was also held attended not only by the instructors and students of the Summer School but also by Robert Visser (OECD Head of the Environmental Health and Safety Division) and Canice Nolan (European Commission Directorate General XII).Discussion led to further understanding of the policy issues and funding matters particularly in the EU regarding Green Chemistry. Not surprisingly all students found this session particularly interesting a fact that indicated a concern not only for fundamental aspects of research but also for its political aspects. Finally also thanks to the relaxed and interactive atmosphere established between attendees and instructors a number of comments and suggestions were collected to improve the Summer School on Green Chemistry in 1999 and 2000. Students wrote a document (see following article) which indicates that they often learned for the first time at this Summer School about the concept of ‘Green Chemistry’ and about the novel idea that chemical technologies and processes can and should be sustainable and environmentally compatible.In this respect the students recognized the importance of the principles laid out during the School. Among other ideas the creation of a mailing list and web server was proposed in order to establish a network of researchers and institutions dedicated to the international exchange of information on Green Chemistry. It is currently being prepared within INCA’s web site and it will hopefully contribute to consolidate the network of young ‘green’ chemists started at the Summer School. Alvise Perosa Dipartimento di Scienxe Ambientali Universita Ca’ Foscari Dorsoduro 2137 30123 Venezia Italy http://www.inive.it/inca alvise@inuve.it Young Chemists establish first European Network on Green Chemistry The students who attended the first Green Chemistry Summer School have established the first European Network on Green Chemistry for students and other young scientists with strong commitments to the principles and practice of green chemistry.A Web page has already been set up and it is hoped that once the network has been established projects can be undertaken in association with related bodies both in industry and academia. Close links have already been established with the Royal Society of Chemistry's Green Chemistry Network (via Professor J. Clark University of York UK) the Green Chemistry Institute and INCA.The website also includes links to other related sites and information about Green Chemistry literature. Our major concern Our driving force is the promotion of Green Chemistry. We consider this to be the implementation of environmentally benign processes in industry private enterprises and academia. We hope to bring the ideas of Green Chemistry closer to chemists of all fields who should act responsibly and in the interests of global sustainability. Our strategy We plan on a rapid and efficient exchange of ideas between chemists both in Europe and throughout the world l the ENGC will provide expertise in Green Chemistry; l we will work on an efficient communication between people from industry academia and politics; l we will participate at meetings involving Green Chemistry; l we plan to organise workshops and meetings; l we will work on improving the reputation of chemistry as a whole.The ENGC is organised by the following individuals Marcella Bonchio University of Padova Italy (marcella@chor.unipd.it) Emanuelle Fromentin University of Poitiers France (fromentin@hotmail.com) Keith Gray University of Nottingham UK (pczwkg@unix.ccc.nottingham.ac.uk) Markus Haider MIT. USA. (mmhaider@mit.edu) Michael Valkenberg RWTH Aachen Germany (Valkenberg@rwth-aachen.de) The ENGC can also be contacted at http://www.engc.org. Statement by participants at the Summer School Introduction We as chemists understand the damage caused to the environment by many chemical processes.We recognize our responsibility to work towards a chemistry that will sustain and improve the quality of life for future generations. We think this can be achieved through a process governed by the principles of Green Chemistry as were laid down during lectures and discussions at this summer school. A revolutionary change like this can only be attained by close cooperation of the chemical industry and academia with responsible politicians economists non-governmental organizations and the general public. To further this cause we have outlined the major objectives that should E V E N T Conclusions Acknowledgments C G be addressed by the chemical community l Education – emphasis on environmental issues.l Solvents in chemical processes – reduction or even replacement by environmentally benign systems. l Atom efficiency of chemical reactions – reduction of chemical waste by increasing yields and selectivities of the processes. l Avoidance of hazardous substances as far as possible. l Energy efficiency of chemical processes. l Remediation–water air and soil Final goal overall sustainability We the participants of this Summer School on Green Chemistry very much appreciate this meeting in Venice. It stimulated intense discussions on all aspects of Green Chemistry. We believe our objectives could be advanced through further meetings of this kind that may lead to the establishment of a European network of young chemists. We anticipate the possibility of exchange and co-operation on these issues with related groups worldwide. In this respect we would greatly appreciate continued funding. We thank all those involved in organizing this event particularly Professor Pietro Tundo Dr. Alvise Perosa their co-workers and all the lecturers. We also would like to express our gratitude to the European Union for funding. Green Chemistry February 1999 G27

ISSN:1463-9262    

DOI:10.1039/gc990g25

出版商:RSC    

年代:1999

数据来源: RSC

摘要:

Summary Here reported are the first applications of methylalumoxane, an oligomeric compound of formula (MeAlO)n, as a catalyst for the epoxidation of allylic alcohols and the oxidation of benzylic, aliphatic (cyclic and linear) alcohols into the corresponding carbonyl compounds. Introduction Epoxidation of allylic alcohols to carbonyl compounds represent two fundamental preparative processes: in fact the appropriate exploitation of the reactivity of the epoxy alcohol or carbonyl functionalities often represents the key step of synthetic sequences leading to more complex molecules.Both the processes are achievable through a wide variety of procedures, which, especially as regards the conversion of alcohols to carbonyl compounds, are often based on the employment of transition metal reagents such as Cr(vi), Mn(vii), Mn(iv), Pb(iv), etc.However, these procedures are frequently affected by serious disadvantages (strong toxicity to humans and the environment, frequent requirement of high oxidant/substrate ratios to complete the reaction with consequent formation of noticeable amount of polluting waste, variable selectivity deriving from the occurrence of secondary reactions, etc.).In recent years these problems have been partially circumvented by supporting or incorporating the oxidative reagents into an inorganic matrix. Our interest has been recently attracted by the unusual catalytic properties showed by aluminosilicates in oxidative processes.1 In particular we found that commercially available aluminosilicates (3 Å and 4 Å molecular sieves), without any previous metal impregnation can be conveniently employed as heterogeneous catalysts in the stereoselective epoxidation of allylic alcohols with tert-butyl hydroperoxide (TBHP).2,3 The observed regioand stereoselectivity have been reasonably explained through the previous formation of tetracoordinate Al centres of type A on the external surface of the catalyst and the subsequent evolution to epoxy an alcohol by a Sharpless-type process.Alumoxanes are aluminium- and oxygen-containing materials, characterized by the presence of at least one oxygen bridge between two aluminium centres.4 In particular, alkylalumoxanes, easily available by carefully controlled hydrolysis of aluminium alkyls, belong to an industrially important class of oligomeric compounds of formula (RAlO)n.5,6 For example, methylalumoxane (MAO) (R = Me, n = 5–12) was found to be an efficient cocatalyst for group 4 metallocene catalyzed ethylene and propylene polymerization,7,8 and for the synthesis of highly syndiotactic polystyrene in the presence of tetrabenzyltitanium.9 Here we report that MAO has been shown to be a more convenient catalyst for the epoxidation of allylic alcohols with TBHP: in fact, because of the presence of a much greater number of active catalytic Al sites in these oligomeric species, in comparison with the ones situated on the outer surface of the molecular sieves, the fast formation of epoxy alcohols 2 was found to occur in a satisfactory way and under milder conditions (Scheme 1).Results and discussion Methylalumoxane can be considered an effective catalyst: in fact comparable results have been observed by the employment of solid MAO, obtained as a white powder after careful removal under reduced pressure of both the solvent and Me3Al,10 a com- Green Chemistry February 1999 27 Epoxidation and oxidation of alcohols A new procedure using the methylalumoxane/tert-butyl hydroperoxide system Laura Palombi,a Arrigo Scettri,*b Alessandra Barrellab and Antonio Protob a Centro CNR per lo Studio della Chimica delle Sostanze Organiche Naturali, Dip.di Chimica, Università ‘La Sapienza’, P.le Aldo Moro 5, 00185 Rome, Italy b Dipartimento di Chimica, Università di Salerno, 84081 Baronissi (Salerno), Italy Received 15th December 1998 Oxidations including epoxidations are of fundamental importance to synthetic organic chemistry—the products are used as intermediates and final products in numerous sectors of the chemical industry including pharmaceuticals and polymers.Unfortunately oxidation chemistry is commonly associated with the employment of toxic reagents and catalysts such as those based on high oxidation state heavy metals.In this article, a non-toxic catalyst is effectively used in a range of oxidation reactions; its ability to function in a hydrocarbon (as opposed to halogenated) solvent is a bonus and adds to the credibility of the chemistry as an environmentally acceptable oxidation methodology. JHC Green Context R1 R R3 Al O O O O R2 O A C GScheme 1 mon contaminant present in 5–10% amounts in the commercial product.With respect to molecular sieves, a lower degree of stereoselectivity was observed in the case of secondary allylic alcohols (with the exception showed in Table 1, entry g) but, rather surprisingly, threo diastereoisomers proved to be invariably the predominant products. It seems reasonable that this stereochemical outcome may be originated by the structural and conformational features of MAO, with the involvement of both linear and cyclic oligomers characterized by different degrees of flexibility. As regards the preparative aspects, it should be noted that no loss of efficiency was observed by performing geraniol epoxidation on a 10 mmol scale or in hydrocarbon solvent (83% yield).The synthetic potential of the MAO/TBHP system has been further confirmed by its employment in a new, highly efficient procedure for the conversion of alcohols into the corresponding carbonyl compounds (Scheme 2).As reported in Table 2, very satisfactory results have been obtained with a variety of secondary benzylic and aliphatic (linear and cyclic) alcohols. Note the high efficiency and selectivity of the process: in fact, final products are usually obtained in very high yields and contaminated only by very low amounts of the starting materials.R1 R R3 O Al O O R2 O OOH 2 1 – tBuOH –CH4 + R3 R1 OH R2 R R3 R1 OH R2 R O Al O Me Scheme 2 As regards the stereochemical aspects, rather poor diastereoselectivity was observed in the case of 4-tert-butylcyclohexanol, employed as a 80/20 trans/cis mixture; in fact, the interruption of the oxidation after 6 h (Table 2, entry g) afforded the carbonyl compound in 45% yield, resulting the recovered starting material as a 70/30 trans/cis mixture.The possibility of the employment of very mild conditions can be highly appreciated in the oxidation of sensitive alcohols, such as, for example, 1-(4-methoxyphenyl)ethanol which is rapidly changed into the corresponding mixed tert-butyl peroxide in 67% yield by treatment with the zeolite/TBHP system.On the grounds of these initial results, the exploitation of the catalytic properties of oligomeric alumoxanes seems to disclose a route to new pro- Table 2 MAO-catalyzed oxidation of alcohols to ketones with TBHP Yield Run Alcohol t/h (%)a a 1-Phenylethanol 2 92 b 1-(1-Phenyl-2-methyl)propanol 4 >95b c a-Tetralol 6 84 (16)b d 1-(2-Naphthyl)ethanol 16 >95b e 1-(4-Bromophenyl)ethanol 3 95 f 1-(4-Methoxyphenyl)ethanol 7 94 g 4-tert-Butylcyclohexanol 6 45 (55)b h 4-tert-Butylcyclohexanol 12 95 i Dihydrocholesterol 14 85 j Octan-2-ol 16 90 k 3-Methylcyclopentanol 12 93 a Yields refer to isolated, chromatographically pure, compounds.Values in parentheses refer to starting materials. b 1H NMR yields.OH R1 R2 O R1 R2 MAO/TBHP CH2Cl2 or n-C6H14 3 4 28 Green Chemistry February 1999 Table 1 Epoxidation of allylic alcohols with MAO/TBHP system Run Alcohol Catalyst Time/h T/°C Yield (%)a d.r. (T/E) a trans-2-Hexen-1-ol MAO 16 r.t. 68 3A Molecular sieves 96 45 63 b Geraniol MAO 2 4 70 MAO 2 r.t. 82 3A Molecular sieves 48 60 67 c trans-2-Nonen-4-ol MAO 20 4 70 (65/35)b 3A Molecular sieves 20 40 70 (37/63) d trans-3-Tridecen-5-ol MAO 2 r.t. 78 (64/36)b 3A Molecular sieves 48 45 81 (34/66) e 3-Methyl-2-nonen-4-ol MAO 2 r.t. 75 (58/42)b 3A Molecular sieves 18 40 71 (14/86) f 4-Methyl-3-nonen-5-ol MAO 3 4 84 (65/35) 3A Molecular sieves 72 45 89 (12/88) g 2-Methyl-2-nonen-4-ol MAO 2 4 80 (>95/5) 3A Molecular sieves 18 45 65 (82/18) a Experimental details for the reactions catalyzed by 3A molecular sieves are reported in ref. 8.All the yields refer to chromatographically pure compounds. Values in parentheses refer to the threo/erythro (T/E) diastereoisomeric ratio (d.r.). b 1H NMR yields.cedures for the oxidation of organic functionalities characterized by high simplicity (as regards both set-up and work-up), efficiency and selectivity.Experimental Preparation of solid MAO A 10% toluene solution of MAO (10 ml) is submitted to distillation under a slow flow of Ar at 80 °C under reduced pressure (2.0 mmHg). After the complete removal of the solvent and of trimethylaluminium, a white powder (800 mg) is obtained, which can be stored without any appreciable loss of activity in a drybox for 8–10 days.Experimental procedure for oxidation reactions Reactions were performed by stirring, in an ice bath and under an argon atmosphere, MAO (1.8 ml, 10% toluene solution), dry CH2Cl2 (12 ml) and the substrate (2 mmol). After 10 min, TBHP (1.5 eq) was added and the reaction, monitored by TLC and/or GLC, was continued at room temperature for the times reported in Tables 1 and 2.Then H2O (2 ml) was added and the filtered solution was directly poured onto the top of a silica gel chromatographic column. Elution with n-pentane/diethyl ether mixtures afforded the pure epoxy alcohols and ketones. Alternatively, the substrate (2 mmol) was added to a solution of solid MAO (100 mg) in n-hexane (6 ml); after addition of TBHP (1.5 eq) the reaction was continued as reported above.Acknowledgement We wish to thank MURST (Rome) for financial support. References 1 L. Palombi, F. Bonadies and A. Scettri, J. Mol. Catal., in press. 2 L. Palombi, F. Bonadies and A. Scettri, Tetrahedron, 1997, 53, 11369. 3 L. Palombi, F. Bonadies and A. Scettri, Tetrahedron, 1997, 53, 15867. 4 M. R. Mason, M. J. Smith, S. G. Bott and A. R. Barron, J. Am. Chem. Soc., 1993, 115, 4971. 5 H. Sinn, W. Kaminsky, H. J. Vollmer and R. Woldt, Angew. Chem., Int. Ed. Engl., 1980, 92, 390. 6 S. Pasynkiewicz, Polyhedron, 1990, 9, 429. 7 J. A. Ewen, J. Am. Chem. Soc., 1984, 106, 6355. 8 N. Ishihara, T. Seymiya, M. Kuramoto and M. Uoi, Macromolecules, 1986, 19, 2465. 9 C. Pellecchia, P. Longo, A. Grassi, P. Ammendola and A. Zambelli, Makromol. Chem., Rapid Commun., 1987, 8, 277. 10 K. Takai, K. Oshima and H. Nozaki, Tetrahedron Lett., 1980, 21, 1657. Paper 8/09768B Green Chemistry February 1999 29

ISSN:1463-9262    

DOI:10.1039/a809768b

出版商:RSC    

年代:1999

数据来源: RSC

摘要:

D I A R Y C G Conference Diary March 21–25 March 24–26 March 31 March 1999 Green Chemistry Symposium and 217th American Chemical Society National Meeting Anaheim USA (natlmtgs@acs.org) 5th European Symposium on Electrochemical Engineering University of Exeter UK (http://sci.mond.org) RSC Carbohydrate Group Spring Meeting March 25–26 Carbohydrates as a base for therapeutic agents University of York UK (robert.field@st-and.ac.uk) Engineering Solutions to Formulation Problems March 25 UMIST Manchester UK (carl.formstone@ukag.zeneca.com) 5th International Conference on Solar Energy March 30– Storage and Applied Photochemistry April 4 (SOLAR’99) and 2nd International Training Workshop on Environmental Photochemistry (ENPHO’99) Sonesta Hotel Heliopolis Cairo Egypt (http://www.photoenergy.org/solar99.html) Biotechnology for Chemists Symposium London UK (conference@rsc.org April 10–13 April 20–23 April 1999 6th Meeting on Supercritical Fluids Chemistry and Materials University of Nottingham UK (http://www.nottingham.ac.uk/supercritical/conf2.htm) 2nd International Conference on Organic Process Research and Development New Orleans USA (scientificupdate@dial.pipex.com) May 2–7 May 1999 195th Meeting of the Electrochemical Society Seattle WA USA (http://www.electrochem.org/meetings/195/meet.html) 16th North American Catalysis Society Meeting May 30– Catalysis and the Environment June 4 Boston MA USA (http://www.dupont.com/nacs/Boston99/) July 1999 Gordon Conference on Green Chemistry Oxford UK (jhc1@york.ac.uk) Advances in Polymerisation Methods Controlled Synthesis of Functional Polymers Prague Czech Republic (sympo@imc.cas.cz) Pre-OMCOS Symposium on Organometallics and Catalysis Rennes France (http://www.univ-rennes1.fr/umr6509/pre-OMCOS) 10th IUPAC Symposium on Organometallic Chemistry Directed towards Organic Synthesis Versailles France (genet@ext.jussieu.fr) 7th International Symposium The Activation of Dioxygen and Homogeneous Catalytic Oxidation–ADHOC99 University of York UK (http://www.rsc.org/lap/confs/adhoc-99.htm) August 1999 218th American Chemical Society National August 22–26 Meeting with symposium on Green Chemistry New Orleans USA (natlmtgs@acs.org) September 1999 4th European Congress on Catalysis (Europacat 4) Catalysis and Chemical Technologies for a Sustainable Future Rimini Italy (http://www.fci.unibo.it/ec4) Euromembrane 99 Leuven Belgium (http://www.vito.be/euromembrane99/) Biotrans '99 Sicily Italy (http://dept.chem.polimi.it/biotrans) G28 Green Chemistry February 1999 July 11–16 July 12–15 July 14–16 July 18–22 July 19–23 September 5–10 September 19–22 September 26– October 1

ISSN:1463-9262    

DOI:10.1039/gc990g28

出版商:RSC    

年代:1999

数据来源: RSC

摘要:

Summary Reaction of the square pyramidal cluster Ru5C(CO)15 with H2S affords the bridged butterfly species (m-H)Ru5C(CO)14(m-SH) in which H and SH coordinate with simultaneous cleavage of one Ru–Ru bond and displacement of one CO. Subsequent reaction with CO regenerates the starting cluster and eliminates elemental sulfur (S8) and dihydrogen. These reactions take place at ambient temperatures and pressures.Introduction Hydrogen sulfide is generated in vast quantities from the hydrodesulfurisation of sulfur compounds prevalent in petroleum and natural gas.1,2 With increasingly stringent environmental legislation the need to remove sulfur from fuels is becoming increasingly important due to the problems associated with their emission into the environment.3,4 The environmental problem does not end with the generation of H2S, but the H2S then must be disposed of in some way.Industry achieves this by the dehydrosulfurisation of H2S to elemental sulfur using the Claus process5 that operates according to the equation below: 2 H2S + SO2 ? 3/8 S8 + 2 H2O The Claus process is comprised of a very efficient heterogeneous alumina catalyst that operates at temperatures in excess of 300 °C.Homogeneous catalysts are also known but offer no significant advantage as they also require relatively harsh conditions6 and bacteria have also been used.7 In this paper we describe some preliminary results concerning a homogeneous system employing Ru5C(CO)15 which has certain differences and therefore possible advantages over the existing systems.Firstly, SO2 is not required and as such the limitations imposed in the equation above are no longer present, and secondly, the process operates under ambient conditions which could potentially reduce energy expenditure. Results and discussion The square pyramidal cluster Ru5C(CO)15, initially prepared8 and studied9,10 by the Johnson–Lewis group, is known to undergo a facile polyhedral rearrangement to a bridged butterfly (pseudotrigonal bipyramidal) geometry on reaction with small nucleo- Homogeneous dehydrosulfurisation under ambient conditions Harnessing the facile polyhedral rearrangement in the ruthenium carbonyl cluster Ru5C(CO)15 Alan J.Bailey,a Sandeep Basraa and Paul J. Dyson*b a Department of Chemistry, Imperial College of Science, Technology and Medicine, South Kensington, London, UK SW7 2AY b Department of Chemistry, The University of York, Heslington, York, UK YO10 5DD.E-mail: pjd14@york.ac.uk Received 15th October 1998 philes (see Scheme 1). For example, the reaction of Ru5C(CO)15 with acetonitrile affords the addition product, Ru5C(CO)15(NCMe), and redissolving this cluster in a non-coordinating solvent such as dichloromethane results in regeneration of the starting compound.10 Poë et al.have established that this polyhedral rearrangement mechanism is important in certain substitution reactions involving 2-electron donor ligands.11 In addition, the framework of Ru5C(CO)15 has also been found to act as a support on which certain organic transformations take place and the chemistry of this cluster has been reviewed recently.12 Scheme 1 Ru5C(CO)15 reacts rapidly with H2S, H2Se and HSR (R = Me, Et) at room temperature to afford HRu5C(CO)14(m-SH), HRu5C(CO)14(m-SeH) and HRu5C(CO)14(m-SR) (R = Me, Et), respectively.13 These derivatives are structural analogues and definitive characterisation of HRu5C(CO)14(m-SEt) has been obtained by a single crystal X-ray diffraction analysis.13 In accordance with a cluster with a total electron count of 76 the Ru atom skeleton adopts a bridged butterfly topology. The SEt group coordinates to one of the hinge Ru atoms and the bridging Ru Nu C –Nu C Ru5C(CO)15 Ru5C(CO)15(Nu) +Nu Green Chemistry February 1999 31 The splitting of hydrogen sulfide into its elements represents a useful reaction, turning a waste product into two valuable feedstocks.The system under study here allows this reaction to proceed under extremely mild conditions under an atmosphere of CO. The CO is not used up in the reaction, but is shuttled on and off the metal cluster, and can be recovered for reuse. At this stage in the work, the system is not catalytic. Further developments towards a genuinely useful system would require a catalytic version of the system to be developed. DJM Green Context C Gatom.The hydride ligand apparently bridges the Ru–Ru hinge bond. Closure of the cluster skeleton to the square pyramid found in the precursor can be achieved by thermal elimination of one carbonyl ligand. In our experiments, instead of heating HRu5C(CO)14(m-SH) to eliminate carbon monoxide, we treated it with CO at atmospheric pressure in a solution of refluxing dichloromethane, ca. 42 °C (Scheme 2).14 Regeneration of Ru5C(CO)15 was complete within 25 minutes. After removal of the solvent the residue was found to contain Ru5C(CO)15 (as indicated by the characteristic IR nCO stretching frequencies) and elemental sulfur which was detected by mass spectrometry. The mass spectrum confirmed the presence of sulfur showing a typical sequential regression from S8 to S1 and a qualitative test for H2 gas proved positive.The entire process (i.e. H2S followed by CO) was repeated several times using the same batch of cluster and slight decomposition was observed with wet solvents. While this process is not catalytic it represents a simple homogeneous method for dehydrosulfurisation under ambient conditions based on the facile structural rearrangement common to Ru5C(CO)15.It is quite remarkable that rupture of the Ru–S–Ru bond is quite so facile and this could be due to the fact that the sulfur ligand bridges an unsupported Ru–Ru vertex rendering it somewhat unstable. While the process operates under very mild conditions that could, in principle, save energy expenditure, it is complicated by the need for CO.However, the CO is not actually consumed and as long as none is lost from the system it could be reused indefinitely. Scheme 2 This work compliments earlier desulfurisation studies carried out by Deeming and co-workers using the triruthenium cluster Ru3(CO)12. Ru3(CO)12 was found to react with benzo[b]thiophene under relatively mild conditions to form Ru3(CO)8(C8H6) in which one Ru–Ru bond has been cleaved.However, this process was not found to be reversible.15 We also intend to study other clusters for related activity such as Os6(CO)18 16–18 which also undergo facile polyhedral rearrangements. Acknowledgements We would like to thank The Royal Society for a University Research Fellowship (P.J. D.) and ICI (Wilton) for financial support (S. B.). References 1 C. M. Friend and J. T. Roberts, Acc. Chem. Res., 1988, 21, 994. 2 R. J. Angelici, Acc. Chem. Res., 1988, 21, 387. 3 J. H. Clark and D. J. Macquarrie, Chem. Commun., 1998, 853. H2 + 'S' C Ru5C(CO)15 HRu5C(CO)14(m-SH) C H2S CO SH CO H 4 D. A. Vicie and W. D. Jones, Organometallics, 1998, 17, 3411 and references cited therein. 5 P. Grancher, Hydrocarbon Process, 1978, 57, 155. 6 A. Shaver, M. El-khateeb and A.-M. Lebuis, Angew. Chem., Int. Ed. Engl., 1996, 35, 2362. 7 J. Gasiorek, F. Domka and P. Gasiorek, Przemysl Chem., 1998, 77, 304. 8 C. R. Eady, B. F. G. Johnson, J. Lewis and T. Mather, J. Organomet. Chem., 1973, 57, C82. 9 D. H. Farrar, P. F. Jackson, B. F. G. Johnson, J. Lewis, J.N. Nicholls and M. McPartlin, J. Chem. Soc., Chem. Commun., 1981, 415. 10 B. F. G. Johnson, J. Lewis, J. N. Nicholls, J. Puga, P. R. Raithby, M. McPartlin and W. Clegg, J. Chem. Soc., Dalton Trans., 1983, 277. 11 D. H. Farrar, A. J. Poë and Y. Zheng, J. Am. Chem. Soc., 1994, 116, 6252. 12 P. J. Dyson, Adv. Organomet. Chem., 1998, 43, 43. 13 A. G. Cowie, B. F. G. Johnson, J.Lewis, J. N. Nicholls, P. R. Raithby and M. J. Rosales, J. Chem. Soc., Dalton Trans., 1983, 2311. 14 Using a two necked flask fitted with a gas inlet port and a reflux condenser, Ru5C(CO)15 (0.020 g, purple, IR nCO CH2Cl2 2067(s) and 2034(m) cm21) in CH2Cl2 (20 m) was reacted with H2S at ca. 20 °C for 5 minutes to afford HRu5C(CO)14(m-SH) (yellow, IR nCO CH2Cl2 2105(w), 2080(m), 2059(s), 2036(w), 2019(w), 2009(w) and 1963(vw) cm21) as described in ref. 9. IR spectroscopy and thin layer chromatography showed that conversion takes place quantitatively. Nitrogen was bubbled through this HRu5C(CO)14(m-SH) solution in order to remove any unreacted H2S. The solution was then heated to reflux (ca. 42 °C) and a steady stream of CO was passed through it for 25 minutes during which time the colour reverted back to the original purple.IR spectroscopy indicated quantitative conversion to Ru5C(CO)15 had taken place and mass spectroscopy was used to confirm the presence of sulfur [m/z 256 (rel. int. 20%) S8, 224 (3%) S7, 192 (11%) S6, 160 (14%) S5, 128 (85%) S4, 96 (20%) S3, 64 (7%) S2]. Mass spectrometry of HRu5C(CO)14(m-SH) did not show the presence of elemental sulfur. The process was repeated several times and the reaction traced by IR spectroscopy. 15 A. J. Arce, Y. de Sanctis, A. Karam and A. J. Deeming, Angew. Chem., Int. Ed. Engl., 1994, 33, 1381. 16 C. R. Eady, B. F. G. Johnson and J. Lewis, J. Chem. Soc., Chem. Commun., 1976, 302. 17 C.-M. T. Hayward and J. R. Shapley, Inorg. Chem., 1982, 21, 3816. 18 B. F. G. Johnson, R. A. Kamarudin, F. J. Lahoz, J. Lewis and P. R. Raithby, J. Chem. Soc., Dalton Trans., 1988, 1205. Paper 8/08023B 32 Green Chemistry February 1999

ISSN:1463-9262    

DOI:10.1039/a808023b

出版商:RSC    

年代:1999

数据来源: RSC

摘要:

Summary A simple, efficient and environment-friendly procedure has been developed for acylation of ferrocene with direct use of carboxylic acid in the presence of trifluoroacetic anhydride on the solid phase of alumina. A wide range of structurally varied carboxylic acids have been found to provide selectively the monoacylated products in high yields. Introduction Ferrocene and its derivatives have been the subject of current interest because of their potential uses as chiral ligands in organic synthesis1 and as important materials in various fields.2 Thus, derivatization of ferrocene has received special attention.3 Acylation of ferrocene is a very important reaction as it introduces a carbonyl functionality which is highly manipulable.Although a number of methods are available in the literature4 for acylation of ferrocenes they have serious disadvantages of producing a mixture of products containing mono- and di-acylated derivatives together with unreacted starting material which requires separation at a subsequent stage.More seriously, the use of toxic chemicals like AlCl3, BF3, PCl3 and acid chlorides entails environment pollution.Thus, an efficient and eco-friendly procedure for this important transformation is needed. Recently, we have introduced a simple procedure for regioselective acylation of aromatic ethers with carboxylic acids on the solid phase of alumina in the presence of trifluoroacetic anhydride5 and we have discovered that this procedure also works very well for acylation of ferrocene. Results and discussion In a typical general procedure, a mixture of carboxylic acid and trifluoroacetic anhydride was added to ferrocene adsorbed on the surface of activated acidic alumina and mixed uniformly with shaking.The mixture was kept at room temperature with occasional shaking for a certain period of time until the reaction was complete. The product was isolated by simple extraction of the solid mass by ether followed by usual workup.Several structurally varied carboxylic acids were used in this acylation reaction to provide the corresponding monoacylated ferrocenes in excellent yields. The results are summarised in Table 1. The reactions with aromatic acids are rather slow and conversions are not complete even after 8 hours. However, no side product is isolated in these reactions; only the unreacted ferrocene and carboxylic acids were recovered.In general, all the Selective monoacylation of ferrocene An eco-friendly procedure on the solid phase of alumina Brindaban C. Ranu,* Umasish Jana and Adinath Majee Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta-700 032, India Received 13th November 1998 reactions are very clean and monoacylated products are obtained as the sole isolable compounds. Presumably, alumina acts here as a Lewis acid in effecting the Friedel–Crafts acylation of ferrocene with the mixed anhydride of the carboxylic acid and trifluoroacetic anhydride.Conclusion This method on the solid surface of alumina provides a very convenient and efficient procedure for acylation of ferrocene. The notable advantages of this methodology are direct use of carboxylic acids, mild conditions (room temperature), operational simplicity, generality, excellent selectivity (only monoacylation occurs), high yields (85–98%) and no environmental pollution, and thus it offers significant improvements over other procedures involving Friedel–Crafts acylation of ferrocenes.4 We believe this will find significant applications in the synthesis of ferrocene derivatives. Representative experimental procedure A solution of ferrocene (186 mg, 1 mmol) in dry CH2Cl2 (2 ml) was adsorbed on the surface of activated (heated at 150 °C for 3 h under reduced pressure and then cooled under nitrogen) alu- Green Chemistry February 1999 33 Functionalised ferrocenes are currently of great interest due to their potential as planar-chiral ligands for, e.g., hydrogenation catalysts.One of the most important methods of functionalisation of these materials is Friedel–Crafts acylation, a process which typically uses substantial quantities of strong Lewis acids such as aluminium chloride. The development of alternative, green procedures is therefore of interest.The use of alumina and trifluoroacetic anhydride as an activating system for carboxylic acids has been shown to allow the highly selective monoacylation of ferrocene. It is thought that the reaction proceeds via a mixed carboxylic/trifluoroacetic anhydride. Yields are excellent in most cases, in others the unreacted carboxylic acid can be easily recovered.Work up procedures are simple and convenient on a small scale, but would need further optimisation to provide a genuinely green overall process. DJM Green Context C Gmina (acidic, 3 g) and then the solvent was evaporated off completely under vacuum. To this was added a mixture of acetic acid (120 mg, 2 mmol6) and trifluoroacetic anhydride (525 mg, 2.5 mmol6) with shaking.The mixture was then kept at room temperature with occasional shaking under a moisture guard for a certain period of time as required to complete the reaction. [In all the reactions, a colour developed (usually pink, but in a few cases green and blue) and darkened with progress of reaction.] The solid mass was then eluted with Et2O, and the ether extract was then washed with an aqueous solution of sodium hydrogen carbonate and brine and dried over anhydrous sodium sulfate.Evaporation of solvent furnished practically pure (by 1H NMR) monoacetyl ferrocene (223.5 mg, 98%). This was further purified by filtering it through a short column of silica gel to afford the analytically pure product, mp 85–86 °C. The other acylated products are also obtained following the same procedure and identified by spectral (IR, 1H and 13C NMR) and analytical data.The unreacted carboxylic acids (Table 1, entries 12, 13) were recovered from the hydrogen carbonate extract by acidification and extraction with ether. However, trifluoroacetic acid, possibly being too water soluble and not being a high boiling liquid (bp 72 °C), was not isolated in this work-up process.Acknowledgements U. J. and A. M. are thankful to CSIR for their fellowships. References 1 (a) A. Togni, Angew. Chem., Int. Ed. Engl., 1996, 35, 1475; (b) H. B. Kagan, P. Ditter, A. Gref, D. Guillaneux, A. Masson- Szymczak, F. Rebiere, O. Riant, O. Samuel and S. Tauden, Pure Appl. Chem., 1996, 68, 29; (c) S.-I. Fukuzawa and H. Kato, Synlett, 1998, 727; (d) W.G. Jary and J. Baungartner, Tetrahedron: Asymmetry, 1998, 9, 2081. 2 (a) A. M. Giroud-Godquin and P. M. Maitlis, Angew. Chem., Int. Ed. Engl., 1991, 30, 375; (b) A. Riklin, E. Katz, I. Willner, A. Stocker and A. F. Brueckmann, Nature, 1995, 376, 672. 3 (a) L. Schwink, S. Vettel and P. Knochel, Organometallics, 1995, 14, 5000; (b) S. Bhattacharyya, Synlett, 1998, 837 and references therein. 4 (a) K. Plesske, Angew. Chem., Int. Ed. Engl., 1962, 1, 312; (b) D. E. Bublitz and K. L. Rinehart, Jr., in Organic Reactions, John Wiley, New York, 1969, 17, 23 and references therein; (c) R. Vukicevic, Z. R. Ratkovic, M. D. Vukicevic and S. K. Konstantinovic, Tetrahedron Lett., 1998, 39, 5837 and references therein. 5 B. C. Ranu, K. Ghosh and U. Jana, J. Org. Chem., 1996, 61, 9546. 6 With 1 equivalent of carboxylic acid and 1 equivalent of trifluoroacetic anhydride the reaction is considerably slow and the conversion is also not complete even after 12 h. However, use of 2 equivalents of carboxylic acid and 2.5 equivalents of TFAA accelerated the reaction to a great extent producing only the monoacylated product. But, interestingly, use of 4 equivalents of carboxylic acid and 8 equivalents of TFAA leads to diacylation quantitatively (2 examples) although the condition is yet to be generalised. Paper 8/08890J 34 Green Chemistry February 1999 Table 1 Acylation of ferrocene with carboxylic acid/ TFAA on the surface of alumina Yield of 2 Entry RCO2H, R = Time/h (%)a 1 CH3 0.5 98 2 CH3CH2 0.5 90 3 PhCH2 1.5 96 4 CH3(CH2)6 1.0 93 5 CH3(CH2)16 1.0 94 6 CH3CH(NO2)(CH2)2 1.0 85 7 PhS(CH2)3 1.5 88 8 (CH3)2CH 0.5 95 9 (Ph)2CH 1.5 93 10 PhSCH2CH(CH3) 1.5 89 11 C6H11 1.0 92 12 Ph 8.0 55b 13 p-OMe–Ph 8.0 58b a Yields refer to pure isolated products, fully characterized by spectral and analytical data. b The rest is recovered starting material.

ISSN:1463-9262    

DOI:10.1039/a808890j

出版商:RSC    

年代:1999

数据来源: RSC

摘要:

Selective para-bromination of phenyl acetate under the control of zeolites, bases, acetic anhydride or metal acetates in the liquid phase Keith Smith,*a Ping Hea and Ashley Taylorb a Centre for Clean Chemistry, Department of Chemistry, University of Wales Swansea, Singleton Park, Swansea, UK SA2 8PP b Rhône-Poulenc Agriculture Ltd., Sweet Briar Road, Norwich, UK NR6 5AP Received 21st October 1998 Summary HBr formed during the bromination of phenyl acetate has a major influence on the selectivity of the reaction.Sodium forms of zeolites X and Y increase the selectivity markedly by a process of cation exchange that removes this HBr. Removal of the HBr prevents formation of phenol and allows the bromination of PA to give almost exclusively the para isomer in quantitative yield.Bases, acetic anhydride and some metal acetates also improve the selectivity. These findings offer a variety of strategies for clean synthesis of para-bromophenyl acetate. Introduction The chemicals industry is increasingly required to minimise its environmental impact.1 The needs are particularly acute in the field of electrophilic aromatic substitution2 where reactions can be poorly regioselective, may produce polysubstituted as well as monosubstituted products, and often use large quantities of Lewis acids, which are destroyed during the work-up process and then require disposal.Because of their special crystalline structures, zeolites can influence the selectivity of aromatic substitution. 3 The para isomer is favoured because steric factors favour the transition state within the zeolitic cages.We have previously shown, for example, how the use of zeolites or other solids can help to gain selectivity over nitration,4 chlorination,5 bromination, 6 methanesulfonylation7 and allylation8 reactions of simple aromatic compounds. Despite the many applications of zeolites in catalytic processes, relatively little attention has been paid to the use of zeolites in the field of aromatic bromination.Several studies have shown that various ion-exchanged zeolites enhance the rates and para-selectivities of brominations of alkyl- or halogenoarenes, 9–14 but in the case of toluene, for example, the selectivities were still not ideal. Sasson et al. reported that sodium exchanged Y zeolite improved the para-selectivity in the bromination of toluene, but that the selectivity and rate of reaction diminished as the reaction proceeded.15,16 We were able to show that there is a highly selective stoichiometric reaction with the zeolite followed by a slower and less selective catalytic reaction and have developed a generally useful method for para-bromination of alkyl- and halogeno-benzenes.6 It was of interest to know if this approach would be useful in providing a cleaner approach to the industrially important production of para-bromophenyl The selective bromination of aromatics represents a major challenge in the preparation of many important intermediates. This contribution investigates the factors influencing selectivity in the bromination of a reasonably activated system, phenyl acetate.The results indicate that the major contribution of zeolites in this reaction is not, as might be expected, due to shape selectivity, but is rather a consequence of their ability to scavenge HBr, which causes a non-selective competitive reaction. The paper goes on to evaluate alternative methods for the effective removal of HBr. The importance of this paper is that it provides a series of highly selective routes to the desired products, with minimal side reactions, and that it demonstrates that a careful study of a reaction can lead to a much improved understanding of the real factors at play.DJM Green Context acetate. It was not obvious what would happen during bromination of phenyl acetate, which is not only reactive (more reactive than halogenobenzenes but less than toluene),17 but also capable of cleavage by HBr to give phenol, an even more highly activated compound.In fact, certain zeolites turned out to provide highly selective reactions, primarily by removing HBr in an efficient manner rather than through any reliance on shape selectivity. Therefore, we investigated alternative approaches for the removal of HBr and now report several possible ways for conducting the reaction in a cleaner manner.Results and discussion 1. Bromination of phenyl acetate over zeolites Preliminary studies on the bromination of phenyl acetate 1 in the presence of a sodium-form mordenite zeolite in dichloromethane showed that the initial reaction rate was much lower than in its absence, but that the selectivity was enhanced.18 After some time, however, the reaction rate suddenly increased dramatically and simultaneously the selectivity declined. A possible explanation was that the HBr generated by the reaction was absorbed by the zeolite, either through direct absorption into the narrow channels Green Chemistry February 1999 35 C Gor via ion-exchange, until the capacity was exceeded, whereupon an unselective HBr-catalysed process took over. Indeed, when HBr was added to a reaction mixture over mordenite, similar results to those without mordenite were obtained.It seems likely that HBr reacts under these conditions with 1 to produce phenol, which reacts more rapidly and less selectively with bromine. The zeolite serves to remove the HBr.In view of these findings, an extensive study on bromination of 1 over various zeolite catalysts was carried out and the results are presented in Table 1. As the results in Table 1 show, use of NaY zeolite as catalyst gave a much better rate enhancement than use of HY, indicating that strong acidity is not preferred for the selective para-bromination of 1.19 Use of NaY and NaX zeolites exhibited excellent para-selectivity and gave high yields under very mild conditions.Indeed, even when the phenyl acetate was completely converted, the only product obtained in the presence of NaY was 4-bromophenyl acetate 2. Sodium forms of other zeolites also gave good para-selectivity but the yields were much lower than with NaY under comparable conditions. These results are consistent with a lower rate of diffusion into the more restricted pores of the other zeolites. A range of different cation-exchanged Y zeolites were next compared (Table 2). The results showed that all the zeolites produced 2 selectively, but the fastest reactions and best yields were obtained with the Na and K forms.We conclude that a highly selective stoichiometric reaction involving the NaY or KY zeolite takes place [eqn.(1)], as found with toluene.6 There appears to be no advantage from the stronger acidity associated with some of the multivalent cations20 nor from the lesser or greater geometrical constraints brought about by other alkali metal cations.21,22 The yield of 2 could be improved further by increasing the reaction temperature, the reaction time, the amount of bromine or the amount of zeolite.The reaction of 1 (10 mmol) with bromine OAc + Br2 + NaY OAc + NaBr + HY Br (1) 1 2 Table 1 Bromination of 1 in the presence of various catalystsa Catalyst 1 (%)c 3b (%)c 2 (%)c Othersb (%)c None 100 — — — Noned 67 — 7 26 HY 99 — 1 — NaY 32 — 68 — NaX 42 — 58 — Nab 96 — 3 — NaMord 97 — 2 — NaZSM-5 100 — — — AlCl3 3 5 52 33 a Bromination of 1 (10 mmol) with bromine (10 mmol) over catalyst (3 g) in CH2Cl2 (30 ml) at room temp.for 2.5 h. b Compound 3 is 2-bromophenyl acetate; others are phenol, 2- bromophenol, 4-bromophenol, 2,4-dibromophenol and 2,4- dibromophenyl acetate. c Absolute yields were determined by quantitative GC. d 20 mmol of 1 and 20 mmol of bromine were used in otherwise identical conditions.(20 mmol) in the presence of NaY (4 g) for 5 h at 25 °C led to a quantitative yield of 2. Although it should be possible to recover the HY zeolite–NaBr solid mixture and heat it to give back the NaY zeolite,6 or to reconvert the HY into NaY by a standard ion-exchange process, such processes would render the overall synthesis more expensive than simple reaction of bromine with 1.Therefore, the effects of alternative additives capable of removing HBr were investigated. An additional benefit from such additives might be the avoidance of the need for solvent. 2. Effect of acetic anhydride (Ac2O) Addition of Ac2O to the reaction medium might limit phenol formation by trapping HBr formed and by converting any incipient phenol back into its acetate [eqn.(2) and (3)]. The effect of Ac2O on the selectivity was therefore investigated. The results showed that with zinc chloride or aluminium bromide as catalyst the reaction produced negligible amounts (<1%) of 2-bromophenyl acetate (3) in the presence of an equimolar amount of acetic anhydride, even at high conversions (>90%) of the substrate. The process could be optimised to produce a final mixture containing ca. 99% of 2 by use of a small excess of bromine, no solvent and a reaction time of 5 h at 24 °C. Without catalyst the reactions were very slow. 3. Influence of bases An alternative method for removal of HBr would be to add a base to the reaction medium. Therefore, reactions were carried out in the presence of solid NaHCO3, Na2CO3 and NaOAc together with dichloromethane as solvent (Table 3).As shown in Table 3, all these bases resulted in high selectivity, though the reactions were slow, being ca. 80% complete after 24 h at 0 °C. 4. Influence of certain metal acetates Electrophilic aromatic bromination over thallium(iii) acetate is highly regioselective.23,24 It is possible in the present case that certain metal acetates could act both as catalysts and as scavengers of HBr, thereby providing another possible way of gain- (2) OH OAc + AcOH (3) Ac2O + HBr AcBr + AcOH Ac2O + 36 Green Chemistry February 1999 Table 2 Effect of compensating cation on the zeolite Y catalysed bromination of 1a Catalyst 1 (%)b 2 (%)b La-Y 97 3 Mg-Y 91 9 Al-Y 91 9 Li-Y 56 43 Na-Y 32 68 K-Y 43 56 Cs-Y 78 21 a See footnote a to Table 1.b Absolute quantities, determined by GC. No other products were observed.ing selectivity. Several metal acetates were therefore tried either in the presence or absence of acetic anhydride (Table 4). Excellent selectivity was obtained, particularly with zinc acetate, even when Ac2O was not used in the reaction. It is likely that the selectivity results because HBr generated in the reaction is trapped by the zinc acetate to give acetic acid and zinc bromide, thereby avoiding the formation of phenol.The reaction occurred much more rapidly than in the absence of the salt. Either the zinc acetate itself or the product zinc bromide could have been responsible for catalysing the reaction, which was complete within 5 h at 0 °C. Although this method is highly selective, however, it will be unattractive for commercial use on grounds of potential environmental impact.Conclusions HBr formed during the bromination of 1 is a main factor influencing the regioselectivity. The HBr reacts with 1 to produce phenol, which then reacts rapidly and indiscriminately. Zeolites NaY and NaX can accelerate the bromination of 1 and significantly increase the selectivity by a process that incorporates cation exchange to remove the HBr formed.Heating the recovered zeolite –NaBr mixture or ion-exchanging the recovered zeolite with aqueous NaCl should regenerate its activity. Simple bases can also improve the selectivity by neutralising the HBr formed, while acetic anhydride increases the selectivity because it can react with both HBr and phenol to prevent the unwanted side reactions.However, these reactions are then slow unless additional catalysts are added. Finally, the bromination of 1 with bromine is also improved by certain metal acetates, notably zinc acetate, which acts both to remove HBr and to catalyse the reaction. These studies reveal a variety of strategies that might have benefit for the clean bromination of phenyl acetate or related substrates.Table 4 Effect of some metal acetates on the brominationa Metal acetate (mass/g) Ac2O/mmol Time/h 1 (%)b 3 (%)b 2 (%)b Cu(OAc)2 (3) 40 3 28 — 71 Co(OAc)2 (5) 40 4 41 1 58 Hg(OAc)2 (5) 40 5 2 1 96 Zn(OAc)2 (5) 40 5 — 1 99 Zn(OAc)2 (5) — 5 — 1 99 a Reaction conditions: 1 (40 mmol), bromine (60 mmol), metal acetate and acetic anhydride, at 0 °C.b See footnote b to Table 2. Experimental Reagents Samples of NaY and NaX zeolites were provided by Union Carbide, while ZSM-5, b and mordenite zeolites were supplied by PQ Zeolites (now Zeolyst International). Other cation forms of zeolites were prepared by a literature procedure.16 All zeolites were heated overnight at 140 °C before use. All bases and metal acetates were dried overnight at 100 °C.Solvents were used without additional purification. Standard procedure used during method development Procedure for zeolite-catalysed bromination of PA. Phenyl acetate (10 mmol), the zeolite (3 g) and dichloromethane (30 ml) were mixed in a three-necked round-bottomed flask fitted with a calcium chloride guard tube and a magnetic stirrer and protected from light.The mixture was stirred at room temperature for 15 min, after which bromine (10 mmol) was added. After a suitable time (typically 2.5 h), the reaction mixture was filtered through a sintered funnel and the solid was rapidly washed with acetone. An aqueous sodium hydrogen sulfite solution (10%, 30 ml) was quickly added to the filtrate to remove bromine and hydrogen bromide.The organic layer was washed with distilled water (3330 ml), dried over anhydrous magnesium sulfate, and filtered. Dodecane (60 ml, 0.045 g) was added as internal standard and the solution was subjected to quantitative GC analysis. The residual solid was stirred with acetone (15 ml) for 30 min in order to desorb any materials in the channels of the zeolite, then filtered.An aqueous sodium hydrogen sulfite solution (10%, 30 ml) was quickly added to the filtrate and the aqueous phase was then extracted with dichloromethane (3310 ml). The organic layer was treated and analysed according to the method described above. Bromination of 1 in the presence of bases. The procedure was similar to the procedure for zeolite-catalysed bromination of 1, but with a base present instead of a zeolite and with the following components and conditions: 1 (50 mmol), bromine (50 mmol), base (50 mmol) and dichloromethane (10 ml), at 0 °C for 24 h.Bromination of 1 in the presence of metal acetates. The procedure was similar to the procedure for zeolite-catalysed bromination of 1, but with a metal acetate present instead of a zeolite and with the following components and conditions: 1 (40 mmol), bromine (60 mmol), Ac2O (40 mmol) and metal acetate (3–5 g), at 0 °C for 3–5 h (see Table 4 for details). No other solvent was used.Bromination of 1 in the presence of acetic anhydride. The procedure was similar to the procedure for zeolite-catalysed bromination of 1, but with acetic anhydride present instead of a zeolite and with the following components and conditions: 1 (40 mmol), bromine (40 mmol), Ac2O (60 mmol), at 0 °C for 5 h.No other solvent was used. Acknowledgements We thank the British Government for an Overseas Research Studentship to Ping He, Rhône-Poulenc for financial support, PQ Zeolites (now Zeolyst International) and Union Carbide for gifts of several zeolites, and the EPSRC and the University of Wales for grants which enabled the purchase of NMR equipment used in this study. Green Chemistry February 1999 37 Table 3 Effect of bases on the selectivity of bromination of 1a Amount of base Othersb Base (mmol) Time/h 1(%)c 3(%)c 2(%)c (%)c — 0 1.5 12 5 76 7 NaHCO3 38 24 21 3 76 — NaHCO3 50 24 19 1 80 — NaOAc 50 24 26 1 73 — Na2CO3 25 24 22 1 77 — a Bromination of 1 (50 mmol) with bromine (50 mmol) in the presence of base and CH2Cl2 (10 ml) at 0 °C.b,c See corresponding footnotes to Table 1.References 1 Chemistry of Waste Minimisation, ed. J. H. Clark, Blackie Academic and Professional, Glasgow, 1995. 2 Electrophilic Aromatic Substitution, ed. R. Taylor, John Wiley and Sons, Chichester, 1990. 3 Solid Supports and Catalysts in Organic Synthesis, ed.K. Smith, Ellis Horwood, Chichester, 1992. 4 K. Smith, K. Fry, M. Butters and B. Nay, Tetrahedron Lett., 1989, 30, 5333; K. Smith, A. Musson and G.A. DeBoos, Chem. Commun., 1996, 469; J. Org. Chem., 1998, 63, 8448. 5 K. Smith, M. Butters and B. Nay, Synthesis, 1985, 1157. 6 K. Smith and D. Bahzad, Chem. Commun., 1996, 467. 7 K. Smith, G. M. Ewart and K.R.Randles, J. Chem. Soc., Perkin Trans. 1, 1997, 1085. 8 K. Smith and G. Pollaud, J. Chem. Soc., Perkin Trans. 1, 1994, 3519. 9 T. M. Wortel, D. Oudijn, C. J. Vleugel, D. P. Roelofsen and H. Van Bekkum, J. Catal., 1979, 60, 110. 10 J. Van Dijk, J. J. Van Daalen and G.B. Paerels, Rec. Trav. Chim. Pays-Bas, 1974, 93, 72. 11 Y. Higuchi and T. Suzuki, EP112722, 1984; Chem. Abstr., 1984, 101, 230115z. 12 K. Sekizawa, T. Hironaka and Y. Tsutsumi, EP171256, 1986; Chem. Abstr., 1986, 104, 224678f. 13 T. Miyake, K. Sekizawa, T. Hironaka and Y.Tsutsumi, US Pat., 4861929, 1989; Chem. Abstr., 1988, 109, 149038v. 14 T. Suzuki and Y. Higuchi, US Pat., 4822933, 1989; Chem. Abstr., 1985, 102, 61913w. 15 J. Dakka and Y. Sasson, J. Chem. Soc., Chem. Commun., 1987, 1421. 16 F. Dela Vega, Y. Sasson and K. Huddersman, Zeolites, 1991, 11, 617; 1993, 13, 341. 17 S. Rozen and M. Brand, J. Chem. Soc., Chem. Commun., 1987, 752. 18 V. Robinson, M.Phil. thesis, University of Wales Swansea, 1995. 19 T. Miyake, K. Sekizawa, T. Hironaka, M. Nakano, S. Fujii and Y. Tsutsumi, Stud. Surf. Sci. Catal., 1986, 28, 747. 20 J. W. Ward, J. Catal., 1968, 11, 238. 21 O. M. Dzhigit, A. V. Kiselev, K. N. Mikos, G. G. Muttik and T. A. Rahmanova, Trans. Faraday Soc., 1971, 67, 458. 22 H. W. Habgood, Can. J. Chem., 1964, 42, 2340. 23 E. C. Taylor, H. W. Altland, G. McGillivray and A. McKillop, Tetrahedron Lett., 1970, 5285. 24 A. McKillop, D. Bromley and E. C. Taylor, Tetrahedron Lett., 1969, 1623; J. Org. Chem., 1972, 37, 88. Paper 8/08242A 38 Green Chemistry February 1999

ISSN:1463-9262    

DOI:10.1039/a808242a

出版商:RSC    

年代:1999

数据来源: RSC

摘要:

Summary Up to 40% ee was obtained in the asymmetric epoxidation of styrene and other unfunctionalised olefins catalysed by the ruthenium( ii) complex [RuCl(PNNP)]PF6 (PNNP = N,NA-{bis(odiphenylphosphino) benzylidene}-(1S,2S)-diiminocyclohexane) using hydrogen peroxide as the primary oxidant. Introduction Catalytic epoxidation of olefins is both a major industrial technology and an essential synthetic method.1 However, several problems are still unresolved, in particular the nature of the oxidant and the product selectivity, including enantioselectivity in the case of asymmetric epoxidation.2,3 Although hydrogen peroxide is a cheap and environmentally friendly oxidant, as required for large-scale applications, its use in homogeneous catalysis is generally hampered by the decomposition reaction which is catalysed by most transition metals.4 Accordingly, the use of H2O2 in ruthenium-catalysed oxidation reactions is scarcely documented. 527 In the field of asymmetric catalysis, the Mn(iii) salen-based methodology2,3 has successfully extended the scope of the epoxidation reaction to unfunctionalised olefins, but a general protocol suitable for trans-substituted and terminal olefins is still lacking.Thus, there is considerable interest in the development of alternative catalytic systems. Lately, ruthenium complexes with chiral N,O- and N,N-donor ligands have been tested as asymmetric epoxidation catalysts.8210 Since metal complexes with either achiral4,11 or chiral4 phosphines are scarcely used in catalytic epoxidation, we have started an investigation of Ru(ii) complexes containing chiral tetradentate P,N-ligands. We find now that the novel cationic complex [RuCl(PNNP)]PF6 1 [PNNP = (N,NA-bis{odiphenylphosphino) benzylidene}-(1S,2S)-diiminocyclohexane)], and its aquo derivative [RuCl(H2O)(PNNP)]PF6 2, catalyse the N Ru N P P Ph2 Ph2 Cl N Ru N P P Ph2 Ph2 H2O Cl [PF6] – [PF6] – 1 2 Asymmetric epoxidation of olefins The first enantioselective epoxidation of unfunctionalised olefins catalysed by a chiral ruthenium complex with H2O2 as oxidant Robert M.Stoop and Antonio Mezzetti* Laboratorium für Anorganische Chemie, ETH-Zentrum, CH-8092 Zürich, Switzerland Received 10th December 1998 asymmetric epoxidation of unfunctionalised olefins with hydrogen peroxide as the primary oxidant under mild conditions (1 mol% catalyst, 20 °C, 2–6 h) (Scheme 1).Most interestingly, Scheme 1 only a small excess of H2O2 is used. The selectivity to epoxide is high (52–80%) with both 1 and 2. The ee values are up to 41%. To the best of our knowledge, this is the first asymmetric epoxidation catalysed by a ruthenium complex that exploits hydrogen peroxide as the primary oxidant. Results and discussion The reaction of [RuCl2(PNNP)]12,13 (see Experimental section) with TlPF6 in dry CH2Cl2 gives a highly reactive species which O R O H R R + + [ox] 1 or 2 (1 mol%) CH2Cl2 RT Green Chemistry February 1999 39 Epoxidation is a vital chemical transformation, which allows the transformation of alkenes into highly reactive and versatile synthetic intermediates, which can be further converted into a wide range of important products.Many epoxidations require reagents such as NaOCl, periodates, or other high oxidation state iodine compounds. These oxidants are used in conjunction with catalysts, and are typically very efficient, but inevitably lead to a great deal of waste. Comparatively little has been done on epoxidations using cleaner reagents such as air or hydrogen peroxide.This article describes an efficient and selective catalyst which allows epoxidation with hydrogen peroxide to occur under mild conditions. Some success has also been achieved with chiral versions of the catalyst. The use of dichloromethane as solvent is not ideal, and a greener solvent would be preferable, but the ability to use one of the most ideal oxidants is a very significant move in the right direction.DJM Green Context C Gwe formulate as [RuCl(PNNP)]PF6 1. Complex 1 behaves as a 1:1 electrolyte in dry CH2Cl2, and is extremely reactive toward most O- and N-donors. Thus, 1 gives adducts with H2O, THF, CH3OH, acetone, diethyl ether, and acetonitrile. In solvents containing traces of water, the aquo complex [RuCl(OH2)(PNNP)]PF6 2 is formed along with 1.Pure 1 can be observed (by 31P NMR spectroscopy) only under rigorously water-free conditions. At this stage, we cannot exclude that 1 is a labile dichloromethane solvate. The reaction of 1 with an excess of H2O gives 2, which is isolated and characterised as a mixture of diastereomers. Addition of 30% aqueous H2O2 (7 equivalents) to a CH2Cl2 solution of styrene and (S,S)-1 (1 mol%) yields (S)-styrene oxide with 81% epoxide selectivity and 37% ee (Table 1, run 1).The oxidative cleavage of the CNC double bond is a minor side reaction. Only 9% of 3 is converted to benzaldehyde after the reaction time, whereas other ruthenium–phosphine epoxidation systems afford substantial amounts of cleavage products.14 Addition of methanol to the reaction solution allows the recovery of polystyrene according to the mass balance.Although the conversion of 3 is only moderate (35%), the system activity (TOF = 5.8 h–1) is an order of magnitude larger than for ruthenium systems containing N- or N,O-donor ligands.15,16 The dichloro species [RuCl2(PNNP)] is catalytically inactive. Next, we investigated the epoxidation of alkenes 4–6 with precatalyst 1 (runs 3–5): 1,2-dihydronaphthalene 4 is converted quantitatively within 2 h giving the (2)-(1S,2R)-epoxide with 55% epoxide selectivity and 41% ee.Minor amounts of 1,2-dihydroxy- 3,4-dihydronaphthalene and 1-oxo-2,3,4-trihydronaphthalene are detected by GC MS among the reaction products. Quantitative conversion of 4 is obtained also with a substrate to catalyst ratio of 200:1.The epoxidation of the cis-disubstituted olefin 6 is highly stereospecific, giving nearly exclusively the cis-epoxide (99:1 cis-to-trans ratio) with 25% ee (the ee of the trans epoxide is 38%). This selectivity is much higher than observed in Mn-catalysed epoxidations,3,17 and suggests a concerted, non-radical addition to the double bond. Substrate 5, a model for trans-olefins, gives nearly racemic epoxide (4% ee) with conversion comparable to that of styrene.Precatalyst 2 3 4 5 6 gives similar results as 1 (runs 6–9), but is less active and affords lower chemo- and enantio-selectivity. We are investigating the co-ordination chemistry of 1 and 2 in order to rationalise this behaviour. The effect of a series of parameters has been investigated using 1 as precatalyst and 3 as substrate.Lowering the reaction temperature (0 °C) or buffering the aqueous phase at different pH values (3.4, 8.0) does not improve either conversion or epoxide selectivity. No reaction is observed in co-ordinating solvents such as pyridine and acetonitrile, due to the formation of relatively inert solvates.18 When THF is used, benzaldehyde is the major product.The use of an aromatic solvent improves very slightly the enantioselectivity:8 1,2-dichlorobenzene gives the highest ee (40%), but lower epoxide selectivity (50%) (run 2). Finally, oxidants other than H2O2 can be used in the epoxidation of styrene in the presence of 1 (1 mol%) under analogous experimental conditions. Iodosylbenzene gives nearly quantitative conversion (95%) to the (S)-epoxide (60% selectivity, 30% ee, 24 h).The O2/heptaldehyde system gives (S)-styrene oxide with 50% selectivity and 27% ee, albeit with low conversion (15% after 4 h). Good conversion (75%) but low chemoselectivity (16% (R)-epoxide with 10% ee) is obtained with NaIO4, which mainly affords oxidative cleavage (57% benzaldehyde). No reaction occurs with aqueous NaOCl, whereas tert-butyl hydroperoxide and [NBu4][HSO5] give oxidation products other than the epoxide.Conclusion We have shown that a new class of ruthenium complexes with a tetradentate chiral phosphinoimino ligand catalyses the asymmetric epoxidation of alkenes with a variety of oxidants. In particular, H2O2 is activated with high efficiency, which is probably related to the oxophilicity of 1.The stereospecifity of the epoxidation reaction with H2O2 suggests that the intermediates involved have little radical character. Our present efforts are directed to improving the activity and enantioselectivity of this system. Experimental Preparation of [RuCl2(PNNP)] Prepared in 91% yield as a 1:4 mixture of the cis- and trans isomers by stirring [RuCl2(PPh3)3] (282 mg, 0.294 mmol) and PNNP (194 mg, 0.294 mmol) in CH2Cl2 (30 ml) for 4 h at room temperature, followed by addition of hexane and partial evapora- 40 Green Chemistry February 1999 Table 1 Asymmetric epoxidation of alkenes with H2O2 as oxidant Selectivity (%)a Run Substrate Catalyst t/h Conv.(%) Epoxide RCHO Configurationb eec(%) 1 3 1 6 35 81 9 S 37 2d 3 1 6 24 50 40 S 40 3 4 1 2 100 55 e 1S,2R f 41 4 5 1 4 26 62 17 1R,2R 4 5 6 1 6 22 72 0 n.d. 25 6 3 2 6 39 68 9 S 30 7 4 2 2 84 50 e 1S,2R f 25 8 5 2 3 14 52 4 1R,2R 10 9 6 2 6 6 70 0 n.d. 22 a By GC analysis (SE 54) with decane as internal standard. b By comparison with an authentic sample (chiral GC analysis). c Determined by chiral GC (Supelco a-DEX 120). d Solvent is 1,2-dichlorobenzene.e Small amounts of overoxidation products have been detected by GC MS (see text). f By the sign of the optical rotation.tion of the solvent. Calc. for C44H40Cl2N2P2Ru: C, 63.62; H, 4.85; N, 3.37. Found: C, 63.46; H, 4.90; N, 3.13. cis-Isomer: dP (101 MHz, CDCl3, 85% H3PO4) 36.1 (d, J = 31.8 Hz, 1 P), 88.3 (d, J = 31.8 Hz, 1 P). Data for the trans-isomer are as in ref. 13. Preparation of complex 1 A CH2Cl2 solution (30 ml) of [RuCl2(PNNP)] (244 mg, 0.294 mmol) and TlPF6 (124 mg, 0.352 mmol) was stirred for 3 h at room temperature under argon. After filtering over Celite and adding hexane, evaporation of CH2Cl2 yielded red-brown 1 in 74% yield. Besides reacting with most oxygen donors, 1 tenaciously retained variable amounts of non co-ordinating solvents, such as hexane.Therefore, no reasonable elemental analysis could be obtained. MS (FAB+) m/z: 796 ([M]+ + H, 100), 760 ([M]+ 2 Cl, 17). dP (101 MHz, CD2Cl2, over molecular sieves, 85% H3PO4) 49.7 (d, JP,PA = 28.2 Hz, 1 P), 59.0 (d, JP,PA = 28.2 Hz, 1 P), 2144.4 (septet, JP,F = 714 Hz, 1 P, PF6). dH (250 MHz, CD2Cl2, over molecular sieves, Me4Si) 8.85 (d, JP,H = 10.0 Hz, 1 H, H–CNN), 8.6 (br s, 1 H, H–CNN).LM = 40 W–1 cm2 mol–1 (10–3 mol dm–3 CH2Cl2 solution). Preparation of complex 2 PriOH–H2O (1:1, 10 ml) was added to a filtered (Celite) CH2Cl2 (40 ml) solution of 1, prepared in situ from [RuCl2(PNNP)] (302 mg, 0.363 mmol) and TlPF6 (165 mg, 0.471 mmol). Evaporation of CH2Cl2 yielded orange-yellow 2 in 83% yield. Calc. for C44H42ClF6N2OP3Ru: C, 55.15; H, 4.42; N, 2.92.Found: C, 55.83; H, 4.94; N, 2.37%. dP (101 MHz, CDCl3, 85% H3PO4), isomer 2a: 45.5 (d, JP,PA = 31.8 Hz, 1 P), 65.0 (d, JP,PA = 31.8 Hz, 1 P); isomer 2b: 42.9 (d, JP,PA = 26.9 Hz, 1 P), 50.9 (d, JP,PA = 26.9 Hz, 1 P), 2144.4 (septet, JP,F = 714 Hz, 1 P, PF6). dH (250 MHz, CDCl3, Me4Si), isomer 2a: 8.80 (d, JP,H = 10.2 Hz, 1 H, H–CNN), 8.68 (br s, 1 H, H–CNN); isomer 2b: 9.21 (d, JP,H = 9.0 Hz, 1 H, H–CNN), 8.88 (d, JP,H = 9.0 Hz, 1 H, H–CNN).MS (FAB+): m/z 813 ([M]+, 10), 795 ([M]+ 2 H2O, 100), 759 ([M]+ 2 Cl 2 H2O, 24). nmax(CHCl3)/cm–1: 3685 (m), 3604 (m), 3485 (m, br) (Ru–OH2); 1630 (m, Ru–NNC), 1602 (m, Ru–OH2). LM = 39 W–1 cm2 mol–1 (10–3 mol dm–3 CD2Cl2 solution). Epoxidation studies In a typical catalytic run, the olefin (0.96 mmol), decane (internal standard, 0.17 mmol) and precatalyst 1 or 2 (9.6 mmol, 1 mol%) were dissolved in dry, distilled CH2Cl2 (5 ml) under argon.Aqueous hydrogen peroxide (0.7 ml 30%, Perhydrol (Merck), 9.8 M solution, 6.86 mmol) was added in one shot to the brown solution under vigorous stirring. The solution darkened immediately, and gas was evolved. The GC traces of the reaction solutions indicated that there was no induction time, the formation of epoxide being observed just after adding H2O2.Continuous addition of H2O2 over 4 h has a negligible effect on the outcome of the reaction. References 1 For recent advances, see: J. Mol. Catal. A, 1997, 117, 1–478, (ed. R. A. Sheldon). 2 T. Katsuki, J. Mol. Catal. A, 1996, 113, 87. 3 E. N. Jacobsen, in Catalytic Asymmetric Synthesis, ed. I.Ojima, VCH, New York, 1993, pp.159–202. 4 Catalytic Oxidation with Hydrogen Peroxide as Oxidant, ed. G. Strukul, Kluwer, Dordrecht, 1992. 5 R. A. Sheldon and G. A. Barf, J. Mol. Catal. A, 1995, 102, 23. 6 J. M. Fisher, A. Fulford and P. S. Bennett, J. Mol. Catal., 1992, 77, 229. 7 A. Behr and K. Eusterwiemann, J. Organomet. Chem., 1991, 403, 215. 8 R. I. Kureshi, N. H. Khan, S. H. R. Abdi and P. Iyer, J. Mol. Catal. A, 1997, 124, 91. 9 Z. Gross and S. Ini, J. Org. Chem., 1997, 62, 5514. 10 A. Berkessel and M. Frauenkron, J. Chem. Soc., Perkin Trans. 1, 1997, 2265. 11 M. Bressan and A. Morvillo, Inorg. Chem., 1989, 28, 950. 12 W.-K. Wong, T.-W. Chik, K.-N. Hui, I. Williams, X. Feng, T. C. W. Mak and C.-M. Che, Polyhedron, 1996, 15, 4447. 13 J.-X. Gao, T. Ikariya and R. Noyori, Organometallics, 1996, 15, 1087. 14 A. Morvillo and M. Bressan, J. Mol. Catal. A, 1997, 125, 119. 15 H. Nishiyama, T. Shimada, H. Itoh, H. Sugiyama and Y. Motoyama, Chem. Commun., 1997, 1863. 16 N. End and A. Pfaltz, Chem. Commun., 1998, 589. 17 C. Bolm, D. Kadereit and M. Valacchi, Synlett, 1997, 687. 18 K. Nakajima, Y. Ando, H. Mano and M. Kojima, Inorg. Chim. Acta, 1998, 274, 184. Paper 8/09640F Green Chemistry February 1999 41

ISSN:1463-9262    

DOI:10.1039/a809640f

出版商:RSC    

年代:1999

数据来源: RSC

摘要:

Summary Recent developments in microwave-accelerated solventless organic syntheses are summarised. This expeditious and solventfree approach involves the exposure of neat reactants to microwave (MW) irradiation in conjunction with the use of supported reagents or catalysts which are primarily of mineral origin. The salient features of these high yield protocols are the enhanced reaction rates, greater selectivity and the experimental ease of manipulation.Among other reagents recently described in the literature on this eco-friendly green approach, the use of recyclable mineral oxides or supported reagents from our laboratory such as Fe(NO3)3–clay (clayfen), Cu(NO3)2–clay (claycop), NH4NO3–clay (clayan), NH2OH–clay, PhI(OAc)2–alumina, NaIO4–silica, CrO3–alumina, MnO2–silica, NaBH4–clay, etc.are highlighted in MW-promoted deprotection, condensation, The combination of supported reagents and microwave irradiation can be used to carry out a wide range of reactions in short times and with high conversions and selectivity, without the need for solvents. This approach can prove beneficial since the recovery of solvents from conventional reaction systems always results in some losses.Recovery of both products and inorganic support/catalyst is generally possible, leading to an efficient and low waste route to a range of products. SJT Green Context Solvent-free organic syntheses using supported reagents and microwave irradiation Rajender S. Varma Department of Chemistry and Texas Research Institute for Environmental Studies (TRIES), Sam Houston State University, Huntsville, Texas 77341-2117, USA.Fax: (+1) 409-294-1585. E-mail: CHM_RSV@SHSU.EDU Received 23rd October 1998 cyclization, rearrangement, oxidation and reduction reactions including the rapid one-pot assembly of heterocyclic compounds from in situ generated intermediates. 1. Introduction Heterogeneous organic reactions have proven useful to chemists in the laboratory as well as in the industrial context.These reactions are effected by the reagents immobilized on the porous solid supports and have advantages over the conventional solution phase reactions because of the good dispersion of active reagent sites, associated selectivity and easier work-up. The recyclability of some of these solid supports renders these processes into truly eco-friendly green protocols.Although the first description of surface-mediated chemistry dates back to 1924,1 it was not until the late 1970s that the technique received genuine attention with the appearance of two reviews,2 followed by a series of books and account articles.3 A related development that had a profound impact on these heterogeneous reaction is the use of microwave (MW) irradiation techniques for the acceleration of organic reactions.Since the appearance of the first article on the application of microwaves for chemical synthesis in polar solvents,4 the approach has blossomed into a useful technique for a variety of applications in organic synthesis and functional group transformations.5–34 The focus has lately shifted to less cumbersome solvent-free methods7 –35 wherein the neat reactants, often in the presence of mineral oxides or supported catalysts, undergo facile reactions to provide high yields of pure products thus eliminating or minimizing the use of organic solvents.Microwave reactions involve selective absorption of MW energy by polar molecules, non-polar molecules being inert to MW dielectric loss.The initial experiments with microwave techniques centered around the use of high dielectric solvents Green Chemistry February 1999 43 Raj Varma was born in India and obtained his Ph.D. from Delhi University in 1976. After postdoctoral research at Robert Robinson Laboratories, Liverpool, UK and Univ. of Tennessee, Knoxville, TN, USA, he was a faculty member at Baylor College of Medicine and Houston Advanced Research Center. Presently, he is Research Professor of Chemistry at Sam Houston State University, Huntsville, TX, USA, with an appointment at the Texas Research Institute for Environmental Studies.His research interests encompass natural product chemistry, new synthetic methods, bioelectronics and environmental sciences which includes the development of eco-friendly solvent-free synthetic methods using microwave or ultrasound irradiation.Further details of the multidisciplinary activity may be found at his home page, http://www.shsu.edu/~chm_rsv/ C Gsuch as dimethyl sulfoxide (DMSO) and dimethylformamide (DMF). The rate enhancements in such reactions are now believed to be due to rapid superheating of the polar solvents.However, in these solution-phase reactions, the development of high pressures and the use of specialized Teflon vessels and sealed containers are some of the limitations. During recent years, a practical dimension to the microwave heating protocols has been added by accomplishing reactions on solid supports under solvent-free conditions. In these reactions, the organic compounds adsorbed on the surface of inorganic oxides, such as alumina, silica and clay, or ‘doped’ supports absorb microwaves whereas the solid support does not absorb or restrict their transmission.The bulk temperature is relatively low in such solventfree reactions although higher localized temperatures may be reached during microwave irradiation. These solvent-free MWassisted reactions provide an opportunity to work with open vessels thus avoiding the risk of high pressure development and increasing the potential of such reactions to upscale. 2. Microwave accelerated solvent-free organic reactions The practical feasibility of microwave assisted solvent-free protocols has been demonstrated in useful transformations involving protection/deprotection, condensation, oxidation, reduction, rearrangement reactions and in the synthesis of various heterocyclic systems on inorganic solid supports.Herein, we describe our results on this environmentally benign microwave approach for the synthesis of a wide variety of industrially important compounds and intermediates, namely enones, imines, enamines, nitroalkenes, oxidized sulfur species and heterocycles which, obtained otherwise by conventional procedures, contribute to the burden of chemical pollution.Recent work in this area by other research groups is also included. Most of the reactions described herein are performed in open glass containers (test tubes, beakers and round-bottomed flasks) using neat reactants under solventfree conditions in an unmodified household MW oven or a focused MW oven operating at 2450 MHz.In many cases, the comparisons of the MW-accelerated reactions have been made by conducting the same reaction in an oil bath at the same bulk temperature. The problems associated with waste disposal of solvents (used many-fold in chemical reactions) and excess chemicals are avoided or minimized. Some of the supported reagents, namely clay-supported iron(iii) nitrate (clayfen), and copper(ii) nitrate (claycop), are prepared according to the literature procedure.36 The general procedure involves simple mixing of neat reactants with the catalyst/promoter or their adsorption on mineral or ‘doped’ supports. 2.1. Protection/deprotection reactions The protection/deprotection reaction sequences form an integral part of organic manipulations such as the preparation of monomer building blocks, fine chemicals and precursors for pharmaceuticals and these reactions often involve the use of acidic, basic or hazardous and corrosive reagents and toxic metal salts.In this section, the MW-accelerated protection/deprotection of functional groups that have been carried out under solvent-free conditions are highlighted. 2.1.1. Formation of acetals and dioxolane. Loupy and coworkers have efficiently prepared acetals of 1- galactono-1,4-lactone in excellent yields by adsorbing the lactone and the aldehyde on montmorillonite K 10 or KSF clay followed by exposing the reaction mixture to microwave irradiation (Scheme 1).34e Scheme 1 Hamelin et al. have successfully protected aldehydes and ketones as acetals and dioxolanes using orthoformates, 1,2-ethanedithiol or 2,2-dimethyl-1,3-dioxolane.37 This acidcatalysed reaction proceeds in the presence of p-toluenesulfonic acid (PTSA) or KSF clay under solvent-free conditions (Scheme 2).The yields obtained with the microwave method are better than those obtained using the conventional heating mode (oil bath). Scheme 2 Villemin et al.have prepared thioacetals using an essentially similar technique.34f The active methylene compounds are adsorbed on alumina–KF, mixed with methanesulfonothioate and are irradiated in a microwave oven to generate thioacetals in good yields (Scheme 3). Scheme 3 In the presence of ethylene glycol and p-toluenesulfonic acid, a mixture of ketone and aldehyde leads to the formation of dioxolane upon exposure to microwaves (Scheme 4).37 Scheme 4 2.1.2.N-Alkylation reactions. A variety of solvent-free N-alkylation reactions have been reported which entail the use of phase transfer agents such as tetrabutylammonium bromide (TBAB) under microwave irradiation conditions. The important recent examples are N-alkylation of phthalimides (Scheme 5)38 or its potassium salt (Scheme 6)39 in the presence of potassium carbonate and TBAB.Scheme 5 Scheme 6 44 Green Chemistry February 1999The approach has been extended to a variety of heterocyclic systems, namely carbazole (Scheme 7),40 other azaheterocycles using K2CO3/KOH and TBAB (Scheme 8)41 including pyrrolidino[ 60]fullerenes (Scheme 9).42 Scheme 7 Scheme 8 Scheme 9 2.1.3.Cleavage of aldehyde diacetates. The diacetate derivatives of aromatic aldehydes are rapidly cleaved on a neutral alumina surface upon brief exposure to MW irradiation (Scheme 10).11 The selectivity in these deprotection reactions is achievable by simply adjusting the time of Scheme 10 irradiation. As an example for molecules bearing an acetoxy functionality (R = OCOCH3), the aldehyde diacetate is selectively removed in 30 s, whereas an extended period of 2 min is required to cleave both the diacetate and ester groups.The yields obtained are better than those possible by conventional methods and the protocol is applicable to compounds encompassing olefinic moieties such as cinnamaldehyde diacetate. Essentially, a similar reaction has been reported using zeolites wherein 1,1-diacetates undergo deprotection under microwave irradiation in solvent-free conditions (Scheme 11).43 However, it was not reported whether the reaction occurs on the surface or inside the zeolite pore structures.Scheme 11 2.1.4. Debenzylation of carboxylic esters. The promising solvent-free debenzylation of esters (Scheme 12)13 paves the way for the cleavage of the 9-fluorenylmethoxy Scheme 12 a Times in parentheses refer to deprotection in an oil bath at the same temperature.carbonyl (Fmoc) group that can be extended to protected amines by changing the surface characteristics of the solid support. The optimum conditions for cleavage of N-protected moieties require the use of basic alumina and irradiation time of 12–13 min at Å130–140 °C.This approach may find application in peptide bond formation that would eliminate the use of irritating and corrosive chemicals such as trifluoroacetic acid and piperidine, as has been demonstrated recently for the deprotection of N-boc groups (see Scheme 13). Scheme 13 2.1.5. Selective cleavage of N-tert-butoxycarbonyl group. The solventless cleavage of the N-tert-butoxycarbonyl (Nboc) group is achieved readily in the presence of aluminium chloride ‘doped’ neutral alumina upon exposure to microwave irradiation (Scheme 13).44 2.1.6.Desilylation reactions. tert-Butyldimethylsilyl (TBDMS) ether derivatives of a variety of alcohols are rapidly deprotected to regenerate the corresponding hydroxy compounds on alumina surface under MW irradiation conditions (Scheme 14).12 This approach circumvents the use of corrosive fluoride ions which are conventionally employed for cleaving the silyl protecting groups.12 2.1.7.Deacylation reactions. The orthogonal deprotection of alcohols is possible on a neutral alumina surface using microwave irradiation (Scheme 15). Interestingly, chemoselectivity between alcoholic and phenolic groups in the same molecule can be achieved simply by varying the reaction time; the phenolic acetates are deacetylated faster than alcoholic analogues.10 Green Chemistry February 1999 45The optimization of relevant parameters with an unmodified household microwave oven such as the power level of microwaves employed and pulsed techniques (multistage, discontinuous irradiation to avoid the generation of higher tempera tures) has been used to obtain good results.10 Scheme 14 Scheme 15 2.1.8.Dethioacetalization reaction. Among the processes for the regeneration of carbonyl compounds, the cleavage of acid and base stable thioacetals and thioketals is quite challenging; the deprotection of thioacetals invariably requires the use of toxic heavy metals such as Hg2+, Ag2+, Ti4+, Cd2+, Tl3+, or reagents such as benzeneseleninic anhydride. 9 We have accomplished the dethioacetalization reaction in high yield and in solid state using clayfen (Scheme 16).9 Scheme 16 2.1.9. Deoximation reactions. The important role of oximes as protecting groups owing to their hydrolytic stability has provided motivation for the development of newer deoximation reagents such as Raney nickel, pyridinium chlorochromate, pyridinium chlorochromate–H2O2, triethylammonium chlorochromate, dinitrogen tetroxide, trimethylsilyl chlorochromate, Dowex-50, dimethyl dioxirane, H2O2 over titanium silicalite-1, zirconium sulfophenyl phosphonate, Nhaloamides, and bismuth chloride.8 The solvent-free deprotection of protected carbonyl compounds has been successfully demonstrated using relatively benign ammonium persulfate on silica (Scheme 17).8 Neat Scheme 17 oximes are admixed with a solid supported reagent and the contents are irradiated at full power in a MW oven to regenerate free aldehydes or ketones in a process that is applicable to both aldoximes and ketoximes.The role of the surface is critical since the same reagent supported on a clay surface delivers predominantly the Beckmann rearrangement products, the amides.34k A facile deoximation protocol with sodium periodate impregnated moist silica (Scheme 18) has been introduced that is applicable exclusively to ketoximes14 Scheme 18 2.1.10.Cleavage of semicarbazones and phenylhydrazones. Aldehydes and ketones are also rapidly regenerated from the corresponding semicarbazones and phenylhydrazones using ammonium persulfate impregnated on montmorillonite K 10 clay (Scheme 19) under either microwave or ultrasound irradiation Scheme 19 conditions.15 However, in these solventless procedures microwave exposure achieves results in minutes whereas ultrasound- promoted reactions require 1–3 h for completion of the deprotection reaction. 2.1.11. Dethiocarbonylation.Several reagents such as trifluoroacetic anhydride, CuCl/MeOH/NaOH, tetrabutylammonium hydrogen sulfate/NaOH, clay/ferric nitrate, NOBF4, bromate and iodide solutions, alkaline hydrogen peroxide, sodium peroxide, bases e.g. KOBu, thiophosgene, DMSO, trimethyloxonium fluoroborate, tellurium based oxidants, photochemical transformations, dimethyl selenoxide, benzeneseleninic anhydride, benzoyl per- 46 Green Chemistry February 1999oxide, halogen-catalyzed alkoxides under phase transfer conditions, NaNO2/HCl, Hg(OAc)2, SOCl2/CaCO3, and singlet oxygen have been used for dethiocarbonylation.16 However, these methods have certain limitations such as the use of the stoichiometric amounts of the oxidants which are often inherently toxic or require longer reaction time or involve tedious procedures.In a process that is accelerated by microwave irradiation, we have accomplished efficient dethiocarbonylation wherein a variety of thioketones are readily converted into the corresponding ketones under solvent-free conditions using clayfen or clayan (Schemes 20, 21).16 Scheme 20 Scheme 21 2.2. Oxidation reactions: oxidation of alcohols and sulfides The conventional oxidizing reagents employed for organic functionalities are peracids, peroxides, manganese dioxide (MnO2), potassium permanganate (KMnO4), chromium trioxide (CrO3), potassium chromate (K2CrO4), and potassium dichromate (K2Cr2O7),45a though these reagents have their own limitations in terms of toxicity, work-up and associated waste disposal problems.Metal-based reagents have been extensively used in organic synthesis.The utility of such reagents in the oxidative transformation is compromised due to their inherent toxicity, cumbersome preparation, potential danger (ignition or explosion) in handling of their complexes, difficulties in terms of product isolation and waste disposal. Introduction of metallic reagents on solid supports has circumvented some of these problems and provided an attractive alternative in organic synthesis because of the selectivity and associated ease of manipulation.Further, the immobilization of metals on the surface avoids their leaching into the environment. 2.2.1. Selective and solvent-free oxidation with clayfen. We have developed a facile method for the oxidation of alcohols to carbonyl compounds wherein montmorillonite K 10 clay-supported iron(iii) nitrate (clayfen) is used under solvent-free conditions.The process is accelerated tremendously by exposure to MW irradiation17 and the reaction presumably proceeds via the intermediacy of nitrosonium ions. Remarkably, no carboxylic acids are formed in the oxidation of primary alcohols. The experimental procedure simply involves mixing of neat alcohols with clayfen and a brief irradiation of the reaction mixtures in a MW oven for 15–60 s in the absence of solvent.This extremely rapid, manipulatively simple, inexpensive and selective protocol avoids the use of excess solvents and toxic oxidants. Using clayfen [iron(iii) nitrate] in the solid state and in amounts that are half that of used by Balogh and Laszlo36 we have achieved a rapid synthesis of carbonyl compounds in high yields (Scheme 22).17 Scheme 22 2.2.2.Activated manganese dioxide–silica. Using manganese dioxide–silica, an expeditious and high yield route to carbonyl compounds is developed. Benzyl alcohols are selectively oxidized to carbonyl compounds using 35% MnO2 ‘doped’ silica under MW irradiation conditions (Scheme 23).18 Scheme 23 2.2.3.Claycop–hydrogen peroxide. Metal ions play a significant role in many of these oxidative reactions as well as in biological dioxygen metabolism. Copper(ii) acetate and hydrogen peroxide have been used to produce a stable oxidizing agent, a hydroperoxy copper(ii) compound, which is also obtainable from copper(ii) nitrate and hydrogen peroxide [eqn.(1)]. The resulting nitric acid, however, requires neutralization by potassium bicarbonate to maintain a pH Å5. Copper(ii) nitrate impregnated on K 10 clay (claycop)–hydrogen peroxide is an effective reagent for the oxidation of a variety of substrates and provides excellent yields (Scheme 24)19 wherein the maintenance of pH of the reaction mixture is not required.Scheme 24 2.2.4. Chromium trioxide impregnated wet alumina. The utility of chromium(vi) reagents in the oxidative transformation is compromised due to toxicity, involved preparation of its various complexes and cumbersome work-up and disposal problems. Chromium trioxide (CrO3) impregnated pre-moistened alumina is an efficient oxidising system which converts benzyl alcohols to carbonyl compounds by simply admixing the substrates with the reagent at room temperature (Scheme 25).The reactions Scheme 25 Green Chemistry February 1999 47are relatively clean with no tar formation, typical of many CrO3 oxidations. Interestingly, no overoxidation to carboxylic acids is observed.20 Acyclic a-nitro ketones are obtained in one-pot operation via a solvent-free approach that utilizes in situ oxidation of the nitroalkanols with premoistened alumina supported chromium trioxide.43b 2.2.5.Nonmetallic oxidants—iodobenzene diacetate (IBD) ‘doped’ alumina. Iodoxybenzene, o-iodoxybenzoic acid (IBX), bis(trifluoroacetoxy) iodobenzene (BTI), and Dess–Martin periodinane are some of the common organohypervalent iodine reagents which have been used for the oxidation of alcohols and phenols, but the use of iodobenzene diacetate (IBD) in this area, in spite of its low cost, has not been fully exploited. Most of these reactions, however, are conducted in high boiling DMSO and toxic acetonitrile media that result in an environmental pollution load.Also, IBX has been reported to be explosive under heavy impact and heating over 200 °C.A facile oxidation of alcohols to carbonyl compounds occurs rapidly with alumina-supported IBD under solvent-free conditions and MW irradiation, in quantitative yields.21 The advantage of using alumina as a support is apparent in marked improvements in yields obtained with the alumina–IBD system as compared to neat IBD (Scheme 26). Interestingly, 1,2-benzenedimethanol undergoes cyclization to afford 1(3H)-isobenzofuranone.Scheme 26 2.2.6. Copper sulfate–alumina or oxone®–wet alumina. The oxidative transformation of a-hydroxyketones to 1,2-diketones has been accomplished by a variety of reagents namely nitric acid, Fehling’s solution, thallium(iii) nitrate (TTN), ytterbium( iii) nitrate, clayfen, and ammonium chlorochromate–alumina. 22 In addition to the extended reaction time, most of these processes suffer from drawbacks such as the use of corrosive acids and toxic metallic compounds that generate undesirable waste materials. Consequently, there is room for the development of an eco-friendly solvent-free protocol for the oxidation of benzoins.Recently, we have found that both symmetrical and unsymmetrical benzoins can be rapidly oxidized to benzils in high yields using solid reagent systems, copper(ii) sulfate–alumina22 or Oxone®–wet alumina23 under the influence of microwaves (Scheme 27).Scheme 27 Interestingly, under these solvent-free conditions, primary alcohols e.g. benzyl alcohol and secondary alcohols e.g. 1- phenylpropan-1-ol undergo only limited oxidative conversion which is of little practical utility.Apparently, the process is applicable only to a-hydroxyketones as exemplified by various substrates including a mixed benzylic/aliphatic a-hydroxyketone, 2-hydroxypropiophenone, that affords the corresponding vicinal diketone.23 2.2.7. Sodium periodate on silica—oxidation of sulfides to sulfoxides and sulfones. Sulfides are usually oxidized to sulfoxides under strenuous conditions using strong oxidants like nitric acid, hydrogen peroxide, chromic acid, peracids, and periodate.24 Using MW irradiation this oxidation is achievable with the desired selectivity, to either sulfoxides or sulfones, using silica ‘doped’ with 10% sodium periodate under reduced power and reaction time (pulsed techniques). 24 Consequently, a much reduced amount of the active oxidizing agent is employed which is safer and easier to handle (Scheme 28).Scheme 28 Importantly, various refractory thiophenes that are often not reductively removed by conventional refining processes can be oxidized under these conditions, e.g. benzothiophenes are oxidized to the corresponding sulfoxides and sulfones using ultrasonic and microwave irradiation, respectively, in the presence of NaIO4–silica.24 A noteworthy feature of the protocol is its applicability to long chain fatty sulfides which are insoluble in most solvents and are consequently difficult to oxidize. 2.2.8.Iodobenzene diacetate–alumina. As described earlier (section 2.2.5), the solid reagent system IBD–alumina is a useful oxidizing agent and its use is extendable to the expeditious, high yield and selective oxidation of alkyl, aryl and cyclic sulfides to the corresponding sulfoxides upon microwave activation (Scheme 29).25a Scheme 29 In a solid state reaction with clayfen, a variety of alkyl, aryl and cyclic sulfides are rapidly oxidised to the corresponding sulfoxides in high yield upon microwave thermolysis.25b 2.3 Other oxidation reactions 2.3.1.Oxidation of enamines. Under solvent-free conditions, Hamelin’s group34g has successfully oxidized b,b-disubstituted enamines into carbonyl compounds with KMnO4–Al2O3 in domestic (255 W, 82 °C) as well as in focused (330 W, 140 °C) microwave ovens. The yields are better in the latter case whereas no ketone formation is observed when the same reactions are conducted in an oil bath at 140 °C (Scheme 30). 48 Green Chemistry February 1999Scheme 30 2.3.2. Oxidation of arenes with permanganate (KMnO4)–alumina. KMnO4 impregnated alumina oxidises arenes to ketones within 10–30 minutes in solvent-free conditions using focused microwaves (Scheme 31).45b Scheme 31 2.4. Condensation reactions 2.4.1. Synthesis of imines, enamines and nitroalkenes. The driving force in the preparation of imines, enamines and nitroalkenes is the azeotropic removal of water from the intermediate, which is normally catalyzed by p-toluenesulfonic acid, titanium(IV) chloride, and montmorillonite K 10 clay.Conventionally, a Dean–Stark apparatus is used which requires a large excess of aromatic hydrocarbons such as benzene or toluene for azeotropic water elimination. MW-induced acceleration of such dehydration reactions using montmorillonite K 10 clay26 (Schemes 32, 33) or Envirocat reagent,27 EPZG® (Schemes 32, 33) has been demonstrated in a facile preparation of imines and enamines via the reactions of primary and secondary amines with aldehydes and ketones, respectively. Scheme 32 Scheme 33 Microwaves, generated at the usual frequency of 2450 MHz, are ideally suited to remove water in imine or enamine forming reactions.For low boiling starting materials, reduced power intensities of microwaves coupled with pulsed techniques have been used.26,27 The Henry reaction, condensation of carbonyl compounds with nitroalkanes to afford nitroalkenes, also proceeds rapidly via this MW approach and requires only catalytic amounts of ammonium acetate involving neat reactants thus avoiding the use of a large excess of polluting nitrohydrocarbons normally employed (Scheme 34).28 Scheme 34 The reduction, oxidation and cycloaddition reactions emanating from a,b-unsaturated nitroalkenes provide easy access to a vast array of functionalities that include nitroalkanes, N-substituted hydroxylamines, amines, ketones, oximes, and a-substituted oximes and ketones.46 Consequently, there are numerous possibilities of using these in situ generated nitroalkenes for the preparation of valuable building blocks and synthetic precursors. 2.4.2. Knoevenagel condensation reactions—Coumarin synthesis. An expeditious Knoevenagel condensation of creatinine with aldehydes has been achieved using focused microwave irradiation (40–60 W) under solvent-free reaction conditions at 160–170 °C (Scheme 35).47 Scheme 35 Villemin and Martin34l have synthesized 5-nitrofurfurylidine by the condensation of 5-nitrofurfuraldehyde with active methylene compounds under microwave irradiation using K 10 and ZnCl2 as a catalyst.The useful synthesis of coumarins via the microwave promoted Pechmann reaction48a has been extended to solventless systems wherein salicylaldehydes undergo Knoevenagel condensation with a variety of ethyl acetate derivatives under basic conditions (piperidine) to afford coumarins (Scheme 36).48b Scheme 36 2.5 Reduction reactions 2.5.1.Borohydride reduction of carbonyl compounds to alcohols. Relatively inexpensive sodium borohydride (NaBH4) has been extensively used as a reducing agent in view of its compatibility with protic solvents and safer nature.The solid state reduction of Green Chemistry February 1999 49ketones has also been achieved by mixing them with NaBH4 and storing the mixture in a dry box for five days. The major disadvantage in the heterogeneous reaction with NaBH4 is that the use of solvent slows down the reaction rate while in the solid state reactions the time required is too long (5 days) for it to be of any practical utility.32 We have developed a rapid method for the reduction of aldehydes and ketones that uses alumina supported NaBH4 and proceeds in the solid state using microwaves.32 The process in its entirety involves a simple mixing of carbonyl compound with (10%) NaBH4–alumina in the solid state and irradiating the mixture in a MW oven for 0.5–2 min (Scheme 37).Scheme 37 The useful chemoselective feature of the reaction is apparent from the reduction of trans-cinnamaldehyde (cinnamaldehyde/ NaBH4-alumina, 1:1 mol equivalent); the olefinic moiety remains intact and only the aldehyde functionality is reduced in a facile reaction that occurs at room temperature.No side product formation is observed in any of the reactions investigated and reaction does not take place in the absence of alumina. Further, the reaction rate improves in the presence of moisture. Alumina absorbs enough moisture during the recovery of the product that it can be recycled again by mixing with fresh borohydride and reused for subsequent reductions without any loss of activity.The air used for cooling the magnetron ventilates the microwave cavity thus preventing any ensuing hydrogen from reaching explosive concentrations. 2.5.2. Reductive alkylation of amines. Reductive amination of carbonyl compounds has been well documented using sodium cyanoborohydride, sodium triacetoxyborohydride or NaBH4 coupled with sulfuric acid. These reagents either produce waste stream or involve the use of corrosive acids. The environmentally benign methods developed in our laboratory have now been extended to a solvent-free reductive amination procedure for carbonyl compounds using wet montmorillonite K 10 clay supported sodium borohydride that is facilitated by microwave irradiation (Scheme 38).33 Scheme 38 These practical applications of NaBH4 reductions on mineral surfaces for in situ generated Schiff bases have been successful.33 The studies pertaining to the solid state reductive amination of carbonyl compounds on various inorganic solid supports such as alumina, clay, silica, etc., and especially on K 10 clay surface C O + H2N R R1 R2 C N R R1 R2 CH R R1 N R2 H Clay MW, 2 min NaBH4-Clay H2O, MW (0.25-2 min) R = i-Pr,Ph, o-HOC6H4, p-MeOC6H4, p-NO2C6H4; R1 = H; R2 = Ph R and R1 = -(CH2)5-; R2 = Ph; R and R1 = -(CH2)6-; R2 = n-Pr R = p-ClC6H4; R1 = H; R2 = o-HOC6H4; R = R1 = Et; R2 = Ph R = n-C5H11; R1 = Me; R2 = morpholine, piperidine R = i-Pr; R1 = H; R2 = n-C10H21 (78–97%) deliver secondary and tertiary amines rapidly.33 Clay not only behaves as a Lewis acid but provides water from its interlayers that enhances the reducing ability of NaBH4. 2.5.3. Reduction of carbonyl compounds with aluminium alkoxides. The efficient reduction of carbonyl compounds using isopropyl alcohol and alumina, as demonstrated in a series of papers by Posner,49a has now been translated to a solventless and expeditious reduction scheme that utilises aluminium alkoxides under microwave irradiation conditions (Scheme 39).49b Scheme 39 2.6.Rearrangement reactions 2.6.1. Pinacol–pinacolone rearrangement. Loupy and colleagues have reported a solventless pinacol–pinacolone rearrangement using microwave irradiation.34i The process involves the irradiation of the gem-diols with Al3+-montmorillonite K 10 clay for 15 min to afford the rearrangement product in excellent yields (Scheme 40).These results are compared to conventional heating in an oil bath where the reaction times are too long (15 h). Scheme 40 An efficient ring expansion transformation is described by Villemin and Labiad under solventless conditions (Scheme 41).34j This solvent-free microwave protocol is superior than the reactions conducted in conventional methanolic solution. Scheme 41 2.6.2. Beckmann rearrangement.Bosch et al. have achieved the Beckmann rearrangement of ketoximes with montmorillonite K 10 clay in ‘dry’ media in good yields (Scheme 42).34k Scheme 42 2.7. Synthesis of heterocylic compounds 2.7.1. Aziridines. Among the various protocols known for the synthesis of the title compounds, the focused microwave approach under ‘dry’ conditions is especially notable in view of the observation that elimination predominates over the Michael addition under MW irradiation when compared to the classical heating under the same conditions (Scheme 43).50 50 Green Chemistry February 1999Scheme 43 2.7.2. Benzimidazoles.Benzimidazoles are prepared rapidly by condensation reaction of ortho-esters with o-phenylenediamines in the presence of KSF clay under either refluxing conditions in toluene or solvent-free conditions using focused microwave irradiation (Scheme 44).51 Scheme 44 2.7.3.Isoflav-3-enes. Isoflav-3-enes, possessing the chromene nucleus, are well known oestrogens and several derivatives of these oxygen heterocycles have attracted the attention of medicinal chemists. Despite the availability of several methods for the synthesis of chromene derivatives, there is demand for the development of eco-friendly synthetic methods for these derivatives.We have discovered a facile and general method for the synthesis of isoflav-3-enes substituted with basic moieties at the 2 position (Scheme 45).29 The results are especially promising in view of the convergent one-pot approach to the Scheme 45 heterocyclic systems such as 2-substituted isoflavenes wherein the generation of the enamine derivatives in situ and inducing subsequent reactions with o-hydroxyaldehydes in the same pot is the key feature (Scheme 45). 2.7.4. Bridgehead nitrogen heterocycles. Microwave energy has found application in the rapid synthesis of bridgehead nitrogen heterocycles under solvent-free conditions.Rahmouni et al. have synthesised pyrimidino[ 1,6-a]benzimidazoles (Scheme 46) and 2,3-dihydroimidazo[ 1,2-c]pyrimidines (Scheme 47) under focused microwave Scheme 46 irradiation in moderate yields from N-acylimidates and activated 2-benzimidazoles and imidazoline ketene aminals, respectively. 34h Scheme 47 2.7.5. Synthesis of 2-oxazolines. Oxazolines are readily prepared from carboxylic acids and a,a,atris( hydroxymethyl)methylamine under microwave irradiation conditions (Scheme 48).52 Scheme 48 2.7.6.Substituted thiazoles. Thiazole and its derivatives are simply obtained by the reaction of a-tosyloxyketones, which are generated in situ from arylmethyl ketones and [hydroxy(tosyloxy)iodo]benzene (HTIB) with thioamides in the presence of K 10 clay using microwave irradiation (Scheme 49A) in a process that is solvent-free in both steps.53 The case of corresponding bridgehead heterocycles, however, is a special one where microwave effects really become apparent since the reactions of a-tosyloxyketones with ethylenethioureas remain incomplete in an oil bath whereas in a microwave oven they are completed in a short time (Scheme 49B).53 Scheme 49 2.7.7.Synthesis of 2-aroylbenzofurans. Naturally occurring and pharmacologically important 2-aroylbenzofurans are easily obtainable in the solid state from a-tosyloxyketones and salicylaldehydes in the presence of a base such as potassium fluoride doped alumina using microwave irradiation (Scheme 50).53 Green Chemistry February 1999 51Scheme 50 2.7.8. Flavones. Flavonoids are a class of naturally occurring phenolic compounds widely distributed in the plant kingdom, the most abundant being the flavones. Members of this class display a wide variety of biological activities and have been useful in the treatment of various diseases.Flavones have been prepared by a variety of methods such as Allan–Robinson synthesis and synthesis from chalcones via an intramolecular Wittig strategy.30 The most prevalent approach, however, involves the Baker–Venkataraman rearrangement, wherein o-hydroxyacetophenone is benzoylated to form the benzoyl ester followed by treatment with base (pyridine/KOH) to effect an acyl group migration, forming a 1,3-diketone.30 The diketone formed is then cyclized under strongly acidic conditions using sulfuric acid and acetic acid to deliver the flavone.Therefore, opportunities exist for the development of an expedient approach using benign and readily available starting materials. We have achieved a solvent-free synthesis of flavones which simply involves the microwave irradiation of o-hydroxydibenzoylmethanes adsorbed on montmorillonite K 10 clay for 1–1.5 min. Rapid and exclusive formation of cyclized flavones occurs in good yields (Scheme 51).30 Scheme 51 2.7.9.Synthesis of 2-aryl-1,2,3,4-tetrahydro-4-quinolones. In yet another solventless cyclization reaction using montmorillonite K 10 clay under microwave irradiation conditions, readily available 2A-aminochalcones provide easy access to 2-aryl- 1,2,3,4-tetrahydro-4-quinolones31 which are valuable precursors for the medicinally important quinolones (Scheme 52).Scheme 52 2.8. Miscellaneous reactions 2.8.1. Transformation of aromatic aldehydes to nitriles. The preparation of nitriles from aldehydes is an important chemical transformation.54 However, in most cases the aldoxime is first prepared and subsequently dehydrated using a wide variety of reagents such as O,N-bis(trifluoroacetyl) hydroxylamine or trifluoroacetohydroximic acid,55a chloramine/base,55b (H2SO4/SiO2),55c p-chlorophenyl chlorothionoformate/pyridine, 55d triethylamine/dialkyl hydrogen phosphinates,55e TiCl4/ pyridine,55f triethylamine/phosphonitrilic chloride55g and 1,1Adicarbonylbiimidazole. 55h These conventional methods entail the dehydration of aldoxime which is a time demanding process even for one-pot reactions.55i We envisaged the application of hydroxylamine ‘doped’ on K10 clay to effect the above conversion in a one-pot synthesis using microwaves. Arylaldehydes are rapidly converted into nitriles in good yields (89–95%) with hydroxylamine hydrochloride supported on montmorillonite K 10 clay in the absence of solvent.55j,k The reaction is a general one as exemplified by a variety of aldehydes (Scheme 53) that undergo this facile conversion to afford high yields of the corresponding nitriles (89–95%) within a short Scheme 53 MW irradiation time (1–1.5 min).55j,k In the case of aliphatic aldehydes, however, only poor yields of nitriles (10–15%) are obtained with complex byproduct formation. 2.8.2.Conversion of aldehydes to alcohols—Solid state Cannizzaro reaction. The title reaction is the disproportionation of an aldehyde to an equimolar mixture of primary alcohol and carboxylic salt56 and is restricted to aldehydes that lack a-hydrogens and therefore can not undergo aldol condensation.Several investigations57 have been made on this oxidation–reduction reaction, which is usually carried out in homogeneous and strongly basic conditions.The relative importance of the Cannizzaro reaction in synthetic organic chemistry decreased considerably after the discovery of lithium aluminium hydride, LiAlH4, in 1946. The lower yields of the desired products has been another limitation of this reaction. However, the crossed Cannizzaro reaction,57a using a scavenger and inexpensive paraformaldehyde to produce alcohol in higher yields, had been another choice prior to the introduction of hydride reducing agents.Normally conducted in solution, we explored this reaction on a variety of mineral oxide surfaces.58a The reaction under microwave irradiation conditions failed completely with calcium hydroxide and in the presence of a strong base such as sodium hydroxide, the reaction remains incomplete with concomitant formation of several unidentified products reminiscent of our earlier observations on basic alumina surface.58b Interestingly, we discovered that the reaction proceeds rapidly on a barium hydroxide, Ba(OH)2·8H2O, surface which demonstrates the first application of this reagent in a solvent-free crossed Cannizzaro reaction.58a Barium hydroxide has been previously used as a catalyst in a variety of organic syntheses59 including the Wittig–Horner reaction,60 the reaction of chalcones with hydroxylamine61 and the synthesis of isooxazolines and pyrazolines.62 In a typical experiment, a mixture of benzaldehyde (1 mmol) and paraformaldehyde (2 mmol) is mixed with barium hydroxide octahydrate (2 mmol) and then irradiated in a microwave oven (100–110 °C) or heated in an oil bath (100–110 °C) (Scheme 54).In general, aldehydes bearing an electron withdrawing substituent undergo reaction at a much faster rate than aldehydes with electron releasing groups appended. 52 Green Chemistry February 1999Scheme 54 2.8.3. Side chain nitration of styrenes—preparation of b-nitrostyrenes. We have recently described a facile solid state synthesis of bnitrostyrenes from readily available feedstock, styrene and its substituted derivatives using inexpensive ‘doped’ clay reagents, clayfen and clayan (Scheme 55).63 In a typical experiment, the neat reagent, styrene and clayfen or clayan are mixed in a glass Scheme 55 container and the solid mixture is heated in an oil bath (Å100–110 °C, 15 min) or irradiated in a microwave oven (Å100–110 °C, 3 min).In the case of clayan, intermittent warming is recommended at 30 s intervals to maintain the temperature below 60–70 °C. Interestingly, we observed the reaction proceeds only in the solid state and leads to the formation of polymeric products in solution phase reactions. 2.8.4 Oxidative coupling of b-naphthols. b-Naphthols undergo a quick and efficient self coupling reaction in the presence of iron(III) chloride, FeCl3·6H2O, under focused microwave irradiation in solvent-free conditions when compared to classical heating mode (Scheme 56).64 Scheme 56 2.8.5. Eugenol isomerization.Isoeugenol, an important feedstock for the flavor industry to manufacture vanillin, is normally prepared by base-catalysed isomerization of naturally occurring eugenol.In the presence of potassium tert-butoxide, t-BuOK, and a catalytic amount of phase transfer reagent, eugenol undergoes isomerization to isoeugenol under solvent-free conditions (Scheme 57).65 Scheme 57 2.8.6. Synthesis and isomerization of octylthiocyanate. Vass and coworkers have examined various non-traditional supports which, although they are chemically inactive and couple poorly with microwaves, produce some useful chemistry. As an example, octylbromide undergoes thiocyanation reaction with potassium thiocyanide, KSCN, in the presence of a phase transfer catalyst, tetrabutylammonium bromide (TBAB) on sodium chloride surfaces and it further isomerizes to isothiocyanate (Scheme 58).39 Scheme 58 2.8.7.Methylenation of 3,4-dihydroxybenzaldehyde. 3,4-Dihydroxybenzaldehyde undergoes methylenation rapidly in the presence of a phase transfer catalyst on a benign calcium carbonate surface; presumably the bonding of the vicinal hydroxyl groups is low thereby enhancing the reaction with the alkylating agent under solvent-free microwave irradiation (Scheme 59).39 Scheme 59 2.8.8.Synthesis of radiolabelled compounds—exchange reactions.Jones and coworkers66b–d have added a new dimension to the classical tritiation efforts of Wilzbach66a using microwave irradiation and solid hydrogen/deuterium/tritium donors with minimal radioactive waste generation. The group has nicely circumvented the traditional disadvantages associated with tritium labeling techniques as exemplified with deuteriated and tritiated borohydride reductions,66b based on similar MWexpedited reduction accomplished on alumina surfaces.32 The hydrogen exchange reactions that require elevated temperatures and extended reaction time (24 h)66c are the real beneficiaries of this microwave approach.66d The high purity of labeled materials, efficient insertion and excellent regio-selectivity are some of the salient features of this emerging technology (Scheme 60).Scheme 60 Green Chemistry February 1999 53In an elegant application of the microwave-accelerated reactions, Stone–Elander and co-workers have synthesised radiolabelled organic compounds via nucleophilic aromatic and aliphatic substitution reactions, esterifications, condensations, hydrolysis and complexation reactions using microwaves.67 The use of monomodal cavities on microscale organic reactions are real success stories of MW-expedited reactions. 3. Conclusion This article summarizes the recent activity and eco-friendly features of the solvent-free reactions that are activated by exposure to microwave irradiation. The solventless approach opens up numerous possibilities for conducting selective organic functional group transformations more efficiently and expeditiously using a variety of supported reagents on mineral oxides.The author’s own work, performed using an unmodified household microwave oven (multimode applicator), demonstrates the immediate practical applications in laboratory scale experiments. Some of the more recent work does point out the advantages of using monomode systems with focused electromagnetic waves (Prolabo) wherein not only improved temperature/power control is possible but also relatively large scale reactions (1 litre capacity) can be conducted68 with additional options available for continuous operation.The engineering and scale-up aspects for the chemical process development have already been discussed.69 The major industrial applications of MW-enhanced clean chemistry include the preparation of hydrogen cyanide, a chlorination plant, drying of pharmaceutical powders and pasteurization of food products.There are distinct advantages of these solvent-free protocols since they provide reduction or elimination of solvents thereby preventing pollution in organic synthesis ‘at source’.Although not delineated completely, the reaction rate enhancements achieved in these methods may be ascribable to non-thermal effects. The chemo-, regio- or stereo-selective synthesis of high value chemical entities may see the translation of these laboratory ‘curious’ experiments to large-scale operations pending the design of bigger microwave reactors and the participation of equally enthusiastic teams of chemical and electrical engineers to harness the true potential of this clean technology. 4. Acknowledgments I am grateful for financial support to the Texas Advanced Research Program (ARP) in chemistry (Grant # 003606-023), the Retina Research Foundation Houston and the Texas Research Institute for Environmental Studies (TRIES). I am indebted to contributions from several research associates whose names appear in the references and especially to Dr.Kannan P. Naicker for his help in the preparation of this manuscript. 5. References 1 Using chemical reagents on porous carriers, Akt.-Ges. Fur Chemiewerte, Br. Pat., 1924, 231,901; Chem. Abstr., 1925, 19, 3571. 2 (a) G. H. Posner, Angew. Chem., Int. Ed. 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ISSN:1463-9262    

DOI:10.1039/a808223e

出版商:RSC    

年代:1999

数据来源: RSC