<p>US-India Summer Program for Research in Green Chemistry Dr. Mohammed Ali, Professor in the chemistry department at Southeast Missouri State University (SEMO) and Dr. Brindaban Ranu, senior professor in the chemistry department at Indian Association for the Cultivation of Science have ongoing, complementary projects in green chemistry and nanochemistry, Dr. Ali has been mentoring undergraduate research in green chemistry at SEMO for more than a decade. He regularly mentors five to six students per semester and has published over a dozen papers in peer reviewed chemistry journals with students as co-author. Dr. Ali’s research has focused on (1) solid-supported reagents and catalysts, (2) using alternate solvents for organic reactions, and (3) in a joint effort with Dr. Bjorn Olesen(Co-Pi) has been investigating microwave assisted organic synthesis (MAOS). Dr. Ranu’s research has focused on using (1) alternate feed-stocks, (2) green reaction media, (3) catalysts and biocatalysts, (4) solid supported reagents and catalysts, and (5) MAOS. d. Nature of Proposed Activities Four students per year will be selected to travel to IACS for eight weeks during the summers of 2011, 2012, and 2013. The participants for this project will be selected from a pool of students from Southeast Missouri State University, Cape Girardeau, MO. The participants will receive training and orientation at Southeast prior to departing for India. Due to his familiarity with the city of Kolkata and his familiarity with the culture, the PI Dr. Mohammed Ali will travel with the participants to India and remain there for two weeks the first year and one week each of the subsequent years. During this time the PI will be available to assist with any problems relating to housing, meals, medical or other issues that may come up during the first few days in India. Also, the presence of PI in India each summer will allow him to participate in the orientation and in assigning each student to his or her specific project. The PI’s knowledge of each participant’s research background and training will allow him to guide the students in selecting projects that match their research background and training. This will also give the PI the opportunity to reinforce expectations of the IRES project with the participants and the host institution. It is critically important for the success of this IRES summer research project that the expectations of the IRES project participants, the PI, co-PI, and the international collaborators are the same. This can best be accomplished by face-to-face meetings. </p><p>1 Project selection. The PI and co-PI and Dr. Ranu have worked together to identify two projects that are particularly well-suited for the students. The projects selected for the participants will come from the following areas.</p><p>RuO4 catalytic oxidations This project addresses the development of new environmentally benign catalytic procedures for oxidative transformation of organic substrates using ruthenium tetroxide.</p><p>Catalytic RuO4 oxidations have made great contributions to organic synthesis since Carl Djerassi first introduced it as an oxidizing agent for various organic substrates in 1953.1a-d Oxidation of alcohols,2 dihydroxylation of alkenes,3 ketoxylation of alkenes,4 oxidative cleavage of carbon- carbon double bonds,5 oxidation of aromatic rings,6 and oxidation of hetoroatoms,7 have all been accomplished using RuO4.</p><p>Catalytic procedures utilizing RuO4 represent a sensible way to utilize expensive ruthenium compounds in organic synthesis. RuO4 is generally generated in situ from RUCl3 or</p><p>RuO2 by reacting either with stoichiometric amounts of reoxidant in a biphasic water- halogenated organic solvent system (See Figure 1).1,8 </p><p>RuO4 can be prepared from RuCl3 or RuO2 by reaction with appropriate oxidizing agents,</p><p>1-8 including NaIO4, NaOCl, NaBrO3, peroxy acids, cyanuric chloride, oxone and K2S2O8. </p><p>Solid-supported heterogeneous RuO4 has emerged as a green, environmentally safe</p><p>9 reagent. Heterogeneous RuO4 catalysts are recyclable, produce enhanced activity due to the dispersion of the catalyst on the solid particles, and have higher turnover number and product selectivity than corresponding homogeneous methods.</p><p>Solid-supported RuO4 catalysts are generally prepared by immobilizing a lower valent ruthenium compound on a solid through encapsulation or covalent bond formation followed by oxidation to the active RuO4. A number of procedures replacing halogenated solvent with ethyl</p><p>10 11 acetate or dimethyl carbonate in RuO4 promoted oxidation reactions have recently been reported</p><p>2 Solid-supported ruthenium catalysts still produce halogenated waste and water contaminated with toxic materials. In addition, water-sensitive organic substrates cannot be used. We propose to address these problems by developing nonaqueous reaction protocols for</p><p>RuO4 oxidations. </p><p>RuO4 catalytic oxidations using solid-supported stoichiometric reoxidant</p><p>As a new approach to catalytic oxidation we propose to investigate catalytic RuO 4 oxidations using solid supported stoichiometric reoxidants (See Figure 1). These reagents will then be used with catalytic solid-supported or homogeneous ruthenium. Figure 1: The catalytic cycle</p><p>Reoxidant Oxidized on silica gel RuO4 organic substrate</p><p>Dimethyl carbonate Reaction Media</p><p>Spent Ru Organic reoxidant (Inactive) substrate on silica gel</p><p>This approach will eliminate the use of water, traditionally used in these oxidations, and should allow for RuO4 oxidation of water-sensitive compounds. The heterogeneous reoxidant will be prepared by immobilizing NaIO4, H5IO6, peroxy acids, NaBrO3, NaOCl, K2S2O8 or oxone on silica gel. We have found that mixing an aqueous solution of the stoichiometric reoxidant with chromatographic silica gel in a 1:2 or higher mass ratio produces a free-flowing, solid-supported reagent. Catalytic amounts of RuCl3 or RuO2 will be used to generate the RuO4 oxidant. The reaction will be carried out by dissolving the organic substrate (alcohols, sulfides, or alkenes) and the ruthenium catalyst in a non-halogenated solvent. As the reaction proceeds, the stoichiometric reoxidant will generate a steady supply of catalytic RuO4. At the end of the reaction, the spent heterogeneous reoxidant on silica gel will be filtered from the organic solution. The RuO4 will be recovered by precipitating it with diethyl ether, reused, and the product will be recovered from the organic solvent.</p><p>3 A few model reactions have been sucessfully done using the above procedure. Using</p><p>RuCl3 as the RuO4 precursor and NaIO4/silica gel as the reoxidant, thioanisole was converted to the corresponding sulfone (95%) in 15 minutes, t-bytyl sulfide to t-butyl sulfone (100%) in 30 minutes, cyclohexene to hexanedioic acid (84%) in one hour, and trans-anethole to 4- methoxybenzoic acid (100%) in one hour (Figure 2). These reactions were all carried out in dimethyl carbonate instead of the traditional aqueous-halogenated organic biphasic media. </p><p>Figure 2: Model Reactions OH O RuO4 R R R R</p><p>RuO4 R CH2OH R CO2H</p><p>O O S RuO R R 4 S R R</p><p>R O RuO4 R R R O</p><p>To find the best stoichiometric reoxidant for preparing catalytic RuO4 , the chemistry of</p><p>NaIO4, H5IO6, NaOCl, NaBrO3, oxone, K2S2O8, and peroxy acids will be investigated. Use of these</p><p>1-8 reoxidents in homogeneous RuO4 oxidation reactions has been reported. Reoxidants with high water solubility will be investigated first, since this will limit the amount of water needed to prepare the supported reagent. This could be important when using the reagent with water sensitive compounds. However, any water used to form the supported reagent should be tightly bound to the silica and should not cause any difficulties.12</p><p>Oxidation using nanoparticle sized RuO4</p><p>4 Nano-metals are known to exhibit very different catalytic properties than the corresponding bulk materials.13 Nano-sized materials are superior catalysts due to their large surface area and high density of active sites. Solid supported ruthenium has been used to oxidize alcohols, alkenes, sulfides, and various other compounds.9 Ruthenium supported on</p><p>9b 9a 9c zeolite, hydoxyapatite, Al2O3, exhibit good activity and selectivity in the oxidation of organic molecules. Importantly, nano-sized ruthenium gave higher catalytic activity than the corresponding bulk ruthenium catalyst.9b Recovery and reusability of the nano ruthenium catalyst was excellent. As an extension of the work described previously, we propose to synthesize ruthenium nano particles and stoichiometric reoxidant, each supported on silica gel and use them to oxidize various organic compounds as described in section one of this proposal. Drs. Ranu and Ali both have ongoing research in using nano-sized particles. Unlike the literature procedures, our reagent will avoid the use of water in these reactions and should extend the reactions to water sensitive compounds.12 Also, simple filtration will remove both oxidant and reoxidant speeding up reaction workup and generating a minimal amount of waste for disposal. The ruthenium nanoreagents will be prepared by the method of Miyazaki.9c According to this procedure, chromatographic grade silica gel will be suspended in a solution of ethylene glycol and RuCl3. The mixture will be heated for one hour at 180, cooled and filtered to remove the silica gel. The excess ethylene glycol will be removed by washing with a NaNO 3 solution and dried in vacuo. Inductively Coupled Plasma Spectroscopy will be used to determine the concentration of ruthenium in the filtrate and on the silica gel. Transmission Electron Microscopy will be used to determine the ruthenium particle size supported on the silica gel. Both instruments are available at IACS. There are other protocols for supporting metal nano particles on solids reported in the literature that could also be used to prepare the reagent, if necessary.14 Oxidation of benzyl and other activated alcohols, primary and secondary alcohols, sulfides, and alkenes will be carried out in an environmentally friendly organic solvent, such as dimethyl carbonate which gave excellent results on model reactions. Other solvents will also</p><p>5 be investigated . We anticipate that product isolation will simply involve filtration since the reagents will be supported on silica gel. Solventless reactions will be also be investigated. The exact project selected by each student will be done in consultation with professor Ranu. The IRES students will participate in various orientation activities organized by the international host to augment the preparation at SEMO. Once the project has been selected, the participants will be assigned appropriate reading materials to provide them with sufficient background knowledge of their research topic. Dr. Ranu will keep the PI at SEMO apprised of student progress and any problems that may surface. The US students will carry out research in green chemistry under close supervision of their mentor. The US students will meet with their mentor regularly to discuss and plan their laboratory work. In addition to research, the US students will participate in seminars and other professional activities regularly scheduled at the host institution and thus become intimately involved with all facets of research at IACS. During the last week, the project participants will conclude their visit by writing a research report. During this week, they will also visit cultural and historical sites. Working side-by-side with Indian students in the laboratory will teach the participants a great deal of chemistry, and will also be an important contribution to our students’ cultural experience in India. Dr. Ranu will provide opportunities for the students to participate in activities that will introduce them to other aspects of Indian culture. Students will have the opportunity to visit other research facilities in India during their time in India. Jadavpur University, The Indian Institute of Chemical Biology, and The Central Ceramic Research Institute are all near the IACS campus. Upon returning to the US, each participant will give a presentation to faculty and students at SEMO. The presentation will summarize the research and cultural experiences each student had in India. It is anticipated that these presentations will play an important role in recruiting new participants for the following years. </p><p>6 The participants are expected to continue their research when they return to the US under the supervision of the PI or co-PI. It is anticipated that the work will result in presentations at regional meetings and in publication in refereed journals. f. U.S. Host Institution Resources The selected students will prepare for their scientific mission to India by participating in a three-day intensive orientation prior to their departure. During this time, they will be introduced to the potential research available to them, will receive cultural orientation, and will have a time to get acquainted and begin functioning as a team. The orientation will be supervised by Dr. Mohammed Ali (PI) and Dr. Bjorn Olesen (Co-PI), and will include specific training developed in collaboration with IACS. Both Drs. Ali and Olesen have personal experience in moving into a foreign culture. We hope to utilize our personal experience and the expertise in the SEMO International Office, whose personnel prepare all SEMO students participating in study abroad programs, in our orientation. g. Foreign Partner’s Research and Education/Mentoring Expertise Professor Brindaban Ranu completed his graduate education at The Jadavpur University, Kolkata, India. After completing his Ph. D., he joined Prof. T. Hudlicky’s research group at Virginia Tech University, U. S. A. during 1982-85 for postdoctoral research. Professor Ranu returned to India in 1985 to accept a position at The Indian Association for the Cultivation of Science and since then he has been working at this institution. He is currently a senior professor in the organic chemistry department at IACS. He was elected Fellow of the Indian Academy of Sciences in 1995 and Fellow of the Indian National Science Academy in 2007. He is a member of the Green Chemistry Task Force Committee of the Department of Science and Technology, India. He was a visiting Scientist at the Centre for Green Chemistry, Monash University, Clayton, Australia during May-June, 2001. Professor Ranu’s research interests cover such areas as development of new reagents and procedures for organic synthesis using green technology (solvent free reaction and ionic liquid) and indium-mediated reactions. He has published more than 165 papers and review articles in international chemistry journals and presented his research at numerous national and international conferences. He has supervised 18 Ph. D. dissertations.</p><p>7 h. Student Arrangements at Foreign Institution All personnel at IACS are fluent in English and the institute uses English in all of its official correspondence. Presentations are delivered in English at the institute. Therefore, US students will not encounter any language barrier in communicating with IACS members. Since there is no dorm at IACS, students will live off campus. IACS is located in the city center close to a number of hotels of international standards. Dr. Ali, visited IACS this during the summer of 2008 to survey the available hotels and eating facilities close to the IACS campus. He has prepared a short list of hotels and restaurants where students could live comfortably and eat during their stay at IACS. These hotels are chosen on the basis of available amenities including air conditioning, pool, workout facility, eating facility, and safety. A transportation company will be hired to transport students daily to and from the IACS campus. After the U. S. students arrive in Kolkata, Dr. Ali will conduct an orientation to familiarize students with the local customs and culture. The orientation will include the following activities. a. Visit a department store. Observe the differences and similarities to shopping in the U. S.</p><p> b. Visit a fast food restaurant. Become familiar with the Indian menu.</p><p> c. Observe people on the streets to see how Indians dress and how they greet each other.</p><p> d. Visit a bank to learn how business is conducted and how to withdraw money from an ATM. </p><p> e. Discuss the local liquor law.</p><p> f. Discuss what to do during medical or other emergencies.</p><p>All students are required to have health insurance. Students not covered by their parents’ policy are able to purchase health insurance through their university. SEMO has an International Program Office staffed by a full-time director and support staff. This office coordinates SEMO’s off-campus study programs including London-Missouri and Immersion Programs. They will assist with the pre-departure orientation and be in place to assist with any</p><p>8 problems or emergencies that may arise. The International Program Office’s resources will available to provide a comprehensive international research experiences for the U. S. students while staying at IACS in India. i. Project Evaluation and Tracking of Participants The impact of the IRES research program will be evaluated by (1) student seminars, (2) publications that result from the work, (3) student reaction, and (4) long-term effects on students. The students will give a seminar at SEMO that will be evaluated by the Pi and the Co-Pi. In addition, Dr. Ranu will be asked to evaluate each student in terms of his/her ability to do research independently, work ethic, independence of thought, and growth in these. The work of our students is expected to be of publishable quality. Publications resulting from the work would serve as external validation of the quality of the project. We will track our students for a period of three years to see if their career choices involve them in research or employment with a global perspective. Also, the IRES students will be encouraged to stay in touch with their mentor in India. We will survey each returning student to determine the impact their summer in India had both personally and professionally. We will use the data from one year to make useful changes for the next year. A website will be created to disseminate the project activities. j. Benefits to students who did not travel to India as an IRES participant Students who have not directly participated in the IRES project will benefit from personal interaction with the students who participated. As our participants share personal experiences, they will enrich the lives of those who did not go. We will encourage our participants to share personal insights into Indian culture and people as they present their seminar. Non-participants will also benefit by being exposed to chemistry not currently done at their home institution. We expect the enthusiasm of our participants to be infective among other students. We are confident that the experiences, both professional and cultural, of the returning students will encourage others to consider participating in research across borders and in joining the global community in solving globally significant problems. </p><p>9</p>