METHODS AND REAGENTS FOR GREEN CHEMISTRY, INNOVATION TECHNOLOGIES Organic & Pharmaceutical Chemistry Department Astrakhan State University Prof. Velikorodov. - презентация

1 METHODS AND REAGENTS FOR GREEN CHEMISTRY, INNOVATION TECHNOLOGIES Organic & Pharmaceutical Chemistry Department Astrakhan State University Prof. Velikorodov A.V.

2 The chemical industry accounts for 7% of global income and 9% of global trade. Production is projected to increase 85% by 2020 compared to the 1995 levels. Over the past half-century, the largest growth volume of any category of materials has been in petrochemical-based plastics; and in terms of revenue it was pharmaceuticals. In the United States, the chemical industry contributes 5% of GDP and adds 12% of the value to GDP by all U.S. manufacturing industries and it is also the nation's top exporter. This information speaks volumes about the importance of chemical industries in our day-to-day life and in supporting the nation's economy. But it is plagued with several problems, such as running out of petrochemical feedstock, environmental issues, toxic discharge, depletion of nonrenewable resources, short term and long-term health problems due to exposure of the public to chemicals and solvents, and safety concerns, others.

3 About 7.1 billion pounds of more than 650 toxic chemicals were realized to the environment in 2000 by the United States alone (Environmental Protection Agency, 2002,

4 An ideal manufacturing process An ideal Product An ideal process is simple, requires one step, is safe, uses renewable resources, is environmentally acceptable, has total yield, produces zero waste, is atom-efficient, and consists of simple separation steps. An ideal product requires minimum energy and minimum packaging, is safe and 100% biodegradable, and is recyclable.

5 An ideal user An ideal user cares for the environment, uses minimal amounts, recycles, reuses, and understands a products environmental impact. In addition, an ideal user encourages "green" Green chemistry involves a reduction in, or elimination of, the use of hazardous substances in a chemical process or the generation of hazardous or toxic intermediates or products. This includes feed-stock, reagents, solvents, products, and byproducts. It also includes the use of sustainable raw material and energy sources for this manufacturing process

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7 GREEN CHEMISTRY Green and sustainable chemistry, a new concept that arose in the early 1990s, gained wider interest and support only at the turn of the millennium. Green and sustainable chemistry concerns the development of processes and technologies that result in more efficient chemical reactions that generate little waste and fewer environmental emissions than "traditional" chemical reactions do. Green chemistry encompasses all aspects and types of chemical processes that reduce negative impacts to human health and the environment relative to the current state-of-the-art practices. By reducing or eliminating the use or generation of hazardous substances associated with a particular synthesis or process, chemists can greatly reduce risks to both human health and the environment.

8 Twelve Principles of Green Chemistry 1. Prevention. It is better to prevent waste than to treat or clean it up after it has been generated in a process. This is based on the concept of "stop the pollutant at the source." 2. Atom economy. Synthetic steps or reactions should be designed to maximize the incorporation of all raw materials used in the process into the final product, instead of generating unwanted side or wasteful products (Trost, 1991, 1995).

9 3. Less hazardous chemical use. Synthetic methods should be designed to use and generate substances that possess little or no toxicity to the environment and public at large. 4. Design for safer chemicals. Chemical products should be designed so that they not only perform their designed function but are also less toxic in the short and long terms. 5. Safer solvents and auxiliaries. The use of auxiliary substances such as solvents or separation agents should not be used whenever possible. If their use cannot be avoided, they should be used as mildly or innocuously as possible. 6. Design for energy efficiency. Energy requirements of chemical processes should be recognized for their environmental and economic impacts and should be minimized. If possible, all reactions should be conducted at mild temperature and pressure.

10 7. Use of renewable feedstock. A raw material or feedstock should be renewable rather than depleting whenever technically and economically practicable. For example, oil, gas, and coal are dwindling resources that cannot be replenished. 8. Reduction of derivatives. Use of blocking groups, protection/de-protection, and temporary modification of physical/chemical processes is known as derivatization, which is normally practiced during chemical synthesis. Unnecessary derivatization should be minimized or avoided. Such steps require additional reagents and energy and can generate waste. 9. Catalysis. Catalytic reagents are superior to stoichiometric reagents. The use of heterogeneous catalysts has several advantages over the use of homogeneous or liquid catalysts. Use of oxidation catalysts and air is better than using stoichiometric quantities of oxidizing agents. 10. Design for degradation. Chemical products should be designed so that at the end of their function they break down into innocuous degradation products and do not persist in the environment. A life-cycle analysis (beginning to end) will help in understanding its persistence in nature.

11 11. Real-time analysis for pollution prevention (Wrisberg et al., 2002). Analytical methodologies need to be improved to allow for real-time, in-process monitoring and control prior to the formation of hazardous substances. 12. Inherently safer chemistry for accident prevention. Substances and the form of a substance used in a chemical process should be chosen to minimize the potential for chemical accidents, including releases, storage of toxic chemicals, explosions, and fires. Green chemistry has introduced several new terms and new research frontiers, including "eco-efficiency", "sustainable chemistry," "atom efficiency or economy," "process intensification and integration," "inherent safety," "product life-cycle analysis," "ionic liquids," "alternate feedstock," and "renewable energy sources."

12 The Green Chemistry Expert System (GCES) developed by the EPA ( allows users to build a green chemical process, design a green chemical, or survey the field of green chemistry. The system is useful for designing new processes based on user-defined input. The various features of GCES are contained in five modules: 1. The "Synthetic methodology assessment for reduction techniques" (SMART) module quantifies and categorizes the hazardous substances used in or generated by a chemical reaction. 2. The "Green synthetic reactions" module provides technical information on green synthetic methods.

13 3. The "Designing safer chemicals" module includes guidance on how chemical substances can be modified to make them safer. 4. The "Green solvents/reaction conditions" module contains technical information on green alternatives to traditional solvent systems. Users can search for green substitute solvents based on physicochemical properties. 5. The "Green chemistry references" module allows users to obtain toxicity and other data about a large number of chemicals and solvents.

14 Green chemistry has become the important philosophy for the 21st century and beyond. Chemical and allied industries have taken this philosophy very seriously due to societal and governmental pressures with respect to environmental issues. In addition, depletion in fossil fuel and increased global competition have forced industries to look at biotechnology and green routes for achieving efficient manufacturing processes.

15 Waste prevention and environmental protection are major requirements in an overcrowded world of increasing demands. Synthetic chemistry continues to develop various techniques for obtaining better products with less damaging environmental impacts. The control of reactivity and selectivity is always the central subject in the development of a new methodology of organic synthesis. Novel, highly selective reagents appear every month. New reactions or modifications of old reactions have been devised to meet the ever-increasing demands of selectivity in modern synthesis. Periodic review articles and books appear in the literature on these newer reagents.

16 Newer Synthetic Methods Synthetic chemistry continues to develop various techniques for obtaining better products with less damaging environmental impacts. The control of reactivity and selectivity is always the central subject in the development of a new methodology of organic synthesis. Novel, highly selective reagents appear every month. New reactions or modifications of old reactions have been devised to meet the ever-increasing demands of selectivity in modern synthesis. In most reactions, the reaction vessel provides three components (as shown in Fig.): solvent, reagent/catalyst, energy input.

17 Hence, efforts to green chemical reactions focus predominantly on "greening" these three components. By "greening," we mean to Use benign solvents or completely dispense with the solvent. Use alternate, more efficient and effective reagents/catalysts. Optimize the reaction conditions by using cost-effective, eco-friendly alternative processes.

18 We now have six well-documented methods of activating molecules in chemical reactions, which can be grouped as follows: the classical methods, including thermal, photochemical, electrochemical, and the nonclassical methods, which include sonication, mechanical, microwave. The most atom-economy-suited reactions are condensations, multicomponent reactions, and rearrangements. Hence, where possible, these reaction types should be adopted, in order to ensure efficient synthesis. The challenges for designing a synthetic route can be he listed as

19 Minimize overall number of steps. Maximize yield per step. Maximize atom-economy per step. Use stoichiometric conditions. In nuiltistep syntheses, perform the following: Maximize frequency of condensations, MCRs, rearrangements, C- С and non-C-C bond-forming reactions. Minimize frequency of substitutions (protecting group strate­gics) and redox reactions. If forced to use oxidations, opt for hydrogen peroxide as oxidant. If forced to use reductions, opt for hydrogen as reductant. Devise electrochemical transformations. Devise catalytic methods where catalysts are recycled and reused. Devise regio-/stereoselective synthetic strategies. Opt for solventless reactions, recycle solvents, or use benign solvents (ionic liquids). Minimize energy demands: heating, cooling, reactions under pressure.

20 Fig. Atom-economy of various reaction types

21 CATALYSIS AND GREEN CHEMISTRY In general, catalysis plays a major role in making industrial processes more efficient and economically profitable. This can be quite obviously attributed to three general characteristics of catalysts: Catalytic reagents reduce the energy of the transition state, thereby reducing the energy input required for a process. Catalysts are required in small quantities. In the case of biocatalysts, the number of catalysts (generally enzymes) needed compared to the quantity of reactants is very low. The regeneration and reversibility of catalysts are good for green processes.

22 The oxidation contained of a secondary alcohol to a ketone using stoichiometric reagents has an atom- efficiency of 42%. The same product obtained through catalytic oxidation improves the atom-efficiency by more than double, to 87%. 3PhCH(OH)CH 3 + 2CrO 3 + 3H 2 SO 4 3PhCOCH 3 + Cr 2 (SO4) 3 + 6H 2 O Атомная эффективность = (360:860) 100 = 42% Атомная эффективность = (120:138) 100 = 87%

23 The use of zeolites in making industrial processes eco- compatible is growing with the widespread research on using these as citalysts. One such example of zeolite being used to better the existing process is that of the Meerwin-Ponndorf-Verly (MPV) reduction. The MPV reduction process is an extensively used technology for reducing aldehydes and ketones to their corresponding alcohols. In practice, the reduction involves a reaction of the substrate with a hydrogen donor (usually isopropanol), in the presence of an aluminum alkoxide. FIGURE 3.8. MPV reduction using zeolite.

24 Zeolite

25 Solutia (USA), in joint work with the Boreskov Institute of Catalysis, Russia, developed a one-step process to manufacture phenol from benzene using nitrous oxide as the oxidant. Biocatalysis is the other option when selectivity (sterio oi regio) is a priority in a reaction. The various aspects of biocatalysil are discussed elsewhere in the book; the following are some examples of biocatalysts that have been used in important synthesis.

26 Kirner (1995) conducted microbial ring hydroxylation and side chain oxidation of hetero-aromatics (see Fig.). Such selectivity is difficult to achieve in one step in traditional chemical synthesis.

27 Catalysts play a significant role in green chemistry by decreasing energy requirements, increasing selectivity, and permitting the use of less hazardous reaction conditions. The central role these catalysts play in directing the course of a reaction, thereby minimizing or eliminating the formation of side products, cannot be disputed. Hence, catalysisor rather, designed catalysisis the mainstay of green chemical practices.

28 In recent years, the development of ionic liquids, which are composed of organic molecules derived from l-alkyl- 3-methyl-imidazolium cation, such as [BMIm][BF 4 ], [MMIm][MeSO 4 ], and [EtPy][CF 3 COO], has attracted much attention to nonconventional biocatalysis (Husum et al., 2001; Kaftzik et al., 2002; Zhao and Malahortra, 2002). Studies using miscible water-ionic liquid mixtures gave controversial results, thus suggesting significant dependence of the solvent effect on the properties of the enzymes. Ionic liquids in mixtures with water display a potential to modify properties of biocatalyst. For instance, enzymatic resolution of N-acetyl amino acids using subtilisin Carlsberg in 15% N-ethyl pyridinium trifluroacetate in water was higher compared to acetonitrile under the same experimental conditions (Zhao and Malhorta, 2002).

29 Common ionic liquids

30 Use of Cyclodextrins The use of enzymes as valuable catalysts in organic solvents has been well documented. However, some of their features limit their application in organic synthesis, especially the frequently lower-enzyme activity under nonaqueous conditions, which constitutes a major drawback in the application of enzymes in organic solvents. In addition, many enzymatic reactions are subject to substrate or product inhibition, leading to a decrease in the reaction rate and enantioselectivity. To overcome these drawbacks and to make enzymes more appealing to synthesis, cyclodextrins are used. The effects of the cyclodextrins range from increasing the availability of insoluble substrates to reducing substrate inhibition to limiting product inhibition.

31 Cyclodextrin

32 1.enzymic cleavage of corn starch 2.Cyclodextrin-Glycosyltransferaze

33 In an interesting study, cyclodextrins were used as regulators for the Psendomonas cepacia lipase (PSL) and macrocyclic additives to enhance the reaction rate and enantioselectivity E in lipase-catalyzed enantioselective transesterification of l-(2-furyl) ethanol in organic solvents (Ghanem, 2003). Alternate Solvents Developing more benign synthetic procedures in chemical synthesis is important in moving toward sustainable technologies, as part of the rapidly emerging field of green chemistry. In reducing the amount of waste, the energy usage, and the use of volatile, toxic, and flammable solvents, several approaches are available, including avoiding the use of organic solvents for the reaction media. At the heart of green chemistry are alternative reaction media. They are the basis of many of the cleaner chemical technologies that have reached commercial development. Most well-known among these alternate reaction media being

34 use of safer solvents, use of water as solvent, reactions under solventless/solvent-free conditions, supercritical carbon dioxide (31.1 °C, 73 atm), supercritical water (374 °C, 218 atm), room-temperature ionic liquids. SubstanceCritical temperature, °С CO 2 31 C2H4C2H4 9 NH H2OH2O374

35 Solvent 1Isoamyl alcohol 22-Ethylhexanol 32-Butanol 4Ethylene glycol 51-Butanol 6Diethylene glycol butyl ether 7T-Butyl acetate 8Butyl acetate 9n-Propyl acetate 10Isopropyl acetate 11Dimethylpropylene urea 12Propionic acid 13Ethylacetate 14Methyl isobutyl ketone

36 Green solvents are environmentally friendly solvents, or biosolvents, which are derived from the processing of agricultural crops. The use of petrochemical solvents is the key to the majority of chemical processes but not without severe implications on the environment. Green solvents were developed as a more environmentally friendly alternative to petrochemical solvents. Ethyl lactate, for example, is a green solvent derived from processing corn. Ethyl lactate is the ester of lactic acid. Lactate ester solvents are commonly used solvents in the paints and coatings industry and have numerous attractive advantages including being 100% biodegradable, easy to recycle, noncorrosive, noncarcinogenic, and nonozone-depleting. Ethyl lactate as green solvent

37 Ethyl lactate is a particularly attractive solvent for the coatings industry as a result of its high solvency power, high boiling point, low vapor pressure, and low surface tension. It is a desirable coating for wood, polystyrene, and metals and also acts as a very effective paint stripper and graffiti remover. Ethyl lactate has replaced solvents such as toluene, acetone, and xylene, resulting in a much safer workplace. Other applications of ethyl lactate include being an excellent cleaner for the polyurethane industry. Ethyl lactate has a high solvency power, which means it is able to dissolve a wide range of polyurethane resins. The excellent cleaning power of ethyl lactate also means it can be used to clean a variety of metal surfaces, efficiently removing greases, oils, adhesives, and solid fuels. The use of ethyl lactate is highly valuable, as it has eliminated the use of chlorinated solvents.

38 Water as Solvent The chemistry in natural systems (biochemical reactions) is based on water. The use of water as solvent for synthetic chemistry holds great promise for the future in terms of the cheaper and less hazardous production of chemicals. It was discovered in pioneering studies on Dies-Alder reactions in water by Breslow's and Biscoe's research groups that such reactions often proceed with much higher rates and higher endoselectivity and exoselectivity than in organic solvents. Water as a solvent favored a more compact endo-transition state in Dies-Alder reactions. The accelerating effect of water has been ascribed to a number of factors, including the hydrophobic effect as well as hydrogen bonding between water molecules and reactants (Breslow, 2004).

39 Solvent-Free Conditions Several advantages are associated with the use of a solvent- free system over the use of organic solvent. These include 1. There is no reaction media to collect, dispose of, or purify and recycle. 2. On a laboratory's preparative scale, there is often no need for specialized equipment. 3. Extensive and expensive purification procedures such as chromatography can often be avoided due to the formation of sufficiently pure compounds. 4. Greater selectivity is often observed. 5. Reaction times can be rapid, often with increased yields and lower energy usage. 6. Economic considerations are more advantageous, since cost savings can be associated with the lack of solvents requiring disposal or recycling.

40 Supercritical Carbon Dioxide: scCO 2 Supercritical Water During the late 1980s it was found that reactions usually carried out in chlorofluorocarbon solvents can be done in liquid or supercritical CO 2. It was also observed that the polymerization of tetrafluoroethylene in CO 2 using fluorinated initiators gave good yields. CO2-based processes can also be used for dry cleaning, metal cleaning, and textile processing. Liquid CO 2 is also used in the microelectronics industry to spin-coat photoresists instead of using traditional organic solvents. Another example is the use of CO 2 to clean integrated circuits and flat-panel displays during manufacturing rather than using large amounts of water and organic solvents.

41 Water has obvious attractions as a solvent for clean chemistry. Both near-critical and supercritical water (scH 2 O) have increased acidity, reduced density, and lower polarity, greatly extending the possible range of chemistry that could be carried out in water. scH 2 O has already been studied extensively as a medium for the complete destruction of hazardous and toxic wastes (Savage et al,, 1995).

42 Green reagents 1. isocyanides

43 Ugi reaction

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46 2. Dimethylcarbonate as green reagent Traditional alkylation's reagents DMC

47 RENEWABLE FEEDSTOCKS

48 Green chemistry and the biorefinery

49 Its hard to be Green