Safety synthesis

The restrictions which apply to a synthesis will depend on the reason the synthesis is being conducted. A synthesis of a material to be prepared in substantial quantity may impose a limitation as to cost of starting materials. Syntheses for commercial production must meet such criteria as economic feasibility, acceptability of by-products, and safety. Synthesis of complex structures with several chiral centers must deal with the problem of stereoselectivity. If an enantiomerically pure material is to be synthesized, the means of controlling enantioselectivity must be considered. The development of a satisfactory plan is the intellectual challenge to the chemist. The task puts a premium on creativity and ingenuity. There is no single correct... 

CTBSSP Commercial Truck and Bus Safety Synthesis Program... 

Safety synthesis of an engineering system is usually conducted by aggregating safety assessments for its sub-systems, components and failure modes. A safety assessment framework may constitute a hierarchical structure with failure modes at the bottom level (Wang et al. (1996)). A failure mode could be described in several ways, for example in terms of failure likelihood, consequence severity and failure consequence probability using linguistic variables. This is a natural and sensible way for capturing ambiguity and uncertainty inherent in safety assessment. 

There are other ways to describe safety. The simplest approach would be to use a scale for scoring the safety of a failure mode. While this may be easy for safety aggregation to produce an average indicator about system safety, it could not capture uncertainty inherent in safety assessment and thereby the credibility of such assessment may become questionable. Unfortunately, several well known multiple criteria decision analysis methods, which could be used for safety synthesis, can only be implemented using certain types of scores. This will be discussed in detail in the next section. 

FK-506 (37) interferes with IL-2 synthesis and release and has a cyclosporin-like profile, but is considerably more potent in vitro. IC q values are approximately 100-fold lower. This neutral macroHde suppresses the mixed lymphocyte reaction T-ceU proliferation generation of cytotoxic T-ceUs production of T-ceU derived soluble mediators, such as IL-2, IL-3, and y-IFN and IL-2 receptor expression (83). StmcturaHy, FK-506 is similar to sirolimus. Mycophenolate mofetil (33), brequinar (34), and deoxyspergualin are in various phases of clinical evaluation. Identification of therapeutic efficacy and safety are important factors in the deterrnination of their utiUty as immunosuppressive agents. 

High Osmolality Contrast Media. An important advance in radiopaques came with the synthesis of aminotriiodoben2oic acid and its acetylated derivative, acetrizoic acid [85-36-9] (5) (8,9). Aqueous solutions of sodium acetrizoate possessed the thermal stabiUty so that they could be autoclaved (10) with minimal decomposition. The higher iodine content, ie, 3 atoms/molecule, increased the contrast efficiency, and the clinical safety of acetrizoate was improved over that of the earlier urographic agents. 

The earliest method for manufacturiag carbon disulfide involved synthesis from the elements by reaction of sulfur and carbon as hardwood charcoal in externally heated retorts. Safety concerns, short Hves of the retorts, and low production capacities led to the development of an electric furnace process, also based on reaction of sulfur and charcoal. The commercial use of hydrocarbons as the source of carbon was developed in the 1950s, and it was still the predominate process worldwide in 1991. That route, using methane and sulfur as the feedstock, provides high capacity in an economical, continuous unit. Retort and electric furnace processes are stiU used in locations where methane is unavailable or where small plants are economically viable, for example in certain parts of Africa, China, India, Russia, Eastern Europe, South America, and the Middle East. Other technologies for synthesis of carbon disulfide have been advocated, but none has reached commercial significance. 

Orga.nic Colora.nts. The importance of coal-tar colorants cannot be overemphasized. The cosmetic industry, in cooperation with the FDA, has spent a great deal of time and money in efforts to estabUsh the safety of these dyes (see Colorants for food, drugs, cosmetics, and medical devices). Contamination, especially by heavy metals, and other impurities arising from the synthesis of permitted dyes are stricdy controlled. Despite this effort, the number of usable organic dyes and of pigments derived from them has been drastically curtailed by regulatory action. 

Understanding the chemistry of the process also provides the greatest opportunity in applying the principles of inherent safety at the chemical synthesis stage. Process chemistry greatly determines the potential impact of the processing facility on people and the environment. It also determines such important safety variables as inventory, ancillary unit operations, by-product disposal, etc. Creative design and selection of process chemistry can result in the use of inherently safer chemicals, a reduction in the inventories of hazardous chemicals and/or a minimization of waste treatment requirements. 

Rasmussen, J. 1979. Notes on human error analysis and prediction. In G. Apostalakis and G. Volta (Eds.), Synthesis and Analysis Methods for Safety and Reliability Studies, Plenum, New York. 

When using the checklist, the reviewer should decide m advance which questions would not be applicable to the toller s operations. For example, the environmental and healthand safety issues associated with a toller that will be used solely to conduct packaging will greatly differ from a of a toller that will be used to perform an organic synthesis step. 

This book briefly reviews ammonia synthesis, its importance in the chemical process industry, and safety precautions. This case study is integrated into several chapters in the text. See the Introduction for further details. 

Basic process chemistry using less hazardous materials and chemical reactions offers the greatest potential for improving inherent safety in the chemical industry. Alternate chemistry may use less hazardous raw material or intermediates, reduced inventories of hazardous materials, or less severe processing conditions. Identification of catalysts to enhance reaction selectivity or to allow desired reactions to be carried out at a lower temperature or pressure is often a key to development of inherently safer chemical synthesis routes. Some specific examples of innovations in process chemistry which result in inherently safer processes include ... 

Rogers and Hallam (1991) provide other examples of chemical approaches to inherent safety, involving synthesis routes, reagents, catalysts and solvents. 

Innovative chemical synthesis procedures have been proposed as offering potential for economical and environmentally friendly routes to a variety of chemicals. These novel chemical reactions also offer potential for increasing the inherent safety of processes by eliminating hazardous materials, eliminating chemical intermediates, or allowing... 

Much of this chemistry is still at an early stage of research, and there are few, if any, commercial applications. However, the potential environmental and safety benefits of these and other innovative chemical synthesis techniques will encourage further research and development. 

Research chemists have many opportunities to incorporate inherent safety in the choice of chemical synthesis route, including ... 

A chemist may think only of optimizing the route of synthesis to avoid a runaway reaction hazard and not consider the safety and design implications of flammable reaction by-products. 

The synthesis of aromatic amines is an active and important area of research.2 Many methods are available in the literature for the synthesis of these compounds. Though some of these are widely used, still they have limitations based on safety or handling considerations. For example, catalytic hydrogenation3 of nitro or azido compounds in the presence of metals such as palladium on carbon or Raney nickel require stringent precautions because of their flammable nature in the presence of air. In addition, these methods require compressed hydrogen gas and a vacuum pump to create high pressure within the reaction flask. To overcome these difficulties, several new methods have been reported in the... 

New systems or processes may also need to be qualified from an operational safety perspective. This is particularly relevant in the case of chemical synthesis involving exothermic reactions. Critical safety aspects are usually identified using hazard operability or HAZOP assessments and studies. For example, a HAZOP analysis of an exothermic reaction vessel would involve consideration of the consequence of failure of the motors for mixers or circulation pumps for cooling water. Thus, the qualification of such a system would involve checks and assessment to ensure that the system/process can be operated safely and that pressure relief valves or other emergency measures are adequate and functional. 

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