Safer Synthesis

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

The wide array of choices available to research chemists necessitates a diligent search for hazards to select the inherently safest chemistry. One of the means to search for hazards is to conduct a literature search, looking in particular for reports of incidents occurring in processes using the same or similar process chemistry being considered. 

---

Itforms impact-sensitive mixtures with ethers (dioxane, etc.) and halocarbons (carbon tetrachloride) and ignites in oxygen at 100°C [1,2]. An improved and safer synthesis of decaborane from pentaborane is given [3],... 

It ignites when heated in air [1], A new and safer synthesis from red phosphorus and grey selenium has been described [2],... 

Design less hazardous chemical syntheses Design syntheses to use and generate substances with little or no toxicity to humans and the environment. A holistic view of a synthetic pathway often allows a chemist to change factors and minimize hazard in a number of steps simultaneously. A safer synthesis may simply reduce the number of isolations and purifications,... 

Major challenges seem today even closer, including the synthesis of homochiral zeolites in the pure and separate form and their evaluation in asymmetric chemical and physicochemical processes, as well as crystalline zeolites with more open spaces, where larger molecules could be processed. Cheaper, faster, environmentally safer synthesis procedures should be sought, in particular with regard to the synthesis of hydrophobic pure-silica materials, where the use of HF should be avoided if a major industrial application is desired. In the coming years we may expect many beautiful new structures and exciting new chemistry within the zeolite field. 

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. 

Select a process chemistry or synthesis route that is inherently safer. 

Select a process chemistry or synthesis route that is inherently safer (e.g., nontoxic, nonflammable materials, less severe operating condition)... 

Hazardous chemicals or mixtures may be replaceable by safer materials. These may be less toxic per se, or less easily dispersed (e.g. less volatile or dusty). Substitution is also applicable to synthesis routes to avoid the use of toxic reactants/solvents or the production, either intentionally or accidentally, of toxic intermediates, by-products or wastes. 

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 ... 

Examples of Synthesis Routes Inherently Safer Than Others As summarized by Bodor (1995), the ethyl ester of DDT is highly effective as a pesticide and is not as toxic. The ester is hydrolytically sensitive and metabolizes to nontoxic products. The deliberate introduction of a structure into the molecule which facilitates hydrolytic deactivation of the molecule to a safer form can be a key to creating a chemical product with the desired pesticide effects but without the undesired environmental effects. This technique is being used extensively in the pharmaceutical industry. It is applicable to other chemical industries as well. 

In spite of the hazardous nature of Sc4N4, this binary selenium nitride has been used for the synthesis of other Se-N compounds, all of which have sulfur analogues (Scheme 5.2). " However, safer alternatives to the use of Sc4N4, e.g., selenium-nitrogen halides and silicon-nitrogen-selenium reagents, are available for the development of Se-N chemistry. ... 

The strategy of intrinsic continuous process safeguarding merits further attention. Consider the example of Grignard s synthesis using highly flammable ether as a solvent. The use of a safer. solvent mixed with a minimum amount of ether to reduce its vapour-phase concentration, along with a more predictable initiation, would be very helpful. We should ensure that in the vapour phase, explosive mixtures are not encountered. 

Potassium is the second most abundant cation in the body and is found primarily in the intracellular fluid. Potassium has many important physiologic functions, including regulation of cell membrane electrical action potential (especially in the myocardium), muscular function, cellular metabolism, and glycogen and protein synthesis. Potassium in PN can be provided as chloride, acetate, and phosphate salts. One millimole of potassium phosphate provides 1.47 mEq of elemental potassium. Generally, the concentration of potassium in peripheral PN (PPN) admixtures should not exceed 80 mEq/L (80 mmol/L). While it is safer to also stick to the 80 mEq/L (80 mmol/L) limit for administration through a central vein, the maximum recommended potassium concentration for infusion via a central vein is 150 mEq/L (150 mmol/L).14 Patients with abnormal potassium losses (e.g., loop or thiazide diuretic therapy) may have higher requirements, and patients with renal failure may require potassium restriction. 

Konieczny, A., and Safer, B. (1983). Purification of the eukaryotic initiation factor 2-eukaryotic initiation factor 2B complex and characterization of its guanine nucleotide exchange activity during protein synthesis initiation. J. Biol. Chem. 258, 3402—3408. 

---