mendations, as well as the likelihood and hazards of equipment failure. Maintenance plans should ensure that any lockout procedures cannot be violated.
Carefully handle and store glassware to avoid damage. Discard or repair chipped or cracked items. Handle vacuum-jacketed glassware with extreme care to prevent implosions. Evacuated equipment such as Dewar flasks or vacuum desiccators should be taped, shielded, or coated. Only glassware designed for vacuum work should be used for that purpose.
Use tongs, a tweezer, or puncture-proof hand protection when picking up broken glass. Small pieces should be swept up with a brush into a dustpan. Glassblowing operations should not be attempted unless an area has been made safe for both fabrication and annealing. Protect your hands and body when performing forceful operations involving glassware. For instance, leather or Kevlar® gloves should be used when placing rubber tubing on glass hose connections. Cuts from forcing glass tubing into stoppers or plastic tubing are a common laboratory accident and are often serious. (See Vignette 6.1.) Constructing adaptors from glass tubing and rubber or cork stoppers is obsolete; instead, use fabricated, commercial adaptors made from plastic, metal, or other materials.
(See Chapter 7 for more discussion.)
6.C.7 Working with Scaled-Up Reactions
Special care and planning is necessary to ensure safe scaled-up work. Scale-up of reactions from those producing a few milligrams or grams to those producing more than 100 g of a product may magnify risks by several orders. Although the procedures and controls for large-scale laboratory reactions may be the same as those for smaller-scale procedures, significant differences may exist in heat transfer, stirring effects, times for dissolution, and the effects of concentration—all of which need to be considered. (See Vignette 6.2.) When planning large-scale work, practice requires consulting with experienced workers and considering all possible risks.
A technician planned to replace the rubber vacuum tubing leading from a vacuum pump to a glass cold trap. While attempting to remove the old rubber tubing from the trap, the glass nipple broke and the broken glass cut the employee’s thumb. The technician did not don protective gloves or attempt to precut the rubber tubing to ease removal. The employee received three sutures.
A researcher scaled up the cycloaddition reaction of maleic anhydride with quadricyclane, a strained high-energy hydrocarbon. This reaction is reported in the literature and was also previously performed in the researcher’s laboratory without incident, albeit at small scale (<10 g). No solvent is used in the procedure. The researcher combined the reagents (approximately 250 g total, a 20-fold scale-up) and began heating to the 60-70 °C target temperature. On reaching 50-60 °C the internal temperature rose very rapidly to more than 220 °C. The subsequent rapid boiling of the reagents dislodged the reflux condenser and expelled some liquid and solid into the chemical fume hood. There was no fire. The materials were fully contained within the chemical fume hood, with no injuries, personnel exposure, or equipment damage.
The likelihood of runaway exothermic reactions must be considered whenever conducting a reaction on a larger scale than previous experience. In the present example this possibility was increased by the use of ultrapure reagents and the lack of solvent. When using high-energy reagents, it is preferable to run them as dilute as possible in a solvent. This practice significantly lowers the energy density and significantly adds to the thermal mass, which help to decrease the chance of a runaway reaction. Slow addition of one reagent also limits the effects of an exothermic reaction.
Although one cannot always predict whether a scaled-up reaction has increased risk, hazards should be evaluated if the following conditions exist:
• The starting material and intermediates contain functional groups that have a history of being explosive (e.g., N—N, N—O, N—halogen, O—O, and O—halogen bonds) or that could explode to give a large increase in pressure.
• A reactant or product is unstable near the reaction or workup temperature. A preliminary test to determine the temperature and mode of de-