1.  Planning Experiments

• Avoid storing organolithium compounds, use them promptly after purchase. If storage is required, do so in an explosion-proof fridge that maintains a temperature of 10°C or lower.
• Become acquainted with your reagents before beginning to work with them; review SDS information for more information about storage, handling, and hazards.
• Do not work alone, ensure a colleague is available to call for help in case of emergencies.

2.  Protection

Due to the various hazards associated with organolithium compounds, wearing appropriate PPE is vital. This includes:

• Eye protection: Safety glass and goggles, or face shields when working with high volumes of reagents
• Body: Flame-resistant lab coats or coveralls
• Gloves: Viton is the most protective but can be costly. Nitrile gloves may be appropriate
• Footwear: Close toed, slip-proof shoes
• Firefighting equipment: Ensure fire extinguishers are operational and easily accessible. Use Class B extinguishers. Do NOT use extinguishers that contain water, CO₂, or halogenated hydrocarbons

3.  Lab setup

• Perform all work in an efficient fume hood that is free of clutter and flammables.
• Set up an inert gas line (nitrogen, argon) with an appropriate delivery system including bubblers, manifolds, and plastic lines to dry glassware. Use gas with the lowest air and moisture content possible.
• Use anhydrous solvents with the lowest moisture content. J&K Scientific’s anhydrous solvent bottles are specifically designed to ensure that your solvents stay fresh for longer.
• Glassware and other apparatuses should be thoroughly dried. This can be done by heating to 120°C for several hours, and either:
  • Assembling in the hood while hot, and allowing to cool in a stream of inert gas
  • Placing in a desiccator to cool, and assembling in the hood under a stream of inert gas
• Prepare your reaction setup with the following:
  • Mechanical stirrer
  • Pressure-equalizing addition funnel with septum
  • Claisen adapter with thermometer
  • Dry ice condenser
  • Inert gas line connected to condenser outlet, which is attached to a bubbler containing mineral oil
  • Second inert gas line for the reagents container
  • Metal bowl to contain the reaction vessel, used as a catch bowl in case glassware breaks, or to contain a cooling medium such as dry ice and inert hydrocarbons
• During the quenching process, toluene, isopropanol, and dry ice should be used. These compounds should be placed in labelled beakers within close reach of the reaction vessel and covered with an appropriately sized watch glass. Approximate required volumes are as follows:
  • Toluene: Same volume as LiR reagent
  • Isopropanol: ~5x more isopropanol than LiR reagent
  • Dry ice pellets: ~10x mor dry ice than LiR reagent

4.  Working with Organolithium Compounds

• Remove organolithium compounds from the refrigerator immediately before use, do not allow them to heat up
• Once the reagent is dispensed, replace the cap, and return it to the fridge
• Place the reaction flask in a metal bowl. This will be used as a catch bowl in case the glassware shatters, or can also to be used to contain a cooling medium
• Clamp the reagent container in the metal to decrease the chance of spills
• Ensure that the flow of gas to the bubbler is appropriate before adding reagents
• Use either a syringe or cannula to transfer RLi between containers. Ensure they have been dried and purged with inert gas

5.  Emergencies and How to Stop A Reaction

• If a reaction needs to be stopped, slowly empty the reagent using a syringe into dry ice. This may produce flames that will be quenched by the dry ice
• If toluene or isopropanol catches fire, place a watch glass on the beaker to smother the flames
• If a fire cannot be contained, immediately use a class B fire extinguisher
• If hair or clothing catches fire, immediately use a safety shower. Contact your lab manager or emergency services for further assistance

6.  Disposal of Organolithium Compounds

• Discard organolithiums if there is an excess of solids or sediment in the container.
• Large volumes of organolithiums should be sent out for disposal as a lab pack
• Small volumes may be quenched in the fume hood by diluting to less than 5 wt% with an inert solvent, then slowly adding to 2M 2-propanol in heptane using an addition funnel
  • Monitor the temperature as you quench the organolithiums. If temperatures exceed 50°C, either slow the rate of addition, or use external cooling
  • Dispose of the resulting solution as flammable or hazardous waste

7.  Alternatives to Organolithium Compounds

If possible, determine if there are safer alternatives that can be used, including:

• 33 wt% n-hexyllithium in hexanes: This is similar in reactivity and boiling point to n-butyllithium, but hexane is easier to contain than butane
• Lithium diisopropylamide (LDA): New formulations may be non-pyrophoric, and produce no emissions from butane co-products
• t-butyl lithium in heptane: This formulation is pyrophoric, but is safer to handle compared to the t-butyl lithium in pentane, as heptane has a higher flashpoint than pentane