Ionic liquid synthesis: safety and good working practices

Independently of the properties of the resulting ionic liquid (i.e. toxicity, thermal and chemical stability, flammability and corrosivity), their synthesis requires the use of organic reagents and solvents, which can generate risks to the laboratory personnel and requires specific attention in the context of risk assessment. For example, the often used 1-methylimidazole is classified as “a very hazardous compound in case of skin contact (irritant) or eye contact (irritant)” with a flash-point of 92° C. These aspects must be taken into consideration during methylimidazole-based ionic liquids synthesis. Analogous safety data sheets characterize most of the often used nucleophiles, having hazardous identification ratings for “health” and “fire” ranging between 2-3. These ratings can however increase in the case of specific nucleophiles-bases, such as pyridine. Analogously, several concerns are related to the use of the alkylating agents. Alkyl halides are usually characterized by high flammability and explosion risk (chlorobutane has a flash-point of -12 °C), that moderately decreases changing from chloroalkanes to iodoalkanes. Thus, flash points of the employed reagents should be considered and appropriate working practices should be used.

Furthermore, these substitution reactions are generally carried out in molecular solvents and, despite the fact that relatively safety media could be selected (i.e. ethyl acetate), it is not so odd to find in literature ionic liquid syntheses carried out in benzene, dichloromethane and other solvents, which due to the hazards associated with their use  should be avoided.

Furthermore, although chloride and bromide based ionic liquids represent the starting materials for synthesis of many other ionic liquids, alkyl halides are not the sole reagents able to give ionic liquids. For example, methylcarbonate-based ionic liquids can be obtained using dimethylcarbonate as the alkylating agent, i.e. a reagent that although characterized by a relatively low flash-point (21 ° C), has a very low toxicity both for humans and environment. Alkyl sulfates and alkyl phosphates or phosphonates represent further alternatives. These latter alkylating agents are generally characterized by higher flash-points, a feature that reduces risks of flammability and explosion; however their reactivity, and consequently their health hazard levels, significantly depends on their structures. Personal Protective Equipment and appropriate working practices should be applied taking into account the risk level.    

Some concerns are related also to the metathesis reaction, generally performed in water, where the used reagents can undergo to hydrolysis and water must be avoided. This is for example the case for tetrafluoroborate and hexafluorophosphate anions that in the presence of water can result in the formation HF. This aspect should be taken into account since prolonged exposure to water or relatively high temperatures could favour this process.

The knowledge of the ionic liquid’s chemical stability as a function of the temperature and presence of other solvents, such as water, is important not only for their application but also for their adequate handling. For example, alkyl sulfate-based ILs hydrolyse in the presence of water as a function of temperature. Their stability depends on anion alkyl chain length: methyl sulfate- and ethyl sulfate-based ionic liquids are not stable in the presence of water whereas butyl sulfate- and octyl sulfate-based ionic liquids start to decompose only under more drastic conditions.

However, anion stability in the presence of water or at high temperature is not the sole aspect to take into account during ionic liquid synthesis. Ionic liquids are not safer by definition: for example, they can be corrosive or they can be designed to become hypergolic fuels. These latter ionic liquids cannot be considered safer and their handling requires particular attention and appropriate working procedures. Attention is required also in the synthesis of ionic liquids whose fate is the “simple” use as solvents and/or reagents, and which contain specific functional groups or anions that are potentially not stable, for example, azide.

Finally, there is the large class of metal containing ionic liquids which share the typical concerns of the included metal: toxicity, stability in the presence of humidity and so on.

In conclusion, ionic liquid synthesis requires the application of all the good working practices that are followed in any chemistry laboratory including an adequate evaluation of the potential risks related to the product nature.