Solventless and Solvent-free Operation

Ionic liquid synthesis is usually performed solvent-free by means of the Menschut-kin reaction, i.e. the two reactants (typically abase and an alkyl derivative with leaving group) are mixed and react in the liquid state and yield the liquid product, with almost complete conversion. The challenge for some of these reactions, such as the conversion of methylimidazole and diethyl sulfate (adiabatic temperature rise 173 K) is the high exothermicity under the high reaction rate [25]. This leads to considerable hot-spot formation with sudden temperature jumps of 100 °C and more. This adversely affects the product quality, as is easily visible by a coloring to yellowish or even brown, and places restrictions on safe process optimization. For these reasons, the reactions may be carried out more slowly than kinetically possible to allow for sufEcient heat transfer. 

For solvent-free ionic liquid synthesis from methylimidazole and diethyl sulfate, a reactor configuration with an integrated microreactor and two capillaries was developed [25]. This three-fold division of the reaction path serves to compromise 

The reaction of methyl chloroformate with amines to give methyl carbamates is exothermic and, due to large heat release, hot spots occur [45]. This is even observed at the laboratory scale when using N-methoxycarbonyl-L-tert-leucine. 

In case of complete malfunction of cooling and stirring systems, the temperature may exceed the solvent reflux temperature [45]. Accordingly, a slow dosing of the methyl chloroformate is necessary to have control over the heat release. After having determined the reaction parameters at the 1 g scale, the reaction was carried out in a microreactor with 91% yield at a 7 min residence time. More than 1 kg of N-methoxycarbonyl-L-tert-leucine was prepared within 12 h. 

---