There is always a gap between "textbook" and "real chemistry." In this topic, I would like to pay more attention to how to develop a rational synthetic route with high safety for the future scale up in industry. For example, the general approach focuses on low exothermic reactions with non- or low-air/moisture sensitive starting materials. Moreover, "greener" chemistry would be introduced to publics and included in this research topic.
Rational Design of Synthetic Route for Real World
In general, safety is always the first priority in the chemistry lab. Thus, in this topic, we will focus on how to minimize the risk at the different stages of your “journey” in synthesis: 1) Setup reactions and addition of reagents; 2) duration of reaction to its completion; 3) reaction workup; 4) waste control.
(1) Setup reactions and addition of reagents
To avoid fire hazard, using non-flammable solvent such as water or solvent featuring high flash point and low vapor pressure (e.g., N, N’-dimethylformamide) is better.
For addition of reagents, staying away from moisture-sensitive or air-sensitive reagents will simplify the setup of reactions and further minimize the incident during the early stage of your synthesis; using liquid or solid reagents may lead to easier setup than gaseous one.
(2) Duration of reaction to its completion
Upon the proper setup with addition of reagents, at this stage, we have to observe/estimate the heat generation/absorption and any system pressure change. Any vigorous pressure change and heat production can make the system/apparatus vulnerable. Inserting a thermocouple to monitor the temperature change is an important method to offer us useful information for further modification of the synthetic route. Lowering the heat generation and reducing pressurization of the system are imperative to the future scale up reaction.
(3) Reaction workup
If the workup procedure gets involved in acid-base reaction, the potential heat generation should be taken into consideration for safety evaluation. Proper pre-treatment (e.g., cooling down the system) to the reaction should be carried out before the neutralization to diminish the temperature ramping.
(4) Waste control
If the waste handling of this reaction is costly and hazardous, we have to redesign the experiment to reduce the expense of waste handling and hazard of temporary waste storage in the laboratory.