During commissioning of the LT (low temperature) unit, a number of problems were identified for various parts of the unit. The major problem spots that were faced at the beginning of the development are summarized in Figure 10. The hexyllithium filter (1) was frequently blocked by a jellylike buildup. Hexyllithium pumps (2) failed every few days due to the deposits in the pump heads and valves. Another problem relating to the pumps concerned the pulsation of flow caused by gas buildup. The problem of clogging in microreactors by gas bubbles is seldom discussed, but it seems to be an important issue, especially in multichannel devices. The hexyllithium precoolers (3) were frequently blocked due to the freezing of impurities if the temperature was too low. The serious problem for the continuous operation was clogging in the structure of the micromixer in the first reaction stage (4). Every 20−40 h of operation, the IKSM reactor became blocked due to the deposits of salts (5). After a few hundred hours of operation, fouling by polymer-like deposits in the residence time reactors occurred (6).
Also the DMS precooler was susceptible to clogging when using an aged DMS−THF solution (7). Finally, the second reaction stage (8) and the downstream part (9) were regularly clogged by the salt deposits. The detailed discussion of the origin of these problems, precautions, and countermeasures is given in the Supporting Information.
Generally speaking, the MRT-based unit was significantly less robust than a classical stirred tank reactor setup. Figure 10 illustrates that in order to make MRT technically viable know-how has to be collected also with the auxiliary equipment. Pulsation-free operation, which is simple to achieve in the laboratory, became a challenge with the industrial equipment. Clogging was certainly the largest obstacle restricting a smooth and continuous operation. There were several causes of the clogging, namely, formation of solids due to moisture in feedstocks, impurities, formation of salt as byproduct, solid formation in the hot spots, and polymerization.
Overall, this is no surprise. However, still, studies intended to overcome such obstacles are rare. Principally, it is well known that the design of the microreactor plays a key role in minimizing clogging, but so far, there is no design available which proves to be completely insensitive to any solid deposition. In a number of studies, use of a second, dispersed phase has been proposed as a measure to eliminate solid deposits. However, for the organolithium-based chemistry described in this paper, use of water in the Taylor flow regime is not possible due to the low temperatures.
Therefore, the only way to free up clogging consisted of a classical approach to remove the deposits by purging after increasing the temperature. However, this method was time-consuming, and after being purged, residues of water needed to be removed to avoid formation of lithium hydroxide.
Finally, it was important to clean the unit before the reactor was completely blocked. Also, the application of external forces, such as ultrasonic treatment, has been proposed. This method is hard to realize, though, when a reaction is performed in a set of reactors as described in this study. Therefore, a clean-in-place concept has been applied.The Supporting Information has even more details on these issues.
Technically, two parallel trains of reactors were installed. One line was in operation, while the second one was in cleaning mode. The reactor trains were supplied by one set of pumps and valves.
The authors' conclusion is reasonably positive, though:
There are no easy solutions available to counter clogging or fouling. However, addressing salt formation or reducing side reactions by optimal temperature control can help to minimize its impact. Furthermore, clean-in-place solutions might help to increase the robustness of this technology. Based on these promising results, commercial units for low-temperature organometallic reactions have been designed.I haven't really worked enough with microreactor systems to have a truly informed opinion on the subject, but it does seem to me (from the experience of coworkers and some perusal of the literature) that the handling of heterogeneous solutions that are prone to clogging is one of the top issues that seem to be unsolved.
1. Laue, S.; Haverkamp, V.; Mleczko, L.* "Experience with Scale-Up of Low-Temperature Organometallic Reactions in Continuous Flow." Org. Process Res. Dev., ASAP. DOI: 10.1021/acs.oprd.5b00183