Drying of Process Intermediates

In performing a single step process, the product is typically dried to constant weight because for a final product you want a uniform consistent material that will have reproducible physical properties every time it is made.

Process intermediates do not automatically need to be consistently dried. Process intermediates are dried because measuring the dry weight of the isolated product is a way to get the percentage yield. It is not necessary to dry the entire amount of the intermediate in order to get a yield so long as a representative sampling can be taken. Similarly, to measure purity only a representative sample needs to be dried. The problem is being sure that your sampling is representative. The process chemist needs to be able to calculate what the weight of completely dried intermediate would be so the quantities of reagents and solvents for the subsequent step should be. Because achieving representative sampling is so uncertain, drying to constant weight is most often followed. 

Solvent drying is also necessary when the next process step requires a different solvent; particularly when the previous step's solvent would interfere.

Drying an intermediate to negligible further weight loss is not a simple task working with kilograms of material. Because drying is very often required after isolation from every step, if one is working different steps of a process in parallel, drying capacity can easily be exceeded. It is, therefore, important to do whatever one can to increase the rate of drying. This will reduce the overall time to complete a run for a particular intermediate and increase the rate at which a campaign can proceed. Not recognizing the capacity limitations of the plant's drying ovens is a serious shortcoming with process chemists.

When the filtrate from which crystals are removed is higher boiling, there can be advantages to washing with a lower boiling anti-solvent before moving it to a drier because this can substantially reduce the drying time. It is important, however, to retain at least one wash with the same solvent mixture as the filtrate before any further wash with low boiling anti-solvent, because, otherwise, you can precipitate impurities caught in the droplets of the original  filtrate still coating the wet cake. 

Drying proceeds both on the filter and in the drying oven. A longer period sitting with air being sucked through a solid cake on the filter will reduce the time required in the drying oven.

     The length of time required for drying is a function of (i) the volatility of the liquid being evaporated  (ii) the temperature of the incoming gas and (iii) the extent of vacuum in the dryer. Water is among the worst solvents to remove.

     Small crystals occlude more solvent than large ones, but small crystals trap comparatively fewer chemical impurities in their lattices. Therefore, there is a trade-off deciding when there is a choice of crystal size. Digestion of organic precipitates can change the crystal habit; dissolving smaller particles and increasing the size of larger ones. 

Tray drying is very irregular. To get a reasonable estimate of the residual solvent, portions of a sample for weight-loss testing must be taken from different locations among the several trays and combined. When tray drying a thick layer of a lower melting solid, it can partially melt in the tray, even though no problem is evident with smaller quantities in a thinner layer. One test for possible melting is to pack wet solid into a glass test-tube and place it, without stoppering in the same oven to dry. This will simulate a thicker layer.

      When convection air drying is being used ta higher inlet air temperature can substantially reduce the drying time.  The inlet temperature can be higher at the beginning of drying because the chemical substance is protected by the cooling from the more rapid solvent evaporation. That is, the temperature inside the solid mass is lower than the inlet air temperature.

     In the laboratory, the drying oven is very large compared to the amount of material to be dried so there is the possibility of underestimating the drying time required. On the other hand, in the laboratory, solids are most often put into the dryer in the late afternoon and left until the next morning. This may easily overestimate the required drying time. All that should be said is to consider and carefully estimate the required drying time. Long drying times or limiting oven capacity can profoundly affect throughput and process chemists need to be aware of this!