Process Wednesday: Volume-Time-Output

From the recent Org. Process Res. Dev. review titled "The Eight Criteria Defining a Good Chemical Manufacturing Process", a fascinating rule of thumb for optimizing "throughput":

Criterion 4: Volume−Time−Output (VTO). VTO is defined as nominal volume of all reactors (m3) multiplied by the hours per batch, divided by the output per batch in kg (eq 3, determination of VTO). If the resulting number is  less than 1, the process for the chemical step is acceptable; if the number is far above 1, the process needs to be improved. Dryer and centrifuge operations during product isolation are not considered for VTO analysis, although these can be the rate-limiting operations. For a particular process, if long drying times define the bottleneck of a process, i.e. product isolation times are greater than reactor processing times, the VTO will have a reduced impact.

If you read further in the review, the authors talk about the reaction to the right (above), where the reaction  concentration of the RCM was improved by 20X by protecting an amide hydrogen with a Boc group. The authors offer a scenario in which they were thinking that they had to build a dedicated plant to handle just these RCMs, before they were able to optimize the process, which allowed them to run it in their current equipment. Count me a little skeptical on that front -- I have a hard time that the narrative was that dire, or that they actually considered building another plant.

Nevertheless, I like this, because it offers an interesting rule of thumb for "process intensification" and when you're close to using your plant/equipment efficiently. Readers, I'd love to hear what you have to say.

1. Dach, R.; Song, J.J.; Roschangar, F.; Samstag, W.; Senanayake, C.H. "The Eight Criteria Defining a Good Chemical Manufacturing Process." Org. Process Res. Dev. ASAP. dx.doi.org/10.1021/op300144g