Being in the industrial minority in the chemistry blogosphere, I like to point out (on occasion) those bits of research that may catch the fancy of process chemists. Naturally, I wouldn’t presume to speak for all process chemists. But it is possible to draw a few generalizations.

One desirable modification of a process is commonly called “telescoping”.  To telescope a process is to collapse a multistep process into a smaller number of steps or unit operations. The overriding production goal is to reduce the unit cost of a product in terms of $/kg produced without sacrificing purity.  There are many ways to do this. Reducing the cost of feedstocks, reducing the number of direct labor hours, increasing the concentration of reaction mixtures (space yield), reducing overhead costs, etc. 

A reaction step is fairly easy to understand- one change or transformation is one reacton step. A unit operation is a little more arcane. A unit operation includes transformations, but also encompasses handling and isolation steps. Centrifugation, filtration, distillation, decantation, precipitation/xtallization, and packaging are examples of unit operations.

Another operation that is frequently underestimated in terms of its cost is “polishing”. This a phase where the crude product is subject to purification to specifications.  Polishing can be quite expensive. Indeed, taking a 96.5 % crude product to a 99 % spec can be more troublesome and require more skill than the initial synthesis.

There are a great many examples of telescoping and other process improvments in the literature. A reasonable example of telescoping is found in a recent JOC article- Lin, Lu J. Org. Chem., 2007, 72, 9757-9760.  The authors were able to demonstrate a one-pot preparation of triarylmethanes in two steps. The first step involved the addition of an arylboronic acid to an aromatic aldehyde through the agency of a Pd(bpy)2 catalyst. To the reaction mixture was added an “unfunctionalized” electron rich aromatic species. In this case, unfunctionalized means that no special leaving groups were on the ring.

The added aromatic underwent a Friedel-Crafts type alkylation with the intermediate diarylcarbinol to give the triarylmethane product in 57 % to 99 % overall yield.  The authors made a contribution to the store of knowledge in reaction chemistry. But they also had the presence of mind to improve the efficiency of the process as well.

There are some negatives. I don’t think anybody is automatically keen on running large scale reactions in nitromethane. Its explosability should give anyone pause when contemplating a scale-up. And, the third arene needs to be substantially electron rich. The addition of 1,4-dimethoxybenzene drops the yield to 57 %.

 

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