Any process has the possibility of continual incremental improvement but practically a point will be reached when it is not worth further effort and one’s time and talents are better expended elsewhere.

In process development how does one judge the good and the better? A good process meets its quality and quantity requirements. The better process does this and goes further. The better process is rugged. In a rugged process if human error or mechanical failure or equipment inadequacy create some small deviations from the prescribed procedure, the result does not suffer seriously either in quality or quantity.

We judge a process by its costs and these include the labor expended, the time utilized in the special equipment, the prices of the starting materials and the price of waste disposal or recycle. A costing not only provides an indication of the efficiency with which inputs are used, but it also provides a running assessment of the particular shortcomings that contribute most to the overall expense. A preliminary costing is an important tool in developing any process because it ranks concerns where one might invest whatever limited time one has to achieve improvement.

Trost has philosophized that the ideal process would be a single step and that there should be no co-product. That is, all the atoms in the reacting substances are retained in the products. Nothing then is thrown away. This is an interesting ideal to contemplate from a philosophical perspective. It dramatically highlights that atom economy, as he calls it, has the benefit of high weight throughput and low waste disposal but it is far from reality in terms of what can be actually practiced. Every process is indeed ideally only a single transformation but the problem is starting materials for this ideal process are not commercially available- and because of this the process creator must move retrosynthetically one process step at a time until we do reach such commercial precursors.

Another useful idealized conception of a process is a sequence of chemical steps in which the reaction mixture from each step is simply treated over and over again with the reagents for each subsequent transformation in turn until the material, which is the synthetic goal, is present in the mixture. Then in one isolation operation, this product is separated pure from the complete complex mixture containing all the by-products and co-products of all the prior steps. This model dramatizes that it is most important to eliminate isolations because it is isolations that usually consume the most time and resources in a process. In practice of course there are very valid reasons for performing isolations of intermediates.

Valid reasons for isolations are:

1. To remove non-productive mass (ballast)
2. To change solvent for reaction optimization
3. To achieve needed purification through phase shifting
4. To correct stoichiometry and so save reagents
5. To provide convenient stops for campaign processing
6. To provide rework opportunities for rugged processing

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• Pamoates or Embonates: crystalline Pharmaceutical Salts or Derivatives for Isolation and Purification
• Symmetrical Bis-N,N-(3-nitrophenyl)urea: A Super Co-crystal Former that might have applications in Product Purification.
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• Reiterating the Objective of the Kilomentor Blog
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• Phosphate Pharmaceutical Salts : Chemical Process Development & Organic Synthesis
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• Kilomentor weighs in as “Pharmaceutical Manufacturing Goes Green”.
• Another Way to Separate Phenolics by Crystallizing of Co-crystals?
• The Complete Blog for the Preparation of Pharmaceutical Salts
• Inverted Filtration: A chemical synthesis laboratory technique particularly helpful at 5-10 litre scales.
• Recovering More Product by Crystallization in Organic Synthesis:Trituration with a Modified Water Phase as a Potential Chemical Process Development Method
• Kilomentor moves the discussion from Steam Distillation to other Co-distillations

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