Testing Catalysts and Inhibitors to Change the Ratio of a Desired Product and an Undesired Coproduct

Suppose you are working with a reaction step that is providing, rather cleanly, a mixture of two products-- the desired one and an undesired byproduct. Perhaps modifications of conditions are not beneficially changing this product ratio. Perhaps a change in the relative rates of the reactions that give rise to these two compounds can be changed to change the final product ratio. Below is a list of molecules that in more than one instance have been found to either speed up a desired reaction or slow down an undesirable one: 

HMPA, water, N,N-dimethylformamide, N,N,N’,N’-tetramethylurea, urea, dimethylsulfoxide, pyridine oxide, 2-pyridone, N-methyl-2- pyridone, polyethylene glycols, DDQ, an HMPA equivalent covalently attached to a tertiary amine for extractive removal, antioxidants, dimethylformamide acetals, 4-dimethylaminopyridine, DBN, DBU,  beta glycine, EDTA, transition metal salts,  phase transfer catalysts.

For any particular reaction, most of these additives will have no impact at all on the reaction you are trying to improve. When one of them does exert its effect it can be expected to be effective at low concentrations. For that reason, they can be tested at low concentrations and for this same reason, groups of them can likely be tested as a small group.  Any small packet of these additives should be chosen so they do not belong to the same general types. If a group of additives shows some activity in changing the important products ratio only then do experiments need to be done to deconvolute the group to discover which cause the improvement.

When trying to improve a procedure, improving a method using an additive needs to be considered as much as completely replacing that reaction.