Exploiting the Low Probability Chemical Result and the Political Experiment

 The Low Probability Result

There can be good accidents as well as the more usual bad ones. Irreproducible results are not always bad; in fact, it is the good result that can neither be accounted for nor duplicated that causes us to figuratively tear our hair out in frustration. It suggests that there is probably something worth knowing that we don’t understand. It is taking advantage of good accidents that more than any other characterizes the inspired process chemist.

For the process chemist the serendipitous result can arise either in the reaction phase or in the purification/isolation part.  Most frequently the pleasant surprise comes from some particular efficient or simple phase shift separation.  Niel Anderson in his book, Practical Process Development,  expresses the point  this way, “When Nature offers a separation, see if it can be exploited to advantage!”

Route selection already includes some very optimistic assumptions that may be difficult for reality to surpass. That is why these pleasant surprises are more likely in the work-up phase.

A strategy for giving serendipity a chance is what I call the ‘wish reaction’. Ask yourself what you really wish would happen so long as it is at least theoretically possible. This single experiment is added at the beginning of an experimental program. If the experiment fails utterly or is confusing or ambiguous, work can return to the most probable main route. A simple example involves the use of a protecting group. First we would try the reaction without protection. If the experiment shows that protection is needed then we apply protection. Otherwise, we are heading towards saving both the protection and deprotection steps.

The Political Experiment

Former R &D Directors who have been promoted to business executives often like to slip back into that former role. Thus, if they were in process-chemistry, they retain interest in its technological problems. They may propose solutions to you. More precisely, they may repeated propose a particular course of action.  It may not be considered promising by the research team.  In this situation I recommend the ‘political experiment’.  One single simple experiment is done to test the proposal. The experiment is done with great care, taking extraordinary precautions (dry, inert, distilled solvents, etc.).  The more likely it is that the result will be an utter failure, the more useful it is to perform the experiment. When the result is as expected, it can be reported and the free advice will stop. Do not report the particular care that was taken. You may be questioned as to whether you did this or that correctly. This is an occasion for a superior to learn how professional you are! Besides if some deficiency is found you could be ask to repeat the experiment and you want to go back to your real experimental program. Of course don’t even mention that you expected or predicted that the idea would fail. If the experiment works, be generous in your praise. This boss might know something about this chemistry that it could be useful to tap further.