The Graduate Student’s Academic Organic Synthesis Project

 So you have convinced your thesis advisor that you should pursue a new synthesis of a previously unknown molecule. Probably it was discovered by separation from a natural product fraction or perhaps this is a new approach to an old molecule of some importance. Whatever; congratulations devising and executing a synthetic project is excellent training for the world of work and besides it is good fun!

You need to understand that working in an academic environment brings some particular advantages and disadvantages. The advantages are numerous and well known. You will probably have access to a broad range of analytic tools for both separation and characterization. Also, you will not need to produce very much of the desired target substance; enough to analyze and characterize. It can be kept in a vial rather than a bottle. Literature access and literature searching will be available and relatively inexpensive.

What is not mentioned is that your own labour will be considered free and money will not be spent to make your work faster. Expensive starting materials will not be purchased. You will probably be limited to substances that cost at least less than $1/gram.

When you work out ‘paper syntheses’ to evaluate for practicality pay attention to your starting materials. Although something may be commercially available, it may be beyond your budget.  Plan to make your starting material if at all possible from things that cost less than $1/gram; preferably much less. This is quite the opposite from what you would encounter in industry. There you would be expected to purchase the most advanced intermediates available. Time is money and your time is costing your company big bucks.

You should not be discouraged though because there is a silver lining to this academic cloud. If you make your own starting material, you can make lots of it which means that you can execute all your steps on a larger scale. You won’t need to spend as much time bringing forward small batches of intermediates and you won’t feel so constrained in what experimental conditions you can risk.

The biggest error I made as an undergraduate and a graduate student was failing to improve the early steps of my route so that I could move larger amounts of material forward quickly. Get the biggest reactors you can find and move forward as much material as your confidence in your early steps will allow. 

An added benefit to learning to quickly scale-up is that this is a major skill required in industry and if you eventually apply for work in the industry citing this experience will enhance your application.