Is Synthetic Organic Chemistry Dead?

Synthetic organic chemistry has come a long way in the course of the last century. At the beginning it was not much more than pure guesswork, mixing different things, heating and taking a guess what heteroaromatic might have formed. Nowadays, we have arrived at a point where it is possible to make almost any conceivable chemical structure by a rational approach, using the large toolbox of synthetic methods available today. Have we thus reached our goal? Is there nothing left to do in synthesis except improving the existing methodology?

Of course not. What we still need is a more profound understanding what is happening on the molecular level. Quite often we find ourselves faced with a synthetic problem where only one specific set of reaction conditions will work. Why this one? Nobody knows, and nobody can predict, so we have to try all possible conditions.

I would argue that the huge improvement in our understanding of reaction mechanisms and the complexity of chemical structures of today is largely related to the availability of more powerful analytical methods. A hundred years ago, melting points and elementary analysis were about the only ones, later on IR spectroscopy became available. But we all know that modern organic synthesis would be unthinkable without the help of NMR spectroscopy. Maybe a new method is just around the corner, waiting to be introduced. To gain more knowledge about mechanisms, we would need the ability to “look at” individual molecules, rather than ensembles of molecules as is the case today. A new method that could do this would definitely have a huge impact on organic synthesis.

While we observe billions of molecules at the same time with our analytics, in our mind we are still stuck with the single molecule that we draw on paper. In this way, we neglect all the interactions between molecules that can be very important for the outcome of a reaction. Take organolithium compounds as a simple example. We usually write “n-BuLi” as if it were an isolated species, although it is well-known that these compounds form clusters up to hexamers in solution, depending on the solvent and the concentration. From a theoretical point of view, it will be very important to devise models that take the interactions between molecules, molecule clusters and the solvent (more) into account.

By November 26, 2008 5 comments opinion, synthetic chemistry

Mandatory Safety Standown

Some of the trappings for working in a government lab are the frequent safety trainings, safety retrainings, safety walkthroughs, safety evaluations, and safety inspections. This year Lawrence Berkeley Laboratory is up for its DOE review. If LBL passes then its contract with the UC system is renewed. If we don’t pass, the contract is opened to other bidders. Since the higher ups are not looking forward to a Clorox owned LBL, the entire lab is in a state of heightened safety righteousness. On Wednesday, the division director (kind of like a department chair) informed us we were not allowed to do research, but were instead to spend the day cleaning and making the lab as safe as possible. Clean labs have historically lower rates of accidents, so messy bench chemists are a serious no-no around here. Being the good graduate student, I went around the lab and disposed of all 50+ of our mercury thermometers [1] (correctly and coordinated with EH&S) except this guy below.

I just couldn’t bring myself to throw this beauty in the trash heap. It will be spending its retirement with me. 

[1]: Mercury thermometers are not illegal per se, but they are strongly discouraged at LBL.


By October 31, 2008 8 comments opinion

The One-Year-PhD Crisis

Who doesn’t remember the time when you started your PhD. You were all enthusiastic about working on your own project, doing all kinds of new chemistry, and generally still believing in every far-flung idea your boss had.

One year later: frustration. Reality has caught up with you. This is like your thirtieth anniversary (so they say ;-): you realize how much time has already passed, and how little you have achieved in that time. Suddenly you start feeling like you will be stuck with your current problems forever and that your PhD is likely to take ten years. Ok, so you needed some time to get used to working independently and for getting to know your project, but still, after one year you should have more results, right?

Wrong. I have experienced this myself and seen it often with colleagues. This feeling of pointlessness usually occurs just before you make some serious progress or even a breakthrough. The feeling of “being stuck” appears to be a psychological phenomenon necessary for solving difficult problems. It’s when your mind can take a broader perspective and start with lateral thinking. This is normally also a good time to take a holiday – it prevents you from becoming too focused to see an obvious solution.

You also tend to forget that it takes much longer to get “into” a project than it seems at first. The fact that you don’t have to ask for advice every day does not mean that you are already familiar with all the details of your work. It usually takes about a year to get there, and that’s when you start to see all the difficulties you are faced with. Don’t worry, you can take it as a sign that you have become an expert on your topic!

By October 23, 2008 9 comments opinion

First Day of Classes

Regardless of wheter you’re an undergrad, grad student, professor, industry worker, retired or anyone else who reads this blog, I wanted to wish everyone a happy start to the new school year!  Though I openly admit I am tired of University life, there’s something refreshing about the first day of classes.  As a scientist, I’m naturally curious to know what you all see on your campuses the first day of classes.  I now present my experience in the first 20 min of the 2008-2009 academic year:



  • The want-to-be sorority girl wearing shorts that are, well, just a little too high (these ones are sort of difficult to pick out, but they make you laugh).
  • Two random guys talking about how [the University] has “a good shot” at winning a national championship this year (in football)
  • The cookie cutter sorority girls complimenting each other’s shirts (“Your top is so cute!” I heard that 3 times between the 200 yards from where I park to where my research building is located)
  • The freshmen girls decked out in Greek letters (shirt, flip-flops and tote bag) wearing huge sunglasses (it’s cloudy today)
  • The fraternity guys wearing either bright, lime green or pink shirts while donning sunglasses (believe me, it’s incredibly cloudy today)
  • I had to register my laptop 3 times with the University network even though I’ve been using the same computer for the past 3 years
  • A full parking lot by 7:45 am (classes start at 8 am)
  • People in suits passing out bibles
  • The poster people in the student union (campus center)
  • The only day you’ll actually see most professors dressed nice
  • The only day you’ll actually see most professors on campus before 9 am
  • The people at Starbucks were actually nice this morning (though somewhat groggy)



By August 20, 2008 4 comments opinion