Triazoles in Peptidomimetic Chemistry

Self Promotion time! Our review on 1,2,3-Triazoles in Peptidomimetic Chemistry was just published in EuroJOC.

Useful stuff if you are working in the peptidomimetic area. You can get it here or by emailing curlyarrow@gmail.com. D!

The Sand Bath - An Alternative to the Oil Bath

Yes, I am still alive! I have been out of the lab for a loooong time so the inspiration hasn't been there. However, I am now finding myself in the lab again and it appears that I will get to stay there for a while. And today inspiration struck.

Let's talk about oil baths. Good way to heat stuff up in a controlled way, BUT, what a bloody mess they are. The oil becomes disgusting after a while, the glassware gets nasty, ocassionally oil baths break and make the mess from hell....
So whenever possible I use an aluminium heating block. However, we have a limited number of these in a limited number of shapes and sizes. When a heating block isn't available my next choice is a sand bath. These are traditionally used when you have to heat something to a ridiculous temperature that oil can't handle. However, I use them for any reflux (see picture). The problem with these things is that heat transfer isn't particularly effective so it's only really good for reflux and not for heating something at a well defined temperature below the boiling point. Also it can be quite tricky for the sand bath to heat up in a well ventilated fume hood so it is generally a good idea to wrap a bit of aluminium foil around the bath to get the heating going. D!

Is there a Future for Organic Chemists in the Pharmaceutical Industry outside China and India?

I have copy/pasted the headline for this post from the editorial in the most recent issue of Organic Process Research and Development. It's a good question that is being asked and I believe that the answer is YES. However, we really need to come up with something new to justify our existence. The Chinese and others are just as good as us at doing Med Chem SAR working their way through methyl, ethyl, propyl, futile...but they can do the work at a much lower cost. The same thing that happened to the textile industry sometime last century is happening to the pharmaceutical industry. The design is made in the western world but the actual product is manufactured at some cheap site in Asia. The way forward is to invent new ingenious stuff. Start biotech companies with crazy, innovative new technologies, start working at the biology/chemistry interface modifying proteins; oligonucleosides etc. in predictable ways for use a medicinal agents and so on. Ultimately this development is a good thing. It is forcing us to think and evolve. In the end humanity will benefit from some great new discoveries and technologies that will spring from the effort we put into this. So get up and go invent something brilliant that will make the world a better place. D!

If it works don't mess with it!

I'm currently in Brussels vistiting a collaborator. The research groups lab is absolutely fascinating and contains several old school mechanical contraptions that do a great job.
For your glassware drying pleasures:
For melting point determination (not sure how useful this device is but its looks cool):
It's not always necessary to upgrade to an expensive model with digitals controls to achieve the goal. Check out this solid phase synthesis shaker and the fantastic sound it makes - music to my ears. D!

NMR Impurities Tabulated

If you didn't already spot this useful paper on NMR impurities you should go get it now. An excellent addition to the classic paper by Gottlieb et al. that you can access here. D!

PhD in Medicinal Chemistry

Design and synthesis of the first selective ligands for the GPRC6A receptor – a novel human G-protein coupled receptor with unknown physiological function

More info at this web site.

DO NOT email us but please follow the application procedure at the bottom of this web page.

There are links to all necessary information on the same web page.

D!

Green

This is what 40 g of the depicted indole looks like after one recrystallisation. It really shouldn't be green but it is very pretty and even better it's analytically pure. D!
Okay, okay people. Is the photo more to your satisfaction? D!

100th Anniversary

Wow, I just realised that I've passed the 100 posts mark a while back.

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The Coffee Break section has been updated with a new comic website called The Perry Bible Fellowship. Fantastic stuff that you really should check out. Also there's been a fair bit of activity at Electra Lady Land so that's worth a visit if your into the arty stuff. D!

Anhydrous Solvents Part 3: Acetone and Molecular Sieves - Bad idea!

I have discussed anhydrous solvents a couple of times and have been advertising the use of molecular sieves (MS) quite strongly. During my MS crusade I have pointed out that MS are no good for drying THF but that pretty much all other standard solvents work well with sieves. As it turns out this is incorrect and I have received a terrible punishment from the MS God. It's all rather embarrassing as a PhD student in the lab was fully aware of the particular problem I'm getting to shortly. The deal with MS is that they are weakly basic. I take advantage of this by always adding some MS to my CDCl3 which keeps it dry and mops up any HCl formed by the slow decomposition of CDCl3. The other day I was running some of 1H NMR and to my great pleasure I had finally (after months of struggling) made a very important target molecule. I had split the fractions from a column up in three batches to be on the safe side. All three 1H NMR spectra were great so I decided to combine them in one flask. I was running NMR in acetone-d6 and decided to use some acetone for the transfer. I couldn't find the HPLC acetone we normally have standing around and was getting a bit frustrated when I remembered that about a year ago I had made a bottle of acetone over MS (This is were all the alarm bells go of with the experienced chemist). I managed to find the bottle and proceeded to transfer all my stuff into a new flask. However to my utter surprise I was unable to remove the solvent on the rotary evaporator. On the high vacuum pump with a fair bit of heating most of it came off but by TLC there was a new UV acitve (and quite polar) compound. I had to re-column my product but it still wasn't pure! Currently I am attempting to crystallise it from the impurities. A fair bit of yelling and acussing people of sabotage took place. Fortunately it was late and there was only one other person in the lab.

Before I proceeded to clean up my compound I decided to figure out what the source of the problem was and I quickly discovered that the acetone smelt funny. Initially, I thought it was contaminated with benzaldehyde but when more dilute it had a floral/perfume scent that reminded me of ketones/esters. At some point the PhD student in the lab realised that I had been adding MS to acetone and mentioned that as far as he knew that was a no go because it goes Aldol in the presence of the weakly basic MS. I cannot believe that this hadn't occurred to me. As it turns out it is well known that ketones go Aldol when exposed to MS and many different compounds are formed. A selection of possible products from acetone are shown in the Scheme above. The polar compound I removed by chromatography is the acetone trimer with one hydroxy group.
In my defence I'll say that acetone can be dried with MS provided you use the acetone within a few days. I successfully used the anhydrous acetone during a week of experiments back in July 2009. The take home message is to bin it after a week and not use it a year later as I did. In fact just don't add MS to acetone but instead dry it with MgSO4 as described here. D!

Hard Science

There's some seriously hard science in the latest issue of ChemComm. D!