Posted by: Mark Foreman | April 14, 2012

An alternative to sodium borohydride / lithium aluminium hydride

Dear Reader,

I was reading Chemistry world recently and I saw an interesting paper. It was about how to reduce a ester while leaving an aldehyde alone. While everyone seems to love sodium borohydride it will normally reduce an aldehyde faster than it will reduce an ester. This is because an aldehyde is a more electrophilic group than an ester.

So reducing an ester while leaving an aldehyde alone is close to impossible unless protecting groups are used, while I have been known to use protecting groups the use of a protecting group normally adds two steps to the synthesis. One to put it on and one to take it back off. I was excited to see the use of diethylaluminium benzenethiolate as a protecting agent for the aldehyde group. This appears to be a very simple reagent to use, I suspect that the simple addition of it to a solution of the aldehyde will make it react instantly. All you have to do is add this reagent to a toluene solution of the aldehyde at -78 oC to put the group on, and to remove the group all you need to use is dilute hydrochloric acid.

To my mind this is easy, the removal of the protecting group is a donkey easy step which will occur in many gentle workups of reactions.

Sadly we will not be able to let our undergraduate students at Chalmers try out the chemistry for themselves, the diethylaluminium benzenethiolate needs to be made from triethyl aluminium and thiophenol. While pure trialkyl aluminiums are very violently reactive towards air, the dilute hexane solutions sold by Aldrich are not that bad to handle. I have had a few frights over the years with 1.6 M (and 2 M) butyl lithium but the dilute solutions in hexane are not too pyrophoric to be used. I recall as an undergraduate using butyl lithium for the first time it was such an easy reagent to use when compared with many other weaker bases.

The thing which worries me more is the thiophenol, my experience of thiophenol is that it is more mobile than many radioisotopes are. The slightest trace of thiophenol in the air imparts the smell of burning car tire to the lab, I have found that with care and a nice big bucket of chlorine bleach it is perfectly possible to work with thiophenol. I did my PhD with phosphorus sulfides and then as a postdoc I encountered thiophenol in John Plater’s lab. It seemed to take horrible evil smelling sulphur compounds to a new level, it seemed to do horrible things which my phosphorus sulphides would never been able to do.

As long as you can not smell anything then you are using the fume hood correctly in terms of not pulling contaminated objects out of it. But at the same time a fume hood is a not a magic disposal chamber which makes toxic and foul chemicals vanish into oblivion, I have come across too many cases of people dumping sulphur compounds up the stack. What happens is that the sulphur compounds tend to get into the air intake of buildings and then start to stink out the buildings. It is important to bear in mind that there is no relationship between how offensive a chemical smells and how toxic it is.

Hydrogen cyanide smells rather nice, I always thought that it smelled a bit like perfume.

I have read that pure sarin has a fruity smell.

Carbon monoxide has no smell, but it is a real nasty toxic killer.

These three examples should make it clear to you that lack of nasty smell does not equal safety.

I was once working in Tony Hill’s lab and suddenly I got an almighty headache. At the time I was working with carbon monoxide, so I quickly took steps to stop me getting exposed to any more. What I had done was to take a small flask of organic solvent which had been bubbled with carbon monoxide out of the fume hood without first having bubbled nitrogen through it to strip out the excess carbon monoxide. This near miss with carbon monoxide was quite a fright for me, and I made sure that I did not make that error again.

The next fright I had with carbon monoxide was the time that a student asked me why CO was bad, I told her how it binds to your hemoglobin and then stops oxygen being transported in your body. I told the young lady about the change in colour which is often seen when people die of CO (they tend to turn orange, while it sends you to the other side it does give your mortal remains a suntanned look to make it look like you have been on holiday in the sun). As I explained this to the student another student nearby looks like she was about to faint, I thought at that point “Oh dear ! I will not look forward to explaining to my head of department that I managed to make a student faint in horror”. I thought that the level of solvent fumes in the air was not high. I have experienced labs with higher levels of solvents (2nd year organic lab course at Imperial back in the 1990s was far worse) without passing out, but I know that some people have a lower/higher tolerance than others. When I was a undergraduate I knew one woman who only had to get the slightest exposure to ether and then she would start to be sick. So I thought it is either solvent fumes or the horror story which is making the student faint.

I took the normal response which most chemists take with people who appear to be suffering from solvent narcosis, I took the student out the lab and into a cleaner environment. I took her to see Dr John the technician, we got her a chair to sit on in a nice and clean environment (John’s office). Then we got the truth out her, she had failed to eat her breakfast. As a result she was feeling faint.

But back to the new protecting group, I do not think that I will be allowing the students to use it as the thiophenol has a very strong foul smell. But the chemistry is interesting. I hope to be able to comment soon on how I think that the chemistry works.


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