We tend to come across bisulfite adducts of aldehydes fairly infrequently and mostly as a means to get rid of aldehydic traces during work-up. I distinctly recall learning this in my undergraduate chemistry lab many years ago. Remember all those “magical” tricks – decolorizing charcoal, sodium bisulfite, etc?
Bisulfite adducts can pull their own weight, though. It has been demonstrated that these compounds are there to not only transfer aldehyde impurities into aqueous phase, but to reversibly protect sensitive molecules. I have been fascinated by these compounds, but I have never seen their solid-state structure. Over the years, I have been searching the Cambridge Crystallographic Database (CCD) in hopes of looking at the crystalline forms of these compounds, but it was all in vain.
Last night I came across a paper published in 2013 by the scientists from Eli Lilly. This manuscript has several nuggets that are worth considering. First of all – there you have it – a crystal structure! It is too bad that our colleagues in industry are not always vigilant about depositing their crystallographic data into the CCD, otherwise I might have seen this report earlier. The cation screen is the most peculiar part of the paper. Why does it always have to be sodium bisulfite? This is a great question. The report by Kissane and Frank shows that potassium salts possess superior properties, at least with their aldehyde. There are additional attributes that were considered by the authors. When was the last time I thought about filterability as a go/no go decision? I can’t recall… This is clearly important in process chemistry. Hygroscopicity is another metric that we do not take seriously in academia (at least not in quantitative terms). Here is a quote: “In a variable humidity solid state experiment, the sodium bisulfite adduct 2a was found to be quite hygroscopic, with a weight gain of 27% at relative humidity of up to 95%”. Hey – now I know why “academic yields” are often inflated… We just don’t think too much about weight gain along similar lines (this is a sarcasm).
similar aldehyde/imine adducts with PhSO2H are quite useful as column-purifiable stabilized aldehydes/ imine synthetic equivalents
I am glad you brought this up. Indeed, PhSO2H adducts are really good (and they are neutral). I know that these adducts have been particularly useful in making imine surrogates (Jerry Murry’s papers come to mind), but I suppose less is known when it comes to aldehydes. I will be very interested in seeing some relevant papers in this regard.
This is a recent paper I just saw (on PhSO2H aldehyde adducts). I have to say that Scheme 2 is super-intriguing: http://pubs.acs.org/doi/pdf/10.1021/jo302724y