Are there any advantages/disadvantages of using toluenesulfonate instead of methylsulfonate as a leaving group in E2 and SN2 reactions? I know they are both excellent leaving groups but how do they compare to each other? Is there a green chemistry aspect to it?

Thank you!

  • From the point of atom efficiency, methylsulfonate is advantageous compared to the p-toluenesulfonate.

  • On the reagent itself, the methanesulfonate is more polar than the p-TsOH; so the later dissolves better in less polar organic solvents than the former. Methanesulfonate even may be used to dissolve some metal salts.

  • If used to generate a better leaving group, on workup, a methanesulfonate enters the aqueous phase easier than the tosylate.

  • p-TsOH is a cheap, widely available solid (sometimes sold as hydrate) you may prepare by your own in large quantities; methanesulfonate however is a liquid, hence potentially easier to add continuously, and more expensive (even more so, per mL, the triflates).

  • Methyl sulfonates are able to alkylate DNA, hence potentially carcinogen. For tosylates, currently there is not such evidence (but obviously the dust of this strong acid is considered harmful).

As a personal note, among other reasons I found consultation of journals like Organic Process Research & Development just under this aspect (including green chemistry) as useful in two ways: i) publications describing how running a particular reaction within a chain of others works well / better than an other -- especially on larger scales of application--, and ii) the sections in line of "Some Items of Interest to Process R&D Chemists and Engineers".

Addendum: There are dedicated compilations to figure out scope and limitations of chemical reagents. To mention only two, Fieser & Fieser and EROS edited by Leo Paquette (there is an e-EROS as electronic ressource, too) are multivolume references.

  • $\begingroup$ Do you have any citations at hand for literature on MSA alkylation of DNA? $\endgroup$ – hBy2Py Feb 25 '17 at 13:57
  • 1
    $\begingroup$ @hBy2Py Thanks to NIH's policy, one I find in PubMed's data bases is Lundin et al. in Nucleic Acids Research, 2005, Vol. 33, No. 12 3799–3811, doi:10.1093/nar/gki681, found at ncbi.nlm.nih.gov/pmc/articles/PMC1174933/pdf/gki681.pdf $\endgroup$ – Buttonwood Feb 25 '17 at 15:32

In my experience mesylate forms more quickly using std conditions of MsCl/Et3N/DCM.


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