More Fun with Fluorous Solvents

Shibata and co-workers at Nagoya Institute of Technology have already published several papers running reactions in hydrofluorocarbon solvents.  Their solvent of choice has been Solkane 365 mfc which is 1,1,1,3,3-pentafluorobutane, CH3-CF2-CH2-CF3.  Solkane 365 mfc is produced by Solvay Fluor GmbH and was introduced as an environmentally more friendly blowing agent for polyurethane foams.  Previously they have shown that Friedel-Crafts alkylations can be be run in Solkane 365 mfc quite well.  Their latest paper describes their work in conducting terminal alkyne homocouplings in the same hydrofluorocarbon.

The homocoupling of terminal alkynes to form 1,3-diyenes is a useful reaction for the synthesis of many compounds including natural products and monomers used in polymer synthesis.  The reaction is generally Pd or Cu catalyzed with or without added base.  Shibata et al started scouting reaction conditions using phenylacetylene as the substrate and Solkane 365 mfc as the solvent.  They found that 10 mol% CuCl and 10 mol% TMEDA at room temperature provided the diyne product in 93% yield after 1 hour.  The authors note that literature reports put the reaction time in methanol at 12h and ionic liquids at 4.5 hours.  They cite the well-known higher gas solubility of fluorous solvents over other solvents as the reason for this reaction rate acceleration.  (Note:  While this is quite true for perfluorocarbons, I could not find any oxygen solubility data to confirm that this is true for a hydrofluorocarbon like Solkane 365 mfc.)

The researchers then tested a variety of terminal alkynes and found that the reaction worked quite well for a number of alkynes including those with electron donating, electron withdrawing, and heterocyclic substituents.  For those alkynes where homocouplooing was sluggish under the standard conditions the addition of a based like DBU accelerated the reaction.  Most reactions were complete somewhere between 1-6 hours.

The main benefit of this chemistry according to the authors is the use of a green solvent.  I’m not completely sold on that as I noted in the previous Friedel-Crafts chemistry post, but in this instance the high yields and short reaction times certainly help the argument.  It’ll be interesting to see if we’ll see large-scale reaction using hydrofluorocarbons.

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2 Responses to More Fun with Fluorous Solvents

  1. milkshake says:

    Even partially fluorinated hydrocarbons have increased oxygen solubility – I was looking at 1,3-bis-trifluoromethylbenzene few years back and I remember it was at least twice the oxygen solubility in plain xylene.

    Another problem is flammability/explosivity of common organic solvents with pure oxygen, which makes oxidations using pure O2 very unpopular in the industry. So if this perfluoro solvent is cheap enough and recyclable, it could be worth trying in such a process.

  2. Marv says:

    I actually did not know that about partially fluorinated solvents increased gas solubility, milkshake. Your comment about the flammability of organic solvents in O2 rich environments is well worth noting.

    Thanks for the input.