Procedure for ozonolysis of alkenes in dichloromethane

For references see:

  • E.V. Boltukhina et al. Tetrahedron. 67 (2011) 5382-5388 page 5385
  • A. Zada et al. Journal of Economic Entomology. 97 (2004) 361-368 page 362
  • Nizkorodov lab SOP for dichloromethane
  • Nizkorodov lab SOP for ozone generator

Reagents/Solvents

  1. Alkene (1 mmol)
  2. Triphenylphosphine (TPP, 1.2 mmol equiv. per alkene double bond)
  3. Acetone in a squirt bottle
  4. Dichloromethane (DCM, ACS grade)

Equipment

  1. 25 mL round-bottom (RB) flask
  2. Septum (rubber)
  3. Scintillation vial
  4. Teflon line for ozone
  5. Lab jack (not optional)
  6. Stand and clamps
  7. Micro stirbar
  8. Low-form round dewar flask (small)
  9. Pasteur pipette (short tip, disposable – get a new one for each time)
  10. Dry ice (keep in foam bucket)
  11. Ozone generator
  12. Mass flow controller
  13. Neoprene short tubing
  14. Needle (for connecting to vacuum source)
  15. Heat gun

Set up

***Obligatory safety warning: trapped ozone may be explosive, do this in the hood and don’t leave unattended.

Procedure

  1. Before you begin (assuming everything is set up)
  2. Warm up ozone generator (MAX setting on the large generator in hood)
  3. Get dry ice
  4. Weigh out TPP and crush between some filter paper. Keep this nearby the set up.
  5. Reaction is water-sensitive so make sure RB is free of water. Put septum on the RB, connect the RB to a vacuum source (housevac) with a needle and turn on the vacuum. With vacuum ON, heat up the RB with the heat gun for a few minutes. Then let RB cool to room temp with vacuum still on.
  6. Weigh out your alkene in a scintillation vial.
  7. When RB is cool, remove needle.
  8. Quantitatively transfer the alkene to the RB with ~ 10 mL DCM. Add stirbar and put the septum back on.
  9. Make your acetone dry ice bath (add acetone FIRST, then slowly add dry ice) in the dewar.
  10. Submerge the RB in the dry ice bath partially (make sure the solution is submerged) and stir for ~ 5 min.
  1. Ozonolysis
  2. Turn on the oxygen and adjust the MFC to ~ 2 SCF per hour or whichever flow is maximum without splashing.
  3. Remove septum (will be slightly difficult) and insert the Pasteur pipette into your reaction mixture.
  4. Should be stirring the entire time and septum is off.
  5. Ozonolysis will last about ~ 10 min per mmol double bond. Make sure you allot enough time and DO NOT leave unattended.
  6. The RB will fog up which will make it hard to see – when this happens squirt some acetone over the foggy areas to clear. Lowering the jack (e.g. removing the RB from the bath) will make it easier to confirm blue color.
  7. Ozonolysis is over when you see a sky blue color in the solution. Turn off the flow from the MFC immediately and remove the pipette tip.
  8. Add the crushed TPP all at once.
  9. Stir in the dry ice bath for ~ 30 then remove RB to room temp.
  10. Stir in the hood for 24 – 72 hours. There are no side reactions but the reduction is very slow. Make sure the RB is clamped! Loosely place septum on top.
  11. After reaction is done, concentrate the crude with rotavap and purify with HPLC reverse phase column with just ACN.