How to Remove Sticky Reagents during Workup

If your product is stable and relatively-non polar, a good way of removing triphenylphosphine oxide (produced in Wittig, Mitsunobu, bromination, ond other reactions) is to concentrate the reaction mixture to a lower follow, suspend the residue in pentane (or hexane)/ether and filter over a silica plug. The compound can then be eluted with ether, leaving most of the phosphine oxide at the top of the column. Sometimes it is necessary to repeat this procedure 2-3 to remove most of the phosphine oxide.

• Quench rxn w/ sat NH ₄Cl aq solution. stir up to a few hours at r.t. or until the solution becomes a dark blue (indicates complexation).
• Remove aq layer and wash organic a few times with sat. NH ₄Cl aq.
• Isolate crude material as in step 4 above.

A number of boron compounds and residues (for example from hydroboration, allylation, reduction, Suzuki coupling, etc) can be removed by concentrating the reaction mixture repeatedly from MeOH. This process forms (MeO) ₃B, which is volatile.

1. Byproducts of tin based reactions such as Bu ₃SnBr can be removed by treatment with AlMe3 to create the nonpolar Bu ₃SnMe or NaOH to create the polar Bu ₃SnOH. See: P. Renaud, E. Lacote, L. Quaranta Tetrahedron Lett. 1998 , 39 , 2123. (partially taken from the Merlic Group at UCLA, The Organic Companion)
2. Filter through a mixture of KF/Celite
3. 1. Dilute rxn with suitable organic solvent
   2. Add aqueous phase (water, sat. NH ₄Cl, etc.)
   3. Remove aq layer and wash organic phase 2-3 times with 1M KF aq solution. Shake in sep funnel for up to 1 minute for each wash. Solid Bu ₃SnF precip may form at organic/aqueous interface. If a problem, filter through celite.
   4. Wash aq 1 X brine, dry organic phase and remove solvent.
4. In many Stille reactions, the Bu ₃SnX junk can be almost entirely removed by filtering through (or columning directly) on silica made up with ~2-5% triethylamine in the eleunt. Run in the same solvent. Quicker than stirring with aq, KF, and more fun than grinding a big bowl of toxic KF with silica or celite for a good dispersion. (contributed by Graham Cumming)
5. For Bu ₃SnH: add I ₂ to convert Bu ₃SnSnBu ₃ and unreacted Bu ₃SnH to Bu ₃SnI, KF treatment (see above) then converts this to Bu ₃SnF, which is more easily removed. (contributed by Thomas Pettus)

Many transition metals can be removed by precipitation of the sulfides. Wash with aqueous sodium sulfide. If necessary, adjust pH to create H ₂S.

Some transition metals can be removed by aqueous extraction with tris(hydroxymethyl)phosphine. See: R. H. Grubs Tetrahedron Lett. 1999 , 40, 4137.

1. To workup a reaction containing x g lithium aluminum hydride:
   1. Dilute with ether and cool to 0oC
   2. Slowly add x mL water
   3. Add x mL 15 % aqueous sodium hydroxide
   4. Add 3x mL water
   5. Warm to RT and stir 15 min
   6. Add some anhydrous magnesium sulfate
   7. Stir 15 min and filter to remove salts
2. To workup a reaction containing x mmol of an agent such as Diisobutyl aluminum hydride (Dibal):
   1. Dilute with ether and cool to 0oC
   2. Slowly add 0.04x mL water
   3. Add 0.04x mL 15 % aqueous sodium hydroxide
   4. Add 0.1x mL water
   5. Warm to RT and stir 15 min
   6. Add some anhydrous magnesium sulfate
   7. Stir 15 min and filter to remove salts

Quench with Aqueous ammonium chloride, the titanium byproduct will partition into the aqueous layer during workup.

1. PCC/PDC: Filter the reaction mixture through a pad of florisil.
2. Jones: Add isopropanol until the reaction turns from orange/red to green: this indicates that the oxidant has been consumed.

If reaction is done in refluxing DCE (for example), cool reaction mixture to 0°C to precipitate out all m-CPBA. Then add 10% aqueous solution of Na ₂SO ₄. Two layers form. Separate and extract with DCM. Repeat the addition of Na ₂SO ₄ several times then combine all organic layers, wash with saturated solution of NaHCO ₃, then saturated aqueous solution of NaCl, then dry (MgSO ₄) and evaporate under reduced pressure. If purifying product by FCC, any m-CPBA still present is easily separated as it is UV active, extremely polar and it ends to deposit on column tip during purification. This is easily taken care of as m-CPBA is soluable in EtOAc.

Filter the reaction mixture through a medium frit, rinsing with a minimal amount of reaction solvent, then work up. Depending one runs reaction in dioxane, THF, DMF, dichloromethane, etc., but urea is mostly insoluble in most solvents and this is a good way to get rid of it (the rest can be flashed away pretty straightforwardly). If it is too soluble, one can concentrate the reaction mixture first and take it up in ether, then filter and rinse. (contributed by Philippe Rabbat)