(Hive Bee)
06-29-02 16:05
No 326962
      The Wittig reaction: phenyl-2-propanone synthesis
(Rated as: good read)

The ancient Greeks knew it already: pride comes before a fall.  However, I hope that the gods will forgive me, because I am particulary proud to present you this ingenious synthetic pathway:
*  triphenyl phosphine reacts with alpha-chloroethyl methyl ether to give a slightly hygroscopic phosphonium salt.  However, you can store this salt indefinitely in a sealed container. Yield: 88 %
* after proton abstraction, the phosphorane reacts with benzaldehyde to provide an enol ether (Yield: 88 %) , which can be subjected to hydrolysis (Yield: quantitative).


1) The phosphonium salt was prepared by dissolving triphenyl phosphine (76.4 g, 0.29 mole) and alpha-chloroethyl methyl ether (28.4 g, 0.30 mole) in 125 mL of benzene.  After standing 40 hours the residue was filtered and washed with ether giving a white solid (111 g, 88 % yield) consisting of the crude phosphonium salt containing one molar equivalent of benzene of crystallization.  This crude phosphonium salt is pure enough for the next reaction.  Attempts to recrystallize this salt resulted in partial of complete conversion to a crystalline dihydrate.

2) The phosphonium salt (33 mmoles) was suspended in 40 mL of glyme at - 40 C under nitrogen.  Potassium t-butoxide (33 mmoles) in 15 mL of glyme was added with stirring over five minutes.  After this point a solution of benzaldehyde (30 mmoles) in 5 mL of glyme was added over five minutes.  The mixture was allowed to warm to room temperature over one hour and was then directly distilled. (Yield: 88 % enol ether)

3) Methyl ketones (phenyl-2-propanone in our case) were conveniently prepared from the enol ethers by mixing with one equivalent of water containing 0.5 % HCl and enough methanol to effect solution.  The solution was heated to boiling and the solvent was then evaporated to give relatively pure samples of ketones in practically quantitative yields.

This reaction is general for the preparation of methyl ketones.  However it seems that the reaction is at its best for the synthesis of P2P (88 %, step 2), since the yield for methyl cyclohexyl ketone is 45 % (step 2), and even worse for 3-methyl-2-nonanone (15 %, step 2).

ref.: D. Robert Coulsen, Tetrahedron Letters (1964) p 3323- 3326
(Chief Bee)
07-01-02 15:45
No 327729
      Great! I have a somewhat shorter version of this ...  Bookmark   

Great! I have a somewhat shorter version of this synthesis at ../rhodium/chemistry /phenylacetone.html#ylide , and I haven't gotten any reports of this method being used by anyone yet, so here is a brand new project for you all!