Rhodium
(Chief Bee)
01-21-03 02:47
No 400040
      P2P by Grignard Addition to Acetic Anhydride
(Rated as: excellent)
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Preparation of Ketones from Grignard Reagents and Acetic Anhydride[1]

We have found that excellent yields of methyl ketones may be obtained by the addition of Grignard reagents to an ether solution of acetic anhydride at about -70C. Primary, secondary, tertiary aliphatic, and aromatic Grignard reagents give 70-79% yields of the corresponding methyl ketones while the allyl and benzyl reagents give 42 and 52%, respectively[2].

We attribute the success of these reactions at low temperature to the thermal stability of the complex formed by the addition of one molecule of Grignard reagent to one of the carbonyl groups of acetic anhydride, and to its decreased solubility. These factors both tend to reduce the further reaction of the complex with more Grignard reagent to form the tertiary alcohol. At the low temperature involved there is probably no cleavage of this complex to form ketone which might further react.

Experimental

In a typical experiment, 0.2 mole of a titrated Grignard reagent was added slowly during one hour to a stirred solution of 40g of acetic anhydride in 100ml of dry ether in a 500ml 3-necked flask cooled by a mixture of Dry Ice and acetone in a Dewar flask. The added reagent was cooled by dripping through a tube externally cooled with Dry Ice. After stirring for two to three hours the cooling bath was removed and the mixture was treated with ammonium chloride solution. After washing out the acetic anhydride and acid with alkali the ether was fractionated and the ketones distilled.

For the most part the ketones were identified by boiling point and index of refraction, although a few derivatives were made. The following Grignard reagents gave the corresponding methyl ketones in the following yields: n-butylmagnesium chloride, 79%; n-butylmagnesium bromide, 79%; s-butylmagnesium bromide, 78%; t-butylmagnesium chloride; 77%; phenylmagnesium bromide, 70%; benzylmagnesium chloride, 52%; and allylmagnesium bromide, 42%. With phenylmagnesium bromide and propionic anhydride a 59% yield of propiophenone was obtained.

References:

[1] Newman & Booth, J. Am. Chem. Soc. 67, 154 (1945)
[2] Fournier treated a series of primary halide Grignard reagents with a series of anhydrides at about -20C and reported general yields in the range 25-50%[3]. We have found that on adding butylmagnesium bromide to acetic anhydride at -33C the yield of somewhat impure ketone is less than 40%.
[3] Bull. soc. chim., (3) 31, 483 (1904); (3) 35, 19 (1906); (4) 7, 836 (1910),
 
 
 
 
    foxy2
(Distinctive Doe)
01-23-03 07:52
No 400681
      ketene  Bookmark   

I think there is a way to shorten this by one step, for bee's who can't buy AA.  I was looking at a grignard book and it seems that ketene would do the same thing when reacted with a benzyl grignard.

If the ketene generator works well then this seems like an intesting possibility.
 
 
 
 
    fallen_Angel
(HyperLab Bee)
01-24-03 06:24
No 401045
      No  Bookmark   

If are you use ketene, the yield will be very small.
 
 
 
 
    BillyBoy
(Stranger)
01-24-03 11:22
No 401080
      ketene yield  Bookmark   

How small would be yield via ketene?
 
 
 
 
    Aurelius
(Hive Addict)
01-24-03 21:41
No 401171
      ketene  Bookmark   

Why bother with Ketene yields if they're smaller, just use the ketene in a controlled water addition to form the anhydride.  then use the anhydride.  it's not like it's a grand and hard procedure.  just some calculations.  if you're worried about water being present, use a slight excess of ketene.
 
 
 
 
    BillyBoy
(Stranger)
01-25-03 10:31
No 401349
      ketene  Bookmark   

Well, first of all note that reaction temp. is -70C, and not everybee has access to dry ice.

Second, this can easely be adapted to make P2P and acetic anhydride in same process.

We can connect ketene lamp to a flask with grignard, and output from that can be attached to 2 flasks with acetic acid. The ketene wich doesent react with grignard will simply form anhydride with GAA.

 
 
 
 
    zorohydride
(Stranger)
02-22-03 16:43
No 410764
      Soft grignard  Bookmark   

Hello Rho. I have followed your work and I found some interesting new grignards that have not made their way into mainstream literature AKA soft grignards. By the way, I tried the above rxn with poor results and difficulty in handling during scale up. A new type of Grignard is the Manganese 'Mn' base. Start with the usual method of a Magnesium, I prefer Butyl DiGlyme as a solvent, and when rxn is done, cool down and add ANHY MnCl to for the new adduct to form. These Mn grignards do react directly with acid halides to form ketones like Cd. I have had 50% yields and could have done better if it were not for my quick and dirty lab philosophy. Happy hunting.