Rhodium
(Chief Bee)
04-22-03 14:15
No 428632
      Piperonal + MEK -> Isosafrole?
(Rated as: good idea!)
 Bookmark   

What do you guys think of the Aldol-Grob reaction, where a benzaldehyde is condensed with a ketone under Lewis catalysis to yield phenyl-2-alkenes? Wouldn't this work nicely to make propenylbenzene from benzaldehyde and methyl ethyl ketone or even more interesting - isosafrole from piperonal?

It should be possible, as in In DOI:10.1016/S0040-4020(01)89414-X they use the reaction to synthesize a derivative of isosafrole, and in the articles below they prepare other phenylpropenes (Entry 13, Table 5, Ref 5), so I see no immediate obstacle to it. And who's the originator of this synthesis? Our old ally George W. Kabalka...


References:

[1] Eur. J. Org. Chem. 1631-1634(2003) (../rhodium/pdf /phenyl-2-alkenes.aldol-grob-1.pdf)
[2] Tetrahedron 54, 15525-15532 (1998) (../rhodium/pdf /phenyl-2-alkenes.aldol-grob-2.pdf)
[3] J. Org. Chem. 63, 6438-6439 (1998) (../rhodium/pdf /phenyl-2-alkenes.aldol-grob-3.pdf)
[4] Phytochemistry 39, 731 (1995) (../rhodium/pdf /phenyl-2-alkenes.aldol-grob-4.pdf)
[5] J. Org. Chem. 64, 3157-3161 (1999) (../rhodium/pdf /phenyl-2-alkenes.aldol-grob-5.pdf)
 
 
 
 
    GC_MS
(Hive Addict)
04-22-03 21:17
No 428715
      NaBH4-cat. Cinnamic Acid synth from Benzaldehyde
(Rated as: excellent)
 Bookmark   

Is this something similar?

A new direct synthesis of cinnamic acids from aromatic
aldehydes and aliphatic carboxylic acids in the presence of
sodium borohydride


Tetrahedron Letters 44 (2003) 3579-3580 (../rhodium/pdf /benzaldehyde2cinnamate.nabh4-cat.pdf)

Abstract Cinnamic acids have been prepared in 5986% yields by a new direct synthesis from aromatic aldehydes and aliphatic carboxylic acids in the presence of sodium borohydride and N-methyl-2-pyrrolidinone (NMP) as solvent, at reflux (185190C), for 912 hours. Without sodium borohydride, this reaction is not possible.

DOI:10.1016/S0040-4039(03)00529-X

I noticed the articles a handful of days ago and was interested in performing the reaction, just for the fun of synthesizing some cinnamic acids. Is the reaction mechanism identical?

The faster you run, the quicker you die.
 
 
 
 
    Rhodium
(Chief Bee)
04-23-03 00:04
No 428756
      Perkin Reaction Variation  Bookmark   

Nope, the reaction you have linked to is a modification of the Perkin Reaction, but where the acetic anhydride usually required has been substituted with NaB(OAc)4, formed in situ from NaBH4 and excess acetic acid. Nonetheless, it is very interesting, as many bees have easier access to NaBH4 than Ac2O.
 
 
 
 
    Protium
(Hive Bee)
04-23-03 06:57
No 428853
      I would be a happy man  Bookmark   

If I could just reflux piperonal and MEK with BF3 in hexane for 2.5 hours and walk out with 89% isosafrole.  That sure would handle some pesky aquisitions problems.  Hell, that would also be quicker than my isomerization workup, and save me all that time cleaning flasks.

Tee-hee

Pr(+)tium
 
 
 
 
    El_Zorro
(Hive Addict)
04-25-03 05:13
No 429245
      Has the thought crossed anyone's mind that...  Bookmark   

Has the thought crossed anyone's mind that styrene is about common as dog shit?  Why styrene?  Because the CuO procedure gives you benzaldehyde cheap as fuck.  Now that you can get benzaldehyde by the kilo, and MEK is at the hardware store by the gallon, that's a shitload of propenylbenzene.  Just a thought.

It is seductive, way too seductive.             -Eleusis
 
 
 
 
    starlight
(Hive Bee)
04-25-03 11:50
No 429299
      are you sure  Bookmark   

are you sure that styrene --> benzaldehyde with CuO is that easy?

the patent for the CuO procedure works on a phenolic propenyl benzene in alkali solution.



I have had little success in attempts to oxidise isodillapiole with CuO. But then I've only had a couple of attempts.
 
 
 
 
    Hedonist_Rex
(Newbee)
06-21-03 11:26
No 441523
      (bump)  Bookmark   

I know bumping without a serious contribution is probably frowned upon in this forum, but this would be the holy grail after all....

Could a newbee aid this cause?

MEK is everywhere and cheap as dirt.
 
 
 
 
    El_Zorro
(Hive Addict)
06-21-03 21:38
No 441579
      Re: MEK is everywhere and cheap as dirt.  Bookmark   


MEK is everywhere and cheap as dirt.




Yeah, but piperonal isn't.


It is seductive, way too seductive.             -Eleusis
 
 
 
 
    Hedonist_Rex
(Newbee)
06-22-03 09:04
No 441648
      Fair enough, but some bees who might be tired...  Bookmark   

Fair enough, but some bees who might be tired of digging root bark may have access to a 500ml soxhlet and unwatched peppercorns by the kilo.
 
 
 
 
    El_Zorro
(Hive Addict)
06-23-03 00:45
No 441777
      I would think if you were going to invest in...  Bookmark   

I would think if you were going to invest in an unproven method, then you might look into using aniline hydrochloride to demethylate vanillin, then methylenate it to piperonal.

It is seductive, way too seductive.             -Eleusis
 
 
 
 
    El_Zorro
(Hive Addict)
06-23-03 08:05
No 441868
      So what all could a bee use as a Lewis acid?  Bookmark   

So what all could a bee use as a Lewis acid?  AlCl3 won't work for any methylenedioxy routes, but what else would work besides BF3, or any of those other chems that a hobby bee can't get?

It is seductive, way too seductive.             -Eleusis
 
 
 
 
    Rhodium
(Chief Bee)
06-23-03 14:07
No 441916
      Which Lewis acids will do the trick?  Bookmark   

I think that is pretty much discussed in detail in the references I linked at the top. Have you read them all? There are well over a dozen catalysts mentioned, and they are all tried on different substrates, so that you can deduce which are compatible with what functionalities.