dormouse (Member)
04-24-00 23:57
No 108810
      new uses of piperonal -rev drone  Bookmark   


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Author  Topic:   new uses of piperonal 
rev drone
Member   posted 10-30-1999 12:32 AM          
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Setting nitroethane aside, what facile alternatives are there in utilizing piperonal towards something clandestinely interesting? I know isosafrole can be prepared from it (the method escapes me at the moment); does anybody have any thoughts on this?
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-the good reverend drone


 
K.C. Nicolaou
Member   posted 10-30-1999 02:09 AM          
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Not that they are more useful than the nitropropene or even close to being as easy, but you could:
1. Do a Wittig rxn to give isosafrole.

2. Reduce the aldehyde to a methyl group, treat with butyllithium to give the benzyl lithium, quench it with an anhydrous THF solution of the imine of acetaldehyde and MeNH2 (CH3N=CHCH3) to give MDMA, or
convert it to the organocuprate, and react with acetyl chloride to give MD2P.

3. Reduce the aldehyde to the alcohol, convert it to the benzyl bromide, make the grignard, and quench the grignard with an anhydrous THF solution of the imine of acetaldehyde and MeNH2 (CH3N=CHCH3) to give MDMA.

4. Oxidize to the acid, homologate the acid to give the 2-(4-(1,2-benzodioxole)) acetic acid(not IUPAC but I don't remember the correct ring numbering system for benzodioxole), and use one of the phenylacetic acid methods to give MD2P.

None of these methods are really worth doing if you have piperonal lying around, but that's what nitroethane is there for . I do think that if one had access to 4-methyl catechol and n-butyllithium, #2 would be the way to go to get MDMA. Once you methylenate the o-diphenol and isolate that, the conversion to the benzyllithium and then to MDMA could be done in one pot. Hard-to-get and nasty chems, but it is only two steps from a completely unwatched precursor to MDMA, if it actually works.

On a side note, has there ever been any discussion on constructing the methylenedioxy bridge in benzodioxole or safrole using paraformaldehyde/catalytic H2SO4/and refluxing in toluene with a Dean-Stark trap to remove water?


 
Rhodium
Administrator   posted 10-30-1999 04:21 PM          
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Darzen condensation with alpha-halopropionic acid ester to give the glycidyl ester, which is treated with base and worked up to give MDP2P.
Around 80% yield of 3,4-dimethoxyacetaldehyde using 3,4-MeO-BA and methyl chloroacetate according to a patent I have lying around somewhere. Should be similar yields of the phenylacetone, right?


Cherrie Baby
Member   posted 10-31-1999 01:27 AM          
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Other Darzens condensations with alpha-halo-nitriles in PTC.
PTC condesation with alanine in strong base:
USP 4501919

JACS 76 (1954) pp 1322-6.

They both used glycine not alanine but the patent implies that alanine works - sorry I haven't tried it yet. Apologies, grovel, grovel.


 
Cherrie Baby
Member   posted 10-31-1999 01:47 AM          
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Isosafrole via MDP-propanol via Grignard with bromoethane.
See Journal of Chemical Education, Oct '99, page 1427 - 'Grignard Reactions in "Wet" Ether' - for the facile Grignard with dirty magnesium, "Wet" ether and an ultrasonic bath.


Osmium
Member   posted 10-31-1999 11:40 AM          
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Cool. Enforce the Grignard by using Mg as the drying agent?
 
Wizard X
Moderator   posted 10-31-1999 09:41 PM          
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Piperonal + Propanoic anhydride ===>>
Ph-CH=C(-COOH)-CH3, reduces the double bond,
Ph-CH2-CH(-COOH)-CH3, then Hoffman degradation.


lost in the sauce
Member   posted 11-02-1999 08:29 PM          
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Make a bisulfite complex of piperonal.
Treat with NaCN..to make cyanide something or other,
Treat with HCl to yeild the MDish-mandelic acid.
Treat with AA & SodiumAcetate to make a
1-MDphenyl-1-hydroxy-2-ketone sumthin sumthin. (maybe)
Glue on some ammonia
Reduce the 'HO' part or turn into an Aminorex-ish compound.
Or did somebody already say that


 
Acme
Member   posted 11-03-1999 06:19 PM          
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Just thought to chime in with this, which is more of a ?? than a suggestion, but it is Piperonal related so here goes.
Piperonal ==>> MD-Nitrostyrene (MeNO2, NH4OAc, HOAc, heat) Henry reaction, they say but no prep JMedChem 1999, 42, 3668 Is this well known (under these conditions), and will it work with nitropropane to get the nitrostyrene?


Rhodium
Administrator   posted 11-04-1999 12:22 PM          
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Acme: Please clarify what you mean here. I don't get it, as bad english isn't my first language.
 
Acme
Member   posted 11-04-1999 01:26 PM          
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Geez what the fuck was I thinking? Well, I was reading the article listed above, and they had a scheme where the intermediate was MDP-nitrostyrene, no prep but they listed MeNO2, Ammonium Acetate, AcOH, & heat above the arrow for the conversion from piperonal. Ding! A little light went off and questions arose about a. exact conditions and yield (not entirely clear, they reference another journal article, Biochem, Biophys Res Commun 1994, 199, 1461-1465, but I didnt have it handy) b. could it be used with EtNO2 (not nitropropane sorry) to get MDP-nitropropene.
On your page there is a reaction writeup that effects the transformation but uses NaOH, No?


Rhodium
Administrator   posted 11-04-1999 06:38 PM          
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For the reaction of piperonal with nitroethane, on my page NaOH in methanol/water is used, Shulgin uses cyclohexylamine in acetic acid, and mentions that ammonium acetate "gives an impure product in poor yields".
 
rev drone
Member   posted 11-05-1999 12:29 AM          
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I have to hand it to you all; most of us involved in this discussion have been talking about chemistry with each other for a long time here, and know each other's approximate degree of skill. Still, the response to my question, both with respect to the creativity and the extensive knowledge-base displayed in this thread has impressed me much more than I was expecting. If I haven't said it lately, its an honor to do chemistry with you all.

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-the good reverend drone


 
rev drone
Member   posted 11-05-1999 12:30 AM          
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I have to hand it to you all; most of us involved in this discussion have been talking about chemistry with each other for a long time here, and know each other's approximate degree of skill. Still, the response to my question, both with respect to the creativity and the extensive knowledge-base displayed in this thread has impressed me much more than I was expecting. If I haven't said it lately, its an honor to do chemistry with you all.

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-the good reverend drone


 
K.C. Nicolaou
Member   posted 11-05-1999 01:45 AM          
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Thiamine or CN- mediated benzoin condensation of piperonal and acetaldehyde to give 1-Hydroxyl-MD2P. Reductive cleavage of benzyl-O bond to give MD2P, or reductive amination to give the ephedrine anologue of MDMA followed by reductive removal of the alcohol.
 
rev drone
Member   posted 11-08-1999 08:19 PM          
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KCN,
Say, do you have any more details on those chemoselective mediated Claissen condensation conditions? This is downright intheresting...

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-the good reverend drone


 
K.C. Nicolaou
Member   posted 11-08-1999 08:39 PM          
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Well Drone, that one was pulled out of my asshole to a certain extent, so I'm not sure if this is a well studied rxn and if journal refs are availiable. But then I'm not quite such a stickler for having a bunch of journal refs to back me up as you are. I do have legitimate resons to believe that that rxn can be carried out with good(not sure exactly how good) selectivity. I'll post a more detailed explanation of my logic when I have more time(p-chem midterm on weds). Also, if you take another look at that, you will notice that it is not a claisen condensation. The carbonyl carbon of acetaldehyde is the nucleophile, not the alpha carbon.
 
rev drone
Member   posted 11-08-1999 10:38 PM          
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Point taken; thanks.
I remember in my organic synthesis course from a couple years ago, our teacherwas especially fond of condensation reactions of carbonyls, and we studied more variations of enolate and enol chemistry than I'd care to mention -- emphasizing mostly enantioselective rather than purely assymetric chemistry. At the time, I was gasping for air; now I wish we went furrther. I'll see what my old notes have to say...

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-the good reverend drone


 
K.C. Nicolaou
Member   posted 11-09-1999 01:29 AM          
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Doh! I made a very bad boo-boo in my previous post. Many profuse apologies to all. The benzoin condensation of piperonal and acetaldehyde would give 1-Oxo-MDP-2-Pol, not what I wrote a few posts ago. For a reasonably informative description of the benzoin condensation, see March, 969-970. I had to do an unsymmetric benzion condensation as part of some "legitimate" chemistry I worked on, so I had to research this a bit. Basically, what it boils down to is this: In these types of condensations, a nucleophillic catalyst adds to a donor aldehyde to give a cyanohydrin. Due to resonance effects, the carbonyl carbon becomes nucleophillic and can add to the carbonyl carbon of a second aldehyde, giving an alpha-hydroxy ketone. In the reaction of two different aldehydes, one aldehyde will preferentially act as a donor, and one as the acceptor, usually giving a mixture of products, but sometimes giving only one. My fuckup happened because I remembered that benzaldehydes with o,p substituents that are electron donating by resonance(like piperonal) can only act as donors, giving a single condensation product with a suitable acceptor aldehyde, and since I hadn't thought much about that reaction in the last six months, I forget which aldehyde, donor or acceptor, ended up as the ketone, and wrote the exact opposite of what should have been the product of that reaction. So thanks for your interest Rev, cause you made me catch myself before anyone got the wrong idea. As for the clandestine applications of 1-Oxo-MDP-2-Pol, one could reduce the ketone to the alcohol and obtain MD2P through the diol rearrangement, or one could tosylate the alcohol and displace with methylamine(none of the rearrangement/elimination problems of MD-2-Pol are the 2-halo compound ) and then effect reductive removal of the ketone function with hydrazine/NaOH, Zn/HCL, etc. Again, sorry about that foul-up. As for the Rev's previous post, I think that assymetric/enantioselective enolate chemistry is cool too. One of the things that fascinates me about organic chemistry is the fact that you can tweak conditions for the same basic rxn by changing the nature of your solvent/base/catalyst/etc. and get high selectivities for the formation of one product.
 
Wizard X
Moderator   posted 11-11-1999 09:26 PM          
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So,MDPh-CHO + CH3CHO ==>> Ph-C(O)-CH(OH)-CH3
1-Oxo-MDP-2-Pol Hmmmm !


K.C. Nicolaou
Member   posted 11-11-1999 10:30 PM          
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Theoretically. You also need a catalyst, which is generally thiamine or KCN.
 
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