NPP: part 2

[Ford Prefect]

Experimental.

C8H11N + C3H6O + 2H2CO -> C13H17NO + 2H2O

12.1 g of phenethylamine is dissolved in 12 ml 50% aq formaldehyde and 7.3 ml of acetone. Glacial acetic acid is then slowly added and solution is brought to reflux. After completion n-phenethyl-4-piperidinone is isolated. It should be slightly yellow solid with a mp around 60 degrees.

Ref.

http://tinyurl.com/bbyw85

I'll ask my good friend Professor Snape to give it a shot next Potions class, but I wanted all yous thoughts before I ask him to potentially waste his precious ingredients. This shit have potential? Am I wasting my time? What should the professor watch out for?

[Irukanji]

Boom?

[Ford Prefect]

Boom?

Probably. :(

Anyways, found some pretty incredible papers regarding this reaction that I thought I's share. Haven't had time to to absorb them quite yet, but we'll do papers first and commentary later...

The Preparation of Some Piperidine Derivatives by the Mannich Reaction - 0.34MB (http://www.zshare.net/download/55382744404de6fd/)
Alpha- and Beta-Prodine Type Compounds - 1.05MB (http://www.zshare.net/download/55382786088fc079/)

Give em a look.

[Irukanji]

Now i understand why you were asking for the first 1....it all makes sense now.....

Hopefully the second isnt corrupt.....hmm....it doesnt say what type of file....

EDIT: Never mind, it's a pdf...lol

[Hydroponichronic]

Where in the world does the piperidinone bit come from? Didn't see any added...Made in situ? ballin'! Post up is this works. Then, post up with some propanoic anhydride tips. :)

[Ford Prefect]

Where in the world does the piperidinone bit come from? Didn't see any added...Made in situ? ballin'! Post up is this works. Then, post up with some propanoic anhydride tips. :)

lool wats tha propionic anhydride 4?

Naw, that's the easy part:
http://www.erowid.org/archive/rhodium/chemistry/propionic.acid.html
then 2 CH3CH2CO2H + CH2=C=O -> (CH3CH2CO)2O + CH3CO2H (1 (http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv3p0164))

or maybe...


Propionic anhydride is made from a propionate salt
like calcium propionate by adding bromine or even
chlorine. Alternatively, propionate esters are
hydrolyzed, the acid component isolated, and combined
with acetic anhydride and allowed to reflux, with the
product being fractionally distilled.


But yeah, it's made in situ. It's a pretty fucking reaction, theoretically that is. Double Mannich will all sorts of things coming together just right to make it all happen, still not exactly sure how it'd work though I'm rather convinced it will.

I'll let you all know when the professor finds time to give it a try. Might be a while yet though. :(

[HeaT]

I absolutely cannot wait. I'm excited.:D

[fcknut]

Forgice me for not being bothered to actually look at these papers, but what is the yield of the procedure in the OP?

I kinda feel that this may not be a particularly efficient process, and that side products may be abundant... Dunno fo sho tho !

Oh, and the link in the OP is bad...

[Ford Prefect]

Forgice me for not being bothered to actually look at these papers, but what is the yield of the procedure in the OP?

I kinda feel that this may not be a particularly efficient process, and that side products may be abundant... Dunno fo sho tho !

Oh, and the link in the OP is bad...

Regarding the usual procedure, refluxing is water or alcohol, shit yields and impure products is definitely the case. But GAA seems to be an ideal solvent, not only can the temp. of reflux be raised but the acid catalyzes the reaction.

This specific chemical isn't mentioned though so you could be quite right. For structurally similar piperdones the yields varies but most are between 40-70% and the isolation of pure product is said to be pretty easy.

And yeah, the link is dead. :( But it was just an cached copy of the paper in my second post and the one you were kind enough to find for me in the references thread.


Can anyone think of any reason why a molar equal of 37% aq formaldehyde might prove an insufficient substitute?

[fcknut]

Regarding the usual procedure, refluxing is water or alcohol, shit yields and impure products is definitely the case. But GAA seems to be an ideal solvent, not only can the temp. of reflux be raised but the acid catalyzes the reaction.

This specific chemical isn't mentioned though so you could be quite right. For structurally similar piperdones the yields varies but most are between 40-70% and the isolation of pure product is said to be pretty easy.

Fair enough, I guess if similar compounds are giving reasonable yields then it's probably OK! Although, aren't there any more recent articles with alternative syntheses? Just so you're not going back to the late 50's ?


Can anyone think of any reason why a molar equal of 37% aq formaldehyde might prove an insufficient substitute?


Nah, that'll be fine i reckon - 50% will just be what they had to hand.

[Ford Prefect]

Fair enough, I guess if similar compounds are giving reasonable yields then it's probably OK! Although, aren't there any more recent articles with alternative syntheses? Just so you're not going back to the late 50's ?

I wish! I found a few obscure semi-references but nothing concrete. If anybody knows Russian there's a patent in the refs section on SM that is said to be more up to date.

All in all it's a damned mysterious synthesis though, which obviously leaves me with some foreboding.

Nah, that'll be fine i reckon - 50% will just be what they had to hand.

Figured it would. My gnomish friends dictated the OP when they had some 50% for they're potions.

[fcknut]

I had a quick look, and it seems that most of the refs are not particularly enlightening, tending to start from piperidone precursors. There are a few which take an open chain secondary amine with ester groups an the termini, and perform a ring closure through the use of sodium metal or sodium ethoxide.

I did find one pretty one (http://www.evilshare.com/c888a566-4b0d-102c-8e73-0007e90cfb90), where they use TFA and phenylethylamine, but I can't get the ref - if anyone has access to it, could you post it up please?


Suh et al.; Heterocycles, (1998), 48 (2), pp 239-242


Looks kinda fun!

[stateofhack]

Being requested hopefully here soon :)

[stateofhack]

http://rapidshare.com/files/169502766/Heterocycles_1998.rar

Got it, too lazy to search in it, so here is all of it, i will mirror it in a little bit. Enjoy!

[fcknut]

Nice work man - Cheers!

Always handy to have a bunch of references - never know when they might come in handy...

FYI, the requested citation is the file 2\COM-97-8056.pdf. However, it looks like the search results were misleading, and the reaction is actually a variation of the same double-mannich procedure previously discussed, this time using allyl silane as a reducing agent, followed by a standard Swern oxidation.

I thought the reaction was a bit weird - was trying hard to figure out how the fuck it went !

Oh well, no matter - thanks again for digging those out !

[nshanin]

lool wats tha propionic anhydride 4?

Naw, that's the easy part:
http://www.erowid.org/archive/rhodium/chemistry/propionic.acid.html
then 2 CH3CH2CO2H + CH2=C=O -> (CH3CH2CO)2O + CH3CO2H (1 (http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv3p0164))

or maybe...



But yeah, it's made in situ. It's a pretty fucking reaction, theoretically that is. Double Mannich will all sorts of things coming together just right to make it all happen, still not exactly sure how it'd work though I'm rather convinced it will.

I'll let you all know when the professor finds time to give it a try. Might be a while yet though. :(

Ketene? Is this some sort of sick joke?

[Ford Prefect]

Ketene? Is this some sort of sick joke?

Hah (http://jchemed.chem.wisc.edu/JCEsoft/CCA/CCA5/MAIN/1ORGANIC/ORG12/KETENE/MOVIE.HTM) ;)

Might somebody possibly post the relevant info from Heterocycles?
I've got a bad case of shitty internet. :tedium:

[stateofhack]

Tell me what you need, give me 5 hours or less and it is here, spit it out boy ( not know tho to drunk and need some sleep).

[Ford Prefect]

Tell me what you need, give me 5 hours or less and it is here, spit it out boy ( not know tho to drunk and need some sleep).

Ha, <3

FYI, the requested citation is the file 2\COM-97-8056.pdf.

This, I think. :)

[fcknut]

Suh et al.; Heterocycles, (1998), 48 (2), pp 239-242 (http://www.evilshare.com/21bb0710-4be9-102c-8617-000b6aa2a5f8)


All credit, of course, to stateofhack

[stateofhack]

Suh et al.; Heterocycles, (1998), 48 (2), pp 239-242 (http://www.evilshare.com/21bb0710-4be9-102c-8617-000b6aa2a5f8)


All credit, of course, to stateofhack

I want your babies!:mad: Thanks for doing the rest of the work :D

Gona read it properly now, lets hope it is tasty!