nagash (Stranger)
08-04-03 04:13
No 451587
      Cocaine analogs - anybee tested?  Bookmark   


has anybee tested the cocaine analogs described around on the hive and in various medical articles? Some are said to be very potent, but that does not equal very fun.

So, does anybee have any personal or second-hand experience with the analogs?

Thanks in advance.
08-04-03 11:08
No 451642
      See  Bookmark   

See Post 446941 (tropine: "Arecoline analogue...freebase success! But....", Serious Chemistry)

Post 449302 (Jubrail: "Cocaine analog not found in TFSE", Novel Discourse)

and UTFSE.
08-04-03 13:02
No 451659
      Still no bioassay  Bookmark   

These threads, as far as I can tell, still contain no qualitative comments on the analogs...
08-04-03 14:58
No 451681
      You don't say.  Bookmark   

Did you read the links? There are no bioassays because no one's successfully made them. (Or, if they have, they haven't told anyone)
08-04-03 20:54
No 451738
      the reaction was tested, but  Bookmark   

the technique used was sloppy, as the reaction scheme is really quite simple.  When the arecoline freebase was made for instance the DCM was already in solution with the water and Arecoline*HBr, and upon addding sodium bi-carbonate, the DCM turn a yellow/red colour.  The DCM layer was extracted dried and then evaporated to yeild a deep amber thick oil.   This was then subjected to the reaction, but the salt wash was left out and it was not recrystalized from EthAOC / Hexane.  This left a dark red/ yellow oil.  It was then dissolved in methanol and dry HCl gas was pumped through it yeilding really small crystals, at what looked to be only a ~5% yeild. Suction filtration left nothing (using filter paper) as the crystals slid right through.  The methanol was removed to reproduce the annoying red oil.  It was really discouraging for this to happen, as I did not think that the pruification procedures that they took would really affect the product to such a miserable mess.  Unfortunately the project cannot be restarted, maybe someone else can carry the torch?
(Chief Bee)
08-05-03 13:37
No 451883
      skipping steps  Bookmark   

I wonder why people compulsively waste so much money and precursors all the time by skipping steps over and over again, especially when trying a synthesis for the first time.

The people writing the original articles aren't adding a heap of purification steps just to annoy you, they do it for a reason: To attain as high yield as possible of a pure substance.
(I'm Yust a Typo)
08-05-03 14:57
No 451894
      Depends. Sometimes, they omit purification...  Bookmark   

Depends. Sometimes, they omit purification details (only column XYZ with a small tinge of ABC works) or they assume that 'everybody knows not to overheat such a sensitive molecule as Y while recrystallizing'. Sometimes, workup steps are omitted or shortened (duh, we assume you knew that aldehydes need nitrogen atmosphere *always* in a hefty basic environment). And sometimes, the product is good enough without recrystallization, simply because other purification steps in your next reaction will deal better with the garbage than a wastefull recrystallization before that reaction.

(I'm thinking specifically of the typical 'aldehyde->nitrostyrene->amine' sequence, where in SWIY's experience the main yield-determining factor was the quality of the LAH used in the last step.)

OTOH, that's not to say that you shouldn't at least try to follow the literature to the letter.
08-06-03 21:46
No 452243
      Rhodium : point taken  Bookmark   

yes it should have been followed to the "T", but I was thinking along the lines of "No big deal if I get a lower yield of lower purity"  what I didn't realize was how incredibly those purification steps are. The acid/base extractions I thought would have given pure enough product with some yield, but, for whatever reason, skipping them
left me with nothing.  A few points that are a bit vague in the paper 1) Under the experimetal section for ::: rac-Methyl 4-(4-Chlorophenyl)-1-methylpiperidine-3-
carboxylate (1, 2).The crude mixture was crystallized from EtOAc/hexane :::  So I assume it is dissolved in a min amount of EtOAc, heated, then hexane is added until the solution just turns cloudy, a drop more EtOAc is added to make the solution clear and it is cooled down slowly with stirring then put into an ice bath to recrystalized.  Comments?

Under the same section

The hydrochloride salts of these compounds were
prepared by dissolution of the free bases in a methanolic
solution of HCl(g), concentration, and final trituration of the crude salts with ether::::.  So it seems that one pre-gasses the methanol, then disolving the freebase in this methanol.  But what of the concentrating and "final trituration" with ether?  Is this a fancy way to say wash the resulting hydrochloride crystals with ether (I assume they fall out of solution when the pre-gasses methanol hits the free-base)?

Anyways my project was a failure, hope someone else tries!
(Chief Bee)
08-06-03 23:30
No 452253
      You have gotten the EtOAc/hexane ...  Bookmark   

You have gotten the EtOAc/hexane recrystallization right.

However, in the prep of the HCl salt, it seems like the HCl salts won't precipitate directly, only after evaporating most of the alcohol (the concentration). Then you cover the residue with diethyl ether, and stir/grind with a spatula (= triturate under ether), and this will probably precipitate the crystals. Do this until the crystals look nice and clean, then filter and wash with some clean ether and dry.