thermal rearangement of ketamide in DMSO

[miss_biggie]

to ketamine..  Anybody want to guess if this will work?  I'm guessing at 180'c it will disolve the amide fine, but the methods I've come across either use decalin, undecane, or gas ethyl benzoate with HCl.  Does it matter that DMSO is aprotic?  Will DMSO favour the thermal rearangement?  What would be the best way to extract the amine from DMSO?  Could it be done up by adding water and extracting with DCM/toulene?   I do not think DMSO/water would solvate the freebase very well at all.  DMSO is more readily and cheaply available then undecane, decalin, and ethyl benzoate.

link to DMSO info, including solubility and rxn info:

http://www.gaylordchemical.com/home/default.asp

[Rhodium]

What is ketamide? What procedure are you trying to follow? Please provide links.

[miss_biggie]

I'm refering to the amide, before the final step of thermal rearangement to the drug commonly called ketamine.  ketamide seems appropriate enough scince ketamine is no more specific of description of the common drug.  Although, the

diagram

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/pcp/pictures/ketamine_synth.gif) refers to a ketone that does not appear to be what is drawn.

I'm refering to the following examples:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/ketamine2.html

https://www.thevespiary.org/rhodium/Rhodium/chemistry/pcp/ketamine.html

[miss_biggie]

It also works on large scale with less solvent and ethyl benzoate.  1.5x weight ethyl benzoate is heated to disolve amide, allowed to cool, gased with HCl to ph 1.5, heated to 180'c for 30min, centrifuged, residue acid/base extracted.  I think in this case they were trying to minimize the amount of solvent heated to 180', for multi-kg batches.

[Rhodium]

There are no amides at all involved in the synthesis of Ketamine. Amides contain the group R¹-(C=O)-NR²R³ and there are no such group present in any intermediate. Perhaps you are thinking about the imine functionality, which is equal to R¹-N=R²

You are correct in that the last intermediate not being a ketone, but it isn't referred to as such either.
The name 1-hydroxycyclopentyl-(o-chlorophenyl)-ketone-N-methylimine uses substitutive nomenclature which implicates that the compound is the N-Methylimine {=N-CH₃} derivative of the actual 1-hydroxycyclopentyl-(o-chlorophenyl)-ketone, as in the second last reaction the {=O} of the bromo ketone is reacted with methylamine to become {=N-CH₃}.

As for the rearrangement, search for recent threads containing posts by 'k0dog' related to ketamine for some related info.

[miss_biggie]

yes, of course, duh.. the imine.  A search on k0dog produced no results.  I've searched for info relating to this already and did not come across any posts, other then the Zealot one.  Please provide a link?

[miss_biggie]

Nevermind found it, although that isn't really any practical info.  Heating a few 100mls of kerosene to 180'c is a little different then heating 50l of it, and as k0dog says there are much more practical ways of producing the salt from the freebase.  IPA seems to be the best solvent to use, and EtOH seems to work well to recrystalize.  But no doubt the people getting rich of ketamine freebase weren't too keen to share their secrets prior to legal changes in china.

Will DMSO dissolve the imine better then the amine?  Can anyone tell me that?  Based on page three, four of

this

(http://www.gaylordchemical.com/bulletins/bulletin116.pdf) info will it hinder the thermal rearangement?

[k0dog]

Ya I know for sure that a thermal re-arrangement will work if you use ultrasene as a solvent and reflux your Hydroxylimide in it for like 2hours (thats what i did I'm pretty sure)..... but you gotta prepare the ulrtasene first...oh ya that was at 180'c

To prepare the ultrasene you have to place it on a hotplate and raise its temperature to about 180'c for like and hour.. that will get rid of the smaller and lighter hydrocarbons in it...

anyways Miss_biggie.. I take offence to your comment about not sharing.. I shared before.. only I had no time to freaking write up a report.. I told people a long time ago I would... and got very little response... even after I posted it little response.. only now that people are craving their little fix does it come up that I didn't share.... but meh...

I doubt that the DMSO will hinder the re-arrangment at all... seriously sultar sene is easy and practical... just make sure to watch it and the temps (especially for the prep cuz it does light up fast some times...)

[k0dog]

Another easitier way is to take a glass tube.... (pretty thick) place your Hydroxylimide .. seal both ends.... this is fun... mmm torch envy..place it in an alcove... with toluene in it.... then just heat it at like I believe 120'c for 2 hours... but you should do some reading.. rhodium provided a great link in one of my post that brought me that info... do some searching...