4-MAR via alkali metal cyanates

woden · Sat Feb 19, 2005 1:15 am

The best synth of 4-MAR was conducted by oldhivebee Bandil...

check this out:

Theory:
When the initial norephedrine hydrochloride is mixed with potassion cyanate, it forms the carbamoyl coumpound in near quantitatie yeilds with respect to the norephedrine. The original patent's uses a slight molar excess of the cyanate in order to give complete conversion. When the first reaction is done, there should thus be a mixture of: N-carbamoyl-norephedrine, potassiumchloride and traces of of cyanate. The remaining cyanate will be destroyed by the huge excess of acid which will be added later. In the end these impurities should have no influence of the ring formation, catalysed by the acid. It should in theory be possible to do the initial reaction and simply add the acid in one portion while heating continusouly till the reaction is over. With this in mind, it seems kind of a waste to isolate the intermediate, so this has to be tested :)

Practice:(in theory of course)
5 grammes of norephedrine.HCl(26,5 mmoles), was placed in a 100 mL FBF, and 2,3 grammes of KOCN(28,4 mmoles) and 25 mL's of distilled water was immediately added in succession. This was heated to reflux directly on the hotplate for two hours.

After this time, 30 mL's of 2M HCl(60 mmoles) was added. This caused a bit of bubbling(probably from the excess cyanate being broken down to gasseus -i-cant-remember-what-). Reflux was continued for an additional two hours. The mixture took on an ever so slight pinkish tint, which the "old" synth also tend to do at this stage.

After 2½ hours of reflux, the mixture was cooled and basified with sodium carbonate and presto a lot of pretty white crystals precipitated on the bottom of the beaker. The yeild looked like that which is expected from the normal reaction. They will be measured shortly.

Conclusion
Total success!!

We'll the usual cyanate route to 4-methylaminorex was easy, but this is more like baking a shake-n-bake cake really Wink

(which is VERY easy if you didn't know). Bioassay's are pending though, but nothing that was put into the flask would have reacted the way, the final product did. The yeild will also be measured shortly!

Have a nice and productive weekend!

The final yield has now been measured: 77% mole wise from the PPA.HCl

From 5,0 grammes of PPA.HCl there where prepared 3,6 grammes of 4-methylaminorex freebase with the new method. Compared to the 3,4-dimethylaminorex synthesis from J Chem Soc, 850-854 (1952), it's at least as high as they get, if not higher(i don't have their article lying around, so it's from my clouded memory). This could be attribited to the fact that no collection of the intermediate product is required.

IndoleAmine · Dreamreader Deluxe

Guest · Mon Mar 28, 2005 7:10 am

I did not know that cyanates were that easy to prepare,

Very nice work!

syn

DrugPhreak · Working Bee

Wouldn't it be better to base with sodium carbonate solution?

IndoleAmine · Dreamreader Deluxe

If you mean the cyanate rxn with norephedrine as described by Bandil: he based with sodium carbonate - or did you put empasis on "solution"?

If you mean for cyanate preparation: no.

i_a

Astrum · Tue Mar 29, 2005 8:51 am

Astrum · Fri Apr 01, 2005 1:07 pm

Well SWIM tried to make some potassium cyanate just now. From what SWIM has been reading it's best to mix the two and heat them directly (no solvent). Anyway, since all of the threads didn't use a solvent, SWIM didn't either.

14g (~250mmol) of KOH was crushed with 15.5g (~258mmol) of CO(NH2)2 into a fine powder. This was placed in a beaker and heated to about 130C when the urea started to liquify. Ammonia evolved quite rapidly for about 10-15 minutes. What was left was a white solid crystalline mass which then turned brownish and liquified again as the temperature rose. No temperature reading but it was quite hot, SWIM is assuming above 315C since that's the mp of KOCN. This was poured into a large shallow pyrex dish where it solidified into a white disc. The disc was brittle and ceramic like with a weight of 15.8g and was soluble in water. SWIM will do some more tests later to make sure this really is KOCN. If it is then yields sucked (SWIM hasn't even purified it yet). Oh well.

IndoleAmine · Dreamreader Deluxe

Considering the price of reagents, ease of procedure and simpicity of workup Laughing

, I would say it is good enough for our purposes..

(provided it is really rather pure KOCN; how did analysis go so far?)

i_a

Bluechip · Fri Apr 01, 2005 6:46 pm

Astrum,follow the tips in this patent and you cant go wrong.[url]

Potassium Cyanate from Urea and KOH:

http://v3.espacenet.com/textdes?DB=EPODOC&IDX=US3935300&F=0&QPN=US3935300[/url]

This is the easiest prep Ive ever done.Yeild was always as expected 90%plus.

P.s, You implied in the PPA thread that the Akabori had been completed with success.Did you mean that you had completed it with good results,or where you just gleening from the numerous hive/wetdreams threads,that someone had done it?
iF YOU HAVE,PLEASE SHAre your experiences.

Oh,and I wouldnt mess around much with trying to purify or analyse your cyanate.If your reagents are fairly clean and your ratios are about right,just go ahead and use the stuff.Works every time from this end,so they tell me.

Cheers,
ballz

ergoamide · Mon Aug 22, 2005 2:39 pm

Can one use NaOCN for this rxn or does it have to be KOCN. I say this only because in SWIM's place of residence it is a bit hard to find any KOH or K2CO3 but NaOH is of course everywhere. Swim doesn't mean ot be ignorant if this has been disscussed before but he couldnt find anything about it on here or the Hive files form what he looked at.

nooneinparticular · Tue Aug 23, 2005 5:15 am

Yes, it can bee used with no consequences.

Just remember to account for molar weights.

ergoamide · Wed Aug 24, 2005 1:45 pm

I went and worked ot the gram ratio for sing NaOCN and decided to post them to save others the time if they wanted.
It's 5g PPA.HCl to 1.8g NaOCN so yoU Use less cyanate Using Na.