Preliminary synthesis of 4-bromo-2,5-dimethoxy-(4-methylaminorex)Practical workThe mixture resulting from the reduction described in
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(Bandil: "Synthesis of 4-bromo-2,5-dimethoxy-PPA", Methods Discourse), was suspended in chloroform and aqueous sodium hydroxide was added. The yellow oil dissolved immediately in the chloroform. The basic mixture was washed with water twice. The chloroform was stripped under vacuum and the remaining yellowish oil, suspended in acidic water. After some stirring, the whole mess turned into white crystals, which where totally insoluble in water. This was taken as a good sign, as the hydrochloride of 2CB does the same thing. A small amount was tested with marquis which turned neon green within seconds; another good sign!
At this point it's pretty obvious that it's the right material, as it's behaviour is rather as is should be. However, it's a problem that it's insoluble in water, as the cyanate reaction will run in this.
The crystal/water slurry was brought up to a total volume of 16 mL's and then 2.0 g's of KOCN was added in one portion. The mixture was brought to reflux. As the temperature rose, the white crystals dissolved, but a brownish oil precipitated. The oil remained throughout the reaction. This has probably been the n-carbamoyl product. It's not a suprising fact that it was insoluble as the PPA version of this compound is only soluble in hot water, and this substituted version seems to be rather insoluble in most things.
After two hours, the remaining cyanate was destroyed with a litte HCl. After bubbling ceased 4½ g's of 30% HCl was mixed with 15 mL's of water, and added in one portion. The brown oil dissolved somewhat over one hour, but not much.
At this point IPA was added till the oil went into the solution. It took about the same amount as was in the flask before(40 mL's). The solution took on a brown tan as it dissolved. As the solution was more dilute than usual, the reaction was left at reflux during the night... and now here we are
Partial conclusion:It is a problem that the compound is so insoluble. It really makes it hard to work with. 50:50 iPrOH:water might be a good idea for future experiments in both of the reactions. This bee is however somewhat optimistic about the reactions run. The aminoalcohol is relativily easy to make, which will make the forthcoming experiments with the CAT analogues easy to work with.
QuestionsI was a bit afraid that the IPA might react with the carbamoyl product, just like it reacts intramolecular with the OH group. But there where really no other options at that point.
Do you think that IPA in the solution is ok, or will it ruin everything?Assuming that the IPA doesn't ruin the reaction, the workup needs some carefull thoughts. I was thinking of the following scheme for workup:
1: Evaporate the IPA under reduced pressure, so only water/product/crap remains.
2: Add carbonate to basify and extract with chloroform.
3: Wash the chloroform with water and brine.
4: Dry the chloroform.
5: Evaporate the chloroform extractions under reduced pressure to leave the freebase.
6: Maybe test it with marqius to check for conversion? Aminorex compounds tend not to give reactions with this.
Any other ideas, folks?
Have a nice weekend!Regards
Bandil
