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All 9 posts Subject: Preliminary work on 4-Br-2,5-Dimeth-(4-mar) Please login to post Down

Bandil
(you can always take some more)
09-26-03 20:07
No 461239
      Preliminary work on 4-Br-2,5-Dimeth-(4-mar)

Preliminary synthesis of 4-bromo-2,5-dimethoxy-(4-methylaminorex)

Practical work
The mixture resulting from the reduction described in Post 460135 (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.

Questions
I 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

I just love the smell of bromine in the morning!

Rhodium
(Chief Bee)
09-26-03 22:51
No 461261
User Picture       THF as co-solvent?

I'd say that THF would be a much better alternative as co-solvent, as it is both water-miscible and inert to the reaction conditions.

Bandil
(you can always take some more)
09-27-03 08:18
No 461316
      Ahhh, yes of course! Do you think that the...

Ahhh, yes of course! Do you think that the reaction mixture is worth extracting on, or is there a good chance, that the whole thing is ruined?

I just love the smell of bromine in the morning!

Barium
(Heavyweight Chempion(eer))
09-27-03 15:55
No 461347
      AA

Acetic acid might be another good option. The acetate is perhaps more soluble than the hydrochloride. Since excess HCl was present in the previous trial excess acetic acid should not hurt anything. Acetic acid is a damn good solvent.

Worthy

Rhodium
(Chief Bee)
09-27-03 16:01
No 461349
User Picture       worth working up?

I doesn't sound like you will get an impressive yield from that reaction, and I'd say it depends on your purifcation capabilities if it is worth working up. It sounds like you need to filter that brown product through some silica gel to have some hope of getting it to crystallize later.

Bandil
(you can always take some more)
09-29-03 12:37
No 461629
      Failure

We'll the final reaction mixture looked very ugly like the carbamoyl compound, after the IPA was stripped. It's very likely that nothing -good- happened...

The mixture will be dumped and the reaction will be retried with THF:water mixture.

Hopefully better news the next time i'll follow up on this thread!

I just love the smell of bromine in the morning!

Barium
(Heavyweight Chempion(eer))
09-29-03 13:30
No 461631
      THF

I very much doubt THF will increase the solubility of the HCl salt in water. But I guess we will find out soon enough.

Worthy

Bandil
(you can always take some more)
09-29-03 15:34
No 461640
      It isn't the HCl salt which should have the...

It isn't the HCl salt which should have the solubility increased, it's the carbamoyl compound. The THF ought to help increasing that. The IPA did that anyway...

I just love the smell of bromine in the morning!

Barium
(Heavyweight Chempion(eer))
09-29-03 15:52
No 461641
      Ooops

I guess I was speaking out of my ass then blush

Worthy

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	All 9 posts		Subject: Preliminary work on 4-Br-2,5-Dimeth-(4-mar)		Please login to post		Down


		Bandil (you can always take some more) 09-26-03 20:07 No 461239				Preliminary work on 4-Br-2,5-Dimeth-(4-mar)
						Preliminary synthesis of 4-bromo-2,5-dimethoxy-(4-methylaminorex) Practical work The mixture resulting from the reduction described in Post 460135 (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. Questions I 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 I just love the smell of bromine in the morning!



		Rhodium (Chief Bee) 09-26-03 22:51 No 461261				THF as co-solvent?
						I'd say that THF would be a much better alternative as co-solvent, as it is both water-miscible and inert to the reaction conditions.



		Bandil (you can always take some more) 09-27-03 08:18 No 461316				Ahhh, yes of course! Do you think that the...
						Ahhh, yes of course! Do you think that the reaction mixture is worth extracting on, or is there a good chance, that the whole thing is ruined? I just love the smell of bromine in the morning!



		Barium (Heavyweight Chempion(eer)) 09-27-03 15:55 No 461347				AA
						Acetic acid might be another good option. The acetate is perhaps more soluble than the hydrochloride. Since excess HCl was present in the previous trial excess acetic acid should not hurt anything. Acetic acid is a damn good solvent. Worthy



		Rhodium (Chief Bee) 09-27-03 16:01 No 461349				worth working up?
						I doesn't sound like you will get an impressive yield from that reaction, and I'd say it depends on your purifcation capabilities if it is worth working up. It sounds like you need to filter that brown product through some silica gel to have some hope of getting it to crystallize later.



		Bandil (you can always take some more) 09-29-03 12:37 No 461629				Failure
						We'll the final reaction mixture looked very ugly like the carbamoyl compound, after the IPA was stripped. It's very likely that nothing -good- happened... The mixture will be dumped and the reaction will be retried with THF:water mixture. Hopefully better news the next time i'll follow up on this thread! I just love the smell of bromine in the morning!



		Barium (Heavyweight Chempion(eer)) 09-29-03 13:30 No 461631				THF
						I very much doubt THF will increase the solubility of the HCl salt in water. But I guess we will find out soon enough. Worthy



		Bandil (you can always take some more) 09-29-03 15:34 No 461640				It isn't the HCl salt which should have the...
						It isn't the HCl salt which should have the solubility increased, it's the carbamoyl compound. The THF ought to help increasing that. The IPA did that anyway... I just love the smell of bromine in the morning!



		Barium (Heavyweight Chempion(eer)) 09-29-03 15:52 No 461641				Ooops
						I guess I was speaking out of my ass then Worthy

All 9 posts	End of thread	Top