Hive Methods Discourse

	Main Index Search Register Login Who's Online FAQ Links
	Main Index Search Register Login Who's Online FAQ Links

	2 Online, 0 Active		You are not logged in

This is a historical archiveThe forum is read-only. Private information has been removed. It is not possible to login.

	Methods Discourse

All 14 posts Subject: Synthesis of 4-bromo-2,5-dimethoxy-PPA Please login to post Down

Bandil
(you can always take some more)
09-20-03 20:58
No 460135
      Synthesis of 4-bromo-2,5-dimethoxy-PPA
(Rated as: excellent)

Synthesis of 4-bromo-2,5-dimethoxy-(phenyl-2-aminopropan-1-ol)

Starting material was 2,5-dimethoxybenzaldehyde.

Bromination:
2,5-dimethoxybenzaldehyde, was dissolved in a minimal amount of GAA, and a solution of chilled bromine in GAA, was added in one portion. This beaker was stirred at room temperature for 24 hours. After this period it was poured into ice water and immediately formed brown/red crystals. These where filtered and recrystallized twice from acetonitrile, to yield 4-bromo-2,5-dimethoxybenzaldehyde(as slightly brownish crystals) in slightly less than 60% yield.

Bromo-2,5-dimethoxybenzaldehyde

Henry rxn:
7 g's of 4-bromo-2,5-dimethoxybenzaldehyde(245 g/moles) which is 0,0286 moles, was put in an beaker and 150 mL's ice cold methanol(-10 degrees) was added. 70% or so dissolved. In another RBF a 1,1 molar equalivent of nitroethane was mixed with a 1 molar equalivent of triethylamine. This was also cooled to -10 degrees and mixed with the contents of the other beaker. This was stirred in an ice/salt bath for two hours, while the temperature remained sub zero. No noticable change in color was noted. The solution was allowed to return to room temperature over one hour(this was probably a mistake as, according to Indian Journal of Chemistry, Section B: Organic Chemistry (2001), 40B(1), 75-77., there will occur racemisation of the stereoisomers with increased temperature, when the catalyst isn't quenched with an acid). After this period, there was added a slow stream of GAA untill the solution was slightly acidic. The solvent was stripped under vacuum and the remaining red oil, was dissolved in 40 mL's of chloroform and washed twice with 50 mL's of water and once with brine. The choloform was stripped leaving a yellowish oil.

For the next trial of this reaction, it's probably a good idea just to use some excess nitroethane and skip on the alcoholic solvent, as it takes huge amounts to get everything in, and it seems that the reaction will run anyway.

4-bromo-2,5-dimethoxy-(phenylnitropropanol)

Reduction:
As it wasn't possible to crystallize the oil, it was used as it was. Theoretically there could be 9 grammes of the nitroalcohol(mw=306 g/mole), so this was used for the reduction. All of the nitroalcohol was dissolved in 30 mL's of methanol and placed in a RBF and fitted with a reflux condensor. The solution was quite reddish. 3 grammes of Zinc was stirred in 5% hydrochloric acid for two minutes, and then filtered, washed twice with water and once with acetone. This was put in the methanol/nitroalcohol solution and stirred. 16 mL's of 85% formic acid(the commercial version), was added in 1 mL's portions. The reaction was VERY vigorous, and required external cooling not to shoot up through the condensor. After the first 5 mL's was added, the reaction was more smooth, and more could be added. After 10 minutes the whole lot had been added. The mixture was stirred for 15 minutes, untill it returned to room temperature(without cooling). This was filtered to remove the remaining zinc and various salts. The mixture was now only slightly tinted yellow. The remaining solvent was removed under vacuum to give a yellowish oil.

Question for the people: Is formic acid a strong enough acid, to cause dehydration of the alcohol? If so, ammonium formate is probably a more wise choice!

4-bromo-2,5-dimethoxy-(phenyl-2-aminopropan-1-ol)

Workup
The workup will be performed soon, but nothing seems to indicate that anything went wrong. Hopefully the tertiary amine catalyst and the low reaction temperature used in the henry reaction will give a high yield of the desired stereoisomer, which can be used to make the aminorex analogue. Once complete, that will be written up aswell. The aminoalcohol is also usefull for preparing the Cat analogue of DOB, which also could be interesting to test.

More to come! cool

Have a nice weekend!

Regards
Bandil

You can always take some more!

pHarmacist
(pHantasticant)
09-20-03 21:55
No 460142
User Picture       hehe

Holy crap, Barium has hacked Bandil's account.. Nice work Bandil wink , keep it coming!

http://www.bassdrive.com/BassDrive.m3u

Chimimanie
(Hive Bee)
09-20-03 21:59
No 460144
      Yeeehaaa!

DOB aminorex!

DO it Bandil! Then taste it and report back! laugh

Very Interesting project!

I am looking forward for more! wink

Btw, how do you know you had the good bromo benzaldehyde, ie 4 and not 6? This bromination appear to bee tricky as to reaction conditions to have the 4 prevail on the 6...

Good luck for the aminorex follow up! cool

pHarmacist
(pHantasticant)
09-20-03 22:03
No 460145
User Picture       Chimi

I wouldn't play around with bioassay of other halogens on aminorex but fluorine... Now come out on IRC.. wink

http://www.bassdrive.com/BassDrive.m3u

Bandil
(you can always take some more)
09-20-03 22:13
No 460147
      Regarding the 6- versus 4- position, there...

Regarding the 6- versus 4- position, there have been some discussion. It should be formed in a 4:1 ratio with regards to 4:6 position. Therefore the two recrystallizations where performed, in order to separate them as throughly as possible.

You can always take some more!

dr_mabuse
(Stranger)
09-20-03 23:32
No 460158
User Picture       subst. aminorex

Last weeks I've been pondering on synthing 2-amino-5-(4'-bromo-2',5'-dimethoxyphenyl)-oxazoline (2C-B aminorex, as SWIM doesn't have any nitroethane yet).

The only hidden danger I fear with aminorex analogues is pulmonary hypertension.

The drugs I took seem to light up my brain!   (Claude Rains, The Invisible Man)

Chimimanie
(Hive Bee)
09-21-03 01:03
No 460167
User Picture       2C-B pemoline

2C-B pemoline look interesting too, i would like taste some one day...

...still looking forward your bioassay on the aminorex bandil, hurry up boy! wink

(but do a careful titration of course)

Rhodium
(Chief Bee)
09-21-03 02:37
No 460173
User Picture       2,5-MeO-BA Bromination Regioselectivity
(Rated as: good read)

Bromination of 2,5-dimethoxybenzaldehyde in GAA gives 87% yield of the 4-bromo- and 5% of the 6-bromo isomer, the former of which is easily purified by recrystallization from ethanol:

Bromination of 2,5-Dimethoxybenzaldehyde
Org. Prep. Proc. Int. 23(4), 419-424 (1991) (https://www.rhodium.ws/chemistry/bromodimethoxybenzaldehyde.html)

A cold solution of 20.0 g (0.12 mol) of 2,5-dimethoxybenzaldehyde in glacial acetic acid (115 mL) was treated with 20.0 g of bromine in glacial acetic acid (60 mL). The solution was stirred at room temperature for 2-3 days and diluted with ice water. The yellow precipitate was collected by filtration and dried (28 g, 95%), mp. 118-126°C (lit. mp 125-126°C). Recrystallization from ethanol gave 15.20 g of 2, mp 132-133°C (lit. mp 132-133°C). Ethanol was removed from the mother liquor in vacuo and the residue was subjected to column chromatography (silica gel, benzene). The solid (10.4 g) collected in initial fractions was 4-bromo-2,5-dimethoxybenzaldehyde (2), total yield 25.6g (87%), mp 132-133°C. Subsequent fractions gave 1.5g (5%) of 6-bromo-2,5-dimethoxybenzaldehyde (3), mp 102-103°C (EtOH).

Bandil
(you can always take some more)
09-21-03 10:28
No 460217
      A question

I think my question on this method drowned in the writeup, so i'll take the liberty of posting it again:

Is formic acid a strong enough acid, to cause dehydration of the alcohol? Could it be a problem that a slight excess of the formic acid was used, thus forming some aminopropene or something like that?

Thanks!

Regards
Bandil

You can always take some more!

Barium
(Heavyweight Chempion(eer))
09-21-03 11:42
No 460226
      Formic acid

I doubt anything bad will happen when using formic acid like you did. Sice the acid is added to the mixture fo Zn and nitroalcohol it won't be any excess acid untill the end of the reaction. Great work by the way smile

The Unworthy

Rhodium
(Chief Bee)
09-21-03 16:51
No 460245
User Picture       Acid-catalyzed dehydration of PPA

Acid-catalyzed dehydration of a phenylpropanolamine does not stop at any 'aminopropene' stage, that intermediate immediately rearranges to the phenyl-2-propanone imine, which in the presence of water hydrolyzes to the free phenyl-2-propanone.

For details, see Phenyl-2-propanone from Ephedrine Derivatives (https://www.rhodium.ws/chemistry/phenylacetone.html#ephedrine).

As you can see, pretty vigorous reaction conditions are needed (the reaction also happens to a varying degree in the hydriodic acid reduction of (pseudo)ephedrine, lowering the yield of methamphetamine, and creating a veritable Zoo of byproducts from condensations of the formed P2P with both unreacted starting material and product, as well as with itself, forming various non-polar hydrocarbon dimers.

I would say that dehydration is more likely to occur with the nitro alcohol, forming the phenyl-2-nitropropene, which in turn reduces to unknown products.

SPISSHAK
(Hive Addict)
09-21-03 17:55
No 460248
      RE: acid catalysed dehydration of amino alcohols.

In the patent literature they say to use 80 mesh (activated I think) Zinc so that it reacts rather quickly with the acid, the acid is added dropwise (they even used H2SO4 and you know that acid will do some dehydrating, but the key was good stirring,adding the acid at the rate that it was consumed, and keeping the temp below 40 degress, the 80 mesh zinc just ensures enough surface area for a rapid reaction with the acid.

silenziox
(Stranger)
11-08-03 18:13
No 469653
      Could someone please show the structure of...

Could someone please show the structure of these babies swim wondered.. I've been trying to post this msg for couple of hours and now I just quickly typed those without "checking the spelling"..

Basically the idea is to ring substitute 4-mar with the properties of amphetamine version of 2c-g-5 (pihkal #30)

2-amino-4-methyl-5-phenyl-2-methoxy-2-(3,6-dimethoxy-4-(2-aminomethyl)benzonorbornane)oxazoline

2-methoxy-2-amino-4-methyl-5-phenyl-2-(3,6-dimethoxy-4-(2-aminomethyl)benzonorbornane)oxazoline

Any ideas of the properties? Duration? I think it could be either very toxic, very intoxicating or very hallucinogenic which will definately put one to a lunar levels for days cool

It's better overdose than lowerdose.

Rhodium
(Chief Bee)
11-08-03 20:11
No 469659
User Picture       Naive idea

I'd suppose that they would be inactive, as you cannot add structural features of two drugs and expect them to be a mixture of both.

	https://the-hive.archive.erowid.org	the-hive@erowid.org



Powdered by Chemical Revolution^® V. 5.05, Copyright 2018, Kanamits Information Services Associates Asia. All rights reserved.
Links Erowid Rhodium

	All 14 posts		Subject: Synthesis of 4-bromo-2,5-dimethoxy-PPA		Please login to post		Down


		Bandil (you can always take some more) 09-20-03 20:58 No 460135				Synthesis of 4-bromo-2,5-dimethoxy-PPA (Rated as: excellent)
						Synthesis of 4-bromo-2,5-dimethoxy-(phenyl-2-aminopropan-1-ol) Starting material was 2,5-dimethoxybenzaldehyde. Bromination: 2,5-dimethoxybenzaldehyde, was dissolved in a minimal amount of GAA, and a solution of chilled bromine in GAA, was added in one portion. This beaker was stirred at room temperature for 24 hours. After this period it was poured into ice water and immediately formed brown/red crystals. These where filtered and recrystallized twice from acetonitrile, to yield 4-bromo-2,5-dimethoxybenzaldehyde(as slightly brownish crystals) in slightly less than 60% yield. Bromo-2,5-dimethoxybenzaldehyde Henry rxn: 7 g's of 4-bromo-2,5-dimethoxybenzaldehyde(245 g/moles) which is 0,0286 moles, was put in an beaker and 150 mL's ice cold methanol(-10 degrees) was added. 70% or so dissolved. In another RBF a 1,1 molar equalivent of nitroethane was mixed with a 1 molar equalivent of triethylamine. This was also cooled to -10 degrees and mixed with the contents of the other beaker. This was stirred in an ice/salt bath for two hours, while the temperature remained sub zero. No noticable change in color was noted. The solution was allowed to return to room temperature over one hour(this was probably a mistake as, according to Indian Journal of Chemistry, Section B: Organic Chemistry (2001), 40B(1), 75-77., there will occur racemisation of the stereoisomers with increased temperature, when the catalyst isn't quenched with an acid). After this period, there was added a slow stream of GAA untill the solution was slightly acidic. The solvent was stripped under vacuum and the remaining red oil, was dissolved in 40 mL's of chloroform and washed twice with 50 mL's of water and once with brine. The choloform was stripped leaving a yellowish oil. For the next trial of this reaction, it's probably a good idea just to use some excess nitroethane and skip on the alcoholic solvent, as it takes huge amounts to get everything in, and it seems that the reaction will run anyway. 4-bromo-2,5-dimethoxy-(phenylnitropropanol) Reduction: As it wasn't possible to crystallize the oil, it was used as it was. Theoretically there could be 9 grammes of the nitroalcohol(mw=306 g/mole), so this was used for the reduction. All of the nitroalcohol was dissolved in 30 mL's of methanol and placed in a RBF and fitted with a reflux condensor. The solution was quite reddish. 3 grammes of Zinc was stirred in 5% hydrochloric acid for two minutes, and then filtered, washed twice with water and once with acetone. This was put in the methanol/nitroalcohol solution and stirred. 16 mL's of 85% formic acid(the commercial version), was added in 1 mL's portions. The reaction was VERY vigorous, and required external cooling not to shoot up through the condensor. After the first 5 mL's was added, the reaction was more smooth, and more could be added. After 10 minutes the whole lot had been added. The mixture was stirred for 15 minutes, untill it returned to room temperature(without cooling). This was filtered to remove the remaining zinc and various salts. The mixture was now only slightly tinted yellow. The remaining solvent was removed under vacuum to give a yellowish oil. Question for the people: Is formic acid a strong enough acid, to cause dehydration of the alcohol? If so, ammonium formate is probably a more wise choice! 4-bromo-2,5-dimethoxy-(phenyl-2-aminopropan-1-ol) Workup The workup will be performed soon, but nothing seems to indicate that anything went wrong. Hopefully the tertiary amine catalyst and the low reaction temperature used in the henry reaction will give a high yield of the desired stereoisomer, which can be used to make the aminorex analogue. Once complete, that will be written up aswell. The aminoalcohol is also usefull for preparing the Cat analogue of DOB, which also could be interesting to test. More to come! Have a nice weekend! Regards Bandil You can always take some more!



		pHarmacist (pHantasticant) 09-20-03 21:55 No 460142				hehe
						Holy crap, Barium has hacked Bandil's account.. Nice work Bandil , keep it coming! http://www.bassdrive.com/BassDrive.m3u



		Chimimanie (Hive Bee) 09-20-03 21:59 No 460144				Yeeehaaa!
						DOB aminorex! DO it Bandil! Then taste it and report back! Very Interesting project! I am looking forward for more! Btw, how do you know you had the good bromo benzaldehyde, ie 4 and not 6? This bromination appear to bee tricky as to reaction conditions to have the 4 prevail on the 6... Good luck for the aminorex follow up!



		pHarmacist (pHantasticant) 09-20-03 22:03 No 460145				Chimi
						I wouldn't play around with bioassay of other halogens on aminorex but fluorine... Now come out on IRC.. http://www.bassdrive.com/BassDrive.m3u



		Bandil (you can always take some more) 09-20-03 22:13 No 460147				Regarding the 6- versus 4- position, there...
						Regarding the 6- versus 4- position, there have been some discussion. It should be formed in a 4:1 ratio with regards to 4:6 position. Therefore the two recrystallizations where performed, in order to separate them as throughly as possible. You can always take some more!



		dr_mabuse (Stranger) 09-20-03 23:32 No 460158				subst. aminorex
						Last weeks I've been pondering on synthing 2-amino-5-(4'-bromo-2',5'-dimethoxyphenyl)-oxazoline (2C-B aminorex, as SWIM doesn't have any nitroethane yet). The only hidden danger I fear with aminorex analogues is pulmonary hypertension. The drugs I took seem to light up my brain! (Claude Rains, The Invisible Man)



		Chimimanie (Hive Bee) 09-21-03 01:03 No 460167				2C-B pemoline
						2C-B pemoline look interesting too, i would like taste some one day... ...still looking forward your bioassay on the aminorex bandil, hurry up boy! (but do a careful titration of course)



		Rhodium (Chief Bee) 09-21-03 02:37 No 460173				2,5-MeO-BA Bromination Regioselectivity (Rated as: good read)
						Bromination of 2,5-dimethoxybenzaldehyde in GAA gives 87% yield of the 4-bromo- and 5% of the 6-bromo isomer, the former of which is easily purified by recrystallization from ethanol: Bromination of 2,5-Dimethoxybenzaldehyde Org. Prep. Proc. Int. 23(4), 419-424 (1991) (https://www.rhodium.ws/chemistry/bromodimethoxybenzaldehyde.html) A cold solution of 20.0 g (0.12 mol) of 2,5-dimethoxybenzaldehyde in glacial acetic acid (115 mL) was treated with 20.0 g of bromine in glacial acetic acid (60 mL). The solution was stirred at room temperature for 2-3 days and diluted with ice water. The yellow precipitate was collected by filtration and dried (28 g, 95%), mp. 118-126°C (lit. mp 125-126°C). Recrystallization from ethanol gave 15.20 g of 2, mp 132-133°C (lit. mp 132-133°C). Ethanol was removed from the mother liquor in vacuo and the residue was subjected to column chromatography (silica gel, benzene). The solid (10.4 g) collected in initial fractions was 4-bromo-2,5-dimethoxybenzaldehyde (2), total yield 25.6g (87%), mp 132-133°C. Subsequent fractions gave 1.5g (5%) of 6-bromo-2,5-dimethoxybenzaldehyde (3), mp 102-103°C (EtOH).



		Bandil (you can always take some more) 09-21-03 10:28 No 460217				A question
						I think my question on this method drowned in the writeup, so i'll take the liberty of posting it again: Is formic acid a strong enough acid, to cause dehydration of the alcohol? Could it be a problem that a slight excess of the formic acid was used, thus forming some aminopropene or something like that? Thanks! Regards Bandil You can always take some more!



		Barium (Heavyweight Chempion(eer)) 09-21-03 11:42 No 460226				Formic acid
						I doubt anything bad will happen when using formic acid like you did. Sice the acid is added to the mixture fo Zn and nitroalcohol it won't be any excess acid untill the end of the reaction. Great work by the way The Unworthy



		Rhodium (Chief Bee) 09-21-03 16:51 No 460245				Acid-catalyzed dehydration of PPA
						Acid-catalyzed dehydration of a phenylpropanolamine does not stop at any 'aminopropene' stage, that intermediate immediately rearranges to the phenyl-2-propanone imine, which in the presence of water hydrolyzes to the free phenyl-2-propanone. For details, see Phenyl-2-propanone from Ephedrine Derivatives (https://www.rhodium.ws/chemistry/phenylacetone.html#ephedrine). As you can see, pretty vigorous reaction conditions are needed (the reaction also happens to a varying degree in the hydriodic acid reduction of (pseudo)ephedrine, lowering the yield of methamphetamine, and creating a veritable Zoo of byproducts from condensations of the formed P2P with both unreacted starting material and product, as well as with itself, forming various non-polar hydrocarbon dimers. I would say that dehydration is more likely to occur with the nitro alcohol, forming the phenyl-2-nitropropene, which in turn reduces to unknown products.



		SPISSHAK (Hive Addict) 09-21-03 17:55 No 460248				RE: acid catalysed dehydration of amino alcohols.
						In the patent literature they say to use 80 mesh (activated I think) Zinc so that it reacts rather quickly with the acid, the acid is added dropwise (they even used H2SO4 and you know that acid will do some dehydrating, but the key was good stirring,adding the acid at the rate that it was consumed, and keeping the temp below 40 degress, the 80 mesh zinc just ensures enough surface area for a rapid reaction with the acid.



		silenziox (Stranger) 11-08-03 18:13 No 469653				Could someone please show the structure of...
						Could someone please show the structure of these babies swim wondered.. I've been trying to post this msg for couple of hours and now I just quickly typed those without "checking the spelling".. Basically the idea is to ring substitute 4-mar with the properties of amphetamine version of 2c-g-5 (pihkal #30) 2-amino-4-methyl-5-phenyl-2-methoxy-2-(3,6-dimethoxy-4-(2-aminomethyl)benzonorbornane)oxazoline 2-methoxy-2-amino-4-methyl-5-phenyl-2-(3,6-dimethoxy-4-(2-aminomethyl)benzonorbornane)oxazoline Any ideas of the properties? Duration? I think it could be either very toxic, very intoxicating or very hallucinogenic which will definately put one to a lunar levels for days It's better overdose than lowerdose.



		Rhodium (Chief Bee) 11-08-03 20:11 No 469659				Naive idea
						I'd suppose that they would be inactive, as you cannot add structural features of two drugs and expect them to be a mixture of both.

All 14 posts	End of thread	Top