dormouse (Member)
04-23-00 05:35
No 108766
      Synthesis of 4-bromo-2,5-dimethoxyphenylpiperazine -Rhodium  Bookmark   


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Author  Topic:   Synthesis of 4-bromo-2,5-dimethoxyphenylpiperazine 
Rhodium
Administrator   posted 07-29-99 08:25 AM          
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1-(4-Bromo-2,5-dimethoxyphenyl)-piperazine is a novel phenethylamine analog with 1/10 the potency of DOB, and 1-(4-Methyl-2,5-dimethoxyphenyl)-piperazine of slightly lower activity. Presumably, most phenethylamine entheogens can be made into phenylpiperazine analogs, and if so, there will be hundreds of new entheogens to be synthesized and bioassayed.

Preparation of phenylpiperazines from the corresponding aniline
Reference: J. Med. Chem. 29, 630 (1986)

1-(2,5-Dimethoxyphenyl)-piperazine Dihydrochloride

A mixture of bis(2-chloroethyl)amine hydrochloride (23.3g, 131 mmol), anhydrous K2CO3 (18g), freshly distilled 2,5-dimethoxyaniline (20.0g, 131 mmol) and diglyme (75 mL) was heated at reflux for 48 h, allowed to cool to room temperature, and then poured into water (200 mL). The aqueous mixture was made basic (about pH 12) by the addition of a saturated KOH solution and was extracted with ethyl acetate (3x200mL). The combined organic portions was washed with water (3x200mL), dried over MgSO4 and evaporated to dryness under reduced pressure to yield a dark oil.

Vacuum distillation afforded 18 grams (62%) of the amine as a light-yellow liquid, bp 142-146C at 0.18 mmHg. A saturated soln of HCl gas in anhydrous diethyl ether was added to a solution of the freebase in a small amount of 100% ethanol (can use methanol) to give the title compound, mp 218-220C after recrystallization from 100% ethanol.

1-(4-Bromo-2,5-dimethoxyphenyl)-piperazine Dihydrobromide

A solution of Br2 (3.2g, 20mmol)in glacial acetic acid (20 mL) was added in a dropwise manner to a solution of 1-(2,5-Dimethoxyphenyl)-piperazine freebase (4.0g, 20 mmol) in 48% HBr (4 mL) and glacial acetic acid (5 mL) at 0C, and after the addition was complete, the solution was stirred at room temperature for another 4 h. The solvent was removed under reduced pressure to afford a white solid material (mp 220-224C after recrystallization from 100% ethanol).

This is the hydrobromide salt. Conversion of it to the hydrochloride is wasteful and may not be necessary. But if wanted, here goes:

1-(4-Bromo-2,5-dimethoxyphenyl)-piperazine Dihydrochloride

2 grams of the above compound was dissolved in 10 mL H2O; the soln was made basic (to ca pH 9) with 10% aqueous NaOH and extracted with ethyl acetate (3x50mL), the combined organic portion was dried over MgSO4 and evaporated under reduced pressure to afford a dark oil. The oil can be distilled (optional step) with some difficulties, bp 72-75C at 0.08 mmHg. The oil is then dissolved in 100% ethanol and dry HCl gas is bubbled through the solution until salt formation ceases. Recrystallization from 100% ethanol gave 0.3 grams of the title compound as small white crystals, mp 203-205C (dec).


 
Paranoid
unregistered   posted 07-29-99 04:02 PM           
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Rhodium,
Have these compounds been bioassayed in humans yet, and if so, what were their subjective comments?

Is a piperazine the name of a substituent that has 5 carbons and one nitrogen in one six-member ring? If so, is the #1 position at the nitrogen or is it at one of the carbons adjacent to the nitrogen?


Paranoid
unregistered   posted 07-29-99 04:23 PM           
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Rhodium,
Sorry for asking such a lazy question.

I have now read that piperazine is a saturated hydrocarbon, six-membered heterocylic ring with 4 carbons and 2 nitrogens. One nitrogen is at position #1, and the other is at position #4, directly across from its twin.

But now I wonder how 1-(4-bromo-2,5-dimethoxyphenyl)-piperazine could be a phenethylamine if there is a nirogen attached directly to the phenyl ring at the phenyl ring's #1 position. Is the piperazine substituent attached to the benzene ring by one of its nitrogens or by one of its carbons?


Rhodium
Administrator   posted 07-29-99 07:08 PM          
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Ok, its not really a PEA analog, it is rather "structurally similar". In animal studies it shows 1/10 the potency of DOB, which 2C-B also does, and it is too structurally similar to DOB.
I do not know of any human experimentation with this compound, feel free to become the first known


Rhenium
Member   posted 07-30-99 04:21 AM          
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Rhodium : Ah ha! A very interesting paper. I was wondering what I was going to do with that kilo of 2,5-dimethoxy aniline which is currently acting as a doorstop.
Questions : Is the statement of 1/10 the potency of DOB from the paper? (i.e. ~20-30 mg)
Is this a Nichols paper? I can't get a copy for a few days.
Yields?

If this material is active, it could really revolutionize the are, no LAH required would be a big step forward.
All I need to do is find a "guinea pig" with a normal physiology to test it on... *evil grin*

Rhenium


Rhodium
Administrator   posted 07-30-99 08:38 AM          
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No, it's a Richard A. Glennon paper.
It describes the above compound to have an ED50 of 4.08 mg/kg in an experiment where DOM has a value of 0.44 mg/kg. The 4-methyl-2,5-dimethoxy compound has an ED50 of 6.23 mg/kg.

Obviously, one should only note the relative potency between the compounds, not the absolute mg/kg values - otherwise an effective dose of DOM would be ~30mg for an acverage human, and I feel that would be a bit strong.

(In my earlier posts I referred to DOB, which was incorrect.)


rev drone
Member   posted 07-31-99 07:43 PM          
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Say, what about the 2-arylpiperazine family of compounds? Anybody hear anything interesting about these phenethylamines?
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-the good reverend drone


 
Rhodium
Administrator   posted 08-01-99 07:57 AM          
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2-arylpiperazines? Never heard of them. Any refs?
 
psychokitty
Member   posted 08-03-99 05:41 PM          
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Beware of extrapolating information from rat studies to that of actual human experience. Dal Cason's fucking rats indicated that dimethylcathinone was equipotent to cathinone, but I can ASSURE you that the experience of taking one from the other is far from the same. Like the contrast between day and night. . . . Well, not THAT big a contrast, but you get the point.
--PK


Rhodium
Administrator   posted 08-04-99 05:43 PM          
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Yes, but until someone finally synthesizes and tastes this compound, we will never know if it's good or not. Just because dimethylcathinone sucked, that doesn't mean this compound will, just that it may.
 
Beagle
Member   posted 08-12-99 10:05 AM          
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Being skeptical of the relationship of rat studies to human effects is wise. Note that old fasioned behavioral assays intended to predict stimulant activity by observation of increased locomotion are unreliable. However, I believe that the newer stimulus generalization assays used by Glennon, when coupled with 5-HT2 receptor binding data, will prove to be very reliable.
Thus, I think that these compounds will be most likely active in humans.

There are too many variables in a locomotor stimulation test to be reliable. This assay has overpredicted the stimulant activity of a number of compounds. Also, since Dal works for the DEA, his tests on unknown compounds for abuse potential are skewed towards positive results.


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