C-POMA 2-chloro-4-propoxy-5-methoxyamphetamine hydrochloride

1-(2-chloro-5-methoxy-4-propoxyphenyl)propan-2-amine hydrochloride

CH3

OCH3

O

NH2

CH3

Cl

SYNTHESIS:

OCH3

OCH3

NH2

CH3O

CH3

OCH3

NH2

CH3

Cl

+ [Cl] / AcOH, AcOEt, H2O

C-POMA was prepared by chlorination of 1.0 g POMA hydrochloride in 5 ml 90% acetic acid and 3 ml ethyl acetate solution cooled in an ice bath. Other specific details about the reaction can not be disclosed yet for a certain reasons I would prefer not to explain. The crude hydrochloride of the product was found to be of low solubility in water and nearly insoluble in 3% HCl(aq). It was thus recrystallized from 3% HCl(aq), yielding tiny, needle-like crystalline product that was washed with three times 3 ml 3% HCl(aq) and air dried on a plate. There was obtained 0.6 g (53%) of the product: mp 173-174°C; IR (KBr disc) 2932, 1601, 1518, 1391, 1269, 1215, 1177, 1040, 836 cm-1. Free base 1H NMR (CDCl3) δ 1.03 (t, 3H, CH3), 1.13 (d, J = 6.3 Hz, 3H, CH3), 1.24 (broad, 2H, NH2), 1.79-1.92 (m, 2H, CH2), 2.54-2.80 (dq, 2H, CH2), 3.18-3.29 (m, 1H, CH), 3.84 (s, 3H, CH3O), 3.94 (t, 2H, CH2O), 6.71 (s, 1H, ArH), 6.86 (s, 1H, ArH). DOSAGE: 160 mg or more (threshold 30 - 45 mg) DURATION: 6 – 8 h SUBJECTIVE DESCRIPTIONS OF ACTIVITY: 80 mg (male; 80 kg): There started something roughly 1:10h after ingestion, but continued to be of low intensity even later on. It expresses as some sort of a tension in my head, a very slight jaw clenching and a strange calm. Nothing particularly interesting and the plateau level seamed to have lasted for 2 hours only. The activity is clearly perceptible, but it seams to be unlike POMA. I don’t particularly like it, but then again I can’t be sure since it is nearly not enough to perceive its character. At +7:30h there was no perceivable activity anymore.

160 mg (male; 80 kg): I drank the bitter and disgusting water solution. It begun 1h and 15 minutes later and at +2 hours I concluded it is going to be disappointment. The activity is clearly perceivable, slightly weaker than the same dose of POMA, but most importantly, it is qualitatively worse. I miss the energizing activity. Half an hour later I comfort my self by thinking that it is developing in something better, a bit more positive and not fully without value. But then again, it is nothing special either. Perhaps it has something to do with the bad weather and the fact that I have to stay home and study mathematics, certainly one of the most anxiety producing activities I know of. I ate two cheese toasts with great appetite. At +5 hours it is still active, but now I got used to it and could easily ignore it. An hour later I feel the only thing left is a tension in the head, almost bordering to a headache, but is more probably just some exhaustion. DISCUSSION: The interest in this compound was in evaluating the substitution on a position where, according to the SAR theory for the psychedelic phenylethylamines, should optimally reside an H-bond acceptor like a methoxy group. 4-propoxy-3-methoxyamphetamine (POMA) lacks such an H-bond acceptor on the ortho position (in relation to the isopropylamine group), but it is still active. A chlorine atom on its ortho position should not cause any noteworthy steric repulsion toward the putative H-bond donor on the receptor site and thus should be relatively well tolerated. Yet, chlorine is unable to interact with H-bonding due to the high electroinductive effect preventing lone electron pairs to be easily shared. POMA has a slightly lower molecular mass than C-POMA and thus the potency should ideally decrease just slightly if the chlorine would have absolutely no role whatsoever in binding and activity. However, the chlorine atom is, besides much larger and heavier that hydrogen, also highly electronegative, hydrophobic and has influence on metabolism of the compound. It would be expectable that the electronwithdrawal effect would not be beneficial since then the meta methoxy group would have slightly less electron density to contribute to the H-bond interaction once in the receptor site. The increased hydrophobicity might have some slight influence on the pharmacodinamics of the compound, especially in regard blood-brain barrier penetration. But nevertheless, the consequence of similar hydrogen to halogen substitution is not easily predictable and there is little known on such compounds. Shulgin mentions 2-bromo-4,5-dimethoxyphenylethylamine (6-BR-DMPEA)1 as having been tested by humans: “Apparently, the intravenous injection of 60 milligrams gave a rapid rush, with intense visual effects reported, largely yellow and black. Orally, there may be some activity at the 400 to 500 milligram area, but the reports described mainly sleep disturbance.” It is interesting that the compound possibly has an oral threshold activity while DMPEA itself gave no threshold activity even up to 1000 mg.2 Another such substitution was reported in Entheogen Review and was later debunked as a hoax. It claimed that 2,6-dichloromescaline is a potent psychedelic at 10 mg already. This was checked by Toad who found that 2,6-dichloromescaline has no activity bellow 75 mg. The 2-chloromescaline was tested up to 150 mg and was found psychoactive but “the experimenter involved was not overly impressed with the effects elicited, and said that he was not interested in exploring things any further”.3 The same person also reported that 2-bromomescaline was active at 130 mg and that to him “it elicited an enjoyable psychoactive state that reminded me of 2cb without the stimulating bzzz”. The only other compound of this type that I could find information on was a report by Tetraedr, a Hyperlab member, who prepared 2,4,5-trichloro-3,6-dimethoxyamphetamine 1 PIHKAL #20 2C-B: http://www.erowid.org/library/books_online/pihkal/pihkal020.shtml2 PIHKAL #60 DMPEA: http://www.erowid.org/library/books_online/pihkal/pihkal060.shtml3 Dichloromescaline: http://www.erowid.org/archive/rhodium/chemistry/dichloromescaline.html

(trichloro-2,5-DMA) when he mistakenly overchlorinated 2,5-DMA in acetic acid with elemental chlorine. He reported a product with an mp of about 203°C, identified the compound by 1H NMR and gave it the codename 3Cl-DOC. The internet forum4 where he posted the results is now dead but what he reported was: “Dosage - 5 mg ([the tester] said, 10 mg should be better). Increasing the action during 1,5 h. Duration - about 6h. This subsance very close to 2-CB, than to DOB. Light visuals, light euphoria. In conclusion, the Tester said, that he satysfied this substance and recommend it for next testers.” So even on DOC which has both favorable methoxy groups present, the chlorination of the remaining ortho and meta positions causes a significant drop in potency. Interestingly 3Cl-DOC is one of just a couple psychedelic compounds without any hydrogens on the aromatic ring that was ever tested by humans. To my subjective judgment, C-POMA seamed about 30 or 40% less potent than POMA by dosage (the intensity of the 160 mg trial was comparable to 100 mg POMA). However, the activity was qualitatively considerably inferior to POMA. I got the feeling there is nothing that would make it worth researching at higher doses, therefore 160 mg is for now also the maximum dose tested. The activity is not really worth much, the compound seams to be without character and this is also reflected by the descriptions of those who tried it. There simply is not much to say. The above description of the effects constantly refers to the slight differences of this compound versus its unchlorinated version POMA. This is done to compensate for the lack of specific and characteristic effects to be described. C-POMA is simply just a bad copy of what POMA is. Demonic

4 The former Synthetikal internet forum.

ppm (t1)1.02.03.04.05.06.0

0

500

1000

1500

2000

6.86

16.

715

3.96

03.

937

3.91

53.

842

3.29

03.

269

3.26

43.

250

3.24

83.

243

3.23

03.

224

3.22

23.

208

3.20

33.

182

2.80

12.

783

2.75

72.

738

2.61

32.

586

2.56

82.

542

1.91

41.

890

1.86

61.

842

1.81

91.

795

112

4

3.002.01

0.98

2.04

1.913.243.19

0.950.97

2.00

C-POMA free base 1H NMR (CDCl3)