3,4-Dimethoxy- -phenethylamine

The reactivity of seven resin-bound thiophenol esters toward 3,4-dimethoxy-phenethylamine (42) was consistent with the trend seen in n-butylamine cleavage reactions i.e. benzimidazole > alkyl > aromatic. However, the rate constant for the same thiophenol esters with 3,4-dimefhoxyphenethylamine was decreased by two to three fold compared with that with n-butylamine. The rate constant of ben-... 

Dopamine may alternatively be formed from tyrosine via hydroxylation of L-dopa which is decarboxylated. However, inverse isotope dilution experiments to study the formation of dopamine and dopa have shown that this is probably a minor pathway in peyote (176). It has been shown that L-tyrosine is incorporated into alkaloids in peyote three times more efficiently than into protein (344). 4-Hydroxy-3-methoxyphenethylamine can be methylated to 3,4-dimethoxy-phenethylamine (homoveratrylamine), which may be viewed as a dead-end product in Scheme 2 (10, 203). Phenylalanine is probably not a precursor of the... 

SYNS DIMETHYOXYDOPAMINE 3,4-DIMETHOXY-PHENETHYLAMINE 3,4-DIMETHOXY-P-PHENETH-YLAMINE DIiMETHOXYPHENYL-ETHYLAMINE ... 

Related work not directly dealing with total synthesis of proaporphine, aporphine, or homoproaporphine alkaloids has appeared. A series of homopro-aporphine-type compounds (110) have been prepared, as shown in Scheme 9.12 7 Compound (106), readily prepared from 3,4-dimethoxy-/ -phenethylamine and the appropriate keto-acid derivative, was transformed by reduction and acetylation to (107). Acetylation effectively blocked any complications from the cyclohexane oxygen function during the subsequent Bischler-Napieralski cyclization. Consecutive reduction, alkylation, and hydrolysis gave the key intermediate (109) which was transformed into the tetracyclic spiro-system (110) by reaction with polyphosphate ester under strictly defined conditions. Other conditions and... 

Reagents i, ys -glucosidase ii, 3, 4-dimethoxy-phenethylamine/NaCNBH3 iii, Ac20/py iv, POCI3 v, NaBH4... 

Baltzly, R. Buck, J.S. Amines Related to 2,5-Dimethoxy-phenethylamine. I Journal of the American Chemical Society (1940) 62 161-164... 

One of the most intriguing aspects of the data presented in Shulgin Shulgin (1991) is the "magic of the 4-position". If we take 2,5 or 2,6 - dimethoxy phenethylamine or phenylisopropylamine, and play with the 4-position, we get a wide variety of compounds with distinct effects. One possible explanation of this data would be the following ... 

To the reduction mixture was then added 3.5 g of 5% palladium on carbon catalyst and the mixture was hydrogenated under a hydrogen pressure of 50 psi at room temperature for 12 hours. The catalyst was removed by filtration and the filtrate was evaporated to a small volume. The concentrated filtrate was dissolved in diethyl ether and the ethereal solution was saturated with anhydrous hydrogen chloride. The reduction product, 3,4-dimethoxy-N-[3-4-methoxyphenyl)-1 -methyl-n-propy 11 phenethylamine was precipitated as the hydrochloride salt. The salt was filtered and recrystallized from ethanol melting at about 147°C to 149°C. 

Phenylalanine derivatives, substituted either with 3,4,5-trimethoxy or 2,5-dimethoxy-4-methyl substituents did not show activity (46). Although these would yield potentially active phenethylamines if decarboxylated in vivo, neither is likely to be a substrate for decarboxylases in the CNS (62). Several additional side chain alkylated compounds are discussed in the next section as rigid analogs. 

Dimethoxy-4 methyl-B-phenethylamine. To a stirred suspension of 3.0 g (80 mmoles) of LiAlH4 in 50 ml of THF (tetra-hydro-furan) is added a solution of 4.4 g (18 mmoles) of the above nitrostyrene (or nitropropene) in 50 ml of THF. Reflux for one hour, then cool this mixture in ice, and treat with a mixture of H2O and THF to decompose the excess LAH. The resulting mixture is then filtered and the filter cake is extraaed with THF. The combined THF solution is evaporated in vacuo leaving 3.7 g of oily product. A solution of this oil in 25 ml of Et20 is... 

Several years later, thi s entire project was reinitiated, and the aldehyde was obtained as a yellow crystal, but again it was not pursued. At that time, the earlier try had been totally forgotten, and a brand new ALEPH- (or 2C-T-) number had been assigned i.e., 20. Thus, the corresponding phenethylamine (2,5-dimethoxy-4-(B-methallylthio)phenethylamine), had it ever been made, which it was not, would have been called either 2C-T-3 or 2C-T-20, and the amphetamine homologue would... 

The pseudo-psychedelics are the 2,4,6-trisubstituted counterparts of the 2,4,5-trisubstituted psychedelics. Almost all of the 2,5-dimethoxy-4-something-or-other compounds are active and interesting whether they be phenethylamines or... 

The lithiated dimethoxybenzene reaction with 2,2-dipyridyl disulfide produced 2,5-dimethoxyphenyl 2-pyridyl sulfide which distilled at 135-150 °C at 0.4 mm/Hg and could be recrystallized from cyclohexane containing 2% EtOH to give aproduct thatmelted at 66-67.5 °C. Anal. (CnHnNO,S) C,H. This would have produced 2,5-dimethoxy-4-(2-pyridylthio)phenethylamine (2C-T-10) but it was never pursued. 

The same reaction with di-(4-bromophenyl) disulfide produced 2,5-dimethoxyphenyl 4-bromophenyl sulfide which distilled at 150-170 °C at0.5 mm/ Hg and could be recrystallized from MeOH to give a product that melted at 72-73 °C. Anal. (C14H 3Br02S) C,H. This was being directed towards 2,5-dimethoxy-4-(4-bromophenylthio)phenethylamine (2C-T-11) but it also was abandoned. 

And it has just occurred to me that there is yet another effort that is certainly worth making, inspired by the observation that 2,2-difluoroethyl iodide is commercially available and not prohibitively expensive. It, with 2,5-dimethoxy-thiophenol, and following the obvious steps to the aldehyde, the nitrostyrenc, and the final amine, would produce 2,5-dimethoxy-4-(2,2-difluoroethylthio)-phenethylamine hydrochloride. It lies exactly half way between the highly potent 2C-T-21 (the mono-fluoro), and the yet to be finished 2C-T-22 (the trifluoro). Let s be weird, and call it 2C-T-21.5. I will wager mucho that it will be very potent. 

EXTENSIONS AND COMMENTARY The rationale for exploring the beta-hydroxylated phenethylamines, especially those with oxygens at the biologically important 3- and 4-positions, has already been presented. Norepinephrine is a 6-hydroxylated phenethylamine with oxygens at these two ring positions. With DME, these are masked as two methyl ethers, and the initials DME stand for 3,4-dimethoxyphenyl-B-ethanolamine. This is an alternate name for 3,4-dimethoxy-B-hydroxyphenethylamine. 

A mescaline analogue with a bromo atom in place of the 4-methoxyl group is an analogue of mescaline in exactly the same way that DOB (a very potent amphetamine) is an analog of TMA-2 (the original trisubstituted amphetamine). This analogue, 3,5-dimethoxy-4-bromoamphetamine, has been found to be a most effective serotonin agonist, and it is a possibility that it could be a most potent phenethylamine. But, as of the present time, it has never been assayed in man. 

And I ll bet you dollars to doughnuts, that if one were to make the two-carbon analog 2,5-dimethoxy-4-(2-fluoroethyl)-phenethylamine, it would be every bit as much a treasure and ally as is 2C-B or 2C-I. In fact, I am sure enough about this prediction that I am willing to name the stuff 2C-EF. It will be easily made from 2C-B by the same reaction scheme that was used above for DOEF. And I will even guess that its activity level will be in the 20-30 milligram area. 

EXTENSIONS AND COMMENTARY These two excerpts give the color and complexity of IP. It has proven to be a completely fascinating phenethylamine. And, as with all the phenethylamines, there is an amphetamine that corresponds to it. This would be 3,5-dimethoxy-4-isopropoxyamphetamine, or 3C-IP. The preparation of it would require access through the O-isopropoxylation product with syringaldehyde, followed by nitrostyrene formation with nitroethane, followed by reduction probably with lithium aluminum hydride. It has not been synthesized, as far as I know, and so it has probably not been evaluated in man. What would be the active level It would probably be more potent than IP, but I would guess not by... 

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