This is a standard reductive amination possible by standard methods as so long as the benzylic halogen is uneffected.

Thats untrue. This logic is very common and the result of Amphetamine chemistry being the #1 way people learn neurochemistry. PSE does not cross because of the hydroxyl but take Morphine as a prime example... two highly exposed hydroxyls and no problems.

I also thought about this compound. I tried severaly derivates, but not exactly this one.

In-situ imine formation with your amine and ~1,2eq of your aldehyde in dry MeOH (for example 100mls for 3g substrate, may take several hours to form the imine completly. You can check progress with TLC by part. reduction with NaBH4/MeOH in a test-tube and an eluent made of DCM and petrol ether 50:50 staurated with NH3) and reduction with excess NaBH4 should work. Add dest. water to stop reaction and remove most of the MeOH under reduced pressure.

Add some aq. NaOH and extract with DCM to get freebase. Dissolve in with HCl (gas) sat. IPA and evaporate to get the HCl salt. Usual A/B extraction does not work (will cause very low yields of about 10%).

Recr. can be done from waterfree EtOH.

Works with 2-MeO-Benzaldehyde and 2-OH-Benzalydehyde at least in >70% yields after recr..
Use only very pure amines and dry MeOH... otherwise you will get a sharp drop in yield.

Another way it to go via the benzoic acid, the amide and reduction with LAH or NaBH4/H2SO4 in THF. Yields are also very nice (in the 90% range in thelast sept). But takes longer.


Tell us if you find an interesting conpound. I enjoyed the 2-MeOs and the 2-OHs very much. The are very very active. Completly different to tbeir 2C counterparts. Much harder, violent and more euphoric. Very strong visuals. Veeery potent. Be careful! The N-Benzyl without further substitution are also active but you need 10-20mgs for the same effects of 500µgs of the 2-MeO or 2-OH stuff.

N-Benzyl Tryptamines should be also interesting.

In Theoretical study of the interaction of agonists with the 5-HT2A receptor by Maria H.Silva, N-benzyl tryptamines are claimed to have very potential effects of the 5-HT2A receptors.
Could be interesting to make a compound and try it out.

it would be practical to just buy the phenylethylamine and reductively aminate it with anisyl aldehyde.
yeilds are good 87% or so.
considering the potency of the stuff it would be logical to buy 2-CI for 125 bucks a gram for example and just do the one reaction.
it retails for between 4 and 10 grand a gram.
LSD prices.
also i'm curious about the n-benzyl-2-methoxyderivative of 5 methoxy tryptamine?
has anyone any pharmacological data on this?
i know it is a potent 5HTa agonist.
i was just wondering how potent it is and it's qualitative effects.
it looks like the closest phamacophore of lsd of all of these compounds and access to 5-methoxy tryptamine is easyly avalialble from melatonin

this is exemplary of how it could be done:


Method 7 (stepwise reductive alkylation)

In a baked dry flask (150 °C, 72 h) 0.35 g (1.84 mmol) 5-Methoxytryptamine under N2-atmosphere in 25 mL absolute MeOH is dissolved. A solution of 0.20 g (1.88 mmol) benzaldehyde in 1.0 mL absolute MeOH, are added at room temperature via syringe within 30 min dropwise and the Reaction solution is stirred at room temperature until the benzaldehyde has completely finished reacting(1.5 h).The DC inspection still shows unreacted 5-Methoxytryptamine, a few drops of the Benzaldehyde are added once again and stirred at room temperature until a quantitative reaction revenue is reached.  The Imine formed in situ is reduced by addition of 0.21 g (5.52 mmol) Sodium Borohydride(NaBH4).  After 1 h the reaction is terminated by carefully adding 10 mL water, MeOH is removed on a rotary evaporator, the residue is basified with NaOH (c = 3 mol ? L-1) (pH = 11) and extracted with CH2Cl2 (5 ×
30 mL). The combined CH2Cl2 phases are diluted with water (3 × 20 mL) and sat. NaCl
Sol (1 × 30 mL), dried over MgSO4, filtered and concentrated under vacuum. The isolated colorless solid is taken up in CH2Cl2 and cleaned via rotation planar chromatography (FM: CH2Cl2 + PE = 6 + 4, NH3-Atm.).

[2-(2,5-Dimethoxy-4-iodophenyl)ethyl]-(2-methoxybenzyl)amine (236)

The synthesis takes place via a gradual reductive alkylation analogous to Method 7  (Abschn. 5.3.2, P. 233) with 0.23 g (0.75 mmol) of the primary Amine 42 and 0.12 g  (0.88 mmol) 2-Methoxybenzaldehyde in 20 mL absolute MeOH. After 5 h again a few drops  of Aldehyde admitted, stirred for 12 h and reduced with 0.28 g (7.5 mmol)  NaBH4. The resulting orange oil (0.45 g) will be dissolved in a little CH2Cl2 and then 45g of silica gel using flash chromatography.(FM:  CHCl3 + MeOH (NH3) = 98 + 2).

Yield:  0.25g (0.59mmol) colorless oil (79% d. Th)
C18H22INO3 (Mr= 427.27) free Base


Crystalization as Hydrochloride:

A part of the free Base (0.20 g, 0.47 mmol) is dissolved in a little absolute Et2O  and under stirring a solution of 1 mL i-PrOH/HCl (c ? 5 - 6 mol * L-1) in 10 mL absolute  Et2O is added dropwise. The Reaction solution, is stored for 48 h at -18 °C, the  colorless solid is centrifuged, washed with absolute Et2O and dried for 8 h in high  vacuum (10-2 Torr, room temperature).

Yield:  0.20g (0.43mmol) colorless solid (92% d. Th)
DC:   CHCl3 + MeOH(NH3)= 98 + 2 (RF=0.20)
Fp:   166*C