A (mostly) kitchen friendly synthesis of 2c-b

[Swirly]

I am not sure if this merits its own thread, but outlined here is a common method for making 2c-b. Starting from the benzaldehyde and utilizing the NaBH4/ CuCl2 reduction+hydrogenation and finally bromination with N-Bromosuccinimide (NBS). A recent methodology with safer procedures and chems. But not the highest yielding nor maybe the best for large amounts.

A post in the style of Benignium's on SM:

Sciencemadness Discussion Board - A foray into phenethylamines of the Shulgin kind - Powered by XMB 1.9.11 (Debug Mode)

and others on The Vespiary. Inspiration from there.

Part 1: Synthesis of 2,5-DMNS (2,5-dimethoxynitrostyrene) from 2,5-DMB (2,5-dimethoxybenzaldehyde), scale of 230g / 1.4 mol+ (The Pretty Bit, Henry Reaction)

Chem info:
1 mol 2,5-DMB: 166.17 g/mol
1 mol 2,5-DMNS: 209.19 g/mol
1 mol nitromethane: 61.04 g/mol, density: 1.1371 g/cm^3
1 mol ethylenediamine: 60.1 g/mol, density: 0.90 g/cm^3
1 mol acetic acid: 60.052 g/mol, density of liquid form: 1.049 g/cm^3
Density of isopropyl alcohol: 0.786 g/cm3, boiling point: 82.6 °C
Density of methanol: 0.792 g/cm3, boiling point: 64.7 °C

1. Weigh out 232.348 g (1.398 mol) 2,5-DMB and place into a 4 L beaker with a 7x amount in mL from grams of 2,5-DMB of isopropyl alcohol (IPA). 1626 mL still does not dissolve the 2,5-DMB so I add about 226 mL more (So actually use an ˜8x amount). I use the cheapest IPA I could find. A 99% industrial grade one. You will need lots of IPA during the synthesis so grab 10 L+.

2. Prepare a 1.05 mol. eq. of nitromethane (NM) or 1.468 mol or 89.6g or 78.8 mL of NM and a 10% mol. eq. of ethylenediamine (ed) or 0.1398 mol or 8.402g or 9.335 mL of ed. Could be that I use less, as a drop or two of the ed spilled. Maybe 9.1 – 9.2 mL. Mix together in an appropriate container.
Note that a mixture of NM with 5% ed is a high explosive, but I believe that you need a strong shock to detonate it, handling either NM or ed gave me no trouble, but ed does fume.

3. Prepare a 0.9 mol eq. of glacial acetic acid (pure) (GAA) or 1.2582 mol or 75.557g or 72 mL. I am not certain of the exact amount of GAA to use. With the GAA you will create ethylenediammonium diacetate (EDDA) in situ or in the reaction mixture. EDDA is 1 mol of ed to 2 mol of GAA so we would need a minimum of 0.2796 mol of GAA. This is a great excess, so in theory one might be able to use less. Maybe with this excess, you could help dissolve the 2,5-DMB if yet undissolved.

4. Pour in the NM + ed mixture under stirring and light heating, a slight colour change should appear. A stronger yellow from the very pale yellow of dissolved 2,5-DMB.

5. Pour in the GAA and the mixture starts to turn orange quickly. Heat to 30 ℃ under medium stirring.

6. I let it spin for 1 hour with heating up to ˜55℃. I am not sure how much to heat, it seems that little is needed. I would certainly not heat above 65. Maybe even 30 is all that is needed.

7. Watch the colour change. When the colour was a darker orange, started changing to a red-orange even a burgundy red this is when I remove from heat and put it aside to return to room temp.

8. Crystals may or may not appear spontaneously. Watch closely, when they start appearing it is a wondrous sight! I would let it sit for a few hours and wait and see, maybe even set it in the fridge. Could be that crystals will appear only after a few hours. If you are impatient like me, you could dip in a glass rod into the reaction mixture, wait for the IPA to evaporate and you should have crystals stuck to the rod. Now dip the rod back in, and twirl it around, this should act as a seed crystal, and you should see crystals appear in the beaker. But I would wait for them to form on their own. I believe not rushing will create needles, which might lead to a cleaner product.

9. The beaker should be a mass of orange crystals. You need to clean, dry, and preferably preform a recrystallization on the formed 2,5-DMNS. But first I stuck the beaker into the freezer, maybe some more will fall out under cooling…

10. Next day I decide to wash the crop of 2,5-DMNS with a 40% sodium bisulfite solution first, then dH2O, then IPA on a büchner funnel under vacuum. The sodium bisulfite should create an adduct (addition product) with unreacted benzaldehyde. If unreacted benzaldehyde was in solution in the reaction mixture, the adduct should create a crystal mass insoluble in the reaction mixture. This does in fact occur, or appears to do so, and some white particulate fall to the bottom of the vacuum flask.

Next I clean with lots of cold water and then maybe IPA. This is a large amount so you might need to run the vacuum for some time. You will need a larger Büchner funnel, maybe even a 4000 mL+ one with a 2.5 L+ vacuum flask. Collect 479.1 g of a still wet orange fluffy monstrosity. Should have run under vacuum longer.

11. In all literature, it is written that a recrystallization of the 2,5-DMNS must be done, but next time I will not bother with this step. Dissolving such a large amount was impossible. I did not have enough methanol (MeOH) on hand, and it seems that one would need to use even more IPA. I did try to dissolve in a boiling IPA/MeOH mixture but had no luck. Consider skipping the recrystallization when dealing with these 200g+ amounts or have lots of MeOH on hand. At a minimum of 15 mL/g. 1.398 mol of 2,5-DMNS is 292g, take a 90% yield so I would first attempt a recrystallization with 3.95 L boiling MeOH. You could begin with 13 mL/g but in IPA such an amount will not fully dissolve the nitrostyrene.

So I settle for a semi-recrystallization. Partially dissolved mass, this also should help clean the product.

Dry under vacuum again, then fully dry under a fan. Yield is 225.764 g (1.079 mol) of ok-ish 2,5-DMNS that should be good enough to use in the next part. I think a 77.2% yield of the cleaned 2,5-DMNS is fair. Maybe some tweaks could be made, maybe you need to react longer, but this part is a success in my books. It is an easy reaction, you could do even larger amounts easily, and 2,5-DMB is not expensive. About 1g 2,5-DMB in, 1g 2,5-DMNS out, good enough.

One could try to react with 2-hydroxyethylammonium acetate (2-HEAA) which I used to prepare 3,4,5-TMNS. But I go with ethylenediamine for 2,5-DMB and ethanolamine for 3,4,5-TMB.

You could take a break at this point and store the 2,5-DMNS for a later date. It could be that 2,5-DMNS degrades so I would store it in a fridge, maybe even a freezer, and try to use it eventually. And as well, one can always react portions of the nitrostyrene in the next step.

IMPORTANT NOTE: 2,5-DMNS is some sort of irritant, and unless you want to be sneezing and with a runny nose all the time, feeling like you are sick, wear a mask AND gloves around it, even with smaller amounts. Seems that other nitrostyrenes as well cause this reaction, but with 2,5-DMNS is seems more severe. IT IS IRRITATING.This compound could be used as a common cold producing agent to mimic an illness but without the fever…

Link with more info about EDDA: https://www.erowid.org/archive/rhodium/chemistry/edda.html
Link with info about 2-HEAA: https://www.thevespiary.org/talk/index.php?topic=17911.50

 

[Swirly]

Part 2: A larger scale NaBH4/ CuCl2 reduction of 2,5-DMNS to 2,5-dimethoxyphenethylamine (2c-h) freebase and conversion to the oxalate salt. 200g/ 1 mol+ scale. (The Reaction, The Difficult Bit).​

Chem info:
1 mol 2,5-DMNS: 209.19 g/mol
1 mol 2c-h freebase: 181.232 g/mol, pKa: 9.6
1 mol 2c-h oxalate: 271.266 g/mol?
1 mol sodium borohydride (NaBH4): 37.83 g/mol
1 mol copper (II) chloride dihydrate (CuCl2): 170.48 g/mol
1 mol oxalic acid dihydrate: 126.065 g/mol

Preface: I suggest you try to do this part of the synthesis over one day. It might take a long time but you will have a stable salt form instead of an unfinished reaction sitting overnight, possibly discoloured in the morning.

1. For this reduction I used a 6 L three-neck flask, but in hindsight a 10 L one would have been better. One could react 300g in a 10 L flask. This time I went with the classic route but used a dH20 to IPA ratio of 1 to 1.5 instead of 1:2. There is a comment on thevespiary.org that even 1:1 is used for 2,5-DMNS. It can be a bit tricky to figure the correct quantity as the sodium borohydride needs to dissolve in water, but you want to use as little as possible to fit in your vessel, AND you have to take into account lots of potential evaporation during the reaction if you go with an open container.

Evaporation is a problem when the reaction really gets going, and I would suggest a properly working system and a controlled reflux with a water cooled condenser. For this run nothing was really working well, and the reaction did not go to plan, but still an ok yield was obtained. Of note as well is that the IPA really boils after addition of copper chloride, and the scent of rubbing alcohol can get very strong.

2. I used a 7.5x mol. eq. of NaBH4 as per literature. This amounts to 306.188 g. Although folks like to toy with this ratio as well. For example even here: https://chemistry.mdma.ch/index/nabh4.copper.reduction.html. (A 7.7 mol. eq. is used). I do not know which is best and whether to use all at once. I left out some for before the addition of copper. Could be that one might be able to use much less NaBH4 with another methodology, like the silica gel one.
End up using 280 g at first, and the rest I leave out. Decide to dissolve the NaBH4 in 1.1 L of dH2O + 1.65 L IPA (1:1.5). A total of 2.75 L or 12.18 mL/g to the 2,5-DMNS (225.764 g 2,5-DMNS we will react). Turns out this was not enough water in the end. Borate salts ended up crashing out post-reaction. Experiment with different amounts. Maybe try a 15 mL/g amount of dH2O+IPA.
My reasoning was to use as little as possible but still get the NaBH4 to dissolve. I forgot to take into account evaporation. https://www.chemister.ru/Databases/Chemdatabase/search-en.php has solubility info. It is written there that NaBH4 is soluble in:
water: 25 (0°C) water: 55 (25°C) water: 88.5 (60°C), water: reaction (100°C)
at g/100 g of solvent.
We will start at close to freezing and end up with close to 80°C, so take this data into account. We need to look now at the 25g/ 100 mL amount. At boiling, the sodium borohydride decomposes, aka it is “quenched”.

3. Before dropping the NaBH4 in the reaction vessel make sure to grind it up finely. It picks up water from the air and clumps together, so also make sure to keep it sealed from moisture if you can.

4. At this time prepare the CuCl2 as well. I used a 13% mol. eq. this time. Other sources write to use a 15% mol. eq. but I used less as I was scared of using so much. Could be that only a 10% amount is needed.
So 0.14027 mol or 23.913 g (this is of the dihydrate) dissolved in a minimum amount of 1:1.5 H2O:IPA. I ended up using about 47 mL H2O and 62.5 mL IPA to fully dissolve the copper metal into a dark green solution. Literature writes that it is 1150 g/ L soluble in water, that would require about 21 mL, but I ended up using much more. Maybe you will have luck dissolving in less. It is important to dissolve the copper chloride in a minimum amount of solvent as we shall soon see.
NOTE: Do not use a metal spoon to scoop up the copper chloride, use glass if you can. Will react, corrode it.

5. At this time you should have a lot of ice on hand as we will need to chill the reaction rather well. Have maybe 3 or 5 kg of ice. Just prepare everything now. I would suggest to work in a giant plastic tub in case of spills or to lay some plastic on the ground as shit is about to get wild!

6. Place your flask in a large bucket with plenty of crushed ice-salt-and cold water. Wait for the temperature to fall to maybe 4 °C. Have extra ice on hand to add as the reaction proceeds. I used a glass dish that barely fit the 6 L flask, was too small. Just submerge in a bucket.
7. Now that 280g of the NaBH4 has dissolved in the water + IPA, start adding in the 2,5-DMNS through a glass funnel on one of the necks of the flask, the other neck should have a thermometer, and the central one, with a manual stirrer that works well, and most importantly sealed well with an adapter that works. (was not the case for me, did not seal properly).
8. Add in about 5 spoonfuls of 2,5-DMNS at a time. During the first addition watch carefully that things do not boil over too much. Hydrogen gas really begins to be released, and the temperature rises as well. At this point I believe the orange nitrostyrene is reduced to 2,5-dimethoxynitroethane. Watch the thermometer so that nothing rises above 25°C. But maybe if it hits 30 °C it is not that big of a deal. Frequent changes of ice and cool water.

And also, what I forgot as well is to watch for the colour to disappear before every addition. Was impatient, should have had better cooling so did not wait for colour to go away. Milky white is what we are looking for.

Now a lot of hydrogen gas evolves during this reaction. I am not exactly certain of the dangers here, but just make sure you have no ignition sources around. I believe that a very specific concentration of hydrogen gas is needed to become dangerously flammable.

I was working with a faulty open system in a small flat, all the hydrogen and fumes were trapped in my apartment, but nothing exploded although in the next step sparks were formed.

9. The addition of 2,5-DMNS took 2 hours, with lots of foaming present. Yellow colour did not fully go away. Could be because I did not wait for colour to disappear with each portion.

10. Add the remaining NaBH4 and spin a few more minutes.

11. Next comes the second step of the reaction, hydrogenation catalyzed by CuCl2. It is a very reactive step, but many sources stress the importance of the addition of the copper in one go. To do this, and to avoid a volcano, you need to transfer your mixture into a large container with straight walls. The three-neck flask’s shape is such that it propels everything out through the necks when a large amount of gas is produced. Things spew everywhere. So pour into a 10 L or even better 20 L beaker. I suppose one could just use a bucket at this step. Set up you overhead stirring. Cover as much as you can with something but leave a hole to pour in the dissolved copper. Maybe some cardboard or foil. Now make sure you are not wearing fancy clothing and have googles on. The copper will ruin your clothes.

Say a prayer and pour directly into the vortex!

A big ass mushroom cloud of hydrogen is produced with an audible woosh.

Yeehaa now we cookin’!

The large beaker should have contained everything, but notice how far up the walls the copper travelled. You really need a container at least 4 times larger than the mixture. What happens as well is that the leading edge of the falling copper hits the IPA+water first, reacts, creates gas which propels the copper still to hit the surface away and out of the beaker. Small unreacted droplets are still a possibility. And to contain truly everything I would suggest working in a large tub.
The CuCl2 is transformed instantly into the black elemental copper nanoparticles which act as the catalyst. It is some sort of complicated process that bombards your molecule with hydrogen. You could opt instead to work in a more sane manner, and pour the CuCl2 at such a rate that it just reaches the top of the flask but does not boil over, with strong overhead stirring, and save yourself the work of pouring into another container. Yields may or may not suffer.

13. Set-up your 3-neck flask with a condenser piping cold water and prepare it for a reflux.
Pour the reaction mixture back into the 3-neck flask and begin stirring with an overhead stirrer. Be careful and watch what is going on, the stirring itself is enough to drive the reaction. And it could be that no heat is required. Apply only a small amount of heat when you are sure things are under control. Watch so that the reaction mixture does not go above 80°C, maybe 75. Literature states to reflux at 80°C for 30 minutes. But that is for gram amounts.

I was not able to set up my condenser or anything properly, tubing slipped off the aquarium pump. and had no heating as at one point the reaction boiled over and fried my mantle. There was even an electrical fire as the copper and IPA short-circuited my mantle. But it did not set off the hydrogen alight.

So I made do with violent stirring for an hour and a half, no heating, IPA boiling off into the room. A controlled reflux of 1 drop every two seconds is the proper way as I understand.

At some point you will see the reaction calm down and come to an end. Maybe only an hour of reflux is needed. And I suggest to not be as foolish as I was and to not do this scale without proper ventilation, or to do it outside.

14. Let the reaction cool a bit, but not all the way to room temp. Could do it even hot. You need to filter before borate salts crash out, so work quickly. I filter twice under vacuum with 180 mm medium speed qualitative filter paper. There is some difficulty filtering but the vacuum manages.

15. As everything cools, loads of shiny borate crystals appear, remember the solubility chart. I decide not to try to extract anything out of the bottom water layer as it is mostly crystal. Have difficulty in dealing with the borates. They would clog a separatory funnel. More water was needed in the reaction, but now it is too late. It would be best after filtering the copper to wait for the mixture to cool to room temp. and then simply decant the top IPA layer, use multiple beakers, more borates might appear, then maybe filtration is an option when little solids are left.
End up with about 1 L of a cloudy light-yellow IPA layer.

16. Now we need to dry this layer (rid it of water). Have a saturated solution of potassium carbonate on hand. To prepare the potassium carbonate brine I used about 500 to 600 g K2CO3 to water (you can decant if there is some undissolved K2CO3). Slightly more K2CO3 than water, a lot of potassium carbonate. In a 2 L separatory funnel wash twice with 200 mL of the brine. One might need a 5 L sep. funnel if starting with 300g+ amounts of 2,5-DMNS.

17. Wash with an excess of magnesium sulfate. The conc. K2CO3 wash should pick up most of the water, the magnesium sulfate will pick up what is left. K2CO3 might somehow help quench any NaBH4.

18. Gravity filter over a large sized medium filter paper folded into a lovely flute.

19. Before we can rest yet, let’s convert the freebase 2c-h dissolved in the IPA into a salt form. There are a few options here. You could try to make 2c-h hemisulfate. In that case, prepare a 10% solution of H2SO4 from pure 98% H2SO4 you distilled out of drain cleaner, and calculate for half the molar amount from a very liberal 80% yield from the 2,5-DMNS.

Again, you need to make the hemisulfate so only half the amount is needed (2 molecules of 2c-h attached to 1 H2SO4). Drop in carefully and watch for the pH to hit 6.6. (will explain why later). Pump off the IPA under vacuum.
One could also use a dry HCl gas rig. Or use IPA saturated with HCl. Hell, you could even drop in aq. HCl now, but boy would you get a mess when evaporating off first the IPA, and then the water. A green slime. But it is an option as well, the most basic route. You will might have a lot of slime product. Would need to clean that very thoroughly though.

That is what we are trying to avoid by making the oxalate or sulfate, any messy HCl. By changing salts, we will leave behind impurities. I have yet to try making the sulfate salt, but it might be superior to other forms. I believe it was Benignium on Science Madness who was advocating sulfate for many amines not just mescaline, so maybe try to make the sulfate.

But I end up using another popular route and make the oxalate salt. Again, calculate for a 80% yield, but use an excess. A 1.05x excess for some reason I chose. Anyway, end up using 0.90636 mol. of oxalic acid dihydrate. Dissolve to 20% in IPA or 114 g in 570 mL.

20. I heat up the oxalic acid/ IPA mixture to allow the oxalic acid to dissolve better. The beautiful clear golden IPA in the other beaker is really waiting for me now…

The IPA with the 2c-h freebase is at a 11.2 pH to begin with, I drop in the oxalic acid under magnetic stirring until a pH of 5.6 is reached. Use only half of the oxalic acid, so maybe the yield was less than 50%?

21. At some point everything will turn into this wheat paste. And it could be that a pH of 5.6 was too low. As beyond 6, addition loosened up the mixture, seemed to make it slightly more watery. Oxalic acid has difficulty dissolving whether in IPA or water.

Note on target pH:
From the Purification of Laboratory Chemicals (6th Edition):
The advantage of using pK values (instead of K values) is that theory (and practice) states that the pK values of[/I] ionisable substances are numerically equal to the pH of the solution at which the concentrations of ionised and neutral species are equal. For example acetic acid has a pK2 5 value of 4.76 at 25o in H2O; then at pH 4.76 the aqueous solution contains equal amounts of acetic acid [AcOH] and acetate anion [AcO-], i.e. [AcOH]/[AcO-] of 50/50. At pH 5.76 (pK + 1) the solution contains [AcOH]/[AcO-] of 10/90, at pH 6.76 (pK + 2) the solution contains [AcOH]/[AcO-] of 1/99 etc; conversely at pH 3.76 (pK - 1) the solution contains [AcOH]/[AcO-] of 90/10, and at pH 2.76 (pK - 2) the solution contains [AcOH]/[AcO-] of 99/1. One can readily appreciate the usefulness of pK value in purification procedures, e.g. as when purifying acetic acid. If acetic acid is placed in aqueous solution and the pH adjusted to 7.76 {[AcOH]/[AcO-] with a ratio of 0.1/99.9}, and extracted with say diethyl ether, neutral impurities will be extracted into diethyl ether leaving almost all the acetic acid in the form of AcO- in the aqueous solution. If then the pH of the solution is adjusted to 1.67 where[I] the acid is almost all in the form AcOH, almost all of it will be extracted into diethyl ether.
So if we use a target pH that is 3 lower than the substance’s pKa, almost all will form as the salt. And you wouldn’t over-acidify. The pKa of 2c-h is given as 9.6 found somewhere online. So a target pH of at least 7.6, probably 6.6 is optimal. Maybe I am wrong about this, please correct me.

22. Had to add some additional IPA to loosen up the sludge, and then I filter over vacuum. The weight of an almost dry 2c-h oxalate is 148.357 g. So 0.547 mol of 2c-h oxalate or a 50.7% yield of a very lightly yellow crème powder. Once completely dry and milled the oxalate is dusty and light, tends to fly everywhere. That is another disadvantage of the oxalate, it is rather dusty.

Conclusion: The idea behind the oxalate is to avoid the 2c-h sludge or dirty 2c-h HCl. The oxalate should leave behind many impurities, and should come out relatively clean. Also you can avoid working with 2c-h freebase directly for now. 2c-h freebase oil picks up CO2 from the air very quickly and can solidify into 2c-h carbonate rather easily.

The yield was not the best, but I did have a spill where maybe 10% was lost, and I could not manage a proper reflux. Maybe 65%+ is possible, and there is a post written of 2 mol+ amounts with 75%+ yield, could be possible with more practice. Maybe an optimized NaBH4/CuCl2 path exists I do not know about.

Looking around, there is something about the NaBH4 on silica gel that I might try next.
The info regarding P2NP reductions apply here, as well as info from here, and a 3,4,5-TMNS reaction.

But what I did notice, the difference between this and 3,4,5-TMNS with which I also have some practice, is that 2,5-DMNS is more reactive, more active cooling is needed to deal with those angry Trump’s fluff. I wonder how P2NP goes, it’s appearance is closer to 3,4,5-TMNS…

This reaction does not exactly scale perfectly. If you are after making a 1kg of 2c-b maybe a few 20 L are needed at once? Reduced amounts of IPA+water and NaBH4 would help as well. Here is where the silica gel or diatomaceous earth might help.

And I would look into catalytic hydrogenation if going for scale. BUT it seems that the catalysts needed have gotten to be prohibitively expensive. I just started reading up on this so can’t say for certain how large amounts of 2c-b get made.

A link to the classic beaker TEK, where one would pick up from after the NaBH4 addition:
https://www.erowid.org/archive/rhodium/chemistry/2cb.beaker.html

Link to silica gel advancements info:
https://www.thevespiary.org/talk/index.php?topic=20862.msg54225705#msg54225705

Well anyway, we should have a decent amount of 2c-h sulfate or oxalate at this point, ready for the next step. But first let’s get some rest. The 2c-h oxalate can be stored for a long time.

 

[Osmosis Vanderwaal]

I may start looking for precursors, there's a lack of this in the us it seems, and at $400/g or something seems pretty lucrative

 

[Swirly]

Ha that is too expensive for a gram. I made say 80 to 100€ is more fair. At least here in Europe. You can also make capsules with a capsule machine. Maybe then at $400/g...

 

[Osmosis Vanderwaal]

Some guy from Poland was trying pretty hard to sell me some, I think that is what he quoted me, close to that, but considering how low the doage is, per portion it was " reasonable", bearing in mind that I rarely try to get a discount on drugs.

 

[Swirly]

Ah yes, 410€/kg for 2,5-DMB from the final frontier; Poland. Go for it.

 

[Swirly]

I seem to have misunderstood the chat. Yeah, $400 for a g of 2c-b is too steep even considering the dosage.

 

[HIGGS BOSSON]

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[Swirly]

Part 3: Conversion and cleaning of salts. 2c-h oxalate to 2c-h HCl​

Chem info:
1 L of 36% hydrochloric acid contains: 11.64 mol of HCl
Density of dichloromethane (DCM): 1.3266 g/cm3, boiling point: 39.6 °C

Up to this point, notwithstanding the cooked mantle, everything had gone rather well. From here it could have been fatigue, but mistakes were made and yield dropped off numerous times. I would suggest to not go about this route and pick another one. Pointless work that kills yield.

At this point, there are a variety of options, one could try to brominate the 2c-h oxalate with N-Bromosuccinimide (NBS), but I would clean it first with ethyl acetate. There are some posts here and there about this on thevespiary. I for one have not tried it out, one would need to use a lot of GAA to dissolve the oxalate, and it might need to spin for a long time before anything occurs. Could be possible though. Might try that sometime.

One could as well at this point freebase the oxalate and pick it up with DCM, then attempt to brominate in DCM with NBS.

I went with a salt conversation, a conservative route that has given poor yields in the past, and gave a poor yield this time, so again, unless you have a better technique than I do, avoid this conversion, and avoid the oxalate for fuck’s sake.
Anyway here is how it went:

1. Dissolve 148g (0.547 mol) of 2c-h oxalate in 8x amount of water or 1.2 dH2O. Heat and mix with magnetic stirring. Once dissolved the pH is 4.420, we are aiming to basify to 12.6 (about +3 from pKa).

2. Carefully prepare a 500 mL sol. of 20% KOH (not NaOH it seems).

3. With careful addition of KOH a pH of 12.6 is reached, the freebase is floating around, but a sticky yellow slime appears as well. I decant the floaters and get rid of them, believe them to be impurities from the reaction. Transfer to a 2 L sep. funnel. Have 1.6 L of liquid. Will extract the freebase with 350, then 200, then 150 mL of DCM. Or so is the plan. Am left with a combined 780 mL of a yellowish DCM – 2c-h freebase mix. Now I will evaporate off the DCM, but distilling off is a better bet. DCM vapour is not the most fun to stick around. But my mantle is fried…

4. Now prepare a dilute sol. of HCl. Calculate the amount for 0.547 mol, so need a max 47 mL of 36% HCl. Dilute this to 250 mL.

5. Set the DCM to evaporate off on a pyrex plate on a hotplate with a fan blowing. Maybe at 80 - 100°C. Initially the DCM goes off quickly, and when little is left you will notice 2c-h carbonate begin to form, do not worry, the HCl will beat it into submission soon. More and more carbonate appears, but you must evaporate off ALL the DCM. The last is difficult to get, the plate could be a white crystal before all of the DCM is gone. You can attempt a sniff test for DCM, but in hindsight this is downright foolish. I once used to love the stuff, oh look how clean everything comes out of it, look how heavy it is, tee-hee. But now am more wary of it, I reason it will be the unhealthiest compound to be around in the entirety of this synth, so try and limit contact with it. Wear a mask. I would try to use maybe diethyl ether next time, much more green, and should be easier to evaporate.

6. Once all DCM is gone, start pouring the aq. HCl onto the carbonate, pour maybe 1/3 of the total and swirl around the plate, mix well, then start adding smaller portions and monitoring the pH after each pour and mix. The HCl will melt the carbonate quickly. Use up ½ to ¾ of the total HCl to reach a pH of 6.5. If all DCM had been evaporated, no sludge will appear, if you had some DCM left over, it will appear as tiny droplets. Good luck getting rid of it now!

7. Once the proper pH has been reached (careful with HCl addition below 7 or 7.5, pH might drop rapidly with little addition), it is time to evaporate off the water. Heat the plate to 100 – 120°C with a fan blowing, and the water should boil off slowly. End up with a mass of sticky crystals, they melt easily, but that is not water left. The crystals might not be fully solid. That’s alright.

We have a yellowish colour, but not green bird shit.

8. Clean with ethyl acetate (EtOAc), I prefer to clean with cold EtOAc as I swear that cold acetone washes away product. So I use only EtOAc now. After the first wash over the pump, I remove, dry some, and mill everything in a coffee grinder. Return the mostly fine powder for a second wash to reach places where the first could not get at. Wash very thoroughly a second time. End up with a mostly clean and dry 2c-h HCl that weighs 73.547 g (0.3378 mol). A huge disappointment. A 61.8% yield for a simple A/B. Maybe I should have added more HCl, or maybe the DCM did not pick up all the freebase. Maybe the yellow slime was actually a part of the product. Did pumping and washing suck product as well?

Another option would have been to clean the initial 2c-h oxalate with ethyl acetate… Or just avoid this route altogether next time. And I am not the only one who has experienced major loss of product with this salt conversion…

 

[HIGGS BOSSON]

Do you need 2c-b in such large quantities?
Without experience, it is better to start with the synthesis of 5-10 g.
The method described above is correct.
I personally used for 2c-b Al\hg method. We have a video, you can check similar synthesis:

http://bbzzzsvqcrqtki6umym6itiixfhni37ybtt7mkbjyxn2pgllzxf2qgyd.onion/media/2-5-dma-fb-synthesis-dob-precursor.66/

 

[Swirly]

The video and the synthesis you linked is one using a Lithium aluminium hydride (LAH) reduction, precisely what I wanted to avoid, hence mostly kitchen friendly.

As for Al/Hg I have not given that a thought, but do not think it would be much of an improvement over the friendlier NaBH4/ CuCl2.

Well yes, it would be nice to end up with 100g or 250g of product

Like I wrote for those amounts catalytic hydrogenation/ catalytic transfer hydrogenation would be something to look into. Wonder if that is still viable?

 

[HIGGS BOSSON]

You can look at the synthesis of mescaline large scale, which is a similar substance to 2C-H

http://bbzzzsvqcrqtki6umym6itiixfhni37ybtt7mkbjyxn2pgllzxf2qgyd.onion/en/threads/mescaline-synthesis-with-nitromethane-1000g-scale.76/

 

[Swirly]

Part 4: Bromination of 2c-h HCl with N-Bromosuccinimide (NBS) to yield 2c-b HCl and cleaning of crude 2c-b (The Final Stretch and a perfect product)​

Chem info:
1 mol N-Bromosuccinimide (NBS): 177.985 g/mol
1 mol 2c-b freebase: 260.128 g/mol, pKa is 9.68
1 mol 2c-b HCl: 296.59 g/mol

Bromination with NBS is simple and quick. NBS is a bromine radical releasing agent. However, it seems fine to handle and I noticed no special precautions are needed. But still be careful around it.

For this synth I did try to recrystallize my yellowish NBS in boiling water and that actually created some problems.

The guideline is to use 10 mL dH2O for 1 g NBS. Your water has to boil for some time for the NBS to fully dissolve, then you let cool, and clean NBS crystals should drop out.

In practice I had difficulty dissolving 100 g of NBS, and as the mixture reached boiling, what seemed like bromine gas started to become evolved, a strong scent appeared, and I put a halt to the experiment, did not perform a successful recrystallization once again, another partial recrystallization.

Later I found posts that write not to recrystallize the yellow NBS. The yellow colour is Br2, and it should actually help in the reaction. Should boost yields and shorten reaction time. So maybe do not attempt a re-x on the NBS, it will only stink up your place when it heats up. Skip this step and go on using straight the yellow NBS.

But if you do go with a re-x you should end up with some very nice white NBS crystals that weigh 70 – 80 g from a starting 100 g.

1. For the bromination try a 1.2 mol. eq. of NBS from the 2c-h HCl. We have 0.3378 mol 2c-h, so need 0.40536 mol NBS or 72.14 g.
Note: Do not handle the NBS with metal as well, stains and ruins metal spoons.

2. Go with an 8x amount in mL of GAA from 2c-h. So we use 590 mL.

Note: If you are working in a cold environment your GAA might be frozen as crystals. Warm in a bain-marie bathe to melt your GAA, hence the name glacial…

3. Dissolve 73.547 g 2c-h in a 1 L beaker with the GAA and begin moderate magnetic stirring.

4. Drop in the NBS, mixture goes from a light yellow (2c-h was not fully pure) to a red quickly. The red is indicative of the presence of Br2, then it goes to an orange as 2c-b is finally born, and crystals begin to fall out. Everything is over rather quickly. Might not even take 5 minutes for your beaker to become clogged in an orange paste, with stirring not possible. Full of precipitate. But it looks cool.
Was a larger portion of GAA needed? Next time maybe use a 9x amount of GAA?, maybe it would stir longer before choking up.

5. Not much else can be done at this point, so we move on to filtration and cleaning.

6. Suck at the pump but do not wash with anything, suck as dry as possible and collect the mother liquor, set it in the freezer, a bit more 2c-b should appear in time.

7. The 2c-b might be a pinkish or a light orange colour at this point, but we shall attempt to clean it as well as we can. Screw the yield, I am after the absolute purest 2c-b! I want an ultra-pure, blindingly white 2c-b that would make Jesus cry. A 2c-b that would not even hurt a newborn’s nostrils, weened on pH 8 milk.
The plan is to solve the enigma mankind has been pondering since the birth of time; how to make a 2c-b that does not hurt to insufflate. What is to blame for the pain 2c-b inflicts on the nose? I believe that it has to be free bromine, not the 2c-b molecule itself. What is the antidote to bromine and other halogens? What is used in accidents to neutralize bromine? Yes, 10% sodium thiosulfate solution!

My innovation is to wash the 2c-b with a 10% sodium thiosulfate solution. I mix up one from this cheap sodium thiosulfate pentahydrate, this stuff stinks like fertilizer, and it is a powder not crystals. So I believe I had an impure product. Best is to buy a stock solution, or get the highest quality sodium thiosulfate.

So I drop in a bit of sodium thiosulfate and at once the 2c-b goes white. I watch as a single drop spreads its white tentacles, destroying, binding the pesky Br2. Oh my! Think what a thousand drops would do!

For me the 2c-b resembles Neapolitan ice cream, and I begin to imagine myself as an artisanal gelateriano on a search for Stracciatella with the perfect composition, and I do get carried away with my quest for the tastiest, and whitest vanilla-2c-b-gelato in creation. I pour too much solution while pumping, and I believe I wash a fair amount of 2c-b away. It might be wise to go by the dropful in a larger dish to whiten the 2c-b, and use the high quality sodium thiosulfate that should come in large crystals. Or one of those 1 M stock solutions.

But I did not stop there, the 2c-b at this point was the whitest I have yet seen, but still I wash two more times with cold ethyl acetate for good measure under pumping and mixing with a spoon. With the ethyl acetate I could also have washed some product away. But I collect everything nonetheless and stick the second mother liquor in the freezer as well.

Next time, would use a smaller amount of sodium thiosulfate, and let it soak, then carefully pump. Still need to figure this part out pat.

8. Leave to fully dry in a crystallizing dish under a fan. Collect from the original crop 26.473 g, then I take what is out of the freezer, and collect that but first pump under vacuum and dry.

The first mother liquor I only freeze for a bit as the GAA freezes solid, so thaw it first.

This second batch is dirtier and has a stronger fertilizer smell, weighs 24.295 g. Total weight is 50.768 g or a 50.6% yield from the 2c-h HCl. Another poor yield.

However the colour of the 2c-b is a grayish white, maybe even a light hint of green, does not look perfect. Could be that there is residual sodium sulfate, or some sort of sulfates there. Maybe even succinimide? It is a lot of 2c-b for sure, and it looks ok, I am very tired of the synthesis at this point as I have been working without a break, but a nagging feeling lingers as I call it a day…

9. Next day I decide to drag out some of the gear once more and try a re-crystallization of the 2c-b at least to rid it of the smell. Snooping around, read that people have trouble with this step. But our beloved Benignium had success with a dual solvent system with acetonitrile (AcN) and methanol (MeOH) to dissolve 2c-b. Ahh, I do have some AcN around and still a fair amount of IPA, but no MeOH, but why not try with more IPA, it might work.

Nope, I first use 724 mL AcN and 275 mL IPA to dry to dissolve the 50.768 g 2c-b when boiling, have no luck. Already this is about 20 mL/g. Add 260, 180, and another 200 mL IPA, solution is boiling but it is cloudy, on the bottom there is a bunch of undissolved 2c-b. Yet another failed recrystallization! Don’t think I did anything with this attempt, but the AcN+IPA mix has turned a light yellow. Maybe I did trap some impurities, and when I pump and dry under vacuum, the 2c-b does indeed look a bit better. A nicer white colour, dry fully and the smell almost all gone! So the semi-recrystallization, the mixing in AcN+IPA did help some I think. In short, use the amount outlined but use MeOH instead to recrystallize, should work.

Weigh, and another damn disappoint, another major loss, have in the end about 36g of white 2c-b. I will settle for this one, grind with a coffee grinder into a truly nice powder. Job finally done.

The yield on the NBS bromination is not the best as well. Is it better to pick another method when dealing with larger amounts? But NBS is so easy to use. You could make 2c-c by using N-Chlorosuccinimide (NCS) instead. But would N-Iodosuccinimide (NIS) work to make the superior 2c-i? NCS is very easy to prepare if not found, but there are sources for it, and NIS as well. A useful synth would be to replace nitromethane with nitroethane and to make 1-(2,5-dimethoxyphenyl)-2-nitropropene (2,5-DMP2NP) from the 2,5-DMB. Then reduce 2,5-DMP2NP to 2,5-dimethoxyamphetamine (2,5-DMA). Use that to make DOC with NCS.

Conclusion: I snort a small amount of 2c-b and the burn is still there, but it is minimal. Another time I snort a few large lines, burn is very real, but not the strong pain I used to experience. So it could be that uncleaned bromine only caused a portion of the pain, and the 2c-b molecule itself is responsible as well...

But my nose is not destroyed at all the next day, this really is better 2c-b. Whether to include the sodium thiosulfate wash is an open question, and a successful recrystallization would be helpful as well. Happy tripping.

Fin​

 

[Swirly]

A step that I missed that could have increased my yields, is after the bromination I could have washed with a large quantity of ethyl acetate into the reaction mixture. Or I could have collected the original reaction mixture after pumping and filtering off the 2c-b, and dumped a large amount of EtOAc in. Then stuck into the freezer. The rm would not have frozen, and I am certain a large amount of 2c-b would have fallen out with the succinimide and other unwanteds in solution. Ah lots of 2c-b lost here.

 

[Swirly]

Addendum:​

Pretty Pictures for Part 1:
Colour once reaction is almost done, before crystals appear


Crystals appear:


Nitrostyrene product


Cleaner nitrostyrene from a previous synth for comparison


Part 2:
6 L 3-neck flask ready for the NS


Addition of NS


After transfer to a 10 L beaker, before addition of CuCl2


Once black copper is filtered, borates crash out


Dry and cleaned layer of IPA with 2c-h freebase


2c-b oxalate


Part 3:
Working with layers possibly DCM here


Part 4:
Bromination after addition of NBS, red colour of Bromine


2c-b is born


Attempt to recrystallize 2c-b HCl


Final product, still damp, not milled

 

[Swirly]

A small correction: where there is a pic of 2c-b oxalate, it is 2c-h oxalate. This forum could allow editing of posts

Also: link to original bromination with NBS post:

NBS bromination of 2,4-dimethoxyphenylethylamine , Hive Methods Discourse