Iodinations of 2C-H/2,5-DMA

[Antoncho]

This work has been performed by Mescalito, the Electronic Performer of HyperLab.

Having initially earned his title by offering the ultimate council in the questions concerning electronic devices and other problems of physical nature, this guy later on turned to bee an aspiring, enthusiastic and innovating workbee.

Here’s what his alter ego has done recently (

Post 464442 (missing)

(mescalito: "DOI - óñïåõ!", Russian HyperLab))… the synthesis was carried out after 

https://www.thevespiary.org/rhodium/Rhodium/chemistry/doisynth.html

Into a RBF there were placed 60mls 96% EtOH, 700mg 2,5-DMA*1/2H2SO4 and all was mixed until full dissolution. Thence was added 1,46g iodine – and also stirred until all dissolved. Lastly, there was added 1,8g finely ground Ag2SO4. The mixture was stirred for 14hrs at RT, after 2hrs iodine was visibly spent.

The mixtr was filtered, the filter cake washed w/a little EtOH, ethanol fractions pooled and  evaporated into the atmosphere on a waterbath. This was mixed with ~30mls water and some (3-4g) alkali. Dark color disappeared and to the surface floated a pinkish-yellow oil, poorly soluble in hexane (as it seems, generally 2,5-diMeO species is poorly soluble in pet ether, but well soluble in C6H6). The oil was extracted 3x10mls and acidified w/HCl. 630mg (61% of theory) of light-pink powder was obtained , mp 200-201 Ñ (lit. 200,5-201,5 - PiHKAL)




Importantly, it should bee noted that this same procedure in hands of Mescalito gave the max. yield of 33% when applied to 2C-H.

Another important point is that under no circumstances a freebase amine should bee used in this reaction. It leads to massive polymerisation, no product possibly isolated.


Antoncho

[imp]

Firstly, good work!
Secondly, yields might turn out significantly better if the procedure is performed under a red lamp, or in the dark. 630mg of a pink powder may easily turn out to be 100mg of pure compound after recrystallization - it's happened before. Furthermore, the pink powder has a m.p. nearly identical to the pure compound? So, somehow there was no 2,5-DMA left in the final product to depress the m.p.? That is difficult for SWIM to accept.
Thirdly, when applying the procedure to the freebase amphetamine, was the freebase 2,5-DMA pure? Polymerization may have been caused by impurities, as the paper on Rhodium's shows that the procedure has been tried out for this particular compound. Also, once again, polymerization might be stunted by performing the reaction in the dark.
Finally, notice how the procedure on Rhodium's states to add the compound to a mixture of I2/AgSO4 in EtOH. This order of reactants is important, as you should be adding your aromatic to the iodinating reagent.

33% yield when applied to freebase 2C-H? or a salt?

Edit: Actually, thinking about it a little more, polymerization may have very well been due to adding the reactants in the wrong order. Prepare the AgSO4/I2 separately, then add the 2,5-DMA all in the dark and SWIM will bet on better results. An inert atmosphere never hurts.

[Erny]

630mg of a pink powder may easily turn out to be 100mg of pure compound after recrystallization - it's happened before.

I don't think so. 2C-I made via the same route and by the same bee was 1,5 times more active than equal amount of 2C-B.

Furthermore, the pink powder has a m.p. nearly identical to the pure compound?

The thermometer that bee was using has a scale from 0° to 360°C. He also has a weak sight   .

So, somehow there was no 2,5-DMA left in the final product to depress the m.p.? That is difficult for SWIM to accept.

No more than 5%. Anyway, we'll soon have TLC down there.

Thirdly, when applying the procedure to the freebase amphetamine, was the freebase 2,5-DMA pure?

2,5-DMA was of dark amber colour. 2C-H was much purer.

Finally, notice how the procedure on Rhodium's states to add the compound to a mixture of I2/AgSO4 in EtOH. This order of reactants is important, as you should be adding your aromatic to the iodinating reagent.

AFAIK he did it that way in all of his syntheses.

33% yield when applied to freebase 2C-H? or a salt?

To the salt (sulphate).

[mescalito]

2 Imp:

Thanks a lot for your post, I will try next time as you suggested. I will write the results, maybe in a week or two.
33% yeild of 2c-i was obtained with 2c-h sulfate.

But only 1 time I got sucsess in this method with 2c-h freebase -

Post 453797 (missing)

(mescalito: "Íå äîæäàâøèñü îòâåòîâ è ñîâåòîâ, ñâèì ñäåëàë...", Russian HyperLab)
- from 2c-h freebase, obtained from 900 mg 2c-h*HCl, I got 680 mg 2c-i*HCl. And then 3 or 4 times I tried to repeat the experiment and got all the product polymerized in flask.
I don't remember, maybe the first (sucsessful) experiment started at night without bright light...it was 2 or 3 months ago.
I will try once more, in the dark.

[imp]

Well, since this is your first post here at The Hive for the username "Erny", SWIM suspects that you are the one who performed this reaction, correct?

You say this...

Finally, notice how the procedure on Rhodium's states to add the compound to a mixture of I2/AgSO4 in EtOH. This order of reactants is important, as you should be adding your aromatic to the iodinating reagent.

AFAIK he did it that way in all of his syntheses.

But Antoncho says something different...

Into a RBF there were placed 60mls 96% EtOH, 700mg 2,5-DMA*1/2H2SO4 and all was mixed until full dissolution. Thence was added 1,46g iodine – and also stirred until all dissolved. Lastly, there was added 1,8g finely ground Ag2SO4. The mixture was stirred for 14hrs at RT, after 2hrs iodine was visibly spent.

So which way did you do it??

When SWIM said 630mg of powder may turn out to 100mg of product, SWIM was just speaking from previous experience with other compounds. SWIM was not saying that the product from your reaction was necessarily very impure, just that in many cases you may be surpised how much impurity is in a blinding white powder.

A TLC would be very informative. Where did you come up with the number 5% 2,5-DMA impurity?? Off the top of your head? Or scientifically? Since an accurate measurement with your thermometer may have been difficult, how could you know how depressed the m.p. was?

If you give it another try, please do it in the dark and see what happens. Nothing bad can come of it, right? So just give it a shot.

Take care

Edit: We cross posted Mescalito! SWIM wants to say good work with the reaction!! Hope it turns out with higher yield next time. Take care!

[Erny]

Well, since this is your first post here at The Hive for the username "Erny", SWIM suspects that you are the one who performed this reaction, correct?

No. I haven't even seen the product yet.

You say this...

Finally, notice how the procedure on Rhodium's states to add the compound to a mixture of I2/AgSO4 in EtOH. This order of reactants is important, as you should be adding your aromatic to the iodinating reagent.

AFAIK he did it that way in all of his syntheses.

But Antoncho says something different...

I guess Mescalito made it exactly the way he described it in his post.

Where did you come up with the number 5% 2,5-DMA impurity?? Off the top of your head? Or scientifically?

This is based on our previous experiences with 2C-I. What scientifical methods of analysis, others than TLC and mp measurement, can you propose to a kitchen chemist?

[Antoncho]

1st – a question to Mescalito:

Any updates on the project yet?


2 Imp:

What makes you beelieve the order of adding reactants is so important? Is this somehow explained by the reaction mechanism? As I beelieve, the role of AgSO4 is solely to bind I^- which otherwise (as HI) would reduce the formed iodocomp’d back to the parent.


Now – to the other goods. Some time after Mescalito’s experiments Assholium posted an interesting ref, which, along with some refs coming from thence, was retrieved by Azole of HyperLab. They proved to bee highly interesting.



1. W.C.Baird, J.H.Surridge, Halogenation with Copper(II) Halides. The Synthesis of Aryl Iodides, J. Org. Chem., 35(10), 3436-3442 (1970).

The 1st one of them, describe iodinations of both activated and deactivated arenes aided by CuCl₂, which works just fine w/out any further catalysis – on, e.g., xylene. Unfortunately, the closest-to-what-we-want arene tested in the article was anisole, yielding 80%. Durene yields 100%.

Moreover, it turns out that, contrary to what was beelieved prior to their work, Lewis acid catalysis promotes the rxn and permits iodination of things like bromobenzene.

Even yet more interesting, metal iodides can bee used directly as both L.A. catalysts and iodine source. And even in hydrated form – like FeI2*4H2O.

All in all, a highly promising, cheap and next-to-OTC approach.

May I also note that, in all of these CuCl2 iodinations, all iodine is stoichometrically spent on aromatic iodination, which is quite nice economically

An xperimental procedure:





2. T.Sugita, M.Idei, Y.Ishibashi, Y.Takegami, Aromatic Iodination with Aluminum and Copper(II) Chlorides and Iodine, Chem. Lett., 1982, 1481-1484.

Arenes are iodinated with iodine + AlCl3 + CuCl2. Yield for anisole – 88%, but only 69% was isolated for some reason.


3. C.A.Horiuchi, A.Haga, J.Y.Satoh, Novel Regioselective Iodination of Estradiol 17â-Acetate, Bull. Chem. Soc. Jpn., 59, 2459-2462 (1986).
C.A.Horiuchi, J.Y.Satoh, A Convenient Procedure for Iodination of Electron-rich Aromatic Compounds using Iodine - Copper(II) Acetate, ibid., 57, 2691-2692 (1984).

In the 1st article (by Baird & Surridge) copper acetate was tested for iodination of xylene without much success (yield <5%). This fact was attributed by much lower activity of Cu(AcO)2 as a Lewis acid. It turns that, when used in GAA and on more activated substrates, this catalyst is very efficient and mild, yielding 70% for anisole and 90% for durene and aniline.







The yields promised aren’t stellar but they should bee better for the more activated polymethoxy- substrates.

Further on, I have a feeling that this procedure might hold the special promise for our lovely 2C-H beecause of the mild character of the catalyst and the acidic rxn medium.


Who wants to give it a try?



Antoncho

[mescalito]

Some months ago I wrote about iodination of 2C-H*1/2H2SO4 and described yield 33% of theory.
The same experiment was performed, with the same quantities and the same equipment, but the flask with the rxn was protected from any light with dark black-coloured polyehylene film. Yield was 62% of theory, and visual purity of 2c-i was  better - it crystallised in  white needle-formed crystals.


Thanks Imp!

[imp]

Edit: BTW, can you translate this post for SWIM??

Post 475245 (missing)

(Erny: "Âîññòàíîâëåíèå 2,5-DiMeOP2NP íà U-Ni-A", Russian HyperLab)?? SWIM always peeks in the hyperlab, although never being able to read anything. That post seemed very interesting.