Sciencemadness Discussion Board

DIPT that's not DIPT

mackolol - 25-4-2020 at 12:44

Recently I'm into chemistry of alkylating big amines, but it is black magic for me at the moment.

I performed synthesis of Diisopropyl Tryptamine as described in literature, dissolved tryptamine in DMSO added isopropyl iodide and triethylamine, stirred overnight at 40C. Then extracted with DCM and after boiling off the solvent, stinky brown oil obtained.

Next presumable DIPT dissolved in hot vinegar and based with NaOH. Tryptamine - like solid came out of solution, but on filtering it turned into oil. So I did two A/B extractions with vinegar and HCL. After second adding of NaOH solid was filtered.

I obtained tryptamine smelling and looking solid, but it is poorly soluble in acetone and IPA and recrystallisation from gasoline didn't work out because it is too poorly soluble.

Neither it is biologically active.
I can add that I used 1.6g tryptamine at the beginning and obtained 2.2g of mysterious solid.

And my question is what it is, why does it behave like that. It blows my mind that it should be DIPT and looks like it but it is not behaving like this.

I attach pictures of the product

94519804_825307641297642_9074309901152419840_n.jpg - 740kB

clearly_not_atara - 25-4-2020 at 13:27

It is most likely monoisopropyl tryptamine. Shulgin performs a similar procedure in TiHKAL but for 12 hours at 100 C in sulfolane with DiPEA. I can only imagine such extreme measures were performed out of necessity.

A note to onlookers: DiPT has interesting effects on auditory processing but all reports indicate it is not a pleasurable recreational drug.

S.C. Wack - 25-4-2020 at 14:04

Indeed what lit uses DMSO and triethylamine. It's weird how people love Shulgin while ignoring his recipes.

I have to wonder if this burns out some unique portion of the brain, as the 5-MeO cpd. is suspected of neurotoxicity. If it's not pleasurable does that mean it's unpleasurable? I'm not sure it's described that way exactly.

mackolol - 25-4-2020 at 14:14

Quote: Originally posted by S.C. Wack  
Indeed what lit uses DMSO and triethylamine. It's weird how people love Shulgin while ignoring his recipes.
Quote: Originally posted by clearly_not_atara  
It is most likely monoisopropyl tryptamine. Shulgin performs a similar procedure in TiHKAL but for 12 hours at 100 C in sulfolane with DiPEA. I can only imagine such extreme measures were performed out of necessity.


Okay... I changed sulfolane for DMSO and DIPEA for triethylamine. I thought that DMSO is similar enough to sulfolane. And with the amines I thought if Shulgin noted that the reaction can be performed with NaHCO3 as a base then changing DiPEA to triethylamine won't be any issue.
Am I wrong?, are these procedures necessarily have to be performed with such reagents and that they differ as much?

[Edited on 25-4-2020 by mackolol]

clearly_not_atara - 25-4-2020 at 15:20

Quote:
Okay... I changed sulfolane for DMSO and DIPEA for triethylamine. I thought that DMSO is similar enough to sulfolane. And with the amines I thought if Shulgin noted that the reaction can be performed with NaHCO3 as a base then changing DiPEA to triethylamine won't be any issue.

You also decreased the reaction temperature by sixty degrees. Doesn't that sound important? If I follow a literature preparation for soup, and make it at 40 C instead of 100 C, what do you think is going to happen?

I don't think triethylamine instead of DiPEA is too big of a deal. I think one major advantage of DiPEA in this case is that it is less volatile at the necessary rxn temperature. Tributylamine is a common alternative for such cases.

Also, by NaHCO3, I think you must mean Na2CO3 or something; bicarbonate will not dissolve in aprotic solvents or deprotonate amines.
Quote:
If it's not pleasurable does that mean it's unpleasurable? I'm not sure it's described that way exactly.

TiHKAL reports that it causes auditory hallucinations with none or very little of the visual effects or tactile activation (a feeling roughly like a sweet taste but to the touch) that are characteristic of recreational psychedelics.

Shulgin suggested using it to study the auditory system; further investigations have found it to be a selective ligand of the serotonin receptor type 6 (5hT6), and suggested that this receptor may play a role in the pathogenesis of schizophrenia. However, since Alzheimer's is much more fashionable, 5-ht6 antagonists have only been trialed for dementia, and those trials have been unsuccessful.

[Edited on 25-4-2020 by clearly_not_atara]

mackolol - 26-4-2020 at 00:52

Quote: Originally posted by clearly_not_atara  

You also decreased the reaction temperature by sixty degrees. Doesn't that sound important? If I follow a literature preparation for soup, and make it at 40 C instead of 100 C, what do you think is going to happen?

[Edited on 25-4-2020 by clearly_not_atara]


All right, I see now, I just ignored the fact that in DIPT's case I'm alkylating an amine with secondary alkyl iodide not primary. I thought that if other tryptamines such as DPT or DET are done in room temperature, it can be done too, especially if I have stirrer. Taken the boiling point of triethylamine and I dont know why, but I thought that in higher temperatures it produces more impurities (I think I even performed it once at 100C but I don't remember exactly, for sure I did it with worse quality tryptamine).

And one more thing can sulfolane be changed for DMSO?
And by the way, what's the role of sulfolane in this particular secondary case instead of IPA in every other primary alkylation?

Cou - 26-4-2020 at 01:43

Holy Sh*t, I can't believe you did this! I fantasized about synthesizing DiPT after reading the TIHKAL entry.

draculic acid69 - 26-4-2020 at 02:12

I'd like to try the 5meo analogue.very interesting

mackolol - 26-4-2020 at 02:30

Quote: Originally posted by Cou  
Holy Sh*t, I can't believe you did this! I fantasized about synthesizing DiPT after reading the TIHKAL entry.


Unfortunately not yet, but I'm trying for quite long time and I'm close. I can share the synthesis and comments when I'll manage to complete it.


Quote: Originally posted by draculic acid69  
I'd like to try the 5meo analogue.very interesting


Maybe someday, when cheap and decent grade melatonin will appear in Poland...

Texium - 26-4-2020 at 06:55

Quote: Originally posted by mackolol  
Okay... I changed sulfolane for DMSO and DIPEA for triethylamine. I thought that DMSO is similar enough to sulfolane. And with the amines I thought if Shulgin noted that the reaction can be performed with NaHCO3 as a base then changing DiPEA to triethylamine won't be any issue.
Am I wrong?, are these procedures necessarily have to be performed with such reagents and that they differ as much?
You can’t possibly claim you performed a synthesis “as described in literature” when you drastically change the solvent, and one of the reagents, and the temperature! Using CNA’s soup analogy, not only did you try to make your soup at 40 C, you also figured replacing the stock with plain water would be fine. Then you just threw some chunks of raw chicken in there and acted surprised when you ended up with lukewarm raw chicken in water instead of chicken soup. But you took it a step further–you had the nerve to take a bite of the raw chicken! That’s the part that really gets me.

There’s nothing wrong with trying those changes, but at that point you can’t claim to have followed a literature procedure. When you change so much stuff and something goes wrong, those changes should be the first place you look for potential problems. And above all you should never test a mystery compound for “biological activity.” That’s how people die. Ingesting “known” compounds made in a home lab is risky enough. Everything you’ve described is reckless, bad science.

mackolol - 26-4-2020 at 07:53

Quote: Originally posted by Texium (zts16)  
Quote: Originally posted by mackolol  
Okay... I changed sulfolane for DMSO and DIPEA for triethylamine. I thought that DMSO is similar enough to sulfolane. And with the amines I thought if Shulgin noted that the reaction can be performed with NaHCO3 as a base then changing DiPEA to triethylamine won't be any issue.
Am I wrong?, are these procedures necessarily have to be performed with such reagents and that they differ as much?
You can’t possibly claim you performed a synthesis “as described in literature” when you drastically change the solvent, and one of the reagents, and the temperature! Using CNA’s soup analogy, not only did you try to make your soup at 40 C, you also figured replacing the stock with plain water would be fine. Then you just threw some chunks of raw chicken in there and acted surprised when you ended up with lukewarm raw chicken in water instead of chicken soup. But you took it a step further–you had the nerve to take a bite of the raw chicken! That’s the part that really gets me.


Oh yes, sometimes I tend to change something in synthesis, because I'm sure that it'll work, that's something that I'm learning to stop. The fact that I have written, I followed the synthesis as in literature.
And for the fact that I tried it biologically, Tryptamines are quite safe and natural, there wasn't much that could harm me and the product acted like tryptamine. Neither do I think that it was Beta Carboline because it is not very likely for it to form in the reaction. But yes it was quite stupid for me.

clearly_not_atara - 26-4-2020 at 08:30

Quote: Originally posted by mackolol  
Quote: Originally posted by clearly_not_atara  

You also decreased the reaction temperature by sixty degrees. Doesn't that sound important? If I follow a literature preparation for soup, and make it at 40 C instead of 100 C, what do you think is going to happen?

[Edited on 25-4-2020 by clearly_not_atara]


All right, I see now, I just ignored the fact that in DIPT's case I'm alkylating an amine with secondary alkyl iodide not primary.

That, exactly. Attaching two isopropyl groups to an alkylamine is hard.
Quote:
And one more thing can sulfolane be changed for DMSO?
And by the way, what's the role of sulfolane in this particular secondary case instead of IPA in every other primary alkylation?

Sulfolane is even more polar than DMSO. In general higher dipole moments speed up SN2 displacements and other dipole-dipole reactions. (I don't quite understand the mechanism myself.)

In some sense, sulfolane is "the polar solvent of last resort" when nothing else will promote a reaction as effectively. See:

https://blogs.sciencemag.org/pipeline/archives/2015/06/03/so...

The common replacements would include hexamethylphosphoric triamide (HMPA), N,N-dimethylimidazolidone (DMI), dimethylpropyleneurea (DMPU), or maybe propylene carbonate. In all cases you want something that complexes cations more strongly than anions. Another "OTC" thing I wonder about sometimes is N-methyloxazolidone, which might form by rxn of methyl isocyanate with ethylene glycol followed by dehydrative ring closing at high temperature. It's hard to make

Sulfolane has D=4.7 and epsilon = 43.4: https://pubs.acs.org/doi/pdf/10.1021/op300108w

PC compares favorably with D = 4.98 and epsilon = 64.9: https://macro.lsu.edu/HowTo/solvents/Propylene%20Carbonate.h...

By comparison DMSO is much lower with D=4.1. So PC may work better than DMSO. The disubstituted cyclic ureas are harder to get but even stronger.

mackolol - 26-4-2020 at 12:28

Quote: Originally posted by clearly_not_atara  

Sulfolane is even more polar than DMSO. In general higher dipole moments speed up SN2 displacements and other dipole-dipole reactions. (I don't quite understand the mechanism myself.)

In some sense, sulfolane is "the polar solvent of last resort" when nothing else will promote a reaction as effectively. See:

stronger.


That's news for me, I didn't actually know that sulfolane is better in such reactions than DMSO ( I guess that luminol luminescence in sulfolane would be total killer ), but unfortunately in Poland there's no sulfolane to buy. I hope that after rising temperature to 100C, I will be able to do it in DMSO. Taken in mind that primary alkylations are done in "just" IPA.

Quote: Originally posted by clearly_not_atara  

Sulfolane has D=4.7 and epsilon = 43.4: https://pubs.acs.org/doi/pdf/10.1021/op300108w

PC compares favorably with D = 4.98 and epsilon = 64.9: https://macro.lsu.edu/HowTo/solvents/Propylene%20Carbonate.h...

By comparison DMSO is much lower with D=4.1. So PC may work better than DMSO. The disubstituted cyclic ureas are harder to get but even stronger.


So does that mean that propylene carbonate is even more polar and better for such purposes than sulfolane? as it has higher D and epsilon values

I wonder how hard is to alkylate with tertiary chains...

[Edited on 26-4-2020 by mackolol]

draculic acid69 - 26-4-2020 at 17:42

Quote: Originally posted by mackolol  
Quote: Originally posted by Cou  
Holy Sh*t, I can't believe you did this! I fantasized about synthesizing DiPT after reading the TIHKAL entry.


Unfortunately not yet, but I'm trying for quite long time and I'm close. I can share the synthesis and comments when I'll manage to complete it.


Quote: Originally posted by draculic acid69  
I'd like to try the 5meo analogue.very interesting


Maybe someday, when cheap and decent grade melatonin will appear in Poland...


5htp is pretty common and easy to acquire seems like a decent starting point

mackolol - 27-4-2020 at 00:20

Quote: Originally posted by draculic acid69  

5htp is pretty common and easy to acquire seems like a decent starting point


It's a lot of work with protecting 5htp with Boc and methyl group as ester. Moreover 5htp is available in form of pills. Extraction would be quite painful and even though I'm pretty sure decarboxylation of it after a lot of work wouldn't be effective as it is probably food grade.

All I have learned about tryptophan is that it must be very high grade to decarboxylate it effectively to tryptamine.

If I purchased 5htp I would rather actually use it as a supplement, as it is quite interesting and worthy compound.

outer_limits - 27-4-2020 at 04:51

Quote: Originally posted by mackolol  

Neither it is biologically active.


Did you check at least its melting point?

mackolol - 27-4-2020 at 05:41

Nope, I don't have laboratory thermometer because it broke sometime ago.

I can also add, that the mysterious compound, which thanks to you I can tell is probably mono isopropyl tryptamine, doesn't darken on air exposure, unlike unsubstituted tryptamine.

[Edited on 27-4-2020 by mackolol]

clearly_not_atara - 27-4-2020 at 10:48

Quote: Originally posted by mackolol  


So does that mean that propylene carbonate is even more polar and better for such purposes than sulfolane? as it has higher D and epsilon values

This is a very difficult question to answer. Even though it is relatively cheap and much more eco-friendly than most solvents, propylene carbonate is almost never used in professional organic synthesis. It is, however, extremely common as a battery electrolyte. Notably, PC supports the electrowinning of lithium metal from its salts. I'm not sure about sodium.

I don't know why PC isn't popular, but it's probably a combination of an excessively high boiling point and the fact that DMPU is widely available (from chemical suppliers at least) with even more dipolarity and it's more stable to boot.

However, based only on the measurable physical properties of the solvent, PC is probably a better replacement for sulfolane than DMSO.
Quote:
I wonder how hard is to alkylate with tertiary chains.

Now this I can answer: it's impossible. Amine alkylation does not occur with tertiary halides. The exception is for tertiary fluorides together with selective Lewis acids.

mackolol - 27-4-2020 at 12:39

Quote: Originally posted by clearly_not_atara  

Now this I can answer: it's impossible. Amine alkylation does not occur with tertiary halides. The exception is for tertiary fluorides together with selective Lewis acids.


So it is possible but in very strict conditions... Maybe someday I will play in being new Shulgin and make Di tert butyl tryptamine haha. Although doubt that it is active.

karlos³ - 27-4-2020 at 17:57

Poorly soluble in acetone, that must be something different and not the monoalkylated product, maybe its some inorganic impurity contamination?
Strange.
Better stick to a working procedure the next time instead of experimenting, if you do not have the means to purify a likely less pure product, which is coming from a procedure you've improvised yourself, that would be my suggestion.
Quote: Originally posted by clearly_not_atara  

A note to onlookers: DiPT has interesting effects on auditory processing but all reports indicate it is not a pleasurable recreational drug.

I can confirm that first-hand.
You can't identify someones voice especially on the phone, you can't enjoy music and not even listen to it, actually the way everything sounds is just really, really exhausting.
I was glad it was over and never took it again.

Better to make the diisopropyl with a 5-methoxy substituent.

mackolol - 28-4-2020 at 00:40

Quote: Originally posted by karlos³  
Poorly soluble in acetone, that must be something different and not the monoalkylated product, maybe its some inorganic impurity contamination?
Strange.


That's why is started this thread. It had crystals looking just like tryptamine and even smelled like tryptamine, but behaved really badly...