LONGECITY

hi there,
does anyone in lonecity.com know something about NMR-modafinil? There is one customer saying that this is adrafinil. but chemists in sun nootropic says that it is high quality modafinil, different from their adrafinil. OK, things happens like this, customer buy modafinil from sun nootropic and then reflect quality problems, sun nootropic send the customer NMR-modafinil of the same batch.
many buy from sun nootropic have a high value on modafinil while this customer reflect this problem, strange problems, right? i believe what the customer reflect is true because it is pointless to lie. so where the problem lies?
so i enclose the NMR, can someone read this NMR?

There are three similar compounds at play here:
1) Modafinil - The originial, racemic mixture (Perscription)
2) Armodafinil - Only the R-enantiomer (Perscription)
3) Adrafinil - Very similar, but the amine group has an alcohol attached to it. (Non-prescription, however, it is somewhat converted into modafinil inside the body)

When you said adrafinil did you mean armodafinil? I ask because in terms of the prescription version of this drug, adrafinil is different.

Also, telling these three compounds apart via an NMR is VERY challenging, considering modafinil and armodafinil are just different mixtures of enantiomers, there is no way to compare them, especially across multiple NMR machines. (I am not 100% about how different two enantiomers NMR readings would be, there may be no difference whatsoever, but at most, it would be a very miniscule difference, probably too little to be able to determine if it was just from a variance in the NMR or compound itself)

Now telling modafinil and adrafinil apart (besides by taking it, there should be a much more obvious difference there) is much more possible with NMR. Based on what I know and some NMR simulator tools I can't link to because of my post count, the NMR you posted does seem to be modafinil. Now my question, however, is did the seller send you that or did you have it independently tested? Obviously the seller could send on a NMR of anything and tell you it was the compound they sent you and that may or may not be the case.

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There's something confusing on this sheet. There's some data listed, one clearly pasted on, not that that's abnormal. But it lists dmso (assuming d6-DMSO) as the solvent, and also CDCl3 in the other one. So, that begs the question, which solvent was used? The peak at 2.5 suggests it's DMSO. DMSO should be a quintet, but a pretty sharp one, I think, so I think that's fine. CDCl3 would have a peak at 7.24, which would be buried in the aromatic H's.

The shifts from the two phenyl groups should be identical since they're on an achiral carbon. Thus, I think you should see three separate peaks from those 10 carbons; one doublet, and two triplets. the para-hydrogen will have a separate triplet from the meta-hydrogen, and the ortho-hydrogen being the doublet. the para-hydrogen would integrate to 2, and the ortho and meta hydrogens to 4 (edited to fix). It's hard to tell from the resolution, but the region 7.2-7.6 seems to show this? However, if CDCl3 was the solvent, there should have been a singlet at 7.24, and usually NMR solutions are prepared in such a way so that the solvent peak is obvious.

The benzyllic hydrogen should be shifted upfield from both the phenyls and the sulfoxide, and should be a singlet. It seems reasonable that the peak at 5.4 is this hydrogen.

Now, there's two hydrogen's on the carbon between the sulfoxide and carbonyl. I don't know if they would have unique peaks, or what, so the really weird peak at 7.65 could be one of these hydrogens. I don't really know what sulfoxide groups do here, but on first pass I would think there wouldn't be two unique peaks since the carbon is achiral. But there could be some strange coupling. Or, it could be that the 7.65 peak is something totally unrelated, and both hydrogens are found in region around 3.25.

Now the only thing left is the amine hydrogens. Those are tricky to assign, since the peak would be weaker, I think, because deuterium should be able to more easily exchange with those hydrogens. Maybe they're in the region around 3.25? I would expect a singlet here, but I also don't know if amine hydrogens would have extra splitting.

I can't assign the peak at 7.65 or those in the 3.25 region with a lot of confidence; you might expect if you had adrafinil, with an OH on the amine, that there would be an additional peak and possibly more splitting on the amine hydrogen. But then again, the signal from the OH might be very weak since it's more easily exchanged with deuterium. Maybe, if you had adrafinil, one of the hydroxylamine hydrogens could be shifted a lot more.

What would be good would be a GC/MS spectrum, I think. If you get a peak with a mass 16 higher than you expect, well, then, you got adrafinil there, fella. I guess I should have started with that. If you then were sure you had modafinil, racemic or not, then you could do an optical polarization measurement to see if you have R or S, or mix.
Edited by PhysicsMaestro, 28 February 2013 - 02:02 PM.

What you could also ask for is the 15N-NMR spectrum. That would conclusively say whether it's adrafinil or modafinil.

There's something confusing on this sheet. There's some data listed, one clearly pasted on, not that that's abnormal. But it lists dmso (assuming d6-DMSO) as the solvent, and also CDCl3 in the other one. So, that begs the question, which solvent was used? The peak at 2.5 suggests it's DMSO. DMSO should be a quintet, but a pretty sharp one, I think, so I think that's fine. CDCl3 would have a peak at 7.24, which would be buried in the aromatic H's.

The shifts from the two phenyl groups should be identical since they're on an achiral carbon. Thus, I think you should see three separate peaks from those 10 carbons; one doublet, and two triplets. the para-hydrogen will have a separate triplet from the meta-hydrogen, and the ortho-hydrogen being the doublet. each of those peaks would integrate to 2. It's hard to tell from the resolution, but the region 7.2-7.6 seems to show this? However, if CDCl3 was the solvent, there should have been a singlet at 7.24, and usually NMR solutions are prepared in such a way so that the solvent peak is obvious.

The benzyllic hydrogen should be shifted upfield from both the phenyls and the sulfoxide, and should be a singlet. It seems reasonable that the peak at 5.4 is this hydrogen.

Now, there's two hydrogen's on the carbon between the sulfoxide and carbonyl. I don't know if they would have unique peaks, or what, so the really weird peak at 7.65 could be one of these hydrogens. I don't really know what sulfoxide groups do here, but on first pass I would think there wouldn't be two unique peaks since the carbon is achiral. But there could be some strange coupling. Or, it could be that the 7.65 peak is something totally unrelated, and both hydrogens are found in region around 3.25.

Now the only thing left is the amine hydrogens. Those are tricky to assign, since the peak would be weaker, I think, because deuterium should be able to more easily exchange with those hydrogens. Maybe they're in the region around 3.25? I would expect a singlet here, but I also don't know if amine hydrogens would have extra splitting.

I can't assign the peak at 7.65 or those in the 3.25 region with a lot of confidence; you might expect if you had adrafinil, with an OH on the amine, that there would be an additional peak and possibly more splitting on the amine hydrogen. But then again, the signal from the OH might be very weak since it's more easily exchanged with deuterium. Maybe, if you had adrafinil, one of the hydroxylamine hydrogens could be shifted a lot more.

What would be good would be a GC/MS spectrum, I think. If you get a peak with a mass 16 higher than you expect, well, then, you got adrafinil there, fella. I guess I should have started with that. If you then were sure you had modafinil, racemic or not, then you could do an optical polarization measurement to see if you have R or S, or mix.

Awesome, dude keep posting!

I enjoyed your reply so much that I'm going to pay a silken voiced strumpet to softly whisper it to me in my sleep.
Edited by peakplasma, 28 February 2013 - 01:57 PM.

On second thought, there shouldn't be much D-H exchange; I think you would only really get this if D2O was used as the solvent.

Also, I just did a pubmed crawl for the NMR assignments. The N-hydroxylamine hydrogens would each be around 8-10, so it's definitely not adrafinil.

Still not sure what the 7.65 peak is. It's either one of the amine hydrogens or the one of the hydrogens between the S=O, C=O. This peak is absent from the paper I read, and has it instead at 6.1. Also, the paper I read has a peak at 3.6, instead of being merged in the 3.25 region. So, there should be two doublets around 3.2-3.3, a singlet around 3.6, and a singlet around 6.1. The two latter hydrogens might be shifted because a different solvent was used, maybe? This would make more sense if these hydrogens were from the amine.

In summary, it likely isn't adrafinil, as the hydroxylamine peaks are missing. If the discrepancy between the literature values I saw and the measured ones given here could be due to solvent effect (i.e., amine hydrogens influenced more by solvent), then it's reasonable that this NMR is indeed modafinil.

@peakplasma: thanks! :)

Intrested to see what the results are..where can this be tested in the us..by the way physicsmaestro sounds like he knows his stuff.. really unbelievable that you can just rant like that..verry impressive..question though. .why such the quick turnaround with stating it definetly is adra to its definetly moda.. has money been exchanged!! Haha..kidding.. but its questionable when bulk moda is cheaper than bulk adra how is this even possible
Edited by rolling thunder, 01 March 2013 - 09:06 PM.

hey, rolling thunder, no worries (I'm also replying to your private message here since it's more or less the same) I understand what you mean about being concerned whether it's adrafinil or not. You can definitely send it to lab if you're concerned, but I have no idea how much it would cost, or where to do it. I would guess it would cost more than the pills themselves.

I'm in the same boat as you-- I ordered some armodafinil from mymodafinil.net, and I want to make sure it's legit. I've had "modafinil" before from nubrain.com, though I never was worried about testing it at the time since I had a mate who ordered from there as well. And it seemed to work. Anyways, I noticed with modafinil that my urine always smelled "sulphurous." With this armodafinil, I didn't notice this, so I was concerned and started looking up how I can test what I've got. I don't really mind if I was given modafinil instead of modafinil as much as if I was given adrafinil, since I've also read that adrafinil is much harder on your liver. But I since gave up my zealousness on testing it (though I'd still like to know), since each time I've taken 150mg of it so far in the morning ( about 9am), I could never get to bed before 3-5am, so I figured it's probably legit (adrafinil, being less effective, would not keep me up so well).

I'm trying to work out if there's a way to test for the amide (modafinil) versus the hydroxamic acid (adrafinil). gwern.net (or googling indicator for amide group) says the amide will give ammonia when reacted with NaOH. What I'm wondering is if the hydroxamic acid will also produce this with NaOH. I'm guessing it wouldn't, since the hydroxylamine released would have to be further reduced to give ammonia; getting ammonia from that would probably need a different reagent like a metal catalyst with HCl or something. So, I'm thinking the NaOH test would be a decent test for the amide versus the hydroxamic acid, I'm just not 100% positive about the hydroxamic acid not producing ammonia. I was trying to read about hydroxamic acid indicators, and the best one I found was iron(III) chloride, which would turn red/purple in their presence. I doubt it would react the same way with an amide or carboxyllic acid, since the hydroxylamine bit would act as a bidentate chelator of the iron (probably responsible for its intense color).

Anyways, tl;dr: NaOH is probably a good, common indicator of modafinil vs adrafinil; it should give ammonia in the presence of modafinil but not adrafinil. Iron(iii) chloride could be used to test for adrafinil as well.

I wouldn't mess around with NaOH and start sniffing for ammonia unless you're careful/know what you're doing. NaOH is extremely corrosive.

p.s.: in my first reply, I never thought conclusively it was adrafinil. I just thought the shifted peak at 7.65 could be caused by the hydroxyl group on the amine, but it turns out if would be shifted much more (and the OH would have its own peak); so I was right that an N-hydrogen shifts upfield when functionalized with an -OH group, but just more so, and that's not what's going on here.

hey, rolling thunder, no worries (I'm also replying to your private message here since it's more or less the same) I understand what you mean about being concerned whether it's adrafinil or not. You can definitely send it to lab if you're concerned, but I have no idea how much it would cost, or where to do it. I would guess it would cost more than the pills themselves.

I could be wrong about this, but I feel like sending controlled substances (albeit a class IV substance) to a lab in the US probably isn't the best idea. Isn't that a good way to get caught?

yeah, you're right. I always forget that modafinil is controlled.

On second thought, there shouldn't be much D-H exchange; I think you would only really get this if D2O was used as the solvent.

Also, I just did a pubmed crawl for the NMR assignments. The N-hydroxylamine hydrogens would each be around 8-10, so it's definitely not adrafinil.

Still not sure what the 7.65 peak is. It's either one of the amine hydrogens or the one of the hydrogens between the S=O, C=O. This peak is absent from the paper I read, and has it instead at 6.1. Also, the paper I read has a peak at 3.6, instead of being merged in the 3.25 region. So, there should be two doublets around 3.2-3.3, a singlet around 3.6, and a singlet around 6.1. The two latter hydrogens might be shifted because a different solvent was used, maybe? This would make more sense if these hydrogens were from the amine.

In summary, it likely isn't adrafinil, as the hydroxylamine peaks are missing. If the discrepancy between the literature values I saw and the measured ones given here could be due to solvent effect (i.e., amine hydrogens influenced more by solvent), then it's reasonable that this NMR is indeed modafinil.

@peakplasma: thanks!

Wow, wonderful analysis. thanks for your reply. i know little about reading NMR
i can promise here that the NMR is for modafinil of the same batch. and if any more infro you need to tell whether it is modafnil or adrafinil, say the solvent, i will find out for your analysis.

hello bobert,
There are three similar compounds at play here:
1) Modafinil - The originial, racemic mixture (Perscription)
2) Armodafinil - Only the R-enantiomer (Perscription)
3) Adrafinil - Very similar, but the amine group has an alcohol attached to it. (Non-prescription, however, it is somewhat converted into modafinil inside the body)

When you said adrafinil did you mean armodafinil? I ask because in terms of the prescription version of this drug, adrafinil is different.
i mean modafinil. it is controlled.

Also, telling these three compounds apart via an NMR is VERY challenging, considering modafinil and armodafinil are just different mixtures of enantiomers, there is no way to compare them, especially across multiple NMR machines. (I am not 100% about how different two enantiomers NMR readings would be, there may be no difference whatsoever, but at most, it would be a very miniscule difference, probably too little to be able to determine if it was just from a variance in the NMR or compound itself)

Now telling modafinil and adrafinil apart (besides by taking it, there should be a much more obvious difference there) is much more possible with NMR. Based on what I know and some NMR simulator tools I can't link to because of my post count, the NMR you posted does seem to be modafinil. Now my question, however, is did the seller send you that or did you have it independently tested? Obviously the seller could send on a NMR of anything and tell you it was the compound they sent you and that may or may not be the case.
i give the modafinil to chemist and he do this NMR for me.

If you gave the sample to an independent chemist and got this NMR back, then your sample is definitely modafinil.
PhysicsMaestro -- thanks for saving me from having to dig out that old organic chem lab book! That's one hell of an interpretation you've done.

Phyaicsmaestro..are you a professor and how old are you..im so intrigued by the level of fluidity in your written knowledge on this stuff..I laughed the first time I read it..its like reading an ancient language..I started a .com in 2001 and consider myself somewhat smart.but after reading your diagnostic rant..I think I have a mancrush for the first time in my life..its making me rethink life as I know it!! Haha kidding. ..and the whole paypal wont let us sell it..what if I was a pp agent and chated with her..she seemed to open up pretty quickly about selling it..whats not to stop pp from doing a little digging. Which further adds to the crap factor..but hey even 250 for 100g is not that bad on a 50/50 risk..if it is adra at least its something
Edited by rolling thunder, 02 March 2013 - 05:03 AM.

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Amine exchange can be fast enough that you won't see anYthing conclusive.

Maybe just an IR spectra to see if an amide.