Question : This has always stumped me...........we all know the pyramid of LSD neeedlepoint, fluff, silver, lavender etc... So my question(s) is how do you get different crystals and why are some cleaner than others?
Answer:
Part 1
I will attempt to answer this and dispell some of the totally ridiculous myths I have heard about LSD crystal purity.
First of all, I would like to point out that I am an x-ray crystallographer. My who job consists of crystallizing molecules. When I worked in organic synthesis, we used crystallization as a purification technique. When it comes to biomacromolecules, crystallization is much more difficult and you are far more likely to come across polymorphs.
The reason that different crystal forms of the same substance can exist, even if they are of the exact same purity, has to partly do with the kinetics of nucleation and crystal growth. Essentially, when a crystal is growing it is trying to arrange itself into a three-dimensional lattice with a minimum of energy. Biomacromolecules are more likely to exibit different crystal forms because they can arrange themselves into lattices of similar energy in a number of different ways. With small molecules like LSD tartrate, there are less ways that the crystal can arrange itself into a stable fashion, so it is less likely that you will run into polymorphs.
So, why do polymorphs exist? Some crystal forms will have approximately the same energy, but sometimes crystallization occurs fast or slow. If crysallization occurs quickly, then the crystal form which has the lowest potential energy barrier to overcome during its growth will be prefferred. However, if crystallization occurs slowly and is reversible, then the thermodynamically most stable crystal form will be preferred. There could then be a mix of kinetic vs. thermodynamic crystal forms in between the two extremes.
Those are not the only two factors in crystallization, even for the exact same substance. Solvation is known to play a role in crystallization, so often solvent molecules will be hidden in the intermolecular spaces of a crystal and will show disorder (and these buggers are damn hard to find sometimes with diffraction data). Solvation can also affect the kinetics of crystallization. That is, with one solvent, crystal form A might be kinetically preferred with one solvent but another solvent might prefer crystal form B.
It is entirely possible to have two very different looking crystals of the same substance with essentially the same purity, just as it is entirely possible to have two similar looking crystals of the same substance with very different purity. You can't tell just by looking!
However, even LSD is known to show crystal polymorphism. This means that, absolutely pure LSD tartrate exists in more than one crystal form.
Please see:
Neville, G A. et al. USP lysergic acid diethylamide tartrate (Lot I) authentic substance recharacterized for authentication of a house supply of lysergide (LSD) tartrate. Can. J. Appl. Spect. 37, pp. 149 - 157. (1992)
In fact,
However, according to our experience more than 50% of various EA derivatives examined within the last few years exhibit two or even more crystalline forms.
from:
Kren, V. and Cvak, L. (eds). Ergot: The Genus Claviceps. Harwood Academic Publishers, 1999. p.285.
EA = "ergot alkaloid"
Furthermore, I will say this. The idea that someone can tell crystal purity by visual inspection alone is complete and utter bullshit. I have seen substances that usually crystallize into beautiful pure white crystals precipitate as purple coloured garbage under the exact same conditions (as far as I can control for, at least). Of course, my first thought upon seeing something like that, is "Oh, my sample sucks. I may as well get rid of it." Further analyses can be very surprising. In this case, it was less than 2% impurity disrupting the crystallization process and adding the purple colour.
I have also seen beautiful crystal that give such garbage diffraction patterns that the purity must have been far below 50%, even though the crystal looked just like the pure ones that gave good diffraction data.
I suggest that you take the "needlepoint, fluff, etc." reports with more than a few grains of salt. It's complete nonsense.
Part 2
In organic chemistry anything over a 95% yield is considered "perfect" and it's not at all unusual to be very, very happy with 80% yields. But, yes, if you calculate a theoretical yield, which is the amount you'd get if you had 100% yield in every step and your crystal weighed more than that, then you'd know there are impurities present.
The thing is that with an LSD synthesis, or any synthesis for that matter, the yields have probably been reported in the literature. So, as long as you reproduce the conditions from the paper you're using as a reference, you can be pretty sure that your end product will have a similar yield.
What I'm more or less trying to get at is that if you had two crystals that weighed, say 0.5 grams, but both were crystallized using different solvents and they both looked nice but just different, you can't really be sure which is more pure just by looking. They might be equally pure, or they might not. Now, generally in organic chemistry, crystallization is a purification technique so the "nicer" (yes, I mean "prettier") a crystal looks, the more sure you can be that it's of high quality.
This isn't always true though. Like I said, crystallization or recrystallization is a purification technique, which ends up wasting some product (but that could be recrystallized too and so forth). Sometimes a substance just doesn't seem to crystallize, which doesn't mean that you don't have a pure substance. Other times you might not get crystals at all, even with a perfect synthesis because of either an impurity* or something simple like dropping the temperature too fast.
* What I mean is that all of your starting material was converted to the product that you want, but something else is still sticking around.
Generally, with something the size of LSD, if you simply can't get the damn thing to crystallize that means that your sample is impure, but you don't know what the impurity is. The impurity might simply be an excess of tartaric acid or methanol, which isn't going to have much effect. You might still have made an absolutely perfect batch of LSD, but you can't get rid of the solvent molecules or some other small molecule that got picked up along the way. You wouldn't really know how much impurity you had just by looking.
So, say you did a by-the-book LSD synthesis and you knew that normally the yield is 89%, which in your case should give you 2.5 g of LSD, but your crystals add up to 2.7 g. You know that you've got some impurity in there, but what is it? It could just be a little solvent (this is often the case, especially with larger molecules).
Also, even if you ignore the "what does the crystal look like?" question and you know you've got some impurity in there, you can say to yourself, "Well, I followed the procedure exactly, so I probably have around an 89% yield." You can just adjust for the added impurities when laying out your blotter. Let's say you don't want to make that assumption and you try the synth again and you recrystallize from a different solvent, but this time you can't even get crystals, just precipitate (i.e. powder). You might have a pure batch of LSD right in front of you, so what happened? The solvent was interfering with crystallization. Maybe the temperature was dropped to fast. Maybe the crystal experienced some mechanical stress during growth and the stress caused so much disorder that your crystal looks really unusual (sometimes you get crystals that look like other crystals are growing from inside them and sometimes this happens to such a large extent that your crystals look like mess).
In the end, there are really far better ways than examining a crystal to determine purity. I have to shoot damn x-rays at my samples to get any idea of how pure they are and I doubt that underground labs are going to have diffractometers.
The best idea is to take the crystal, use a simple method to determine the quantity of LSD (ie. the purity) and then simply recrystallize it. You'll still have the same amount of LSD, regardless of what your crystals look like.
EDIT -
Now, don't get me wrong here. Many small molecules will crystallize in only one way, especially under the same conditions. That's never a guarantee that you know their purity by visual inspection, but in some cases it is a good indication of it. LSD, though I would call it a small molecule, is still large enough that I see solvation as a potential problem and don't think that visual inspection of crystals is at all meaningful. Also, think about this: I've never seen an analysis of purity of any substance done according to visual inspection of crystals, period. And, like I also said, I have seen beautiful crystals that are garbage and garbage "crystals" (ie. precipitates) that are of excellent purity. Crystals, for small molecules can often be a good indicator of purity, but it's not that reliable. Also, even if you end up finding out that the crystal (or precipitate) you have is only 50% pure, what does it matter if your impurity is something like methanol or tartaric acid? Half your crystal would still be pure LSD.
And I think that, is essentially my point. Though examining a crystal visually can sometimes be a good indicator of purity, it doesn't at all tell you what the impurities are. You could still have done an absolutely perfect synthesis and gotten garbage crystals with only 40% LSD, but what does that matter if the other 60% doesn't have any effect?
Part 3:
One last thing and I'll dig up the reference for this later (I don't feel like it now).
Colour, when there should be no colour, clearly means that there are impurities, but some substances are really highly coloured. As in my example above, even less than 5% impurities can totally change the colour of a sample.
In the case of LSD, many ergot alkaloids are known to dimerize, I think at the two position. The organic chemists in the crowd should be able to figure out what the effect of dimerization would be: extension of the pi system. What else does that do? Reduces the HOMO-LUMO gap. Meaning? The photons that the dimer absorbs will be of lower energy than plain old LSD. This means that the dimer will appear coloured.
Ergot alkaloid dimers are known to be dark purple or black in appearance. So, the appearance of purple or black in the crystal suggests that some of the product has dimerized. Still, even less than 5% of this stuff in the product could change an otherwise beautiful clear LSD crystal to a purple or black mess! Throwing away such a product would be a waste!
Part 4:
I guess one thing I should point out is this:
say you did the same synthesis in the same way a bunch of different times and you crystallized the product the same way a bunch of different times. If you had crystals of different appearance, of course you could determine their purity and this would give you a rough guide as to the correspondence between purity and crystal appearance. It would still, however, only be a rough guide and subject to a lot of error.
For example, if your main crystals were well characterized, 20 times over and they were consistently of high purity, then you could be pretty confident that the next time you saw those crystals under the same conditions, they're of similar purity. If the 'junk' you collected from the recrystallization gave different looking crystals and you assed their purity 20 times over and they were of the similar purity, then of course you could be pretty confident about purity the next time you saw them (provided all of the conditions are the same).
When it comes to the types of LSD crystal I've heard about though, I've never seen anybody describe how any type of crystal had its purity determined in the first place (it just seems to be an assumption). The only assays of purity I've ever seen have been bioassays, which are not (at all!) anywhere near reliable. You're talking about someone trying to assay the purity of a psychedelic drug, when they know beforehand what the crystal looks like.
I mean, honestly, just think about this: you do two syntheses. One gives beautiful crystals. One gives black precipitate. They could both be 95% pure. Are you really going to tell me that you would not be biased to believe that something was wrong with the black ppt? And you honestly think that upon ingesting them, your subjective experience would be in no way affected by that bias? Even though you're under the influence of the most potent hallucinogenic drug known to man?
Or, even if you did assay it's purity, and found that the black stuff was 60% pure and the nice crystal 98%, do you believe that wouldn't influence the effects in some way?
To be reliably convinced that the statements about needlepoint, fluff, etc. are anywhere near accurate and reliable, you would want to know that: (1) the synthetic method used was exactly the same each time. I don't just mean almost exactly. I mean exactly. Down to the same solvent and everything. (2) The different crystals or precipitates resulting from the synthesis and purification had already been well characterized by RELIABLE methods.
So, even if one synthesis, under certain conditions, produces a specific type of crystal (or ppt.) when it's X% pure, doesn't mean that a similar looking crystal (or ppt.) from a different (or even very similar) synthesis is amywhere near X% pure.
I hope that's clear.
