As a solid state chemist, I've done suprisingly little crystal growth from solution at temperatures under 100 oC. (I've also never taken an inorganic chemistry laboratory course; there wasn't one offered at my undergraduate institution. I've run across a few paper that talks about layering solvents - a 1:1 ethanol:water solution containing the ligand was layered over an aqueous solution containing the metal source. I'd like to give the reaction a try. Having never done this, I thought that I could do this reaction in a small vial. A postdoc in the lab that I'm working in thought that you needed to do this in a thin tube (he has no experience with layering reactions either).
Could anyone provide some advice on growing crystals via layering?
I've done layerings in a number of ways, all of which work, but some of which are more elegant that others. I've used everything from a thin tube (best when you want to get that one phenomenal crystal for an x-ray structure) to a bucket (best when you're trying to purify that 20 g synthesis of Pd2(dba)3 and you just want a high yield of reasonably good stuff from which you have separated (a) the dust bunnies and (b) the Organic Road Tar (O.R.T, pronounced phonetically)).
Here are a few moderately useful things I've learned along the way:
1) If you need to do it carefully, use vapor diffusion, not a true layering.
2) If you need to do it fairly carefully, use a gradient. On the bottom, have water, followed by a thin layer of 50 proof, followed by 100 proof, followed by Bacardi 151, followed by a big layer of Everclear. This gives you slower crystal growth, and mimics the effect of vapor diffusion, but works in places where vapor diffusion is too slow (e.g. a mesitylene/ligroin recrystalization in a -35C glovebox freezer).
3. Decaf is your friend when pipetting on the top layer.
4. If you need it done crude, you can put your bottom layer down (which presumably contains your solute) followed by a thin cushion of the same solvent, followed by your co-solvent. When recrystalizations go pear-shaped, one of the biggest reasons is that your layers mixed while you were making up the layering. The cushion gives you a safety margin in case your hands aren't rock-steady (see point 3).
5. Sometimes the best way to do it is to fill your vial with the co-solvent, and pipette or cannula your solute solution onto the bottom of the flask, which raises the co-solvent as it fills in. This works amazingly well with some solvent pairs, and is so easy, it should be illegal.
6. I always start a layered recrystalization at -35, and if that doesn't give me something, I'll move to RT to accelerate mixing.
7. The best way to monitor your crystals is to forget that you're growing crystals. When you clean out the freezer on lab cleanup day, voila! You have xtals.
I actually do layering (crystal engineering) quite a bit. I usually dissolve about 20-25mg of my ligand in dichloromethane or chloroform(5 mL), and place that in a testtube. I then dissolve an equal molar amount of my metal salt in methanol (5 mL) and carefully layer that on top of the ligand solution. I then cover the test tube with parafilm, puncture a hole at the top, and let it sit for a week. Check for crystals every couple of days. We have been very successful growing single crystals like this at room temperature. Hope this helps. One of our papers describes this (Acta Cryst. 2007, C63, m436-m439).
Sibrina Collins, PhD College of Wooster
I would second Scott's advice.
Also, there is a simple guide called "Layman's Guide to Crystal Growing", of which you can get a pdf if you google it (hosted by texas A&M). I don't know who the original author was, but its a useful little document.
In my view, crystallization depends significantly on the desired product. It also involves a lot of luck. You've got a head start if you are following a reported prep, as you don't have to try all sorts of solvents.
Yes, you do need to pray to the crystal Gods to get it to work.
Sibrina Collins, PhD College of Wooster
I have experience of H-tube which is a sort of layering, and it works very well.
All you need a good clean practice + some good luck and lot of pray to the chemistry God.
I've recently been introduced to this fairly nice diffusion method. Take a disposable glass pipette and flame seal the thin end. Essentially put the flame right about where the pipette begins to taper, heat, pull and round off the closed end. If you are luck (and want them) you can even get some TLC spotters out of it. Dissolve your sample in this sealed pipette. Place it in a culture tube (https://www.sigmaaldrich.com/US/en/product/aldrich/cls7082516x) that contains the solvent you want to diffuse in. Of course make sure you do have too much solvent in the culture tube, you don’t want it to flow directly in to your pipette when you put it inside. I’ll generally start at room temp and see what happens. Go cold if need be. The fairly narrow opening of the pipette works pretty nice to keep things slow. I’ve also learned it isn’t a bad idea to make a really concentrated solution of the sample you want to grow crystals of, take a little bit of that and dilute it in a second pipette. This way you set up two attempts for the same sample. This technique also works nicely if you want to do a slow evaporation. Dissolve your sample as before, but put something like DMF or DMSO in the culture tube. This will give you fairly slow ‘reverse diffusion’ as your solvent diffuses into the DMF/DMSO.
In reply to I've recently been introduced by Chip Nataro / Lafayette College
that is actually very helpful, I have a question though, how much do you fill the sealed pipette? I understand you should fill it enough to allow the co-solvent to diffuse, so can we say it should be half filled as a start?