How to make organic single crystals - Part 1

How do you look at molecules?

The author specializes in organic synthesis, but I am really interested in visualizing molecular structures through X-ray crystallography.

I usually imagine molecular structures in my mind from information such as NMR.

In recent years, it is also possible to look at molecular structures in isolated systems by calculation.

This is exciting, but X-ray crystallography enables us to view not only the structure of a single molecule, but also the beautifully organized arrangement of molecules in the solid phase.

The aesthetic beauty of the unnatural alignment, which is a product of weak intermolecular forces, is indescribable, and stands in stark contrast to nature's ruthless law of increasing entropy.

However, X-ray crystallography is not easy.

Single crystals are required to view molecular structures in X-ray crystallography.

Once the technique is mastered, it doesn't take much effort, and if you enjoy it, you may even become as eager to grow single crystals as the author.

This time, I would like to discuss how to grow single crystals.

For me, making crystals is a nice break from my busy schedule because I can do it while waiting for concentration of reaction mixture or 13C NMR.

The reason I chose the title "organic single crystals" is because I believe that those in the inorganic field have know-how in the inorganic field.

I hope you will refer to it as the know-how in the organic field.

The availability of results from X-ray crystal structure analysis can enrich not only laboratory discussions but also academic presentations.

Why not take a photograph of the target compound you have synthesized and purified with your own hands?

Well, that's enough of the long preamble.

I would like to introduce how to make a single crystal.

The flow is as follows

1. Purify the sample

↓

2. Perform solubility test

↓ 

3. Single crystal preparation

It's easy, isn't it? (Once you get the hang of it, you may even skip the solubility test in STEP 2.)

1. Purify the sample

This is the process of removing dust from a chemically purified sample.

• Filtration using a syringe filter

This is easy. If you have the time, I highly recommend this method. 

Please be careful of the dust in the container to be filtered.

http://www.monotaro.com/s/c-85732/?sort=price

• Filtration during heat

If you can afford it, this method is preferable. 

If you are lucky, single crystals may be formed from the filtrate as it is, so you must act quickly.

*Make sure that the funnel and the flask to receive the filtrate are as dust-free as possible to avoid missing any chance opportunities.

2. Perform a solubility test

You only need a few milligrams of the sample in a vial to roughly determine the degree of solubility (dissolves easily, dissolves when heated, does not dissolve when heated).

As mentioned earlier, if you already know the solubility to some extent or have dealt with a sample with a similar structure before, you may skip this test.

Non-polar solvent

Protic polar solvent

Non-Protic Polar Solvents

Benzenes (non-polar and polar)

can be used.

*By attempting to grow single crystals in a single solvent system without changing the sample used for the solubility test, you can determine the solubility of the sample in that solvent system. This will give you a rough idea of the solvents' tendency to form crystals and the type of crystals they produce.

 3. Single crystal preparation

Finally, it is time to fabricate single crystals.

Generally, a sample of about 1 mg is sufficient for one examination.

Even if the sample has poor solubility, it can still be used if it dissolves even a little.

Microtubes or small vials are used as containers.

• Simple precipitation

Simple precipitation is easy to perform.

(1) Cover the solubility test sample with a simple lid made of wrapping paper, etc. and make a hole.

↓

(2) Leave it to stand.

• Precipitation from supersaturated solution

It is easy.

(1) Referring to the result of the solubility test, add solvent to the extent that the sample is not completely dissolved.

↓

(2) Heat the solvent to dissolve the sample completely.

↓

(3) Allow the sample to cool (if it can be cooled in a bath, try that as well).

• Precipitation by poor solvent

It is a little time-consuming, but various conditions are possible.

(1) Dissolve the sample in a good solvent based on the solubility test results.

↓

(2) Divide the solution into microtubes or small vials (less than 1/4 of the volume is desirable).

↓

(3) Prepare several large vials that can be put microtubes or small vials, and pour  a different poor solvent into each large vials.

↓ 

(4) Put the microtubes or small vials mentioned above into the large vials and close the lids to seal them. Needless to say, please do not put lids on the containers inside. I often do this when I am careless. lol

The above is an introduction to [how to make organic single crystals], which is longer than a useless story.

If you are already experienced in making single crystals, this may have been a bit of a "what's new" story.

In Part 2, I will share my personal tips and special techniques.

See you soon!