[dcunhana]

Hi Guys,

I am a graduate student. Unfortunately I Work in my lab by myself and was hoping to get some guidance in some techniques. I have looked online. But doesn't seem to help my problem.
 
I  have been trying to do Recrystallization of my product. I have approximately 100mg and have been using ethyl acetate and hexane. I use a medium size Test tube to carry out my recrystallization. All I keep getting is powder like substance. I hope i could get some help with my problem and as well get answers to some questions I have in regards to Recrystallization

1. Does all compound have the capacity to recrystallize?
2. What are some good two solution system to use for recrystallization?
3. What would be the best way to purify 100mg of crude product?
4. Best way of making crystals for X-Ray crystallography. I have tried to dissolve few product in DCM and hexane, it does not seem to give me good crystals

Thanks for your help in advance.

Nap

[opsomath]

I've posted on here several times about general guidelines for recrystallization, try searching the topic.

If you post the structure, we can probably suggest a good solvent; however, I can almost guarantee you that EtOAc/hexane is a bad choice.

[dcunhana]

Thanks alot opsomath. I browsed and came across one of your post that I found useful for my problem.

http://www.chemicalforums.com/index.php?topic=66438.msg239102#msg239102


On another note. Why would EtOAc/hexane be a bad choice?

[opsomath]

EtOAc is too good a solvent to be good at recrystallizing most organic compounds, and both EtOAc and hexane have too low a boiling point, so that the total temperature swing isn't enough to really change the solubility a lot.

I remember having to recrystallize an unusual organic compound (iodoaniline) from heptane one time. The extra 10-20 degrees of boiling point made a big difference vs. hexane.

If you are doing a one-solvent recrystallization, you want your solvent to be an okay-but-not-great match for the polarity of your molecule. So, for most big flat nonpolar things, ethanol is a good choice; the ethyl end is a good match for the molecule, but the alcohol end is not, so it takes some heat to get it into solution. Then you take the heat away, and bam, crystals.

[orgopete]

I have done many many recrystallizations, including for x-ray crystallography. My preferred solvent is a two phase system. It isn't that a single solvent doesn't work, it is simply that one can create a saturated solution more quickly with  two solvents. My preferred is a solvent in which my compound is quite soluble and a higher boiling solvent in which my compound is less soluble. Ethyl acetate-hexane doesn't fit well to that description. 

However, that does not sound like the problem here, though the details have not been given. A recrystallizations is an experiment. What is happening? Let us take a hypothetical 99:1 mixture. If the 1% is more soluble, then the recrystallizations will succeed without problems. If the reverse, then perhaps before crystallization begins, you may see cloudiness from the less soluble impurity. Even if it is not being noted, if a hard and dense crystal is not forming, I suspect that may be the case here, an impurity can prevent formation of a pure crystal. Use a magnifying glass.

An impurity will affect one's results. If one had a 90:10 mixture, I would think it unrealistic to attempt to recover 90% of the product as 100% pure. The more pure your mixture, the greater the recovery one may target. If the product has a larger amount or a less soluble impurity, then you should expect a lower percent recovery of pure product.
If you want a pure product, try recovering less material.

[Archer]

X-Ray is all about slow growth.

My favorite technique for non air sensitive substances is to use a high boiling solvent (recently I used amyl acetate for a diazepine substance) one which the substance will actually crystalise from rather than making a glass. Make as saturated a solution as possible and then filter the solution in to a 10 ml volumetric flask (syringe filter is best). Protect the opening from dust without blocking it completely (glass wool is good for this) and let the solvent evaporate very slowly (weeks) if you get this right then this often yields big crystals.

Air sensitive substances are troublesome, you need to find two miscible solvents, one of which your compound is soluble in (i.e. ethyl acetate) and one it isn't (i.e. hexane). Dissolve the substance in the minimum ammount of the solvent in which it will dissolve and put this solution in an open GC vial under Argon. Place the vial in a quickfit flat bottomed flask containing the other solvent under Argon, make sure that the level of the solvent in the outer resevoir is well below the top of the vial. Seal the flask and keep the atmosphere inert while the solvents mix in the vapour phase and, eventually, they will mix in the liquid phase. Again this grows good crystals of air sensitive substances (or non-air sensitive, just omit the Argon) substances for X-Ray.

[opsomath]

There are some great responses on here. I just want to point out that there are two "schools" of crystal growth; one is trying to make large crystals for X-ray structures, one is trying to purify a compound from a crude mixture. The X-ray people care primarily about getting a small quantity of perfect crystals; the purification people just want an easy procedure that strikes a good balance between "getting most of your stuff back" and "reasonably pure product."

All the ones I've ever done are in the second category.

[dcunhana]

You'll guys are all awesome. I am gonna get my solvent evaporated and then try re-crystallization.

The compound I have is a conjugated compound that has a stilbene (-OH group on one of the phenyl) attached to a imidizopyridine and that is attached to pyridine. I am just gonna try using DCM and Hexane or petroleum ether or ethanol(slightly soluble). Fingers crossed.

Will keep you'll updated. Thanks once again

[Archer]

There are some great responses on here. I just want to point out that there are two "schools" of crystal growth; one is trying to make large crystals for X-ray structures, one is trying to purify a compound from a crude mixture. The X-ray people care primarily about getting a small quantity of perfect crystals; the purification people just want an easy procedure that strikes a good balance between "getting most of your stuff back" and "reasonably pure product."

All the ones I've ever done are in the second category.

I agree completely with opsomath, for X-Ray you only need one crystal which is at least 0.1 mm on two sides! that may only weigh a fraction of a milligram. Any other big crystals left once you have selected your prize are either going to look pretty in a vial forevermore or be difficult to get into solution for the next reaction step so percentage recovery is of no importance.

There is a good chapter on purification in the following book. I got this when I was emplyed as the only chemist as my first job, it proved invaluable.

http://www.amazon.com/Advanced-Practical-Organic-Chemistry-Leonard/dp/0748740716

One thing is for sure, the more you do the better you will become at them, good luck!