Suppose I have a mixture of 2 pure binary compounds, a white powder. What is the best method to separate the 2 compounds?

What I have thought of so far is to dissolve powder in DI water and carry out filtration if one compound is soluble and the other is not. However, I have not been able to think of any other methods to separate the 2 compounds if both are either water-soluble or water-insoluble. I considered fractional distillation but the compounds may become anhydrous. Furthermore, the boiling points of the compounds are not given and they could end up being too close for fractional distillation to work.

Is there any efficient, and preferably simple, method to achieve the above-mentioned desired result?

Edit: Is there any general method of approach for separating such 2 compounds as there is for separating water-soluble and water-insoluble compounds?[Filtration] Or does it have to be achieved purely by trial and error of various methods?

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    $\begingroup$ I think, for the most part, designing a separation procedure depends on you knowing the chemical identity of the two compounds. Like if you have AgCl and AgBr (not exactly a white powder, but I'm just trying to make a general point) you can separate them by addition of ammonia. The key is to find a reagent that reacts differently with both solids. Water is a possibility (e.g. Na2CO3 and AgCl), acid is a possibility (e.g. Ca(OH)2 and BaSO4). But if you don't know what the solids are, you're not going to know what that reagent is. $\endgroup$ Sep 28, 2015 at 14:09
  • $\begingroup$ Could also vary the volume and temperature used for dissolving the solids. Cold di water extractions? Or whatever solvents you are using That's if you don't want other information of your unknowns. Without solubility info, if it's weak acid/base, would be doing lot of trial and error and quantitative analysis just to see if any the solvents you may find are reactive. Maybe try using a spectrometer to get better idea of the compounds? $\endgroup$
    – Long dong
    Jun 14, 2023 at 1:46

2 Answers 2


Your question is about as broad as chemistry itself. Like you said, you may try dissolving them in water, if one is soluble and the other is not. If it's not working with water, chances are it will work with ethanol, or acetone, or... see, there are many solvents on the shelf. No luck? Maybe by now you've found something that dissolves them both, so you may try fractional crystallization. Still no luck? Maybe the compounds differ in density or selective adhesion of something, so flotation might help. Still no luck? Chromatography, by any chance? No? Distillation, like you said (provided they both would survive until boiling point), or maybe sublimation (good for $\ce{NH4Cl + NaCl}$)? No? Well, there is a multitude of chemical processes; some of them might change (that is, destroy) one compound or both, but probably in such a way that they can be regenerated later.

And if everything else fails, you can always look at the mixture under a microscope and separate the crystals manually.

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    $\begingroup$ "And if everything else fails, you can always task an undergraduate with looking at the mixture under a microscope and separating the crystals manually," you mean? ;-) $\endgroup$
    – hBy2Py
    Sep 28, 2015 at 14:53

If the powdered compounds are of different density you can separate them based on density in a liquid that does not dissolve them. For example, if you want to separate caffeine (density=1.36 g/cm3) from lidocaine HCl (density=1.20 g/cm3) you can tune the density of you separation medium to be between the two compounds in density. The more dense compound will sediment and the less dense will float achieving separation. A good hydrophobic separation medium in this case could be a mixture of tetrachloroethylene (density=1.62 g/cm3) and hexane (density=0.661 g/cm3)-tune the ratio of the two to tune the density of the separation medium. If the compounds do not dissolve in water you can tune the density of water solutions for used as separation mediums using compounds such as sodium chloride, or zinc bromide or similar to achieve high density solutions if necessary. In this case collect your separated fraction and rinse it with DI water to get rid of the salts.


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