Extraction Flowchart Example

You may have an entire lab dedicated to separating organic compounds using extraction methods, but you will likely be using extraction in numerous labs throughout the year. The lab dedicated to extraction often has the students separating two or three organic compounds from each other by using only extraction techniques. In this post, I'm going to walk through the flowchart for separating three compounds: 3-methylphenol, 2-ethyl-3-methylbenzoic acid, and ethylbenzene.

Let's assume we have these molecules in a single solution of dichloromethane. Our goal is to separate them by extraction.

Eachof these molecules have aromatic rings (hydrophobic) but two of them also have ionizable groups (OH for 3-methylphenol and COOH for 2-ethyl-3-methylbenzoic acid). By using acid/base reactions, you can make these molecules charged/ionized which makes them more polar and therefore able to partition to the aqueous phase.

The following is a flowchart designed to separate these three molecules. In this example, the steps are already predetermined, the task is for the student to identify the structures of the molecules at each step:

In the first step, treating with a weak base (sodium bicarbonate) will convert the COOH to a carboxylate salt (COO- Na+) which is more water-soluble:

RCOOH  +  NaHCO3    <---->    RCOO-  +   Na+    +     H2CO3

By doing so, the benzoic acid molecule would become negatively charged (this makes it very polar), and because of this, it becomes much more soluble in water and will partition to the aqueous phase.

The 3-methylphenol has an OH group, but alcohols typically require strong base to deprotonate the H and become charged. Therefore, treatment with sodium bicarbonate (weak base) will have no effect on 3-methylphenol, and it will remain in the dichloromethane phase (organic layer).

Ethylbenzene has no ionizable groups, so treatment with any base or acid will have no effect on ethylbenzene. 

After the first step, the flowchart would now look like this:

 
In your aqueous layer, you would have your 2-ethyl-3-methyl benzoic acid molecule, but as the carboxylate ion form. In order to get it back to its carboxylic acid form, you just have to add acid:

RCOO-  +   Na+   +   HCl   <----->    RCOOH  +  NaCl

In your organic layer, you would still have a mixture of 3-methylphenol and ethylbenzene. Since 3-methylphenol has an ionizable OH group, you can treat this with a strong base:

ROH  +  NaOH   <----->   RO-   +   Na+    +   H2O

By doing so, the molecule becomes negatively charged (polar) which makes it able to partition to the aqueous phase. Ethylbenzene is not affected by NaOH, so would remain hydrophobic and remain in the organic layer. 

The flowchart would now look like this:

At this point, we have successfully isolated 2-ethyl-3-methylbenzoic acid as well as ethylbenzene.

In the last step, we just have to acidify the ionic form of 3-methylphenol. Like before, we just need to treat this with acid:

RO-  +  Na+   +   HCl    <------>     ROH    +    NaCl

The flowchart is now complete:

We started out with a mixture of three different organic molecules in a single solution of dichloromethane. There are numerous separation techniques that organic chemists use to isolate their molecules of interest, but extraction is one of the simplest approaches because it is generally quick and only requires a separatory funnel. 

By taking advantage of the ionizable groups of the molecules here, we were easily able to manipulate their water-solubility by treating with acid/bases accordingly. Ultimately, we were successfully able to design a extraction protocol to isolate all three components!

Extraction

Common questions about extraction:

• What is extraction?
• Why do we do extraction?
• What's the difference between extraction and "washing"
• What's the organic phase?
• What's the aqueous phase?
• Why is the organic phase sometimes on top and other times on bottom?
• How do we know which layer is the organic phase???

Extraction is an important skill that is learned early on because you end up using it in nearly every lab afterward. It is a very fast and (often) efficient way to separate a compound of interest from a mixture, and it only requires solvent and a separation funnel.

What is extraction?

The term "extraction" in this context means that your compound of interest is initially in one solvent and then partitions to a different, immiscible solvent (the extraction solvent). For example, you have caffeine dissolved in water, and you want to remove it from the water. To do this, you can mix with dichloromethane (immiscible organic solvent). By mixing, a fraction of the caffeine will partition into the dichloromethane solvent because it is more soluble in dichloromethane than water. Two solvent layers will then form (water and dichloromethane), and the majority of the caffeine will now be in the dichloromethane.

Why would you want to do this? Often in a case like this, there would be other impurities present in the initial water layer, and our goal would be to purify the caffeine from these other impurities. It doesn't get much simpler than mixing another solvent in and shaking. Also, another common reason for an extraction like this is to have your compound of interest in a more volatile solvent that is easy to remove. If your caffeine is in water, it'll take a VERY long time to remove the water and have an idea of how much caffeine you have. Instead, you can extract it into dichloromethane which has a low boiling point, and you can remove the solvent by roto-evaporation in minutes.

What's the difference between extraction and washing?

Sometimes you will see in your procedure that you need to perform "extraction" and other times it says you need to perform "washing," but both are using the same types of solvents and using a separatory funnel, so it sounds like it's the exact same thing. I never knew there was an actual difference until someone dumbed it down for me in grad school.

Simply, extraction is moving your compound of interest from one solvent to another. Washing is keeping your compound of interest in the same solvent, but the second solvent is used to "extract" other impurities.

Using the same caffeine example before, let's say you have your caffeine in your dichloromethane solvent, but you know there are traces of water droplets and salt still present in your sample. The easiest way to clean this up is to add some water and separate the two layers. This would be called "washing" because your compound of interest (caffeine) remains in the same solvent layer (dichloromethane). The impurities are actually the ones getting extracted because they are going from dichloromethane to the water layer.

What's the organic phase?

In every case (in orgo lab at least), the organic phase is an organic solvent that is NOT miscible with water. Common organic phase solvents used in the lab are diethyl ether, ethyl acetate, dichloromethane (aka methylene chloride), chloroform, hexanes, and benzene.

What's the aqueous phase?

The aqueous phase is the water-based phase that is NOT miscible with the organic phase. So obviously water would be an aqueous phase, but this also includes most acids, bases, and salt solutions. So this would include any time you have 10% HCl, 10% NaOH, acetic acid, sodium chloride, brine, sodium bicarbonate, etc.

Why is the organic phase sometimes on top and other times on bottom?

This is one of my favorite questions, and fortunately the answer is so simple! It's simply based on the density of the organic solvent. If the organic solvent is MORE dense than water, the organic phase will be on the bottom. If the organic solvent is LESS dense than water, it will be on top. It doesn't matter much if the aqueous phase contains HCl, NaOH, or some salt, the density of the aqueous phase will be roughly 1 g/mL. So for example, if you extract with chloroform or dichloromethane, your organic phase will be on bottom. If you extract with diethyl ether or ethyl acetate, your organic phase will be on top.

How do we know which layer is the organic phase???

If you're in the lab and don't have quick access to density values for your solvents (this is why we have you do pre-lab reagent tables!!), then you can do the water drop test. First, your layers must be separated, so either you have two layers in your sep funnel, or you've actually collected them separately into two separate flasks. Let's say they are both in your sep funnel. Simply add a drop or two of water from the top, and see where the water droplets go. If they seem to disappear in the top layer, then your top layer is the aqueous. If you see your water droplets fall down to the bottom layer, then your bottom layer is aqueous. 

Tips for lazy chemists:

• Make a flowchart if there are multiple extraction/wash steps and understand which components will be in the aqueous or organic phase. It can get confusing and overwhelming very quickly when you're doing it in the lab.
• Don't discard anything until the lab is finished. You don't want to accidentally throw away your product during one of the steps.
• When in doubt about which phase is which, do the water drop test! 
• For a practice flowchart problem, check out our example here.