How To Purify Solvents in the labs?

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There are quality requirements for solvents used in organic synthesis. As one of the most reliable research chemical suppliers in China, we have a lot of custom synthesis to do and many solvents to process every day. Today we share some of our processing methods for solvent drying and purification used in our labs. Please check if they are also useful for you.

Acetone

Boiling Point: 56.2°C, Refractive Index: 1.358 8, Relative Density: 0.7899.

Ordinary acetone from the market often has a little water and reducing impurities within, such as methanol and acetaldehyde. Our purification method is as follows:

#1. Add potassium permanganate 2.5g to acetone 250ml and reflux. If the purple color of potassium permanganate disappears, continue to add potassium permanganate and reflux until the purple does not fade. Distill to collect acetone, then dry it over anhydrous potassium carbonate or calcium sulfate, then filter and distill to collect the fraction at 55-56.5 °C. When we purify acetone in this way, its reducing matter can’t be too much, or it will consume a lot of potassium permanganate and acetone and take longer to run the whole process.

#2. Put 100mL of acetone into the separating funnel, add silver nitrate solution 10% 4ml, 1mol/L sodium hydroxide solution 3.6mL, shake it for 10min. Then separate the acetone layer, and add anhydrous potassium sulfate or anhydrous calcium sulfate. Finally, collect the fraction at 55~56.5 °C by distillation.

The second method is faster, but the silver nitrate is expensive and it is only suitable to purify acetone by small amounts.

Benzene

Boiling Point: 80.1 °C, Refractive Index: 1.5011, Relative Density: 0.87865.

Ordinary benzene from the market often contains a little water and thiophene. The boiling point of thiophene is 84 °C, which is close to benzene’s 80.1°C, so we cannot remove thiophene from benzene by distillation.

Thiophene detection: Pur 1ml of benzene in a test tube and add in 2ml of concentrated sulfuric acid with indoloquinone 2mg dissolved. Shake the solution for a while, if you see blue-green color in the acid layer, it means thiophene exists.

Removal of thiophene and water: put benzene into a separating funnel, add concentrated sulfuric acid by one-seventh volume, shake to make the thiophene sulfonate. Then discard the acid layer, and add another one-seventh volume of concentrated sulfuric acid. Repeat the shaking and discarding several times till the acid layer is colorless to pale yellow, then run tests to make sure there is no more thiophene.

Wash the thiophene-free benzene with 10% sodium carbonate solution and water by turns, till it is neutral and then dry it with calcium chloride. Later distill it to collect the fractions at 80 °C, and finally, remove the trace water with pure sodium (Na) to obtain anhydrous benzene.

Chloroform

Boiling point: 61.7 °C, Refractive index: 1.445 9, Relative density: 1.4832

Chloroform can be oxidized easily into chlorine, hydrogen chloride and phosgene (very toxic) by sunlight, so we must store chloroform in brown bottles. Chloroform we get from the market has 1% alcohol as a stabilizer to eliminate phosgene. We can detect the ethanol in chloroform by iodoform reaction and the free hydrogen chloride by silver nitrate solution of alcohol.

Purification method #1: We can add a half volume of water to separate the lower chloroform several times to remove ethanol. Later dry it over calcium chloride for 24 hours, and then distill to get it.

Purification method #2: shake the solution of 200ml chloroform with 10ml concentrated sulfuric acid several times. After removing the acid layer, wash the chloroform with water, dry it, and then distill it to get anhydrous chloroform.

Anhydrous chloroform should be stored in a brown bottle and stored away from light to avoid phosgene from photochemical action.

Dichloromethane

Boiling point: 40 °C, Refractive index: 1.4242, Relative density: 1.3266

It is safer to use dichloromethane than chloroform, so dichloromethane often replaces chloroform as the extractant that is heavier than water. Ordinary dichloromethane can be used directly as an extractant. If you need to purify it, you can wash it with a 5% sodium carbonate solution, then with water, and then dry it over anhydrous calcium chloride. Collect the fractions at 40 ~ 41 °C by distillation and store the anhydrous dichloromethane in brown bottles.

Dioxane

Boiling Point: 101.5 °C, Melting Point: 12 °C, Refractive Index: 1.4424, Relative Density: 1.033 6.
You can mix dioxane with water by any ratio. Dioxane often has a little water and acetaldehyde. Dioxane may contain peroxides (see ether for identification and removal) after long-term storage.

How to purify: Add a solution of 8ml concentrated hydrochloric acid and 50 mL of water to 500mL dioxane and reflux for 6 to 10 hours. During the refluxing, nitrogen is slowly introduced to remove the acetaldehyde. After cooling, add solid potassium hydroxide till KOH could not dissolve. Separate the aqueous layer and dry it with solid potassium hydroxide for 24 h. Then filter and reflux 8-12 hours over Na. Finally, distill it with Na. We should store refined 1,4-dioxane from the air with Na wire.

Carbon disulfide

Boiling Point:46.25 °C, Refractive Index: 1.631 9, Relative Density: 1.2632.

Carbon disulfide is a toxic compound that could poison your blood and nervous system. It is highly volatile and flammable, so avoid any contact with its vapor.

For custom synthesis without strict purity requirement on carbon disulfide, add some anhydrous calcium chloride to dry it for several hours, and then distill in a water bath at 55 °C to 65 °C to collect the fractions.

If you need purer Carbon disulfide, add a solution of 0.5% potassium permanganate to wash it three times. This is to remove hydrogen sulfide. Then add mercury and shake it to remove sulfur. Finally, wash it with a solution of 2.5% mercury sulfate to remove hydrogen sulfide (wash until there was no H2S odor), dry it over calcium chloride, and then distill to collect.

DMF

Boiling Point: 149 ~ 156 °C, Refractive Index: 1.4305, Relative Density: 0.948 7.

It is a colorless liquid that can be mixed with most organic solvents and with water by any ratio. Both organic and inorganic compounds are easy to dissolve in it.

DMF often contains a little water. It will decompose during atmospheric distillation, producing dimethylamine and carbon monoxide. Its decomposition is accelerated by acids or bases. If you add in solid potassium hydroxide (sodium) for several hours at room temperature, it will partially decompose. Therefore, we must use neutral substances to dry it such as molecular sieves, calcium sulfate, magnesium sulfate, barium oxide, silica gel, followed by distillation under reduced pressure to collect the fraction at 76 °C/ 4800Pa (36mmHg).

if there is too much water in it, add 1/10 volume of benzene, and distill to remove water and benzene below 80 °C at normal pressure. Then dry it over anhydrous magnesium sulfate or barium oxide, and finally distill it under reduced pressure. The purified DMF should be stored away from light.

If free amine is present in DMF, we can detect it by color reaction with 2,4 dinitrofluorobenzene.

DMSO

Boiling Point: 189 °C, Melting Point: 18.5 °C, Refractive Index: 1.4783, Relative Density: 1.100.
DMSO often absorbs water and we get rid of water by molecular sieves. We can distill it under reduced pressure to collect the fraction of 76 ℃ by 1600Pa 12 mmHg. During distillation, the temperature can not be higher than 90 °C, otherwise, disproportionation will occur to produce dimethyl sulfone and dimethyl sulfide. We can also dry it with calcium oxide, calcium hydride, barium oxide or anhydrous barium sulfate, and then distill it under reduced pressure.
DMSO may explode when you mix it with sodium hydride, periodic acid or magnesium perchlorate, please note.

Ethanol

Boiling Point: 78.5 °C, Refractive Index: 1.361 6, Relative Density: 0.7893

There is more than one method to get anhydrous ethanol, so we choose different methods according to the different qualities required.

If you need 98% ~ 99% ethanol, you can choose those 2 methods as follows:

(1) As ethanol will form an azeotrope with benzene and water, we add benzene to ethanol for fractional distillation. We will get the ternary azeotrope of benzene, water, and ethanol at 64.9 ℃. We will get the binary azeotrope at 64.9 ℃, and finally, we get ethanol. This is also the industrial way to get tech-grade anhydrous ethanol.

(2) Dry with quicklime. Add 20g of fresh quicklime lumps to 100mL of 95% ethanol, reflux it for 3-5 hours, and then distill to get it.

If you need ethanol 99% as min, check the following method:

(1) Add 7 g of Sodium into 99% ethanol 100ml. After the reaction of Na and water is over, add 27.5 g of diethyl phthalate or 25 g of diethyl oxalate, reflux for 2 to 3 hours, and then we distill to get it.

Although Na can react with water in ethanol, the sodium hydroxide will react with ethanol in equilibrium to produce water. Therefore, Na alone cannot completely remove the water in ethanol, and we have to add high-boiling-point esters, such as diethyl phthalate, to interact with the sodium hydroxide to inhibit its reaction with ethanol. Then we can get rid of the water within.

(2). Add 5 g of magnesium and 0.5 g of iodine into 60 mL of 99% ethanol. After the magnesium is dissolved to form magnesium alkoxide, add 900 mL of 99% ethanol. After refluxing for 5 h, we can get 99.9% ethanol by distillation.

Because ethanol is very hygroscopic, we must act fast during the whole process. Minimize the transfers to prevent moisture in the air from entering. At the same time, the instruments to be used must be dried beforehand.

Ether

Boiling Point: 34.51 °C, Refractive Index: 1.3526, Relative Density: 0.71378. 

Ether from the market usually contains 2% ethanol and 0.5% water. It even contains peroxide after long-term storage.

Peroxide detection and removal: 

Drip 2~3 drops of concentrated sulfuric acid, 1ml of potassium iodide 2% solution and 1~2 drops of starch solution in a clean test tube. Shake it to mix them, then add ether. If you see a blue color, it means there is peroxide. 

Peroxide Removal: We can use the solution of ferrous sulfate to get rid of peroxide. Put ether 100ml and newly-prepared ferrous sulfate solution 10ml in a separatory funnel and wash them several times until there is no more peroxide.

Ethanol/water Inspection and Removal: 

Put a little potassium permanganate powder and a grain of sodium hydroxide in ether. If you see a brown resin on the surface of sodium hydroxide, it means there is ethanol within. We can detect water by anhydrous copper sulfate through color reaction. We can remove most of the water by anhydrous calcium chloride and then get rid of the trace water by Na. Detailed methods as follows: 

Pour 100ml of ether in a dry conical flask, add 20~25 grams of anhydrous calcium chloride, then seal the flask with a cork stopper for at least one day, shake it intermittently. Then distill to collect the fractions at 33~ 37 ℃. Add Na slices 1g into the flask containing ether, and then plug a cork with a calcium chloride drying tube. if Na slice becomes yellow and thick, distill the ether again, and then add Na slices in again for storage.

Ethyl acetate

Boiling Point: 77.06 °C, Refractive Index: 1.3723, Relative Density: 0.9003

Ethyl acetate is generally 95% to 98% and may contain water, ethanol and acetic acid. 

You can purify it by adding 100 ml of acetic anhydride, 10 drops of concentrated sulfuric acid to ethyl acetate 1000ml. Reflux for 4h to get rid of ethanol and water, and then distill. Then add 20-30 g of anhydrous potassium carbonate to the distillate, and distill again. The final product has a boiling point of 77 °C and its purity will be 99% as min.

Methanol

Boiling Point: 64.96 °C, Refractive Index: 1.3288, Relative Density: 0.7914

Unrefined methanol contains 0.02% acetone and 0.1% water within. Impurities can reach 0.5%~1% for the industrial type. 

To get methanol 99.9%, you can distill it with a fractionation column. Collect fractions at 64 °C and dry it with magnesium (the same as for ethanol). 

Methanol is toxic and you should avoid inhaling during handling.

Petroleum ether

Boiling Range: 30 ~ 150 ℃, Collection Temperature Range: around 30 ℃.
Petroleum ether is from light petroleum. It is a mixture of alkanes with low molecular weight. There are petroleum ethers with different boiling ranges: 30 ~ 60 ℃, 60 ~ 90 ℃, 90 ~ 120 ℃.

It contains a little unsaturated hydrocarbon with similar boiling points we can not remove by distillation.

How to purify: wash it 2 to 3 times with the same volume of concentrated sulfuric acid, and then with the saturated solution of 10% sulfuric acid and potassium permanganate until purple in the water layer no longer disappears. Wash with water and dry over anhydrous calcium chloride. Distill to get it at last. To get absolute anhydrous petroleum ether, add Na slices to get rid of trace water.

Pyridine

Boiling Point: 115.5 °C, Refractive Index: 1.5095, Relative Density: 0.9819.

Analytical-grade pyridine contains a little water but you can still use it for ordinary experiments. To get anhydrous pyridine, reflux it with granular potassium hydroxide (or sodium hydroxide), and then collect the fractions. Pyridine is very hygroscopic and we should seal the container well with paraffin during storage.

In case you have other better methods to purify those solvents in the labs, leave us a comment below and let’s discuss together.