Drying solvents

Having properly functioning solvents is an absolute necessity for fine home chemistry work, especially for those interested in organic chemistry. Removal of water and other impurities from these which is often required for store-bought or homemade solvents, can be accomplished by many means, depending on the solvent.

General Techniques

Salting out

Main article: Salting out

Salting out is a technique that takes advantage of one solvent's reduced solubility in a solution of some compound relative to its solubility in pure water. This is mostly used for polar solvents that are miscible or highly soluble in water, especially when normal distillation produces an azeotrope. This technique is often used prior to distilling with a salt, as it cannot remove all of the water, but is a convenient way to remove most of it without having to use any anhydrous compounds, and it is one of the only ways to break an azeotrope outside of vacuum distillation. Examples of salting out include the separation of ethanol and water using potassium carbonate, the removal of isopropanol from water using sodium chloride, sodium hydroxide, or a mix of the two.

Anhydrous salts / Desiccants

Probably the most commonly used method for removing water from a solvent is by using the anhydrous form of a salt as desiccant. This process, which is useful for both polar and non-polar solvents, involves adding the salt (such as anhydrous magnesium sulfate, sodium sulfate, calcium sulfate, calcium chloride) directly to the solvent. Once the salt has hydrated, it can be removed by filtration or decantation, followed by distillation if necessary.

If water is present, a finely powdered anhydrous salt tends to "clump up" upon absorbing the water. Desiccants used for this process typically need to be checked beforehand to ensure that they will not react with the solvent in any way.

Chemical drying

In this technique, an appropriate water-reactive substance (a drying agent) is added to the solvent. Usually, drying agent is chosen so that the products of reaction with water are easily removed, eg by filtration or distillation. Substances commonly used for this purpose include magnesium (for alcohols), calcium oxide, calcium hydride, phosphorus pentoxide, and sodium metal (sometimes in combination with benzophenone).

Sodium should only be used in very clean solvents with a low starting water content, otherwise the risk is run of fire or explosion.

Molecular sieves

Main article: Molecular sieve

Molecular sieves are precise tools for the removal of water or other liquid components of a mixture. Using precisely sized pores in a material such as silica, clay, or alumina, they selectively trap molecules of a certain size by adsorption. While they may not be particularly cheap and can be difficult to re-dry after their use, molecular sieves have the advantage of being able to remove a significant amount of water from a solvent without introducing any of their own impurities. A disadvantage of molecular sieves, however, is the long amount of time they must be given to complete the water-removal process, often in excess of 24 hours.

Azeotropic distillation

Certain solvents can be efficiently dried by azeotropic distillation, sometimes using a Dean-Stark trap.

Determination of water content

In simple (binary) mixtures of an organic solvent and water, it is often possible to determine the approximate water content by measuring the density and consulting an appropriate lookup table/graph. This is somewhat imprecise and normally only usable for mixtures containing >= 1% water. However, the drying techniques presented on this page can usually get solvents much drier than that. For reactions requiring totally anhydrous conditions, it is valuable to have a means of verifying the water content of solvents which have been dried (part-per-million levels of water).

One relatively-simple technique is to use benzophenone and sodium. Sodium can reduce benzophenone to produce the benzophenone ketyl radical, which is a strong blue colour. The ketyl is very reactive and is destroyed by traces of water or dissolved oxygen. Therefore, a persistent blue colouration indicates very low water content in the solvent (typically around 20 to 50ppm). This technique is not compatible with protic solvents (like alcohols) or halogenated solvents, as these will react directly with the sodium. It can be used with non-polar solvents (for example, toluene or hexane) and with polar aprotic solvents, such as diethyl ether.

Quantitation of water levels is more difficult, but possible, using Karl-Fischer titration. This is an iodometric technique based on the reduction of I₂ by SO₂, which can only take place in the presence of water. Modern KF titration normally uses expensive specialised automated KF titrators, however it is possible to perform KF titration manually using simple equipment.

Solvent-specific recommendations

This section includes a commonly used method for drying a solvent that is sufficient enough for that solvent's typical use, either for solvation or as a reagent. This is not an exhaustive list by any means, and other methods can most likely be used.

Solvent	Method
Acetic acid	Anhydrous copper(II) sulfate Phosphorous pentoxide Fractionally distillation over 5% acetic anhydride and 2% CrO3.
Acetic anhydride	Drying with phosphorous pentoxide then fractionally distill over potassium carbonate Sodium wire (some sources)
Acetone	Salting out with sodium acetate, simple distillation to remove it from water followed by distillation over anhydrous calcium sulfate or magnesium sulfate. Drying with boron trioxide. Drying with anhydrous copper(II) sulfate
Acetonitrile	Drying with calcium chloride, followed by either distillation or decantation; Calcium chloride can also be used to keep the solvent dry Drying with anhydrous potassium carbonate, then 3A molecular sieves, followed by distillation Drying with phosphorous pentoxide (5% w/v), followed by distillation (tip: avoid this method if using in reactions with acid sensitive substrates)
Aniline	Distillation over potassium hydroxide Drying over calcium hydride, followed by distillation. Drying with barium oxide, decantation or filtration, followed by distillation over fresh barium oxide.
Anisole	Drying with calcium chloride/sulfate, another drying with sodium wire, followed by distillation over fresh sodium wire
Benzene	Drying with anhydrous sodium sulfate, followed by either decantation or distillation. Drying with phosphorous pentoxide, sodium, lithium aluminum hydride, calcium hydride, 4A molecular sieves, calcium sulfate, followed by decantation or filtration, usually with a fritted funnel Drying with alumina, calcium hydride or 4A molecular sieves, followed by distillation. Store over molecular sieves or sodium wire.
Butanol	Drying with magnesium sulfate, calcium oxide or potassium carbonate, followed by distillation over magnesium/iodine, sodium or calcium metal Drying with 3A moloecular sieves (powder)
sec-Butanol	Drying over potassium carbonate or calcium sulfate, followed by fractional distillation. Distillation over calcium oxide, then over magnesium. Distillation over calcium hydride.
tert-Butanol	Drying with calcium hydride (5% w/v), followed by distillation. Drying with calcium oxide, potassium carbonate, calcium sulfate or magnesium sulfate, followed by fractional distillation. Distillation over magnesium/iodine or calcium, sodium, potassium metal. Storage over 3A molecular sieves.
Carbon tetrachloride	Anhydrous calcium chloride, magnesium sulfate, 4A molecular sieves Refluxing with phosphorus pentoxide, followed by distillation.
Chloroform	Distillation over anhydrous magnesium sulfate Drying with phosphorus pentoxide followed by distillation.
Dichloromethane	Drying with anhydrous sodium sulfate or calcium hydride, followed by distillation Phosphorus pentoxide can also be used.
Diethyl ether	Dried using anhydrous calcium chloride, molecular sieves, followed by distillation For higher purity, sodium metal and benzophenone are used.
Dimethyl sulfoxide	Distillation in partial vacuum over molecular sieves; molecular sieves alone can be used for a few days Calcium hydride, calcium oxide, barium oxide, drierite, dry activated alumina can also be used to achieve near-dry DMSO, though further drying using molecular sieves and vacuum distillation is required to remove the last traces of water. Storage in the presence of dry 4A molecular sieves to keep it dry
Dimethylformamide	Drying with barium oxide or molecular sieves, followed by partial vacuum distillation.
Ethanol	Distillation of the 95% azeotrope followed by salting out with anhydrous potassium carbonate and a second distillation over anhydrous calcium or magnesium sulfate Direct drying can be done with magnesium metal, followed by distillation or filtration.
Ethyl acetate	Drying with anhydrous sodium sulfate, ethanol removal can be facilitated by salting out using potassium carbonate, followed by distillation of the ethyl acetate layer over anhydrous magnesium sulfate. Phosphorus pentoxide
Isopropanol	Salting out to 91% using sodium chloride, followed by salting out to 100% using sodium hydroxide. Once sodium hydroxide has been added and the two layers separated, the entire mixture should be cooled as low as possible to precipitate/freeze sodium hydroxide, which will hurt glassware in a distillation. The isopropanol layer can be poured off the frozen sodium hydroxide solution and distilled over anhydrous magnesium sulfate, preferably with a small amount of sulfuric acid present to mitigate glassware damage from hot sodium hydroxide.
Methanol	Salting out with potassium carbonate or simple distillation to remove from water with or without a desiccant Direct drying can be done with magnesium metal turnings, followed by distillation or filtration.
Methyl ethyl ketone	Drying with calcium sulfate, magnesium sulfate, sodium sulfate or potassium carbonate. Drying over boron trioxide
Nitromethane	Low alkaline 4A molecular sieves Anhydrous neutral magnesium sulfate, sodium sulfate.
Pyridine	Refluxing with calcium hydride or oxide, followed by distillation Activated 3A molecular sieves Anhydrous magnesium sulfate, sodium sulfate, potassium carbonate, CaO, BaO, NaOH, KOH.
Tetrahydrofuran	Distillation over molecular sieves Adding metallic potassium under inert conditions for complete removal of water, followed by distillation.
Toluene	Adding sodium metal with benzophenone, followed by distillation Azeotropic distillation with benzene, molecular sieves.
Triethylamine	Addition of sodium metal, followed by distillation Drying with calcium hydride followed by distillation.
Xylene	Drying with molecular sieves followed by distillation or decantation Distillation over sodium metal.

Desiccant compatibility

While most desiccants can be used safely to dry most common solvents, some cannot be used as they will either react with the said solvent or dissolve in it.

Desiccant	Compatible	Incompatible	Notes
Alkali metals	Alkanes, arenes, ethers	Acetone, alcohols, halogenated solvents, DMSO, nitromethane	Reacts violently with halogenated solvents, less so with alcohols and DMSO; air sensitive
Alkali metal hydroxide	Amines and pyridines	Acids, base-sensitive solvents, nitromethane	Reacts with acids releasing water
Alkaline earth metals	Alcohols, alkanes, arenes, ethers	Acetone, alcohols, halogenated solvents, DMSO	Reacts violently with halogenated solvents, less so with alcohols and DMSO; Reaction with alcohols give their respective alkoxides, that can be regenerated back to alcohol by adding water; air sensitive (except magnesium)
Alkaline earth metal oxides	Alcohols, alkanes, arenes, basic solvents, ethers, halogenated solvents	Acetone, esters, dipolar aprotic solvents	May react with alcohols in excess, will cause aldol condensation with ketones; not useful with dipolar aprotic solvents
Alumina	Alcohols, alkanes, arenes, esters, ethers, halogenated solvents	Acetone, acids	Reaction with acetone and acids
Boron trioxide	Acetone, acetonitrile, esters, ethers, halogenated solvents	Alcohols, basic solvents	Reacts with alcohols and basic solvents
Calcium chloride	Alkyl and aryl halides, esters, ethers, halogenated solvents	Acetone, acids, alcohols, aldehydes, amines, carbonyl compounds	Reaction of CaCl2 with acetone forms an addition compound
Calcium hydride	Alcohols, alkanes, amines, DMF, ethers, HMPA, pyridines	Esters, acids, nitromethane	Reacts with esters; air sensitive
Calcium sulfate	Acetone, alcohols, aldehydes, halogenated solvents, ketones and pretty much all solvents	Inert	Drying may be strongly exothermic
Cement (Portland)	Alcohols, alkanes, arenes	Acids, esters, nitromethane	Reacts with acids, esters; after hydration results in a very hard mass
LiAlH4	Alkanes, arenes	Alcohols, esters, halogenated solvents, nitromethane	Reaction with alcohols, esters, halogenated solvents
LiBH4	Alkanes	Alcohols, halogenated solvents, esters, nitromethane	Reaction with alcohols, halogenated solvents, esters
Lithium chloride	Alkanes, arenes, halogenated solvents	Butanol, propanol, methylformamide, hydrazine	Dissolution in alcohols, methylformamide, hydrazine
Magnesium sulfate	Acetone, alcohols, aldehydes, alkanes, arenes, esters, ethers, halogenated solvents, ketones, pretty much all solvents	Inert	May cause small traces of aldol condensation with acetone
Molecular sieves	Alcohols, ethers	Acetone, acids	Will cause aldol condensation of acetone; reacts with acids
Phosphorus pentoxide	Halogenated solvents	Alcohols, amines, organic acids and carbonyl compounds; HMPA, DMSO, acetone	Reaction; decomposition
Potassium carbonate	Acetone, alcohols, aldehydes, halogenated solvents, various ketones, methyl ethyl ketone	Acids	Reaction with acids releases carbon dioxide and water
Silica gel	Alkanes, arenes, esters, ethers	Acetone	May cause self-condensation with acetone
Sodium sulfate	Acids, alcohols, esters, ethers, halogenated solvents	Acetone, ketones	Will cause some aldol condensation with ketones

References

• http://ccc.chem.pitt.edu/wipf/Web/Solvent_Drying.pdf
• http://www.chem.ucla.edu/~bacher/General/30BL/tips/dryingofsolvents.html
• http://chemwiki.ucdavis.edu/Reference/Lab_Techniques/Distillation/Drying_Solvents
• https://www.scripps.edu/shenvi/Education_files/Drying%20Solvents%20handout.pdf
• http://www.sas.upenn.edu/~marisa/documents/drying.pdf

Relevant Sciencemadness threads

• Drying with molecular seives - how fast?
• drying with sodium metal

http://www.gaylordchemical.com/wp-content/uploads/2015/07/GC-Literature-109B.pdf