Hello DePaul Chemistry Community!
Dr. Grice here, I’m an inorganic chemistry professor in the Department. I teach general chemistry, inorganic chemistry, and other courses, and do research on inorganic chemistry and related areas. Here’s my departmental faculty page. Kyle Grice | Faculty A-Z | Faculty & Staff | College of Science and Health | DePaul University, Chicago
I want to talk about something near and dear to my heart in this post – Solvent properties! This information is useful for laboratory classes and also for students doing research projects (Did you know you can do research as a class for your experiential learning LSP requirement if you are a DePaul student?). Solvents are everywhere, and a solvent is just the major component in a mixture, usually the liquid that things are dissolved in, so most of the time when we talk about solvents, we are talking about liquids. Chemists use solvents as reaction media, for analytical methods like spectroscopy and titration, and in purifications such as crystallizations, acid-base extractions, and chromatography. In living systems and in nature, the common solvent is water, but many more solvents exist and their properties vary considerably.
Safety and Physical Properties
When working with solvents, it’s always good to review basic parameters: safety (toxicity/flammability/carcinogenicity/etc.), boiling point, freezing point, density, molar mass, polarity and if it’s miscible with water. That info is available in many places, including Wikipedia. The Safety Data Sheet (SDS) for a chemical also has basic properties and safety info. These can be found on supplier websites and other locations. Learning about the safety and physical properties of a compound is important for any chemical you will be working with, not just solvents. Many solvents have very flammable vapors, so you should not be working with open flames (like a Bunsen burner) at the same time as working with flammable solvents. The boiling point of a solvent is valuable to know because a lower boiling point means a higher vapor pressure (so the solvent will evaporate faster/will be easier to remove on a rotary evaporator for the o-chem folks!). Also, if you do a reaction in a boiling solvent, often called a reflux reaction, the temperature of the reaction will be approximately at the boiling point temperature.
I should note that freezing points of solvents is something we often ignore when thinking about solvent properties because many freezing points are very very low, but there are solvents that freeze close to room temperature. For example, if you have very pure DMSO or DMSO-d6 and your lab space is relatively cold (18 degrees Celsius or colder, which is about 64 degrees Fahrenheit), it can freeze on you because it’s freezing point is 19 degrees Celcius! I’ve had to run my bottles under warm water (tightly closed) or put them on a hot plate to get it to melt before dispensing. Once you make a DMSO solution by dissolving something in the DMSO, it’s freezing point drops, so it’s not as much of an issue. This is due to “colligative properties”, a concept I taught this quarter in Gen Chem II Lecture!
Some solvents are very polar and mix with water (“like dissolves like”) and some do not and will make two layers if you try to mix them with water (like oil and vinegar dressing or oil spills floating on water). Here’s a nice little table showing what solvents are miscible (can mix) or not. I have this posted in my research lab: https://www.precisionlabware.com/content/18-solvent-miscibility
Note that even if solvents are listed as immiscible (meaning they don’t mix and will form two layers if you combine them in a container, with the more dense liquid on the bottom), some small amount may dissolve in the other solvent. For example, when you take a Nuclear Magnetic Resonance (NMR) spectrum of a compound in chloroform-d (CDCl3), there’s always some water there even though chloroform is technically not miscible with water.
However, thinking about solvents doesn’t stop there! There are several other solvent properties/concepts that are important to think about and understand.
Acid-Base Characteristics – The Importance of Protons (or Lack Thereof)
One important aspect of solvents is acid-base chemistry. Remember that the pH scale and pKa values we usually look at are in water…. but as soon as you are doing chemistry in a different solvent, the pH scale and pKa values become different! A pKa tells you how acidic an acid is relative to other acids, and similarly a pKb tells you how basic a base is compared to other bases. Acid-base chemistry is discussed in general chemistry and in organic chemistry and is critical to understand for working with buffers, doing reactions with acids and bases, and in purifications like acid-base extractions.
So, how can you think about acid-base chemistry/pKa values in other solvents besides water? First of all, in any solvent, the strongest acid you can make is protonated solvent, and the strongest base you can make is deprotonated solvent. Anything stronger than those will just form the protonated or deprotonated solvent as soon as it touches it. This is sometimes called “the solvent levelling effect” because the solvent defines the levels of acidity and basicity that you can access. In water, you can’t have an acid stronger than hydronium (H3O+) or a base stronger than hydroxide (OH–). For example, if you try to put n-butyllithium, nBuLi (a compound with an extremely basic anionic carbon), in water, it’s so basic it will just react with water right away to make LiOH and butane (a gas at room temperature and pressure). You have to use aprotic organic solvents (not having any acidic or hydrogen bonding groups like OH or NH) like THF or diethyl ether when working with alkyl-lithium reagents (R-Li) or Grignard reagents (R-Mg-X) because they are so basic that they react nearly instantly with protic or somewhat acidic things like water. Similarly, putting a strong acid in water just makes hydronium, so you can’t make an acid stronger than hydronium in water.
For pKa values of organic compounds outside of water, often the numbers are reported in DMSO solution, and you can use those pKa values as a rough approximation for similar polar aprotic solvents in terms of what is more acidic/basic than what, but not quantitatively. The concept of “pH” doesn’t really work well outside of water, so we generally just consider pKa and pKb values to understand relative acidity and basicity in non-aqueous solutions.
Here are good resources for looking up pKa numbers:
The Evans pKa table is great, it’s a summary of a larger set of data:
A larger set of data for DMSO can be found here: https://organicchemistrydata.org/hansreich/resources/pka/pka_data/pka-compilation-reich-bordwell.pdf
An even larger set of pKa data in water: https://organicchemistrydata.org/hansreich/resources/pka/pka_data/pka-compilation-williams.pdf
For other solvents besides water and DMSO, my go-to has been Dr. Ivo Leito’s work. He’s a chemist in Estonia who has collected great pKa data for a variety molecules in a variety of solvents, including DCM, acetonitrile (one of the polar aprotic solvents I commonly use my catalysis research), and others. Here’s a compilation of his papers relevant to pKa’s in solvents:
https://analytical.chem.ut.ee/HA_UT/
DISCLAIMER: Some measurements in the literature can be wrong and mistakes could be made in writing or data processing, so there may be errors in large datasets! Mistakes get made in science because it’s a human endeavor and we make mistakes, it’s normal and inevitable. However, as scientists keep studying things and reproduce previous results, those mistakes eventually get caught and corrected. In this way, you can think of science as being self-correcting. Doing science in a team can also help prevent errors slipping into the literature because more eyes look over the results before they are published. If something can’t be reproduced by other scientists, its probably not real. A single paper or report on something new is exciting and interesting, but more than one paper is needed to build scientific consensus and further verify a result is reproducible and happening as initially described. This is also why it’s so important to share/publish all science, even if it’s not “big news” or “game-changing” for technology and society. News articles and social media posts about science sometimes over-inflate the real findings of a research article to make it sound more exciting, which can damage public understanding of what science is and how science is done. TV shows and movies also usually portray the process of science inaccurately to make things appear quicker and more dramatic than real science.
Here’s a blog post about a recent paper where researchers found that some literature pKa values were wrong: Incorrect pKa values have slipped into chemical databases and could distort drug design | Research | Chemistry World
Polarity – How Polar is Polar?
Ok… what about Polarity? We generally classify solvents as polar or non-polar, but really it’s a spectrum of polarity from low to high and different solvents lie at different values along the spectrum. Also, solvents can be protic (having acidic or hydrogen bonding groups like OH or NH) or aprotic (not having acidic or hydrogen-bonding protons). Methanol, ethanol, acetic acid, and water are polar protic solvents, whereas DCM, DMF, THF, and acetonitrile are polar aprotic solvents. Pentane, hexane, and heptane, etc. would be non-polar (and aprotic). If you have taken organic chemistry, you know that some reactions are more favored in polar protic solvents and others are more favored in polar aprotic solvents, such as SN1 vs. SN2 reactions.
Polarity can be measured or calculated a few different ways. Often a “dielectric constant” is reported for a solvent. These show up commonly on solvent property tables, including the miscibility table in the link I posted above in the “Safety and Solvent Properties” section. The dielectric constant is measured by capacitors, and it is not a dipole moment, which is another common way of thinking of polarity of a molecule. A dipole moment is the sum of the bond dipoles, something we teach in Gen Chem I Lecture. You can calculate overall molecular dipole moments using computational chemistry, and often dipole moments are correlated with dielectric constants. Basically, the higher the dielectric or dipole moment, the more polar the molecule!
But, I like some other ways of measuring polarity. My favorite is the ET(30) scale, which uses a “solvatochromic” dye from Dimroth and Reichardt, which is generally called “Reichardt’s Dye”. The dye changes color in a solvent due to the polarity of the solvent affecting the energy of the ground or excited state of the dye. Light excites a molecule from its ground state to an excited state, and the energy difference between those states is equal to the energy of light absorbed by the molecule, so different energy gaps give different colors of the dye (we see the complementary color to the absorbed color, so if a dye absorbs red, we see green, and vice versa). Many dyes are solvatochromic (change color based on solvent) and many dyes are also often pH-dependent (like phenolphthalein, a common indicator used in titrations… it changes color from colorless to pink when going from acidic to basic conditions!).
Here’s a table of ET(30) values: https://www.stenutz.eu/chem/dimroth.php
There are some limitations to Reichardt’s dye, but it’s pretty good and has been used in 1000’s of research papers! You can even use it to look at polarity of complex solvent mixtures, on surfaces, or in solids like polymers. I’ve got some in my research lab if anyone wants to try using it. Polarity will affect how well polar or non-polar things will dissolve in a solvent (that “like dissolves like” idea), which is valuable to know for reactions, crystallizations, acid-base and other extractions, and chromatography! Sometimes you can design a reaction (or just have it happen by luck) where your reactants are soluble but your product crystallizes/precipitates out of your reaction mixture, making purification a breeze. You just filter the solid off, rinse it, and dry it, and you’ve got your pure product.
Ok… so far, I’ve talked about simple physical properties, acid-base chemistry, and polarity… what else is there to know about solvents?
Hydrogen Bonding and Lewis Acid-Base Characteristics
But wait, there’s more! I want to mention two more topics: solvents as hydrogen bond donors/acceptors and solvents as Lewis Acids/Bases.
Hydrogen bonding kind of relates to polarity, but it’s a separate thing conceptually. Remember that Hydrogen bonding is the strongest intermolecular force (IMF) for pure substances, so it can have an outsized effect on molecular properties compared to dipole-dipole and dispersion IMFs. Protic solvents can do hydrogen bonding. This is why water, which has 2 O-H bonds and 2 lone pairs to accept hydrogen bonding, is a liquid at room temperature and doesn’t boil until 100 Celsius, even though it’s a relatively small molecule. Non-polar molecules of similar sizes (like CH4, methane) are gases at room temperature and can only be made into liquids at extremely low temperatures (-183 Celcius for methane)!
So, how can you tell how good a solvent is at being a hydrogen bond donor or acceptor?
Well, there are parameters for that! One set that I like is the Kamlet-Taft parameters, where one parameter tells you how good a solvent is a being a hydrogen bond donor (it has the H doing the hydrogen bonding) and one parameter tells you how good a solvent is at being a hydrogen bond acceptor (having a long pair to interact with the H from another molecule). For example, pyridine is a liquid that doesn’t have any OH’s or NH’s but it’s a great hydrogen bond acceptor because it has a relatively basic N lone pair.
Here’s a table of those Kamlet-Taft parameters:
https://www.stenutz.eu/chem/solv26.php
Another way of thinking about molecules is as them behaving as Lewis Acids (electrophiles) or Lewis Bases (nucleophiles), and this is true of solvents too! I think about this a lot because Lewis Bases make good “ligands” to bind metals (metals can be thought of as Lewis Acids). Water can be a ligand bound to metals, so can methanol, THF, pyridine, acetonitrile, etc.
I love the Gutmann parameters, AN and DN, which are Acceptor Number (how Lewis Acidic is the molecule) and Donor Number (how Lewis Basic is the molecule). You can measure these with calorimetry or spectroscopy, and I’ve had students use 31P NMR spectroscopy of triethylphosphine oxide to measure AN of a solvent mixture. Solvents that have high AN and DN values are good at dissolving ionic solids because the solvent can act as a Lewis Base to the cation of the ionic species and as a Lewis Acid to the anion of the ionic species. This is why many ionic species (like NaCl) are soluble in water but not in other solvents. We sometimes call those interactions “ion-dipole” forces between the solvent and solute, but considering them as Lewis-Acid-Base interactions is a little deeper of an understanding. In fact, when we write “Na+(aq)”, the reality is that the sodium ion is bound to about 6 water molecules, so it would be better described as “[Na(H2O)6]+”.
Here’s a great table of AN and DN values:
https://www.stenutz.eu/chem/gutmann.php
Solvents and Green Chemistry
Green chemistry is another thing you can think about when considering solvents. The 12 principles of Green Chemistry define the various ways you can think about making things more “Green”: 12 Principles of Green Chemistry – American Chemical Society
Fundamentally, Green Chemistry attempts to make chemistry less damaging to the global environment by making less waste, using less energy, and using safer chemicals. Some solvents take more steps and energy to make than others, and so are “less green”. Similarly, a solvent that doesn’t biodegrade well or is significantly damaging to the environment is “less green” than others. It’s good practice to try to find ways of reducing energy consumption and waste in reactions. You can substitute a “Greener” solvent for less green solvents, and there are some good articles and tables out there about this. As with many things, “Greenness” is not a black-and-white decision, it’s a judgement call and there are many aspects of “Greenness” to consider.
Table 7 in this paper shows some solvents’ “Greenness”, but other sources will have other rankings depending on what specific parameters they are considering: https://pubs.rsc.org/en/content/articlelanding/2016/gc/c5gc01008j
There’s also mechanochemistry, where you grind reactants together instead of heating them up in a solvent, and mechanochemistry can be very green because you usually eliminate the need for solvent in the reaction. Not all reactions work via mechanochemistry, but it’s a growing area of modern research with modern instrumentation (such as electronic ball mills or planetary mills and mixers). It’s also a very old area of research because the concept of mechanochemistry has been around since alchemists, the precursors to chemists, reported grinding chemicals together in mortars and pestles over 1000 years ago, and mortars and pestles themselves have been around since the stone age. We have a modern electronic ball mill in the department, and I am happy to show folks how to use it.
One More Important Point About Safety – Peroxide-Forming Solvents
We started with safety on this post, and I think we should end with safety, as we should always think about safety when we do our work. In addition to toxicity, carcinogenicity, and flammability, when working with a solvent, check to see if they are peroxide formers! These solvents slowly get oxidized by the O2 in air over the course of weeks/months/years make peroxides (R-O-O-H), which are potent oxidants that can affect your reactions and are explosive if they get concentrated enough. THF and other ethers (R-O-R) are the most common culprits, so if you have a bottle of THF or diethyl ether that’s been opened for while, it’s important to test it for peroxides. This is because the C-H bond next to the ether group has a weak C-H bond dissociation energy, so can be broken to make a radical that binds O2 to make a peroxide. You can get test strips to test solvents to see if peroxides have formed – you put a drop of solvent on the strip and look for a color change from white to blue. If you see solid crystals at the bottom of an old bottle of an ether solvent… consider it to be a very very very dangerous thing. So much peroxide has formed over time that the peroxide is now crystallizing out because it is so concentrated. Those crystals can be explosive even just from vibrations/scraping/etc., so do not touch the bottle, and contact your departmental safety or EHS representative. For us, that person to contact would be your research advisor or the lab managers.
Many THF bottles and other ethers are sold with BHT or another radical inhibitor in it that slows down that oxidation, but it won’t completely stop it over the course of months/years if it’s exposed to air. It also means that if you use those solvents, the BHT or other inhibitor in there that could affect your chemistry. Another way to prevent the peroxide problem is just store your solvents under N2 or Argon, but that usually can only be done well with smaller containers, not large solvent bottles. Keeping bottles dark/away from sunlight also slows down the oxidation. This is why most solvents are sold and stored in brown bottles! The UV light in sunlight is higher energy than visible light, and can make excited states that can break bonds and make the peroxides form quicker. Similarly, beer/wine/etc is sold in brown bottles to prevent damage that sunlight can cause (“off”/”skunky” odors and flavors). This is how sunburns work too, the UV light damages the molecules in your skin cells
Isopropanol (also called 2-propanol or “rubbing alcohol”) also forms peroxides over time, so an old bottle of isopropanol should be tested for peroxides. If you do a reaction or purification using isopropanol or an etheric solvent that’s been opened for a long time and you get products that are somehow more oxidized than you expected, peroxides could be the culprit!
Here’s a good paper on isopropanol forming peroxides: https://pubs.acs.org/doi/10.1021/acs.oprd.2c00112
The table in this paper has a list of molecules that can form peroxides: https://pubs.acs.org/doi/10.1016/S1074-9098(01)00247-7
Here’s a similar newer paper that also has a table of peroxide formers: https://pubs.acs.org/doi/10.1016/j.jchas.2013.12.011
The test for peroxides is based on the reaction of a peroxide with an iodide salt and starch in the presence of some acid. Peroxides oxidize two iodide (I–) ions into I2, which reacts with another iodide to form I3–, which is very bright blue/purple in the presence of starch. That’s all that’s in those test strips, so in a pinch you could do the test as a solution method with NaI or KI, some acid, and starch in water. Make the solution, add some of your solvent (even if not miscible with water), shake it up and look for a blue color. You could even make a calibration curve for it (using H2O2 or another commercially available peroxide to make standards of known concentration) using Beer’s Law and UV-Visible spectrophotometry, a tool we use in Gen Chem Labs, in other classes, and in research.
Organic peroxides do get used in organic synthesis, and can be used safely if you are using them properly and understand their reactivity. They are great oxidizing agents so can be used to oxidize things by installing an oxygen atom or removing a formal H2 equivalent from a molecule. meta-Chloroperbenzoic acid (mCPBA) is one of the more safe peroxide reagents and is a solid, while other peroxides can be viscous liquids or oils, or sold as solutions.
Ok, that’s enough for now!
Ok. I think that’s enough for now. You can see that thinking about solvents is more than just looking up their safety and basic physical properties! Hopefully this will help you have more appreciation for and understanding of solvents when using them in the future. They’re more than just a liquid you do a reaction in!
I’m hoping to do more of these blog posts about chemistry information and resources in the future, so if there’s any specific topic you want me to post about, shoot me an email. I might do posts about Redox Chemistry, NMR spectroscopy, Green Chemistry, and/or Catalysis in the future. Finally, if anyone has any other useful tables or links to resources about solvents or molecules that they like, I’d love to hear about them!
We have a Department of Chemistry and Biochemistry discord server that DePaul students (any major), faculty, staff, and alumni can join to continue the conversation about chemistry as well. Here’s the invite link: https://discord.gg/gYT8Juk
Sincerely,
Dr. Grice
PS – Many chemists have a favorite solvent or favorite solvents. My favorite polar aprotic solvents are acetonitrile and DMF, and my favorite non-polar solvent is heptane, because it’s less toxic than hexane and can be used to azeotrope/co-evaporate other solvents. I like water and ethanol for polar protic solvents because they are relatively “Green” and safe (although ethanol is flammable).
The Catalyst 