Solvent of the week #1: 2-Methyltetrahydrofuran MP: -136 °C BP: 80 °C Density: 0.854 g/mL
Description: This virtuous solvent is a flammable organic liquid. It is like a version of THF that is not miscible in water and has higher BP (80 instead of 66 °C) so can be used at higher temp for reactions under reflux. While expensive, 2-MeTHF is popular due to its complete and very clean organic-water phase separation. Its solubility in water decreases as temperature increases; a rare property. Also with a lower density than ethyl acetate (0.854 instead of 0.897 g/mL) there is less chance of an emulsion during workup. With MP of -136 °C, 2-MeTHF is a valued solvent for low temperature reactions. 2-MeTHF forms a glass (does not crystallize), so is often used as a solvent for spectroscopic studies at −196 °C. 2-MeTHF is used in biphasic Grignard reactions and is great for azeotropic removal of water. I've ordered a bottle and I look forward to trying a reaction in it. 2-MeTHF: Don't leave home without it.
Solvent of the week #2: Formamide MP: 2 °C BP: 210 °C Density: 1.133 g/mL
Description: Formamide (aka methanamide), is a clear, hygroscopic, oily liquid that is miscible with water & alcohols. It dissolves many ionic compounds that are insoluble in water, making it a great solvent for salty/sugary reactions. Its high BP and decomposition to small amounts of HCN at reflux lead chemists to prefer dimethylformamide (DMF). Neither formamide or DMF are easily removed by vacuum but formamide has lower solubility in benzene/toluene than DMF so it's possible to remove an organic reaction product from formamide by benzene extraction. Can be used in microwave assisted syntheses. Degrades in microwave at 170 °C to CO & NH3 which may be done deliberately as a source of CO or NH3. A quirky solvent to be saved for a special occasion. Formamide: Formula 1.
Solvent of the week #3: Tertiarybutylmethylether (TBME) MP: -109 °C BP: 55 °C Density: 0.740 g/mL
Description: This virtuous solvent is a flammable organic liquid. It has very low miscibility in water and has higher BP than diethyl ether which makes it easy to use outside fumehood. Azeotropes with H2O (53 °C; 96.5% TBME) and methanol (51 °C; 69% TBME). As a recrystallization solvent, methanol may be added as anti-solvent with the flask cooled slowly to give crystals. TBME is known to permeate and contaminate groundwater. TBME is well used for separation by column chromatography in various blends with hexane. TBME typically has no radical scavenger stabilizers and formation of peroxides is negligible; so a good choice for high dilution experiments or evaporating large column fractions with only milligram quantities of desired material. TBME: We'll get you there.
Solvent of the week #4: Chloroform MP: -64 °C BP: 61 °C Density: 1.483 g/mL
Description: Chloroform (CHCl3) is a dense organic liquid, well known for use in extraction due to phase separation from water. Deuterochloroform (CDCl3) is a common NMR solvent. Commercially available CHCl3 is stabilized by ethanol (slightly more acidic so gives up its proton first); to prevent formation of reactive dichlorocarbene species (:CCl2). In some syntheses :CCl2 is produced intentionally by addition on conc. NaOH (eg; preparation of isocyanides from amines). Most times, CHCl3 should be kept away from strong base. Old publications tell of using either "neat" or "alcohol free" CHCl3. Label on bottle: "Contains 99 - 99.4 % chloroform. Contains 0.6 - 1 % ethanol". My 1968 book on thin layer chromatography has a solvent section:
"The elutive action of chloroform that contains the usual 0.5 to 1% ethanol is quite different from that of pure chloroform. Ethanol is most easily removed from chloroform by passing it through a column of activated alumina. 250 mL commercial chloroform is allowed to percolate through a column 20 cm high and 3 cm diameter, containing 125 g Woelm basic alumina (activity grade I), at a rate of 1 mL eflux per minute. The first 150 mL is discarded."
A more modern small scale preparation of alcohol free CHCl3 is:
Prepare just prior to use. Shake 20 mL of CHCl3 gently but thoroughly with 20 mL of H2O, draw off the CHCl3 layer and wash twice more with 20 mL portions of H2O. Shake for 5 min with 5 g of powdered anhydrous MgSO4. Pass CHCl3 through dry filter paper.
Alcohol free CHCl3 should be used:
when reactions are hydroxyl sensitive
to keep organic phase anhydrous in biphase reactions
for complete separation in H2O/CHCl3 extraction
Chloroform: Not just for muggers.
Solvent of the week #5: Carbon Tetrachloride MP: -23 °C BP: 77 °C Density: 1.587 g/mL
Description: A colourless dense liquid, carbon tetrachloride (CCl4) has been banned, despite its great properties for dissolving fats, oils and other non-polar compounds. CCl4 was previously used as a refrigerant and a dry cleaning solvent. It has no C-H bonds so is non combustible and may be used to extinguish flames. CCl4 is useful in synthesis as it can dissolve iodine (I2) and can be used to extract rare earth metals from an aqueous phase. CCl4 was used as a 1H-NMR solvent. You might add 1-2 drops of CCl4 to an NMR tube when the deutero-solvent fails to dissolve a compound. It'll be easier to remove than d6-DMSO. Carbon Tetrachloride: Duck's guts of solvents.
Solvent of the week #6: 1,2-Dichloroethane MP: -35 °C BP: 84 °C Density: 1.253 g/mL
Description: This virtuous solvent is a flammable organic liquid. 1,2-DCE is in the family of chlorinated solvents with similar properties to chloroform, however is not ethanol stabilized so holds less water. It gives organic-water phase separation, but it is less dense than CHCl3 so emulsions can form more often in an extraction. 1,2-DCE is useful for keeping H2O to a minimum without the need for alkali drying/inert atmosphere. 1,2-DCE azeotropes nicely with water at just 70 °C. Thus 1,2-DCE is great for those reactions where H2O can react with your intermediate and reduce your yield; rotavap dry when start material gone, then workup in another organic solvent like ethyl acetate or CHCl3. I've found that 1,2-DCE is surprisingly good at dissolving polylactic acid (PLA), a highly insoluble polymer. 1,2-DCE: Has the solution.
Solvent of the week #7: 2-Ethoxyethanol MP: -70 °C BP: 135 °C Density: 0.930 g/mL Description: 2-Ethoxyethanol (aka ethyl cellosolve) is a clear, colourless liquid that is miscible with water, ethanol, diethyl ether, acetone & ethyl acetate. It can dissolve chemically diverse compounds: oils, resins, grease, waxes, nitrocellulose & lacquers. This is an ideal property for multi-purpose cleaners, therefore it is used in products such as varnish removers and degreasers. Mixes nicely with water and organics, so you might try 2-ethoxyethanol as a blend for your next tricky reaction. 2-Ethoxyethanol: shits upon reason's back.
Solvent of the week #8: Acetic Acid MP: 16 °C BP: 118 °C Density: 1.049 g/mL
Description: Acetic acid; known as glacial when is it removed from H2O, is a colourless fuming liquid that is a weak acid. It may be used as a solvent when very polar solvating properties are desired along with a low pH. Not the most benign solvent but miscible in hexane or CHCl3, so can dissolve compounds that dissolve in these. Acetic acid is the key ingredient in vinegar, thus used to remove grease stains from floors. A high BP so hard to remove by vacuum, but may be removed by cooling as in many cases it will be first to precipitate. An even better way to remove from an organic phase is by an aqueous sodium bicarbonate wash. Sodium bicarb is gentle enough to only make sodium salts of carboxylic acids. Don't open glacial acetic acid outside fumehood or prepare for glare from co-workers. Acetic acid is known to dissolve many types of basic celite. Given its reactivity (solvents should be non reactive), I recommend to save this one for a more adventurous reaction. Acetic Acid: Spray and wipe.
Solvent of the week #9: N-methylpyrrolidone MP: -24 °C BP: 202 °C Density: 1.028 g/mL
Description: NMP is a liquid miscible with H2O, ethyl acetate, CHCl3, benzene and lower alcohols or ketones. It is a high BP solvent, but may be washed away from reaction mixtures by EtOAc phases over 1M LiCl(aq). It is widely used in polymer chemistry to reduce viscosity of polymer blends. When I worked as a polyurethane chemist, we used a deep fryer filled with NMP, placed in a fumehood. To clean cured polymer from drill bit spindles or glass we'd turn on the deep fryer for 30 min to find cleaned metal/glassware in a steaming hot NMP bath. Smelled like almonds. NMP: Smells like almonds!
Solvent of the week #10: Diethylformamide MP: -46 °C BP: 177 °C Density: 0.874 g/mL
Description: Diethylformamide (DEF), a dipolar aprotic solvent, has similar properties to its well known cousin DMF. DEF has been used to synthesize metal-organic framework ligands, is of interest as a cryogen since it won't easily co-crystallize with water, and it often gives cleaner reactions than DMF which tends to be cruder as its C-N bond cleaves more readily than DEF. Have a compound that's too organic to dissolve in DMF, but you need dipolar aprotic properties for your mechanism or catalyst? Try DEF. Today's price from Sigma-Aldrich is AU$146 for 100 g. DEF: Like a fine Scottish whiskey.
Solvent of the week #11: n-Heptane MP: -90 °C BP: 98 °C Density: 0.680 g/mL Description: n-Heptane is a clear liquid hydrocarbon. The n refers to it being a normal alkane with no branching. It will clearly not dissolve in water. Classically, aqueous bromine is distinguished from aqueous iodine by extraction into heptane. In water the bromine and iodine are both brown. Iodine turns purple when dissolved in heptane while the bromine stays brown. Similar dissolution properties to hexane, but won't harm brain cells by axonal swelling - you might consider you and your fellow co-workers' health by using heptane in place of hexane for your next flash chromatography. Heptane also comes much purer than hexane when used neat from commercial sources. You can recrystallize something in boiling heptane - 98 °C - you're much more likely to dissolve compound in an n-alkane at 98 °C than at hexane's BP of 68 °C. n-Heptane: By the people, for the people.
Solvent of the week #12: m-Xylene MP: -48 °C BP: 139 °C Density: 0.860 g/mL
Description: m-Xylene, a non-polar hydrocarbon is found in petrol. The m refers to the meta isomer of xylene (1,3-methyl-benzene). m-Xylene has very low water miscibility and high BP. However, it has lower MP than the o and p isomers of xylene so has wider scope for recrystallizations as it won't solidify in the freezer. Pentane may be added as anti-solvent, then removed at will by evaporation. m-Xylene is curiously more viscous at RT than related hydrocarbons like benzene, toluene & n-alkanes. m-Xylene is the more stable xylene; heating p-xylene with HCl & AlCl3 causes irreversible alkyl migration to give the m-xylene isomer. I've removed m-xylene from crystals by placing on a vacuum schlenk line with flask in 60 °C water. The compound had an increased MP and a much sharper IR spectrum. Alignment of pi electrons above and below the plane of the ring makes m-xylene more able to dissolve ionic compounds than you'd think, especially at high temp. Solubility of more polar organic compounds is well achieved by increase to 120 °C and cooling back to room temp often gives a good amount of precipitate. This gives an advantage over benzene/toluene which boil before 120 °C. Example: Solubility of Benzamide in m-Xylene Benzamide, Wt. % of Total Solution Temp., °C 0.5 57 1.0 68 5.0 95 10 105 20 108 40 110 50 112 m-Xylene: No. 1 for customer satisfaction.
Solvent of the week #13: Ammonia MP: -78 °C BP: -33 °C Density: 0.860 g/mL (at BP)
Description: Liquid ammonia (NH3) is a widely used non-aqueous ionizing solvent. It has a most conspicuous property: it can dissolve alkali metals to give deep blue or bronze, electrically conductive solutions with solvated electrons. Much of the chemistry in liquid NH3 can be compared with related reactions in aqueous solutions, however NH3 has lower MP, BP, density, viscosity, dielectric constant and electrical conductivity than water. Hence it will dissolve your metals, but have a much better chance to dissolve your organic compound compared to an aqueous solution. Metal-ammonia solutions can be used as a tool for structure elucidation of natural products by their ability to split bisbenzylisoquinoline alkaloids to simple benzylisoquinolines. A solution of sodium in liquid NH3 allows many targeted syntheses by selective hydrogenation of aromatic rings with ethanol as a proton source (Birch reduction). Ammonia: Don't try at home.
Solvent of the week #14: Magic Acid MP: -78 °C BP: 150 °C Density: 2.415 g/mL
Description: Magic acid consists of fluorosulfuric acid and antimony pentafluoride in a 1:1 ratio. With stronger proton yielding power than sulphuric acid, magic acid is considered a superacid. Clearly not a benign solvent, magic acid can be used to dissolve ionic substances when a water free substrate is required. It is often used at <50 °C. Magic acid is strong enough to protonate saturated alkanes to form pentavalent carbonium ions, therefore it can ionize and dissolve solid paraffin candles. You definitely don't want this one on your skin. Magic Acid: Used by Wizards.
Solvent of the week #15: Isopropanol MP: -89 °C BP: 83 °C Density: 0.786 g/mL
Description: Isopropanol (aka isopropyl alcohol, 2-propanol) is a colourless liquid that is miscible with water and organic solvents. Isopropanol is used in sanitary wipes, so no need to be afraid of contact with skin. Along with methanol and acetonitrile, isopropanol is compatible with aqueous ESI conditions (mass spectrometry). If a molecule won't ionize in ESI, change the pH of the isopropanol/water solvent. Unlike ethanol or methanol, isopropanol is just organic enough to be separated from aqueous solutions by adding salts such as NaCl or LiCl, as isopropanol is much less soluble in brine than salt-free water. This salting out gives conc. isopropanol in a distinct layer. Isopropanol is great for recrystallization of compounds on its own or by addition of varied levels of water. Isopropanol: Hot or not?
Solvent of the week #16: Hexamethylphosphoramide (HMPA) MP: 7 °C BP: 233 °C Density: 1.030 g/mL
Description: Hexamethylphosphoramide (HMPA) is a colourless liquid. Often unpopular due to its gazetted toxicity, HMPA can be a very effectual solvent when handled correctly. Don't get it on your skin. HMPA is a polar aprotic solvent. Because it selectively solvates cations, it accelerates some difficult SN2 reactions. The basic oxygen atom in HMPA coordinates strongly to Li+. You will have to carefully distill HMPA in order to get this benefit. DMSO can be used for this same purpose, but HMPA is often more effective. A molybdenum peroxide complex of HMPA is used as an oxidant in organic synthesis. HMPA: Cancer in a bottle.
Solvent of the week #17: Dimethoxyethane (DME) MP: -58 °C BP: 85 °C Density: 0.868 g/mL Description: Dimethoxyethane(DME) (aka monoglyme) is a clear, colorless liquid ether used as an aprotic solvent. DME is miscible with water and is often used as a higher boiling alternative to diethyl ether or THF. DME chelates with cations and acts as a bidentate ligand, therefore it's often used with organometallic reagents like Grignard reactions, hydride reductions, and palladium-catalyzed reactions like Suzuki reactions and Stille coupling. Also Heck and Ullmann reactions. A good solvent for different kinds of oligo- and polysaccharides and is frequently used in sugar/carbohydrate chemistry. DME has lower BP and viscosity compared to other solvents that dissolve such polysaccharides. DME: Chemists helping chemists.
Solvent of the week #18: Benzonitrile MP: -13 °C BP: 191 °C Density: 1.001 g/mL
Description: This clear liquid is a more polar version of benzene, still capable of pi-stacking but with considerably higher BP. When you consider that pi electron interactions greatly enhance the solubility of ionic solutes, you can imagine benzonitrile as a very effectual solvent at high temp. Benzonitrile is prepared a number of ways:
heat sodium benzenesulfonate in an NaCN solution containing copper sulfate; the product is distilled away from the reaction mixture
react benzoic acid and ammonia; the mixture is heated to ~ 400 °C over aluminium oxide
react HCN and arylhalide in the vapor phase over a nickel(II) oxide or nickel catalyst supported on aluminum oxide
react toluene with nitrogen monoxide in the presence of a dehydration catalyst such as silver on an inert support
Benzonitrile is known to act as a weak coordination complex ligand, readily replaced by stronger ligands, thus benzonitrile complexes are useful intermediates for targeted organometallic syntheses. Some warn of benzonitrile reacting with primary amines to give N-substituted benzamides, or yielding HCN from exposure to strong acids. Both are unlikely to happen by accident as aromatic nitriles are very robust. Like many compounds, benzonitrile is said to smell like almonds. The Secret of Scent: Adventures in Perfume and the Science of Smell by Luca Turin says:
"Benzaldehyde, nitrobenzene, benzonitrile, hydrogen cyanide and trans-2-hexenal all smell of bitter almonds, but anyone, even a naive observer, can easily tell them apart by smell after just one showing. Benzaldehyde is the proper bitter-almonds smell (contained in bitter almonds), whereas nitrobenzene smells like a mixture of amaretto and shoe polish, and benzonitrile smells like metallic almonds, and hexenal like cut-grass and almonds."
Benzonitrile: original opioid free formula.
Solvent of the week #19: Propylene carbonate MP: -55 °C BP: 240 °C Density: 1.205 g/mL
Description: This colourless, odourless liquid is a polar aprotic solvent. While propylene carbonate has a chiral centre, the racemic mixture is used exclusively as a solvent. It has a high dipole moment, so is good at dissolving ionic reagents/catalysts and also good for microwave reactions (eg; poly-aspartic acid). It gives good phase separation when mixed with n-hexane, thereby possibly isolating a compound. Propylene carbonate is found in adhesives, paint strippers and cosmetics. It is also used as polymer plasticizer, where its high BP helps it stay put. Propylene carbonate: do not drink while driving.
Solvent of the week #20: 2,2,2-Trifluoroethanol MP: -45 °C BP: 74 °C Density: 1.382 g/mL
Description: This more acidic version of ethanol is suitable for reactions that like a slight acid environment. It is colourless and water miscible like ethanol, but with slightly lower BP. Sulfur compounds may be oxidized by H2O2 in 2,2,2-trifluoroethanol where, as with many other reactions, the majority is recoverable by distillation for reuse. 80% 2,2,2-trifluoroethanol(aq) can better dissociate salts such as KCl or t-Butyl bromide than 80% ethanol(aq). You might try 2,2,2-trifluoroethanol/water blends when ethanol/water is being difficult. If you seek to replace DCM and keep high density/low BP, you might consider trifluoroethanol. 2,2,2-Trifluoroethanol: Reactant or reagent?
Solvent of the week #21: Nitroethane MP: -90 °C BP: 112 °C Density: 1.054 g/mL Description: Nitroethane is a clear organic liquid. Highly combustible, it is used as a fuel additive, solvent for polymers such as polystyrene and to dissolve cyanoacrylate superglue. Industrially, nitroethane can be used to extract rosin from wood, to dewax diesel fuels and as a stabilizer in halogenated hydrocarbons to stop their corrosive attack on metals. Nitroethane can dissolve a variety of compounds and can be used to recrystallize, particularly compounds with aldehyde groups. An excellent solvent, nitroethane can also be a reagent (Henry reaction). Nitroethane gives phase separation from water. If an emulsion happens, add some alcohol free chloroform and your organic layer will dash neatly for the bottom. I've used water to purify nitroethane; by sitting water over it for 1-2 weeks, yellow impurity removes itself to the water fraction. The yellow is a slowly formed carbanion as the CH3 is gently acidic. This is repeated until the nitroethane is clear. It is then dried with anhydrous MgSO4 and filtered. To be adventurous, you could concentrate and use the water fraction as a base in a reaction. Nitric acid and uranyl ions will dissolve in nitroethane and can thus be extracted from water. Nitroethane: Famous for twin lobster rolls.
Solvent of the week #22: Perfluorohexane MP: -90 °C BP: 56 °C Density: 1.672 g/mL
Description: Perfluorohexane (PFH) is a clear liquid that, like CCl4 is non-flammable as it lacks C-H bonds. PFH can be used to separate compounds by fluorousphase chemistry. You can mix an organic solvent, fluorousphase solvent and water to get a three phase system. Note that PFH has density 1.672, hexane only 0.654; fluorous solvents are dense so tend to be the bottom phase. Enantiomer tagging can be done with this class of fluorous solvents to resolve racemic mixtures; a glass U-tube with PFH on the bottom and organic solvent on the top of both sides allows fluorous-tagged enantiomer to migrate from one organic phase, through the PFH, then stay in the organic solvent on the other side. Resolved! PFH dissolves gases like oxygen from the air to higher levels than other liquids. This is due to the nature of the fluorine atom causing low intermolecular forces between PFH molecules, which allows space for gas molecules to partition into the liquid. Animals can be submerged in a bath of PFH and may be uncomfortable, but there is enough oxygen in the solvent for respiration to continue. PFH is used to treat burn victims; the lungs can be filled with PFH vapour or in extreme cases liquid PFH to allow breathing to continue without the problems seen when lungs have been burnt by smoke. PFH: Now with more P.
Solvent of the week #23: Lithium-Potassium Nitrate Eutectic Melt MP: 170 °C BP: 880 °C Density: 2.020 g/mL
Description: Not the best known solvent system among organic chemists, eutectic nitrate melts have peculiar properties for high temp reactions. This class of solvents has lowered MP and increased thermal stability compared to their individual components. They may be employed to explore the chemistry of redox reactions under high temp, non-aqueous conditions as they have the benefit of very large liquid range (typically ~700 °C). When you blend LiNO3 (MP 255 °C) and KNO3 (MP 334 °C) in a 38:62 mole ratio you get a mixture that melts at 170 °C and remains liquid up to 880 °C. This must be done in a glovebox as both are very hygroscopic. If the eutectic blend is cooled to a solid and then placed on a bench in air, it will become a puddle in 2-3 seconds. Some examples of eutectic ratios: Cation Proportion (weight %) Melting point (°C) of anhydrous salt Ca/K 51/49 142 Ca/NH4 29/71 111 K/Li 62/38 170 K/Mg 42/58 178 71/29 195 K/NH4 14/86 157 K/Na 50/50 220 Li/NH4 27/63 90 Li/Na 55/45 196 Mg/Na 51/49 135 NH4/Na 79/21 121
Solvent of the week #24: Tetrachloroethylene(TCE) MP: -19 °C BP: 121 °C Density: 1.622 g/mL
Description: A dense chlorinated solvent, tetrachloroethylene (aka TCE or perchloroethylene) is the main solvent used in the dry clean industry. As it is easily recovered by distillation, the same TCE can be used many times to clean garments. This works best in a closed system with continuous distillation/filtration. For this purpose, TCE has the added advantage of being non-flammable due to absence of C-H bonds. TCE is a good solvent for reactions that achieve an acid chloride with chlorinating reagents, eg, thionyl chloride (SOCl2). There are two reasons for this: Acid chlorides' tendency to be quenched by water to give a carboxyl (TCE is very immiscible with water so stays dry); Protic chlorinated solvents (DCM, CHCl3, 1,2-DCE) can form HCl in the presence of strong chlorinating reagents like SOCl2, which causes the acid chloride to fall apart. TCE can replace CCl4 (which can no longer be purchased!) in, for example, Rigaku's OIL-20A oil content meter. Aqueous environmental & food samples are tested by extracting lipophilic content into TCE, then analyzing by IR for absorbtivity at the C-H stretch region. As C-H bonds are absent in TCE, this correlates to oil content. TCE: Dry clean only.
Solvent of the week #25: 2-Butanol MP: -115 °C BP: 99 °C Density: 0.808 g/mL
Description: 2-Butanol (aka sec-butanol) is a clear, low density alcohol, normally a racemic mixture of two stereoisomers. It smells like isopropanol and has similar dissolution properties. 2-Butanol is slightly more viscous than isopropanol (3 cP, compared to 1.96 cP for isopropanol @ 25 °C). 2-Butanol won't dissolve sucralose, guar gum, urea or tartaric acid, but will dissolve vanillin. 2-Butanol is miscible with hexane so can be used for chromatography or TLC. You might grow a single crystal for diffractometry by dissolving in 2-butanol, then introducing hexane as anti-solvent. 2-Butanol is less water miscible than isopropanol or 1-butanol which makes it good to extract hydrophilic (polar) organics from water (compounds that are probably highly soluble in methanol). Water will hold about 10-12% 2-butanol, so you must wash the water fraction a few times with more 2-butanol to recover your compound. On the flip side, 2-butanol is used to extract water from aqueous DNA solutions (it seems that DNA is particularly insoluble in 2-butanol). 2-Butanol: Dog's breakfast.
Solvent of the week #26: Sulfolane MP: 27.5 °C BP: 285 °C Density: 1.261 g/mL
Description: Developed by Shell in the 1960s, sulfolane is a water soluble aprotic organosulfur. It won't corrode steel at 200 °C, (no decomposition to SO2), however it seems our olfactory sense detects minute quantities of sulfur impurities as I haven't met a bottle of sulfolane without a garlicky smell (this could be impurities or the solvent). Sulfolane can be thought a dirty solvent, but in many cases it gives cleaner reactions than DMF. It is a solvent of choice for acid-catalyzed reactions at elevated temperatures and is compatible with reagents such as PCl5, POCl3 and SOCl2. Sulfolane dissolves most transition metal catalysts and has even been used with non-metallic catalysts like DABCO. Sulfolane is solid at RT so you'll have to melt it before use. Sulfolane with 3 % water has MP ~10 °C, 10 % water has MP ~0 °C (these solutions are commercially available). It is miscible in all proportions with most organic solvents. Some say that tert-butyl methyl ether (TBME) gives complete phase separation from sulfolane. This is untrue, dry sulfolane holds some TBME, the rest layers on top. You can wash your sulfolane fraction repeatedly with TBME (if you get an emulsion add a little water), then with combined TBME fractions, wash a few times with water. An even cleaner, water free separation comes from diisopropyl ether (DIPE) over sulfolane. If your compound dissolves in DIPE, this is the ideal solvent to extract it from sulfolane. Sulfolane finds use in halo exchange reactions to selectively fluorinate compounds. If you want to fluorinate or trifluoromethylate a nucleophilic aromatic carbon, there's a good chance you will be directed toward sulfolane. Sulfolane: Since 1964.
Solvent of the week #27: 1,4-dioxane MP: 12 °C BP: 101 °C Density: 1.033 g/mL
Description: 1,4-Dioxane (often called dioxane as the 1,2 and 1,3 isomers are rare) is a heterocyclic solvent used for organic synthesis. Dioxane has very close density and BP to water. Opening a bottle at room temp you will find quite low vapour pressure for an ether and it is easy to pour. While quite non-polar, it is fully miscible with water and hygroscopic. As a consequence, it is hard to dry compared to other solvents. It may be dried over NaOH or CaCl2, followed by sodium metal. Dioxane is removed by evaporation; it azeotropes with water at 88 °C in a ratio of 18% dioxane to 82% water. Just a little dioxane can remove that last bit of water from a reaction. Note the similar structure to THF, but with BP of 101 °C instead of 66 °C. This allows you a higher reflux temp than THF. Dioxane can act as a ligand which should be remembered when using transition metal catalysts for a reaction; you might get chelation. It is known to bind to AlCl3 and quench its catalysis. Dioxane replaces the oxygen monolayer on surfaces of aluminium containers where, as a more organic version of oxygen, it stabilizes chemicals in storage/transport. Dioxane: Tickles your innards.
Solvent of the week #28: Diisopropyl ether MP: -60 °C BP: 69 °C Density: 0.725 g/mL
Description: Diisopropyl ether (DIPE) is a clear liquid that is immiscible with water. It smells like a garboligist's green tea leaves. DIPE readily separates from water free sulfolane (#26). It won't phase separate from dry DMF, but add a little water and you will get two layers. One secret that I've discovered is that DIPE gives phase separation from anhydrous DMSO. So you can do a reaction in dry DMSO and repeatedly wash the product into DIPE. Or, you could try a biphase reaction between DIPE/DMSO with a phase transfer catalyst. Bear in mind that as an ether, DIPE can form explosive peroxides. These can be stymied a number of ways:
Store in the dark
Keep bottle sealed
Stabilize with butylated hydroxytoluene (BHT) or NaOH
Remove peroxides by acidic iron(II) sulfate wash
Pass through alumina (does not destroy the peroxides; merely traps them)
A more drastic method that also removes water/oxygen is to distill from sodium/benzophenone
DIPE is also an under-utilized recrystallizing solvent. DIPE: Straight to the pool room.
Solvent of the week #29: Benzyl alcohol MP: -15 °C BP: 205 °C Density: 1.044 g/mL
Description: Benzyl alcohol is a colourless liquid with a faint sweet nutty odour. It is a solvent for inks, paints and glue. It is common in fruits, teas and essential oils. No need to avoid contact with skin; it is found in topical antiseptics, anti-itch products and head-lice treatments. Benzyl alcohol is oxidized rapidly in the body to benzoic acid, conjugated with glycine in the liver and excreted as hippuric acid. Benzyl alcohol has nearly the same refraction index as quartz & wool fibre. Immerse a clear quartz object in benzyl alcohol and it becomes almost invisible, thus non-destructively showing an object made of true quartz. White wool immersed in benzyl alcohol also becomes almost invisible to reveal contaminants such as dark/medullated fibres or vegetable matter. Benzyl alcohol is a precursor to esters for soap, fragrance and flavour compounds. In perfumery, it is an excellent solvent for nitro musks. It's high BP means that it only releases these components slowly. It is a component of Vera Wang Bouquet (floral topnote, powdery finish), where it acts as a solvent and a scent. I would guess that the benzyl alcohol gives its scent somewhere in the middle of this assortment which is an eau de parfum with at least 15 fragrance compounds. Benzyl alcohol: Just what the doctor ordered.
Solvent of the week #30: Methyl isobutyl ketone MP: -85 °C BP: 117 °C Density: 0.802 g/mL
Description: Methyl isobutyl ketone (MIBK) is a clear solvent that dissolves nitrocellulose, waxes and inks. It has a smell that is sweet but a bit too sweet. Unlike acetone and butanone, MIBK has quite low solubility in water. It has a similar polarity to ethyl acetate, but greater acid/base stability. This and its low density make it good for liquid-liquid extraction. Don't put water on an MIBK fire, it will separate like a petrol fire. Use CO2, dry chemical or foam. MIBK is used to denature ethanol, as a solvent for tear gas spray and to extract gold/silver from cyanide solutions on mine sites to determine ore concentrations. MIBK is popular to dissolve metals and is often used for flame AAS analysis. It can separate the group 4 transition metals zirconium and hafnium by MIBK/water extraction; The chloride salts of these two metals are dissolved in water at low pH and ammonium thiocyanate (NH4SCN) is dissolved in the MIBK fraction. The Hf-thiocyanate complex is far more soluble in the MIBK layer and finds its way there, leaving the Zr-thiocyanate complex mostly in the aqueous layer. MIBK: Wide world of solvents.
Solvent of the week #31: Ethylbenzene MP: -95 °C BP: 136 °C Density: 0.867 g/mL
Description: Ethylbenzene (EB) is a clear liquid hydrocarbon found in petrol. It is chemically similar to xylene and is used as a solvent in many paints. EB has been used as a solvent for aluminium bromide in the anhydrous electrodeposition of aluminium. EB can be dehydrogenated to give styrene (desirable to make polystyrene). Crude xylenes usually contain a few percent EB. It is clear from the BP of EB (136 °C) that it does not easily separate by distillation from o, m or p xylene (BP of 144, 139 and 138 °C respectively). All 4 molecules are C8H10, one difference being that EB can convert to styrene if exposed to catalyst & heat. If this is a problem for you, there are ways to remove EB from the xylenes, or even isolate any of the xylenes as pure compounds. Example: p-xylene can be crystallized at 13 °C in methanol. It is removed and o-xylene then crystallizes at -24 °C, followed by m-xylene at -48 °C, leaving only EB in the MeOH since it has MP of -95 °C. MeOH is then removed from the EB by evaporation. EB: Up before dawn to do schoolwork.
Solvent of the week #32: Formic acid MP: 8 °C BP: 100 °C Density: 1.220 g/mL
Description: Half formyl, half carboxyl, this simple acid is a colourless liquid with a pungent, acrid odour. Formyl, if you are not aware, is another word for an aldehyde group (CHO). Formic acid is often used as an anti-bacterial or preservative. If you want to sterilize a surface you may wipe it with formic acid. Synthetically, formic acid can be used as a formylating reagent, for example, N-formylation of methylaniline. It will react with alcohols of course, to form esters. It is also mildly hydridic and can be used as a source of hydrogen for hydrogenation of a compound. When heated in acid, it decomposes to CO and H2O, which can be done as an in pot source of CO for a reaction. Most bee and ant venom contains formic acid and in fact, the name formic acid comes from the latin word formica meaning ants. In ancient times formic acid was prepared by distillation of ants. You can add formic acid to clean your electrospray mass spec. It helps ionize and remove overflow from previous samples. You might add formic acid to a reaction to enhance miscibility. Like acetic acid (#8), removal of formic acid from organic phase is by aqueous sodium bicarb which is gentle enough to only make sodium salts of carboxylic acids. This gives sodium formate (water soluble) plus H2O and CO2. Expect effervescence! Formic acid: Small strokes fell great oaks.
Solvent of the week #33: Propionitrile MP: -93 °C BP: 97 °C Density: 0.772 g/mL
Description: Propionitrile (aka ethyl cyanide) is a colourless, water soluble liquid. Just one carbon larger than acetonitrile, it has low density and BP close to water. Despite its high cost, propionitrile is a coveted solvent for the mobile phase of HPLC analysis of triacylglycerols. It is said to have an ether-like odour, but I'd describe it as more almondy. Propionitrile is most comparable in polarity to isopropanol (#15) in terms of its miscibility with water and organic compounds. It is miscible with pure water but it can be salted out to a discrete layer, just like isopropanol. In fact, if you mix it with saturated brine, it will suck some of the water from the brine and cause the NaCl to recrystallize. Propionitrile is miscible with hexane in all proportions, unlike acetonitrile which will separate from hexane. If you have some, you might want to try as a recrystallizing solvent. Propionitrile: Purer than distilled eggs.
Solvent of the week #34: Dimethylaniline MP: 2 °C BP: 194 °C Density: 0.956 g/mL
Description: Dimethylaniline (DMA) is a clear oily liquid. It can turn yellow due to a minor amount of resinification of the molecule. DMA has an affinity to cling to things, which is put to good use in the preparation of acetyl chloride; one prep is to react acetic acid with an inorganic chlorodehydrating agent like PCl3, PCl5, SO2Cl2, or SOCl2. However this gives acetyl chloride which is contaminated by phosphorus/sulfur impurities that can interfere with organic reactions. A cleaner method is to react HCl with acetic anhydride: (CH3CO)2O + HCl → CH3COCl + CH3CO2H. This gives only hydro chloride impurities that are removed by distilling the acetyl chloride from DMA. Sometimes a reactant, DMA may be used for base catalyzed reactions and is great when high temp is required. DMA: Means to stay.
Solvent of the week #35: Methyl acetate MP: -98 °C BP: 57 °C Density: 0.932 g/mL
Description: Methyl acetate (MeOAc) is a low boiling, flammable solvent. It smells of ethyl acetate (EtOAc), but old bottles will have a hint of acetic acid. MeOAc is slightly more polar than it's cousin EtOAc. Ethyl acetate washes away dow corning high vac grease from glass joins. MeOAc dissolves it almost as much. Ethyl acetate is more common as it is less water miscible and alkali sensitive. MeOAc is more toxic due to methanol as its by product, as opposed to ethanol for EtOAc. You may want a solvent with similar dissolution properties to EtOAc, but lower BP to be removed by vacuum. You can get MeOAc to separate from water by placing your sep funnel in the fridge; at RT MeOAc holds 25-30% water. But water only holds 10% MeOAc and at 4 °C it holds just 3%. MeOAc is miscible in all proportions with hexane. MeOAc is not always held is stock by chem stores. A whole winchester can be made easily from methanol and acetic acid with a little H2SO4. Acetic acid is added in slight excess and MeOAc is distilled from the reaction flask (reactive distillation). What's more, MeOAc will revert back to MeOH and acetic acid in the presence of NaOH, both of which are highly water soluble. If you have trouble removing MeOAc from your compound, you can split it into its constituents to be washed off in water. In this way, MeOAc can be seen as a solvent you assemble yourself and then dismantle. Methyl acetate: If taken, consult physician.
Solvent of the week #36: Methyl benzoate MP: -13 °C BP: 200 °C Density: 1.084 g/mL
Description: Methyl benzoate is a clear fruity liquid that finds use in perfumery and as a pesticide solvent where it attracts insects. It gives feijoas their pleasant smell. If you have not tried a feijoa they are quite delicious, I recommend you go out and get one. It is hard to find a solvent that is immiscible with methyl benzoate. It blends in all proportions with DMSO, DMF, MeOH, acetonitrile, nitroethane, sulfolane, morpholine, m-xylene, benzene & hexane. It separates from water and formamide. Methyl benzoate is made by condensing MeOH and benzoic acid in presence of a strong acid. It can react at the ring or the ester. Electrophilic substitution, for example nitration with nitric acid gives methyl-3-nitrobenzoate. NaOH hydrolyzes methyl benzoate back to methanol and sodium benzoate, which is acidified with HCl to benzoic acid. Methyl benzoate can be isolated from feijoas or in large amounts from the freshwater fern Salvinia molesta. As the smell of methyl benzoate attracts males orchid bees (which gather it to synthesize pheromones) it is used as bait to collect these bees for study. Like most alkaloids, cocaine is too large and nitrogenated to readily have an odour profile (more C-N bonds quickly dilute the odour of a compound) and cocaine hydrochloride (a salt) is even less smellable. However, small amounts of cocaine hydrochloride hydrolyze in moist air to yield methyl benzoate and with its strong odour profile, airport drug dogs smell for methyl benzoate. If you want trouble, carry a methyl benzoate soaked hanky in your bag on your next overseas trip. Methyl benzoate: Pedal to the metal.
Solvent of the week #37: Diisobutyl ketone MP: -46 °C BP: 169 °C Density: 0.800 g/mL
Description: Diisobutyl ketone (aka 2,6-dimethyl-4-heptanone or DIBK) is a clear, non-polar solvent. DIBK has a strong odour of fruit salad on an old colour TV with the colour turned up too high. It smells pleasant at first, but gets old quickly. It is immiscible with water and formamide. It blends with dry DMSO, DMF, methanol, acetonitrile and sulfolane, but all of these will separate from the DIBK with a bit of water. Trace levels of copper, nickel and titanium can be determined by complexation, extraction into DIBK and analysis by flame AAS. DIBK is at the non-polar end of the polarity scale, and with high BP, you might find luck recrystallizing a compound from hot DIBK. You can wash the DIBK from your crystals with n-pentane. DIBK: Smells like teen spirit.
Solvent of the week #38: Bromoform MP: 8 °C BP: 149 °C Density: 2.889 g/mL
Description: Bromoform is a clear liquid that yellows as it starts to decompose. Its smell compares to chloroform. It is interesting that a C-Cl bond smells colder, while a C-Br bond smells sweeter and fruitier. However they are both in the same family, much like lemon and lime. The density of bromoform is exploited to separate minerals as many heavy solids will float upon it. Bromoform is non-flammable and is a former flame retardant in chemical formulations. It has been replaced by the cheaper diethyl ethylphosphonate (DEEP). Bromoform can be a reagent; like chloroform it forms a dihalocarbene in strong base which reacts neatly with aliphatic C=C bonds to give a dibromocyclopropane. Bromoform: Limited time only.
Solvent of the week #39: Dimethyl ether MP: -141 °C BP: -24 °C Density: 0.730 g/mL (at BP)
Description: Dimethyl ether (DME) is a good solvent for low-temp reactions and extractions. You'll need a special setup to use DME as it has poor handleability at RT. It being a gas under standard conditions (BP -24 °C) makes it easy to remove. DME can be a refrigerant (instead of CFCs), an aerosol propellant and a freezing agent for wart removal products. DME is made by acid catalyzed condensation of MeOH. It is used as a methylating reagent in the dye industry. Reacting DME with SO3 gives dimethyl sulfate - a more powerful methylating reagent. DME's cetane number of 55 makes it a good hydrocarbon to blend into diesel fuel. Dimethyl ether: Sharpest tool in the shed.
Solvent of the week #40: Trifluorotoluene MP: -29 °C BP: 102 °C Density: 1.199 g/mL
Description: A versatile solvent for all concerned, trifluorotoluene (TFT) can replace DCM when higher temp is needed. DCM boils at 40 °C, TFT boils at 102 °C and gives similar solvation in most acylation, tosylation and silylation reactions. The dielectric constants for DCM and TFT are 9.04 and 9.18 respectively. Their dipole moments compare less closely; 1.89 D for DCM and 2.86 D for TFT. Since C-F bonds are more polar than C-H bonds, TFT is naturally more polar than toluene, but it still separates from water. As a solvent, TFT is useful in mild Lewis-acid catalyzed reactions like Friedel-Crafts preparations. The most common Friedel-Crafts catalyst, AlCl3 reacts with TFT at room temperature; however ZnCl does not. Worth remembering. Trifluorotoluene: Low in cholesterol.
Solvent of the week #41: Supercritical CO2 MP: -78 °C BP: -57 °C Density: 0.770 g/mL (at 56 atm and 20 °C) Description: A supercritical fluid is one that is above the pressure/temperature at which there is no distinct liquid and gas phases, but only a single supercritical phase. Supercritical CO2 (sc-CO2) is probably hardly ever the first solvent to try a reaction in but it is an appealing process solvent. It has a very accessible critical point of 31 °C and 74 bar. It is also nontoxic, nonflammable, and naturally abundant. A good solvent for low molecular mass nonpolar solutes and gases, sc-CO2 can dissolve compounds that readily dissolve in hexane or benzene. It has even successfully replaced diethyl ether and acetonitrile. The largest commercial application of sc-CO2 is in food processing as an extraction solvent, eg; decaffeinated of coffee. This replaced DCM extraction, which was harder to remove from food grade products and gave inferior results. sc-CO2 is used in separation chemistry as a mobile phase in supercritical fluid chromatography. H2, CO, and O2 are miscible in all proportions with sc-CO2 so you can use it as a solvent for reactions involving these (hydrogenation!). Lack of reactivity towards O2 (some metal-catalysed oxygen exchange has been seen at high temperatures) and nonflammability, makes sc-CO2 an ideal solvent for oxidation reactions using O2. The keto–enol tautomeric equilibrium of many ketones is known to be solvent sensitive. Some publications reckon that the keto form exists in increased levels in sc-CO2, where the enol form dominates in hexane. Every compound is different, you will have to try it out if you seek keto-enol control. Carbon dioxide: Do not emit.
Solvent of the week #42: Benzyl benzoate MP: 21 °C BP: 323 °C Density: 1.114 g/mL
Description: This solvent is a colourless liquid that is readily prepared; it is the product of benzoic acid and benzyl alcohol condensation; Sodium benzoate can be condensed with benzyl chloride; A preferred high yield method is the Tishchenko condensation which reacts benzaldehyde, benzyl alcohol and metallic sodium. Benzyl benzoate may be used in combination with disulfiram as a topical insecticide to kill scabies. On its own it is said to treat sweet itch in horses and scaly leg mites in chickens. Benzyl benzoate's high BP and low vapour pressure allow its use as a fixative in perfume compositions (slows the release of ingredients). Perfumery and flavoring synthetics by Bedoukian gives that benzyl benzoate is a most suitable solvent for artificial nitro musks which are not readily soluble in alcohols. Citral is soluble in both benzyl benzoate and propylene glycol, but insoluble in glycerol. Benzyl benzoate is also an artificial food flavour, a polymer plasticizer and a high temp reaction solvent. Benzyl benzoate: More zest than the rest.
Solvent of the week #43: Methylamine MP: -93 °C BP: -7 °C Density: 0.899 g/mL Description: Methylamine, the simplest organic amine is gas at room temp but can be cooled to use as a liquid solvent, or blended with water, ethanol, methanol, isopropanol, acetone, THF or hydrocarbons. It smells like a fishier version of ammonia. Liquid methylamine can be used as a solvent analogous to liquid ammonia. It shares some properties of liquid ammonia but better dissolves organic substances (in the same way that methanol is better than water). Gibbs wrote about distilling methylamine into a cold vessel to use as solvent and in this capacity it has a tenacious ability to co-crystalize with organic compounds, especially phenolics and anilines, and that reactions in methylamine tend to be cleaner when done at lower temp. The co-crystallized compounds can be left pure of the excess methylamine simply by opening the stopcock of the vessel. Gibbs also wrote that acetylene is readily soluble in methylamine and that hippuric acid forms the methyl ammonium hippurate salt which is very soluble in cold water. He concludes that methylamine is a better solvent than ammonia for organic compounds and slightly less reactive, but that ammonia is better for inorganic compounds. A 1941 organic syntheses entry gives a methylamine HCl preparation from formaldehyde & ammonium chloride, recrystallized from EtOH. It can be freebased easily enough and in fact this might provide a more dry source of methylamine to bubble through a reaction. As an amine it is of course able to accept a proton and is a basic solvent (like ammonia/pyridine). Don't use as solvent for acid halide or acid anhydride reagents as the NH2 will acylate to give an amide. Methylamine is known to complex with cadmium double halides, so bear this in mind when doing reactions with cadmium. Methylamine can be used to scavenge H2S during hydrocarbon refinement ans is also an N-methylating reagent (methamphetamine synthesis with Al/Hg amalgam). Methylamine: Not quite a cakewalk.
Solvent of the week #44: Hexafluoroisopropanol MP: -3 °C BP: 58 °C Density: 1.596 g/mL
Description: Hexafluoroisopropanol (HFIP) is a clear, dense, low viscosity liquid with a volatile pungent odour. This fluorinated alcohol finds use as solvent and synthetic intermediate. As a solvent for organic synthesis HFIP is quite polar and its strong hydrogen bonding affinity enhances dissolution of hydrogen-bond acceptors (amides & ethers) and most importantly stabilizes anions better than other alcohols to allow reaction mechanisms with anionic intermediates. It has successfully been used as solvent to hydrogenate aromatic carbons on indoles with H2 at 7 bar. HFIP is transparent to UV light, has low refractive index and excellent thermal stability. Be mindful it can form stable distillable hydrogen bonding complexes with ethers or amines. HFIP is a specialty solvent for some polar polymers not soluble in common organics; polyamides, polyacrylonitriles, polyacetals, polyesters (e.g. polyglycolide), and polyketones. Many of these polymers are dissolved at RT by HFIP which means that they may be analyzed by refraction or chemically functionalized without heat. It has also found use in biochemistry to solubilize peptides and to monomerize β-sheet protein aggregates. Because of its acidity (pKa 9.3), it can be used as acid in volatile buffers for ion pair HPLC - mass spectrometry of nucleic acids. HFIP has corrosive vapours that quickly cause eye and lung damage. Do not open outside fume hood. HFIP: Phone rang while you were doing the dishes.
Solvent of the week #45: Carbon disulfide MP: -111 °C BP: 46 °C Density: 1.261 g/mL Description: Carbon disulfide (CS2) is a clear, flammable, poisonous liquid. It has high density and low BP and is used industrially as a non-polar solvent. It phase separates from water but is miscible in hydrocarbons, ethers, alcohols and chlorinated solvents. It readily dissolves oils, waxes and sulfur compounds. These properties mean it could be a dry cleaning solvent if you wanted. It is often used to fumigate insects. Ease of removal from organics make it tempting to use in a reaction but be careful; its vapors can ignite on contact with an incandescent light globe. Captured in the cold trap of a high vacuum pump it presents quite a handling problem. A small amount (<10 mL) allowed to evaporate slowly in a fume hood won't pose a problem. CS2 reacts profoundly with primary and secondary amines, it does not react with tertiary amines. It has an affinity for elemental Se which it can extract from water to measure concentration. CS2 has an ethereal odor, but is often contaminated with foul-smelling impurities like carbonyl sulfide. CS2 is used as a building block in syntheses of organosulfur compounds and can act as a ligand in organometallic complexes. Carbon disulfide: Has no clothes.
Solvent of the week #46: Limonene MP: -74 °C BP: 176 °C Density: 0.841 g/mL
Description: Limonene is a terpene produced from the oil found in citrus rinds. It is used in fragrances, flavours and cosmetics. Limonene is an ingredient in ~ 90% of perfumes as a solvent and citrus note. Relatively stable, it can be distilled without decomposition. Limonene has similar solvation capability to turpentine but with a more coveted scent. It is a major component in wipes to clean ones hands when fishing. The smelly oily residue from fish scales is particularly well dissolved in limonene, leaving a fresh smell. This differentiates these wipes from other disposable sanitizers that contain isopropanol or ethanol as key ingredients. Limonene can remove oil from machine parts, loosen postage stamps and strip paint from wood. Like acetone, limonene can dissolve polystyrene so can replace acetone for polymer applications. To prepare tissues for histology, D-limonene can replace xylenes for clearing dehydrated specimens. Clearing agents are liquids miscible with alcohols and melted paraffin wax in which specimens are embedded to cut thin sections for microscopy. Limonene: A hint of mockery.
Solvent of the week #47: Tertiary butanol MP: 25 °C BP: 82 °C Density: 0.775 g/mL
Description: Tertiary butanol (t-butanol) is a clear liquid (solid below 25 °C) soluble in alcohols & ethers and mostly miscible with water. It has a minty scent much like TBME (#3). t-Butanol is used in paint removers, to denature ethanol, to boost octane number and oxygen level in petrol and as a key start material for many flavour/perfume compounds. As the simplest tertiary alcohol, t-butanol is less reactive than other butanol isomers. When t-butanol is deprotonated by dry reflux with potassium metal it gives the anion t-butoxide; a common organic reagent. This t-butoxide species is useful as a strong, non-nucleophilic base that can take acidic protons from a compound. Its steric bulk discourages SN2 reactions; it's hard for a nucleophile (deprotonated atom on compound) to approach the hydroxyl to form an ether (C-O bond). However, t-butanol reacts with HCl to form tert-butyl chloride via an SN1 mechanism. If you want to do a reaction with HCl and alcohols/water, don't use t-butanol. The rest of the time it should be very robust against side reactions. t-Butanol: Where others fear to tread.
Solvent of the week #48: Methyl ethyl ketone MP: -86 °C BP: 80 °C Density: 0.805 g/mL
Description: Methyl ethyl ketone (aka MEK, butanone) is a clear liquid that can be thought of as a more organic, high BP version of acetone. For most intents and purposes, it can be said to possess intermediate polarity. MEK is used in dry erase white board markers. It smells like acetone with a twist of butterscotch. Not as pleasant as it sounds. You can make MEK by dehydrogenation of 2-butanol with Na2Cr2O7.H2O in H2SO4. Extract from water layer with ether, then distill to remove the ether. MEK dissolves polystyrene and is sold as "polystyrene cement" to connect parts on scale models. Though it appears to act as adhesive it actually functions as a welding agent by dissolving just a little bit of polystyrene before evaporating. MEK readily dissolves vinyl and nitrocellulose films. MEK better removes superglue than acetone as its higher BP allows it to sit longer until the glue dissolves. MEK: Loose lips sink ships.
Solvent of the week #49: N-methylmorpholine-N-oxide MP: 71 °C BP: 280 °C Density: 1.260 g/mL
Description: N-methylmorpholine-N-oxide (NMMO or NMO) is a morpholine derived, low melting ionic solvent. When used as a monohydrate it can dissolve cellulose to process into fibre products. Cellulose is abundant but its strongly structured intermolecular hydrogen bonds resist most solvents making it hard to process. As NMMO is prized for its ability to break the cellulose hydrogen bonding network to dissolve it. Wood is composed of cellulose fibres coated with a hydrophobic lignin matrix (a complex structure of mostly substituted methoxy phenols) to make a 'composite system' with the physical strength of cellulose and the water resistance of lignin. Highly crystalline cellulose fibres give wood a high tensile strength with a low mass but it needs protection from water or it will swell. Pine furniture is often varnished to cheaply achieve this goal but high lignin/slow growth hardwoods give better properties. Incidentally, lignin gives wood it's calorific value which is why you get little heat from pine or pure white paper (mostly cellulose), but Jarrah or high lignin newsprint burn well. A solvent (NMMO) that dissolves cellulose fibres to coat with a hydrophobic matrix allows access to the physical properties of natural hardwood, without cutting down old growth. You might think synthetic wood sounds silly, but there is not enough high quality wood to meet demand. For example railway sleepers when made from woody materials have more give, so provide a smoother ride. Tetrapropylammonium perruthenate (organometallic oxidizing reagent) is used in NMMO to make aldehydes from primary alcohols. The reagent is expensive but is used in catalytic amounts and continually replenished by the oxygen in the excess NMMO. The water produced is absorbed by molecular sieves. Another use of NMMO is to dissolve scleroprotein (found in animal tissue). This dissolution occurs in the crystal areas which are more homogeneous and contain mostly glycine and alanine residues. N-methylmorpholine-N-oxide: Worth two in the bush.
Solvent of the week #50: Acetonitrile MP: -46 °C BP: 81 °C Density: 0.786 g/mL Description: Acetonitrile (often written as MeCN) is the simplest organic nitrile. It is miscible with water and many organic solvents. Synthetic reactions are often done in acetonitrile when high polarity is required with aprotic conditions (no hydroxyl). It is stable and dissolves most compounds when at reflux. Acetonitrile can be a mobile phase for liquid chromatography and is a useful aprotic solvent, for example in chemiluminescent reactions it won't protonate luminol (which would alter its signal). Even water free acetonitrile separates from hexane. This can be used to remove high vacuum grease from a precious compound and get a clean NMR (to prove purity and publish in a journal). Acetonitrile: Plenty of pluck.
Solvent of the week #51: Methanol MP: -97 °C BP: 65 °C Density: 0.792 g/mL
Description: Methanol (sometimes written as MeOH) is the simplest alcohol. The old school chemists would say consumption causes blindness, madness and death in that order. However it is easily handled; don't breathe or drink it and try to keep it off your skin. While it is an organic alcohol, 1 hydrocarbon to the hydroxyl gives it low organic-ness; you can easily imagine replacing the methyl with a hydrogen to get water; very many water soluble compounds find solubility in methanol. I tend to think that organic compounds rich in amide or N-methyls dissolve better in methanol than other solvents (they might also go into acetontrile). Many compounds are found to recrystallize cleanly from hot methanol. It is a good solvent to clean glassware when acetone, water, ethyl acetate and hexane have not worked. Methanol can be added to solvents for flash chromatography but don't use more than 10% or it may start to 'dissolve' the silica through the frit. 20-30% methanol may be used in DCM with a high quality pre-packed column that has even particle size distribution silica. It is said that a methanol/hexane extraction gives two phases for natural product extraction. I've tried methanol with both hexane and hexane fraction (impure hexanes). Both give a single phase with enough shaking, however a tiny bit of water sends the hexane to the top. In contrast, pure (dry) acetonitrile separates completely from pure hexane. Different phase separation may be observed with extractants present. Methanol can be a component of windshield fluid as anti-freeze. Its octane rating allows it to be used neat in racing car engines where in a crash the fuel burns clear, unlike petrol which burns hotter and with black smoke causing pileups. Also, methanol fires can be extinguished with water. Methanol: Blindness, Madness, Death.
Solvent of the week #52: Dimethylformamide MP: -60 °C BP: 153 °C Density: 0.948 g/mL
Description: Dimethylformamide (DMF) is a well known solvent. It is miscible with water in all proportions and organic solvents, including hexane. As a dipolar aprotic solvent, DMF facilitates reactions that proceed by polar/bimolecular (SN2) mechanisms. There are lots of reactions that work best in DMF. NaH reactions are often done in DMF as it stabilizes the Na salt intermediate formed when this reagent removes an acidic hydrogen from a compound. DMF is hydrolyzed by strong bases like NaOH or strong acids like HCl or H2SO4 to give formic acid and dimethylamine (fishy smell); this degradation is accelerated at high temp and DMF often smells fishy due to trace amounts of dimethylamine. As it is miscible with both water and organic phases, DMF is a nuisance to remove by extraction. It is possible to remove DMF from EtOAc fractions with enough vigilance but better to remove most by vacuum. DMF is removed by rotavap at 10 Torr in 55 °C water bath, save for the last few drops. A high vacuum pump with a cold trap takes the rest. Partial double bond character of the carbonyl C-N bond gives what appears in NMR spectra to be a locked conformation. Slow rotation about the C-N axis at RT makes the two methyls inequivalent on the NMR time scale. H-NMR shows two singlets of 3 protons each at δ 2.97 and 2.88, instead of one singlet of 6 protons. DMF can be a catalyst as its charged resonance form facilitates some mechanisms and often forms intermediates with compounds or reagents (synthesis of acid halides). DMF: In the Sin Bin.
Solvent of the week #53: Benzene MP: 6 °C BP: 80 °C Density: 0.877 g/mL
Description: Originally isolated as a compound in 1845, it's structure was solved in the 1860s by August Kekulé who famously claimed to see it's conjugation dancing around in a dream. Benzene is immiscible with water so you can use it for a liquid liquid extraction. However, benzene forms an azeotrope with water (their gas phases are miscible) so water free benzene can be obtained by distilling off the first fraction. Due to its convenient viscosity and vapour pressure, benzene has long been a favoured recrystallizing solvent. It is common to see in old journal articles "was recrystallized from benzene, mp 108-109". Despite its great properties, benzene has become restricted due to health concerns, although most petrol is still 1-5% benzene. Many suggest using toluene instead of benzene, but it just doesn't evaporate or dissolve salts in the same way. It is also great for columns, use in a well ventilated area. Benzene: Does what it's told.
Solvent of the week #54: Methylcyclohexane MP: -126 °C BP: 101 °C Density: 0.770 g/mL
Description: Methylcyclohexane (MCH) is a low density hydrocarbon that is said to smell like benzene. It is a component of jet fuel and 'liquid paper' correction fluids. Regular cyclohexane is often used for recrystallizations in a 9:1 ratio with benzene and MCH can also work well this way. All cyclohexanes can ring flip between two chair conformations, but MCH spends most of its time with its methyl in the equatorial position which reduces its steric crowding. This free conformational rotation gives MCH the ability to retain low viscosity even with dissolved solutes. MCH undergoes a sudden and significant increase of viscosity when cooled below -110 °C. This property has been exploited by Yehor Novikov - with specially made glassware he used the MCH as a coolant to cleanly prepare 1-bromo-1-lithioethene; a reagent that selectively reacts in situ with carbonyl compounds to give 2-bromo-1-alken-3-ols (J. Org. Chem. 2005, Vol. 70, No. 25, p10247-10259). The MCH was cooled by a tube of liquid nitrogen which at low viscosity, made a cold spot only near the reaction chamber of -127 °C which caused the 1-bromo-1-lithioethene to crystallize, increasing its lifetime from 1 to 4 hours to allow it to react cleanly with carbonyl compounds. MCH: Not for bogans.
Solvent of the week #55: Ethyl acetate MP: -84 °C BP: 77 °C Density: 0.897 g/mL
Description: Ethyl acetate, abbreviated to EtOAc is a water immiscible solvent which is used in perfumes and skin care products. It is made by the condensation of ethanol and acetic acid. It is polar enough to make most compounds move easily through flash grade silica, but it is also non-polar enough to dissolve dow corning high vacuum grease. EtOAc is my preferred solvent for wiping this grease off of quickfit joins on taps or pre-weighed flasks. Often the last bit of ethyl acetate seems to stick to a compound even under strong vacuum to give a gel which can become a foam and may not solidify without many hours on very high vacuum. It azeotropes with lower alcohols so can be removed in favour of these. I've had success removing the last bit of EtOAc using a little methanol as an azeotrope. EtOAc is excellent to pass compounds through columns of silica, large or small and can be blended with more or less polar solvents depending on the elution required. If you pass EtOAc neat through the silica it will give off heat, which is due to an interaction effect with the silica. Ethyl acetate: Picks the low fruit first.
Solvent of the week #56: Dichloromethane MP: -97 °C BP: 40 °C Density: 1.330 g/mL
Description: Dichloromethane (DCM) is a non-polar, low boiling solvent. It is also known as methylene chloride (a methylene group is a -CH2-). It was first prepared by Henri Victor Regnault in 1839. Even though it is symmetrical, DCM retains enough polarity to dissolve compounds better than most other chlorinated solvents. A popular solvent system for column chromatography is 10% methanol in 90% DCM. Even 20% methanol in 80% DCM can be used as long as the silica is high grade and well packed. One of the most popular aspects of DCM is its ease of removability. With a BP of only 40 it can be removed under mild vacuum but you'll need to take the chill off the flask, or even just a hair dryer in a fumehood can remove it. You can then smell the flask to see if there is any left. DCM is commonly used for dry loading crude samples onto silica before running a chromatography column. It is also good for loading compound into a ball tube for a 'bulb to bulb distillation' (commonly known as a Kugel rohr - German for ball tube). The DCM washes the compound to the bottom of the ball so that none of it coats the inner of the glass tube. In this way the ball tube is then attached directly to the high vacuum system to remove the DCM before it is assembled for the bulb to bulb distillation. DCM: A stroke of genius.
Solvent of the week #57: Ethanol MP: -114 °C BP: 78 °C Density: 0.789 g/mL Description: Ethanol, abbreviated to EtOH, is a lower alcohol which has many uses. Simply enough, ethanol tends to be great to wash off marker pen marks from glassware. I often pre-weigh my vials and flasks so that I can keep track of the number of mg of compound. Ethanol and a tissue is handy to alter these markings. Ethanol is very good at hanging on to water, but this can be removed by adding benzene and distilling off the water and benzene together, which azeotrope. However this leaves a little bit of benzene in the ethanol. There can be times on upscale of a reaction where THF is sough to be replaced with something cheaper or more biodegradable. A good option is a 50:50 mixture of ethanol/toluene or ethanol/benzene. Ethanol can also be added to a TLC solvent system to get compounds to move further than they would in EtOAc alone. Ethanol: Not just for drinking.
Solvent of the week #58: Tetrahydropyran MP: -45 °C BP: 88 °C Density: 0.880 g/mL
Description: Tetrahydropyran (THP) is a cyclic ether solvent which has similar properties to its better known cousin THF. Ethers tend to make excellent solvents due to their low reactivity, but strong affinity to dissolve compounds and reagents. In part, an exposed oxygen lends stability to regents and/or mechanisms without lending reactivity which can allow reactions to occur which would not in other solvents. It is also pertinent for a solvent to have a low viscosity, particularly if you decide to use it to purify a compound by chromatography as the viscosity must be low enough to pass through the packed silica. Alcohols quickly increase in viscosity as they become larger, but ethers such as THP tend to have low viscosity even with five or more carbons. However it is often useful to blend ethers with alcohols. For example a 50:50 THP/ethanol mixture has been used to dissolve human cholesterol gallstones. THP is less water soluble than THF which may make it better for extractions or biphasic reactions. Keep in mind that it's freezing point (-45 °C) is significantly higher than that of THF (-108 °C). THP: Indulgent.
Solvent of the week #59: 2-Nitropropane MP: -91 °C BP: 120 °C Density: 0.982 g/mL
Description: 2-Nitropropane is immiscible in water and smells a lot like isopropanol. It is usually produced by high-temp vapour-phase nitration of propane, a process that also produces 1-nitropropane. The anion of 2-nitropropane forms readily, as it also does for nitroethane. With nitroethane it is the neighbouring methylene which becomes deprotonated, but on 2-nitropropane it is the central carbon which is acidic. This brønstead acidity comes from two effects, an electron withdrawing effect and also an electron resonance effect. If it were a cyano group instead of a nitro, only the electron withdrawing effect would be in place, but the nitro group has the property of allowing delocalization of electrons. So here you have a solvent with ionic stabilization capability, but which is immiscible with water, this is a rare combination. 2-Nitropropane is actually a great leaving group. I've been able to obtain it from a compound by reactive distillation. It also has commercial value as it can be sold as a racing fuel additive. I have often tried it for recrystallizations, but so far I have not found a compound that recrystallizes in 2-Nitropropane. 2-Nitropropane: Uncanny.
Solvent of the week #60: Tetrahydrofuran MP: -108 °C BP: 66 °C Density: 0.889 g/mL
Description: Tetrahydrofuran (THF) is a cherished and well worn solvent. It has a low freezing point and is a component of the well known Trapp solvent mixture that is used for reactions at low temperature. THF is the classic cyclic ether and is found in the repertoire of any solvent dispensing system. It is mostly immiscible in water and has a typical ethereal smell. One of the benefits of ethereal solvents such as THF is that they are aprotic, but still loan electron pairs. The exposed oxygen of the cyclic ether on THF loans its electron density to stabilize Lewis acids such as Li+, Mg2+ and boranes. The classic example is the Grignard reaction, where the reagent is more stabilized by the exposed THF oxygen than that of diethyl ether. Commercial THF usually has a small amount of butylated hydroxytoluene (BHT) which prevents the formation of peroxides. BHT can of course be removed by distilling the THF, but the THF will then contain a small amount of peroxide impurities. The presence of BHT can disturb THFs ability to dissolve some catalysts, so you may have to choose between BHT or peroxides. These peroxides are generated by dissolved oxygen so a combination of distillation and degassing may achieve THF that is free of both. Reactions done at high temperature or with sensitive catalysts may need degassed THF to succeed. This can be done by the freeze/pump/thaw method as follows:
Place the solvent/solution in a closed Schlenk flask (<50% full), pump off the atmosphere and seal the flask. Keep it attached to the vacuum line throughout this procedure. Place the flask in liquid N2. When the solvent has frozen, open the stopcock and pump off the atmosphere for 10-30 min. Seal the flask and thaw the solvent in a tepid water bath until it just melts and you see gas bubbles evolve. Try not to disturb the liquid, don't let the solvent thaw by itself and don't use a container of water that melts only the bottom of the frozen solvent as this increases the chances of the flask breaking. Replace the water bath with the cooling bath and refreeze the solvent. Repeat these steps until you no longer see the evolution of gas as the solution thaws. This should be at least three cycles. Fill the flask with nitrogen and it is ready to use.
THF: Tells it like it is.
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