=chemistry =suggestion =chemical safety


Lots of solvents have been toxic, and toxic solvents have often been dumped down drains. There is no need to use very nasty solvents. When we consider toxicity as well as solvent power and cost, what solvents should you use?


don't use:

benzene, phenol, chlorobenzene, nitrobenzene, nitromethane, chloromethanes, trichloroethane, tetrachloroethylene, other chlorocarbons, hexamethylphosphoramide, carbon disulfide, cyclohexanone, ethylene diamine, phosphate triesters

do use:

water, calcium chloride in water, urea in water, ethanol, isopropanol, 2-butanol, n-butanol, n-pentane, n-heptane, propylene glycol, propylene carbonate, acetic acid, propionic acid, ethyl acetate, ethyl propionate, ethyl butyrate, propyl propionate, butyl butyrate, ethyl lactate, butyl glycolate (from dibutyl oxalate), gammabutyrolactone, methyl and ethyl benzoate, acetone, benzaldehyde, acetaldehyde diethyl acetal, acetone glycerol acetal, dimethylethanolamine



Those are chemicals that are good at dissolving some things, relatively easy to make, and relatively non-toxic. But just having a big list of possible solvents doesn't help you choose one for your particular application.


There are several important ways that solvents can be divided:

protic | aprotic

acidic | neutral | basic

polar | non-polar

hard | soft/polarizable


If replacing a toxic solvent with something safer, you probably want something in the same categories.


If you're replacing nitrobenzene or chlorobenzene, using another polar aromatic compound is logical, and from the above list, ethyl benzoate and benzaldehyde are options to try. Maybe one of your reactants would react with benzaldehyde, so you use ethyl benzoate. (Some people have a weird blind spot when it comes to side reactions with their solvent, and will do a reaction with an amine in chloroform and then wonder why their yield is poor.)


Maybe you're operating on an industrial scale, and cost is more important than moderate toxicity, so you use methyl isobutyl ketone (from acetone) because acetone is cheap because of the cumene process. Or maybe you use o-xylene, which is moderately polar. You just have to be aware of the safety issues; if solvent costs matter, then that means you're probably releasing solvent, which means toxicity matters too, even if it's not as important as for solvents in consumer products or factories.


There are several types of acidity. Calcium chloride isn't an acid, but it makes water vaguely acidic, so it can make vaguely basic things dissolve better. For example, many proteins are dissolved by a solution of calcium chloride in water.


Esters are generally good for moderately-polar organic molecules. Butyl butyrate is obviously less polar than ethyl acetate. If you want higher polarity, gammabutyrolactone and propylene carbonate are much more polar than non-cyclic esters. Ethyl lactate and butyl glycolate, being partly polar, can work for complicated biomolecules that are partly polar but nonpolar enough not to dissolve well in water. If you want to dissolve something with hydroxyl groups and acidity isn't a problem, then carboxylic acids tend to work well.


Tetrahydrofuran is an ether, and if you look at the above list for ethers, you'll see acetaldehyde diethyl acetal. That dissolves things better than you might think, and is probably safer than tetrahydrofuran. 2-ethoxyethyl acetate can also often replace tetrahydrofuran, but 2-ethoxyethyl acetate is metabolized to ethoxyacetic acid, which is bad for humans. Dimethylethanolamine is another possible alternative to tetrahydrofuran; it's a volatile base like ammonia but isn't bad longer-term, being a precursor to choline in animals.


Chlorocarbons and bromocarbons have often been used as solvents, but they're generally bad. Before using a chlorocarbon solvent, you should at least consider: ethyl acetate, ethyl butyrate, ethyl benzoate, methyl benzoate, acetone, acetaldehyde diethyl acetal, and diethyl ether. Also note that some chlorocarbons are more toxic than others; chloroethane and isopropyl chloride are not as bad as tetrachloroethylene or 1,2-dichloroethane.





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