Safer Solvents for Purifying Polar Reaction Mixtures

DCM Alternatives to Normal-Phase Flash Chromatography

For many organic chemists purifying polar reaction mixtures, normal-phase flash chromatography is the go-to method. However, these polar reactions can often result in compounds eluting too early or too late in the separation or not separating at all.

This study utilizes Hansen Solubility Parameter theory and TLC testing to identify safer solvents or solvent blends that are capable of replacing DCM for reaction mixture purification. The solvents and solvent blends identified are then evaluated using chemical hazard classification approaches.

1. Dioxane

A colorless, flammable liquid, 1,4-dioxane is found in the environment at sites where it has been released by industrial discharges or from petroleum distillation. 1,4-Dioxane is persistent in the environment, bioaccumulates and can be toxic when ingested or inhaled.

It also is a skin irritant and has been linked to several health problems, including liver damage, kidney disease and nervous system damage. The Environmental Working Group (EWG) has called on the EPA to set a federal limit for the chemical.

Researchers have developed green solvents such as tert-butyl acetate, sec-butyl acetate, ethyl isobutyrate and methyl pivalate that are safer, more sustainable alternatives to DCM in TLC mobile phases analysing common, small drug molecules [6]. They were selected because they lie below the less polar zone of the Kamlet-Taft solubility parameter diagram (Fig. 2) and are predicted to have similar or improved Rf values than DCM. A statistical thermodynamic framework enabled chemists to interpret chromatographic results in ways not possible with interpretation using traditional solubility parameters alone.

2. Methyl acetate

Methyl acetate is a clear liquid that has an ester odor similar to glues and nail polish remover. It is a low toxicity solvent used in early drying paints and wood coatings, industrial applications, perfumes and lubricants. It is also an intermediate in the manufacture of chlorophacinone, diphacinone, fenfluramine and o-methoxyphenyl acetone and an acidic reagent for the preparation of cellulose adhesives.

It is miscible with most organic solvents (alcohols, ketones and esters) but it is only sparingly soluble in water at elevated temperatures. It can be disposed of in a chemical incinerator equipped with an afterburner and scrubber.

Methyl acetate is toxic if swallowed and can cause drowsiness or dizziness. Following oral exposure, it is rapidly cleaved by esterases in the digestive tract and blood to form methanol and acetic acid. It is readily absorbed through the skin and may cause eye irritation. It is also a moderate hazard to the environment with an estimated BCF of 3 (SRC). Methyl acetate can be released to the environment through various waste streams and may biodegrade in soil.

3. Ethyl acetate/acetone

Ethyl acetate is a clear, colorless liquid solvent that has a light fruity odor and is soluble in many organic compounds. It is used in chemical synthesis and for extracting organic compounds from plant material. It is also used as an industrial paint and varnish thinner and for removing casual stains and grease from surfaces.

It can be absorbed into the body via inhalation, but only at low doses (2000 ppm). Chronic exposure may cause eye irritation, lung damage, and liver & kidney damage. Ethyl acetate is metabolized to acetic acid & ethanol in the liver and blood.

A method was developed to identify nonhazardous replacements for DCM using thin-layer chromatography (TLC) and Hansen Solubility Parameter theory. A number of safer solvent blends were identified and down-selected based on their dissolution properties and safety. The final selections were then evaluated by three separate chemical hazard classification approaches to determine the best nonhazardous DCM replacement. The resulting four solvent blend combinations were then compared to DCM in TLC performance testing.

4. Chloroform

Chloroform (CHCl) is a volatile liquid, a colourless and odourless compound. It is a useful solvent for manufacturing pesticides, film, lacquers, floor polishes, alkaloids and resins. It is also used as an anaesthetic during medical procedures.

Chronic exposure to chloroform can cause headaches, dizziness and fatigue. It can also damage the liver and kidneys. If it comes in contact with the skin, it can cause sores and blisters.

It enters the environment mainly through industrial effluent, waste from paper mills and chlorination of drinking water. It evaporates quickly from lakes and rivers and can seep into groundwater. On prolonged heating, it decomposes to formic acid, carbon monoxide and hydrogen chloride.

This is a dangerous chemical that can be found in many different places in the environment. It is often contaminated with other chemicals such as petroleum, ammonia and chloride. It can be difficult to identify because it has similar physical characteristics to other substances like ether and methyl acetate. The best way to identify chloroform is by chemical analysis.

Slide back to the main page

Leave a Reply

Your email address will not be published. Required fields are marked *