Chloroform
Properties
| State | Liquid at room temperature |
| Color | Colorless |
| Solubility | Slightly soluble in water (0.8 g/100 mL at 20 °C); miscible with organic solvents |
| Melting Point | -63.5 °C |
| Boiling Point | 61.2 °C |
About Chloroform
CHCl3 is what you reach for when you need a dense, non-flammable extraction solvent that's miscible with most organic liquids and forms the bottom layer when shaken with water. The density (1.49 g/mL at 20 °C) and low surface tension make it the cleanest-separating solvent in a separatory funnel — better than DCM in that respect, since DCM is closer to water's density and gives slower phase separation. The single most common use of chloroform in a modern lab is as the deuterated form, CDCl3, which is the default solvent for proton NMR. The deuterium gives a residual peak at 7.26 ppm (the protio-impurity), it dissolves practically every neutral organic, and a 100 mL bottle from Cambridge Isotope Labs runs around $50 versus $300+ for d6-DMSO, so for routine 1H NMR you go with CDCl3 unless your sample protonates the deuterium or shows acidic exchange. Industrially, chloroform is mostly an intermediate — about 90% of production goes into making chlorodifluoromethane (HCFC-22, R-22), which gets either used as a refrigerant (declining under the Montreal Protocol) or pyrolyzed to tetrafluoroethylene for PTFE manufacture. The Simpson 1847 anesthesia history is well-known but mostly historical curiosity at this point; nobody has used chloroform clinically since the early 20th century because the therapeutic index is dangerous (the LD50 sits maybe 4x above the surgical anesthetic dose, and chloroform sensitizes the myocardium to circulating catecholamines, so a stressed patient on chloroform anesthesia could go into ventricular fibrillation from their own adrenaline).
Where you'll encounter it
If you've used a 400 MHz NMR in an organic chemistry teaching lab, the brown bottle with the silver foil seal next to the spectrometer is almost certainly CDCl3. The 7.26 ppm singlet you see in every spectrum is the residual CHCl3 from incomplete deuteration. In a process chemistry lab, chloroform shows up in liquid-liquid extractions for natural-product isolation where DCM gives an emulsion or where you specifically want the heavier organic phase to settle on the bottom (helpful when you're working with multi-phase aqueous workups containing dense salts). It's also the solvent of choice for the classic Reimer-Tiemann reaction that ortho-formylates phenols via dichlorocarbene generated in situ from CHCl3 + base.
Common Uses
- Deuterated form CDCl3 as the default 1H and 13C NMR solvent in synthetic organic labs
- Dense lower-phase extraction solvent for natural product isolation and multi-phase aqueous workups
- Industrial precursor to chlorodifluoromethane HCFC-22 and onward to tetrafluoroethylene for PTFE
- Source of dichlorocarbene CCl2 in Reimer-Tiemann phenol formylation and cyclopropanation reactions
- Solvent for thermosetting plastic adhesives that bond polystyrene and acrylic by partial dissolution
- Mobile phase component in normal-phase TLC and column chromatography of medium-polarity organics
- Historical clinical anesthetic from 1847 to early 1900s, now obsolete due to cardiac toxicity
- Reagent for the Stetter modification of the haloform reaction in acetyl-group cleavage
Safety Information
Chloroform is GHS Acute Toxicity Category 4 (oral and inhalation), Carcinogen Category 2 (IARC Group 2B, suspected human carcinogen based on rodent hepatocellular carcinoma data), and Specific Target Organ Toxicity (liver and kidney) on repeated exposure. The OSHA PEL is 50 ppm ceiling — relatively permissive by modern standards — but ACGIH TLV is 10 ppm TWA, which is what most labs target. The smell threshold is around 85 ppm, well above the TWA, so you cannot rely on odor to detect overexposure. Use a fume hood for any extraction or column larger than about 50 mL. The other practical hazard is decomposition: chloroform exposed to air, light, and heat oxidizes slowly to phosgene (COCl2), which is far more acutely toxic than CHCl3 itself. Stabilized commercial chloroform contains 0.5-1% ethanol or amylene as a phosgene scavenger, but old bottles or distillate run on a hot still without stabilizer can build up dangerous phosgene levels.
This safety summary is for educational reference only and may not be complete. It is not a substitute for Safety Data Sheets (SDS), medical advice, or professional chemical safety guidance. Always consult appropriate SDS and qualified professionals before handling chemicals.