Bromoform
Bromoform (CHBr₃), systematically named tribromomethane, is a trihalomethane organic compound that exists as a colorless liquid at room temperature, exhibiting a sweet odor reminiscent of chloroform.[1][2] With a density of 2.89 g/cm³, it sinks in water where it possesses limited solubility (about 3.1 g/L at 25°C) and is nonflammable under standard conditions.[1][3] Bromoform occurs naturally in marine environments, primarily produced by phytoplankton and macroalgae such as seaweeds, contributing to atmospheric bromine loading as a volatile trace gas.[4] Industrially, it serves as a solvent, a reagent in organic synthesis, and in laboratory applications like density gradient centrifugation for separating minerals or biological materials.[1][2] It also forms as a disinfection byproduct during chlorination of bromide-containing water, representing a key route of human exposure through drinking water.[5][6] Despite historical use as a sedative and expectorant in medicine—replaced due to adverse effects—bromoform is acutely toxic via ingestion, inhalation, and dermal absorption, targeting the liver, kidneys, and central nervous system, with evidence of carcinogenicity in animal studies.[1][7][8] Regulatory bodies monitor its levels in water supplies owing to potential health risks from chronic low-level exposure.[2][9]History
Discovery and development
Bromoform, or tribromomethane (CHBr₃), was first synthesized in 1832 by German chemist Carl Jacob Löwig, who obtained it by distilling bromal (tribromoacetaldehyde) with potassium hydroxide, in direct analogy to the contemporaneous preparation of chloroform from chloral.[10] This method highlighted bromoform's status as a haloform, a class of compounds featuring a methyl group tri-substituted with halogens, and established its chemical kinship to chloroform, which had been isolated just a year prior.[10] Löwig's work built on his earlier discovery of bromine in 1825, underscoring the rapid exploration of bromine-based organics following the element's isolation. During the mid-19th century, bromoform's properties were further characterized, revealing its colorless, heavy liquid state with a chloroform-like odor and sweet taste, alongside reactivity patterns typical of haloforms, such as susceptibility to hydrolysis under alkaline conditions.[1] By the late 19th century, its sedative potential was noted, paralleling chloroform's anesthetic applications; it was administered in small doses (1–2 drops, approximately 15–20 mg/kg) to children for whooping cough relief, though its use remained limited compared to chloroform due to observed higher toxicity, including reports of fatalities from overdosing.[11][12] These early pharmacological trials, spanning into the early 20th century, ceased as safer alternatives emerged, shifting focus to bromoform's role as a chemical intermediate rather than a therapeutic agent.[13] Key advancements in the mid-to-late 20th century involved refined analytical techniques like gas chromatography, which enabled detection of trace bromoform in environmental samples, uncovering its natural production by marine macroalgae and planktonic organisms through bromoperoxidase-mediated halogenation of organic precursors.[14] This revelation, building on 1970s studies of volatile halocarbons, marked a milestone in recognizing bromoform not solely as a synthetic compound but as a biogeochemical player, with atmospheric implications traced to oceanic emissions.[14] Such insights paralleled broader understandings of natural organohalogen cycles, distinct from anthropogenic sources.[15]Early industrial applications
In the late 19th and early 20th centuries, bromoform was employed as a solvent for extracting waxes, greases, and oils, leveraging its high density and non-polar properties to facilitate separations in industrial and laboratory settings.[1][16] Its use extended to geological applications, where it served as a heavy liquid medium for density-based separation of minerals and ores, allowing differentiation based on specific gravity differences in assays.[1][17] Medically, bromoform saw limited adoption around the early 1900s as a sedative to alleviate coughing in children with pertussis (whooping cough), administered in small doses for its calming effects similar to chloroform but with observed greater risks of hepatotoxicity and overdose fatalities.[13][18] Empirical reports documented multiple child deaths from accidental overdoses, highlighting its narrower therapeutic window and higher acute toxicity profile compared to chloroform, which curbed broader clinical uptake despite initial interest as an anesthetic alternative.[18][19] By the mid-20th century, particularly post-1940s, bromoform's industrial roles diminished as safer, less toxic solvents and anesthetics emerged, confining it to niche laboratory reagent applications such as extraction solvents and geological testing where its density remained advantageous.[1][8] This shift reflected accumulating evidence of its hazards, including liver damage, prompting replacement in broader commercial contexts.[13]Properties
Physical properties
Bromoform is a colorless to pale yellow liquid at room temperature, possessing a sweet odor similar to that of chloroform.[1] It is denser than water and nonflammable under standard conditions, exhibiting stability without decomposition at ambient temperatures and pressures.[1][3] Key physical constants of bromoform include the following:| Property | Value | Conditions |
|---|---|---|
| Density | 2.89 g/cm³ | 25 °C |
| Boiling point | 149–151 °C | 760 mmHg |
| Melting point | 8 °C | - |
| Refractive index | 1.600 | 20 °C, n_D |
| Vapor pressure | 5 mmHg | 20 °C |
| Water solubility | 0.1–3.1 g/L | 20–25 °C |