Chemical Properties
Colourless Liquid
Originator
Floropryl,MSD,US,1949
Uses
Diisopropyl Fluorophosphate is a potent inhibitor of serine proteases such as trypsin and chymotrypsin, and of acetylcholinesterase. Diisopropyl fluorophosphate is a very potent neurotoxin.
Uses
DFP served as a basis for developing nerve gases during World War II. It is not used as a nerve gas; it is employed as a pharmacology tool to investigate the toxic properties of nerve gases. It is applied as a miotic and in ophthalmic use.
Definition
ChEBI: Diisopropyl fluorophosphate is a dialkyl phosphate.
Manufacturing Process
212 lb (3.54 lb-mols) of isopropanol containing less than 0.2 wt % of water
was cooled with brine to -5°C in a jacketed reactor. 160 lb (1.16 lb-mols) of
phosphorus trichloride was gradually added to the isopropanol with cooling
and stirring during a period of 4 hours. The temperature of the reaction was
not allowed to exceed 12°C and the system was maintained under slight
negative pressure (about 700 mm) to remove undesirable vapors.
After completion of the addition, the mixture was stirred for ? hour and then
subjected to a pressure of 12 to 100 mm of mercury. Chlorine was then
passed into the crude reaction product at a rate of 12 lb/hr, the temperature
of the reaction being kept below 12°C by brine cooling. The end of the
reaction was indicated by a temperature drop which occurred after a total of
122 lb of chlorine (1.72 lb-mols, 48% excess) was used.
To remove excess chlorine, hydrogen chloride and isopropyl chloride, the wellstirred mixture was subjected to a pressure of 12 to 100 mm of mercury for 2
hours. The temperature was gradually raised to 20°C during this time by
passing steam into the jacket of the reactor. 10 gallons of benzene was then
added and distilled off under reduced pressure, gradually raising thetemperature of the reaction mixture to 30°C. The last traces of hydrogen
chloride were removed by adding an additional 10 gallons of benzene which
was distilled off under reduced pressure at reactor temperatures not
exceeding 50°C. The total time required for the removal of the volatile acid
components of the reaction mixture was 4 hours.
The mixture was then cooled to 20°C and 19 gallons of benzene was added.
This was followed by the introduction of 123.5 lb (2.80 lb-mols) of dry
powdered sodium fluoride (95% pure). The mixture was stirred and heated to
the refluxing temperature in a period of 1 hour and held at this temperature
(95° to 98°C) for 4 hours. The product obtained was cooled and filtered to
yield a filter cake which was washed with three 5-gallon portions of benzene.
The filtrate and washing were then combined and distilled under reduced
pressure. There was obtained 158 lb (74% yield of theory based on PCl3) of
diisopropyl fluorophosphate, BP 62°C at 9 mm and 46°C at 5 mm.
brand name
Floropryl(Merck).
Therapeutic Function
Cholinergic (ophthalmic)
Synthesis Reference(s)
Canadian Journal of Chemistry, 44, p. 501, 1966
DOI: 10.1139/v66-067
General Description
Oily liquid. Clear, colorless or faintly yellow liquid. DIISOPROPYL FLUOROPHOSPHATE is used as a research tool in neuroscience for its ability to inhibit cholinesterase (by phosphorylation) on an acute/sub-acute basis and to produce a delayed neuropathy. An insecticide. Used in Germany as a basis for "nerve gases".
Air & Water Reactions
Forms hydrogen fluoride in presence of moisture; decomposes in water at pH about 2.5.
Reactivity Profile
Organophosphates, such as DIISOPROPYL FLUOROPHOSPHATE, are susceptible to formation of highly toxic and flammable phosphine gas in the presence of strong reducing agents such as hydrides. Partial oxidation by oxidizing agents may result in the release of toxic phosphorus oxides.
Health Hazard
This is an organophosphate pesticide. Extremely toxic: probable oral lethal dose in humans is 5-50 mg/kg, between 7 drops and 1 teaspoonful for 70 kg person (150 lb.). The material is a cholinesterase inactivator. Even traces of the vapor cause pinpoint pupils.
Health Hazard
DFP is a highly toxic organophosphate. Its chemical structure is similar to that of sarin and soman. It is a potent inhibitor of acetylcholinesterase, and its toxic actions are lower but similar to those of sarin and soman. Subcutaneous administration of 1.5 mg/kg causedcholinergicsymptomsinrats,inducing a progressive dose-related necrosis (Dettbarn 1984). DFP administered to rats produced muscle fiber discharges from the peripheral nerves as well as from the central nervous system (Clinton et al. 1988). This was significantly reduced when the animals were pretreatedwithatropinemethylnitrate,ketamine, or phenytoin.
In humans, exposure to its vapors at 1.5 ppm concentration in air for 10 minutes may produce headache and constriction of the pupil of the eye.
LD50 value, oral(rabbits): 10 mg/kg (NIOSH 1986)
LD50 value, subcutaneous (rats): 2 mg/kg (NIOSH 1986).
Fire Hazard
May burn but will not ignite readily. Container may explode in heat of fire. Fire and runoff from fire control water may produce irritating or poisonous gases. Forms hydrogen fluoride in presence of moisture; decomposes in water at pH about 2.5. Keep away from sources of heat. Anhydrous compounds or oil solutions are stable in glass containers at room temperature.
Biochem/physiol Actions
Potent inhibitor of serine proteases such as trypsin and chymotrypsin, and of acetylcholinesterase; also inhibits cathepsin G, cholinesterase, coagulation factor Xa, leucocyte elastase, pancreatic elastase, tissue kallikrein, plasmin, subtilisin, and thrombin. Inhibition of acetylcholinesterase makes this compound especially toxic. Inhibits apoptosis induced by ricin and bacterial toxins.
Waste Disposal
It is dissolved in a combustible solvent and burned in a chemical incinerator. It may be destroyed by treating with molten metal at 800-1000°C (1472-1832°F). It may be decomposed by treatment with dilute acid. Care should be taken, as highly toxic HF may be generated.
