triclofos Property

Boiling point:

321.2±52.0 °C(Predicted)

Density 

1.891±0.06 g/cm3(Predicted)

pka

1.65±0.10(Predicted)

EPA Substance Registry System

Ethanol, 2,2,2-trichloro-, dihydrogen phosphate (306-52-5)

Safety

Hazardous Substances Data

306-52-5(Hazardous Substances Data)

Toxicity

LD50 orl-rat: 850 mg/kg GISAAA 33(11),101,68

Hazard and Precautionary Statements (GHS)

triclofos Chemical Properties,Usage,Production

Chemical Properties

White powder with saline taste; soluble in water, almost insoluble in ether, and slightly soluble in alcohol (1 g/ 250 mL). Hygroscopic in air. Stable in light; unstable in above ambient temperatures.

Originator

Triclos,Merrell National,US,1972

Uses

Triclofos is a hypnotic and sedative recommended for insomnia, nocturnal awakening, and early morning awakening.

Production Methods

Chloral is reduced with sodium borohydride and the resulting trichloroethanol is esterified with polyphosphoric acid to give the dihydrogen phosphate. The ester is then reacted with an equimolar quantity of sodium hydroxide.

Definition

ChEBI: Triclofos is a monoalkyl phosphate.

Manufacturing Process

Trichloroethanol (500 grams) and phosphorus oxychloride (510 grams) were added to dry diethyl ether (3.5 liters) and stirred at 10°C with ice/water cooling. Dry pyridine (270 ml) was added dropwise over 1 hour, maintaining the temperature below 25°C. The resulting suspension was stirred for a further 1 hour and then stood at 0°C overnight. The pyridine hydrochloride was removed by filtration and washed with diethyl ether (2 x 300 ml) and dried in vacuo over P2O5 to give 380 grams.
The ether filtrate and washings were evaporated at room temperature under reduced pressure to give a clear liquid residue (801 grams). This residue was distilled under high vacuum to give trichloroethyl phosphorodichloridate (556 grams, 62.4% of theory), boiling point 75°C/0.8 mm.
The phosphorodichloridate was hydrolyzed by adding to a stirred solution of sodium carbonate (253 grams) in water (2.9 liters). After 1 hour the solution was cooled and acidified with a solution of concentrated sulfuric acid (30 ml) in water (150 ml) and then extracted with a mixture of tetrahydrofuran and chloroform (2.3/1; 3 x 1 liter). The tetrahydrofuran/chloroform liquors were bulked and evaporated to dryness to give a light brown oil. This was dissolved in water (1 liter) and titrated with 2 N sodium hydroxide solution to a pH of 4.05 (volume required 930 ml). The aqueous solution was clarified by filtration through kieselguhr and then evaporated under reduced pressure to a syrup (737 grams).
Hot acetone (4.5 liters) was added to this syrup and the clear solution stood at room temperature for 2 hours and then at 0°C overnight. The white crystalline solid was filtered off, washed with acetone (2 x 400 ml) and dried at 60°C in vacuo to give sodium trichloroethyl hydrogen phosphate (414 grams, 49.3% of theory from trichloroethanol).

Therapeutic Function

Sedative, Hypnotic

Safety Profile

Moderately toxic by ingestion.When heated to decomposition it emits toxic vapors ofPOx and Clí.