306-52-5

Basic information

• Product Name: triclofos
• Synonyms: triclofos;2,2,2-TRICHLOROETHANOLDIHYDROGENPHOSPHATE;2,2,2-TRICHLOROETHYLPHOSPHATE;Triclofos (base and/or unspecified salts);Ethanol, 2,2,2-trichloro-, dihydrogen phosphate;Phosphoric acid 2,2,2-trichloroethyl;Phosphoric acid 2,2,2-trichloroethyl ester;Phosphoric acid dihydrogen 2,2,2-trichloroethyl ester
• CAS NO: 306-52-5
• Molecular Formula: C₂H₄Cl₃O₄P
• Molecular Weight: 229.383
• EINECS: 206-185-6
• Product Categories: Organics
• Mol File: 306-52-5.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 321.2 °C at 760 mmHg
• Flash Point: 148.1 °C
• Appearance: /
• Density: 1.891 g/cm³
• Vapor Pressure: 6.26E-05mmHg at 25°C
• Refractive Index: 1.53
• PKA: 1.65±0.10(Predicted)
• CAS DataBase Reference: triclofos(CAS DataBase Reference)
• NIST Chemistry Reference: triclofos(306-52-5)
• EPA Substance Registry System: triclofos(306-52-5)

Safety Data

• Hazardous Substances Data: 306-52-5(Hazardous Substances Data)

Usage

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.

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.

InChI:InChI=1/C2H4Cl3O4P/c3-2(4,5)1-9-10(6,7)8/h1H2,(H2,6,7,8)

Upstream product

• 115-20-8 1,1,1-trichloroethanol 
• 7719-12-2 phosphorus trichloride 
• 10026-13-8 phosphorus pentachloride 
• 29175-89-1 phosphoric acid 2-hydroxy-phenyl ester 2,2,2-trichloro-ethyl ester; triethylamine salt 
• 67154-52-3 2-(2,2,2-trichloro-ethoxy)-[1,3,2]dioxaphospholane 2-oxide 
• 1069-93-8 tris-(2,2,2-trichloroethyl) phosphite 
• 18868-46-7 2,2,2-trichloroethyl phosphorodichloridate 

Downstream Products

• 83919-70-4 Phosphoric acid (2R,3R,4R,5R)-2-[bis-(4-methoxy-phenylsulfanyl)-phosphoryloxymethyl]-4-(4-methoxy-tetrahydro-pyran-4-yloxy)-5-[6-oxo-2-(trityl-amino)-1,6-dihydro-purin-9-yl]-tetrahydro-furan-3-yl ester 2,2,2-trichloro-ethyl ester 
• 71260-19-0 Hexadecanoic acid 2-[(2,3-bis-benzyloxy-propoxy)-(2,2,2-trichloro-ethoxy)-phosphoryloxy]-1-hexadecanoyloxymethyl-ethyl ester 

Relevant articles and documents

Catalysis of the cleavage of uridine 3′-2,2,2-trichloroethylphosphate by a designed helix-loop-helix motif peptide

A 42-residue peptide that folds into a helix-loop-helix motif and dimerizes to form a four-helix bundle has been designed to catalyze the hydrolysis of phosphodiesters. The active site on the surface of the folded catalyst is composed of two histidine and four arginine residues, with the capacity to provide general acid, general base, and/or nucleophilic catalysis as well as transition state stabilization. Uridine 3′-2,2,2 trichloroethylphosphate (2) is a mimic of RNA with a leaving group pKa of 12.3. Its hydrolysis is energetically less favorable than that of commonly used model substrates with p-nitrophenyl leaving groups and therefore a more realistic model for the design of catalysts capable of cleaving RNA. The second-order rate constant for the hydrolysis of 2 at pH 7.0 by the polypeptide catalyst was 418 × 10-6 M-1 s-1, and that of the imidazole catalyzed reaction was 1.66 × 10-6 M-1 s -1. The pH dependence suggested that catalysis is due to the unprotonated form of a residue with a pKa of around 5.3, and the observed kinetic solvent isotope effect of 1.9 showed that there is significant hydrogen bonding in the transition state, consistent with general acid-base catalysis. The rate constant ratio k2(Pep)/k2(Im) of 252 is probably due to a combination of nucleophilic and general acid-base catalysis, as well as transition state stabilization. Substrate binding was weak since no sign of saturation kinetics was observed for substrate concentrations in the range from 5 to 40 mM. The results provide a platform for the further development of catalysts for RNA cleavage with a potential role in the development of drugs.

Evaluation of Natural and Synthetic Phosphate Donors for the Improved Enzymatic Synthesis of Phosphate Monoesters

Undesired product hydrolysis along with large amounts of waste in form of inorganic monophosphate by-product are the main obstacles associated with the use of pyrophosphate in the phosphatase-catalyzed synthesis of phosphate monoesters on large scale. In order to overcome both limitations, we screened a broad range of natural and synthetic organic phosphate donors with several enzymes on a broad variety of hydroxyl-compounds. Among them, acetyl phosphate delivered stable product levels and high phospho-transfer efficiency at the lower functional pH-limit, which translated into excellent productivity. The protocol is generally applicable to acid phosphatases and compatible with a range of diverse substrates. Preparative-scale transformations using acetyl phosphate synthesized from cheap starting materials yielded multiple grams of various sugar phosphates with up to 433 g L?1 h?1 space-time yield and 75% reduction of barium phosphate waste. (Figure presented.).