Fluoroacetates

These compounds contain, in general, the CHgF group. Until work was undertaken at Cambridge at the beginning of the war httle serious attention had been paid to these compounds or to their systematic physiological examination. 

Methyl fiuoroacetate, a mobile hquid, has an extremely faint odour. Animals did not usually exhibit any symptoms while being exposed to lethal concentrations of this vapour, and no obvious effects were noted until some 30-60 min. (depending upon the concentration) after exposure. Violent convulsions then took place and death usually followed within a few hours. For rabbits and guinea-pigs the lethal concentration (l.c. 50) for a 10 min. exposure was of the order of 01 mg./l. Mice were rather more resistant. Intravenous injection produced symptoms similar to those displayed after exposure to the vapour. Even with large doses a delayed action was observed. The L.D. 50 for rabbits (intravenously) was found to be about 0-25 mg./kg. 

W propyl and isopropyl fluoroacetates were also readily prepared by heating the corresponding esters of chloroacetio acid with potassium fluoride in the rotating autoclave. Their toxicities were similar to that of methyl fiuoroacetate. (It 

The following three acyl halides were prepared and their toxicities examined  

These findings were in accordance with expectation, and it was now obvious that the toxicity was bound up with the FCHgCO group, whereas the FCO group was ineffective. Further confirmation of this point was provided by the observation that ethyl fluoroformate, FCOOEt, was non-toxic. Fluoro-Bcetic anhydride was slightly more toxic (by inhalation) than method fluoroacetate. 

Fluoroacetamide, FCH2CONH2, and many new substituted amides of the type FCH2CONHiZ, were all convulsant poisons with delayed action. The magnitude of their toxicities su ested that they were hydrolysed in the animal body to fluoroacetic acid. In short, the efiTective part of the molecule was the FCHjOO grouping. Swarts was unable to obtain fluoroethyl 

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Sodium fluoroacetate, which is not volatile and not irritating to the skin, is used as a rodenticide. It is made from CH2ClC02Et and KF, which react to give ethyl fluoroacetate, which is then hydrolysed with NaOH in methyl alcohol. 

If this electrostatic treatment of the substituent effect of poles is sound, the effect of a pole upon the Gibbs function of activation at a particular position should be inversely proportional to the effective dielectric constant, and the longer the methylene chain the more closely should the effective dielectric constant approach the dielectric constant of the medium. Surprisingly, competitive nitrations of phenpropyl trimethyl ammonium perchlorate and benzene in acetic anhydride and tri-fluoroacetic acid showed the relative rate not to decrease markedly with the dielectric constant of the solvent. It was suggested that the expected decrease in reactivity of the cation was obscured by the faster nitration of ion pairs. 

Chloroacetate esters are usually made by removing water from a mixture of chloroacetic acid and the corresponding alcohol. Reaction of alcohol with chloroacetyl chloride is an anhydrous process which Hberates HCl. Chloroacetic acid will react with olefins in the presence of a catalyst to yield chloroacetate esters. Dichloroacetic and trichloroacetic acid esters are also known. These esters are usehil in synthesis. They are more reactive than the parent acids. Ethyl chloroacetate can be converted to sodium fluoroacetate by reaction with potassium fluoride (see Fluorine compounds, organic). Both methyl and ethyl chloroacetate are used as agricultural and pharmaceutical intermediates, specialty solvents, flavors, and fragrances. Methyl chloroacetate and P ionone undergo a Dar2ens reaction to form an intermediate in the synthesis of Vitamin A. Reaction of methyl chloroacetate with ammonia produces chloroacetamide [79-07-2] C2H ClNO (53). 

Fluoroacetic acid [144-49-OJ, FCH2COOH, is noted for its high, toxicity to animals, including humans. It is sold in the form of its sodium salt as a rodenticide and general mammalian pest control agent. The acid has mp, 33°C bp, 165°C heat of combustion, —715.8 kJ/mol( —171.08 kcal/mol) (1) enthalpy of vaporization, 83.89 kJ /mol (20.05 kcal/mol) (2). Some thermodynamic and transport properties of its aqueous solutions have been pubHshed (3), as has the molecular stmcture of the acid as deterrnined by microwave spectroscopy (4). Although first prepared in 1896 (5), its unusual toxicity was not pubhshed until 50 years later (6). The acid is the toxic constituent of a South African plant Dichapetalum i mosum better known as gifirlaar (7). At least 24 other poisonous plant species are known to contain it (8). 

Chemically, fluoroacetic acid behaves like a typical carboxylic acid, although its acidity is higher K — 2.2 x 10 ) than the average (9). It can be prepared from the commercially available sodium salt by distillation from sulfuric acid (10). 

Sodium Fluoroacetate. Sodium fluoroacetate [62-74-8] FCH2COONa, known as Compound 1080, is a hygroscopic white soHd, mp,... 

Toxicity. Sodium fluoroacetate is one of the most effective all-purpose rodenticides known (18). It is highly toxic to all species of rats tested and can be used either in water solution or in bait preparations. Its absence of objectionable taste and odor and its delayed effects lead to its excellent acceptance by rodents. It is nonvolatile, chemically stable, and not toxic or irritating to the unbroken skin of workers. Rats do not appear to develop any significant tolerance to this compound from nonlethal doses. However, it is extremely dangerous to humans, to common household pets, and to farm animals, and should only be used by experienced personnel. The rodent carcasses should be collected and destroyed since they remain poisonous for a long period of time to any animal that eats them. 

Fluoroacetamide. Fluoroacetamide [640-19-7], FCH2CONH2, is a white water-soluble soHd having mp 108°C (14). It has been used as a rodenticide and has been reported to have a better acceptability to rats than sodium fluoroacetate (29). However, like the latter compound, its misuse has caused deaths to farm animals and pets (20). 

TuU Chemical Co. (Oxford, Alabama) is the only producer of sodium fluoroacetate. It is sometimes colored with the black dye nigrosine. It is usually packed in 8 oz (227 g) or 5 kg cans and is almost exclusively exported. There is very limited use in the United States. 

Difluoroacetic acid is much less toxic than fluoroacetic acid (LD q = 180 mg/kg mouse iv) (41). It is available in research quantities for about 5/g... 

Health and Safety Factors. Unlike fluoroacetic acid, trifluoroacetic acid presents no unusual toxicity problems. However, owing to its strong acidity, its vapors can be irritating to tissue, and the Hquid acid can cause deep bums if allowed to contact the skin. The acid can be safely stored in containers made of glass or common corrosion-resistant alloys and metals such as stainless steel or alurninum. 

Eluoropyridine derivatives can be constmcted from fluoroaUphatic feedstocks. 5-Eluoro-2,6-dihydroxynicotinamide [655-15-OJ, a precursor to the anti-bacterial, enoxacin [74011-58-8] was prepared in 63% yield from ethyl fluoroacetate [459-72-3] ethyl formate [109-94-4], and malonamide [108-13-4] (394). 

Fluoropyrknidine derivatives are of tremendous importance in cancer chemotherapy, eg, 5-fluorouracil [51-21-8] (5-FU). The original 5-fluorouracil process featured a multistep low yield route based on ethyl fluoroacetate (451). Direct fluorination (fluorine) of uracil [66-22-8] gives high yields of 5-FU (452—455). This process has now been commercialized. 

Benzamidomethyl-A -methylcysteine has been prepared as a crystalline derivative (H0CH2NHC0C6H 5, anhydr. CF3CO2H, 25°, 45 min, 88% yield as the tri-fluoroacetate salt) and cleaved (100% yield) by treatment with mercury(II) acetate (pH 4, 25°, 1 h) followed by hydrogen sulfide. Attempted preparation of S-acetamidomethyl-N-methylcysteine resulted in noncrystalline material, shown by TLC to be a mixture. ... 

Sodium fluoroacetate (mono) [62-74-8] M 100.0, m 200-205 (dec). A free flowing white TOXIC powder which is purified by dissolving in ca 4 parts of H2O and the pH is checked. If it is alkaline, add a few drops of FCH2CO2H to make the solution just acidic. Evaporate (fumehood) on a steam bath until crystals start to separate, cool and filter the solid off. More solid can be obtained by adding EtOH to the filtrate. Dry at 100 in vacuum. [7 Chem Soc 1778 1948.]... 

Zineb Rodenticides Sodium Fluoroacetate Strychnine Thallium Sulphate Warfarin 5200 0.05 SK 0.15 0.1 as Tl, SK 0.1... 

Sodium 2,4-dichloro-phenoxyethyl sulphate, see Sesone Sodium fluoroacetate SK -... 

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