Sodium fluoroacetate containing

It is interesting to note that the toxic sodium fluoroacetate (above, p. 11) occurs in the poisonous South African plant gifblaar (Dichapetalum cymosum, PI. I). It has recently been shown that sodium fluoroacetate is a highly effective systemic insecticide, but it is difficult to say exactly how this substance will be applied on a large scale.6 There are many other insecticides containing fluorine and phosphorus, and special precautions must be taken when handling these toxic compounds. 

Sodium fluoroacetate.1 To methyl fluoroacetate (46-0 g., 0-5 mol.) suspended in water (100 c.c. containing a few drops of phenolphthalein) sodium hydroxide (0-5 mol., 20 g. in 100 c.c. water) is added slowly. The mixture is kept well stirred, and the rate of addition governed by the disappearance of the red coloration. When the addition of sodium hydroxide is complete, a few more drops of M.F.A. are added to render the solution acid. It is then evaporated on the water-bath until crystallization starts, cooled and the solid filtered off. More solid is obtained from the filtrate by the addition of alcohol total yield 45-5g. (91-0 per cent). (Found F, 19-0. Calc, for C2H202FNa F, 19-0 per cent.) This is characterized as p-nitrobenzyl fluoroacetate as follows. p-Nitrobenzyl bromide (0-9 g.), dissolved in alcohol (10 c.c.), is added to a solution of sodium fluoroacetate (0-3 g.) in the minimum amount of water. The mixture is heated under a reflux condenser for 2 hr. and allowed to cool the solid is collected by filtration, and crystallized from ethanol as long needles, m.p. 76°. 

It should be stressed that we are not yet aware of all the hazards in connexion with the use of sodium fluoroacetate, or indeed of any compounds containing the FCH2CO group, as insecticides. 

The method developed for sodium fluoroacetate is based on collection of the sample with cellulose ester filters especially low in extractables (Toyo-cel cellulosic ester membrane filters from Nuclepore were used). The samples were extracted with water and analyzed by ion chromatography. Other MCE filters contained high levels of extractables Cfrom wetting agents, surfactants) that... 

Among the most deadly of simple compounds is sodium fluoroacetate. The LD50 (the dose lethal for 50% of animals receiving it) is only 0.2 mg/kg for rats, over tenfold less than that of the nerve poison diisopropylphosphofluoridate (Chapter 12).a b Popular, but controversial, as the rodent poison "1080," fluoroacetate is also found in the leaves of several poisonous plants in Africa, Australia, and South America. Surprisingly, difluoroacetate HCF2-COO is nontoxic and biochemical studies reveal that monofluoroacetate has no toxic effect on cells until it is converted metabolically in a "lethal synthesis" to 2R,3R-2-fluorocitrate, which is a competitive inhibitor of aconitase (aconitate hydratase, Eq. 13-17).b This fact was difficult to understand since citrate formed by the reaction of fluorooxalo-acetate and acetyl-CoA has only weak inhibitory activity toward the same enzyme. Yet, it is the fluorocitrate formed from fluorooxaloacetate that contains a fluorine atom at a site that is attacked by aconitase in the citric acid cycle. 

Sodium fluoroacetate was prepared with the idea of obtaining a stable water-soluble compound containing the CHjF CO group, suitable for feeding experiments. The method of obtaining this salt is described in detail below. It consists essentially in adding cold aqueous sodium hydroxide to methyl fluoro-acetate and evaporating the solution. Subsequent to our initial work, sodium fluoroacetate has been recommended and used as a rodenticide. 

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). 

In each class the problem may be resolved into two essential parts (i) the breakdown of the organic compound under appropriate conditions to give a quantitative yield of fluoride ions in aqueous solution, and (ii) the determination of the concentration of these fluoride ions. Methods of breaking down the organic compounds were examined and the procedure adopted for the phosphorofluoridate was different from that used for the fluoroacetate series. From both, however, sodium fluoride was obtained as the breakdown product containing all the fluorine present. After numerous preliminary experiments we came to the conclusion that on the macro-scale a very convenient method of determining the quantity of fluoride ions in the products was by precipitation as lead chlorofluoride,2 PbCIF, which was then dissolved in dilute nitric acid and the chloride was determined by the Volhard method and calculated to the equivalent amount of fluorine. We determined carefully the conditions for the quantitative precipitation of lead chlorofluoride. 

---