Methyl fluoroacetate

Methyl Fluoroacetate Methyl Fluorosulfate Methyl Hydrazine Methyl Iodide Methyl Isocyanate Methyl Mercaptan Methyl Vinyl Ketone Methyltrichlorosilane Nickel Carbonly (Nickel... 

Methyl fluoroacetate. Methyl chloroacetate (108 5 g., 1 mol.) and neutral anhydrous potassium fluoride (70 g., 1-2 mol.) are mixed and heated (with glass marbles) in an indined rotatai autoclave at a... 

VII-I-7. Methyl 2,2-Di-fluoroacetate [Methyl Difluoroacetate, CHF2C(0)0CH3]... 

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. 

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). 

Both methyltriethylphosphonium fluoride and methyltributylphospho-nium fluoride have been prepared The latter generates benzyl fluoride from benzyl chloride in 80% yield and ethyl fluoroacetate from ethyl bromoacetate in 53% yield Methyltnbutylphosphonium fluoride converts 1-bromododecane to a 50 50 mixture of 1-fluorododecane and 1-dodecene Methyltnbutylphosphonium fluoride also quantitatively forms styrene from 1-bromo-1-phenylethane [26] Methyl-tnbutylphosphonium fluonde is the reagent of choice for the conversion of N,N dimethylchloroacetamide to its fluoride, but it is not able to convert chloro-acetonitnle to fluoroacetomtrile Methyltnbutylphosphonium fluoride changes chloromethyl octyl ether to the crude fluoromethyl ether in 66% yield The stereoselectivity of methyltnbutylphosphonium fluoride is illustrated by the reac tions of the 2-tert-butyl-3-chlorooxiranes [27] (Table 2)... 

Methyl 2-methoxy-2-polyfluoroalkyl-2-fluoroacetates, generated from poly-fluoroalkyltrifluoroethylene oxides and methanol, give, on heating with concentrated or fuming sulfuric acid, methyl polyfluoroalkylglyoxylates [29] (equation 32). 

The combination of CsF with Si(OMe)4 58 is an efficient catalyst for Michael additions, e.g. of tetralone 130 to methacrylamide, followed hy cyclization of the addition product to the cyclic enamide 131 in 94% yield [67]. Likewise, addition of the lactone 132 to methyl cinnamate affords, after subsequent cyclization with tri-fluoroacetic acid, the lactam 133 in 58% yield [68] whereas < -valerolactam 134, with ethyl acrylate in the presence of Si(OEt)4 59/CsF, gives 135 in 98% yield [69]. Whereas 10mol% of CsF are often sufficient, equivalent amounts of Si(OEt)4 59 seem to be necessary for preparation of 135 [69] (Scheme 3.11). 

B. Reactions.—(/) Halides. Whereas ylides are alkylated in the normal way on treatment with a-bromo- or a-iodo-esters, quite different reactions occur with a-fluoro- and a-chloro-acetates. When salt-free ylides were refluxed in benzene with ethyl fluoroacetate or trifluoroacetate normal Wittig olefin synthesis took place with the carbonyls of the ester groups to give vinyl ethers, e.g. (14). On the other hand, methyl chloroacetate with... 

Methyl fluoroacetate, a mobile liquid, 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 0-1 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. 

Ethyl, n-propyl and isopropyl fluoroacetates were also readily prepared by heating the corresponding esters of chloroacetic acid with potassium fluoride in the rotating autoclave. Their toxicities were similar to that of methyl fluoroacetate. (It... 

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

The work described in this section was carried out in Cambridge during the war, and was originally submitted by us to the Ministry of Supply in communications entitled Fluoroacetates and related compounds . These communications were made available to American workers from the inception of the work. The present section is concerned mainly with a description of methyl fluoroacetate, CH2F C02Me, and of certain other derivatives of fluoroacetic acid. 

Methyl fluoroacetate (M.F.A.) is a liquid of b.p. 104° and f.p. ca. — 32° and is almost odourless. During a 10 min. exposure to a lethal concentration of the vapour, small animals did not appear to be affected in any way. After exposure, no very obvious symptoms developed until some 30-60 min. later (depending upon the concentration). The symptoms then shown depended to some extent upon the species, but all animals suffered convulsions, from which a partial recovery was sometimes made. Finally, however, a recurrence of the convulsions would cause death. 

The fluorine atom in methyl fluoroacetate (and in many other compounds containing the CH2F group) is quite firmly bound. When M.F.A. was boiled with 10 per cent aqueous potassium hydroxide for 1 hr., no free fluoride was formed. 

It was obviously of interest to determine whether other esters of fluoroacetic acid would prove to be more or less toxic than the methyl ester. In the phosphorofluoridate series, for example, we found that esters of secondary alcohols were far more potent than those of primary alcohols for instance, di-isopropyl fluorophosphonate (I) was a compound of considerable activity. Accordingly ethyl, ra-propyl and isopropyl fluoroacetates were prepared by heating the corresponding esters of chloroacetic acid in the rotating autoclave with potassium fluoride. The toxicity figures of these esters were very similar to those of methyl fluoroacetate. 

In the phosphorofluoridate series, we found that the diphenyl ester (p. 53) was relatively non-toxic. Phenyl fluoroacetate, however, was toxic with an l.d. 50 of 6-10 mg./kg. for subcutaneous injection into mice. The symptoms were similar to those displayed by methyl fluoroacetate. 

In Report no. 5 on fluoroacetates to the Ministry of Supply2 we described the preparation of methyl 1 Z-difluoroacetoacetate, CH2F CO CHF C02Me, in 10 per cent yield by the action of sodium on methyl fluoroacetate. Later we reported that if the condensation were carried out in the presence of methyl alcohol, the yield of methyl difluoroacetoacetate could be increased to 23 per cent, and allowing for recovered methyl fluoroacetate the overall yield was 35 per cent. 

It is interesting to compare the toxicity of fluoroacetyl chloride with the isomeric chloroacetyl fluoride. The former possessed a toxicity comparable to that of methyl fluoroacetate, whereas the latter was relatively non-toxic. This is readily understandable in that fluoroacetyl chloride gives the toxic fluoroacetic acid, whereas chloroacetyl fluoride hydrolyses to chloroacetic acid and the relatively non-toxic (at the concentrations employed) hydrogen fluoride. Fluoroacetyl fluoride also possessed a toxicity comparable with that of fluoroacetyl chloride or of methyl fluoroacetate, again showing that the COF group contributed practically nothing. Acetyl fluoride was also non-toxic. 

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