Fluoroacetamidation

C, which decomposes when heated above the melting point. Its solubility at 25°C in g/100 g solvent is water. 111 methanol, 5 ethanol, 1.4 acetone, 0.04 and carbon tetrachloride, 0.004. Because its carbon—fluorine bond is unreactive under most conditions, this salt can be converted by standard procedures to typical carboxylic acid derivatives such as fluoroacetyl esters (11,12), fluoroacetyl chloride [359-06-8] (13), fluoroacetamide (14), or fluoroacetonitrile [503-20-8] (14). 

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). 

Electrochemical oxidation of 1,2-dihydronaphthalene or an indene in acetoni-tnle containing triethylamine tris(hydrogen fluoride) provides a mixture of tereoisomeric difluorides and vicinal fluoroacetamides [201] (equation 38)... 

Control of the stereochemistry of the product has proved problematic when fluoroacetates or fluoroacetamides are used in this process. However, introduction... 

Compare these two basis sets and note the differences between them for carbon, nitrogen, oxygen and fluorine (you can use GFPrinf or GHnput with a system containing these elements one example, fluoroacetamide, is illustrated at the left). What would you expect to be the advantages of the changes that you see ... 

ALmethyl-/V-( triinethylsilyl)-tri-fluoroacetamide 6971 methyl (triphenylphosphoranylidene)-acetate 553 methyl homosecodaphni-phyllate 465 ff. 

Fluoroacetamide, FCHaCONHa, and many new substituted amides of the type FCHaCONHI2, were all convulsant poisons with delayed action. The magnitude of their toxicities suggested that they were hydrolysed in the animal body to fluoroacetic acid. In short, the effective part of the molecule was the FCHsCO grouping.3 Swarts4 was unable to obtain fluoroethyl... 

Fluoroacetyl chloride, CH2FCOCl, was prepared by the action of phosphorus pentachloride on the free fluoroacetic acid (p. 121).1 It is extremely useful as fluoroacetylating agent in synthetic work. Because of its importance we have recently reinvestigated other methods of preparation.2 These may be summarized as follows (1) direct from fluoroacetamide (p. 125) by the action of phosphorus oxychloride and water (2) the action of phosphorus oxychloride on either sodium fluoroacetate (p. 121) or on barium fluoroacetate (p. 121). Good yields are obtained in both (1) and (2), and in each case the starting materials are more easily available than fluoroacetic acid itself. 

Fluoroacetamide has also been prepared by heating a mixture of potassium fluoride and chloroacetamide at 135° under reduced pressure when fluoroacetamide and unchanged chloroacetamide distil over.3 The reaction can also be carried out in xylene solution at ordinary pressure,4 but the yield is only 55 per cent. However, the method has been improved lately, although the product still contains unchanged chloroacetamide. ... 

The preparation of free fluoroacetic acid from methyl fluoroacetate via the barium salt is described on p. 121. An alternative and convenient method1 for preparing the free acid consists in treating fluoroacetamide with nitrous fumes, the pure acid being produced in 90 per cent yield. The two methods may be summarized thus ... 

The group Cl CH2 CH2 N< occurs in the nitrogen mustards which are powerful vesicants, e.g. CH3,N(CH2,CH2C1)2. It was decided therefore to introduce this group into the fluoroacetamide molecule in the hope of combining vesicant properties with the delayed convulsant action of the fluoroacetates. For this purpose N-2 hydroxyethylfluoroacetamide (IV) was prepared by the action of monoethanolamine on methyl fluoroacetate and was readily converted into N-2-chloroethylfluoroacetamide (V) by the action of thionyl chloride ... 

N-2-Chloroethylfluoroacetamide was also prepared by the direct action of 2 mol. of fluoroacetyl chloride on ethanolamine, although we carried out this reaction with the intention of preparing 2-(fluoroacetamide)ethyl fluoroacetate,... 

Injection of (V) into mice showed that the l.d. 50 was similar to that of fluoroacetamide or of fluoroacetic acid, and the symptoms produced appeared to be similar in each case (V), however, showed no vesicant action. It is probable then that hydrolysis of the molecule occurs in vivo, resulting in the formation of fluoroacetic acid and the relatively harmless 2-chloroethylamine. 

By reactions similar to the above we also prepared NN-di-(2 hydroxyethyl)fluoroacetamide and NN-di - (2 chloroethyl)fluoro -acetamide. 

The action of bromine and potassium hydroxide solution on fluoroacetamide might be expected to give fluoromethylamine. Under certain conditions, however, no fluoromethylamine was obtained, but a crystalline solid containing both fluorine and nitrogen was produced.1 Analysis and general reactions showed that it was N fluoroacetyl -N fluoromethylurea,... 

Class B Fluoroacetic acid and salts, e.g. sodium fluoroacetate, triethyl-lead fluoroacetate all simple esters of fluoroacetic acid fluoroacetamide and substituted amides fluoroacetamidine hydrochloride fluoroacetyl chloride and fluoride fluoro-ethanol and its simple esters fluoroacetaldehyde. 

Standardization, of the sodium peroxide bomb method with pure fluoroacetamide... 

In addition to the circumstantial iji vivo evidence for fluorocitrate as the ultimate biochemical lesion we desired to demonstrate unambiguously that it was produced as a metabolite of 29-fluorostigmasterol. The toxicity of fluorocitrate and the resulting lethal accumulation of citrate in mouse, fly and cockroach tissues have been shown in early experiments with fluoroacetamide and fluoroacetate(24). However, to our knowledge, complete characterization of (2R,3R)-2-fluorocitrate as the lethal metabolite in vivo has not previously been reported. We thus prepared( ) [29- ]-29-fluorostigmasterol, [29- H]-29-Huorositosterol and [16- H]-16-fluorohexadec-9-enoic acid to enable isolation of [2-3H]-2-fluorocitrate from vivo incubations using Manduca sexta. 

B. Tecle, J.E. Casida, Enzymatic defluorination and metabolism of fluoroacetate, fluoroacetamide, fluoroethanol, and (-)-erythro-fluorocitrate in rats and mice examined by F and C NMR, Chem. Res. Toxicol. 2 (1989) 429-435. 

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