Fluoroacetates esters

Under photo-stimulation, isoindolyloxyl radical (5) abstracts primary, secondary, or tertiary hydrogens from unactivated hydrocarbons including cyclohexane, isobutane, or n-butane (Scheme l).23 The nitroxide (5) traps the resultant carbon-centred radical (R ) and so afford the A -aI koxyisoindo les (6). Blank photolysis experiments with no added hydrocarbon have shown some unprecedented / -fragmentation of (5) to afford the nitrone (7). A number of C60 nitroxide derivatives have been synthesized and characterized by ESR spectroscopy which show features common to nitroxide radicals.24 Reaction of nitroxide and thionitroxide radicals with thiyl radicals have been observed, from which sulfinyl, sulfonyl, and sulfonyloxy radicals were generated.25 The diisopropyl nitroxide radical was generated in the reaction of lithium diisopropylamide with a-fluoroacetate esters.26... 

Jagodzinska, M., Huguenot, F. and Zanda, M. (2007) Studies on a three-step preparation of P-fluoroalkyl acrylates from fluoroacetic esters. Tetrahedron, 63, 2042-2046. 

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). 

Alkyl diethylphosphononuoroacetates have been used extensively in ol fi-nanon procedures [69], principally forming the ffJ-a-fluoro-a.P-unsaturated esters with very high stereoselectivity [70] (equation 61) (Table 22). Preparation of the ethyl diethylphosphonofluoroacetate from ethyl fluoroacetate has obviated the necessity to prepare ethyl bromofluoroacetate from bromine fluoride and ethyl diazoacetate [71],... 

Table 23. Preparation of Ethyl Alkylidene Fluoroacetates RCH=CFCOOEt from Esters Reduced in situ with Diisobuty laluminum Hydride [73]...

For synthetic purposes, aldol-rype condensations of aldehydes with esters or amides are potentially of great utility because the carbonyl group is easily transformed either by further additions or by oxidation or reduction. Deprotonation of an ester [7, 19, 20] or amide of fluoroacetic acid [9, 27] has led to aldol condensations in high yields (equation 17) (Table 7)... 

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... 

Secondary Alkyl Alcohols. Treatment of secondary alkyl alcohols with tri-fluoroacetic acid and organosilicon hydrides results only in the formation of the trifluoroacetate esters no reduction is reported to occur.1,2 Reduction of secondary alkyl alcohols does take place when very strong Lewis acids such as boron trifluoride126 129 or aluminum chloride136,146 are used. For example, treatment of a dichlo-romethane solution of 2-adamantanol and triethy lsilane (1.3 equivalents) with boron trifluoride gas at room temperature for 15 minutes gives upon workup a 98% yield of the hydrocarbon adamantane along with fluorotriethylsilane (Eq. 10).129... 

Other applications dealt with the development of a luciferin ester substrate to measure the luciferase activity in living cells [141], the detection of toxic compounds such as sodium azide, fluoroacetic acid, and antibiotics [142], the development of a biosensor for the determination of bioavailable mercury [143], the use of eukaryotic luciferases as bacterial markers with different colors of luminescence [144], the determination of complement-mediated killing of bacteria [145], and the development of a bioassay for the determination of HIV type 1 virus and HIV-1 Tat protein activity, valuable also for analysis of HlV-inhibi-tory agents [146],... 

Burke, D.G., D.K.T. Lew, and X. Cominos. 1989. Determination of fluoroacetate in biological matrixes as the dodecyl ester. Jour. Assoc. Offic. Anal. Chem. 72 503-507. 

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... 

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 view of the fact that fluoroethanol is as toxic as methyl fluoroacetate (or as fluoroacetic acid), it seemed worth while preparing a compound in which the active parts of these molecules were combined, in the hope of obtaining a compound of increased potency. Such a compound is 2-fluoroethyl fluoroacetate, first prepared and described by us in 1943.1 This ester was readily prepared by the action of fluoroacetyl chloride on fluoroethanol. It is a stable, mobile liquid possessing an extremely faint odour. 

In view of the biological importance of nicotinic acid, it was decided to prepare a quaternary salt from the acid or ester and bromofluoroethane. S Carbethoxy- N-2-fluoroethylpyridinium bromide (XIX) was therefore prepared and examined. The l.d. 50 for subcutaneous injection into mice was 200 mg. /kg., i.e. it was relatively non-toxic compared with methyl fluoroacetate. 

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. 

CH2F CH2 N-ftjX, chlorofluoroethane sulphur-containing compounds, e.g. CH2F CH2 Si2 esters of 1-alkylated fluoroacetic acids, CH-ft F C02iZ and CiZ iZ F C02B acetyl and chloroacetyl fluoride. 

Sodium fluoroacetate (but not methyl fluoroacetate) is practically without action on frog nerve or brain in vitro. The ester decreases the action potential of frog sciatic nerve and reduces the conduction velocity.5 The inactivity of the salt may be related partly to its inability to penetrate cells. 

From a study of the fluoroacetates so far mentioned, it appears that any compound which can give rise to fluoroacetic acid (or the fluoroacetate ion), either by hydrolysis or by oxidation (or both), is toxic. The toxic grouping is thus F-CH2-CO, and any substitution in this radical destroys the toxicity as far as relatively simple compounds are concerned. We had reached this conclusion by May 1943.1 We subsequently showed that esters of / -fluoropropionic acid were non-toxic, whereas esters of y-fluorobutyric acid were shown by American workers to be toxic. In 19442 we reported the synthesis of ethyl 5-fluoro-pentanecarboxylate, F,[CH2]g C02Et (I). This is a stable, colourless liquid and we showed that it possessed very potent toxic properties of the fluoroacetate type. By subcutaneous injection of the propylene glycol solution into mice the l.d. 50 was 4 mg./kg. Methyl fluoroacetate (II) may be taken as a convenient standard (p. 115) and has a l.d. 50 of about 6 mg./kg. for saline solutions, and 15 mg./kg. for propylene glycol solution.3 Therefore ethyl 5-fluoropentanecarboxylate was about 7 times as toxic as methyl fluoroacetate (molecule for molecule).4... 

We see from the above that there is a striking alternation in the physiological properties of w-fluorocarboxylic esters of the general formula of F- [CH2]w-C02.R. Thus when n is an odd number the compound is highly toxic to animals, whereas when n is even the compound is non-toxic. All the toxic compounds are powerful convulsant poisons and showed symptoms of the fluoroacetate type. 

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