Acetyl hypofluorite

Eused-ring polycycHc fluoroaromatics can be made from the corresponding amino fused-ring polycycHc or from preformed fluoroaromatics, eg, 4-fluorophenyl-acetonitrile [459-22-3] (275). Direct fluorination techniques have been successfully appHed to polycycHc ring systems such as naphthalene, anthracene, benzanthracenes, phenanthrene, pyrene, fluorene, and quinoHnes with a variety of fluorinating agents xenon fluorides (10), acetyl hypofluorite (276), cesium fluoroxysulfate (277), and electrochemical fluorination (278,279). 

The product from fluonnation of sodium acetate is acetyl hypofluorite [64], which IS isolated and characterized [65] The value of this reagent lies in its relative mildness, because it reacts cleanly with most olefins adding the elements of acetoxyl and fluorine [66] Tnfluoroacetyl hypofluorite adds cleanly only to benzylic or electron-rich double bonds... 

Fluoroxytrifluoromethane (trifluoromethyl hypofluorite) and acetyl hypofluorite are the most commonly used neutral hypofluontes, cesium fluoroxysultate is an inorganic anionic fluoroxy derivative... 

Fluoroxy reagents became of general synthetic utility after the discovery of a relatively simple preparation of acetyl hypofluorite [i5] (equation 2)... 

The synthetic procedure has been extended to the preparation of trifluoro-acetyl hypofluorite [16, 17], long-chain perfluorinated hypofluorites [18, 19], and radiolabeled hypofluorites [II, 12],... 

The white cesium fluoroxy sulfate precipitates from the reaction medium and may be kept for several months in the cold (0 to -15 °C) Metal surfaces can cause detonation of the reagent. The reaction scope of cesium fluoroxysulfate seems narrower than that of acetyl hypofluorite because of its limited solubility in organic solvents Cesium fluoroxysulfate has not been prepared with a fluorine-18 label. 

Fluororesorcinol can be prepared from derivatives of resorcinol and fluo-roxytrifluoromethane [15, 24] (equation 4) or by fluorination of resorcinol with cesium fluoroxysulfate [25] (equation 5). Reaction of acetyl hypofluorite with M-acetyl-O-methyltyrosine methyl ester provides a good route to 3-fluorotyrosine derivatives [26] (equation 6). 

The heterocyclic system bimane produces a difluorinated product on fluonnation with acetyl hypofluorite [34] (equation 11)... 

Acetyl hypofluorite is very effective m the fluorination of the aryl-metal (Hg, Ge, or Si) bond, but yields are frequently low. With aryl silicon compounds some competition exists for replacement of an aromatic hydrogen [5i, 52, 55, 54] (equations 25-27). Fluoroxytrifluoromethane fluorinates p-methoxypheny 1 mercuric acetate to givep-fluoroanisole in 86% yield [52]... 

The aryl tin compounds are better substrates for fluorination because they give high yields of fliiorinated aromatics and they may be fluorinated with acetyl hypofluorite, cesium fluoroxysulfate, or fluorine [52, 54 (equation 28). Aryl boronic esters react with cesium fluoroxysulfate to produce fluoroaromatics [55] (equation 29). 

Acetyl hypofluorite gas is used in a reaction with an arylmercunc acetate to produce a derivative of L-DOPA [56] (equauon 30). 

Table 3. Comparison of Electrophilic Fluorination of Aromatic Amino Acids with [ F]fluorine or [ F]acetyl Hypofluorite" [25]...

A, [ F]fluorine diluted with an unreactive gas B, [ F]acetyl hypofluorite. For companson with F]F2, the radiocherracal yields obtained with acetyl hypofluonte need to be divided by 2... 

Preparation of o- and p-Fluoroacetanilide, 164, 165 Fluorination witli Acetyl Hypofluorite... 

In a related procedure, even benzene and substituted benzenes (e.g., PhMe, PhCl, xylenes) can be converted to phenols in good yields with sodium perborate F3CS020H. " Aromatic amines, N-acyl amines, and phenols were hydroxylated with H2O2 in SbFs—HF. Pyridine and quinoline were converted to their 2-acetoxy derivatives in high yields with acetyl hypofluorite AcOF at -75°C. ... 

CF3OCI has been discussed ), fluorine (F2, diluted with inert gases), xenon difluoride (XeF2), acetyl hypofluorite (MeC02F), and related compounds. As basic aspects of reactions using some of these reagents have been described by Penglis in this Series, developments after 1978 will mainly be described. 

A-Acetyl-9-deoxy-9-fluoroneuraminic acid (591) was prepared by treatment of a protected 6-hydroxyl precursor with A, A-diethylaminosulfur trifluoride (DAST) or through condensation of 2-acetamido-2,6-dideoxy-6-fluoro-D-mannopyranose with potassium di(/ >r/-butyl) oxaloacetate. Compound 591 is a substrate for cytidine monophosphate (CMP)-sialic acid synthetase, giving rise to CMP-5-A-acetyl-9-deoxy-9-fluoroneuraminic acid, which is cytotoxic against tumor cells. 5-A-Acetyl-3-fluoroneuraminic acids 592-594 were prepared through fluorine (or acetyl hypofluorite) addition (in AcOH) to methyl 5-acetamido-4,7,8,9-tetra-0-acetyI-2,6-anhy-dro-2,3,5-trideoxy-D- /ycm>D- a/arto-non-2-enopyranosate. Compound 592 was found to be a potent neuraminidase inhibitor. 

Fluorination can be carried out using fluorine diluted with an inert gas. However, great care is necessary to avoid uncontrolled reaction.21 Several other reagents have been devised that are capable of aromatic fluorination.22 Acetyl hypofluorite can be prepared in situ from fluorine and sodium acetate.23 This reagent effects fluorination... 

A minor explosion in the use of gaseous acetyl hypofluorite was caused by inadvertent contact of the gas inlet tube with a cooling bath, which condensed liquid hypofluorite which subsequently exploded on contact with organic material or air [1], More detail on the isolation of this compound of limited stability, particularly in the liquid phase, is given [2],... 

A comparison of the yields of para-substituted [18F]fluoroarenes indicate that (i) acetyl hypofluorite is an inferior fluorination agent for the fluorodegermylation reaction and (ii) the aromatic substituents have considerable influence over the reactivity of the fluorination. A decrease in the fluorodegermylation yield was observed with electron-withdrawing aromatic substituents. The electrophilic aromatic degermylation reaction is thought to proceed via a cr-complex intermediate (Scheme 3). It has been hypothesized that the yield of aryl fluoride is influenced to some extent by the aromatic substituents ability to stabilize the cr-complex intermediate. 

Acetyl hypobromite, 0729 Acetyl hypofluorite, 0751 Caesium fluoroxysulfate, 4256 Chlorodifluoroacetyl hypochlorite, 0603 Difluoroacetyl hypochlorite, 0653 Fluorine fluorosulfate, 4324 Heptafluorobutyryl hypochlorite, 1352 Heptafluorobutyryl hypofluorite, 1369 Hexafluoroglutaryl dihypochlorite, 1806 Pentafluoropropionyl hypochlorite, 1034 Pentafluoropropionyl hypofluorite, 1056 Propionyl hypobromite, 1154 Rubidium fluoroxysulfate, 4309 Trifluoroacetyl hypochlorite, 0594 Trifluoroacetyl hypofluorite, 0633... 

The selective electrophilic aromatic substitution carried out by displacement of a metallic substituent (Hg, Sn) ( F-fluorodemetallation) using [ F]p2 or [ F]AcOF remains a method of choice to introduce a fluorine atom on a specific position. In the early preparations of [6- F]fluoro-L-DOPA, the reaction of a 6-substituted mercuric derivative with [ F]acetyl hypofluorite yielded the expected compound in 11 % yield [73,74]. Reaction of a mercuric precursor, free or on a modified polystyrene support P-CH2-COOHg(DOPA precursor) allows the preparation of [ F]fluoro-L-DOPA in an overall yield up to 23 %. The polymer supports are easily prepared, require no special treatment for storage and are convenient to use in automated production [75]. 

C.Y. Shiue, P.A. Salvadori, A.P. Wolf, A new synthesis of 2-deoxy-2-[ F]fluoro-D-glucose from F-labeled acetyl hypofluorite, J. Nucl. Med. 23 (1982) 899-903. 

H.H. Coenen, S.M. Moerlein, Regiospecific aromatic fluorodemetallation of group IVb metalloarenes using elemental fluorine or acetyl hypofluorite, J. Fluor. Chem. 36 (1987) 63-75. 

These compounds can be prepared by using either classical processes for synthesis of amino acids (starting from the ad hoc precursor bearing fluorine on the aromatic moiety) or electrophilic fluorination of the arene moiety (e.g., elemental fluorine, xenon fluoride, acetyl hypofluorite). Although these methods are often poorly regioselective, they are useful for the preparation of F labeled molecules used in PET, for example, F tyrosine and dihydrophenylalanine (L-Dopa). ... 

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