Fluoroformates, formation

There are some reactions in which boron trifluoride and boron trifluoride-diethyl ether complex are used as fluorinating agents, but they are not so frequently used and widespread. The best-known reaction is the decomposition of fluoroformates. In this type of reaction boron trifluoride or pyridine are essentially required as catalysts for the decomposition process. The formation of fluoroformates is established4 5 and the decomposition proceeds cither by heating in pyridine at higher temperature6 or by addition of boron trifluoride-diethyl ether complex at 0-50°C.7... 

Like thallium(I) fluoride (see Section 18.2.), silver(I) tetrafluoroborate is used to convert chloro-formates into the corresponding fluoroformates, which are decomposed to the fluorides as described in Section 16.1.2. Phenyl fluoroformate (4) is obtained in moderate yield in this way from 3.68... 

The fluoroform reaction has also been observed with higher perfluoroalkyl aldehydes and perfluoroalkyl ketones, which react with formation of l//-perfluoroalkanes and carboxylic acids. 

Much better results can be obtained with substituted aromatics. The reaction of aryl chloro- or fluoroformates which have alkyl groups in position 2 and 6 gives fluoroaromalic compounds in good yield. The Friedel-Crafts reaction is widely suppressed although Lewis acids or hydrogen fluoride are present in the reaction mixture. Another advantage of this process is that the fluoroaromalic compounds can be obtained from the fluoro- as well as from the chloroformates. which, in general, are easier to prepare, A typical example is the formation of 2-fluoro-1.3-dimethylbenzene (2). ... 

Attempts to apply the thermal decarboxylation reaction in the liquid phase to aromatic halofor-mic acid esters have shown that their reaction is different from that ol the aliphatic haloformates. It was found that evolution of carbon dioxide occurs, but only high boiling products could be isolated.136 On heating in the presence of aromatics and Lewis acids, aryl chloroformates do not react to give chlorinated aromatics with concomitant decarboxylation, but undergo a Friedel-Crafts reaction to give phenyl benzoates.137 Under similar conditions phenyl fluoroformate undergoes only polymerization and carbonate formation.137... 

In contrast to the carbamate chemistry, thermal elimination of hydrochloric acid from 1-chloroalkyl carbonates requires much higher temperature and is accompanied by major yield destructive side reactions. The key to an economical route to vinylic carbonates was discovered by Olofson and coworkers (Ref. 129). This discovery was the consequence of a beautiful observation made by Dang, Olofson s student, on the formation of neopentyl fluoroformate and, unexpectably of vinyl neopentyl carbonate while heating 1-chloroethyl neopentyl carbonate with KF in benzonitrile (Ref. 130). 

Carbonyl difluoride is a particularly versatile fluorinating agent, and an important material for the synthesis of organofluorine compounds [1079], Its reactions with perfluoroalkenes gives perfluoroacyl fluorides in the presence of a fluoride ion source, and its facile reaction with amines or alcohols results in the formation of carbamoyl fluorides or fluoroformates, respectively. The fluorination of carbonyl compounds, such as aldehydes and ketones, with COF can give gem-difluorides by replacement of the carbonyl oxygen atom with two atoms of fluorine e.g.-. 

Alcohols react with carbonyl difluoride in a similar way to that described for phosgene (see Section 10.3.1). The first stage of the reaction is the formation of the fluoroformate. 

In a related system, the reaction of [CgFjO]K with an 8 1 excess of COF3 at 23 C, but using much shorter reaction times (8 min), results in the formation (29% yield) of the corresponding perfluorinated aromatic fluoroformate, CgF50C(0)F. When an excess of COFj was not employed, the carbonate, (CgF30)2C0, was formed [610]. 

Where a deficiency of COFj is employed in these reactions, the yield of fluoroformate tends to fall owing to the formation of carbonates. 

However, since the ui-chloroalkyl fluoroformate may also be formed in the absence of hydrogen chloride (albeit in lower yield), it may be assumed that the reaction can proceed directly, without formation of the intermediate alcohol. 

Treatment of a thiol or thiophenol with carbonyl chloride fluoride in the presence of a tertiary amine (in an inert solvent such as heptane) results in the formation of the corresponding thiol fluoroformate in 75-85% yield [1555a] ... 

Peptide synthesis, N-protection Acetic-formic anhydride. Adamantyl chloroformate. Benzylthiocarbonyl chloride. /-Butoxycarbonyl-N-hydroxysuccinimide ester. /-Butyl azido-formate. /-Butylcarbonic diethylphosphoric anhydride. /-Butyl fluoroformate. /-Butyl oxycarbonyl fluoride. /-Butyl pentachlorophenyl carbonate. /-Butyl 2,4,5-trichlorophenyl carbonate. Carbobenzoxy chloride. 3,5-Dimethoxybenzyl p-nitrophenyl carbonate. [2-(Diphenyl)isopropyljphenyl carbonate. /-Pentyl chloroformate. 

The decarboxylation of arylchloroformate (ref. 8) or thiochloroformate (ref. 9) into the corresponding chloroaromatic and the decarboxylation of aliphatic fluoroformate occurs by an ionic mechanism (ref. 10). But, the arylfluoroformate decomposition by this mechanism does not lead to the formation of fluorinated aromatics but instead to phenols and tars (ref. 4a). 

Pioneering studies showed that attack by strong nucleophiles (alcoholates...) on the larger halogen X can occur, as shown by the formation of fluoroform in protic medium (Fig. 3) (ref. 8). 

When trifluoroiodomethane is treated with a solution of chromium(u) ions, the brownish orange [Cr(OH2)s(CF3)] + is obtained. This complex is stable towards aquation compared with the corresponding methylchromium species, slowly giving hydrogen fluoride and carbon monoxide but no detectable fluoroform. With sodium fluoride [Cr(OH2)4F(CFs)]+ is formed. The formation of Cr[C(CFs)2(CN)]2 in good yield from Cr(OAc)2 and (CF3)2CH CN under naild conditions has been reported. ... 

Abstract - This work is concerned with the origin of effects on rate equilibrium processes when reactions are performed in dipolar aprotic media such as dimethyl sulfoxide and dimethyl-formamide compared to typical hydroxylic media. An example of processes studied in our laboratory is the competition between proton abstraction and a-complex (Meisenheimer adduct) formation in the interaction of nitroaromatic compounds with basic systems (e.g. 1,3-dinitrobenzene in DMF-D20-Na0D). Other reactions studied are the base catalyzed isotopic exchange of D2 in aqueous DMSO mixtures, and also isotopic exchange of fluoroform. It has been found possible in certain cases to dissect the initial state and transition state contributions to the reaction rates from the kinetically measured enthalpies of activation and the thermodynamically evaluated enthalpies of transfer of the reactants. This procedure affords insight into transition state properties and behaviour. 

In most of 43 pure and binary solvent mixtures, solvolysis of isobutyl chloroformate proceeded via formation of a TI, but in pure 2,2,2-trifluoroethanol, an 5 1 pathway took over. Similar results were found for l-adamantylmethyl, ° alkyl, and vinyl chloroformates, with an 5 1 pathway predominant in highly polar solvents. However, an addition-elimination pathway for the solvolysis of 1-adamantylmethyl fluoroformate prevailed for all solvent-water combinations. ... 

Bright and coworkers investigated pyrene-excimer formation in supercritical fluids from a somewhat different angle using not only steady-state but also time-resolved fluorescence techniques (47,167). They measured fluorescence lifetimes of the pyrene monomer and excimer at a pyrene concentration of 100 p,M in supercritical ethane, CO2, and fluoroform at reduced densities higher than 0.8. Since the kinetics for pyrene-excimer formation was found to be diffusion controlled in ethane and CO2 and less than diffusion controlled in fluoroform, they concluded that there was no evidence for enhanced pyrene-pyrene interactions in supercritical fluids. The less efficient excimer formation in fluoroform was discussed in terms of the influence of solute-solvent clustering on excimer lifetime and stability. Experimentally, their fluorescence measurements were influenced by extreme inner-filter (self-absorption) effects due to the high pyrene concentration in the supercritical fluid solutions (35). 

Although, supercritical carbon dioxide has the advantage of being non-toxic and abundant, it is practically immiscible with water. Also, side reactions such as carbamate formation and carbonic acid formation can occur when carbon dioxide is employed as the supercritical fluid in enzymatic reactions. Therefore, supercritical fluids used as the reaction medium in enzyme catalyzed reactions include fluoroform, sulfur hexafluoride and ethane, while lipases are the enzymes utilized in such reactions." However, ethane and propane have the disadvantages of being expensive and flammable. 

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