Direct Fluorination of Aromatics

The distribution of isomers is consistent to an electrophilic mechanism with fluorine cation intermediates. 

A small amount of side-chain fluorination was observed [65]. Benzyl fluoride was formed in about the same extent as the meta-isomer. Small amounts of difluoro- and trifluorotoluenes as well as some unidentified high-boiling compounds were found as well [65]. Addition products were not detected [119]. 

The reaction cannot be performed in fully fluorinated apolar solvents such as octafluorotoluene, which is probably because of missing polarization of fluorine that is necessary to attack the aromatic system. Polar solvents such as methanol or acetonitrile provide better environments for fluorination [119]. Formic acid as a protic solvent gives even better results and is also quite inert as this small molecule has no labile site for fluorine attack [65]. 

Conversion rises, as expected, with increasing temperature, as to be expected [119]. Forthefallingfilm microreactor, conversionisincreasedfroml5% to 30% whenheating up from —40°Cto—15°C. The selectivity varies largely and exhibits no clear trend. 

Using the falling film microreactor or a microbubble column, yields of up to 28% were obtained with acetonitrile as solvent at conversions ranging from 7% to 76% and selectivities from 31 to 43% with regards to the monofluorinated product [119]. Using the dual-channel reactor, conversions from 17% to 95% and selectivities from 37% to 10% were achieved using methanol as solvent [65]. The conversion of a laboratory bubble column, taken for comparison, ranged from 6% to 34% with selectivities of 17-50%, which is equivalent to yields of 2-8% [119]. 

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M. A., Jensen, K. F., Microchemical systems for direct fluorination of aromatics, in Matlosz, M., Ehreeld, W, Baselt,... 

DE Mas, N., Heat effects in a microreactor for direct fluorination of aromatics, in Proceedings of the 6th International Conference on Microreaction Technology, IMRET 6, pp. 184-185 (11-14 March 2002), AIChE Pub. 

De Mas N, Gunther A, Schmidt MA, Jensen KF (2003) Microfabricated Multiphase Reactors for the Selective Direct Fluorination of Aromatics. Ind Eng Chem Res 42 698-710... 

Several studies on the direct fluorination of aromatic compounds have been carried out and, although the reaction conditions were not the same in each case, there are several generalisations that can be made [136-143]. 

A somewhat related report in which equally impressive selectivity and yield (60—90%) were obtained Cacou and Wolf have studied the low temperature direct fluorination of aromatic compounds in CC13 F (100). They have established that under appropriate conditions molecular fluorination proceeds on substituted benzenes and tolulenes with similar selectivity and orientation as has been commonly observed for other halogens. For example reaction with nitrobenzene gives 80% meta substitution and reaction with tolulene gives 60% ortho substitution. The conversions were reported in this study and found to average 0.01%. 

Direct fluorination of aromatic rings is so exothermic that a tarry mixture of products is obtained. Reaction of benzene with the xenon fluorides, XeF2 or XeF4, does give fluorobenzene, but the mechanism is probably free radical rather than polar.137... 

The exploration of new process regimes is tightly correlated to the task of chemical production [3, 8, 25]. Microreactors will then not only serve to investigate processes of macroreactors under ideal or otherwise not feasible conditions, but are expected to partially replace macroreactors for different applications. An example for a reaction which can hardly be achieved even on a laboratory scale is the direct fluorination of aromatics. 

Hessel, V., Ehrfeld, W Golbig, K Haverkamp, V., Lowe, H., Storz, M., Wille, C., Guber, A., Jahnisch, K. and Baerns, M. (2000) Gas/liquid microreactors for direct fluorination of aromatic compounds using elemental fluorine, in Microreaction Technology 3rd International Conference on Microreaction Technology, Proceedings... 

Fluorine. Direct fluorination of aromatic rings with F2 is not feasible at room temperature, because of the extreme reactivity of F2. It has been accomplished at low temperatures (e.g., —70 to —20°C, depending on the... 

Although clean, direct fluorination of aromatic compounds is possible [21], the selectivity of this process is not yet high enough for commercialization. Arenes are best fluorinated in acidic solvents such as sulfuric acid or formic acid, to obtain an electrophilic mechanism (Scheme 2.8). The main obstacle to large-scale industrial application of the potentially inexpensive direct fluorination of aromatic compounds is the difficult separation of the regioisomers and other by-products ivith higher or lower fluorine content. 

V. Hessel, W. Ehrfeld, K. Golbig, V. Haverkamp, H. Lowe, M. Storz, C. Wille, Gas/ Liquid Microreactors for direct Fluorination of Aromatic Compounds Using Elemental Fluorine, in W. Ehrfeld (Ed.), Proceedings of the 3rd International Conference on Microreaction Technology (IMRET3), Springer, Berlin, 1999, p. 526. 

Direct fluorination of aromatics is not a preparatively important reaction because it can occur with explosive violence. Mechanistic studies have been done at very low temperatures and with low fluorine concentrations. For toluene, the fp and fm values are 8.2 and 1.55, respectively, indicating that fluorine is a very unselective electrophile. The p value in a Hammett correlation with o- is -2,45. Thus, fluorination exhibits the characteristics that would be expected for a very... 

V. Hessel, P. Lob, H. Lowe, Direct fluorination of aromatics with elemental fluorine in microstructured reactors. Chimka Oggi - Chemistry Today, 2004, 22, 10. 

N. de Mas, et al., Microfabricated multiphase reactors for the selective direct fluorination of aromatics, Industrial and Engineering Chemistry Research, 2003, 42, 698-710. 

Electrophilic Addition to Aromatics. Aromatic compounds are fluorinated with 1 by heating without a solvent to about 100-150 °C, or, for low-boiUng compounds, up to reflux temperature. Activated aromatics, such as anlsole or N-acetylaniline, react smoothly, whereas toluene requires considerably longer reaction times and gives low yields (eqs 9 11). In all cases, the regioselectivities are consistent with an electrophilic addition mechanism ortho- and para-substituted products predominate over the meta-isomers. 1 has recently been used in orthometalation-directed fluorination of aromatics. ... 

Direct fluorination of aromatics is not a preparatively important reaction because it can occur with explosive violence. Mechanistic studies have been done... 

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