Toluene, direct fluorination

Figure 1.31 Electrophilic and radical paths in direct-fluorination chemistry leading to substitutions, additions and polymerizations with the example of toluene as substrate.

Cas/liquid reaction [CL 1] Direct fluorination of toluene using elemental fluorine... 

Using methanol as solvent, the conversions ranged from 12 to 42% at selectivities of 9-58% [38]. This corresponds to yields of 3-14%. Hence the performance of the direct fluorination in methanol is generally worse than that in acetonitrile. The highest yield was found for a liquid volume flow of 11.1 ml h using a 1.1 mol 1 toluene concentration at -17 °C. The fluorine/toluene molar ratio was 0.925. 

Figure 5.18 Comparison of space-time yields of direct fluorination of toluene for the falling film micro reactor (FFMR), micro bubble column (MBC) and laboratory bubble column (LBC) referred to the reaction volume (a) and referred to an idealized reactor geometry (b) [38],...

Jahnisch K, Baerns M, Hessel V, Ehrfeld W, Haverkamp V, Lowe H, Wille C, Guber A (2000) Direct Fluorination of Toluene Using Elemental Fluorine in Gas/Liquid Microreactors. J Fluor Chem 105 117-128 Jahnisch K, Hessel V, Lowe H, Baerns M (2004) Chemistry in Microstructured Reactors. Angew Chem Int Ed 43 406 -46 Jensen KF (2001) Microreaction Engineering - is Small Better Chem Eng Sci 56 293-303... 

Falling-film gas/liquid microreactors, as shown in Figure 8.2, are also useful for direct fluorination of organic compounds, such as toluene with F2 (Scheme 8.2). In this reactor a liquid reactant falls down through the channels and the gas also falls down on to the surface of the liquid flow to attain a high gas/liquid surface-to-volume ratio to accelerate the gas/liquid reaction. 

K. Jahnisch, M. Baerns, V. Hessel, W. Ehrfeld, V. Haverkamp, H. Lowe, C. Wille, A. Guber, Direct fluorination of toluene using elemental fluorine in gas/liquid microreactors, J. Fluor. Chem. 105 (2000) 117. 

In another example, Hessel et al. [42] and Loewe et al. [43] studied the direct fluorination of toluene with F2 in a microsystem consisting of reaction channels as well as mass transfer and heat transfer in close proximity. They claim a change in the reaction mechanism from radical in nature to an electrophilic substitution, through careful control of the reaction conditions. This type of microreactor is well described in the literature and is commonly known as a falling film microreactor [44, 45]. 

Jahnisch, K, Baerns, M, Hessel, V, Ehrfeld, W, Haverkamp, V, Lowe, H., Wille, C., and Guber, A. (2000) Direct fluorination of toluene using elemental fluorine in gas/liquid microreactors. /. Fluorine Chem., 105 (1), 117-128,... 

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... 

Direct fluorination of toluene and nitrotoluene Falling film and bubble column MSR Jahnisch et al. [30]... 

Direct fluorination of toluene using elemental fluorine is not feasible since the heat release cannot be controlled with conventional reactors. So the process is deliberately slowed down. Hence, the direct fluorination needs hours in a laboratory bubble column. It can be completed within seconds or even milliseconds when using a miniature bubble column, operating close to the kinetic limit. The Bayer-Villiger oxidation of cyclohexanol to cyclohexanone with fluorine and aqueous formic acid (5% water) is done in miniature bubble column reactors at 60% conversion at 88% selectivity. 

The Introduction of Fluorine Into Aromatic Rings.— The direct fluorination (F2-N2) of nitrobenzene, benzotrifluoride, benzoic acid, and toluene, usually in trifluoroacetic acid at 5 C, has been described by Russian workers. Where direct comparisons can be made, the isomer distributions of the monofluoroarenes obtained are qualitatively similar to those formed in acetonitrile during concurrent American work, sununarized in Vol. 1 (p. 189). However, the Russians favour a homolytic mechanism, the preference for attack at the /wc/o-position in nitrobenzene being attributed to the electrophilic character of the attacking fluorine atom. Electrophilic displacement of a proton by F, via the usual addition-elimination mechanism, was preferred in the American paper, and this view has been emphasized in a recent review of the field by the same author. ... 

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. ... 

Figure 11.9 Direct fluorination of toluene in a falling film microreactor.

Direct fluorination of toluene dissolved in acetonitrile Falling film microreactor Safer process. Yield in microreactor 2.5 times higher than in a lab bubble column... 

When R2 substituent is flourocontaining alkyl group, the transformation 17 18 becomes hindered and its proceeding requires some special methods. For example, in [48] Biginelli-like cyclocondensations based on three-component treatment of 3-amino-l,2,4-triazole or 5-aminotetrazole with aldehydes and fluorinated 1,3-dicarbonyl compounds were investigated. It was shown that the reaction can directly lead to dihydroazolopyrimidines 20, but in the most cases intermediate tetrahydroderivatives 19 were obtained (Scheme 10). To carry out dehydration reaction, refluxing of tetrahydroderivatives 19 in toluene in the presence of p-TSA with removal of the liberated water by azeotropic distillation was used. The same situation was observed for the linear reaction proceeding via the formation of unsaturated esters 21. 

Directed introduction of fluorine and the 18F isotope has been achieved by reactions of acetyl hypofluorite with tin or mercury derivatives 29 or 30, respectively.25 The course of the reaction with mercury derivatives depends on the structure of the substrate and as well as fluorinated products, acetates and toluenes are also formed.26-27... 

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