Aromatics, direct fluorination

Direct fluorination of aliphatics and non-C moieties Direct fluorination of benzenoid aromatics Direct fluorination of heterocyclic aromatics Oxidations of alcohols, diols and ketones with fluorine Photo-oxidation of a-terpinene and cyclopentadiene Oxidation of benzyl alcohol to benzaldehyde Homogeneously catalyzed oxidation of butyraldehyde Oxidation of sulfite to sulfate Photochlorination of aromatic isocyanates... 

The preparation of aromatic fluorine compounds may be accomplished by direct fluorination or by fluonnation of organometallic intermediates. Tlte ipso fluorination of an aryl organometallic derivative with a positive fluorine reagent allows control over the regioselectivity of the fluorination and offers advantages in the preparation of F-labeled materials [II, 50],... 

Dream reactions can be performed using chemical micro process engineering, e.g., via direct routes from hazardous elements [18]. The direct fluorination starting from elemental fluorine was performed both on aromatics and aliphatics, avoiding the circuitous Anthraquinone process. While the direct fluorination needs hours in a laboratory bubble column, it is completed within seconds or even milliseconds when using a miniature bubble column. Conversions with the volatile and explosive diazomethane, commonly used for methylation, have been conducted safely as well with micro-reactors in a continuous mode. 

For example, direct fluorinations with elemental fluorine are kept imder control in this way, at very low conversion and by entrapping the molecules in a molecular-sieve reactor. As with some other aromatic substitutions they can proceed by either radical or electrophilic paths, if not even more mechanisms. The products are dif ferent then this may involve position isomerism, arising from different substitution patterns, when the aromatic core already has a primary substituent further, there may be changed selectivity for imdefined addition and polymeric side products (Figure 1.31). It is justified to term this and other similar reactions new , as the reaction follows new elemental paths and creates new products or at least new... 

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. 

Accordingly, for decades scientific investigations have been carried out to achieve the direct fluorination which would be attractive as a one-step synthesis alternative. Although the early reports concerned gas-phase direct fluorinations, the most relevant work in the last three decades was based on contacting fluorine gas with the aromatic compound dissolved in a liquid phase. These attempts at gas/liquid... 

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... 

Two nitrogen-containing polymeric materials with extended aromatic ladder structures have been chosen for direct fluorination studies (Figure 14.9).57 Pyrolyzed polyacrylonitrile (3) and paracyanogen (4) [poly(pyrazinopryazine)] have been subjected to direct fluorination to produce perfluorinated analogues. 

The consistent poor regioselectivity in direct aromatic electrophilic fluorination has privileged the use of fluorodemetallation reactions. Tin clearly appears to... 

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]. 

Direct fluorination, therefore, is not particularly effective for the preparation of mono-fluorinated aromatic compounds from monosubstituted precursors since, in these cases, electrophilic fluorination gives mixtures of isomeric products. However, when there are two or more groups in the aromatic substrate which activate the same carbon atom towards electrophilic attack, as in the case of 4-fluorobenzoic acid (Table 5), then direct fluorination is an efficient method for the preparation of fluoroaromatic compounds (Fig. 57) [148]. 

Dichloro-l-fluoropyridinium triflate (lm)55 has been used for the direct fluorination of biologically important aromatic compounds. Reaction of estra-1.3,5(10)-triene-3,17/ -diol and... 

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. 

Direct Fluorination of Aliphatics and Non-C Moieties The basic limitations of direct fluorinations are similar for aliphatic compounds as discussed already using the example of aromatic derivatives and so is the potential of microreactors. The fluorination of ethyl acetoacetate was carried out in an annular-flow microreactor. 

Direct Fluorination of Heterocyclic Aromatics Selective fluorination of quinoline aromatics leads to various commercially important products such as 5-fluoroadl, 5-fluoroprimaquine and ciprofloxacin with the fluorine moiety being decisive of their chemical and biological properties. 

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... 

Methods for the chlorination of secondary amines, secondary amides and imides have been reviewed. Secondary alkylamines can be chlorinated by r-butyl hypochlorite at low temperature, or by sodium hypochlorite or iV-chlorosuccinimide. A(-Bromination and A(-iodination can be brought about using the appropriate halogen, but these N-halodialkylamines are unstable and are rarely isolated. A(-Flu-oroamines and Mfluoroamides are also rare. The A(-fluoroimide (CP3S02)2NF, has, however, been prepared by direct fluorination widi fluorine. It is a stable liquid which shows promise as a fluorinating agent for aromatic compounds. ... 

The changing perspective on the viability of fluorine as a reagent is illustrated by the fact that many selective fluorinations of substrates [8] containing carbon centres of high electron density have now been described, including a variety of enolate derivatives [71, 72], stabilised carbanions [73, 74], steroids [75] and 1,3-dicarbonyl derivatives [76] (Table 3.2) as well as some aromatic compounds [77]. Fluorinated aminoacids have been obtained by direct fluorination [78] (Figure 3.10). 

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