Fluorinating agents, heterocyclic

Gas-phase fluorination of hydrocarbon heterocycles using C0F3 as fluorinating agent was successfully apphed for the preparation of some perfluorinated heterocychc compounds" (see Fig. 9.9). 

Fluorinated Heterocyclic Compounds. HeterocycHc compounds containing the CF group are prepared by methods similar to those used in the fluorination of aHphatic compounds. The direct action of fluorine on uracil yields the cancer chemotherapy agent, 5-fluorouracil [51-21-8] as one special example of a selective fluorination on a commercial scale (25). 

Fluorinated heterocycles have many uses and the following are some typical examples. Trifluoromethyl pyridines are useful building blocks for agrochemicals (91MI1). Fluorinated quinolones have evoked considerable interest in the last 10 years as antibacterial agents (90MI1, 90MI2). The... 

Terminal perfluoroolefins have two fluorine atoms at the double bond. The carbon atoms of the latter bear a significant positive charge, and the nucleophilic agents easily replace the fluorine atoms at the multiple bond. The reactions of binucleophilic reagents with terminal perfluoroolefins form heterocyclic systems. The first step of the reaction involves a nucleophilic attack at the carbon atom of the double bond, generating a carbanion. The latter is stabilized by elimination of the fluoride ion and formation of a new double bond. Subsequent cyclization by the intramolecular attack of the nucleophilic center at the double bond leads to the formation of a heterocyclic system. For example, when a reaction mixture of hexafluoropropylene and sodium dialkylaminodithiocarbamate in dimethylacetamide is heated with aqueous sodium tetraphenylborate, one obtains the tetraphenylborate salt of 2-dialkylamino-4-trifluoromethyl-4,5-difluoro-l,3-dithiolan-2-yl (78JFC(12)193). This compound is formed by intramolecular cyclization of the S-nucleophilic center. 

Fluorinated Purines and Benzimidazoles The importance of fluorinated purine and pyrimidine derivatives as antiviral and anticancer agents has increased the need for efficient methods for introduction of fluorine into these heterocyclic systems. This discussion will be confined to examples wherein the fluorine functionality is on the imidazole ring of purines and related compounds. A review of the substantial literature dealing with 2-fluoro-substituted purines, for example, will not be included. 

Brief mention will be made here of the use of fluorinated 1,2,4-triazolones as agrochemical agents. Novel 4-difluoromethyl-l-aryl-l,2,4-tiiazolm-5-ones function as important herbicidal compounds for broad-spectrum weed control for use on such crops as corn, soybean, and wheat. The mode of action has been identified as inhibition of protoporphyrinogen oxidase. Two examples are sulfentrazone 151 and carfentrazone-ethyl 152. A more detailed and comprehensive discussion of agrochemical applications of fluorinated heterocyclic compounds can be found in another chapter of this book. 

There are numerous reports in the patent literature of trifluoromethyl and other perfluoroalkyl-substituted tetrazoles, particularly with 1,5-subtitution, as pharmaceutical and agrochemical agents. Space does not allow a survey of this material here, but a detailed report of the application of fluorinated heterocyclic compounds in crop protection is given in another chapter of this book. ... 

Other papers concerning amides of fluorinated acids include (i) the compounds CFa CO NHMe and (CFs CO)aNMe as new trifluoroacetylating agents (ii) heterocycles from 3,3-dichloro-2,2-difluoropropionimidate and (iii) reactions... 

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