Perfluorinated heterocyclic compound

A large number of perfluorinated heterocyclic compounds was prepared (mostly using ECF technology) in 1970-1990 during the quest for the best materials to be used as oxygen carriers in perfluorocarbon emulsions, so-called blood substitutes (for detailed review on this effort, see Ref. 34). The list of synthesized materials includes perfluorinated A-alkyl(cycloalkyl) pyrrolidines, oxazolidines, piperidines and... 

Other examples of electrophilic reactions of perfluorinated heterocyclic compounds include mentioned earlier hydrolysis of cyclic chlorinated ethers 20 (Fig. 9.5), unsaturated ether 27 (Fig. 9.8), and cyclic amines leading to fluorinated lactams (Fig. 9.10). 

The double bonds in certain heterocyclic compounds, such as furans, Af-acylpyrroles and A-acylindoles are also susceptible to photoaddition of carbonyl compounds to form oxetanes (equation 106) (77JHC1777). A wide range of carbonyl compounds can be used, including quinones, a-diketones, acyl cyanides, perfluorinated aldehydes and ketones and esters. A remarkable case of asymmetric induction in oxetane formation has been reported from optically active menthyl phenylglyoxylate and 2,3-dimethyl-2-butene the oxetane product obtained after hydrolysis of the ester group had an optical purity of 53% (79AG(E)868). 

Syntheses of heterocyclic compounds with perfluorinated side chains are mainly performed by substitutional fluorinations of the available fragments or by the introduction of a perfluoroalkyl group in the heterocycle. The development of convenient approaches and direct perfluoro-alkylation methods is a current challenge. 

Small heterocycles are of interest in view of their high reactivity and role in biosynthesis. Moreover, for the three-membered ring with an oxygen atom, the ease of ring cleavage creates conditions for polycondensations and heterocyclizations. The former give perfluorinated polyethers with a broad spectrum of practical applications, and the latter affords various heterocyclic compounds. 

Simons process — Electrochemical polyfluorination reactions of organic compounds are the only efficient way to industrial production of perfluorinated compounds. The reaction proceeds in the solution of KF in liquid HF (b.p. 19.5 °C), where the starting substances as alcohols, amines, ethers, esters, aliphatic hydrocarbons and halo-hydrocarbons, aromatic and heterocyclic compounds, sulfo- or carboxylic acids are dissolved. During anodic oxidation, splitting of the C-H bonds and saturation of the C=C bonds occur and fluorine atoms are introduced. 

The action of a Zn/Cu couple on 1,3-dibromo ketones and secondary amides yields 2-dialkylamino-1,3-dioxolanes (451 equation 208). Fluorosulfonic peracid anhydride adds to trifluoroacetonitrile to give an amide acetal (452 equation 209). In the addition of (Z)-2-butene-l,4-diol to trichloroacetoni-trile, catalyzed by sodium, the 1,3-dioxepin (453 equation 210) is produced. Bicyclic amide acetals (454 equation 211) are byproducts in the reaction of lactim ethers with diketene. TTie methyl esters of perfluorinated carboxylic acids react with diethanolamine to afford bicyclic amide acetals (455 equation 212). Heating of maleic anilides (456 equation 213) with acetic acid anhydride/sodium acetate gives heterocyclic compounds (457) containing an amide acetal structure. ... 

Perfluorochemicals make up an important area of fluorine chemistry, in particular with respect to industrial applications. " Among these, perfluorinated nitrogen-containing heterocyclic compounds have received attention for a variety of applications, and this topic will be discussed briefly in this section. 

Additional information on the reactivity of perfluorinated aromatic heterocyclic compounds can be found in Chapter 8. 

This chapter is one of the first attempts of systematic review of the synthetic methods and chemistry of nonaromatic saturated and unsaturated perfluorinated heterocycles. It summarizes data on the synthesis and chemical transformation of perfluorinated six- and to some extent five- membered nonaromatic heterocyclic compounds containing oxygen, nitrogen, sulfur, selenium, and phosphorous. It should be pointed out that the review is not all-inclusive one, but it is an attempt to provide representative examples of synthetic methods and chemistry of perfluorinated nonaromatic hetero-cychc materials. 

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). 

Reactions of Saturated Perfluorinated Heterocycles Due to the strong electron withdrawing effect of perfluorinated framework, saturated ethers or amines are extremely week bases and they do not form stable compounds as a result of protonation or alkylation of heteroatom. Unshared electron pair(s) of heteroatom, however, manifests itself in different manner—through the activation of a-fluorine substituents. 

It should be pointed out that perfluorinated aromatic heterocyclic compounds is another valuable feedstock for the synthesis of unsaturated fluorinated heterocycles. For example, fluorination of F-pyridine over C0F3 at 120°C results in saturation of both C=C, leading to 81 as principal product, along with smaller amount of F-l-azacyclohexadiene-1,3." Fluorination of substituted pyridine 115 over C0F3 gives diene 116 in a high yield. 

Pushkina, L.N. Kollegov, V.E. Stepanov, A.P. Mazalov, S.A. Sokolov, S.V. Methods of preparation and properties of organofluorine compounds. VI. Some tertiary perfluorinated heterocyclic amines and products of their transformations. Zh. Obshch. Khim. 1966, 36(9), 1619-1625. 

Since perfluorinated heterocycles have distinct and often unique chemistry, this group was considered as a separate category and data on perfluorinated aromatic and nonaromatic compounds are given in Chapters 8 and 9, respectively. The information on seven-membered and larger ring heterocycles, including perfluorinated crown ethers and polyfluorinated macrocycles, is provided in Chapter 10, which concludes Part I of the book. 

Bicyehe nitrogen-containing heterocyclic compounds were also fluorinated by ECF. ECF of AT-methyl-decahydroquinoline forms a mixture of cis- and tra/j5-isomerie perfluorinated derivatives. Ring contraction and formation of per-fluorocyclohexanes are side processes. Trows-quinolizidine gives perfluoro-tra/w-quinolizidine (yield 16-23%) and a large amount of other compounds with unknown... 

When subjected to ECF, heterocyclic bicyclic compounds with rings of varying composition lead to perfluorinated cyclic compounds, which are useful as components of blood substitutes and as liquids for conservation of organs (85USP4526969, 81/82JAP(K)59204192, 85USP4534978) (Scheme 73). 

The material presented in this chapter indicates that the synthesis of fluorinated heterocyclic compounds has attracted considerable attention from the viewpoint of new methods and approaches the specific features of perfluorinated organic compounds are extensively used to create new fluorinated materials with wide applications. Recent growth of fluoroorganic chemistry has led to the discovery of new fluorine-containing heterocyclic compounds with unique structures many of these compounds exhibited specific biological activity and proved to be effective drugs and pesticides. It is hoped that more original methods for the synthesis of heterocyclic... 

Petrov VA (2009) Perfluorinated six-membered aromatic heterocycles containing one or more heteroatom. In Fluorinated heterocyclic compounds synthesis, chemistry, and applications. WUey, Hoboken... 

Pubhcations have described the use of HFPO to prepare acyl fluorides (53), fluoroketones (54), fluorinated heterocycles (55), as well as serving as a source of difluorocarbene for the synthesis of numerous cycHc and acycHc compounds (56). The isomerization of HFPO to hexafluoroacetone by hydrogen fluoride has been used as part of a one-pot synthesis of bisphenol AF (57). HFPO has been used as the starting material for the preparation of optically active perfluorinated acids (58). The nmr spectmm of HFPO is given in Reference 59. The molecular stmcture of HFPO has been deterrnined by gas-phase electron diffraction (13). 

In a recent review, Tao etal. [34] describe the partial fluorination and the perfluorination of organics with particular emphasis on medically important compounds and pharmaceuticals. The selective electrofluorination (SEF) of olefins and active methylene groups is reviewed by Noel et al. [35] In the case of heterocycles, nuclear fluorination is known to be the predominant process. However, in aromatic compounds, nuclear substitution as well as addition proceeds simultaneously, leading to the formation of a mixture of products. The influence of solvents, supporting electrolytes, and adsorption on product yield and selectivity is summarized and evaluated. Dimethoxyethane is found to be a superior solvent for SEF processes. Redox mediators have been employed to minimize anode passivation and to achieve better current efficiencies. 

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