II. Internal perfluoroolefins as intermediates in synthesis of heterocyclic compounds.

2.1. Reactions of internal perfluoroolefins with 1,1-binucleophilic reagents.

Intermolecular nucleophilic cyclization is the basis of obtaining 4-membered heterocycles. Primary alkylamines are binucleophilic reagents and the both hydrogen atoms of the amino group are affected in reactions with unsaturated compounds. But one should have in mind that primary alkylamines are rather strong bases that can catalyze the isomerization process of perfluoroolefins. So, isomerization of olefin1 may result in perfluoro-2-methyl-1-pentene which terminal multiple bond is very labile towards nucleophilic reagents. That may bring to the change in direction of heterocycle formation and give a big number of polycyclic heterocycles with one nitrogen atom. In fact, interaction of perfluoro-2-methyl-2-pentene and tert-butyl amine results in formation of tert-butyl(pentafluoroethyl)-2-trifluoromethyl-1-ethylidene amine 3 . The latter in the excess of tert-butyl amine in the presence of Et₃N in acetonitrile was subjected to intermolecular cyclization to form tert-butyl-[1-tert-butyl-4-pentafluoroethyl-3-trifluoromethyl-1H-azet-2-yliden] amine 4 [8-10].

Probably, compound 3 is formed at the expense of intermediate formation of tert-butyl(octafluoro-2-trifluoromethylpent-1-enil) amine 5 followed by hydrogen fluoride elimination and generation of C=C=N group by dehydrofluorination. Compound 3 reacts with tert-butylamine affecting the carbon atom of the C=C=N group and is subjected to intermolecular cyclization to form compound 4 [8-11].

Scheme 2 of transformations can be presented as follows:

Scheme 2

Olefin 1 with another spatially difficult amine, isopropylamine, behaves in a similar way. In this case the formation of 4-memebered hetrocycle may be interpreted as processes of addition to the C=C bond , dehydrofluorination and replacement of the fluorine atom in isomerized perfluoro-2-methyl-1-pentene. Further intermolecular cyclization of the compound of type 4 gives isopropyl[1-isopropyl-4-pentafluoroethyl-3-trifluoromethyl-1H-azet-2-ilidene] amine 6 [12].

But in this case the formation of compound 7 takes place that points to the direct reaction of olefin 1 with isopropylamine. This is an evidence of a role of steric factors in this reaction. In fact, the interaction of olefin 1 with ethylamine is realized according to the second reaction way. If such a perfluoroolefin isomerization does not occur under the action of the initial alkylamine or formation of a simmetrically substituted structure takes place, then only one heterocyclic compound is obtained. This is in the case of azaalkene 2. A derivative of diazete 8 is obtained independently of the character of the nucleophilic reagent.

The reaction of two equivalents of 2-amino derivatives, N-methylbezimidazole and benzthiazole, with perfluoro-5-azanon-4-ene gives perfluoropropyl derivatives of diazete 8 c,d; the reaction of isopropylamine and tert-butylamine with this perfluoroazaalkene 2 takes place probably by the same route resulting in formation of the diazetine ring. Formation of these compounds takes place probably at the expense of intermolecular nucleophilic cyclization when the fluorine at the internal double bond is replaced and the heterocyclic ring is formed [11].

This route turned out to be general for reactions of series of different perfluoroolefins with primary alkylamines [8,12,14]. These reactions obviously point to the dependence on the reagent and its structure.

Interaction of hexamethyldisilazane with adduct of perfluoro-2-methyl-2-pentene and triethylamine results in formation of perfluoro-3-methyl-4-ethylazete 9 and perfluoro-2-methyl-3-ethylazetine-3,4 10 in the excess amount of the first compound. But compounds 11 and 12 are also obtained in small quantities.

Formation of these compounds can be explained by the following transformations. At first low-nucleophilic hexamethyldisilazine affects the carbon atom of the multiple bond, elimination of fluoride ion to form terminal double bond takes place in a new zwitter-ion. Further catalysis with fluoride ion results in generation of the active N-nucleophile and intermolecular cyclization with its participation gives the 4-membered heterocycle.

These results allow the understanding of importance of steric factors in the reaction of perfluoro-2-methyl-2-pentene with primary alkylamines.

Aromatic primary amines are not only 1,1-binucleophiles regarding the nitrogen atom but also exhibit properties of C,N-binucleophiles. Their reactions with series of perfluoroolefins lead to formation of quinoline derivatives [15,16]. We showed that the reaction of perfluoro-2-methylpent-2-ene with aniline in the absence of base or in the presence of triethylamine resulted in formation of [2-pentafluoroethyl-3-trifluoromethylquinoline-4-il]phenyl amine which structure was confirmed by X-ray analysis [16].

We have found [17] that perfluoro-2-methyl-2-pentene and perfluoro-5-azanon-4-ene react smoothly with two moles of aniline, 4-fluoroaniline and 4-methoxyaniline in the presence of 3 moles of Et₃N in acetonitrile to form derivatives of quinoline 13-15 and pyrimidine 16-18.

Probably the reactions occur according to scheme3:

Scheme3

Introduction of a nitro-group into the benzene ring or of two chlorine atoms to the 2,6-positions of the phenyl frame decreases considerably nucleophilic properties of the C-anion center comparing with the N-anion and formation of diazetine derivatives 19-21 takes place.

If electron-donating substituents (Me, MeO) are in the 2,6-positions of aniline then cyclization by C-anion center is possible. Thus, interaction of compounds 1 and 2 with 2,6-dimethylaniline results in formation of dihydroquinolines 22,23 and dihydroquinoazolines 24,25 respectively [17].

So, anilines with electron-donating substituents in the benzene ring give quinazoline derivatives whereas with electron-deficient ones or with haloids in ortho-positions promotes formation of 4-memebered heterocycles.

It seems possible to reveal appropriate reaction conditions which may result in formation of a proper compound and with assistance of nucleophiles of different types these reactions may present a potentially useful route to fluorinated heterocyclic compounds.