Study of the zinc action on the 2-chloroethyl 2-bromo-2-perfluoroalkylethanoates

ABSTRACT 2-Bromo-2-perfluoroalkyl acids are converted into the corresponding esters by a reaction of alcoholysis in the 2-chloroethanol. The action of zinc on perfluoroalkylated bromo-esters resulted in the bromine reduction products formation via zinc organic intermediates. When heated at 100°C, for 48 h, in the presence of an excess of zinc, the bromo-esters produce the symmetrical bis(vinyl perfluoroalkyl ester) ethoxide compounds, resulting from the BrZnF elimination reaction, followed by a dimerization reaction. GRAPHICAL ABSTRACT


Introduction
In recent years, a particular interest is accorded to the synthetic methods of highly fluorinated organic compounds. The perfluoroalkyl chains constitute an important source of reagents for these syntheses. These chains have particular chemical [1,2], physical [3][4][5][6] and biological [7][8][9][10] properties. Their introduction into organic molecules gives them particular properties compared to their non-fluorinated homologues [11].
We have previously described the action of zinc and vinyl zinc bromide on the 2-bromo-2-perfluoroalkylethanoic acid and the methyl 2-bromo-2-perfluoroalkylethanoate compounds [52]. As a continuation, we describe herein an attempt of the synthesis of some perfluoroalkylated lactones [54], via an intramolecular cyclization reaction, using the 2chloroethyl 2-bromo-2-perfluoroalkylethanoate substrate with the zinc.
Compounds 2 are reacted with activated zinc for 6 h at 70°C, in tetrahydrofuran (THF), then hydrolysed. The reaction leads exclusively to the corresponding 2-chloroethyl 2-perfluoroalkylethanoates 3, resulting from the reduction reaction of the bromine atom in middle yields (Scheme 2).
The zinc atom inserts between carbon and bromine atoms, yielding the bromozincic organometallic intermediate. This nucleophilic intermediate is unable to act on the electrophilic chloro-substituted carbon atom. So, the expected perfluoroalkylated lactones 4 are not obtained even by modifying some reaction conditions (zinc amount, temperature and reaction duration).
This result may be explained on the basis of the weak bromozincic carbon atom (CHZnBr) nucleophilicity [62] to act on the chloro-substituted carbon atom, neither via an intramolecular nucleophilic substitution (S Ni ) to produce the heterocyclic five-membered lactones 4, nor via an intermolecular nucleophilic substitution reaction to yield the dimeric compounds 5 (Scheme 2).
The reaction of the 2-chloroethyl 2-bromo-2-perfluoroalkylethanoate 2 in the presence of a zinc excess, in THF at 100°C for 48 h, conduce to the symmetrical bis(vinyl perfluoroalkyl ester) 6 (Scheme 3) as unique product, resulting from a trans BrZnF elimination reaction, followed by an ethane molecule elimination than an O-alkylation (Scheme 5).
The formation of the esters 3 as well as the dimeric compounds 6 show that the reaction involves in all cases the bromozincic intermediate A (Scheme 4). While fluorine atom elimination reaction is not well frequent, because strength and the short length of the carbon-fluorine covalent single bond, such reaction occurs on compounds 2. The high and prolonged heat, of perfluotoalkyleted bromoester 2, conduces exclusively, through an elimination reaction of (BrZnF) to the Z geometrical configuration isomer B, [63] highly stabilized from a conjugated system. The geometrical structure of the bromozincic intermediate A (Scheme 4) is in favour of a trans elimination, because the β-carbon atom is bonded to two fluorine atoms (CF 2α ). So, regardless the absolute configuration of the α-carbon atom, in both cases, there is always a fluorine atom in the trans position to the ZnBr living group (Scheme 4).
The presence of a zinc excess in the reaction with the ester 2, in the above-described reaction conditions, gives rise also to a second zinc insertion reaction between chlorine and carbon atoms.  The NMR spectroscopic data confirm the obtained structures. In particular, the 1 H NMR spectra show a doublet at 6.05 ppm, corresponding to the two enonic protons (=CH), coupled with the single vinylic fluorine atom (=CF, 3 J HFtrans ∼ 31 Hz). The 19 F NMR spectra are in agreement with the 1 H NMR spectra and show a signal corresponding to two vinylic fluorine atoms at −108 ppm. The 13 C NMR spectra show a singlet at ∼106 ppm, attributed to the enonic (HC=) carbon atoms and a doublet of multiplet at 152 and 156 ppm, relative to fluorinated vinylic carbon atoms (=CF) with a coupling constant 1 J FC ∼ 285 Hz.

Conclusion
The 2-chloroethyl 2-bromo-2-perfluoroalkylethanoates 2 are synthesized by an alcoholysis reaction of 2bromo-2-perfluoroalkyl acids 1 in the 2-chloroethanol. Reacted with the zinc in middle conditions, the bromo-esters 2, yield the bromine atom reduction products 3 and no trace of the desired perfluoroalkyl lactones 4 is detected. Such results justify again the low reactivity of the zincic carbon atom to act as a nucleophile on the primary chloro-substituted carbon atom. The prolonged heat of the same reagents 2 with a zinc excess, yield the bis(vinyl perfluoroalkyl) oxyethylene 6 as exclusive products.