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C. Tonelli et al. / Journal of Fluorine Chemistry 128 (2007) 46–51
Exhaustive carbonyl hydrogenation was excluded because the
chloro-derivative RfCH2Cl was never observed (reaction b).
Moreover, the possibility that this intermediate, if formed,
immediately converts by a further hydrogenolysis step to the
corresponding HFPE (RfCH3), contradicted the evidence that,
when synthesised on-purpose, it proved completely unreactive
in the same experimental conditions (reaction c).
A partial hydrogenation of the starting RfC(O)Cl is very
unlikely and, in any case, the corresponding a-chloro-alcohol
[RfCH(OH)Cl] was never detected (reaction d), so it must be
considered, if present, a highly reactive species quickly reduced
to the corresponding alcohol (reaction e).
Several other reactions, consistently with the proposed
mechanism and the observed product distribution, can justify
the presence of the alcohol (RfCH2OH) as the main side product.
First of all, the aldehyde can be further reduced to alcohol by a
one step process (reaction f), or by two subsequent steps,
consisting of hydration and reduction, respectively (reaction g).
Water can be present as impurity (humidity) or generated by
some of the described reaction pathways. The hydrated
intermediate [RfCH(OH)2], analogously to other OH containing
intermediates reported in the reaction scheme, could react with
the starting acyl chloride forming the corresponding esters
(reaction h), which in principle could undergo hydrogenolysis to
alcohol (carboxylic acid as side product), or to aldehyde and its
hydrated form (reactions i and l, respectively) [32]. However, the
strong hydrolysis sensitivity of these fluorinated esters makes
these reactions highly improbable and for this reason they have
been shown as dotted lines. The hydrolysis reactions have not
been reported in the simplified reaction scheme.
Scheme 2. Reaction mechanism for hydrofluoropolyethers formation.
Due to the high temperature selected for the reduction
process (100 8C) the equilibrium between hydrated and
anhydrous aldehyde should be shifted toward the anhydrous
form. As a consequence, a new aldehyde molecule is available,
so activating a cyclic catalytic process. However, the cycle
could also be sustained by the hydrated aldehyde that could
give directly the hemiacetal by reaction with the alcohol.
Interestingly, while the cleavage in position 1 is ineffective
for the direct synthesis of HFPE, this pathway affording only
alcoholic species, the cleavage in position 2 gives formally 50%
yield of the desired HFPE. However, the evaluation of the
whole reaction Scheme 2 justifies the observed higher yield
(60–80%), because the hydrated aldehyde (or its anhydrous
form) reacts with the alcohol generating a new active and
effective intermediate (hemiacetal).
Taking into consideration the above analysis of experimental
results, it is evident that the key intermediate for the synthesis of
target HFPE is the corresponding aldehyde.
The typical product composition is 60–81% HFPE + 40–
19% (alcohol + carboxylic acid), the carboxylic acid, always
present as minor impurity, being strongly dependent on the
water present in the system.
A cleavage in position 2 with a regioselectivity of 65–70%
would give a HFPE yield close to 100% because equivalent
amount of side products (alcohol and hydrated aldehyde) are
formed.
Surprisingly, the alcohol, easily generated by aldehyde
reduction, is stable to hydrogenation and does not further
convert to HFPE, as confirmed by specific experiments carried
out on pure product. Consequently, the aldehyde must form
HFPE by a different pathway not involving two direct reduction
steps, unlike the well-known exhaustive reduction of hydro-
genated acyl chlorides [33].
Considering the observed yield (excluding any further
contribution of different reaction pathways to HFPE forma-
tion), the actual regioselectivity is ca. 60% for the cleavage in
position 2.
According to the above discussion, that considers the
aldehyde as the key intermediate, its use as starting reagent
should assure a yield in HFPE comparable to the one obtained
This aldehyde, like other fluorinated carbonyl containing
species, is highly reactive with respect to nucleophilic attack to
the C atom of the carbonyl group. Therefore, a hemiacetal is
easily formed by reaction with alcohol (reaction m). Moreover,
this addition could be speeded up by the presence of an acid
catalyst (HCl is a by-product of the hydrogenation process).
The proposed mechanism considers this acetal easily con-
vertible by hydrogenolysis to further reduced species. The
structure and composition of these species essentially depend
on the regioselectivity of this hydrogenolysis (see Scheme 2).
Reaction 1 generates two alcoholic molecules, whereas through
reaction 2 the target HFPE and aldehyde (as hydrated form) are
obtained.
Table 1
Structures and molecular weights of Ac-n1-5 series and Ac-Z
Product
Structure
Molecular weight
Ac-n1
Ac-n2
Ac-n3
Ac-n4
Ac-n5
Ac-Z
Cl–CF2CF(CF3)OCF2COCl
Cl(C3F6O)2CF2COCla
312
478
644
810
846
459
Cl(C3F6O)3CF2COCla
Cl(C3F6O)4CF2COCla
Cl(C3F6O)4CF(CF3)OCF2COCla,b
ClOCCF2O(CF2CF2O)2CF2COCl
a
Two isomers: ClCF2CF(CF3)– = 30%; CF3CF(Cl)CF2– = 70% (molar
base).
b
The unit –CF(CF3)O– is randomly distributed along the oligomeric chain.