Fitting the Eyring equation[20] to the experimental data
such that they avoid edge positions, presumably due to
unfavorable 1,4-H,F steric interactions which would arise if a
fluorine atom was located at one of the four transannular
positions above (or below) the plane of a [3333] ring. Features
of the structure of 5 suggest substantial ring strain. The C-
C(CF2)-C angles are 119.48 and 120.28 the widest observed in
this family of structures so far. Nonetheless, the CF2 groups
organize the ring in such a manner that they maintain corner
locations.
In summary, we have used cyclododecane as a molecular
framework to explore the steric and geometric influence of
the CF2 group. It emerges from this study that there is a very
strong geometric preference for the CF2 to locate at corner
positions of the ring, to relieve both angle strain and relax 1,4-
H,H transannular interactions. The cyclododecane [3333]
conformation is particularly tensioned due to transannular H–
H interactions and the system avoids 1,4-H,F transannular
interactions due to the small but increased van der Waals/
steric influence of fluorine. Judicious spacing of two CF2
groups can lead to relatively stable ring conformations, for
example, in the case of structures 3 and 4. It follows that
strategic incorporation of one or more CF2 groups could
stabilize larger alicyclic rings. The polar nature and conforma-
tional preference of the CF2 group offers potential as a
strategy in the design of performance aliphatic compounds
which require both molecular order and polarity, such as
organic liquid crystals and polymer chains.
allowed determination of the activation parameters: DG° =
9.54 kcalmolÀ1,
DH° = 9.16 kcalmolÀ1,
and
DS° =
À1.26 calKÀ1 molÀ1 (see Supporting Information). Thus,
cyclododecane 3 has a conformational energier barrier
3.0 kcalmolÀ1 higher than cyclododecane itself indicating
that the CF2 groups introduce conformational stability.
1,1,7,7-Tetrafluorocyclododecane (4) resulted in a much
higher melting solid (1438C) which was also readily amenable
to X-ray structure analysis, and the resultant structure is
shown in Figure 2d. A quantum chemical study (MP2/6-311 +
G(2d,p)//B3LYP/6-311 + G(2d,p) + ZPE)[17] on 4, similar to
that carried out for 2, indicated that the corner/corner
structure was more stable than the alternative edge/edge
[3333] structure by 5.91 kcalmolÀ1 (see Supporting Informa-
tion). The fluorine of the CF2 groups at the corner locations
are exo to the ring and they provide conformational stability
to the ring structure. This corner/corner structure has C2
symmetry, and unlike 3 low-temperature 19F NMR spectros-
copy did not resolve these fluorines. However, 1H NMR
lineshape analysis and coalescence of exo and endo edge CH2
groups of 4 allowed evaluation of the free-energy barrier
(DG° = 10.6 kcalmolÀ1) at the coalescence temperature
(233 K), which is significantly higher than for cyclododecane
(7.3 kcalmolÀ1) and 1,1,4,4-tetrafluoroclododecane (3)
(9.54 kcalmolÀ1). This increased stability to ring interconver-
sion for 4 relative to 3 may be due to its zero dipole moment.
Analysis of the structures of cyclododecanes 3 and 4
reveal that the CH2-C(F2)-CH2 angles are wide, ranging from
115–1188 consistent with the CCDC survey described in
Figure 1.[9] This presumably relieves some angle strain relative
to the native cyclododecane structure 1. The angle widening
also has the consequence of relaxing 1,4-H,H transannular
interactions above and below the face of the ring. These non-
covalent interactions are lengthened by the presence of the
CF2 group at a corner position relative to those interactions
with CH2 at the corner (e.g. 2.24 ꢁ/2.20 ꢁ versus 2.14 ꢁ/
2.15 ꢁ in 4). Thus there are two effects, angle widening and
transannular relaxation, favoring the corner location of the
CF2 group. Additionally, if CF2 were located at an edge, the
1,4-H,F interaction of the endo fluorines would be raised in
energy relative to the corresponding 1,4-H,H interaction due
to the slighly larger steric influence of fluorine.
Received: July 19, 2011
Published online: September 20, 2011
Keywords: conformational analysis · multivicinal fluorines ·
.
organic materials · organofluorine chemistry
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In order to gain further insight into the influence of CF2
groups within the cyclododecane motif a synthesis of 1,1,6,6-
tetrafluorocyclododecane (5) was carried out. This molecule
was selected because one of the CF2 groups is forced to an
edge position, if the cyclododecane maintains a square [3333]
structure. Tetrafluoroclododecane 5 was prepared by the
route illustrated in Scheme 1. This compound has the lowest
melting point (408C) of the series 1–5, and it was significantly
more amorphous in nature than 3 and 4. Accordingly it
proved very difficult to find a suitable crystal for X-ray
analysis. After extended trials a small crystal of 5 was
identified which diffracted X-rays, and the resultant structure
is shown in Figure 2e. It is clear that the ring conformation
has changed significantly from the [3333] square type
conformation to a distorted [4332] pseudo-rectangular struc-
ture. The 1,6-CF2 groups force this conformational change
ˇ
ˇ
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[9] A search of the Cambridge Crystallographic Data Centre
(CCDC) was carried out using the ConQuest Software.
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631.
Angew. Chem. Int. Ed. 2011, 50, 10581 –10584
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim